Обзор американских кардиологических журналов за неделю (ссылки)

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TV Time Increases CV Mortality
Culprit or Multivessel PCI in STEMI?
FDA Approves Rosuvastatin for High CRP
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Title: Statins and Risk of Incident Diabetes: A Collaborative Meta-Analysis of Randomised Statin Trials
Topic: General Cardiology
Date Posted: 2/17/2010
Author(s): Sattar N, Preiss D, Murray HM, et al.
Citation: Lancet 2010;Feb 17:[Epub ahead of print].
Clinical Trial: No
Study Question: Is there a relationship between statin use and development of diabetes?
Methods: The authors conducted a MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials search, from 1994–2009, for randomized controlled endpoint trials of statins. Trials included had more than 1,000 patients, with identical follow-up in every group, and duration of more than 1 year. Trials were excluded if they involved organ transplant or hemodialysis. The I2 statistic was used to measure heterogeneity between trials, and calculated risk estimates for incident diabetes were performed with a random-effect meta-analysis.
Results: Thirteen statin trials with 91,140 participants were identified, of whom 4,278 (2,226 assigned statins and 2,052 assigned control therapy) developed diabetes (defined as a fasting blood sugar >126 mg/dl) during a mean 4 years. Statin therapy was associated with a 9% increased risk for incident diabetes (odds ratio [OR], 1.09; 95% confidence interval [CI], 1.02-1.17), with little heterogeneity (I2 = 11%) between trials. Meta-regression showed that risk of development of diabetes with statins was highest in trials with older participants, but neither baseline body mass index nor change in low-density lipoprotein cholesterol (LDL-C) accounted for residual variation in risk. Treatment of 255 (95% CI, 150-852) patients with statins for 4 years resulted in one extra case of diabetes.
Conclusions: Statin therapy is associated with a slightly increased risk of development of diabetes, but the risk is low both in absolute terms and when compared with the reduction in coronary events.
Perspective: The findings are of interest, but should have no impact on clinical practice. The lay literature has waved a flag of concern about statins inducing diabetes. But the modest 9% increase in diabetes is more than balanced by the benefits of statins in diabetics and nondiabetics alike. In the Cholesterol Treatment Trialists’ meta-analysis, for every 38.7 mg/dl reduction in LDL-C with statins, there was a 5.4 reduction in major coronary events per 255 patients treated for 4 years. As yet, there is no clear biologic or genetic explanation for the findings. In the PROVE-IT TIMI-22 trial, there was a slight increase in diabetes attributable to 80 mg of atorvastatin compared to 40 mg of pravastatin. Whether this is related to statin dosing or achieved LDL-C levels is not clear, but in the present meta-analysis, there was no difference between water-soluble and fat-soluble statins. Melvyn Rubenfire, M.D., F.A.C.C.

Title: Association Between a Literature-Based Genetic Risk Score and Cardiovascular Events in Women
Topic: Prevention/Vascular
Date Posted: 2/17/2010
Author(s): Paynter NP, Chasman DI, Pare G, et al.
Citation: JAMA 2010;303:631-637.
Clinical Trial: No
Study Question: What is the ability of a literature-based genetic risk score to predict cardiovascular disease (CVD)?
Methods: Data from the Women’s Genome Health Study, a prospective cohort study of 19,313 women, were used for the present analysis. Women were followed for a median of 12.3 years. Genetic risk scores were created using the National Human Genome Research Institute's catalog of genome-wide association study results published between 2005 and 2009. The outcomes of interest included myocardial infarction (MI), stroke, arterial revascularization, and cardiovascular death.
Results: A total of 101 single nucleotide polymorphisms reported to be associated with CVD or at least one intermediate CVD phenotype (at a published p value of <107) were identified and risk alleles were added to create a genetic risk score. A total of 777 CVD events occurred during follow-up, including 199 MIs, 203 strokes, 63 CVD deaths, and 312 revascularization events. After adjustment for age, the genetic risk score was associated with CVD events (hazard ratio [HR], 1.02 per risk allele; 95% confidence interval [CI], 1.00-1.03). The corresponding absolute CVD risk was 3% over 10 years in the lowest tertile of genetic risk and 3.7% over 10 years in the highest tertile of genetic risk. After further adjustment for traditional risk factors, the genetic risk score did not improve discrimination or reclassification in risk score. The genetic risk score was not associated with CVD risk (HR, 1.00 Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults-adjusted/allele; 95% CI, 0.99-1.01). Family history remained significantly associated with CVD risk.
Conclusions: The authors concluded that after adjustment for traditional risk factors, a genetic risk score was not significantly associated with incidence of CVD.
Perspective: This is an important study, which advances our understanding regarding the potential use of genetics in CVD risk. Given these results, continued use of traditional risk factors including the prevention of risk factors such as hypertension, hypercholesterolemia, diabetes, and obesity are the foundations of CVD practice. Elizabeth A. Jackson, M.D., F.A.C.C.

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Title: Perioperative Management of Patients With Drug-Eluting Stents
Topic: Interventional Cardiology
Date Posted: 2/15/2010 5:00:00 PM
Author(s): Abualsaud AO, Eisenberg MJ.
Citation: JACC Cardiovasc Interv 2009;2:131-142.
Clinical Trial: No
Study Question: What is the best strategy for perioperative use of antiplatelet agents in patients with drug-eluting stents (DES) who need to undergo noncardiac surgery to avoid stent thrombosis?
Perspective: The following are 10 points to remember from this state-of-the-art paper about perioperative management of patients with DES:

1. DES are associated with a small, but significant increased risk of late and very late stent thrombosis compared with bare-metal stents.

2. Stent thrombosis is a platelet-mediated phenomenon that usually manifests as sudden death ST-segment elevation myocardial infarction, or malignant arrhythmias. It appears to be associated with a mortality ranging from 9-45%.

3. Premature cessation of dual antiplatelet therapy is the most important predictor of stent thrombosis. Current guidelines support continuation of dual antiplatelet therapy for 12 months after DES implantation.

4. The risk of perioperative stent thrombosis is increased in patients undergoing noncardiac surgery within 6 weeks of stent-based percutaneous coronary intervention (PCI).

5. In patients undergoing noncardiac surgery, continuation of aspirin is associated with a 1.5-fold increase in risk of bleeding while withdrawal of aspirin leads to an increase in cardiac, cerebral, and peripheral vascular events. Dual antiplatelet therapy is associated with an increased risk of bleeding complications.

6. All elective surgical procedures should be delayed by at least 6 months and ideally 12 months after DES placement.

7. Patients undergoing surgical procedures 12 months after PCI are at a lower risk of perioperative stent thrombosis compared with earlier surgery. However, if possible, dual antiplatelet therapy should be continued if bleeding risk is low. If the risk of perioperative bleeding is significantly high, then clopidogrel should be discontinued 5 days before surgery, and aspirin should be maintained. Clopidogrel should be restarted as soon as realistically feasible.

8. In patients with DES, when surgery cannot be delayed beyond a year after PCI and thienopyridine or dual antiplatelet therapy must be discontinued, intravenous small molecule glycoprotein IIb/IIIa inhibitors have been used as bridging therapy preoperatively, followed by early (usually immediately postop) resumption of dual antiplatelet therapy. The efficacy of this strategy has not been definitively proven. Use of heparin, low molecular weight heparin, Coumadin, or fondaparinux as bridge therapy for patients after discontinuing dual antiplatelet therapy is not advisable.

9. Primary PCI is the reperfusion therapy of choice in patients who develop perioperative myocardial infarction due to stent thrombosis.

10. The challenges associated with thienopyridine use could be overcome once ticagrelor is approved for clinical use. Its short half-life and its rapid onset of action would allow patients to discontinue ticagrelor only 1 day before surgery and resume it immediately after surgery, thereby potentially diminishing both the risk of perioperative bleeding and stent thrombosis. This hypothesis is also unproven at this point. Hitinder S. Gurm, M.B.B.S., F.A.C.C.

[Chevychelov]

Title: Intracardiac and Extracardiac Markers of Inflammation During Atrial Fibrillation
Topic: Arrhythmias
Date Posted: 2/22/2010
Author(s): Marcus GM, Smith LM, Ordovas K, et al.
Citation: Heart Rhythm 2010;7:149-154.
Clinical Trial: No
Study Question: Does atrial fibrillation (AF) result in sequestration of inflammatory mediators in the left atrium (LA)?
Methods: C-reactive protein (CRP) and interleukin-6 (IL-6) levels were measured in blood samples drawn from 167 patients with AF and 207 control subjects with no history of AF. Venous samples were obtained in all subjects, and in 46 patients undergoing catheter ablation of AF, blood samples also were obtained from the LA, coronary sinus (CS), and femoral artery. LA volume was measured by computed tomography.
Results: The presence of AF at the time of blood sampling was associated with higher CRP and IL-6 levels (odds ratio, 1.7-1.8), independent of the type of AF and LA volume. Among the 46 patients who underwent blood sampling at multiple sites, the CRP level was higher in the LA than in the CS in the patients who were in AF, but were lower in the LA than in the CS in the patients who were in sinus rhythm at the time of sampling.
Conclusions: An ongoing episode of AF is independently associated with higher levels of inflammatory markers. Measurements of the relative levels of CRP and IL-6 in the LA and CS suggest that inflammatory mediators are sequestered in the LA during AF.
Perspective: Several studies have indicated that inflammatory markers such as CRP are associated with AF. For example, higher CRP levels pre-cardioversion are predictive of an early recurrence of AF post-cardioversion. A plausible explanation for this is that inflammation in the LA promotes atrial remodeling. The results of this interesting study suggest that AF itself results in higher levels of inflammatory cytokines in the LA, providing a potential mechanism by which ‘AF begets AF.’ Fred Morady, M.D., F.A.C.C.

Title: Nonsteroidal Anti-Inflammatory Drug Treatment for Postoperative Pericardial Effusion: A Multicenter Randomized, Double-Blind Trial
Topic: Cardiovascular Surgery
Date Posted: 2/22/2010
Author(s): Meurin P, Tabet JY, Thabut G, et al.
Citation: Ann Intern Med 2010;152:137-143.
Clinical Trial: yes
Study Question: Is the nonsteroidal anti-inflammatory drug (NSAID) diclofenac effective in reducing postoperative pericardial effusion volume after cardiac surgery?
Methods: A multicenter, randomized, double-blind, placebo-controlled trial was conducted at five postoperative cardiac rehabilitation centers. A total of 196 patients with moderate to large pericardial effusion (grade 2, 3, or 4 on a scale of 0 to 4; measured by echocardiography) persistent more than 7 days after cardiac surgery were randomly assigned treatment with either diclofenac 50 mg or placebo twice daily for 14 days. Endpoints were change in effusion grade after 14 days of treatment and frequency of late cardiac tamponade.
Results: The initial mean pericardial effusion grade was 2.6 ± 0.7 in the placebo group and 2.8 ± 0.8 in the diclofenac group. The two groups showed similar mean decreases from baseline after treatment (-1.1 ± 1.2 grades for the placebo group vs. -1.4 ± 1.2) for the diclofenac group. The mean difference between groups was -0.28 grade (95% confidence interval, -0.63 to 0.06 grade, p = 0.105). There were 11 cases of late cardiac tamponade in the placebo group and nine in the diclofenac group (p = 0.64). Differences persisted after adjustment for grade of pericardial effusion at baseline, treatment site, and type of surgery.
Conclusions: In patients with pericardial effusion after cardiac surgery, the NSAID diclofenac neither reduced the size of postoperative pericardial effusions nor prevented late cardiac tamponade.
Perspective: Although not supported by data, NSAIDs might be used to treat postoperative pericardial effusion; rationale is based on the belief that their anti-inflammatory properties would result in a decrease, or cessation of increase, in effusion size, thereby avoiding cardiac tamponade. These data, although limited by relative small sample size that could have led to failure to detect a small benefit, refute the efficacy of the NSAID diclofenac (at a dose of 60 mg BID) for the treatment of postoperative pericardial effusion. In light of potential adverse effects associated with NSAID use (including renal insufficiency, volume retention exacerbating heart failure, and upper gastrointestinal disease), supporting data should be provided before the routine use of NSAIDs in this scenario. David S. Bach, M.D., F.A.C.C.

[Chevychelov]

Title: When Children With Kawasaki Disease Grow Up: Myocardial and Vascular Complications in Adulthood
Topic: Congenital Heart Disease
Date Posted: 2/19/2010
Author(s): Gordon JB, Kahn AM, Burns JC.
Citation: J Am Coll Cardiol 2009;54:1911-1920.
Clinical Trial: No
Perspective: The following are 10 points to remember from this state-of-the-art paper.

1. The cause of Kawasaki disease (KD) is unknown. The self-limited nature of illness, seasonality, and nationwide epidemics suggest an infectious trigger. Some element of genetic susceptibility is suspected.

2. Symptoms of KD include high fever for at least 4 days, rash, conjunctival infection, erythema of the lips and oropharynx, edema of the hands and feet, and palmar erythema.

3. Up to 25% of patients with untreated KD will develop coronary artery aneurysms. Aneurysm of systemic arteries can also occur.

4. Prompt treatment (within 10 days of onset of fever) will decrease incidence of aneurysms from 25-35%. The long-term coronary outcomes of children treated with intravenous immunoglobulin who do not develop aneurysms are unknown.

5. In young adults with coronary symptoms of unclear etiology, presence of proximal coronary aneurysms with or without calcification followed by normal distal coronary segments should prompt questioning about antecedent KD.

6. Impaired coronary flow reserve has been shown in patients with previous KD with no known coronary involvement, resolved coronary dilatation, and known coronary artery aneurysms.

7. A complete understanding of long-term outcomes of patients with KD will require a prospective registry.

8. Calcification at the site of previous coronary aneurysms can be helpful diagnostically and can be seen on chest radiography.

9. Tests which could be considered for adults with a previous history of KD and known coronary involvement include lipid screening, electrocardiogram, echocardiogram, functional studies such as stress echocardiograms, or nuclear studies.

10. For patients with persistent giant (≥8 mm) aneurysms, anticoagulation with warfarin for a goal international normalized ratio of 2.0-2.5 should be considered. Timothy B. Cotts, M.D., F.A.C.C.

Title: Association Between 9p21 Genomic Markers and Heart Disease: A Meta-Analysis
Topic: General Cardiology
Date Posted: 2/17/2010
Author(s): Palomaki GE, Melillo S, Bradley LA.
Citation: JAMA 2010;303:648-656.
Clinical Trial: No
Study Question: How strong is the association between genetic variation on chromosome 9p21 and coronary heart disease?
Methods: English-language articles that tested for 9p21 single-nucleotide polymorphisms (SNPs) with coronary heart/artery disease or myocardial infarction as primary outcomes were included. Included articles also provided race, number of participants, and data to compute an odds ratio (OR). Two independent reviewers performed data extraction, and 22 articles were included.
Results: Forty-seven data sets from the 22 articles were analyzed, including 35,872 cases and 95,837 controls. The summary OR for heart disease among individuals with two versus one at-risk allele was 1.25 (95% confidence interval [CI], 1.21-1.29). Age at disease diagnosis was a significant covariate, with ORs of 1.35 (95% CI, 1.30-1.40) for age 55 years or younger, and 1.21 (95% CI, 1.16-1.25) for age 75 years or younger. For a 65-year-old man, the 10-year heart disease risk for two versus one at-risk allele would be 13.2% versus 11%. For a 40-year-old woman, the 10-year heart disease risk for two versus one at-risk allele would be 2.4% versus 2.0%. Nearly identical results were found when comparing one versus zero at-risk alleles. Three studies showed net reclassification indexes ranging from −0.1% to 4.8%.
Conclusions: A statistically significant association between 9p21 SNPs and heart disease was found that varied by age at disease onset, but the magnitude of the association was small.
Perspective: Several studies have shown that SNPs in an intergenic region of 9p21 are associated with coronary artery disease. The magnitude of this association and the clinical utility of this genetic marker for risk stratification are controversial. The current meta-analysis casts doubt on use of these SNPs for practical management of patients, as this information is unlikely to affect treatment decisions. However, there is still much to be learned about the biological mechanisms underlying this association, which may lead to novel treatment strategies in the future. Daniel T. Eitzman, M.D., F.A.C.C.

[Chevychelov]

Title: Statins and Risk of Incident Diabetes: A Collaborative Meta-Analysis of Randomised Statin Trials
Topic: General Cardiology
Date Posted: 2/17/2010
Author(s): Sattar N, Preiss D, Murray HM, et al.
Citation: Lancet 2010;Feb 17:[Epub ahead of print].
Clinical Trial: No
Study Question: Is there a relationship between statin use and development of diabetes?
Methods: The authors conducted a MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials search, from 1994–2009, for randomized controlled endpoint trials of statins. Trials included had more than 1,000 patients, with identical follow-up in every group, and duration of more than 1 year. Trials were excluded if they involved organ transplant or hemodialysis. The I2 statistic was used to measure heterogeneity between trials, and calculated risk estimates for incident diabetes were performed with a random-effect meta-analysis.
Results: Thirteen statin trials with 91,140 participants were identified, of whom 4,278 (2,226 assigned statins and 2,052 assigned control therapy) developed diabetes (defined as a fasting blood sugar >126 mg/dl) during a mean 4 years. Statin therapy was associated with a 9% increased risk for incident diabetes (odds ratio [OR], 1.09; 95% confidence interval [CI], 1.02-1.17), with little heterogeneity (I2 = 11%) between trials. Meta-regression showed that risk of development of diabetes with statins was highest in trials with older participants, but neither baseline body mass index nor change in low-density lipoprotein cholesterol (LDL-C) accounted for residual variation in risk. Treatment of 255 (95% CI, 150-852) patients with statins for 4 years resulted in one extra case of diabetes.
Conclusions: Statin therapy is associated with a slightly increased risk of development of diabetes, but the risk is low both in absolute terms and when compared with the reduction in coronary events.
Perspective: The findings are of interest, but should have no impact on clinical practice. The lay literature has waved a flag of concern about statins inducing diabetes. But the modest 9% increase in diabetes is more than balanced by the benefits of statins in diabetics and nondiabetics alike. In the Cholesterol Treatment Trialists’ meta-analysis, for every 38.7 mg/dl reduction in LDL-C with statins, there was a 5.4 reduction in major coronary events per 255 patients treated for 4 years. As yet, there is no clear biologic or genetic explanation for the findings. In the PROVE-IT TIMI-22 trial, there was a slight increase in diabetes attributable to 80 mg of atorvastatin compared to 40 mg of pravastatin. Whether this is related to statin dosing or achieved LDL-C levels is not clear, but in the present meta-analysis, there was no difference between water-soluble and fat-soluble statins. Melvyn Rubenfire, M.D., F.A.C.C.

Title: Dose of Prophylactic Platelet Transfusions and Prevention of Hemorrhage
Topic: General Cardiology
Date Posted: 2/17/2010 5:00:00 PM
Author(s): Slichter SJ, Kaufman RM, Assmann SF, et al.
Citation: N Engl J Med 2010;362:600-613.
Clinical Trial: yes
Study Question: What is the effect of platelet dose on bleeding in patients with hypoproliferative thrombocytopenia?
Methods: The investigators randomly assigned hospitalized patients undergoing hematopoietic stem-cell transplantations or chemotherapy for hematologic cancers or solid tumors to receive prophylactic platelet transfusions at a low dose, a medium dose, or a high dose (1.1 x 1011, 2.2 x 1011, or 4.4 x 1011, platelets per square meter of body-surface area, respectively) when morning platelet counts were 10,000 per cubic millimeter or lower. Clinical signs of bleeding were assessed daily. The primary endpoint was bleeding of grade 2 or higher (as defined on the basis of World Health Organization criteria).
Results: In the 1,272 patients who received at least one platelet transfusion, the primary endpoint was observed in the 71%, 69%, and 70% of the patients in the low-dose group, the medium-dose group, and the high-dose group, respectively (differences were nonsignificant). The incidences of higher grades of bleeding and other adverse events, were similar among the three groups. The median number of platelets transfused was significantly lower in the low-dose group (9.25 x 1011) than in the medium-dose group (11.25 x 1011) or the high-dose group (19.63 x 1011; p = 0.002 for low vs. medium, p < 0.001 for high vs. low and high vs. medium), but the median number of platelet transfusions given was significantly higher in the low-dose group (five, vs. three in the medium-dose and three in the high-dose group; p < 0.001 for low vs. medium and low vs. high). Bleeding occurred on 25% of the study days on which morning platelet counts were 5000 per cubic millimeter or lower, as compared with 17% of study days on which platelet counts were 6000 to 80,000 per cubic millimeter (p < 0.001).
Conclusions: The authors concluded that at doses between 1.1 x 1011 and 4.4 x 1011 platelets per square meter, the number of platelets in the prophylactic transfusion has no effect on the incidence of bleeding.
Perspective: The current study evaluated the effect of different platelet dosages on hemostasis and transfusion endpoints and suggests that the dose per prophylactic platelet transfusion (at doses between 1.1 x 1011 and 4.4 x 1011 platelets per square meter) does not significantly affect bleeding in patients with hypoproliferative thrombocytopenia. The median platelet increment after transfusion was higher after larger doses, as expected. Overall, the data suggest that when prophylactic transfusions are administered after a trigger threshold dose of 10,000 platelets/cubic millimeter is reached, dose has no effect on bleeding. A strategy of low-dose transfusion may therefore significantly reduce the quantity of transfused platelets, preserving scarce blood components. However, this may increase the total number of platelet transfusions. Additional studies to determine optimal dose and frequency of platelet transfusions in hypoproliferative thrombocytopenia are indicated. Debabrata Mukherjee, M.D., F.A.C.C

[Chevychelov]

Title: Serum Soluble ST2: A Potential Novel Mediator in Left Ventricular and Infarct Remodeling After Acute Myocardial Infarction
Topic: General Cardiology
Date Posted: 2/22/2010
Author(s): Weir RA, Miller AM, Murphy GE, et al.
Citation: J Am Coll Cardiol 2010;55:243-250.
Clinical Trial: No
Study Question: What is the relationship between serum concentrations of the soluble interleukin-1 receptor family member ST2 (sST2) and changes in left ventricular (LV) function after acute myocardial infarction (AMI)?
Methods: sST2 levels were measured in 100 patients (mean age 58.9 ± 12.0 years), admitted with AMI and resultant LV systolic dysfunction, at baseline, and 12 and 24 weeks. Patients underwent cardiac magnetic resonance imaging and measurement of N-terminal pro-brain natriuretic peptide, norepinephrine, and aldosterone at each time point.
Results: Median sST2 decreased from 263.3 pg/ml at baseline to 140.0 pg/ml at 24 weeks (p < 0.001). Serum sST2 correlated significantly with LVEF at baseline (r = -0.30, p = 0.002) and 24 weeks (r = -0.23, p = 0.026); change in sST2 correlated with change in LV end-diastolic volume index (r = -0.24, p = 0.023). Level of sST2 was positively associated with infarct volume index at baseline (r = 0.26, p = 0.005) and 24 weeks (r = 0.22, p = 0.037), and with change in infarct volume index (r = -0.28, p = 0.001). Level of sST2 correlated significantly with norepinephrine and aldosterone, but not with N-terminal pro-brain natriuretic peptide.
Conclusions: The authors concluded that measurement of sST2 early after AMI assists in the prediction of medium-term LV functional recovery.
Perspective: A soluble form of ST2 is found in the circulation that lacks intracellular and transmembrane domains. Thus, sST2 may act as a decoy receptor that interferes with cellular signaling via its ligand, IL-33. Preclinical studies indicate that IL-33 signaling may mediate cardioprotective effects. The current study demonstrates an intriguing association between levels of this potential inhibitor of IL-33/ST2 signaling with LV function and neurohormonal activation following AMI. sST2 may therefore serve as a potential useful biomarker in AMI patients. Additional studies are necessary to confirm these observations, as well as to explore the pathophysiological role of sST2 in LV remodeling and renin-angiotensin-aldosterone system activation. Daniel T. Eitzman, M.D., F.A.C.C

Title: Efficacy and Safety of Immediate Angioplasty Versus Ischemia-Guided Management After Thrombolysis in Acute Myocardial Infarction in Areas With Very Long Transfer Distances: Results of the NORDISTEMI (NORwegian study on DIstrict treatment of ST-Elevation Myocardial Infarction)
Topic: Interventional Cardiology
Date Posted: 2/18/2010
Author(s): Bшhmer E, Hoffmann P, Abdelnoor M, Arnesen H, Halvorsen S.
Citation: J Am Coll Cardiol 2010;55:102-10.
Clinical Trial: yes
Study Question: What is the benefit of immediate transfer for percutaneous coronary intervention (PCI) (compared with an ischemia-guided approach) after thrombolysis in patients with very long transfer distances to PCI?
Methods: The authors randomized 266 patients treated with fibrinolytics for ST-elevation myocardial infarction (STEMI) with more than 90-minute transfer delays to PCI to immediate transfer for PCI or to management in the local hospitals, with early transfer if indicated for rescue or clinical deterioration. All patients were treated with tenecteplase, aspirin, enoxaparin, and clopidogrel. The primary outcome was a composite of death, reinfarction, stroke, or new ischemia at 1 year.
Results: Coronary angiography was performed in almost all patients (99% in the early invasive arm and 95% in the conservative arm), although the average delay to angiography was 5.5 days in the conservative arm. In the conservative arm, 27% (36) of patients were referred for rescue PCI. Overall, 89% of patients in the early invasive arm and 71% in the conservative arm underwent PCI. The primary endpoint occurred in 28 patients (21%) in the early invasive group compared with 36 (27%) in the conservative group (hazard ratio, 0.72; p = 0.19). The incidence of 30-day reinfarction (1.5% vs. 5.3%) and recurrent ischemia (6.0% vs. 12.1%) was nonsignificantly lower in the early invasive arm. The composite of death, reinfarction, or stroke at 12 months was significantly reduced in the early invasive compared with the conservative group (6% vs. 16%; hazard ratio, 0.36; p = 0.01). There was no significant difference in bleeding or infarct size.
Conclusions: A strategy of immediate transfer for PCI of patients with STEMI, treated with thrombolysis and clopidogrel in areas with long transfer distances did not improve the primary outcome significantly, but reduced the rate of death, reinfarction, or stroke at 12 months.
Perspective: This trial assessed the role for an early invasive approach in patients when rapid PCI or rapid transfer for primary PCI is not feasible. Although this trial did not meet its primary endpoint, the trends in ischemic events are similar to those seen in the larger TRANSFER-AMI trial (Cantor WJ, et al., N Engl J Med 200925;360:2705-18), supporting a strategy of early transfer for PCI after thrombolysis in patients with STEMI. Hitinder S. Gurm, M.B.B.S., F.A.C.C.

[Chevychelov]

Title: Second-Generation Everolimus-Eluting and Paclitaxel-Eluting Stents in Real-Life Practice (COMPARE): A Randomised Trial
Topic: Interventional Cardiology
Date Posted: 2/19/2010
Author(s): Kedhi E, Joesoef KS, McFadden E, et al.
Citation: Lancet 2010;375:201-209.
Clinical Trial: yes
Study Question: What is the safety and efficacy of the second-generation everolimus-eluting stent (EES) and paclitaxel-eluting stents (PES) in real-life practice?
Methods: The authors randomized 1,800 consecutive patients (ages 18-85 years) undergoing percutaneous coronary intervention (PCI) at their center to treatment with EES or PES in a single-blind fashion. The primary endpoint was a composite of all-cause mortality, myocardial infarction, and target vessel revascularization within 12 months.
Results: The primary endpoint occurred less frequently with the EES compared with the PES (6% vs. 9%, p = 0.02). This difference was driven by a lower risk of stent thrombosis (0.7% vs. 3%, p = 0.002), myocardial infarction (3% vs. 5%, p = 0.007), and target vessel revascularization (2% vs. 6%; p = 0.0001). There was no difference in all-cause mortality (2% vs. 2%) or cardiac mortality (1% vs. 1%).
Conclusions: The authors concluded that the EES was superior to PES in patients undergoing contemporary PCI.
Perspective: The results of this study corroborate those of the recently presented SPIRIT IV trial, suggesting that the EES is a superior stent to PES. Interestingly, there was no difference in outcome with the two stents in diabetic patients in the two trials. However, neither trial was powered specifically for this subset, and in the absence of a trial specifically evaluating outcomes in diabetic patients, EES should be preferentially used over PES in both diabetic and nondiabetic patients undergoing PCI. Hitinder S. Gurm, M.B.B.S., F.A.C.C.

Title: A Randomized Trial of a Low-Carbohydrate Diet vs Orlistat Plus a Low-Fat Diet for Weight Loss
Topic: Prevention/Vascular
Date Posted: 2/16/2010
Author(s): Yancy WS Jr, Westman EC, McDuffie JR, et al.
Citation: Arch Intern Med 2010;170:136-145.
Clinical Trial: yes
Study Question: What is the relative value of two potent weight loss therapies, a low-carbohydrate, ketogenic diet (LCKD) and orlistat therapy combined with a low-fat diet (O + LFD), for weight loss and metabolic parameters?
Methods: Overweight or obese outpatients (n = 146) from Department of Veterans Affairs primary care clinics in North Carolina, were randomized to either LCKD instruction (initially, <20 g of carbohydrate daily) or orlistat therapy, 120 mg orally 3 times daily, plus LFD instruction (<30% energy from fat, 500-1000 kcal/day deficit) delivered at group meetings over 48 weeks. Main outcome measures were body weight, blood pressure, fasting serum lipid, and glycemic parameters.
Results: The mean age was 52 years, and mean body mass index was 39.3 kg/m2; 72% were men, 55% were black, and 32% had type 2 diabetes mellitus. Of the study participants, 57 of the LCKD group (79%) and 65 of the O + LFD group (88%) completed measurements at 48 weeks. Baseline kcal/day energy intake and g/day of carbohydrates (carb), total fat, and type of fat were similar between groups. At 48 weeks, the reduction in total energy intake was similar (25%); the LCKD group had an average carb intake of 62 g/day and total fat 107 g/day compared to the O + LFD with 186 g/day of carbs and 57 g/day of total fat. The group assigned a LFD (defined as <30% of calories) averaged about 25% fat. The majority of weight loss for both interventions occurred in the first 12-24, weeks with maximum weight loss achieved at 24-36 weeks. Weight loss was similar for the LCKD (mean change, -9.5%) and the O + LFD (-8.5%) (p = 0.60 for comparison) groups. The LCKD had a more beneficial impact than O + LFD on systolic (-5.9 vs. 1.5 mm Hg) and diastolic (-4.5 vs. 0.4 mm Hg) blood pressures (p < 0.001 for both comparisons). High-density lipoprotein cholesterol and triglyceride levels improved similarly within both groups. Low-density lipoprotein cholesterol levels improved within the O + LFD group only, whereas glucose, insulin, and hemoglobin A1c levels improved within the LCKD group only; comparisons between groups, however, were not statistically significant.
Conclusions: In a sample of medical outpatients, an LCKD led to similar improvements as O + LFD for weight, serum lipid, and glycemic parameters, and was more effective for lowering blood pressure.
Perspective: The results in the high-fat LCKD are more impressive than usual because in most other studies, patients do not have the ability to tolerate the fat-induced ketosis and resume a higher carb intake and reduce the fat intake. This was not the case in this study lasting a year, which is also longer than most. As in other studies, this one demonstrated that weight loss is greater in those who attend more group sessions, which implies that these were effective, and that the patients were highly motivated. While the high-fat and low-carb diet is clearly helpful for weight reduction, studies are necessary to determine whether it improves cardiovascular and other outcomes without inducing unintended consequences. Until such studies are available, the Mediterranean diet with a 500-1000 kcal/day deficit seems to be the safest and most effective for long-term weight control and metabolic health. Melvyn Rubenfire, M.D., F.A.C.C.

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Title: Association Between a Literature-Based Genetic Risk Score and Cardiovascular Events in Women
Topic: Prevention/Vascular
Date Posted: 2/17/2010
Author(s): Paynter NP, Chasman DI, Pare G, et al.
Citation: JAMA 2010;303:631-637.
Clinical Trial: No
Study Question: What is the ability of a literature-based genetic risk score to predict cardiovascular disease (CVD)?
Methods: Data from the Women’s Genome Health Study, a prospective cohort study of 19,313 women, were used for the present analysis. Women were followed for a median of 12.3 years. Genetic risk scores were created using the National Human Genome Research Institute's catalog of genome-wide association study results published between 2005 and 2009. The outcomes of interest included myocardial infarction (MI), stroke, arterial revascularization, and cardiovascular death.
Results: A total of 101 single nucleotide polymorphisms reported to be associated with CVD or at least one intermediate CVD phenotype (at a published p value of <107) were identified and risk alleles were added to create a genetic risk score. A total of 777 CVD events occurred during follow-up, including 199 MIs, 203 strokes, 63 CVD deaths, and 312 revascularization events. After adjustment for age, the genetic risk score was associated with CVD events (hazard ratio [HR], 1.02 per risk allele; 95% confidence interval [CI], 1.00-1.03). The corresponding absolute CVD risk was 3% over 10 years in the lowest tertile of genetic risk and 3.7% over 10 years in the highest tertile of genetic risk. After further adjustment for traditional risk factors, the genetic risk score did not improve discrimination or reclassification in risk score. The genetic risk score was not associated with CVD risk (HR, 1.00 Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults-adjusted/allele; 95% CI, 0.99-1.01). Family history remained significantly associated with CVD risk.
Conclusions: The authors concluded that after adjustment for traditional risk factors, a genetic risk score was not significantly associated with incidence of CVD.
Perspective: This is an important study, which advances our understanding regarding the potential use of genetics in CVD risk. Given these results, continued use of traditional risk factors including the prevention of risk factors such as hypertension, hypercholesterolemia, diabetes, and obesity are the foundations of CVD practice. Elizabeth A. Jackson, M.D., F.A.C.C.

Title: Effectiveness of Extended-Duration Transdermal Nicotine Therapy: A Randomized Trial
Topic: Prevention/Vascular
Date Posted: 2/22/2010
Author(s): Schnoll RA, Patterson F, Wileyto EP, et al.
Citation: Ann Intern Med 2010;152:144-151.
Clinical Trial: yes
Study Question: Does extended nicotine therapy improve abstinence from tobacco?
Methods: This was a randomized controlled trial, which compared extended-duration nicotine replacement (24 weeks), standard-duration nicotine replacement (8 weeks), and placebo (16 weeks) for abstinence from tobacco. Participants were blinded to assignment. Subjects were eligible if they sought treatment for smoking from October 2004 to March 2008, were age 18-65 years, smoked 10 or more cigarettes per day for the past year or more, and had no comorbid conditions such as heart attack or stroke within the prior 6 months. Women who were pregnant or lactating, and people with a history of drug or alcohol abuse were excluded, as were those who were under current treatment for nicotine addiction. Abstinence from tobacco was confirmed by carbon monoxide levels at weeks 24 and 52. Secondary outcome measures included quitting characteristics such as lapses, relapse, and recover events.
Results: A total of 568 adult smokers were included. At 24 weeks, subjects randomized to extended-duration nicotine replacement had higher rates of point-prevalence abstinence compared to standard-duration therapy (31.6% vs. 20.3%; odds ratio [OR], 1.81; 95% confidence interval [CI], 1.23-2.66). Similar patterns were noted for prolonged abstinences (41.5% vs. 26.9%; OR, 1.97; 95% CI, 1.38-2.82) and continuous abstinence (19.2% vs. 12.6%; OR, 1.64; 95% CI, 1.04-2.60). Extended-duration therapy also reduced risk for lapse (OR, 0.77; 95% CI, 0.63-0.95) and improved chances for recovery after a lapse (OR, 1.47; 95% CI, 1.17-1.84). At 52 weeks, extended-duration therapy was associated with higher quit rates for prolonged abstinence. Time to relapse was longer among those randomized to extended-duration therapy compared to those on standard-duration therapy.
Conclusions: The investigators concluded that extended-duration nicotine therapy increased continuous abstinence at 24 weeks, with lower lapses and increased recovery after a lapse.
Perspective: Further study is warranted regarding the use of extended duration of nicotine therapy for smokers, including research in other populations such as those with heart disease, prior to widespread acceptance of extended-duration therapy. However, these data suggest the potential benefit for nicotine replacement beyond 8 weeks in many smokers. Elizabeth A. Jackson, M.D., F.A.C.C.

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Cocaine Sudden Death in Europe
ICTUS: Five Year Outcomes
ACC Members Fight Fee Schedule Cuts
[Ссылки доступны только зарегистрированным пользователям ]

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Title: Vascular Inflammation in Obesity and Sleep Apnea
Topic: Prevention/Vascular
Date Posted: 2/24/2010
Author(s): Jelic S, Lederer DJ, Adams T.
Citation: Circulation 2010;121:1014-1021.
Clinical Trial: No
Study Question: Both obesity and obstructive sleep apnea (OSA) are associated with vascular endothelial inflammation and increased risk for cardiovascular diseases. Are the endothelial alterations that are attributed commonly to obesity in fact related to OSA?
Methods: Seventy-one subjects with a body mass index ranging from normal to obese underwent attended polysomnography. To assess vascular inflammation and oxidative stress directly, the expression of nuclear factor-ĸB and nitrotyrosine were quantified by immunofluorescence in freshly harvested venous endothelial cells. Basal endothelial nitric oxide (NO) production and activity were quantified by the expression of endothelial NO synthase (eNOS) and phosphorylated eNOS. Vascular reactivity was measured by brachial artery flow-mediated dilation.
Results: Expression of eNOS and phosphorylated eNOS and flow-mediated dilation were significantly lower, whereas expression of nitrotyrosine was significantly greater in OSA patients (n = 38) than in OSA-free subjects (n = 33) regardless of central adiposity. Expression of nuclear factor-ĸB was greater in obese OSA patients than in obese OSA-free subjects (p = 0.004). Protein expression and flow-mediated dilation were not significantly affected by increasing body mass index or central obesity in OSA patients and in OSA-free subjects. After 4 weeks of continuous positive airway pressure therapy, flow-mediated dilation and expression of eNOS and phosphorylated eNOS significantly increased, whereas expression of nitrotyrosine and nuclear factor-ĸB significantly decreased in OSA patients who adhered to continuous positive airway pressure ≥4 hours daily.
Conclusions: Untreated OSA rather than obesity is a major determinant of vascular endothelial dysfunction, inflammation, and elevated oxidative stress in obese patients.
Perspective: This study adds to the body of evidence that OSA may contribute to coronary risk and cardiovascular events. A few of the cardiometabolic effects of OSA include hypertension, increase in high-sensitivity C-reactive protein, heightened sympathetic tone, reactive platelets, dysglycemia, insulin resistance, and increase in cortisol, leptin, and growth hormone. Melvyn Rubenfire, M.D., F.A.C.C.

Title: Early and Late Outcome of Treated Patients Referred for Syncope to Emergency Department: the EGSYS 2 Follow-Up Study
Topic: Arrhythmias
Date Posted: 2/24/2010
Author(s): Andrea U, Attilio DR, Franco G, et al., on behalf of the Evaluation of Guidelines in Syncope Study 2 (EGSYS 2) Group.
Citation: Eur Heart J 2010;Feb 18:[Epub ahead of print].
Clinical Trial: yes
Study Question: What is the prognosis of patients with syncope?
Methods: This was a multicenter, prospective study of 380 patients (mean age 66 years) with syncope initially evaluated in an emergency department (ED). Therapy was at the discretion of the treating physician. The mean duration of follow-up was 20 months. The 1° endpoint was death from any cause or syncope recurrence.
Results: The most common causes of syncope were neurocardiogenic syncope in 64% of patients, orthostatic hypotension in 17%, cardiac syncope in 15%, and an arrhythmia in 11%. All-cause mortality was 9.2%. The strongest predictors of mortality were structural heart disease or an abnormal electrocardiogram (hazard ratio [HR], 5.6), hypertension (HR, 3.0), and trauma from syncope (HR, 2.24). Mortality in patients with cardiac syncope was significantly higher than in patients with other causes of syncope (37% vs. 7-11%). Syncope recurred in 16% of patients and the recurrence rate was unrelated to the etiology of syncope. The strongest predictors of recurrent syncope were palpitations before syncope (HR, 3.4), male gender (HR, 1.8), and absence of prodrome (HR, 0.4).
Conclusions: The risk of death during follow-up in patients with syncope is related to associated cardiac disease. Syncope recurrence is unrelated to the cause of syncope.
Perspective: A limitation of this study is that left ventricular ejection fraction was not included in the analysis and probably would have been a stronger predictor of mortality than simply the presence of structural heart disease. Fred Morady, M.D., F.A.C.C.

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Title: Drug Elution and Distal Protection in ST-Elevation Myocardial Infarction (DEDICATION: Distal Protection Study)
Trial Sponsor: N/A
Year Published 2008
Topic(s): Interventional Cardiology
Summary Posted: 2/22/2010 5:00:00 PM
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
Description
The goal of the trial was to evaluate distal embolic protection prior to percutaneous coronary intervention (PCI) compared with PCI without embolic protection in native vessels in patients with ST-elevation myocardial infarction (STEMI).
Hypothesis
Distal embolic protection prior to PCI would be more effective in improving myocardial perfusion than PCI without embolic protection.
Drugs/Procedures Used
Patients were randomized to distal embolic protection prior to PCI (n = 312) or PCI without embolic protection (n = 314). Patients also received a drug-eluting stent versus bare-metal stent by 2 x 2 factorial design (results presented separately).
Principal Findings
Patients were well matched with baseline characteristics. In the embolic protection group, 81% received the FilterWire device, 13% received the SpideRx device, and in the remaining patients, distal protection could not be achieved. Initial Thrombolysis In Myocardial Infarction (TIMI) 0 or 1 flow was present in 67% of the embolic protection group and 68% of the PCI alone group. Similarly, visible thrombus was present in 68% and 75%, respectively.

For the primary outcome, complete ST-segment resolution occurred in 76% of the embolic protection group and 72% of the PCI alone group (p = 0.29). There was no difference in the primary outcome among any subgroup tested. There was no difference in the maximum level of creatine-kinase (p = 0.99), troponin T (p = 0.87), or wall motion index (p = 0.35) between the groups. There was also no difference in 30-day major adverse cardiac events (5.4% vs. 3.2%, p = 0.17), respectively for embolic protection versus PCI alone.

At 15 months, definite stent thrombosis had occurred in 2.9% of the embolic protection group versus 0.3% of the PCI alone group (p = 0.02) and target lesion revascularization was 12.5% versus 7% (p = 0.02), respectively.
Interpretation
Among patients with STEMI, distal embolic protection prior to PCI did not reduce the incidence of complete ST-segment resolution, maximum level of cardiac enzymes, wall motion index, or major adverse cardiac events compared with PCI alone. In fact, there were increased adverse events late in follow-up.

This trial complements the earlier EMERALD trial, which failed to show that GuardWire balloon occlusion improves the myocardial circulation compared with standard PCI alone. These findings are in contradistinction to the recently published TAPAS trial, which revealed that thrombus aspiration by the Export catheter significantly improved myocardial reperfusion.
Conditions
• Coronary heart disease / Acute MI
• Coronary heart disease
Therapies
• Stent
• PTCA
Study Design
Randomized.
Patients Screened: 1,687
Patients Enrolled: 626
Mean Follow-Up: 15 months
Mean Patient Age: 62 years
% Female: 26%

Primary Endpoints
Rate of complete (>70%) ST-segment resolution 90 minutes after PCI detected by continuous ST-segment monitoring
Secondary Endpoints
Time to >70% ST-segment resolution, maximal cardiac biomarkers, wall motion index by echocardiography at discharge, and major adverse cardiac events
Other Design Considerations
At the time of enrollment, patients underwent a second randomization to a drug-eluting stent versus a bare-metal stent.
Patient Population
STEMI within 12 hours of symptom onset with total ST-elevation of 4 mm in contiguous leads, age at least 18 years, and occluded or severely stenosed coronary artery without excessive calcification or tortuosity
Exclusions:
Previous MI, left main infarct-related artery, history of gastrointestinal bleeding, pregnancy, renal failure, limited (<1 year) life expectancy, or linguistic problems
References: Kaltoft A, Kelbжk H, Klшvgaardet L, al. 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. J Am Coll Cardiol 2010;55:867-71.

Presented by Dr. Leif Thuesen at the i2 Summit/American College of Cardiology Annual Scientific Session, New Orleans, LA, March 2007.

Kelbaek H, Terkelsen CJ, Helqvist S, et al. Randomized comparision of distal protection versus conventional treatment in primary percutaneous coronary intervention: The Drug Elution and Distal Protection in ST-Elevation Myocardial Infarction (DEDICATION) Trial. J Am Coll Cardiol 2008;51:899-905.

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Title: Comparison of Platelet Function Tests in Predicting Clinical Outcome in Patients Undergoing Coronary Stent Implantation
Topic: Interventional Cardiology
Date Posted: 2/23/2010 4:00:00 PM
Author(s): Breet NJ, van Werkum JW, Bouman HJ, et al.
Citation: JAMA 2010;303:754-762.
Clinical Trial: No
Study Question: Can platelet function tests performed at time of percutaneous coronary intervention (PCI) predict clinical outcome?
Methods: The authors prospectively studied 1,069 consecutive patients that underwent elective stent-based PCI at their institution between December 2005 and December 2007. All patients were on clopidogrel, and on-treatment platelet reactivity was measured in all patients using light transmittance aggregometry, VerifyNow P2Y12 assay, Plateletworks assay, IMPACT-R, and the platelet function analysis system (PFA-100). Cut-off values for high on-treatment platelet reactivity were established by receiver operating characteristic curve analysis. The primary endpoint was a composite of all-cause death, nonfatal acute myocardial infarction, stent thrombosis, and ischemic stroke. The primary safety endpoint included TIMI major and minor bleeding.
Results: One-year follow-up was available for 99.8% of the patients. Adherence to clopidogrel was 95% after 6 months and 82% at 1 year. Over 1-year follow-up, there were 18 deaths (1.7%), 6.0% had nonfatal acute myocardial infarction, 1.2% presented with definite stent thrombosis, and 1.3% had a nonfatal ischemic stroke. There were three possible stent thromboses (0.3%), and bleeding events occurred in 5.1% of the patients (TIMI-major 3.1%, TIMI-minor bleeding 2.2%).The primary endpoint occurred more frequently in patients with high on-treatment platelet reactivity when assessed by light transmittance aggregometry (11.7% vs. 6.0%; p < 0 .001 area under the curve [AUC], 0.63), VerifyNow (13.3% vs. 5.7%, p < 0.001, AUC 0.62), and Plateletworks (12.6% vs. 6.1%, p = 0.005, AUC 0.61). The other assays were not able to discriminate between those with or without ischemic events. None of the tests identified patients at risk for bleeding.
Conclusions: Assessment of platelet function using light transmittance aggregometry, VerifyNow, and Plateletworks was significantly but modestly associated with ischemic events at 1 year.
Perspective: Multiple studies have established an association between a lesser degree of platelet inhibition and the occurrence of atherothrombotic events. The field has been clouded by the use of multiple platelet function assays with little inter-assay correlation. This study, with its large population and nearly 100% follow-up, provides much needed clarity to the field. Only three assays demonstrated a significant albeit moderate association between ischemic outcomes and degree of platelet inhibition. Given the moderate strength of the association, it would be premature to use platelet function testing to guide routine clinical practice at present. Hitinder S. Gurm, M.B.B.S., F.A.C.C.

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Title: Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment (ISAR-REACT 3)
Trial Sponsor: Nycomed Pharma GmbH, Unterschleibheim, Germany, and Deutsches Herzzentrum, Munich, Germany
Year Presented: 2008
Year Published 2008
Topic(s): General Cardiology, Interventional Cardiology
Summary Posted: 2/22/2010
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
Downloadable Slide Set: Bivalirudin Versus Unfractionated Heparin in Biomarker Negative Patients With Stable and U...
Summary Slide: ISAR-REACT 3 Trial
Related Trial: Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment (ISAR-REACT 2)
Related Trial: Intracoronary Stenting and Antithrombotic Regimen Rapid Early Action for Coronary Treatment (ISAR REACT)
Journal Scan: Bivalirudin Versus Unfractionated Heparin During Percutaneous Coronary Intervention

Description
The goal of this trial was to assess whether bivalirudin is superior to unfractionated heparin (UFH) in terms of ischemic and hemorrhagic endpoints in troponin-negative patients undergoing percutaneous coronary intervention (PCI), after pretreatment with clopidogrel.
Hypothesis
Bivalirudin would be superior to UFH as an adjunct anticoagulant in troponin-negative patients undergoing PCI.
Drugs/Procedures Used
Patients who were biomarker negative, and who were undergoing PCI for stable or unstable angina were randomized to receive either UFH (bolus of 140 U/kg, followed by placebo infusion) or bivalirudin (bolus of 0.75 mg/kg, followed by infusion of 1.75 mg/kg/hr) during the procedure, in addition to 600 mg of clopidogrel and ≥325 mg aspirin at least 2 hours prior to the procedure.
Concomitant Medications
All patients received aspirin 80-325 mg indefinitely. Clopidogrel was continued as 75-150 mg/day for ≤3 days, and then 75 mg/day for at least 1 month after balloon angioplasty or implantation of bare-metal stents and for at least 6 months after implantation of drug-eluting stents.
Principal Findings
A total of 4,570 patients were randomized, 2,289 to the bivalirudin arm, and 2,281 to the UFH arm. The baseline characteristics of the two arms were comparable. About 27.4% of the patients were diabetic. The majority of patients (81.7%) had stable angina; the rest had unstable angina. The baseline ejection fraction was 58%, and 80% had evidence of multivessel disease. The majority of stents (87.7%) were drug-eluting stents.

The primary endpoint, a composite rate of death, myocardial infarction (MI), urgent target vessel revascularization, or in-hospital major bleeding at 30 days, was similar between the two arms (8.3% vs. 8.7% for bivalirudin and UFH, respectively; relative risk [RR] 0.94, 95% confidence interval [CI] 0.77-1.15; p = 0.57). The incidence of death, MI, and urgent target vessel revascularization (TVR) was 0.1% and 0.2% (p = 0.7), 5.6% and 4.8% (p = 0.24), and 0.8% and 0.7% (p = 0.75), for bivalirudin and UFH, respectively. The secondary endpoint of death, MI, and urgent revascularization at 30 days was 5.9% in the bivalirudin arm and 5.0% in the UFH arm (RR 1.16, 95% CI 0.91-1.49; p = 0.23).

The incidence of major bleeding was significantly reduced by 33% with bivalirudin (3.1%) compared with UFH (4.6%) (RR 0.66, 95% CI 0.49-0.90; p = 0.008). Similarly, the incidence of minor bleeding was significantly reduced (p = 0.0001). The incidence of transfusions and thrombocytopenia was similar between the two groups at 30 days.

At 1 year, the incidence of the primary endpoint was similar between the bivalirudin and heparin arms (17.1% vs. 17.5%, p = 0.82). Other endpoints such as death (1.9% vs. 1.7%, p = 0.67), MI (6.0% vs. 5.3%, p = 0.32), TVR (11.2% vs. 12.5%, p = 0.18), and definite stent thrombosis (0.7% vs. 0.7%, p = 1.0) were also similar between the two arms.
Interpretation
Bivalirudin had outperformed UFH (without glycoprotein IIb/IIIa) in a few trials, but pretreatment with clopidogrel was not routinely accomplished in these trials. This randomized trial sought to define the optimal adjunct anticoagulation therapy for troponin-negative patients with stable and unstable angina undergoing PCI, who were pretreated with 600 mg of clopidogrel. The results of this trial indicate that bivalirudin is not superior to UFH in these patients in reducing the incidence of death, MI, or need for urgent revascularization, although the incidence of major and minor bleeding is significantly reduced at 30 days. No difference was noted in any of the ischemic endpoints up to 1 year of follow-up.

The dose of heparin used in this study (140 U/kg) is higher than the dose used in other recent PCI trials. Moreover, activated clotting time was not routinely monitored in these patients. It is unknown to what extent this may have affected the primary endpoint, especially bleeding.
Conditions
• Coronary heart disease
Therapies
• Antiplatelet agent / Clopidogrel
• Anticoagulant / Heparin
• Anticoagulant / Bivalirudin
Study Design
Randomized. Blinded. Parallel.
Patients Enrolled: 4,570
Mean Follow-Up: 1 year
Mean Patient Age: 67
% Female: 24

Mean Ejection Fraction: 58%
Primary Endpoints
Composite rate of death, MI (creatine kinase-myocardial band [CK-MB] >2x upper limit of normal [ULN]), urgent TVR within 30 days, or in-hospital major bleeding
Secondary Endpoints
Composite rate of death, MI (CK-MB >2x ULN), or urgent TVR
Patient Population
Biomarker-negative (troponin T <0.03 μg/L or CK-MB less than ULN) patients undergoing PCI
Received 600 mg of clopidogrel at least 2 hours prior to the procedure
Age >18 years
Exclusions:
Acute coronary syndromes with positive biomarkers or ST-elevation MI <48 hours
Cardiogenic shock
History of heparin-induced thrombocytopenia or other bleeding diatheses
Creatinine >3 mg/dl
References: Schulz S, Mehilli J, Ndrepepa G, et al., on behalf of the ISAR-REACT 3 Trial Investigators. Bivalirudin vs. unfractionated heparin during percutaneous coronary interventions in patients with stable and unstable angina pectoris: 1-year results of the ISAR-REACT 3 trial. Eur Heart J 2010;Feb 11:[Epub ahead of print].

Kastrati A, Neumann FJ, Mehilli J, et al., on behalf of the ISAR-REACT 3 Trial Investigators. Bivalirudin versus unfractionated heparin during percutaneous coronary intervention. N Engl J Med 2008;359:688-96.

A Randomized, Double-Blind, Active-Controlled, Multi-Center Trial (ISAR-REACT 3) of Bivalirudin Versus Unfractionated Heparin in Troponin-Negative Patients Undergoing Percutaneous Coronary Interventions After Pre-Treatment With 600 mg of Clopidogrel. Presented by Dr. Adnan Kastrati at the SCAI-ACC i2 Summit/American College of Cardiology Annual Scientific Session, Chicago, IL, March/April 2008.

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Title: Outcomes and Complications of Catheter Ablation for Atrial Fibrillation in Females
Topic: Arrhythmias
Date Posted: 2/23/2010
Author(s): Patel D, Mohanty P, Biase L, et al.
Citation: Heart Rhythm 2010;7:167-172.
Clinical Trial: No
Study Question: Are there gender-based differences in the results of radiofrequency catheter ablation (RFCA) of atrial fibrillation (AF)?
Methods: This was a retrospective analysis of 518 women and 2,747 men who underwent RFCA of AF with a 3.5-mm irrigated-tip ablation catheter. All patients underwent pulmonary vein antrum isolation, with superior vena cava isolation and ablation of fractionated atrial electrograms as clinically indicated. Daily event monitor recordings were obtained for the first 5 months post-ablation, and a 48-hour or 7-day Holter monitor was performed at 3- to 6-month intervals. Efficacy was defined as freedom from AF/atrial tachycardia in the absence of antiarrhythmic drug therapy after an 8-week blanking period.
Results: The women were significantly older than the men (mean age 59 vs. 56 years) and the interval from diagnosis to referral for RFCA was significantly longer in the women (6.5 vs. 4.8 years). At a mean of 24 months of follow-up, efficacy was significantly lower in the women (68.5% vs. 77.5%). In women, higher body mass index, persistent AF, and nonpulmonary vein triggers were independent predictors of failure. There were no significant differences in the rate of complications other than vascular complications, which were more common in women (2.7% vs. 1.0%).
Conclusions: The authors concluded that women are referred for ablation of AF less often and later than men, and the efficacy of RFCA of AF is lower in women than men.
Perspective: Women also appear to be under-referred for diagnostic cardiovascular testing, defibrillator implantation, and coronary artery bypass grafting. The reason for this gender discrepancy is unclear. The lower efficacy of RFCA in women may be related to greater atrial remodeling associated with the longer interval from diagnosis to ablation. Fred Morady, M.D., F.A.C.C.

Title: Characterization of Conduction Recovery After Pulmonary Vein Isolation Using the “Single Big Cryoballoon” Technique.
Topic: Arrhythmias
Date Posted: 2/26/2010
Author(s): Furnkranz A, Chun KR, Nuyens D, et al.
Citation: Heart Rhythm 2010;7:184-190.
Clinical Trial: No
Study Question: What is the pattern of pulmonary vein (PV) reconnection after PV isolation using a 28-mm cryoablation balloon?
Methods: Thirty-five of 71 patients with paroxysmal atrial fibrillation (AF) had recurrent AF after undergoing PV isolation using a cryoablation balloon. The subjects of this study were the 26/35 patients (mean age 59 years) who underwent a repeat ablation procedure. The PVs were mapped with a ring catheter to identify sites of PV reconnection, and PV isolation was performed by radiofrequency catheter ablation (RFCA).
Results: PV reconnection was found in all patients. One PV was reconnected in 15% of patients, two PVs in 31%, three PVs in 35%, and four PVs in 19%. Conduction gaps were identified most commonly at the inferior aspect of the right PVs and the anterior ridge between the left PVs and the left atrial appendage. All PVs were successfully re-isolated by RFCA. During a mean follow-up of 98 days, 69% of the 26 patients remained AF-free.
Conclusions: When a 28-mm cryoablation balloon is used to isolate the PVs, the most common sites of conduction recovery are the inferior ostial sites and the left atrial appendage-PV ridge.
Perspective: An advantage of cryoablation over RFCA for PV isolation is a much lower risk of PV stenosis and esophageal injury. However, reliable cryoablation requires continuous tissue contact between the balloon and antral or ostial tissue. This can be difficult to attain because of variable shapes and sizes of the PV ostia, particularly when only a 28-mm balloon is used. Published clinical experience suggests that more reliable PV isolation can be achieved when the balloon size is tailored to individual PVs. Fred Morady, M.D., F.A.C.C.