Обзор американских кардиологических журналов за неделю (ссылки)

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Trial Summary GRAVITAS
Title: Gauging Responsiveness with A VerifyNow Assay—Impact on Thrombosis And Safety
Trial Sponsor: Accumetrics
Year Presented: 2010
Topic(s): General Cardiology, Interventional Cardiology, Prevention/Vascular
Summary Posted: 11/16/2010
Writer: Anthony A. Bavry, M.D., M.P.H., F.A.C.C.
Author Disclosure: NOTHING TO DISCLOSE
Reviewer: Deepak L. Bhatt, M.D., M.P.H., F.A.C.C.
Reviewer Disclosure: RESEARCH/RESEARCH GRANTS: Astra Zeneca(SIGNIFICANT), Eisai(SIGNIFICANT), Sanofi Aventis(SIGNIFICANT), The Medicines Company(SIGNIFICANT), Ethicon(SIGNIFICANT), Bristol Myers Squibb(SIGNIFICANT), Heartscape(SIGNIFICANT), Cogentus(NONE), PLx Pharma(NONE), Takeda(NONE)

Description:

The goal of the trial was to evaluate treatment with an additional loading dose and higher maintenance dose of clopidogrel compared with no additional loading dose and standard maintenance dose of clopidogrel among patients with high residual platelet activity after percutaneous coronary intervention (PCI).
Hypothesis:

An additional loading dose and higher maintenance dose of clopidogrel will be more effective at preventing cardiovascular outcomes.
Drugs/Procedures Used:
Patients with high residual platelet activity after PCI with drug-eluting stents were randomized to clopidogrel 600 mg post-PCI, then 150 mg daily (n = 1,109) versus no additional loading dose and 75 mg daily (n = 1,105).

Platelet activity was assessed by the VerifyNow P2Y12 test 12-24 hours after PCI. High residual platelet activity was defined as a platelet reactivity unit ≥230.
Concomitant Medications:

All patients received aspirin 81-162 mg daily.
Principal Findings:
Overall, 2,214 patients were randomized. In the high-clopidogrel dose group, the mean age was 64 years, 35% were women, 44% had diabetes, 60% had stable angina, and total stent length was 30 mm. At 30 days, persistently high platelet reactivity was present in 40% of the high-clopidogrel dose group versus 62% of the standard-dose group (p < 0.001).

The primary outcome of cardiovascular death, myocardial infarction, or stent thrombosis occurred in 2.3% of the high-clopidogrel dose group versus 2.3% of the standard-dose group (p = 0.98). The primary outcome was compared among patients with high platelet reactivity treated with standard-dose clopidogrel versus screened/nonrandomized patients who had low platelet reactivity: 2.3% versus 1.4% (p = 0.20).

GUSTO moderate or severe bleeding occurred in 1.4% versus 2.3% (p = 0.10), whereas any GUSTO bleeding occurred in 12.1% versus 10.3% (p = 0.18), respectively.
Interpretation:
Among patients with high residual platelet reactivity after PCI with drug-eluting stents, treatment with high-dose clopidogrel was not beneficial. High-dose clopidogrel for 6 months did not reduce the primary ischemic outcome; however, GUSTO moderate or severe bleeding was not increased. Routine testing of platelet reactivity after PCI is not warranted. It is unknown if a more potent antiplatelet agent would have achieved different results.
Study Design:
Blinded. Parallel. Randomized. Placebo Controlled.
Primary Endpoints:
Composite of cardiovascular death, myocardial infarction, or stent thrombosis at 6 months
Secondary Endpoints:
GUSTO moderate or severe bleeding
Patient Population:
Patients undergoing PCI with a drug-eluting stent for stable or unstable coronary syndromes

Number of screened applicants: 5,429
Number of enrollees: 2,214
Duration of follow-up: 6 months
Mean patient age: 64 years
Percentage female: 35%
Exclusions:
Bleeding event prior to platelet function testing
Recent use of a glycoprotein IIb/IIIa inhibitor
References:
Presented by Dr. Matthew Price at the American Heart Association Scientific Sessions, Chicago, IL, November 16, 2010.

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Trial Summary BASKET-PROVE
Title: Basal Stent Kosten-Effektivitats Trial‒Prospective Validation Examination
Trial Sponsor: Basel Cardiovascular Research Foundation, and Swiss National Foundation for Research
Year Presented: 2010
Year Published: 2010
Topic(s): Interventional Cardiology, General Cardiology, Prevention/Vascular
Summary Posted: 11/16/2010
Writer: Anthony A. Bavry, M.D., M.P.H., F.A.C.C.
Author Disclosure: NOTHING TO DISCLOSE
Reviewer: Deepak L. Bhatt, M.D., M.P.H., F.A.C.C.
Reviewer Disclosure: RESEARCH/RESEARCH GRANTS: Astra Zeneca(SIGNIFICANT), Eisai(SIGNIFICANT), Sanofi Aventis(SIGNIFICANT), The Medicines Company(SIGNIFICANT), Ethicon(SIGNIFICANT), Bristol Myers Squibb(SIGNIFICANT), Heartscape(SIGNIFICANT), Cogentus(NONE), PLx Pharma(NONE), Takeda(NONE)

Description:

The goal of the trial was to compare percutaneous coronary intervention (PCI) with sirolimus-eluting stents versus everolimus-eluting stents versus bare-metal stents among patients with coronary artery disease.
Hypothesis:

Adverse cardiovascular outcomes will be similar between drug-eluting stents and bare-metal stents in large coronary arteries.
Drugs/Procedures Used:

Patients undergoing coronary artery disease were randomized to sirolimus-eluting stents (n = 775), everolimus-eluting stents (n = 774), or bare-metal stents (n = 765).
Concomitant Medications:

Aspirin 75-100 mg daily indefinitely and clopidogrel 75 mg daily for 1 year
Principal Findings:
Overall, 2,314 patients were randomized. There was no difference in baseline characteristics between participants. In the sirolimus-eluting stent group, the mean age was 66 years, 26% were women, 18% had diabetes, ST-elevation myocardial infarction (MI) was present in 34%, and mean total stent length per patient was 30 mm. The proportion of patients on aspirin and clopidogrel at 1 year was 82% and at 2 years was 19%.

The primary outcome, death from cardiac causes or nonfatal MI, was 2.6% in the sirolimus-eluting stent group, 3.2% in the everolimus-eluting stent group, and 4.8% in the bare-metal stent group (p = 0.13 for sirolimus-eluting vs. bare-metal stents and p = 0.37 for everolimus-eluting vs. bare-metal stents).

Target vessel revascularization occurred in 4.3% of the sirolimus-eluting stent group, 3.7% of the everolimus-eluting stent group, and 10.3% of the bare-metal stent group (p = 0.005 for sirolimus-eluting vs. bare-metal stents and p = 0.002 for everolimus-eluting vs. bare-metal stents). Cardiac death occurred in 1.7%, 1.7%, and 2.9% (p = NS), nonfatal MI occurred in 0.9%, 1.7%, and 2.6% (p = NS), and definite stent thrombosis occurred in 0.4%, 0.3%, and 0.8% (p = NS), respectively, for sirolimus-eluting, everolimus-eluting, and bare-metal stents.
Interpretation:

Among patients undergoing PCI with a 3-4 mm diameter stent, there was no difference in the composite outcome of cardiovascular death or nonfatal MI between drug-eluting versus bare-metal stents. Sirolimus- and everolimus-eluting stents were associated with reduced need for long-term revascularization (~4% rate) compared with bare-metal stents (~10% rate). Stent thrombosis was similar between stent types. Compliance with long-term dual antiplatelet therapy was high, which may have contributed to lower than expected cardiovascular outcomes. This reduced the ability of the trial to detect a difference in cardiovascular outcomes between treatment groups. Another limitation of the trial is that one-third of events were adjudicated in a nonblinded fashion.
Study Design:
Randomized. Parallel.
Primary Endpoints:
Death from cardiovascular cause or nonfatal MI at 2 years
Secondary Endpoints:
Target vessel revascularization
Stent thrombosis
Patient Population:
Patients with acute or chronic coronary artery disease undergoing PCI with a 3-4 mm diameter stent

Number of screened applicants: 2,323
Number of enrollees: 2,314
Duration of follow-up: Median 2 years
Mean patient age: 66 years
Percentage female: 26%
Exclusions:
Cardiogenic shock
Treatment of in-stent restenosis or thrombosis
Unprotected left main PCI
Bypass graft stenosis
Anticipated surgery within 12 months
Need for anticoagulation
Increased risk for bleeding
Noncompliance to long-term antiplatelet therapy
References:

Kaiser C, Galatius S, Erne P, et al. Drug-eluting versus bare-metal stents in large coronary arteries. N Engl J Med 2010;Nov 16:[Epub ahead of print].

Presented by Dr. Christoph Kaiser at the American Heart Association Scientific Sessions, Chicago, IL, November 16, 2010.

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Trial Summary TAMARIS
Title: NV1FGF Gene Therapy on Amputation-Free Survival in Critical Limb Ischemia
Trial Sponsor: Sanofi-Aventis
Year Presented: 2010
Topic(s): General Cardiology, Interventional Cardiology, Prevention/Vascular
Summary Posted: 11/16/2010
Writer: Anthony A. Bavry, M.D., M.P.H., F.A.C.C.
Author Disclosure: NOTHING TO DISCLOSE
Reviewer: Deepak L. Bhatt, M.D., M.P.H., F.A.C.C.
Reviewer Disclosure: RESEARCH/RESEARCH GRANTS: Astra Zeneca(SIGNIFICANT), Eisai(SIGNIFICANT), Sanofi Aventis(SIGNIFICANT), The Medicines Company(SIGNIFICANT), Ethicon(SIGNIFICANT), Bristol Myers Squibb(SIGNIFICANT), Heartscape(SIGNIFICANT), Cogentus(NONE), PLx Pharma(NONE), Takeda(NONE)

Description:
The goal of the trial was to evaluate treatment with NV1FGF gene therapy compared with placebo among patients with critical limb ischemia.

NV1FGF is a nonviral recombinant DNA plasmid, containing a gene encoding FGF1, which promotes proliferation of vascular cells.
Hypothesis:

Local delivery of NV1FGF gene therapy will improve amputation-free survival.
Drugs/Procedures Used:

Patients with critical limb ischemia unsuitable for revascularization were randomized to eight intramuscular injections of NV1FGF gene therapy (n = 259) versus intramuscular injections of placebo (n = 266). Injections occurred on days 1, 15, 29, and 43.
Principal Findings:
Overall, 525 patients were randomized. In the gene therapy group, the mean age was 71 years, 31% were women, 52% had diabetes, 59% were current or former smokers, 23% had prior myocardial infarction, 15% had prior stroke, and 20% had prior congestive heart failure.

Death or major amputation at 12 months occurred in 37% in the gene therapy group versus 33% in the placebo group (p = 0.48). Death occurred in 18% versus 15% (p = 0.53), and major amputation occurred in 26% versus 21% (p = 0.31), respectively. Serious adverse events occurred in 61% versus 59%, malignant neoplasm occurred in 2.6% versus 1.6% (p = 0.55), and retinal disorder occurred in 4.1% versus 5.8% (p = 0.42), respectively.
Interpretation:

Among patients with critical limb ischemia, there was no benefit (or important safety signals) at 12 months from intramuscular gene therapy compared with placebo. Treatment of patients with advanced lower extremity vascular disease remains challenging.
Study Design:
Blinded. Randomized. Placebo Controlled. Parallel.
Primary Endpoints:
Composite of death or major amputation at 12 months
Secondary Endpoints:
All amputations
Death
Ulcer healing
Pain relief
Functional status
Patient Population:
Patients at least 50 years of age with lower extremity ischemic ulcer or gangrene
Unsuitable for revascularization
Ankle pressure <70 mm Hg, or toe pressure <50 mm Hg, or a transcutaneous oxygen pressure ≤30 mm Hg in the treated leg
Inflow to the femoral artery confirmed by imaging
Negative cancer screen

Number of enrollees: 525
Duration of follow-up: 12 months
Mean patient age: 71 years
Percentage female: 31%
Exclusions:
Major amputation of the treated leg
Infected gangrene
Nonischemic ulcer
Cardiovascular event in the last 3 months
Proliferative retinopathy
References:

Presented by Dr. William Hiatt at the American Heart Association Scientific Sessions, Chicago, IL, November 16, 2010.

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Trial Summary ACT
Title: Acetylcysteine for the prevention of Contrast-induced nephropaThy
Trial Sponsor: Ministry of Health Brazil
Year Presented: 2010
Topic(s): General Cardiology, Interventional Cardiology, Prevention/Vascular
Summary Posted: 11/16/2010
Writer: Anthony A. Bavry, M.D., M.P.H., F.A.C.C.
Author Disclosure: NOTHING TO DISCLOSE
Reviewer: Deepak L. Bhatt, M.D., M.P.H., F.A.C.C.
Reviewer Disclosure: RESEARCH/RESEARCH GRANTS: Astra Zeneca(SIGNIFICANT), Eisai(SIGNIFICANT), Sanofi Aventis(SIGNIFICANT), The Medicines Company(SIGNIFICANT), Ethicon(SIGNIFICANT), Bristol Myers Squibb(SIGNIFICANT), Heartscape(SIGNIFICANT), Cogentus(NONE), PLx Pharma(NONE), Takeda(NONE)

Description:

The goal of the trial was to evaluate treatment with acetylcysteine compared with placebo among patients at risk for contrast-induced nephropathy (CIN) undergoing an angiographic procedure.
Hypothesis:

Acetylcysteine will be superior at preventing CIN.
Drugs/Procedures Used:

Patients at risk for CIN were randomized to acetylcysteine 1200 mg twice daily for 2 days (n = 1,172) versus placebo (n = 1,136). Patients in both groups underwent prehydration with normal saline or bicarbonate.
Principal Findings:
Overall, 2,308 patients were randomized. In the acetylcysteine group, the mean age was 68 years, 38% were women, 15% had chronic renal failure, 61% had diabetes, 67% underwent diagnostic coronary angiography, and the mean volume of contrast delivered was 100 cc.

The primary outcome, CIN, occurred in 12.7% of the acetylcysteine group versus 12.7% of the placebo group (p = 0.97). Doubling of serum creatinine occurred in 1.1% versus 1.5% (p = 0.41), total mortality occurred in 2.0% versus 2.1% (p = 0.80), cardiovascular mortality occurred in 1.5% versus 1.6% (p = 0.93), need for dialysis occurred in 0.3% versus 0.3% (p = 0.97), and serious adverse events occurred in 1.3% versus 2.2% (p = 0.09), respectively, for acetylcysteine versus placebo.
Interpretation:

Among patients at risk for CIN undergoing an angiographic procedure, the use of acetylcysteine was not effective at preventing CIN or important clinical outcomes. This represents the largest and most definitive trial on the topic. Adequate prehydration remains the principal measure to prevent CIN.
Study Design:
Blinded. Placebo Controlled. Randomized.
Primary Endpoints:
CIN defined as 25% increase in creatinine from baseline
Secondary Endpoints:
Total mortality
Cardiovascular mortality
Dialysis
Doubling of serum creatinine
Side effects
Patient Population:
Patients at risk of CIN undergoing an angiographic procedure
Risk factors for CIN defined as age >70 years, chronic renal failure, diabetes, heart failure, left ventricular ejection fraction <45%, or shock

Number of enrollees: 2,308
Duration of follow-up: 30 days
Mean patient age: 68 years
Percentage female: 38%
References:

Presented by Dr. Otavio Berwanger at the American Heart Association Scientific Sessions, Chicago, IL, November 16, 2010.

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Meeting News
Title: Comparative Effectiveness Of Exercise Electrocardiography Versus Exercise Electrocardiography Plus Myocardial Perfusion SPECT In Women With Suspected Coronary Artery Disease: Results From The What’s The Optimal Method For Ischemia Evaluation In Women Trial
Event: AHA 2010
Topic(s): General Cardiology, Noninvasive Cardiology
Presenter: Leslee Shaw
Writer(s): Xiushui Ren
Date Posted: 11/16/2010

Summary

In women with low-intermediate CAD likelihood and who are capable of exercising, exercise ECG testing is more cost-effective than exercise myocardial perfusion testing, with similar outcomes at two years.
Background

In women with suspected CAD, myocardial perfusion (using single photon emission computed tomography) with exercise ECG (ECG+MPS) is frequently added to exercise ECG testing (Ex ECG) because of known false positives of Ex ECG alone in this population. However, The effectiveness of Ex ECG compared to Ex ECG+MPS as a strategy for diagnosis and prognosis in women with suspected CAD is unknown.
Study Design

The What is the Optimal Method for Ischemia Evaluation in Women (WOMENs) trial is a multicenter study comparing Ex ECG to ECG+MPS in women with suspected CAD with low-intermediate CAD likelihood and who were capable of performing exercise testing. Women randomized to the Ex ECG group underwent standard or modified Bruce protocol with standard ECG criteria for ischemia. For women assigned to the ECG+MPS group, summed stress score (SSS) was calculated based on American Society of Nuclear Cardiology recommendations. ECG and MPS were interpreted at local sites.

The primary endpoint was a combination of major adverse cardiac events (MACE), which consisted of CAD death, MI, or hospital admission for unstable angina or heart failure. Events were adjudicated by an external committee blinded to randomization.
Results and Conclusions

A total of 44 centers enrolled 824 women. At baseline, the two groups were similar. The mean age was 63 years, and 78% of women were post-menopausal. The presenting symptom was chest pain in 90% of women, and dyspnea in 50%. The mean METs achieved during testing was 8.5, and 88% of women achieved at least 85% of age-predicted maximal heart rate. At least 1 mm of stress-induced ST-segment deviation occurred in 35% of women.

Exercised-related ECG results for both groups were not statistically different between the two groups, with about 65% categorized as normal, 15% equivocal, and 20% abnormal. MPS result was normal in 90% of women (in the ECG+MPS group). At 2-year follow-up, the MACE-free survival by testing group was similar (~98%). Using coronary angiography as the gold standard, Ex ECG had a sensitivity and specificity of 33% and 59%, respectively, whereas ECG+MPS had a sensitivity and specificity of 73% and 71%, respectively. Over the 2-year follow-up, 18% of women in the Ex ECG group crossed over to receive ECG+MPS, and 9% of women in the ECG+MPS group had repeat ECG+MPS, p<0.001. The median total cost of testing (including initial cost and follow-up cost) for was $174 for Ex ECG group and $493 for ECG+MPS group, p<0.001).

Thus Ex ECG and ECG+MPS had similar outcome at two years with Ex ECG being more cost-effective.
Perspective

It is important to note that, because both groups had very low event rates (MACE of 2%) over two years, the statistical power to detect potential differences is limited. In addition, this trial studied relatively low-risk women with suspected chest pain, and the results should not to be generalized to other populations such as women with higher risk or with poor functional capacity.
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Meeting News
Title: PROTECT: Benefits of Natriuretic Peptide Guided Heart Failure Therapy for Patients with Chronic Left Ventricular Systolic Dysfunction: Primary Results of the Pro-BNP Outpatient Tailored Chronic Heart Failure Therapy (PROTECT) Study
Event: AHA 2010
Topic(s): Cardiac Biomarker, General Cardiology, Heart FailureTransplant
Presenter: James Januzzi
Writer(s): Xiushui Ren
Date Posted: 11/16/2010
Summary

In patients with systolic heart failure, NT-proBNP-guided therapy was superior to standard HF therapy in reducing adverse cardiac outcomes and improving quality of life.
Background

In patients with chronic heart failure (HF), concentrations of amino-terminal pro-B type natriuretic peptide (NT-proBNP) are associated with the presence and severity of HF and predict outcome.

One of several randomized trials of chronic HF patients showed that standard HF therapy plus BNP-guided therapy (not NT-proBNP) was superior to standard HF treatment alone, largely through an increase in angiotensin-converting enzyme inhibitors (ACE-I) and beta-blocker dosages. A meta-analysis of these trials confirmed the findings the BNP-guided HF therapy may be beneficial. However, it is unclear whether NT-proBNP tailor HF therapy is superior to standard HF as previous trials with heterogeneous patient populations have returned mixed results.
Study Design

This is a prospective, single-center trial of 151 patients with systolic HF. Patients were randomized to receive either standard HF therapy plus a goal to reduce NT-proBNP ≤1000 pg/mL versus standard HF therapy alone. Inclusion criteria included age of at least 21 years, LV ejection fraction ≤ 40%, NYHA class II to IV symptoms, and acute heart failure therapy within previous 6 months. Exclusion criteria included serum creatinine > 2.5 mg/dl, expected heart transplant or coronary revascularization in the next six months, severe lung disease, PCI or CABG in previous 3 months, and inoperable valve disease.

Patients were seen every three months plus additional visits if necessary.

The primary endpoint was total cardiovascular events, a combination of worsening HF, HF hospitalization, acute coronary syndrome, ventricular arrhythmia, cerebral ischemia, and cardiovascular death. Secondary endpoints included effects of NT-proBNP-guided care on quality of life (QOL) assessed with the Minnesota Living with HF Questionnaire, and cardiac structure and function.
Results and Conclusions

At baseline, the two treatment arms were similar. The mean age was 63 years, and 85% were men. The mean LV ejection fraction was 26%, and 85% of patients were NYHA class II or III. Implantable defibrillators were present in 67% of patients, and cardiac resynchronization therapy (biventricular pacemaker) was present in 40%. There was no significant difference in baseline medical therapy, with 95% use of beta-blockers, 66% ACE-inhibitor, 50% aldosterone antagonist, and 90% loop diuretics.

After a mean follow up of 10±3 months, patients in the NT-proBNP group had a reduction in total cardiovascular events as compared with standard HF group (58 versus 100 events; P =.009). Kaplan-Meier curves demonstrated significant differences in time to first event, favoring NT-proBNP guided care (P =.03). No age interaction was found. Patients in the NT-proBNP group also had greater improvements in QOL and had greater relative improvements in LV ejection fraction, LV end-systolic index, and LV end-diastolic volume index.

At follow-up, the NT-proBNP and standard HF groups had similar beta-blocker use (97% and 96%, respectively, p=0.56) and ACE-inhibitor use (56% and 46%, p=0.20). However, the NT-proBNP group had more aldosterone antagonist use (63% vs. 45%, p=0.001), less loop diuretic use (85% vs. 96%, p=0.05), and less angiotensin receptor blocker use (12% vs. 22%, p=0.05). NT-proBNP was not significantly changed over follow-up in the control group (1946 pg/ml vs. 1844 pg/ml, p=0.61), but significantly decreased in the NT-proBNP group (2344 pg/ml vs. 1125 pg/ml, p=0.01).
References

Jourdain P, Jondeau G, Funck F, et al. Plasma brain natriuretic peptide-guided therapy to improve outcome in heart failure: the STARS-BNP Multicenter Study. J Am Coll Cardiol. 2007 Apr 24;49(16):1733-9.

Porapakkham P, Porapakkham P, Zimmet H, Billah B, Krum H. B-type natriuretic peptide-guided heart failure therapy: A meta-analysis. Arch Intern Med. 2010 Mar 22;170(6):507-14.

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Meeting News
Title: CICERO: Event: Intracoronary Versus Intravenous Abciximab in ST-Elevation Myocardial Infarction: Results of the CICERO Trial in Patients Undergoing Primary Percutaneous Coronary Intervention With Thrombus Aspiration
Topic(s): Interventional Cardiology
Presenter: Youlan L Gu
Writer(s): Xiushui Ren
Date Posted: 11/16/2010

Summary

In patients undergoing primary PCI for STEMI, intracoronary vs. intravenous administration of abciximab did not improve myocardial reperfusion as assessed by ST-segment resolution but did lead to improved myocardial blush grade and a smaller enzymatic infarct size.
Background

Abciximab is a glycoprotein IIb/IIIa inhibitor used as an adjunctive agent during primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI). Although small studies have shown that intracoronary (IC) administration of abciximab reduces infarct size as compared with intravenous (IV) administration, IV administration is more widely used.

The current study sought to compare IC administration of abciximab with IV administration in improving myocardial reperfusion in patients undergoing primary PCI with thrombus aspiration.
Study Design

This is a single-center, prospective, randomized, open-label trial of 534 consecutive patients with STEMI undergoing primary PCI with thrombus aspiration within 12 hours of symptom onset. Patients were pre-treated with aspirin, heparin, and clopidogrel. After thrombus aspiration, patients were randomized to either IC (through the coronary guide catheter) or IV abciximab. Abciximab (IC or IV) was given as a bolus at 0.25 mg/kg without infusion. Exclusion criteria included rescue PCI, need for coronary bypass surgery, and cardiogenic shock.

The primary endpoint was myocardial reperfusion, defined as complete ST-segment resolution. Secondary endpoints included myocardial reperfusion as assessed by myocardial blush grade, enzymatic infarct size peak creatinine kinase CK, CK-MB, troponin, and major adverse cardiac events (MACE) at 30 days. Endpoints were evaluated in a blinded fashion.
Results and Conclusions

Baseline characteristics were similar between the two groups. The mean age was 64 years, and 74% were men. Diabetics comprised 12% of the population, and 47% of MIs were anterior. Thrombus aspiration was formed in 98% of patients, and stent implantation was performed 95%.

The incidence of complete ST-segment resolution (>70% ST-segment resolution) was similar between IC and IV groups (64% versus 62%, respectively, p=0.56). The incidence of myocardial blush grade 2 or 3 was higher in the IC group than in the IV group (76% versus 67%, respectively, p=0.02). Enzymatic infarct size was approximately 30% smaller in the IC than in the IV group (peak CK 1214 U/L vs. 1746 U/L, respectively, p<0.008). The incidence of MACE was similar (5.5% in IC versus 6.1% in IV, p=0.786). The incidence of TIMI major bleeding was also similar (3.7% in IC versus 3.4% in IV, p=0.867).
Perspective
This agent is not approved for use with intracoronary administration, but these findings are consistent with the benefit on infarct size seen in other studies. It is also worthy noting the differences in reperfusion rate as measured by ST-segment resolution and myocardial blush grade. This discrepancy has been previous studies. Finally, whether abciximab IC bolus followed by IV infusion is superior to IC bolus alone is not known.
References
Thiele H, Schindler K, Friedenberger J, et al. Intracoronary compared with intravenous bolus abciximab application in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention: the randomized Leipzig immediate percutaneous coronary intervention abciximab IV versus IC in ST-elevation myocardial infarction trial. Circulation. 2008 Jul 1;118(1):4.
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EMPHASIS-HF: Eplerenone reduced death, hospitalization by 37% in systolic HF

American Heart Association Scientific Sessions 2010

CHICAGO — Eplerenone was associated with a 37% reduction in the risk of death or hospitalization among patients with systolic HF, according to data from the EMPHASIS-HF trial.

Currently, aldosterone antagonists, including eplerenone, are only recommended in patients with moderate to severe HF and reduced heart function or among patients with HF who have had a recent MI.

Patients from 272 sites in 29 countries were randomly assigned 25 to 50 mg eplerenone (n=1,364; 21 patients were lost to follow-up or did not receive the study drug) or placebo (1,373; 19 patients were lost to follow-up or did not receive the study drug). The median follow-up was 21 months. The primary endpoint was CV death or hospitalization for HF.

Eplerenone was associated with a significant decrease in CV death or hospitalization for HF (HR=0.63; 95% CI, 0.54-0.74) and a 24% reduction in mortality from any cause (HR=0.76; 95% CI, 0.62-0.93). In addition, eplerenone reduced the rate of hospitalization for any cause by 23% (HR=0.77; 95% CI, 0.67-0.88) and the rate of HF hospitalization by 42% (HR=0.58; 95% CI, 0.47-0.70).

“The conclusions are straightforward: In patients with systolic HF and mild symptoms, the addition of eplerenone to recommended medical therapy was well tolerated, improved survival and prevented hospitalization,” Faiez Zannad, MD, PhD, professor of therapeutics at the University of Nancy in France, said during a press conference. “Of course we need to take this into context of the RALES AND EPHESUS trials and this, again, shows a very important external validity and consistency with the earlier trials, and provides compelling evidence to change medical practice.”

Zannad reports receiving grants and contracts from Pfizer, and has also consulted for Pfizer. – by Stacey Fisher

For more information:
Zannad F. LBCT I, Abstract 23221. Presented at: American Heart Association Scientific Sessions 2010; Nov. 13-17; Chicago.

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RAFT: CRT, ICD plus medical therapy beneficial in patients with mild-to-moderate HF

American Heart Association Scientific Sessions 2010

CHICAGO — Rates of mortality and hospitalization were lower in patients with mild-to-moderate HF who were treated with cardiac resynchronization therapy, implantable cardioverter defibrillators and medical therapy compared with those treated with implantable cardioverter defibrillators and medical therapy alone, new study data suggested.

The RAFT was a parallel, randomized control trial featuring patients with NYHA class II or III HF, left ventricular ejection fraction ¡Ü30% and wide QRS duration. In addition to medical therapy, patients received either an ICD (n=904) or an ICD with cardiac resynchronization therapy (CRT; n=894).

After a mean follow-up of 40 months, the primary outcome of composite of all-cause mortality or hospitalization for HF was observed in 33.2% of patients in the ICD-CRT arm and 40.3% of those in the ICD arm (ICD-CRT HR=0.75; 95% CI, 0.64-0.87). The secondary outcomes all favored the ICD-CRT group, including rates of death from any cause (6.1% vs. 20.8%; P=.003), death from CV cause (17.9% vs. 14.5%; P=.019) and rates of hospitalization for HF (26.1% vs. 19.5; P¡Ü.0001).

Among patients in this study, Anthony S.L. Tang, MD, with the Royal Jubilee Hospital, Victoria, British Columbia, Canada, and trial researcher concluded in a news conference, ¡°The addition of CRT to ICD reduces death and hospitalization for HF, and reduces all-cause mortality with an absolute reduction of 6% over a treatment period of 5 years. This translates to 14 patients needing to be treated for 5 years to prevent one death. We also demonstrated that [CRT plus ICD] reduces hospitalization for HF, translating to 11 patients needing to be treated for 5 years to prevent one hospitalization for HF.¡±

Dr. Tang has received research support MedTronic, St. Jude Medical and Boston Scientific. - by Brian Ellis

For more information:
Tang ASL. LBCT I, Abstract 21768 . Presented at: American Heart Association Scientific Sessions 2010; Nov. 13-17; Chicago.

The first statement that can be made is that there is no longer any need for equipoise. It is very clearly evident that the ICD-CRT combination works and works well in patients with mild-to-moderate HF.

The next thing that represents a take home [message] is that we will have to revisit our clinical practice guidelines and understand that we will need to expand the indications from those with class III or ambulatoryclass IV HF to those that have lesser degrees of HF with regards to severity. Importantly, we should then anticipate that to a certain extent clinical practice should change. But we also need to be somewhat circumspect. We¡¯re waiting for the cost-effectiveness data from this investigation. We have to understand there is a finite risk of certain morbid events that are important to patients, and we increasingly struggle with how be best characterize the phenotype of patient that responds to CRT.
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ASCEND-HF: Nesiritide did not improve outcomes in decompensated HF

American Heart Association Scientific Sessions 2010

CHICAGO – Nesiritide was not associated with a statistically significant reduction in dyspnea, rehospitalization or death among patients with acute decompensated HF, according to late-breaking data from the ASCEND-HF trial.

Researchers enrolled 7,141 patients with severe HF to determine whether nesiritide (Natrecor, Scios) was superior to placebo in reducing the HF-related hospitalization rate or all-cause mortality at 30 days and improvement in dyspnea at six or 24 hours. Safety endpoints included all-cause mortality, renal function and both symptomatic and asymptomatic hypotension.

Patients were randomly assigned to continuous intravenous nesiritide or placebo plus standard treatment for 30 days.

Compared with placebo, nesiritide was not associated with a reduction in 30-day death or HF rehospitalization (10.1% vs. 9.4%; P=.31). Nesiritide improved dyspnea at 6 hours (15.0% vs. 13.4%; P=.030) and at 24 hours compared vs. placebo (30.4% vs. 27.5%; P=.007), but the differences did not meet the study’s protocol criteria for statistical significance.

“No evidence of a major benefit lead us to a situation as an executive committee to say that, in terms of clinical implications, we need to show people the data and they can make their decisions about the value of the effect of this drug on dyspnea,” Robert M. Califf, MD, researcher and vice chancellor for clinical research at Duke University School of Medicine in Durham, said during a press conference. “It certainly does not have a long-term effect on clinical outcomes one way or the other.”

Data from previous meta-analyses linked nesiritide with reduced renal function. However, data from ASCEND-HF showed no association between the two. According to Califf, there was an expected increase in hypotension among patients in the treatment arm vs. placebo (26.6% vs. 15.3%; P<.001).

“[W]hat I think is most important about this trial [is that] we constantly put drugs on the market without doing the right outcome trials,” Califf said. “If this outcome trial had been done earlier, clinicians and patients would’ve had a much better idea of the potential, very limited role of this treatment but they also would’ve known that it was not harmful.”

Dr. Braunwald reports receiving research support from Johnson and Johnson and is a member of the Cardiorentis Scientific Advisory Board. - by Stacey L. Fisher

For more information:
Califf R. LBCT I, Abstract 21828. Presented at: American Heart Association Scientific Sessions 2010; Nov. 13-17; Chicago.

The good news for nesiritide from the ASCEND-HF trial [is that] it does not support the concerns raised by Sackner-Bernstein and colleagues in their two meta-analyses. [There is] no evidence of nesiritide being associated with an increased risk for mortality and renal dysfunction. This really joins the FUSION II trial conducted by Yancy and colleagues. The less good news for nesiritide is that the trial provides very little evidence that its addition would improve the outcome of patients with acute decompensated HF who are receiving excellent standard care. The economic implications for widespread use of a drug with these effects are self evident. ASCEND-HF joins a large number of other trials conducted with a variety of agents since the 1970s in acute HF who have not shown clinical benefit. How to improve outcomes in this very common condition remains a serious challenge.

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ADVANCE: Experimental LVAD comparable to approved bridge-to-transplant devices

American Heart Association Scientific Sessions 2010

CHICAGO — A novel ventricular assist device implanted in patients with advanced HF waiting for transplants was associated with outcomes comparable to those of currently approved bridge-to-transplant devices, according to early results from a nonrandomized study.

Researchers for the ADVANCE study enrolled 140 patients with HF from the United Network for Organ Sharing’s heart-transplant waiting list scheduled to receive the HeartWare left ventricular assist device (HVAD), and 499 comparable control patients with HF on nationwide waiting lists to receive an HVAD. The primary outcome measure was survival and success defined as survival (on the originally implanted device, transplant or explant for ventricular recovery) at 180 and 360 days after implantation. Secondary measures included a comparison of survival between treatment and control groups, as well as functional quality of life outcomes and adverse events in the treatment group.

According to the study results, 92.0% of patients in the treatment group achieved success vs. 90.1% in the control group, with 0.9% difference in the 95% upper confidence limit. This was less than the prespecified 15% noninferiority margin, suggesting that the success in the treatment group was noninferior to the control group (P<.001). The secondary outcome comparison of survival was similar between groups. Patients in the HVAD treatment group also were able to walk 113 meters farther in a six minute walk test than control patients.

“The success rate with this novel device was quite high, survival was quite good, there was a favorable adverse events profile and there were marked improvements in functional class and quality of life similar to what we achieve with cardiac transplantation,” Keith Aaronson, MD, associate professor of internal medicine at the University of Michigan Medical Center in Ann Arbor, said at a press conference. “This provides a new opportunity for patients who require ventricular support as a means to get to a heart transplant.”

Dr. Aaronson reports having received research support from HeartWare, Thoratec and Terumo, and is on the clinical steering committee for HeartWare. - by Eric Raible

For more information:
Aaronson K. LBCT I, Abstract 21723. Presented at: American Heart Association Scientific Sessions 2010; Nov.13-17; Chicago.

The main positive point of this trial is adding an attractive new device with a lot of potential [as a treatment option], for all of the reasons the authors have mentioned. It is small, simple to insert and it does not require a pocket. Importantly, there are also technical innovations in this particular device (a third generation VAD) which could hopefully translate into clinical benefit. This is only the beginning, however, as these are early results.
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Body weight, physical activity critical in cardiorespiratory fitness

American Heart Association Scientific Sessions 2010

CHICAGO — The two most important determinants for optimal cardiorespiratory fitness are body mass index and physical activity, according to an analysis presented at the annual meeting.

Researchers enrolled 20,015 patients who presented for comprehensive medical examinations. Cardiorespiratory fitness was determined via exercise testing, and the researchers developed a physical activity index. The index was divided into five categories (0=inactive; 1=non-running activities; 2=0 to 10 miles per week running; 3=11 to 20 miles per week running; 4=>20 miles per week running), and linear regression modeling was used to determine clinical factors associated with time achieved on the treadmill.

According to the results, age, sex, BMI and physical activity were the factors most associated with fitness, and they explained 56% of the variance of cardiorespiratory fitness. Apart from those, the combined factors of current smoking, systolic BP, glucose, HDL and LDL levels and health status were associated with cardiorespiratory fitness (P<.05).

In addition, the researchers reported a significant relationship between BMI and physical activity on cardiorespiratory fitness, suggesting that individuals with normal body weight achieved higher levels of cardiorespiratory fitness for a given level of physical activity than obese individuals. This interaction was driven by percent body fat rather than lean body mass.

“Body weight and physical activity are the most important modifiable determinants of fitness,” Susan Lakoski, MD, assistant professor of internal medicine at the University of Texas Southwestern Medical Center in Dallas, said in a presentation. “These data suggest that we need to attain normal weight status to obtain the most benefit from physical activity.”

Lakoski reported no relevant disclosures. – by Eric Raible

For more information:
Lakoski S. Abstract 11438. Presented at: American Heart Association Scientific Sessions 2010; Nov. 13-17; Chicago.

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Revascularization improved myocardial ischemia vs. medical therapy in BARI 2D substudy

American Heart Association Scientific Sessions 2010

CHICAGO — Compared with intensive medical therapy, revascularization was associated with near-term improvements in myocardial ischemia in patients with type 2 diabetes and stable coronary artery disease, according to new data from the BARI 2D trial.

Although previous study results demonstrated similar clinical efficacy between revascularization and intensive medical therapy, little information exists regarding their respective influence on postintervention ischemic burden, researchers said.

For the substudy, researchers examined differences in stress myocardial perfusion SPECT abnormalities at 1 year in 1,505 patients enrolled in the BARI 2D trial. All patients who were randomly assigned to revascularization in BARI 2D underwent stress myocardial perfusion SPECT at 1 year compared with 16% of patients assigned to intensive medical therapy.

Results indicated that stress perfusion abnormalities were absent more often in patients who received revascularization compared with patients assigned to intensive medical therapy (P=.002). In addition, patients receiving intensive medical therapy experienced more extensive ischemia involving at least three myocardial segments (P<.001), according to the researchers.

At 3%, patients in the revascularization arm had a lower median quantitative percentage of the myocardium with stress perfusion compared with 9% in patients receiving intensive medical therapy (P=.01). The researchers also noted comparable differences in the percentage of ischemic myocardium among the treatment arms. The percentage of scarred myocardium, however, did not differ between groups.

Fifty-nine percent of patients who underwent revascularization had no inducible ischemia after 1 year compared with 49% of patients receiving intensive medical therapy (P<.001), the researchers said. Data demonstrated a relationship between ischemic burden and higher death rates and major CV events (HR=2.19 for ≥10% stress abnormality vs. 0%; P<.001).

When the researchers adjusted for demographic and clinical factors, analysis revealed a significant association between selected myocardial perfusion SPECT variables and an increased hazard of cardiac death or MI (HR=1.8 for ≥10% stress abnormality vs. 0%; P=.01).

Based on these results, “patient management strategies that focus on ischemia resolution can be useful to guide efficacy of near-term therapeutic approaches,” the researchers concluded.

For more information:
Shaw LJ. Abstract 12697. Presented at: American Heart Association Scientific Sessions 2010; Nov. 13-17, 2010; Chicagо

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Prehypertension linked to low vitamin D

American Heart Association Scientific Sessions 2010

CHICAGO — Low serum vitamin D levels appear to be independently associated with the development of prehypertension, new data suggest.

Researchers conducted a cross-sectional study of 9,215 participants included in the National Health and Nutrition Examination Survey (NHANES) III who were free of hypertension at baseline. Participants were divided into quartiles based on serum vitamin D levels. The main outcome of interest was prehypertension (n=3,712), which was defined as systolic BP of 120 mm Hg to 139 mm Hg or diastolic BP of 80 mm Hg to 89 mm Hg.

According to the results, low serum vitamin D levels were associated with the development of prehypertension, independent of risk factors such as age, sex, race, smoking, alcohol intake, BMI, physical inactivity, diabetes, HDL ratio, CRP and glomerular filtration rate.

When compared with the highest quartile of serum vitamin D (>32.4 ng/mL), the odds of developing prehypertension were increased in the lowest quartile (≤17.7 ng/mL; OR=1.48; 95% CI, 1.16-1.90). On continuous analysis, each standard deviation decrease in vitamin D was associated with an odds ratio of 1.14 (95% CI, 1.05-1.24) for prehypertension.

“These findings are largely consistent with previous studies that examine the association [between low vitamin D levels] and prehypertension,” Charumath Sabanayagam, MD, PhD, of West Virginia University, said during his presentation.

The researchers concluded that future randomized trials are needed to determine if vitamin D supplementation during the prehypertension stage can prevent the onset of full-blown hypertension.

Sabanayagam reported no relevant disclosures. – by Eric Raible

For more information:
Sabanayagam C. Abstract 21058. Presented at: American Heart Association Scientific Sessions 2010; Nov. 13-17; Chicago.

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In postmenopausal women, aromatase predictive of CVD mortality

American Heart Association Scientific Sessions 2010

CHICAGO — An indirect method of measuring aromatase activity in postmenopausal women may also aid in the assessment of 25-year risk for CVD mortality, according to an analysis of participants in the Rancho Bernardo study.

The study researchers examined 817 non-estrogen-treated postmenopausal women aged 50 to 90 years who were enrolled in the Rancho Bernardo study between 1984 and 1987. The participants were then followed for 25 years. They then examined aromatase activity by use of the aromatase activity index, defined as the ratio of serum estrone to androstenedione.

A total of 247 deaths were attributed to CVD, according to the study results. The aromatase index was positively associated with age, BMI and waist-to-hip ratio (P<.01 for all relationships). Following adjustment for age, adiposity and lifestyle, proportional hazards regression analysis suggested that CVD mortality was higher in women in the lowest (P=.002) and highest (P=.043) quintiles of aromatase index compared with the middle quintiles.

Serum estrone and androstenedione levels alone were not predictive of CVD mortality, and aromatase index was not related to non-CVD death.

“These findings suggest that aromatase may be a novel endocrine factor that is predictive of CV mortality among postmenopausal women, but additional studies are needed to determine whether the association of aromatase with CV death reflects genetic influences or perhaps some underlying disease influences that we did not test,” Gail A. Laughlin, PhD, assistant adjunct professor of medicine at the University of California San Diego Medical Center in La Jolla, said in her presentation. “If confirmed, these results raise concerns about the long-term CV health of a large number of breast cancer patients who are now being treated with aromatase inhibitors.”

Laughlin reports no relevant disclosures. – by Eric Raible

For more information:
Laughlin G. Abstract 13804. Presented at: American Heart Association Scientific Sessions 2010; Nov. 13-17; Chicago.
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Symptoms of obese HF patients improved after bariatric surgery

American Heart Association Scientific Sessions 2010

CHICAGO — A small study has found that morbidly obese patients with HF who undergo bariatric surgery gain long-lasting and meaningful improvements in disease symptoms and quality of life.

“This tells us that bariatric surgery may become part of the treatment of patients with HF and obesity if there are no major contraindications for the surgery — and that this might be especially important for patients with significant obesity,” Francisco Lopez-Jiminez, MD, said in a press release.

The study results were presented at the American Heart Association Scientific Sessions 2010.

Lopez-Jiminez cautioned, however, that because the study tested the effects of bariatric surgery on just 13 patients, “these results should be considered preliminary and suggestive of some benefit, but additional research is needed to confirm these results.”

It appears that cardiologists do not often refer obese patients with HF for bariatric surgery, despite statistics showing that one-third of HF patients are obese, Lopez-Jiminez said.

The researchers reviewed the outcomes of 13 patients, aged 44 to 64 years, who underwent bariatric surgery at Mayo Clinic in Minnesota between 1990 and 2005, as well as six HF patients, aged 52 to 72, who were followed at the Mayo Nutrition Clinic and did not receive the surgery.

In the group that received surgery, the mean BMI was 53, and in the comparison group, it was 42. After 4 years of follow-up, the mean BMI dropped in the surgery group to 37 and rose in the comparison group to 45.

Based on patient surveys, the researchers found that quality of life was significantly improved in those who received weight-loss surgery, compared with HF patients who did not. Researchers also determined that symptoms such as swelling in the legs and labored breathing during exercise improved only in the surgery group.

Lopez-Jimenez said that the health advantages seen in the patients who had bariatric surgery occurred even though most remained obese.

“These patients had very advanced levels of obesity before the surgery, and although they lost significant amounts of weight, most remained obese. So, these good results suggest that the benefit does not require patients to reach a normal weight,” he said.

For more information:
Miranda WR. Abstract 19531. Presented at: American Heart Association Scientific Sessions 2010; Nov. 13-17; Chicago.

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Meeting News
Title: Comparative Effectiveness Of Two Telephone-delivered Behavioral Interventions To Improve Hypertension Control. Primary Outcomes Of A Randomized Controlled Trial
Event: AHA 2010
Topic(s): General Cardiology, PreventionVascular
Presenter: Sundar Natarajan
Writer(s): Xiushui Ren
Date Posted: 11/16/2010

Summary

Patient-tailored counseling to modify behavior results in improved blood pressure control.
Background

Despite known benefits of aggressive blood pressure (BP) control, the rate of adequate blood pressure control achieved in clinical practice is suboptimal.

The current study used telephone-delivered behavioral interventions targeting patients with uncontrolled BP in primary care settings.
Study Design

This is a randomized controlled trial comparing the effect of stage-matched intervention (SMI), health education intervention (HEI), and usual care (UC) to improve BP control in adults with uncontrolled BP despite treatment with antihypertensive drugs for ≥ 6 months. SMI and HEI patients received monthly phone counseling targeting diet, exercise and BP medication adherence for 6 months. In the SMI group, a social worker assessed each participant's behavior and delivered the appropriate tailored SMI based on their stage of change, decisional balance, and the skills model questions. Patients in the HEI group received nontailored education via calls by a social worker, during which participants received standard education about hypertension management based on national guidelines. The UC group participated in all clinical visits but did not receive monthly phone calls.

After a six-month active intervention phase, there was 6-month monitoring phase to assess sustainability. Patients were blinded to the intervention arms (SMI or HEI) and social workers were blinded to patient's BP. Research staff measuring outcomes were blinded to study assignment. The study was analyzed using longitudinal data analysis methods using an intention to treat strategy.

The primary endpoint was measured BP.
Results and Conclusions

A total of 533 participants from Department of Veterans Affairs with sustained uncontrolled BP from 2 large hospital-based outpatient clinics.

The baseline BP control rates were 42.6%, 40.6%, and 44.6% in SMI, HEI, and UC, respectively (p=0.74).

At 6 months, BP control rates were 62.3% (SMI), 52.4% (HEI), and 47.2% (UC); p values for pairwise comparisons were 0.02 for SMI vs. UC, 0.28 for HEI vs. UC, and 0.07 for SMI vs. HEI.

Thus, compared to usual care, patient-tailored counseling (stage-matched intervention) improved BP control whereas nontailored counseling (health education intervention) did not. Stage-matched intervention, therefore, should be considered a potentially effective approach to assisting patients reach BP control goals..

Finally, although clinicians were required to document their responses (such as change in therapy) to telemonitoring data, they did not record these responses systematically. However, telemonitoring sites in this study were highly motivated and the lack of systematic documentation probably did not significant alter the results. Thus, if monitoring of patients was coupled with more systematic and detailed interventions, it might still show some benefit.
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Meeting News
Title: State-Wide Care is Improved in the Reperfusion of Acute MI in Carolina Emergency Department Emergency Response (RACE-ER) Systems Improvement Program
Event: AHA 2010
Topic(s): General Cardiology
Presenter: Christopher B Granger
Writer(s): Xiushui Ren
Date Posted: 11/16/2010

Summary

A program focused on improving systems of care improves time to reperfusion in patients with STEMI.
Background

According to ACC/AHA recommendations, care for ST-segment elevation myocardial infarction (STEMI) should include the development of systems of care with a focus on reducing first medical contact to reperfusion time. Reperfusion of Acute MI in Carolina Emergency Department Emergency Response (RACE-ER) is a program to integrate care in all hospitals and EMS systems in North Carolina to increase speed and rate of reperfusion. RACE-ER is part of the AHA’s Mission:Lifeline program..
Study Design

The investigators measured delays of coronary reperfusion using ACTION Registry/Get With The Guidelines in STEMI patients from July 2008 through December 2009, including before and a year-long implementation in the 21 percutaneous coronary interventions (PCI) hospitals and 98 non-PCI hospitals, and over 500 associated EMS systems in North Carolina. The implementation focused on early diagnosis, early reperfusion activation, and optimizing performance at each point of care: EMS, emergency department, catheterization laboratory, and transfer.
Results and Conclusions

A total of 6841 patients were included in the study, of whom 57% presented directly to PCI centers and 43% were transferred from non-PCI centers. The mean age of patients was 59 years, and 30% were women.

Over the course of the study, the proportion of patients in the entire group treated with primary PCI increased from 77% to 82%, p=0.0003 for trend. Among transfer patients eligible for PCI, the rate of primary PCI increased from 52% to 66%, p<0.0001 for trend. Compared to pre-implementation, post-implementation median reperfusion times significantly improved according to first door-to-device (presenting to PCI hospital 67 vs. 60 minutes, respectively, p=0.0001; transferred to PCI hospital among transfer-designated centers 119 vs. 108 minutes, respectively, p=0.01) and first medical contact to device (presenting to PCI hospital via EMS 103 vs. 91 minutes, respectively, p<0.0001).

While significantly improved, only 32% of post-implementation patients had transfer to device time < 90 minutes and 64% < 120 minutes. Eligible but not treated with reperfusion dropped from 5.5% to 4.0%. In contrast to the original RACE data from 2006 when in-hospital mortality was 7.5%, mortality in RACE-ER was 5.8% pre- and 5.6% post- intervention.< 120 minutes. Eligible but not treated with reperfusion dropped from 5.5% to 4.0%. In contrast to the original RACE data from 2006 when in-hospital mortality was 7.5%, mortality in RACE-ER was 5.8% pre- and 5.6% post- intervention.

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Meeting News
Title: Telemonitoring to Improve Outcomes after Heart Failure Hospitalization: A Randomized Clinical Trial
Event: AHA 2010
Topic(s): Heart FailureTransplant
Presenter: Sarwat I. Chaudhry
Writer(s): Xiushui Ren
Date Posted: 11/16/2010

Summary

Telemonitoring in heart failure patients is no better than usual care.
Background

Telemonitoring is the use of communication technology to monitor a patient’s clinical status and has been used in patients with heart failure (HF). This system of monitoring typically includes daily symptom assessment and weight measurements with results sent to practitioners. The goal of telemonitoring is to provide an opportunity for intervention before patients require hospitalization for decompensated HF.

This study hypothesized that telemonitoring in HF patients is superior to standard of care.
Study Design

This was a multicenter study of 1653 patients hospitalized for heart failure within the previous 30 days. Between 2006 and 2009, patients from 33 centers were randomized to telemonitoring versus usual care. Telemonitoring patients received heart failure educational materials and guideline-based care. In addition, they provided answers via key pad entry to an interactive voice response telephone system that solicited questions on HF symptoms and body weight on a daily basis. The data was transferred to clinicians via secure electronic messaging. Patients randomized to control group received heart failure educational materials and guideline-based care.

The primary endpoint was combined outcome of all-cause readmission or death within six months.
Results and Conclusions

Baseline characteristics between the two groups were similar. The mean age was 61 years, and 42% were women. Approximately 71% of patients have LV ejection fraction < 40%, and 87% of patients were NYHA class III or IV. Approximately 79% of patients were on beta-blockers, and 67% of patients were on ACE-inhibitors, 33% were on aldosterone-receptor antagonists, and 78% were on loop diuretics.

The primary endpoint of all-cause readmission or death within 6 months was similar for telemonitoring and standard of care groups (52.3% vs. 51.5%, respectively, p=0.75). Secondary endpoints were also similar for telemonitoring or standard of care groups (death 11.1% vs. 11.4%, respectively, p=0.88; readmission rate 49.3% vs. 47.4%, respectively, p=0.45; HF readmission rate 27.5% vs. 27.0%, respectively, p=0.81). There were no significant differences in subgroup analyses.
Perspective

Thus in patients recently hospitalized for heart failure, this telemonitoring approach and protocol did not improve outcomes. The authors expressed the importance of careful analysis of management strategies (in this case, telemonitoring) before their adoption.

It is important to note that 14% of patients randomized to the telemonitoring group did not use the system. In addition, by the end of the study, only 55% of patients in the telemonitoring group still used the technology at least 3 times per week. Thus, although poor compliance may contribute to the lack of benefit in telemonitoring, is it also reasonable to assume that adherence to telemonitoring would be even lower in clinical practice. Finally, although clinicians were required to document their responses (such as change in therapy) to telemonitoring data, they did not record these responses systematically. However, telemonitoring sites in this study were highly motivated and the lack of systematic documentation probably did not significant alter the results. Thus, if monitoring of patients was coupled with more systematic and detailed interventions, it might still show some benefit.

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DEFINE: Anacetrapib raises HDL, lowers LDL

American Heart Association Scientific Sessions 2010

CHICAGO — The experimental cholesteryl ester transfer protein inhibitor anacetrapib was associated with marked increases in HDL levels and decreases in LDL levels without raising BP, according to new study results.

Researchers for the Determining the Efficacy and Tolerability of CETP Inhibition with Anacetrapib (DEFINE) trial enrolled 1,623 patients with known or prior CHD taking statins and randomly assigned in a double-blinded, 1:1 fashion to receive either 100 mg daily of anacetrapib (n=811; Merck) or placebo (n=812). The primary outcomes of interest were the percent changes from baseline in LDL at 24 weeks, with percent changes from baseline in HDL as a secondary endpoint.

According to the study results, LDL was reduced by 39.8% from 81 mg/dL to 45 mg/dL (P<.001) in patients taking anacetrapib vs. placebo. The researchers also reported a 138.1% increase in HDL levels in the anacetrapib group (from 41 mg/dL at baseline to 101 mg/dL at 24 weeks; P<.001). There were no reported changes in BP through 76 weeks, nor were changes in electrolyte or aldosterone levels reported.

Additionally, prespecified adjudicated CV events occurred in 16 patients in the anacetrapib group vs. 21 in the placebo group (P=.40). Torcetrapib, a previously evaluated cholesteryl ester transfer protein inhibitor, was associated with an increase in CV events, but the researchers suggested that the event distribution in DEFINE (via Bayesian analysis) yielded a predictive probability of 94% that anacetrapib would not be associated with a 25% increase in CV events seen with torcetrapib.

“We’re very encouraged with these results,” Christopher P. Cannon, MD, of Brigham and Women’s Hospital in Boston and senior investigator of the TIMI study group, said in a press conference. “This is a moderate-sized safety study, so we have reassurance that we can move forward and really test this [drug].”

Cannon announced the next step in testing anacetrapib – a study enrolling 30,000 patients with heart disease and a background of statin use. The study is scheduled to have 4-year follow-up.

The DEFINE study was funded by Merck Research Laboratories. – by Eric Raible and Stacey Fisher

For more information:
Cannon C. LBCT IV, Abstract 21824. Presented at: American Heart Association Scientific Sessions 2010; Nov. 13-17; Chicago.
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ASCOT: High-sensitivity CRP screening produced no significant improvements in CVD assessment

American Heart Association Scientific Sessions 2010

CHICAGO — High-sensitivity CRP was not found to be useful in improving risk factor prediction of CV outcomes in patients with hypertension, according to late-breaking clinical trial data.

The Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) included 9,098 adults with hypertension who were randomly assigned to either calcium channel blocker or beta blocker treatment. Further, 4,853 patients who had <6.5 mmol/L total cholesterol were randomized to atorvastatin (Lipitor, Pfizer) or placebo.

At six months, researchers found that atorvastatin reduced LDL cholesterol by 40.3% and median high-sensitivity CRP (hsCRP) by 27.4%. Among those assigned to atorvastatin, LDL cholesterol lower than the median (2.1 mmol/L) correlated with a significant reduction in CV events vs. patients with LDL at or above the median.

Conversely, hsCRP levels in patients assigned to atorvastatin were not associated with CV events (OR=0.86; 95% CI, 0.49-1.51) when researchers compared patients with less than the median hsCRP (1.83 mg/L) to those having at least the median hsCRP.

At a press conference, Peter Sever, FRCP, professor of clinical pharmacology and therapeutics, Imperial College London and study investigator, said of the study, “neither baseline nor on-treatment CRP provide any useful information about the efficacy of statin treatment to reduce CV events beyond LDL cholesterol reduction. These results do not support current proposals to measure CRP in the clinical setting either to assign statins to individuals on the basis of an elevated CRP alone or to monitor CRP levels as an indicator of the efficacy of statin treatment.” – by Brian Ellis

For more information:
Sever PS. LBCTIV, Abstract#21685. Presented at: American Heart Association Scientific Sessions 2010; Nov. 13-17; Chicago.

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ASSERT: Novel drug did not significantly raise apoA-1 levels

American Heart Association Scientific Sessions 2010

CHICAGO — New data from ASSERT has shown that RVX-208, a new drug designed to raise apolipoprotein A-1 levels, had no significant effect on apoA-1 levels vs. placebo in patients with coronary artery disease.

The ApoA1 Synthesis Stimulation Evaluation in Patients Requiring Treatment for Coronary Artery Disease (ASSERT) trial was a double-blind, randomized study conducted at 35 medical centers in the US. All patients (n=299) had CAD and were already taking a cholesterol-lowering statin drug at baseline. They were divided into four groups: three given different doses of RVX-208 (Resverlogix Corp.; doses: 100 mg, 200 mg, 300 mg) and one given placebo. All four groups were treated for 12 weeks.

Researchers reported that the primary endpoint of percentage change in apoA-1 levels in patients treated with RVX-208 vs. placebo did not reach statistical significance. However, they did note that as the dose of RVX-208 increased so did apoA-1 levels, culminating with an increase of 8.3% in HDL levels in the 300 mg group compared with placebo (PM.01).

According to Stephen J. Nicholls, PhD, who presented the results of the ASSERT trial at a press conference, a 2-D gel analysis demonstrated that the highest dose of RVX-208 was associated with a statistically significant increase in the amount of alpha-1HDL compared with placebo (P<.05). Nicholls also noted that the majority of increases in HDL occurred in the latter part of the study with no plateau in effects.

“While this (induction of apoA-1 synthesis) remains a novel approach to HDL functionality rather than necessarily quantitative changes in terms of primary impact, the impact ultimately on plaque in the artery wall and cardiovascular outcomes remains to be determined in future studies,” Nicholls, who is assistant professor of molecular medicine, Lerner College of Medicine, Case Western Reserve University, Cleveland, said.

Nicholls reports receiving research support from Resverlogix. The ASSERT study was funded by Resverlogix. – by Brian Ellis and Stacey Fisher
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Symplicity HTN-2: Renal denervation therapy plus medication lowered BP vs. medication alone

American Heart Association Scientific Sessions 2010

CHICAGO — Patients with high systolic BP treated with renal denervation therapy and medication had a significant drop in BP compared with patients treated with just medication alone.

Researchers of the multicenter, prospective, randomized, controlled trial of Endovascular Selective Renal Sympathetic Denervation for the Treatment of Hypertension (Symplicity HTN-2) compared 52 participants who received catheter treatment (Symplicity Catheter System, Ardian Inc.) plus medication to 54 controls who received medication only. Patients were aged 18 to 85 years and had systolic BP of 160 mm Hg or more.

At baseline, both groups had nearly identical mean BP (treatment, 178/98 mm HG vs. control, 178/97 mm HG). Six-month data showed that BP in the renal denervation group dropped by 32/12 mm HG (P<.0001), whereas there was no difference in the control group (systolic BP, P=.77; diastolic BP, P=.83). Eighty-four percent of patients undergoing renal denervation had reduced systolic BP of 10 mm Hg or more vs. 35% of controls (P<.0001).

“In patients with resistant, very difficult to control hypertension, renal denervation has a very material effect on BP. It could be achieved with almost complete safety and no significant side effects,” said Murray Esler, MD, associate director of the Baker IDI Heart and Diabetes Institute, Melbourne, Australia and principal investigator on the trial, said in a press conference. “This technique is to be trialed in the US starting early next year. For the future, I think this treatment will probably become part of more general care for very severe hypertension.”

Dr. Esler reported receiving research grant, travel and consultancy funding from Ardian. – by Brian Ellis

For more information:
Esler M. LBCTIV, Abstract #21826. Presented at: American Heart Association Scientific Sessions 2010; Nov. 13-17; Chicago.

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Overweight diabetics can improve CRP levels with nutrition, exercise

American Heart Association Scientific Sessions 2010

CHICAGO — Patients with type 2 diabetes who engage in lifestyle behaviors aimed at weight loss and improved glucose control may also improve their high-sensitivity C-reactive protein levels, data suggest.

Researchers measured CRP levels at baseline and at 1 year in 1,759 patients with diabetes who were enrolled in the Look AHEAD (Action for Health in Diabetes) study. Look AHEAD is a multicenter clinical trial evaluating the effects of improved lifestyle behavior for weight loss on CVD in overweight and obese people with diabetes in the United States. Participants were randomly assigned to receive either lifestyle intervention or usual care. The lifestyle intervention group received frequent counseling to increase moderate-intensity exercise to 175 minutes per week and reduce caloric intake; the usual care group received three information sessions in the year. Forty percent of participants were taking statin therapy at baseline.

At baseline, the patients’ mean CRP level was 4.2 mg/dL. Results showed that lifestyle intervention reduced the average CRP level by 43.6% compared with a 16.7% reduction with usual care. In addition, researchers found a significant reduction in CRP levels with lifestyle intervention in both statin and non-statin users when compared with the usual care group.

The researchers concluded that “efforts to improve lifestyle behaviors may be beneficial in patients who are taking statins and still have elevated levels of CRP.”

For more information:
Belalcazar LM. Abstract 14666. Presented at: American Heart Association Scientific Sessions 2010; Nov. 13-17; Chicago.
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Adolescent dietary salt reductions may improve adult heart health S

American Heart Association Scientific Sessions 2010

CHICAGO — A 3-g decrease in daily salt intake may decrease the number of hypertensive adolescents and young adults by more than 60%, according to a recent study funded by the American Heart Association.

At 9 g per day, adolescents not only exceed the American Heart Association (AHA) recommended 1,500 mg of daily sodium intake, but also consume more salt than any other group, according to Kirsten Bibbins-Domingo, PhD, MD, associate professor of medicine and epidemiology at the University of California, San Francisco.

Using a sophisticated computer modeling analysis, Bibbins-Domingo and colleagues calculated projections of the nationwide health effects of a 3-g reduction in dietary salt from processed foods consumed by adolescent boys and girls.

The findings were presented at the American Heart Association Scientific Sessions 2010.

Benefits of dietary salt decreases

The researchers’ projections linked the 3-g decrease in salt intake with a 44% to 63% decline in the number of hypertensive adolescents and young adults and a 30% to 43% reduction (2.7 to 3.9 million people) in the number of hypertensive adults at ages 30 to 50 years.

“Reducing the amount of salt that is already added to the food that we eat could mean that teenagers live many more years free of hypertension,” said Bibbins-Domingo, who is also co-director of the UCSF Center for Vulnerable Populations. “The additional benefit of lowering salt consumption early is that we can hopefully change the expectations of how food should taste, ideally to something slightly less salty.”

She noted that a 1-g daily decrease in salt consumption also results in a small 0.8 mm Hg decrease in systolic BP.

“Reducing the salt in the teenage diet from an average of 9 g to 6 g would get teenage boys and girls to appropriate levels of salt intake,” she added.

By age 50, health benefits would also include the following:
7% to 12% reduction in coronary heart disease (120,000 to 210,000 people).
8% to 14% reduction in MI (36,000 to 640,000 people).
5% to 8% reduction in stroke (16,000 to 28,000 people).
5% to 9% reduction in death from any cause (69,000 to 120,000 people).

Major sources of sodium

“The hidden places of salt in our diet are in breads and cereals, canned foods and condiments and of course fast foods,” Bibbins-Domingo said. “Most of the salt that we eat is not from our salt shaker but salt that is already added in food that we eat.”

Approximately 80% of salt comes from processed foods or prepared foods, 35% of which is in cereals, breads and pastries.

Data from the National Center for Health Statistics, however, indicate that pizza is largely responsible for the high amount of dietary salt among adolescents.

Bibbins-Domingo urged manufacturers to collaborate with local, state and federal regulatory agencies to continue to reduce salt in their foods. She noted that a number of major companies have already joined the National Sodium Reduction initiative and have voluntarily agreed to work to lower the salt content that is in processed and prepared foods.

For more information:
Bibbins-Domingo K. Abstract 18899/P2039. Presented at: American Heart Association Scientific Sessions 2010; Nov. 13-17; Chicago.