Обзор американских кардиологических журналов за неделю (ссылки)

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Official Title: The Impact of Remote Monitoring with Automatic Clinician Notifications on the Clinical Care of ICD and CRT-D Patients (CONNECT)
Event: ACC Annual Scientific Session 2010
Topic(s): Arrhythmias
Presenter: George H. Crossley, III
Writer(s): Xiushui Ren
Date Posted: 3/15/2010
Related Resources
Presentation Slides: CONNECT

Summary
Remote monitoring in patients with implantable cardioverter defibrillators (ICDs) and cardiac resynchronization therapy defibrillators (CRT-Ds) appears to improve patient care and reduce healthcare utilization.

Background
Because expanded indications for ICDs and CRT-D have resulted in a substantially increased number of device implants, clinicians have adjusted their practices to enable proper follow-up. Newer ICD and CRT-D devices provide remote monitoring capabilities that are designed to allow for more efficient follow-up and reduce healthcare utilization.

The Clinical evaluation Of remote NotificatioN to rEduCe Time to clinical decision (CONNECT) study is a randomized controlled trial to examine the clinical and health care utilization impact of wireless remote monitoring versus routine in-office care.

Study Design
The CONNECT study randomized 1997 patients implanted with a Medtronic wireless ICD or CRT-D to remote monitoring (n=1014) versus routine in-office care (n=983). Patients monitored remotely were given a wireless home monitor for transmitting device diagnostics to the clinician's office. Examples of key diagnostics include atrial tachycardia (AT) and atrial fibrillation (AF) daily burden, rapid ventricular response during AT/AF, and shocks delivered. Both groups had lead and device integrity (including lead impedance out of range, VF detection, low battery voltage, and excessive charge time) alerts on.

All patients were followed for 15 months post-implant. Patients in the remote monitoring arm had office visits at only one month and 15 months post-implant. Patients in the routine care arm had office visits at one, three, six, nine, 12, and 15 months post-implant.

The primary objective was to compare time to clinical decision between patients managed remotely and patients managed with routine in-office care. The key secondary objective was to assess the impact of remote monitoring and early notification on healthcare utilization.

Results and Conclusions
Baseline characteristics were similar between the two groups. The mean age was 65 years, and 71% were men. CRT-D comprised 35% of the total devices. The mean LV ejection fraction was 29%, and approximately 88% of the patients were NYHA class II and III.

At follow-up, there were a total of 317 events (172 in remote monitoring arm and 145 in routine in-office care) triggering clinical decisions. The majority of events were high AT/AF burden, fast V rate, and ICD shocks. The median time from event to clinical decision was significantly shorter for the remote monitoring arm (4.6 vs 22 days, p<0.001). The total yearly clinic visits per patient were 3.9 and 6.3 for remote monitoring and routine care groups, respectively. The length of stay per hospitalization for remote monitoring and routine care groups was 3.3 and 4.0 days, p=0.002, respectively.

Thus remote monitoring in patients with ICD and CRT-D resulted in a significant reduction in time from onset of events to clinical decisions in response to arrhythmias and device issues. In addition, remote monitoring seemed to reduce overall healthcare utilization including reduced number of clinic visits and short hospital stay. These data support the use of remote monitoring ICD and CRT-D.

Perspective
It is important to note that, the effect of remote monitoring on battery life and device cost is unclear.

[Chevychelov]

Title: 2010 ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM Guidelines for the Diagnosis and Management of Patients With Thoracic Aortic Disease: Executive Summary: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, American Association for Thoracic Surgery, American College of Radiology, American Stroke Association, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society of Interventional Radiology, Society of Thoracic Surgeons, and Society for Vascular Medicine
Source: Developed in Collaboration With the American College of Emergency Physicians, Endorsed by the North American Society for Cardiovascular Imaging
Topic: Noninvasive Cardiology
Date Posted: 3/16/2010 8:00:00 AM
Author(s): Hiratzka LF, Bakris GL, Beckman JA, et al.
Citation: J Am Coll Cardiol 2010;Mar 16:[Epub ahead of print].
Clinical Trial: No
Related Resources
JACC Article: 2010 ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM Guidelines for the Diagnosis and Management of Patients With Thoracic Aortic Disease: Executive Summary
Guideline: Thoracic Aortic Disease: Guidelines for the Diagnosis and Management of Patients With

Perspective: The following are 12 points to remember about the 2010 thoracic aortic disease guidelines.

1. The goal of this guideline is to improve the health outcomes and quality of life for all patients with thoracic aortic disease. Thoracic aortic diseases are usually asymptomatic and not easily detectable until an acute and often catastrophic complication occurs.

2. Imaging of the thoracic aorta with computed tomographic imaging (CT), magnetic resonance imaging (MRI), or in some cases, echocardiographic examination is the only method to detect thoracic aortic diseases and determine risk for future complications. Measurements of aortic diameter should be taken at reproducible anatomic landmarks, perpendicular to the axis of blood flow, and reported in a clear and consistent format.

3. The identification and treatment of patients at risk for acute and catastrophic disease presentations (e.g., thoracic aortic dissection and thoracic aneurysm rupture) prior to such an occurrence are paramount to eliminating the high morbidity and mortality associated with acute presentations.

4. Aortic imaging is recommended at the time of diagnosis of Marfan syndrome or Loeys-Dietz syndrome to determine the aortic root and ascending aortic diameters, and 6 months thereafter to determine the rate of enlargement of the aorta. Annual imaging is recommended for patients with Marfan syndrome and if stability of the aortic diameter is documented. Loeys-Dietz patients should have yearly MRI from the cerebrovascular circulation to the pelvis.

5. Aortic imaging is recommended for first-degree relatives of patients with thoracic aortic aneurysm and/or dissection to identify those with asymptomatic disease.

6. Providers should routinely evaluate any patient presenting with complaints that may represent acute thoracic aortic dissection to establish a pretest risk of disease that can then be used to guide diagnostic decisions. This process should include specific questions about medical history, family history, and pain features, as well as a focused examination to identify findings that are associated with aortic dissection.

7. Urgent and definitive imaging of the aorta using transesophageal echocardiogram (TEE), CT scanning, or MRI is recommended to identify or exclude thoracic aortic dissection in patients at high risk for the disease by initial screening.

8. Initial management of thoracic aortic dissection should be directed at decreasing aortic wall stress by controlling heart rate and blood pressure with beta-blockers or nondihydropyridine calcium channel-blockers in those with contraindications to beta-blockers. If systolic blood pressures remain >120 mm Hg after adequate heart rate control has been obtained, then angiotensin-converting enzyme inhibitors and/or other vasodilators should be administered intravenously to further reduce blood pressure that maintains adequate end-organ perfusion.

9. Urgent surgical consultation should be obtained for all patients diagnosed with thoracic aortic dissection regardless of the anatomic location (ascending vs. descending) as soon as the diagnosis is made or highly suspected.

10. For patients with ascending thoracic aortic dissection, all aneurysmal aorta and the proximal extent of the dissection should be resected. A partially dissected aortic root may be repaired with aortic valve resuspension. Extensive dissection of the aortic root should be treated with aortic root replacement with a composite graft or with a valve sparing root.

11. Stringent control of hypertension, lipid profile optimization, smoking cessation, and other atherosclerosis risk-reduction measures should be instituted for patients with small aneurysms not requiring surgery, as well as for patients who are not considered surgical or stent graft candidates.

12. For patients with degenerative or traumatic aneurysms of the descending thoracic aorta exceeding 5.5 cm, saccular aneurysms, or postoperative pseudoaneurysms, endovascular stent grafting should be strongly considered when feasible. Debabrata Mukherjee, M.D., F.A.C.C.

[Chevychelov]

Title: Paclitaxel-Eluting Stent Versus Conventional Stent in ST-Segment Elevation Myocardial Infarction (PASSION: 5-Year Follow-Up)
Year Presented: 2006
Year Published 2006
Topic(s): General Cardiology, Interventional Cardiology, Prevention/Vascular
Summary Posted: 3/16/2010 11:00:00 AM
Writer: Ms. Sabina A. Murphy
Author Disclosure: Consulting Fees: Eli Lilly
Reviewer: Deepak L. Bhatt, M.D., M.P.H., F.A.C.C.
Author Disclosure: Research/Research Grants: Astra Zeneca; Consultant Fees/Honoraria: Duke Clinical Research Institute; Research/Research Grants: Heartscape; Research/Research Grants: PLx Pharma; Research/Research Grants: Cogentus; Research/Research Grants: Sanofi Aventis; Data Safety Monitoring Board (Gov’t/Nonprofit): Duke Clinical Research Institute; Research/Research Grants: Bristol Myers Squibb; Research/Research Grants: Eisai; Research/Research Grants: Takeda; Research/Research Grants: The Medicines Company; Research/Research Grants: Ethicon
Supplemental Reviewer: Anthony A. Bavry, M.D., M.P.H., F.A.C.C.
Author Disclosure: This author has nothing to disclose.

Related Resources
Summary Slide: PASSION Trial
Presentation Slides: PASSION
Related Trial: Trial to Assess the Use of the Cypher Stent in Acute Myocardial Infarction Treated With Angioplasty (TYPHOON )
Related Trial: Helsinki Area Acute Myocardial Infarction Treatment Re-Evaluation - Should the Patients Get a Drug-Eluting or Normal Stent (HAAMU-STENT - Presented at TCT 2006)
Related Trial: MISSION (MISSION – Presented at AHA 2006)
Related Trial: Drug Elution and Distal Protection in Acute Myocardial Infarction (DEDICATION: Stent Study)
Guideline: ST-Elevation Myocardial Infarction: Guidelines for the Management of Patients with

Description
The goal of the trial was to evaluate treatment with paclitaxel-eluting stents compared with bare-metal stents among patients undergoing primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI).
Hypothesis
Paclitaxel-eluting stents would be superior at reducing the need for revascularization.
Drugs/Procedures Used
Patients undergoing primary PCI were randomized to paclitaxel-eluting Express2 stent (n = 309) or bare-metal stents (n = 310) with either the Express2 or Liberte platform. Use of the glycoprotein IIb/IIIa inhibitors abciximab or tirofiban was at the discretion of the treating physician. Patients did not undergo angiographic follow-up in this trial, but were followed for clinical events.
Concomitant Medications
Aspirin (80-100 mg) and clopidogrel (300 mg loading dose followed by 75 mg/d for 6 months)
Principal Findings
Mean time from symptom onset to angioplasty was 3 hours. Left anterior descending artery was the culprit in 50% of patients, and 45% of patients had multivessel disease. Procedural success was 95%. An average of 1.3 stents was used in both arms.

The primary endpoint of death, reinfarction, or target lesion revascularization (TLR) at 1 year did not differ between treatment groups (8.8% for paclitaxel-eluting stent group vs. 12.8% for bare-metal stent group, p = 0.12). Cardiac death or MI occurred in 5.5% of the paclitaxel-eluting stent group and 7.2% of the bare-metal stent group (p = 0.40). There was also no difference in TLR (5.3% vs. 7.8%, p = 0.23). There were three cases of stent thrombosis in each group.

At 5 years, cardiac death, MI, or TLR was 18.3% versus 22.0% (p = 0.24), cardiac death was 8.9% versus 11.5% (p = 0.28), MI was 6.5% versus 4.3% (p = 0.28), and TLR was 7.3% versus 10.5% (p = 0.16), respectively, for paclitaxel-eluting stents versus bare-metal stents. Cummulative definite stent thrombosis was 3.6% versus 1.7% (p = 0.20), definite or probable stent thrombosis was 3.9% versus 3.4% (p = 0.85), and possible stent thrombosis was 6.8% versus 6.7% (p = 0.93), respectively. Censoring events that occurred within 30 days, the cummulative 5-year incidence of definite stent thrombosis, was 2.9% versus 0.8% (p = 0.06), respectively.
Interpretation
Among patients undergoing primary PCI for STEMI, use of paclitaxel-eluting stents was not associated with a difference in the primary composite endpoint at 1 year compared with bare-metal stents.

Drug-eluting stents have been widely studied in the setting of elective PCI, but relatively little randomized data exist in the setting of STEMI. The present trial is the first large-scale randomized study with paclitaxel-eluting stents compared with bare-metal stents conducted exclusively in the STEMI population.

The TYPHOON trial demonstrated a reduction in target vessel revascularization with sirolimus-eluting stents over bare-metal stents in STEMI patients. However, there were several important differences between the trial in addition to the different drug-eluting stent used, including an angiographic follow-up in the TYPHOON trial, which may have increased the repeat revascularization rate. The TLR rate in the present study was very low in both arms.

At 5 years, cardiac death, MI, or TLR was similar between the groups; however, late stent thrombosis (between 30 days and 5 years) was increased with paclitaxel-eluting stents.
Conditions
• Coronary heart disease
• Coronary heart disease / Acute MI
Therapies
• Stent
• Stent/drug-eluting
Study Design
Randomized. Blinded.
Patients Enrolled: 619
Mean Follow-Up: 5 years
Mean Patient Age: 61 years
% Female: 24

Primary Endpoints
Composite of death, recurrent MI, or TLR (within 5 mm of stent edges) at 1 year
Secondary Endpoints
MACE at 5 years
Individual components of MACE
Stent thrombosis
Patient Population
STEMI with chest pain for >20 minutes and ST elevation in ≥2 contiguous leads;
Infarct-related artery with a de novo lesion suitable for stenting on diagnostic angiography
Exclusions:
Cardiogenic shock
Mechanical ventilation
Failed fibrinolysis
Expected mortality of <6 months
References: Presented by Dr. Maarten Vink at the ACC.10/i2 Summit, Atlanta, GA, March 2010.

Laarman GJ, Suttorp MJ, Dirksen MT, et al. Paclitaxel-eluting versus uncoated stents in primary percutaneous coronary intervention. N Engl J Med 2006;355:1105-13.

Presented by Dr. Maurits T. Dirksen at the March 2006 i2 Annual Scientific Session, Atlanta, GA.

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Title: Diuretic Optimization Strategies Evaluation in Acute Heart Failure (DOSE)
Trial Sponsor: National Heart, Lung, and Blood Institute
Year Presented: 2010
Topic(s): General Cardiology, Heart Failure/Transplant
Summary Posted: 3/16/2010 8:00:00 AM
Writer: Dharam J. Kumbhani, M.D., S.M.
Author Disclosure: This author has nothing to disclose.
Reviewer: Deepak L. Bhatt, M.D., M.P.H., F.A.C.C.
Author Disclosure: Research/Research Grants: Astra Zeneca; Consultant Fees/Honoraria: Duke Clinical Research Institute; Research/Research Grants: Heartscape; Research/Research Grants: PLx Pharma; Research/Research Grants: Cogentus; Research/Research Grants: Sanofi Aventis; Data Safety Monitoring Board (Gov’t/Nonprofit): Duke Clinical Research Institute; Research/Research Grants: Bristol Myers Squibb; Research/Research Grants: Eisai; Research/Research Grants: Takeda; Research/Research Grants: The Medicines Company; Research/Research Grants: Ethicon
Related Resources
Presentation Slides: DOSE

Description
Although intravenous (IV) diuretics are routinely used in clinical practice, the optimal dosage and route of administration are not well understood. In addition, observational studies have demonstrated worsening creatinine and clinical outcomes with higher dose of furosemide. Accordingly, the DOSE study sought to evaluate the safety and efficacy of different strategies for diuretic dosing in patients with acute decompensated heart failure (ADHF).
Hypothesis
The DOSE study sought to evaluate the safety and efficacy of two strategies for furosemide dosing in patients with ADHF: 1) route of administration (Q12 hour bolus vs. continuous infusion), and 2) dosing (low intensification to 1x oral dose vs. high intensification to 2.5x oral dose).
Drugs/Procedures Used
Patients were randomized in a 2x2 factorial design to either Q12 hour bolus versus continuous infusion, or low intensification to 1x oral dose versus high intensification to 2.5x oral dose of furosemide. About 48 hours after randomization, patients could be changed over to oral diuretics, continued on same strategy, or undergo a 50% increase in dose, as deemed appropriate.
Concomitant Medications
Angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers (64%), beta-blockers (83%), aldosterone antagonists (28%)
Principal Findings
A total of 308 patients were randomized in a 2x2 factorial fashion. The mean ejection fraction was 35 ± 18%, with a baseline furosemide dose of 131 mg/day. About 57% of the patients had ischemic cardiomyopathy, 53% had atrial fibrillation or atrial flutter, and 51% had diabetes. The mean systolic blood pressure was 119 mm Hg, with a mean heart rate of 78 bpm. Mean sodium was 138 mg/dl, and mean creatinine was 1.6 mg/dl. The mean N-terminal B-type natriuretic peptide (NT-proBNP) was 7439 pg/ml.

There was no difference between Q12 dosing and continuous infusion of furosemide on the visual analog scale (VAS) area under the curve (AUC) (4236 vs. 4373, p = 0.47). Change in creatinine was also similar (0.05 vs. 0.07 mg/dl, p = 0.45). Secondary endpoints such as net volume loss (4237 vs. 4249 ml, p = 0.89), % treatment failure (38% vs. 39%, p = 0.88), change in weight at 72 hours (-6.8 vs. 8.1 lbs, p = 0.20), dyspnea VAS AUC at 72 hours (4456 vs. 4699, p = 0.36), and length of stay (5 vs. 5 days, p = 0.97) were similar between the two arms. The incidence of a composite of death, rehospitalization, or emergency department visit was similar between the two arms (hazard ratio [HR] 1.19, 95% confidence interval [CI] 0.86-1.66, p = 0.3).

For the low and high intensification of furosemide dosing analysis, there was no difference on the VAS AUC (4171 vs. 4430, p = 0.06). Change in creatinine was also similar (0.04 vs. 0.08 mg/dl, p = 0.21). Secondary endpoints such as net volume loss (3575 vs. 4899 ml, p = 0.001), change in weight at 72 hours (-6.1 vs. 8.7 lbs, p = 0.011), and dyspnea VAS AUC at 72 hours (4478 vs. 4688, p = 0.04) were significantly worse in the low intensification arm, as compared with the high intensification arm, respectively.

Other outcomes such as length of stay (6 vs. 5 days, p = 0.55), and % treatment failure (37% vs. 40%, p = 0.56) were similar between the two arms. The % of patients with increase in creatinine of >0.3 mg/dl within 72 hours was lower in the low intensification arm (14% vs. 23%, p = 0.04). However, this was transient, since there was no overall change in creatinine or cystatin C between the two groups. There was also no difference between the two groups in serum creatinine over the 60 day follow-up period. The incidence of a composite of death, rehospitalization, or emergency department visit was similar between the two arms (HR 0.83, 95% CI 0.60-1.16, p = 0.28).
Interpretation
The results of the DOSE trial illustrate that there is no difference in global symptom relief, as assessed by the VAS AUC, or change in renal function, with a Q12 versus continuous infusion, or low versus high intensification of furosemide dosing. Further, continuous dosing was not associated with an improvement in any of the secondary outcomes assessed, including net diuresis, weight loss, or treatment failure. On the other hand, high intensification (2.5x oral dose) of furosemide was associated with a significant reduction in net diuresis, weight loss, and symptom relief, as compared with low intensification. Changes in creatinine noted in the high intensification arm are transient.

These results are important, and aim to address two important clinically relevant questions regarding the use of diuretics in patients with ADHF. One of the limitations is that the study protocol permitted change in congestive heart failure (CHF) medications 48 hours after randomization, based on clinical response. This could have biased the results towards the null. An analysis of outcomes at 48 hours may be helpful to address this issue. Also, these results are applicable to patients with chronic CHF, who did not require inotropes or intravenous vaspodilators, and who were on moderate to high doses of diuretic at baseline.
Conditions
• Heart failure
Therapies
• Diuretic
Study Design
Randomized. Parallel. Factorial.
Patients Enrolled: 308
Mean Follow-Up: 60 days
Mean Patient Age: Median age: 66 years
% Female: 27

Mean Ejection Fraction: 35
Primary Endpoints
Efficacy:
Patient Global Assessment by VAS over 72 hours using AUC
Safety:
Change in creatinine from baseline to 72 hours
Secondary Endpoints
Change in weight over 24, 48, 72, and 96 hours
Freedom from signs and symptoms of congestion at 72 hours
Bivariate vector of change in creatinine and weight at 72 hours
Dyspnea VAS AUC over 24, 48, and 72 hours
Change in serum creatinine at 24, 48, and 96 hours, day 7 (or discharge), and day 60
Change in cystatin C at 72 hours, day 7 (or discharge), and day 60
Persistent or worsening HF
Development of worsening renal function (increase in creatinine >0.3 mg/dl at any time during initial 72 hours)
Treatment failure (persistent HF, worsening renal failure, or death)
Index hospitalization length of stay
Death, rehospitalization, or emergency department visit within 60 days
Patient Population
≥18 years old
Prior clinical diagnosis of HF with daily home use of oral loop diuretic for at least 1 month
Daily oral dose of furosemide ≥80 mg and ≤240 mg (or equivalent)
Identified within 24 hours of hospital admission
HF defined by at least one symptom and one sign
Anticipated need for IV loop diuretics for at least 48 hours
Willingness to provide informed consent
Exclusions:
Received or planned IV vasoactive treatment (inotropes, vasodilators) or ultra-filtration therapy for HF
Systolic blood pressure <90 mm Hg
Serum creatinine >3.0 mg/dl at baseline or renal replacement therapy
BNP <250 ng/ml or NT-proBNP <1000 mg/ml (if measured for clinical purposes)
Acute coronary syndrome within 4 weeks
Anticipated need for coronary angiography or other procedures requiring IV contrast
References: Presented by Dr. G. Michael Felker at the ACC.10/i2 Summit, Atlanta, GA, March 2010.

[Chevychelov]

Title: Comparison of AngioJet Rheolytic Thrombectomy Before Direct Infarct Artery Stenting to Direct Stenting Alone in Patients With Acute Myocardial Infarction (JETSTENT)
Trial Sponsor: Medrad Interventional/Possis
Year Presented: 2010
Topic(s): General Cardiology, Interventional Cardiology, Prevention/Vascular
Summary Posted: 3/16/2010 11:00:00 AM
Writer: Anthony A. Bavry, M.D., M.P.H., F.A.C.C.
Author Disclosure: This author has nothing to disclose.
Reviewer: Deepak L. Bhatt, M.D., M.P.H., F.A.C.C.
Author Disclosure: Research/Research Grants: Astra Zeneca; Consultant Fees/Honoraria: Duke Clinical Research Institute; Research/Research Grants: Heartscape; Research/Research Grants: PLx Pharma; Research/Research Grants: Cogentus; Research/Research Grants: Sanofi Aventis; Data Safety Monitoring Board (Gov’t/Nonprofit): Duke Clinical Research Institute; Research/Research Grants: Bristol Myers Squibb; Research/Research Grants: Eisai; Research/Research Grants: Takeda; Research/Research Grants: The Medicines Company; Research/Research Grants: Ethicon
Related Resources
Presentation Slides: JETSTENT
Related Trial: Thrombus Aspiration During Percutaneous Coronary Intervention in Acute Myocardial Infarction (TAPAS)
Related Trial: AngioJet Rheolytic Thrombectomy In Patients Undergoing Primary Angioplasty for Acute Myocardial Infarction (AiMI)

Description
The goal of the trial was to evaluate treatment with AngioJet rheolytic thrombectomy plus stenting compared with direct stenting alone among patients with acute myocardial infarction (MI).
Hypothesis
AngioJet rheolytic thrombectomy would be superior at improving myocardial perfusion and clinical outcomes.
Drugs/Procedures Used
Patients with ST-elevation MI (STEMI) were randomized to AngioJet rheolytic thrombectomy plus stenting (n = 256) versus direct stenting alone (n = 245).

Temporary pacemaker and balloon pre-dilatation were strongly discouraged.
Concomitant Medications
Routine abciximab in both groups
Principal Findings
Overall, 501 patients were enrolled. There was no difference in baseline characteristics between the groups. In the rheolytic thrombectomy group, the mean age was 63 years, 24% were women, 14% had diabetes, cardiogenic shock was present in 2.7%, time from symptoms to the emergency room was 125 minutes, time from the emergency room to percutaneous coronary intervention was 34 minutes, reference vessel diameter was 2.9 mm, and Thrombolysis in Myocardial Infarction (TIMI) flow 0/1 was 84%.

Procedural time was 60 minutes in the rheolytic thrombectomy group versus 46 minutes in the direct stenting group (p < 0.001), mean stents per patient were 1.3 versus 1.4 (p = 0.022), and mean stent length was 24 mm versus 26 mm (p = 0.050), respectively.

The primary outcome of at least 50% ST resolution was 86% with rheolytic thrombectomy versus 79% with direct stenting alone (p = 0.043). Infarct size was 12% versus 13% (p = 0.40), respectively.

Major adverse cardiac events (MACE) at 1 month was 3.1% versus 6.9% (p = 0.05), death 1.6% versus 2.9%, MI 0.8% versus 1.2%, target vessel revascularization (TVR) 0.8% versus 2.5%, and stroke 0 versus 0.4%, respectively.

MACE at 6 months was 12.0% versus 20.7% (p = 0.012), death 3.0% versus 4.9%, MI 0.8% versus 1.3%, TVR 7.7% versus 14.1%, and stroke 0.4% versus 0.4%, respectively.

TIMI major bleeding was 3.9% versus 1.6% (p = 0.12), need for pacing was 0.08% versus 0% (p = 0.17), and perforation was 0% versus 0.04% (p = 0.33).
Interpretation
Among patients with STEMI, the use of rheolytic thrombectomy was beneficial. This device improved myocardial reperfusion as well as 6-month MACE. Rheolytic thrombectomy increased procedural time; however, it did not appear to increase procedural complications such as need for pacing or vessel perforation. The thrombectomy group was also associated with slightly fewer stents per patient and shorter total stent length.

Importantly, there was no signal for increased strokes, which was a concern in the AiMI trial. Notable differences in the current trial are that pacing was not routinely employed and the use of lytics was excluded.

While this trial demonstrated benefit for rheolytic thrombectomy, the use of simpler aspiration thrombectomy catheters likely remains preferential. The Export catheter was beneficial in the TAPAS trial, and meta-analyses of aspiration thrombectomy devices have also demonstrated their benefit.
Conditions
• Coronary heart disease / Acute MI
• Coronary heart disease
Therapies
• Rheolytic Thrombectomy (AngioJet)
Study Design
Randomized. Parallel.
Patients Enrolled: 501
Mean Follow-Up: 6 months
Mean Patient Age: 63 years
% Female: 24%

Primary Endpoints
Early ST-segment resolution, defined as 50% ST resolution at 30 minutes
Final infarct size by scintigraphy at 1 month
TIMI flow, TIMI blush, and corrected TIMI frame count
Secondary Endpoints
Composite of death, MI, urgent TVR, and stroke at 1, 6, and 12 months
Composite of death and readmission for congestive heart failure at 12 months
Patient Population
Patients with STEMI within 12 hours of symptom onset
TIMI thrombus grade 3-5
Infarct artery vessel diameter ≥2.5 mm
Exclusions:
Lysis
Stroke within 30 days
Surgery within 6 weeks
Pre-stented infarct-related artery
References: Presented by Dr. David Antoniucci at the ACC.10/i2 Summit, Atlanta, GA, March 2010.

[Chevychelov]

Title: Radial Artery Grafts Versus Saphenous Vein Grafts in Coronary Artery Bypass Surgery: VA Cooperative Study (VA CABG)
Trial Sponsor: VA Cooperative Studies Program
Year Presented: 2010
Topic(s): Cardiovascular Surgery, General Cardiology, Prevention/Vascular
Summary Posted: 3/16/2010 11:00:00 AM
Writer: Anthony A. Bavry, M.D., M.P.H., F.A.C.C.
Author Disclosure: This author has nothing to disclose.
Reviewer: Deepak L. Bhatt, M.D., M.P.H., F.A.C.C.
Author Disclosure: Research/Research Grants: Astra Zeneca; Consultant Fees/Honoraria: Duke Clinical Research Institute; Research/Research Grants: Heartscape; Research/Research Grants: PLx Pharma; Research/Research Grants: Cogentus; Research/Research Grants: Sanofi Aventis; Data Safety Monitoring Board (Gov’t/Nonprofit): Duke Clinical Research Institute; Research/Research Grants: Bristol Myers Squibb; Research/Research Grants: Eisai; Research/Research Grants: Takeda; Research/Research Grants: The Medicines Company; Research/Research Grants: Ethicon
Related Resources
Presentation Slides: VA CABG
Related Trial: Radial Artery Patency Study (RAPS)

Description
The goal of the trial was to evaluate coronary artery bypass grafting (CABG) with radial artery grafts compared with saphenous vein grafts among patients with stable coronary artery disease (CAD).
Hypothesis
Radial artery CABG would be more effective at improving long-term graft patency.
Drugs/Procedures Used
All patients with stable CAD received a left internal mammary artery graft to the left anterior descending artery whenever possible. The best remaining recipient vessel was then randomized to a radial artery graft (n = 366) versus a saphenous vein graft (n = 367).
Principal Findings
Overall, 733 patients were randomized. Overall mortality was 2%, operative mortality was 0.7%, myocardial infarction was 1%, and stroke was 2%.

The primary endpoint, graft patency at 1 year, was 89% for radial artery grafts versus 89% for saphenous vein grafts (p = NS). Graft patency was also similar between the groups with the following anastomoses: left anterior descending (83% vs. 88%), circumflex (93% vs. 89%), and right coronary artery (86% vs. 88%).

High-grade disease (string sign) in the graft was observed in 8% versus 1% (p < 0.001), respectively. Endoscopic harvesting resulted in no difference in radial artery patency (100% vs. 89%, p = NS); however, it did lower saphenous vein graft patency (78% vs. 91%, p = 0.009).
Interpretation
Among patients undergoing elective CABG, the use of radial grafts was not superior to saphenous vein grafts. Angiographic graft patency was similar between the groups at 1 year. Endoscopic harvest of saphenous vein grafts appeared to lower patency.
Conditions
• Coronary heart disease
• Coronary heart disease / Saphenous vein grafts
• Prevention
• Coronary heart disease / Angina pectoris / Stable
Therapies
• CABG
Study Design
Randomized. Parallel.
Patients Enrolled: 733
Mean Follow-Up: 5 years
Primary Endpoints
One-year angiographic graft patency
Patient Population
Patients with stable CAD undergoing elective CABG
References: Presented by Dr. Steven Goldman at the ACC.10/i2 Summit, Atlanta, GA, March 2010.

[Chevychelov]

Title: Drug Elution and Distal Protection in Acute Myocardial Infarction (DEDICATION: Stent Study)
Trial Sponsor: Supported by unrestricted grants from Cordis/Johnson & Johnson, Medtronic, Abbott, and Boston Scientific.
Year Presented: 2007
Year Published 2008
Topic(s): Interventional Cardiology
Summary Posted: 3/16/2010 11:00:00 AM
Writer: Dharam J. Kumbhani, M.D., S.M.
Author Disclosure: This author has nothing to disclose.
Reviewer: Deepak L. Bhatt, M.D., M.P.H., F.A.C.C.
Author Disclosure: Research/Research Grants: Astra Zeneca; Consultant Fees/Honoraria: Duke Clinical Research Institute; Research/Research Grants: Heartscape; Research/Research Grants: PLx Pharma; Research/Research Grants: Cogentus; Research/Research Grants: Sanofi Aventis; Data Safety Monitoring Board (Gov’t/Nonprofit): Duke Clinical Research Institute; Research/Research Grants: Bristol Myers Squibb; Research/Research Grants: Eisai; Research/Research Grants: Takeda; Research/Research Grants: The Medicines Company; Research/Research Grants: Ethicon
Supplemental Reviewer: Ms. Sabina A. Murphy
Author Disclosure: Consulting Fees: Eli Lilly

Related Resources
Summary Slide: DEDICATION STENT
Presentation Slides: DEDICATION Stent Study
Related Trial: Drug Elution and Distal Protection in ST-Elevation Myocardial Infarction (DEDICATION: Distal Protection Study)
Related Trial: Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI — Presented at TCT 2009)
Journal Scan: Increased Rate of Stent Thrombosis and Target Lesion Revascularization After Filter Protection in Primary Percutaneous Coronary Intervention for ST-Segment Elevation Myocardial Infarction: 15-Month Follow-Up of the DEDICATION (Drug Elution and Distal Protection in ST Elevation Myocardial Infarction) Trial
Related Trial: Paclitaxel-Eluting Stent Versus Conventional Stent in ST-Segment Elevation Myocardial Infarction (PASSION: 5-Year Follow-Up)
Related Trial: Sirolimus-Eluting Stent Versus Bare-Metal Stent in Acute Myocardial Infarction (SESAMI)

Description
The goal of the trial was to evaluate use of a drug-eluting stent (DES) compared with a bare-metal stent (BMS) among patients undergoing primary percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI).
Hypothesis
DES would be superior to BMS for AMI.
Drugs/Procedures Used
Patients undergoing primary PCI were randomized to the use of a DES (n = 313) or BMS (n = 313). Choice of DES was at the discretion of the investigator. Angiographic follow-up was performed at 8 months. Patients also received distal embolic protection versus PCI without embolic protection by 2 x 2 factorial design (results presented separately).
Concomitant Medications
Patients received 300-500 mg aspirin, 300-600 mg clopidogrel, and 10,000 U unfractionated heparin. A beta-blocker was administered if blood pressure and heart rate allowed. Patients were treated with a glycoprotein (GP) IIb/IIIa inhibitor in the catheterization laboratory.
Principal Findings
The infarct artery was the left anterior descending in 42% of patients, and 63% had single-vessel disease. GP IIb/IIIa inhibitors were used in 96% of cases. In the DES arm, the sirolimus-eluting stent was used in 47% of cases and the paclitaxel-eluting stent in 40%. Final Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow was present in 90% of patients at the end of the PCI.

At 8-month angiographic follow-up, in-stent late lumen loss was smaller in the DES group compared with the BMS group (0.09 mm vs. 0.69 mm, p < 0.001). Percent diameter stenosis was lower in the DES group (21.7% vs. 34.0%, p < 0.001), as was binary restenosis (4.8% vs. 16.6%, p < 0.001). Major adverse cardiac events (MACE) at 8 months were lower in the DES group compared with the BMS group (8.9% vs. 14.4%, p < 0.05), driven by a reduction in target lesion revascularization (TLR) (5.1% vs. 13.1%, p < 0.001). There was no difference in MI (1.6% vs. 2.6%, p = 0.42). Cardiac death trended higher in the DES group (4.2% vs. 1.6%, p = 0.09), as did overall mortality (5.1% vs. 2.6%, p = 0.14). There was no difference in stent thrombosis, with seven cases in the DES group versus eight cases in the BMS group (p = 0.72).

At 3 years, the incidence of MACE was significantly lower in the DES arm, as compared with the BMS arm (11.5% vs. 18.2%, p = 0.024). This was driven predominately by a reduction in the need for TLR (6.1% vs. 16.3%, p < 0.001). There was no difference in MI between the two arms (1.9% vs. 3.2%, p = 0.45). The trend towards an increase in all-cause mortality with DES noted at 8 months was still present at 3 years (10.5% vs. 6.4%, p = 0.08). However, there was a significant increase in cardiovascular mortality with DES at the end of 3 years (6.1% vs. 1.9%, p = 0.013). However, the incidence of stent thrombosis was similar between the two arms (p = 0.5).
Interpretation
Among patients undergoing primary PCI for AMI, use of a DES was associated with a reduction in late lumen loss at 8 months compared with use of a BMS, but cardiac mortality trended higher. At 3 years, there was a significant reduction in MACE, driven predominantly by a significant reduction in TLR in the DES arm, as compared with BMS. Of concern though, all-cause mortality at 3 years showed a trend towards being higher with DES, as compared with BMS, and cardiovascular mortality was significantly higher.

The reasons for the increase in cardiovascular mortality with DES noted in this trial are not clear. Although there was no difference in stent thrombosis between the two arms, the total duration of dual antiplatelet therapy was not reported.

These results are contrary to the 2-year results of the HORIZONS-STENT trial, which showed an improvement in TLR, but no difference in mortality between DES and BMS. These outcomes need to be studied in other long-term trials of patients with AMI receiving DES versus BMS.
Conditions
• Coronary heart disease
• Coronary heart disease / Acute MI
Therapies
• Stent
• Stent/drug-eluting
Study Design
Randomized. Parallel.
Patients Screened: 1,687
Patients Enrolled: 626
Mean Follow-Up: 3 years
Mean Patient Age: 62 years
% Female: 27

Mean Ejection Fraction: 48%
Primary Endpoints
Late lumen loss at 8 months
Secondary Endpoints
Cardiac events at 8 months
Patient Population
Acute onset typical chest pain within 12 hours
ST-elevation of >4 mm in contiguous leads
High-grade stenosis or occlusion of a native major coronary artery that can be crossed with a soft or intermediate tip guidewire
Possibility to perform distal protection of the infarct-related artery
Exclusions:
History of previous MI
Use of fibrinolytic agents for the index infarction
Left main stenosis
Heavy calcification of abdominal aorta or occlusive iliofemoral disease hampering access to the coronary ostias by the femoral route
Known renal failure
Other significant cardiac disease
Other severe disease with an expected survival <1 year
Known allergy to clopidogrel or contrast media
Gastrointestinal bleeding within 1 month
References: Presented by Dr. Peter Clemmensen at the ACC.10/i2 Summit, Atlanta, GA, March 2010.

Kelbaek H, Thuesen L, Helqvist S, et al., on behalf of the DEDICATION Investigators. Drug-eluting versus bare metal stents in patients with ST-segment-elevation myocardial infarction: eight-month follow-up in the Drug Elution and Distal Protection in Acute Myocardial Infarction (DEDICATION) trial. Circulation 2008;118:1155-62.

Presented by Dr. Henning Kelbaek, at TCT 2007, Washington, DC

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Title: Surgical Treatments for Ischemic Heart Failure Hypothesis 2 (STICH)
Trial Sponsor: National Heart, Lung, and Blood Institute; and National Institutes of Health
Year Presented: 2009
Year Published 2009
Topic(s): Cardiovascular Surgery, Heart Failure/Transplant
Summary Posted: 3/16/2010 9:00:00 AM
Writer: Ms. Sabina A. Murphy
Author Disclosure: Consulting Fees: Eli Lilly
Reviewer: Deepak L. Bhatt, M.D., M.P.H., F.A.C.C.
Author Disclosure: Research/Research Grants: Astra Zeneca; Consultant Fees/Honoraria: Duke Clinical Research Institute; Research/Research Grants: Heartscape; Research/Research Grants: PLx Pharma; Research/Research Grants: Cogentus; Research/Research Grants: Sanofi Aventis; Data Safety Monitoring Board (Gov’t/Nonprofit): Duke Clinical Research Institute; Research/Research Grants: Bristol Myers Squibb; Research/Research Grants: Eisai; Research/Research Grants: Takeda; Research/Research Grants: The Medicines Company; Research/Research Grants: Ethicon
Supplemental Reviewer: Dharam J. Kumbhani, M.D., S.M.
Author Disclosure: This author has nothing to disclose.

Related Resources
Summary Slide: STICH Trial
Presentation Slides: STICH QOL
Presentation Slides: STICH
Related Trial: Coronary Artery Surgery Study (CASS)
Guideline: Heart Failure in Adults: 2009 Focused Update of the 2005 Guidelines for the Diagnosis and Management of
CVN: STICH Trial: CABG vs CABG + SVR

Description
The goal of the trial was to evaluate medical therapy versus surgical therapy for patients with obstructive coronary disease and congestive heart failure.
Hypothesis
Coronary artery bypass grafting (CABG) with surgical ventricular reconstruction (SVR) in patients with anterior-apical regional left ventricular (LV) dysfunction would be superior to CABG alone in reducing death and cardiac hospitalization, and improving quality of life.
Drugs/Procedures Used
Patients with coronary artery disease and anterior-apical regional LV dysfunction were randomized to CABG (n = 499) or CABG + SVR (n = 501).
Concomitant Medications
For the CABG and CABG + SVR groups: beta-blockers (85%, 87%), angiotensin-converting enzyme inhibitor (80%, 82%), digoxin (17%, 14%), diuretics (69%, 66%), aspirin (77%, 77%), and statins (79%, 75%)
Principal Findings
No significant differences in baseline clinical characteristics were present between groups. However, more arterial conduits were utilized in patients undergoing CABG alone. SVR added a median of 27 minutes of cardiopulmonary bypass time to the procedure. A greater reduction in LV end-systolic volume index (LVESVI) was observed in the SVR group (-19% vs. -6%, p < 0.001). However, there was no significant difference in the primary endpoint of death and cardiac hospitalization (58% vs. 59%, p = 0.90). There was no greater improvement in New York Heart Association heart failure classification or Canadian Cardiovascular Society angina classification with SVR in addition to CABG.

Quality of life, as assessed by the Kansas City Cardiomyopathy Questionnaire, Seattle Angina Questionnaire, and Center for Epidemiological Studies Depression Scale, was not significantly different between groups. In the US cohort, medical costs were greater with CABG + SVR than with CABG alone ($70,717 vs. $56,122, p = 0.004).

In a subgroup of 595 patients in whom LVESVI could be calculated, patients with a baseline LVESVI ≤90 ml/m2 had a significant reduction in mortality with CABG + SVR, as compared with CABG alone (hazard ratio [HR] 0.59, 95% confidence interval [CI] 0.35-1.00, p = 0.05). However, in patients with LVESVI >90 ml/m2, there was no difference between the two groups (HR 1.24, 95% CI 0.75-2.06, p = 0.41).
Interpretation
The STICH trial represents the first multicenter randomized trial of CABG + SVR in patients with coronary artery disease. Although SVR was demonstrated to reduce LVESV to a greater extent than CABG alone, this result did not translate into an improvement in cardiovascular morbidity or mortality in this study. Based on these results, routine SVR at the time of CABG should not be recommended at this time. Although there seemed to be a mortality benefit in patients with an LVESVI <90 ml/m2 (normal LVESVI ~25 ml/m2), this is exploratory, and needs to be confirmed in further studies.

The hypothesis 1 substudy of the STICH trial, comparing medical therapy alone with medical therapy + CABG, is ongoing.
Conditions
• Heart failure
• Heart failure / Ischemic
Therapies
• CABG
Study Design
Randomized.
Patients Enrolled: 1,000
NYHA Class (% I, II, II, IV): 49% class III or IV
Mean Follow-Up: 48 months
Mean Patient Age: 62 years
% Female: 15%

Mean Ejection Fraction: 28% (median)
Primary Endpoints
For the comparison of medical versus surgical therapy, the primary endpoint is long-term survival.
For the comparison of CABG plus surgical ventricular reconstruction versus CABG alone, the primary endpoint is long-term survival free of cardiac hospitalization.
Secondary Endpoints
Cost-effectiveness and quality of life for each treatment
Exercise capacity
30-day mortality
Cardiac hospitalization
Noncardiac hospitalization
Myocardial infarction
Stroke
Patient Population
Coronary artery disease amenable to CABG
LV ejection fraction ≤35%
Dominant anterior wall akinesia or dyskinesia
Exclusions:
Recent myocardial infarction
Need for aortic valve replacement
Planned percutaneous coronary intervention
Noncardiac disease resulting in a life expectancy <3 years
References: Presented by Dr. Robert E. Michler at the ACC.10/i2 Summit, Atlanta, GA, March 2010.

Surgical Treatment for Ischemic Heart Failure (STICH) Trial: CABG Versus CABG + SVR. Presented by Drs. Robert H. Jones and Daniel Mark at ACC.09/i2, Orlando, FL, March 2009.

Jones RH, Velazquez EJ, Michler RE, et al., on behalf of the STICH Hypothesis 2 Investigators. Coronary bypass surgery with or without surgical ventricular reconstruction. N Engl J Med 2009;360:1705-17.

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Title: Lenient Versus Strict Rate Control in Patients With Atrial Fibrillation
Topic: Arrhythmias
Date Posted: 3/15/2010
Author(s): Van Gelder CI, Groenveld HF, Crijns HJ, et al.
Citation: N Engl J Med 2010;Mar 15:[Epub ahead of print].
Clinical Trial: yes
Related Resources
Trial: Rate Control Efficacy in Permanent Atrial Fibrillation: A Comparison Between Lenient Versus Strict Rate Control II (RACE II)

Study Question: Does strict heart rate (HR) control improve outcomes in patients with persistent atrial fibrillation (AF)?
Methods: In this multicenter study, 614 patients (mean age 68 years) with persistent AF were randomized to lenient HR control (n = 311, resting HR <110/minute) or strict HR control (n = 303, HR <80/minute at rest and <110/minute during moderate exercise) using beta-blockers, calcium-channel blockers, and/or digoxin. Follow-up was every 2 weeks until HR targets were reached and at 1, 2, and 3 years. The 1° endpoint was a composite of cardiovascular death, heart failure hospitalization, stroke, embolism, major hemorrhage, and major arrhythmic events.
Results: The HR targets were reached in 98% of patients in the lenient-control group and 67% of patients in the strict-control group, and the mean HRs after dose-adjustment were 93 bpm and 76 bpm in the two groups, respectively. There was no significant difference in the 3-year incidence of the 1° endpoint between the lenient-control (12.9%) and strict-control (14.9%) groups. A similar proportion of patients (approximately 46% in each group) had symptoms from AF at the end of the study.
Conclusions: Strict HR control does not improve outcomes or symptoms compared to lenient HR control in patients with persistent AF.
Perspective: The AFFIRM study used the same target HRs that were used in the strict-control group of this study, and the target HRs were achieved in >80% of patients. Yet in this study, adequate HR control was achieved in only 67% of patients in the strict-control group. Therefore, the study does not rule out the possibility that successful implementation of a strict-control strategy improves outcomes or symptoms compared to a lenient HR-control strategy. Fred Morady, M.D., F.A.C.C.

Title: Progression From Paroxysmal to Persistent Atrial Fibrillation: Clinical Correlates and Prognosis
Topic: Arrhythmias
Date Posted: 3/12/2010
Author(s): De Vos CB, Pisters R, Nieuwlaat R, et al.
Citation: J Am Coll Cardiol 2010;55:725-731.
Clinical Trial: No
Related Resources
JACC Article: Progression From Paroxysmal to Persistent Atrial Fibrillation: Clinical Correlates and Prognosis

Study Question: What are the predictors of arrhythmia progression in patients with paroxysmal atrial fibrillation (AF)?
Methods: The data in this study were gathered from 1,219 patients (mean age 64 years) with paroxysmal AF who were entered into the Euro Heart Survey on AF. Progression of paroxysmal to persistent AF was evaluated at 1 year of follow-up.
Results: Progression to persistent AF occurred in 15% of patients. The independent predictors of AF progression were history of heart failure (odds ratio [OR], 2.2), history of stroke/transient ischemic attack (OR, 2.0), age >75 years (OR, 1.6), chronic obstructive pulmonary disease (OR, 1.5), and hypertension (OR, 1.5). A scoring system (HATCH) was developed based on these five predictors. Approximately 50% of patients with a HATCH score of 6-7 had AF progression, compared with only 6% of patients with a HATCH score of 0.
Conclusions: Paroxysmal AF progresses to persistent AF at 1 year of follow-up in approximately 15% of patients. AF progression is associated with factors that predispose to atrial structural remodeling, including heart failure, hypertension, and age.
Perspective: It is noteworthy that treatment with rhythm-control drugs was not a negative predictor of AF progression. This suggests that a pharmacological rhythm-control strategy is unlikely to be effective in the face of factors that promote atrial structural remodeling. The efficacy of catheter ablation of paroxysmal AF in preventing AF progression in the presence of these factors remains to be well-defined. Fred Morady, M.D., F.A.C.C.

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Title: Lead Extraction in the Contemporary Setting: The LExICon Study. An Observational Retrospective Study of Consecutive Laser Lead Extractions
Topic: Arrhythmias
Date Posted: 3/9/2010
Author(s): Wazni O, Epstein LM, Carrillo RG, et al.
Citation: J Am Coll Cardiol 2010;55:579-586.
Clinical Trial: No
Related Resources
JACC Article: Lead Extraction in the Contemporary Setting: The LExICon Study. An Observational Retrospective Study of Consecutive Laser Lead Extractions

Study Question: How safe and effective is laser-assisted lead extraction (LALE)?
Methods: This was a multicenter, retrospective analysis of 1,449 consecutive patients (mean age 63 years) who underwent LALE of 1,684 pacemaker leads and 703 defibrillator leads in 2004-2007. Complete success was defined as removal of all lead material and partial success was defined as removal of all but <4 cm of the lead.
Results: The median lead age was 82 months. The two most common indications for extraction were infection (57%) and a nonfunctional lead (27%). LALE was completely successful in 96.5% and partially successful in 2.3% of patients. Predictors of procedure failure were a body mass index <25 kg/m2, lead age >10 years, and an extraction volume of <60 cases/4 years. A major adverse event (MAE) occurred in 4% of patients, and a MAE directly related to LALE (most commonly cardiac avulsion or vascular tear) occurred in 1.4%. In-hospital mortality was 1.9%, and mortality directly related to LALE was 0.3%. The predictors of in-hospital mortality were a history of pocket infection, endocarditis, diabetes, and renal insufficiency.
Conclusions: LALE has a high success rate and a low rate of MAEs. In-hospital mortality is largely a function of comorbidities.
Perspective: Prior to the advent of laser sheaths, the success rate of lead extraction using locking stylets and telescoping sheaths was approximately 65%. With the use of laser sheaths, studies published in 1999-2002 reported success rates of 90-94%. The present study indicates that technological refinements in the laser sheaths and additional operator experience have improved the success rate of LALE in contemporary practice to approximately 98%. Fred Morady, M.D., F.A.C.C.

Title: Percutaneous Pacemaker and Implantable Cardioverter-Defibrillator Lead Extraction in 100 Patients With Intracardiac Vegetations Defined by Transesophageal Echocardiogram
Topic: Arrhythmias
Date Posted: 3/9/2010
Author(s): Grammes JA, Schulze CM, Al-Bataineh M, et al.
Citation: J Am Coll Cardiol 2010;55:886-894.
Clinical Trial: No
Related Resources
JACC Article: Percutaneous Pacemaker and Implantable Cardioverter-Defibrillator Lead Extraction in 100 Patients With Intracardiac Vegetations Defined by Transesophageal Echocardiogram

Study Question: Can lead extraction be safely accomplished in patients with endocarditis and intracardiac vegetations?
Methods: This was a retrospective review of 100 patients (mean age 67 years) who underwent extraction of an infected lead and had an intracardiac vegetation by transesophageal echocardiography. The timing of reimplantation depended on resolution of the vegetations and blood culture sterility.
Results: The mean diameter of vegetations was 1.6 cm (range 0.2-4 cm). Two hundred leads with a mean implant duration of 51 months were extracted percutaneously and no patient required a surgical intervention. The most common pathogens were methicillin-resistant and methicillin-sensitive Staphylococcus aureus. Embolization of a vegetation occurred in 2/100 patients (2%). A new pacemaker or implantable cardioverter defibrillator was implanted in 54% of patients a median of 7 days after extraction and none had a relapse of infection during a mean follow-up of 15 months. Long-term follow-up data were available in 71 patients. Among these patients, in-hospital mortality rate was 14% and late mortality was 13%. The most common cause of death was septicemia.
Conclusions: Standard techniques for percutaneous lead extraction are safe and effective in patients with intracardiac vegetations as large as 4 cm.
Perspective: Patients with an intracardiac vegetation often undergo thoracotomy and lead extraction under direct visualization to avoid septic embolization during percutaneous lead extraction. This study demonstrates that percutaneous lead extraction can be accomplished safely by a skilled operator even in the presence of intracardiac vegetations. However, operator experience is an important determinant of outcomes and should be taken into consideration when deciding on percutaneous versus surgical lead extraction. Fred Morady, M.D., F.A.C.C.

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Достижения по врожденным порокам сердца за прошлый год

Title: The Year in Congenital Heart Disease
Topic: Congenital Heart Disease
Date Posted: 3/9/2010
Author(s): Graham TP, Jr.
Citation: J Am Coll Cardiol 2010;55:147-155.
Clinical Trial: No
Related Resources
JACC Article: The Year in Congenital Heart Disease

Perspective: The following are 10 points to remember about the past year in congenital heart disease:

1. van den Berg et al. studied exercise performance, biventricular reserve, and N-terminal pro-B-type natriuretic peptide, and exercise performance in relation to right ventricular (RV) volume in patients following repair of tetralogy of Fallot (TOF) at less than 2 years of age. At mid-term follow-up, all parameters were well-preserved, and unrelated to RV volume (Int J Cardiol 2009;133:363-70).

2. Knauth et al. used cardiac magnetic resonance to predict clinical outcomes in patients with TOF, with a median time from clinical repair to evaluation of 21 years. Adverse outcomes, defined as death, sustained ventricular tachycardia (VT), and increase in New York Heart Association functional class to grade II or IV, occurred in 21% of patients. Severe RV dilation and right or left ventricular systolic dysfunction predicted major adverse events (Heart 2008;94:211-6).

3. In an additional study of pulmonary insufficiency after tetralogy repair, Harrild and colleagues compared patients with TOF and RV dilatation who had undergone pulmonary valve replacement, as compared with those who had not. No significant differences were seen in sudden death, VT, or a combined endpoint of sudden death/VT in patients who had undergone pulmonary valve replacement (Circulation 2009;119:445-51).

4. Shiraishi et al. studied the impact of the age at Fontan on exercise capacity, hemodynamics, and ventricular function in children with systemic left ventricles. VO2max, left ventricular ejection fraction, and cardiac index were all higher in patients undergoing Fontan at <3 years of age (Ann Thorac Surg 2009;87:555-61).

5. The Nationwide Inpatient Sample was used by Karamlou and colleagues to determine surgical practice patterns for adults with congenital heart disease. In-hospital mortality was lower (1.87%) for adults operated on by pediatric heart surgeons, as compared with 4.84% for those operated on by nonpediatric heart surgeons (Circulation 2008;118:2345-52).

6. Vida et al. studied the optimal timing of patent ductus arteriosus ligation in premature infants. Medical treatment was successful in 149 of 201 patients. More than two cycles of ibuprofen were associated with increased risk for bronchopulmonary dysplasia and acute renal failure (Ann Thorac Surg 2009;87:1509-16).

7. Bovй et al. investigated 93 children following the arterial switch procedure for D-transposition of the great arteries (D-TGA). At a mean follow-up of 5 years, aortic regurgitation >2+ developed in 10% of patients with D-TGA with intact ventricular septum and 23% of patients with D-TGA and ventricular septal defect (VSD). Freedom from re-intervention at 1, 5, and 10 years was 98%, 96%, and 96% for D-TGA/intact VSD and 65%, 63%, and 63% for D-TGA/VSD (Ann Thorac Surg 2008;85:823-30).

8. Because of a previous study implicating balloon atrial septostomy (BAS) as a cause of brain injury, Petit and colleagues reported on magnetic resonance imaging of patients prior to surgical repair of TGA. Of 26 patients, 14 underwent BAS. No strokes occurred, although 10 of 26 patients were found to have hypoxic brain injury in the form of periventricular leukomalacia. No association was seen between this finding and BAS. Infants with periventricular leukomalacia had lower preoperative oxygenation and longer time to surgery than infants without the finding (Circulation 2009;119:709-16).

9. Sharma et al. reported outcomes of children undergoing anatomic repairs for congenitally corrected TGA. A total of 31 patients underwent an atrial switch/Rastelli procedure with 17% early deaths and no late deaths. A total of 37 patients underwent a ‘double switch’ with 13.5% early mortality and 10.8% late mortality. An additional four patients required re-operations, four had left ventricular ejection fraction <40%, five had moderate aortic regurgitation, and five patients had symptomatic tricuspid insufficiency, one with tricuspid stenosis, and one with superior vena cava obstruction (J Thorac Cardiovasc Surg 2009;137:404-12).

10. Tabbutt et al. studied neurodevelopmental outcomes for 83 infants undergoing staged palliation for hypoplastic left heart syndrome at 1 year of age. The neuromuscular examination was abnormal or suspect in 65% of patients. The mean Mental Developmental Index score was 90, and 20 patients had scores <70. The mean Psychomotor Development Index was 74, with 42 patients having scores <70. In multivariate analysis, younger gestational age, presence of a genetic syndrome, and need for preoperative intubation had negative effects on neurodevelopmental outcomes. Operative factors, including duration of deep hypothermic circulatory arrest, were not shown to impact neurodevelopmental outcomes (Pediatrics 2008;121:476-83). Timothy B. Cotts, M.D., F.A.C.C.

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Title: Efficacy and Safety of Zotarolimus-Eluting and Sirolimus-Eluting Coronary Stents in Routine Clinical Care (SORT OUT III): A Randomised Controlled Superiority Trial
Topic: Interventional Cardiology
Date Posted: 3/15/2010
Author(s): Rasmussen K, Maeng M, Kaltoft A, et al., on behalf of the SORT OUT III Study Group.
Citation: Lancet 2010;Mar 15:[Epub ahead of print].
Clinical Trial: yes
Related Resources
Trial: Comparison of Zotarolimus-Eluting Stents and Sirolimus-Eluting Stents in Patients With Coronary Artery Disease (SORT OUT III)

Study Question: What is the safety and efficacy of the zotarolimus-eluting stent (ZES) compared with the sirolimus-eluting stent (SES) in patients with coronary artery disease who are receiving routine clinical care?
Methods: The authors performed a single-blind superiority trial comparing SES to ZES in all adult patients with chronic stable coronary artery disease or acute coronary syndromes undergoing percutaneous coronary intervention (PCI) at five high-volume centers in Denmark. Follow-up data were obtained from national administrative and health care registries. The primary endpoint was a composite of cardiac death, myocardial infarction, and target vessel revascularization events within 9 months. Intention-to-treat analyses were done at 9 and 18 months.
Results: The study randomized 1,162 patients to the ZES and 1,170 to a SES. The randomly allocated stent was implanted in 1,589 (98%) lesions allocated to the ZES and 1,569 (97%) lesions allocated to SES (p = 0.15). Six patients were lost to follow-up. All other patients were included in analyses at 30-day and 9-month follow-up. Eighteen-month follow-up was completed for 94% of the patients. At 9 months, patients treated with a ZES were more likely to have met the primary endpoint (6% vs. 3%; hazard ratio, 2.15; 95% confidence interval, 1.43-3.23; p = 0.0002). This difference was sustained at 18 months (10% vs. 5%; 2.19; 1.58-3.04; p < 0.0001). There was no difference in the all-cause mortality at 9 months (2% vs. 2%), whereas it was higher in the ZES patients at 18 months (4% vs. 3%; 1.03-2.50; p = 0.035).
Conclusions: The SES is superior to the ZES for patients undergoing PCI in routine clinical practice.
Perspective: Multiple studies have evaluated the relative efficacy and safety of a SES and a paclitaxel-eluting stent (PES), and most (but not all) of them suggest better outcomes with the SES. Data on comparative efficacy of the ZES and the everolimus-eluting stent (EES) are rather limited. The SPIRIT IV and COMPARE trials suggest that the EES is probably safer and more efficacious than the PES. The relative position of the ZES in the DES spectrum is harder to define. This trial suggests a lower rate of target lesion revascularization with SES that is not surprising since the SES has better anti-restenotic efficacy. The Endeavour III trial had demonstrated a late catch-up phenomenon with the SES, and longer-term follow-up of the SORT OUT III trial will be needed to establish the relative long-term safety and efficacy of ZES and SES. Hitinder S. Gurm, M.B.B.S., F.A.C.C

Title: Low Diagnostic Yield of Elective Coronary Angiography
Topic: Interventional Cardiology
Date Posted: 3/10/2010 4:00:00 PM
Author(s): Patel MR, Peterson ED, Dai D, et al.
Citation: N Engl J Med 2010;362:886-895.
Clinical Trial: No
Study Question: What is the diagnostic yield of coronary angiography among patients with coronary artery disease (CAD) in a contemporary national sample?
Methods: From January 2004 to April 2008, at 663 hospitals in the American College of Cardiology National Cardiovascular Data Registry, the authors identified patients without known CAD who were undergoing elective cardiac catheterization. The patients' demographic characteristics, risk factors, and symptoms and the results of noninvasive testing were correlated with the presence of obstructive CAD, which was defined as stenosis of 50% or more of the diameter of the left main coronary artery, or stenosis of 70% or more of the diameter of a major epicardial vessel.
Results: A total of 398,798 patients were included in the study. The median age was 61 years; 52.7% of the patients were men, 26% had diabetes, and 69.6% had hypertension. Noninvasive testing was performed in 83.9% of the patients. At catheterization, 149,739 patients (37.6%) had obstructive CAD. No CAD (defined as <20% of stenosis in all vessels) was reported in 39.2% of patients. Independent predictors of obstructive CAD included male sex (odds ratio [OR], 2.70; 95% confidence interval [CI], 2.64-2.76); older age (OR per 5-year increment, 1.29; 95% CI, 1.28-1.30); presence of insulin-dependent diabetes (OR, 2.14; 95% CI, 2.07-2.21); and presence of dyslipidemia (OR, 1.62; 95% CI, 1.57-1.67). Patients with a positive result on a noninvasive test were moderately more likely to have obstructive CAD than those who did not undergo any testing (41.0% vs. 35.0%, p < 0.001; adjusted OR, 1.28; 95% CI, 1.19-1.37).
Conclusions: The authors concluded that in this study, only a minority of patients without known coronary disease who underwent elective cardiac catheterization had obstructive CAD.
Perspective: This analysis of a contemporary national sample of patients suggests that only a minority of patients undergoing coronary angiography have obstructive CAD. The assessment of coronary stenosis was made by the interpreting/performing physician and it is possible that more stringent assessment may further lower the fraction of patients with obstructive CAD. It should also be noted that this study addresses only overutilization and not underutilization of coronary angiography in appropriate patients. However, it is obvious from this study that the current strategies used to make decisions for proceeding to coronary angiography, including clinical assessment and noninvasive testing, need substantial modification and improvement to increase the diagnostic yield of coronary angiography and prevent over- or underutilization to improve overall quality of patient care. Debabrata Mukherjee, M.D., F.A.C.C.

[Chevychelov]

Title: Endovascular Stenting for Vertebral Artery Stenosis
Topic: Interventional Cardiology
Date Posted: 3/11/2010
Author(s): Jenkins JS, Patel SN, White CJ, et al.
Citation: J Am Coll Cardiol 2010;55:538-542.
Clinical Trial: No
Related Resources
JACC Article: Endovascular Stenting for Vertebral Artery Stenosis

Study Question: Is catheter-based therapy for symptomatic vertebral artery stenosis (VAS) safe and durable?
Methods: One-hundred five patients from 1995-2006 with symptomatic VAS (112 arteries, 71% male) underwent stent placement for extracranial (91%) and intracranial (9%), primarily in the V1 segment (83%). By angiography, 57 patients (54%) had bilateral VAS, 71 patients (68%) had concomitant carotid disease, and 43 patients (41%) had a prior stroke.
Results: A total of 133 stents were placed, which were primarily balloon-expandable bare metal (114). Procedural and clinical success was achieved in 105 (100%) and 95 (90.5%) patients, respectively. One-year follow-up was obtained in 87 (82.9%) patients, of which 69 patients (79.3%) remained symptom-free. Median follow-up was 29.1 months, with 74% of patients asymptomatic at last follow-up. At 1 year, 6 patients (5.7%) had died and 5 patients (5%) had a posterior circulation stroke.
Conclusions: The authors concluded that in “experienced hands,” stenting for symptomatic VAS has a very high procedural and clinical success rate, with few periprocedural complications, and is associated with durable symptom resolution in the majority of patients. They concluded that "endovascular stenting of vertebral artery atherosclerotic disease is safe and effective compared with surgical controls” (historical controls implied) “and should be considered first-line therapy for this disease.”
Perspective: Symptomatic VAS is a morbid and lethal disease, carrying a 5-year 30-35% risk of stroke and a 2-year mortality for medically managed patients of 30%. Despite this relative failure of medical therapy to prevent strokes in these patients, surgical revascularization is rarely performed, also due to the relatively high morbidity and mortality rates associated with surgery. Clearly, an endovascular option for the treatment of these patients is obviously attractive. While most of these stents were placed in the proximal vertebral artery, which has been reported to be less treacherous for stenting than the V2-V4 vertebral artery segments, the present report contains an order of magnitude of more patients than the next largest series. The authors of this large series document outstanding results, stenting a cohort of complex patients with vertebrobasilar disease. Let’s see if this approach becomes standard of care for this disease. Gilbert Upchurch, Jr., M.D.

Title: Effects of Combination Lipid Therapy in Type 2 Diabetes Mellitus
Topic: Prevention/Vascular
Date Posted: 3/14/2010
Author(s): The ACCORD Study Group.
Citation: N Engl J Med 2010;Mar 14:[Epub ahead of print].
Clinical Trial: yes
Related Resources
Trial: Action to Control Cardiovascular Risk in Diabetes Lipid Trial (ACCORD Lipid)

Study Question: Does combination therapy with a statin plus a fibrate, as compared with statin monotherapy, reduce risk for cardiovascular disease (CVD) in patients with type 2 diabetes who are at high risk for CVD?
Methods: The Action to Control Cardiovascular Risk in Diabetes (ACCORD) study was designed to examine the effects of intensive blood glucose control and either blood pressure or plasma lipid control on cardiovascular outcomes. The trial includes 10,251 diabetics from 77 sites in the United States and Canada. In the ACCORD Lipid study, 5,518 subjects were treated with open-label simvastatin (40 mg/day or less), with randomization of masked fenofibrate or placebo. All subjects had type 2 diabetes, defined as glycated hemoglobin (HgA1c) of 7.5% or greater and were at high risk for CVD (defined as evidence of clinical CVD [age 40-79 years] or two additional risk factors [age range 55-79 years]). Baseline lipid criteria included having a low-density lipoprotein cholesterol (LDL-C) between 60 and 180 mg/dl, high-density lipoprotein cholesterol (HDL-C) of 55 or less for women or blacks, 50 or less for all others, and triglycerides below 750 mg/dl not on lipid therapy (400 mg/dl if on lipid-lowering therapy). Fasting lipids were measured at 4, 8, and 12 weeks and annually thereafter. Secondary outcomes included the combination of the primary outcomes and revascularization or hospitalization for congestive heart failure. The primary outcomes of interest were first occurrence of nonfatal myocardial infarction, nonfatal stroke, or CVD death. Mean follow-up was 4.7 years.
Results: Subjects had a mean age of 62 years, 31% were female and 37% had a history of CVD. Use of statin therapy prior to enrollment was present in 66% of the study population. Mean LDL-C on treatment was 81.1 mg/dl in the fibrate group and 80.0 mg/dl in the placebo group. Mean HDL-C on treatment was 41.2 mg/dl in the fibrate group and 40.5 mg/dl in the placebo group. Annual rate of CVD events was 2.2% in the fenofibrate plus simvastatin groups and 2.4% in the placebo group (hazard ratio [HR], 0.92; 95% confidence interval [CI], 0.79-1.08; p = 0.32). No significant differences between the two groups were observed for the secondary outcomes (HR, 0.94; 95% CI, 0.85-1.05; p = 0.30). Annual rates of death were 1.5% in the fenofibrate group and 1.6% in the placebo group (HR, 0.91; 95% CI, 0.75-1.10). In prespecified subgroup analysis, men appeared to have a benefit as opposed to women (p = 0.01 for interaction). In addition, the investigators observed a possible interaction according to the lipid subgroup, with a potential benefit for patients with both high triglycerides and low HDL-C levels at baseline (p = 0.057 for interaction).
Conclusions: The authors concluded that simvastatin plus fenofibrate did not reduce nonfatal myocardial infarction or stroke, and also did not reduce CVD mortality compared to simvastatin alone. Thus, these findings from ACCORD Lipid do not support the use of combination therapy (statin plus a fibrate) in high-risk patients with diabetes.
Perspective: This study provides data for clinicians treating diabetes who are at high risk for CVD, suggesting that therapy with statins should remain the core management strategy in prevention of CV events. However, the subgroup analysis warrants further evaluation; given the difference observed in benefits related to gender, statins without fibrate may be the treatment strategy of choice. Elizabeth A. Jackson, M.D., F.A.C.C.

[Chevychelov]

Title: Effects of Intensive Blood-Pressure Control in Type 2 Diabetes Mellitus
Topic: Prevention/Vascular
Date Posted: 3/14/2010
Author(s): The ACCORD Study Group.
Citation: N Engl J Med 2010;Mar 14:[Epub ahead of print].
Clinical Trial: yes
Related Resources
Trial: Action to Control Cardiovascular Risk in Diabetes Blood Pressure Trial (ACCORD BP)

Study Question: Does lowering systolic blood pressure (SBP) to <120 mm Hg reduce risk for cardiovascular disease (CVD) in patients with type 2 diabetes?
Methods: The Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial was designed to examine the effects of intensive blood glucose control and either blood pressure or plasma lipid control on cardiovascular outcomes. The trial includes 10,251 diabetics from 77 sites in the United States and Canada. In the ACCORD BP study, 4,733 subjects were randomized to intensive therapy for a goal SBP <120 mm Hg or standard therapy for a goal SBP of <140 mm Hg. All subjects had type 2 diabetes defined as glycated hemoglobin ≥7.5%, and were at high risk for CVD (defined as evidence of clinical CVD (age 40-79 years) or two additional risk factors (age range 55-79 years). Exclusion criteria included a body mass index >45, a serum creatinine of 1.5 mg/dl or greater, or protein excretion rate of <1.0 g. Baseline SPB had to be between 130 and 180 mm Hg on three or fewer antihypertensives. The primary outcomes of interest were nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. The secondary outcomes included the combination of the primary outcomes and revascularization or hospitalization for congestive heart failure. Mean follow-up was 4.7 years. Clinic visits were monthly for the first 4 months, then every 2 months thereafter.
Results: Mean age was 62 years for this study population, with 47.7% women and 37% having a history of CVD. After 1 year, the on-treatment SBP was 119.3 mm Hg in the intensive therapy group and 133.5 mm Hg in the standard therapy group. The annual rate of primary outcome events was 1.8% in the intensive therapy group and 2.09% in the standard therapy group (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.73-1.06; p = 0.20). The annual rate of all-cause mortality was 1.28% for the intensive therapy group and 1.19% for the standard therapy group (HR, 1.07; 95% CI, 0.85-1.35; p = 0.55). The annual rate of stroke was 0.32% in the intensive therapy group and 0.53% in the standard therapy group (HR, 0.59; 95% CI, 0.39-0.89; p = 0.01). Reduced rates of nonfatal stroke were observed for the intensive therapy group (HR, 0.63; 95% CI, 0.41-0.96; p = 0.03). No significant differences were noted for major CVD events (fatal coronary events, nonfatal myocardial infarction, and unstable angina) (HR, 0.94; 95% CI, 0.79-1.12; p = 0.50) and fatal or nonfatal heart failure (HR, 0.94; 95% CI, 0.70-1.26; p = 0.67). Serious adverse events attributed to the antihypertensive treatment occurred in 3.3% of the intensive treatment group and 1.3% of the standard treatment group (p < 0.001).
Conclusions: The investigators concluded that among patients with type 2 diabetes who are at high risk for cardiovascular events, lowering SBP to <120 mm Hg did not reduce rates of fatal or nonfatal major cardiovascular events compared to a goal of SBP of <140 mm Hg.
Perspective: This landmark study adds to our understanding of management goals for high-risk diabetics and does not support aggressive lowering of SBP in high-risk diabetics. However, whether a blood pressure goal of <130 mm Hg provides significant benefit as compared to <140 mm Hg remains unanswered. Elizabeth A. Jackson, M.D., F.A.C.C.

Title: Effect of Valsartan/Nateglinide on the Incidence of Diabetes and Cardiovascular Events
Topic: Prevention/Vascular
Date Posted: 3/14/2010
Author(s): The NAVIGATOR Study Group.
Citation: N Engl J Med 2010;Mar 14:[Epub ahead of print], and N Engl J Med 2010;Mar 14:[Epub ahead of print].
Clinical Trial: yes
Related Resources
Trial: Nateglinide And Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR)

Study Question: Does use of short-acting insulin secretagogues and/or rennin-angiotensin-blockers reduce the risk of diabetes or cardiovascular (CV) events among patients with impaired glucose tolerance?
Methods: The NAVIGATOR study was designed as a 2 x 2 factorial, double-blind, randomized trial of patients with impaired glucose tolerance and either established CV disease (CVD) or risk factors for CVD. Patients were randomized to valsartan (up to 160 mg daily) or placebo and to nateglinide (up to 60 mg three times per day) or placebo and to valsartan (up to 160 mg/day) or placebo. Subjects also received lifestyle modification. Impaired fasting glucose tolerance was defined as a fasting plasma glucose concentration between 95 mg/dl and 125 mg/dl. Patients were excluded if they had taken antidiabetic medication within the prior 5 years. Participants were followed for a median of 5.0 years (median 6.5 years for vital status), with the primary outcomes being incident diabetes and CV events (CVD death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure). The third primary outcome, extended composite CV outcomes, includes the core CV events (listed above) together with hospitalization for unstable angina or arterial revascularization.
Results: A total of 9,518 participants (mean age 63 years, 50% female) from 40 countries were enrolled in the study between January 2002 and January 2004. A total of 1,674 subjects developed diabetes during the follow-up period (36.0% in the nateglinide group and 33.9% in the placebo group). A total of 1,365 subjects experienced a CV event (14.2% in the nateglinide group and 15.2% in the placebo group). After adjustment for multiple comparisons, nateglinide did not significantly reduce cumulative incidence of diabetes, as compared with placebo (hazard ratio [HR], 1.07; 95% confidence interval [CI], 1.00-1.15; p = 0.05). CV outcomes also did not differ between subjects randomized to nateglinide or placebo (HR, 0.94; 95% CI, 0.82-1.09; p = 0.43 for core composite outcomes and HR, 0.93; 95% CI, 0.83-1.03; p = 0.16 for extended composite outcomes). Approximately 10% of the study population lost 5% of their baseline body weight, with those in the placebo group having a lower mean body weight compared to those in the nateglinide group. Mean waist circumference was also lower in the placebo group, as compared to the nateglinide group. Rates of adverse events did not differ in the two groups.

The cumulative incidence of diabetes was 33.1% in the valsartan group and 36.8% in the placebo group, with a significantly reduced risk for incidence of diabetes observed in the valsartan group (HR, 0.98; 95% CI, 0.80-0.92; p < 0.001). No difference was observed in extended CV outcomes (14.5% vs. 14.8%; HR, 0.96; 95% CI, 0.86-1.07; p = 0.43) or core CV outcomes (8.1% vs. 8.1%; HR, 0.99; CI, 0.86-1.14; p = 0.85).
Conclusions: The investigators concluded that among patients with impaired glucose tolerance and either established CVD or risk factors for CVD, nateglinide for 5 years did not reduce the incidence of diabetes or CV events. Use of valsartan for 5 years did not lead to reduction in the rate of CV events; however, a relative reduction (14%) was observed for incidence of diabetes.
Perspective: This large study of nateglinide and valsartan for prevention of diabetes and/or CVD was largely negative, with no benefit observed in reduction of CV outcomes for either drug, and a small benefit observed with valsartan in reduction of diabetes. In the face of prior studies, continued use of aggressive lifestyle modification, which has been shown to reduce these outcomes, as opposed to use of nateglinide and/or valsartan, is recommended. Elizabeth A. Jackson, M.D., F.A.C.C.

[Chevychelov]

Title: Effects of β blockers and Calcium-Channel Blockers on Within-Individual Variability in Blood Pressure and Risk of Stroke
Topic: Prevention/Vascular
Date Posted: 3/12/2010
Author(s): Rothwell PM, Howard SC, Dolan E, et al.
Citation: Lancet Neurol 2010;Mar 12:[Epub ahead of print].
Clinical Trial: No
Related Resources
Journal Scan: Prognostic Significance of Visit-to-Visit Variability, Maximum Systolic Blood Pressure, and Episodic Hypertension

Study Question: What are the effects of beta-blockers and calcium-channel blockers on variability in blood pressure (BP), and do they explain the disparities in effect on stroke risk?
Methods: The Anglo-Scandinavian Cardiac Outcomes Trial Blood Pressure Lowering Arm (ASCOT-BPLA) compared amlodipine-based regimens with atenolol-based regimens in 19,257 patients with hypertension and other vascular risk factors, and the Medical Research Council (MRC) trial compared atenolol-based and diuretic-based regimens versus placebo in 4,396 hypertensive patients ages 65-74 years. The investigators expressed visit-to-visit variability of BP during follow-up in the two trials as standard deviation (SD) and as transformations uncorrelated with mean BP. For ASCOT-BPLA, they also studied within-visit variability and variability on 24-hour ambulatory blood pressure monitoring (ABPM).
Results: In ASCOT-BPLA, group systolic BP (SBP) SD was lower in the amlodipine group than in the atenolol group at all follow-up visits (p < 0.0001), mainly because of lower within-individual visit-to-visit variability. Within-visit and ABPM variability in SBP were also lower in the amlodipine group than in the atenolol group (all p < 0.0001). Analysis of changes from baseline showed that variability decreased over time in the amlodipine group and increased in the atenolol group. The lower risk of stroke in the amlodipine group (hazard ratio, 0.78; 95% CI, 0.67-0.90) was partly attenuated by adjusting for mean SBP during follow-up (0.84, 0.72-0.98), but was abolished by also adjusting for within-individual SD of clinic SBP (0.99, 0.85-1.16). Findings were similar for coronary events. In the ABPM substudy, reduced variability in daytime SBP in the amlodipine group (p < 0.0001) partly accounted for the reduced risk of vascular events, but reduced visit-to-visit variability in clinic SBP had a greater effect. In the MRC trial, group SD SBP and all measures of within-individual visit-to-visit variability in SBP were increased in the atenolol group compared with both the placebo group and the diuretic group during initial follow-up (all p < 0.0001). Subsequent temporal trends in variability in BP during follow-up in the atenolol group correlated with trends in stroke risk.
Conclusions: The authors concluded that the opposite effects of calcium-channel blockers and beta-blockers on variability of BP account for the disparity in observed effects on risk of stroke.
Perspective: The current study suggests that patients with good control of mean BP, but a high residual variability in SBP had a five times higher risk of stroke than did those with low residual SBP variability in ASCOT-BPLA. Atenolol-based treatment and amlodipine-based treatment had opposite effects on within-individual variability in BP independent of their effects on mean BP. The reduced event rates in the amlodipine group, which could not be fully accounted for by changes in mean BP or in other risk factors, may possibly be explained by effects on visit-to-visit variability in SBP. These findings may have implications for the routine management of hypertension, particularly the choice of medication, since specific agents may have different effects on variability of BP leading to differences in clinical efficacy. Additional studies are indicated to assess treatment effects and clinical outcomes in relation to variability in BP. Debabrata Mukherjee, M.D., F.A.C.C.