Обзор американских кардиологических журналов за неделю (ссылки)

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SADHART-CHF: Sertraline safe but provided no benefits for patients with HF, depression vs. placebo
Goodlin S. J Am Coll Cardiol. 2010;56:700-701.
O’Connor C. J Am Coll Cardiol. 2010;56:692-699.

Sertraline vs. placebo was safe in patients with HF and depression, but did not provide greater reduction in depression or improved CV status, study results suggested.
The Sertraline Against Depression and Heart Disease in Chronic Heart Failure (SADHART-CHF) trial was a randomized, double blind, placebo-controlled trial, which compared 50 to 200 mg/day of sertraline vs. matching placebo for 12 weeks. Patients (n=469) were at least 45 years of age and had HF (left ventricular ejection fraction ≤45%, NYHA Class II-IV) and clinical depression (DSM-IV criteria for current major depressive disorder). Primary endpoints were change at 12 weeks in depression severity determined by the Hamilton Depression Rating Scale total score and composite CV status.
According to study results, the mean ± SE change from baseline to 12 weeks for the sertraline patients (n=234) was–7.1 ± 0.5, and for those in the placebo arm (n=235), it was –6.8 ± 0.5 (mean change between groups, 0.4; 95% CI,–1.7 to 0.92). Additional statistics in the sertraline group indicated that the percentage of patients with a composite CV score that worsened was 29.9%, improved was 40.6% and unchanged was 29.5%; in the placebo group, the percentages were 31.1% for those with worsened scores, 43.8% for those whose scores improved and 25.1% for those whose scores did not change.

“Sertraline did not adversely affect CV outcomes in this population, and it may be an appropriate therapeutic strategy in patients who remain depressed despite nonpharmacologic interventions and who otherwise have an indication for sertraline,” researchers concluded.

In an accompanying editorial, Sarah J. Goodlin, MD, with Patient-Centered Education and Research, Salt Lake City, summarized the key findings from the trial.

“The SADHART-CHF trial tells us that discontinuation or adverse event rates were a bit higher with low-dose sertraline than with placebo, that low to moderate doses of sertraline are not associated with increased HF decompensation or death, and that supportive nursing interventions seem as effective as low-dose sertraline for HF patients with moderate depressive symptoms,” she said. “Further research is needed to tell us whether higher doses of sertraline or other antidepressants are both safe and effective.”
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Binge drinking in patients with hypertension associated with high risk for CV mortality
Sull JW. Stroke. 2010;doi:10.1161/strokeaha.110.586347.

Older adult Koreans with hypertension and habits of binge drinking had a markedly higher risk for CV mortality, which was increased nearly threefold in those considered heavy binge drinkers.

Researchers conducted this study with residents (n=6,100) of Kangwha County, Korea, who were at least 55 years old as of March 1985. They followed participants for a maximum of 20.8 years until Dec. 31, 2005, and calculated HRs for CV mortality by BP and binge drinking habits. Binge drinking was defined as having at least six drinks on one occasion, and heavy binge drinking was defined as having at least 12 drinks on one occasion.

During follow-up, 759 patients died of CVD. Compared with nondrinkers with normal BP, male heavy binge drinkers with grade 3 hypertension had a 12-fold higher risk of CV mortality (HR=12.7; 95% CI, 3.47-46.5), whereas male binge drinkers with the same grade hypertension had a fourfold increased risk for CV mortality (HR=4.41; 95% CI, 1.38-14.1). Conversely, the separate effects on CV mortality risk for heavy binge drinking (HR=1.88; 95% CI, 1.10-3.20) and hypertension (HR=2.00; 95% CI, 1.70-2.35) when compared with nondrinkers with normal BP were considerably lower than when combined.

Limitations with this study, in particular the study population of people aged at least 55 years living in an agricultural community with a small population of female drinkers, led the researchers to propose that future studies examine the joint effects of hypertension and binge drinking in a population more inclusive of both genders.

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Drug-eluting stents shown to confer better long-term CV benefits than bare metal stents
Bental T. Catheter Cardiovasc Interv. 2010; doi:10.1002/ccd.22507.

The use of drug-eluting stents vs. bare metal stents improved the overall long-term clinical outcome in a group of “all comers,” including rates of death, MI and target vessel revascularization.
The study featured in Catheterization and Cardiovascular Interventions utilized a registry of 6,583 consecutive patients who underwent percutaneous coronary intervention, which was broken into two arms: those treated with drug-eluting stents (n=2,633) and those treated with bare metal stents (n=3,950). Researchers used a propensity score for stratified analysis of outcomes and matching, and defined outcomes as total mortality, MI, repeat target vessel revascularization rates and risk-adjusted event-free survival.
After a mean follow-up of 3 years (range, 6 months to 5.18 years), results indicated that patients in the drug-eluting stent group were more likely to be diabetic, have use of longer or more stents, and have treatment of more lesions and proximal main vessels.
Propensity score matching revealed a cumulative mortality rate of 12.85% in the drug-eluting stent group vs. 14.14% in the bare metal stent group (P=.001). The use of drug-eluting stents vs. bare metal stents reduced the occurrence of MI (5.17% vs. 5.83%, P=.046), clinically driven target vessel revascularization (9.76% vs. 12.28%, P<.001) and the composite endpoint of death, MI and target vessel revascularization (23.38% vs. 26.07%; P<.001).
“The use of drug-eluting stents improves the long-term clinical outcome (death/MI/target vessel revascularization) among a group of ‘all-comer’ patients in a wide variety of clinical scenarios,” researchers concluded. “We assume that this benefit is probably a combination of a drug-eluting stent’s advantage as a stent and of a more aggressive treatment strategy, given the higher confidence in long-term patency.”
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U.S. EDs experienced significant increases in patient visits during 10-year interval
Tang N. JAMA. 2010;304:664-670.

Results from a survey of hospital EDs indicated that ED visits were on the rise from 1997 and 2007 and that EDs increasingly served as the safety net for medically underserved patients, particularly adults with Medicaid.
“The total annual visits to U.S. EDs increased by 23% — corresponding to an estimated 21 million additional ED visits nationwide,” the researchers reported in their study. “This is roughly twice the rate of growth of the U.S. population over the same time period.”
In this study, researchers from the University of California, San Francisco, used publicly available ED visit data from the National Hospital Ambulatory Medical Care Survey from 1997 through 2007. The data were stratified by the following: age, sex, race, ethnicity, insurance status, safety-net hospital classification, triage category and disposition. The researchers used codes from the ICD-9 to extract visits related to ambulatory care–sensitive conditions and determined visit rates using annual U.S. Census estimates.
During the 10 years, ED visit rates rose from 352.8 to 390.5 per 1,000 people (rate difference, 37.7; 95% CI, –51.1 to 126.5), with the median ED wait time to see physicians increasing from 22 to 33 minutes (P<.001). Adults with Medicaid accounted for most of the increase in ED visits, with increases in visit rate during 1999 and 2007 from 693.9 to 947.2 visits per 1,000 enrollees (rate difference, 253.3; 95% CI, 41.1-465.5).
Additionally, during the same 8-year period, ED visit rates among adults with Medicaid increased from 66.4 to 83.9 (rate difference, 17.5; 95% CI, -5.8 to 40.8), despite ED visit rates for adults with ambulatory care–sensitive conditions remaining stable. The number of facilities qualifying as safety-net EDs also increased, with numbers starting at 1,770 in 2000 and rising to 2,489 in 2007.
“Even though our study includes the latest available data on U.S. ED visits through 2007, a critical concern is what has happened in more recent years,” the researchers wrote, citing the Medicaid enrollment spike as their main concern, which resulted from an increase in the number of the uninsured due to the severe economic recession that began in 2008.
“Our findings suggest that increased enrollments in Medicaid between 1999 and 2007 have had substantial effects on ED volume and crowding, and that at least part of this may reflect limited access to primary care services for Medicaid enrollees,” they wrote. “A deeper examination of the differential access to primary care by insurance type is needed to better understand health care utilization patterns by patients with Medicaid and to develop more effective strategies for reducing pressure on the safety net.”

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Title: Chocolate Intake and Incidence of Heart Failure: A Population-Based Prospective Study of Middle-Aged and Elderly Women
Date Posted: August 23, 2010
Authors: Mostofsky E, Levitan EB, Wolk A, et al.
Citation: Circ Heart Fail 2010;Aug 16:[Epub ahead of print].

Study Question:
Does chocolate intake reduce incidence of heart failure among women?
Methods:
This was a prospective cohort study of women enrolled in the Swedish Mammography Cohort. Women, ages 48-83 years, with no history of diabetes, heart failure, or myocardial infarction at baseline, were followed from January 1998 through December 2006. Women completed surveys on health and lifestyle, in addition to completing a food frequency questionnaire. The primary outcomes of interest were hospitalization for heart failure, or death due to heart failure, which were obtained through the Swedish inpatient and cause-of-death registries.
Results:
A total of 31,823 women were included in this analysis. Over 9 years of follow-up, 379 women were hospitalized for heart failure, and 40 died from heart failure. Compared to women who reported no regular intake of chocolate, women who consumed chocolate were less likely to have heart failure, with decreasing risk associated with moderate intake. For women consuming between 1-3 servings of chocolate per month, the risk ratio was 0.74 (95% confidence [CI], 0.58-0.95), for women consuming 1-2 servings per week, the RR was 0.68 (95% CI, 0.50-0.93), whereas for women consuming 3-6 servings per week, the RR was 1.09 (95% CI, 0.74-1.62), and for women consuming one or more servings per day, the RR was 1.23 (95% CI, 0.73-2.08).
Conclusions:
The investigators concluded that moderate chocolate intake was associated with decreased risk for heart failure.
Perspective:
This study suggests that moderate chocolate consumption has health benefits for women, specifically in regards to incident heart failure. However, to fully explore the investigators’ hypothesis, that cocoa is inversely associated with heart failure, understanding the intake of different types of chocolate in relation to cocoa content is needed. It is also possible that other dietary factors differed among the groups examined; thus, exploring the addition of other dietary factors beyond milk consumption would be recommended.
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Title: Gender Differences in Time to Presentation for Myocardial Infarction Before and After a National Women’s Cardiovascular Awareness Campaign: A Temporal Analysis From the Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation (CRUSADE) and the National Cardiovascular Data Registry Acute Coronary Treatment and Intervention Outcomes Network-Get With the Guidelines (NCDR ACTION Registry–GWTG)
Date Posted: August 17, 2010
Authors: Diercks DB, Owen KP, Kontos MC, et al.
Citation: Am Heart J 2010;160:80-87.

Study Question:
Does a national awareness campaign regarding heart disease result in reducing time from symptoms to presentation for acute coronary syndrome among women?
Methods:
Data from two large-scale registries were used for this analysis. Patients with non-ST-elevation myocardial infarction (NSTEMI) from the Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation (CRUSADE) and the National Cardiovascular Data Registry Acute Coronary Treatment and Intervention Outcomes Network-Get With the Guidelines (NCDR ACTION Registry–GWTG) were grouped into three time periods (preintervention 2002-2003, intermediate 2004-2005, and post-intervention 2006-2007), according to timing of a national American Heart Association and National Heart, Lung, and Blood Institute awareness campaign for women. Patients enrolled in the CRUSADE registry between January 1, 2001 and December 31, 2006, from 568 sites, and patients enrolled in the NCDR ACTION Registry from January 1, 2007 to December 31, 2007, were included in this analysis. Patients were excluded if they were admitted with a STEMI or unstable angina, if they were missing data on symptoms or had symptom onset <0 hours or >500 hours from admission, or were transferred from another hospital.
Results:
A total of 125,161 patients were included, of which 50,152 (40.1%) were women. The median time from symptom onset to presentation was longer in women compared to men (3 hours vs. 2.8 hours, p < 0.0001), which remained significant after adjustment for clinical characteristics. No measureable reduction in time from symptom onset to presentation over the period of time in which the national awareness campaign was conducted was observed. After adjustment for covariates, women ages 40-60 years had a 3.46% longer time to presentation compared to men (95% confidence interval, 1.06-5.92).
Conclusions:
The investigators concluded that no reduction in time from symptom onset to hospital presentation for MI in patients has been observed since the initiation of national awareness campaigns for women. A significant gender gap in presentation time remains.
Perspective:
These data suggest that national awareness campaigns do not translate into meaningful reductions in time from onset of cardiac symptoms to presentation. However, further analyses of these data are likely to provide more detailed and clinically useful information on specific factors that may relate to delay in presentation and could be used in future educational interventions.

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FDG-PET scans detected metabolic activity differences between visceral, subcutaneous adipose tissue

Christen T. J Am Coll Cardiol Img. 2010;3:843-851.
Gropler R. J Am Coll Cardiol Img. 2010;3:852-853.
Fluorodeoxyglucose-PET imaging revealed that visceral adipose tissue had increased glucose uptake vs. subcutaneous adipose tissue, according to a study.

Researchers retrospectively analyzed tissue-specific glucose uptake in vivo in clinically obtained, whole-body fluorodeoxyglucose (FDG)-PET scans in patients obese (n=31) and lean (n=26). The scans were performed for the diagnosis of primary lung cancer staging with respect to the intensity of FDG uptake in abdominal visceral adipose tissue and subcutaneous adipose tissue.
Researchers found that visceral adipose tissue had higher FDG uptake vs. subcutaneous adipose tissue (P<.0001), which was independent of age, sex, BMI, medications and comorbidities. They conducted additional research that investigated mechanisms underlying this observation in diet-induced C57BL/6 obese mice and determined that stromal vascular cells from visceral adipose tissue exhibited higher glucose uptake than those from subcutaneous adipose tissue (P=.01). Additionally, evaluation of expression of glucose transporters (GLUT1, GLUT3, and GLUT4) and hexokinases (HK1 and HK2) revealed increased expression of HK1 in visceral adipose tissue-derived vs. subcutaneous adipose tissue-derived stromal vascular cells.

“Visceral adiposity has become a therapeutic target for numerous novel pharmacologic and other strategies aimed at the improvement of dysmetabolism. Although plasma biomarkers provide one window on efficacy, availability of an imaging modality to directly probe the target tissue would help drug development programs evaluate efficacy and perform better dose selection in clinical trials,” the researchers commented in their study.

In an accompanying editorial, Robert J. Gropler, MD, and Linda R. Peterson, MD, both with the cardiovascular division of the department of internal medicine at Washington University School of Medicine in St. Louis, said there are two important contributions of this study’s findings.

“This article moves our understanding beyond the initial findings that 1) not all adipose tissue is alike and 2) adipocytes can make and respond to hormones and cytokines to realizing that adipose tissue is a complex environment composed of varying amounts of many different types of cells including the stromal vascular cell fraction,” they wrote. “[These findings] emphasize the need for the development of molecular imaging approaches that noninvasively target specific cell types and/or biological processes that comprise visceral adipose tissue and contribute to CVD.”
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Subclinical MI observed in patients with patent foramen ovale
Wöhrle J. J Am Coll Cardiol Img. 2010;3:833–839.

More than 10% of patients with patent foramen ovale had detected subclinical MI, according to new study data.
Researchers from Ulm, Germany, analyzed patients (n=74) with patent foramen ovale (PFO) who had a first cryptogenic cerebral ischemic event and did not have a history of MI. The patients underwent CV MRI and coronary angiography, and had right and left ventricular volumes and ejection fractions measured.

Eight (10.8%) of the patients had late gadolinium enhancement (LGE). Researchers determined LGE pattern to be transmural or subendocardial. There was no difference in CV risk factors, type of ischemic event, presence of atrial septal aneurysm, right and left ventricular mass volumes, and ejection fraction in patients with or without LGE. LGE volume was small and consisted of only 7.9 ± 2.4% of LV muscle mass. Overall, patients with LGE vs. those without had a larger PFO size (16.0 ± 2.8 mm vs. 13.2 ± 4.1 mm).

“We were able to demonstrate using CV MRI a 10.8% prevalence of subclinical MIs in patients with PFO after a first cryptogenic cerebral ischemic event,” the researchers commented in their study. “Our results strengthen the pathophysiologic role of a PFO with paradoxical embolism in patients with cryptogenic cerebral ischemic events.”

In accompanying editorial, Y. Chandrashekhar, MD, DM,of the VA Medical Center and University of Minnesota in Minneapolis, explained that this study takes a novel detour compared to previously published literature and adds important information.

“It adds to the growing body of evidence that a PFO has multiple, potentially adverse, consequences that are often not noticed. Although a plethora of literature addresses stroke in patients with a PFO, no systematic study has evaluated embolism in other organ systems,” he wrote. “[This study] also encourages the introduction of better imaging to detect currently unidentified pathology.”

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Quantitative perfusion reserve by CMR differentiated moderate from severe stenoses in patients with CAD
Patel A. J Am Coll Cardiol. 2010;56:561-569.

Researchers were able to distinguish between moderate and severe stenosis with quantitative perfusion reserve via cardiac magnetic resonance in patients with known or suspected coronary artery disease.

This prospective, head-to-head comparison study comprised patients (n=41) with an abnormal single-positron emission CT stress test who were awaiting or had undergone a diagnostic X-ray angiogram. Patients were excluded if they had a recent MI, were older than 85 years or had any contraindications to cardiac magnetic resonance (CMR) or adenosine.

Of the remaining population who had complete quantitative data (n=30), researchers observed that perfusion reserve (mean ± SD) decreased as coronary artery stenosis severity increased: 2.42 ± 0.94 for <50%, 2.14 ± 0.87 for 50% to 70%, and 1.85 ± 0.77 for >70% (P<.001). Researchers noted similar diagnostic accuracies with perfusion reserve and qualitative interpretation for detection of coronary artery stenosis >50% (83% vs. 80%) and coronary artery stenosis >70% (77% vs. 67%). Additionally, the use of perfusion reserve in patients with triple-vessel CAD had a higher burden of detectable ischemia vs. patients with single-vessel CAD (60% vs. 25%; P=.02), whereas qualitative interpretation detected no difference (31% vs. 21%; P=.26).

“We have shown … that perfusion reserve analysis of first-pass CMR images provides additional clinically relevant information compared with qualitative interpretation,” the researchers concluded. “Specifically, compared with qualitative interpretation, quantification of perfusion reserve can differentiate moderate from severe CAD and can better discriminate patients with triple-vessel CAD from patients with single-vessel CAD. … These findings have important implications for ascertaining prognosis in an individual patient and determining an optimal therapeutic approach.”
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Title: Automatic Remote Monitoring of ICD Lead and Generator Performance: The TRUST Trial
Date Posted: August 18, 2010
Authors: Varma N, Michalski J, Epstein AE, Schweikert R.
Citation: Circ Arrhythm Electrophysiol 2010;Aug 17:[Epub ahead of print].

Study Question:
What is the efficacy of remote home monitoring (HM) with automatic daily surveillance, as compared to conventional in-office follow-up, for the management of patients receiving implantable cardioverter-defibrillators (ICDs)?
Methods:
A total of 1,339 patients were randomized post-ICD implant 2:1 to HM or to conventional (C) groups. Both groups underwent scheduled checks every 3 months and were followed for 15 months. In HM, in-person office visits were scheduled at 3 and 15 months. At 6, 9, and 12 months, HM only was used with subsequent office visits if necessary. Between these time points, ICDs triggered event notifications for system integrity problems. Patients randomized to C follow-up were evaluated with office visits only.
Results:
HM and C patients were similar (age 63.3 ± 12.8 vs. 64.0 ± 12.1 years, 72.0 vs. 73.1% male, New York Heart Association class II 55.9 vs. 60.4%, left ventricular ejection fraction 29.0 ± 10.7 vs. 28.5 ± 9.8%, coronary artery disease 64.8 vs. 71.7%; primary prevention 72.2 vs. 73.8%, DDD devices 57.8 vs. 56.6%). Four patients crossed over from C to HM because of advisories. Scheduled checks were more successfully accomplished with HM (92.7% vs. 89.2% in C, p < 0.001). Sixty-two device-related events (53 in HM vs. 9 in C) were observed in 46 patients (40 [4.4%] in HM vs. 6 [1.39%] in C, p = 0.004); 47% were asymptomatic. HM detected generator and lead problems earlier (HM vs. C: median 1 vs. 5 days, p = 0.05). A total of 20 device problems (e.g., lead fracture, ERI) requiring surgical revision (0.012 per patient-year) were found—15 in HM and 5 in the C groups. Other events were managed nonsurgically (e.g., reprogramming, initiation of antiarrhythmics).
Conclusions:
The authors concluded that automatic HM enhanced discovery, permitted prompt detection, and facilitated management decisions.
Perspective:
This study suggests that remote HM may provide a stringent method of post-implant ICD evaluation in which system components are tested daily and out of range values are reported rapidly. The near continuous remote surveillance of ICD performance combined with automatic self-declaration of system problems, and the ability to collect detailed device-specific data, with component function assessed daily, sets a new precedent for establishing lead and generator performance and for longitudinal evaluation in an era of advancing device (and patient) complexity. Further studies are indicated to assess cost-effectiveness, timeliness of physician intervention, and/or response to the data and effect on actual clinical outcomes with this model of home monitoring of ICDs.

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Optimal Left Ventricular Endocardial Pacing Sites for Cardiac Resynchronization Therapy in Patients With Ischemic Cardiomyopathy
Spragg DD, Dong J, Fetics BJ, et al.
J Am Coll Cardiol 2010;56:774-781.
Study Question: What is the best left ventricular (LV) pacing site for cardiac resynchronization therapy (CRT) in patients with ischemic cardiomyopathy (ICM)?

Mitral Valve Replacement With or Without a Concomitant Maze Procedure in Patients With Atrial Fibrillation
Kim JB, Ju MH, Yun SC, et al.
Heart 2010;96:1126-1131.
Study Question: How effective is the Maze procedure in patients undergoing mitral valve replacement (MVR)?


Repair of Regurgitant Bicuspid Aortic Valves: A Systematic Approach
Boodhwani M, de Kerchove L, Glineur D, et al.
J Thorac Cardiovasc Surg 2010;140:276-284.
Study Question: What are the early and midterm outcomes for surgical bicuspid aortic valve repair?


Telemonitoring and Self-Management in the Control of Hypertension (TASMINH2): A Randomised Controlled Trial
McManus RJ, Mant J, Bray EP, et al.
Lancet 2010;376:163-172.
Study Question: Does self-management by people with poorly controlled hypertension result in better blood pressure control compared with usual care?

Optimal Timing of Coronary Angiography and Potential Intervention in Non-ST-Elevation Acute Coronary Syndromes
Katritsis DG, Siontis GC, Kastrati A, et al.
Eur Heart J 2010;Aug 13:[Epub ahead of print].
Study Question: What is the optimal time of coronary angiography in patients with non–ST-elevation acute coronary syndromes (NSTE-ACS)?


Nonoptimal Lipids Commonly Present in Young Adults and Coronary Calcium Later in Life: The CARDIA (Coronary Artery Risk Development in Young Adults) Study
Pletcher MJ, Bibbins-Domingo K, Liu K, et al.
Ann Intern Med 2010;153:137-146.
Study Question: Do nonoptimal lipid levels during young adulthood result in atherosclerotic changes that persist into middle age?


Plasma Renin Activity Predicts Blood Pressure Responses to β-Blocker and Thiazide Diuretic as Monotherapy and Add-On Therapy for Hypertension
Turner ST, Schwartz GL, Chapman AB, et al.
Am J Hypertens 2010;Aug 19:[Epub ahead of print].
Study Question: What are the patient characteristics that predict blood pressure (BP) responses to commonly prescribed antihypertensives such as beta-blocker (atenolol) and thiazide diuretic (hydrochlorothiazide)?

Ethnic Differences in Blood Pressure Response to First and Second-Line Antihypertensive Therapies in Patients Randomized in the ASCOT Trial
Gupta AK, Poulter NR, Dobson J, et al., on behalf of ASCOT Investigators.
Am J Hypertens 2010;Aug 19:[Epub ahead of print].
Study Question: What is the blood pressure (BP) response to first- and second-line drugs in white, black, and South-Asian hypertensive patients?

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Title: Plasma Renin Activity Predicts Blood Pressure Responses to β-Blocker and Thiazide Diuretic as Monotherapy and Add-On Therapy for Hypertension
Date Posted: August 20, 2010
Authors: Turner ST, Schwartz GL, Chapman AB, et al.
Citation: Am J Hypertens 2010;Aug 19:[Epub ahead of print].

Study Question:
What are the patient characteristics that predict blood pressure (BP) responses to commonly prescribed antihypertensives such as beta-blocker (atenolol) and thiazide diuretic (hydrochlorothiazide)?
Methods:
The investigators evaluated predictors of BP response in 363 men and women ≤65 years of age with primary hypertension (152 blacks, 211 whites), 86 of whom (24%) were untreated and 277 of whom (76%) were withdrawn from previous antihypertensive drugs before randomization to either atenolol followed by addition of hydrochlorothiazide (n = 180) or hydrochlorothiazide followed by addition of atenolol (n = 183). Responses were determined by home BP averages before and after each drug administration. Race, age, plasma renin activity, and other characteristics including pretreatment BP levels were incorporated into linear regression models to quantify their contributions to prediction of BP responses.
Results:
Plasma renin activity and pretreatment BP level consistently contributed to prediction of systolic and diastolic responses to each drug administered as mono- and as add-on therapy. Higher plasma renin activity was consistently associated with greater BP responses to atenolol and lesser responses to hydrochlorothiazide. The predictive effects of plasma renin activity were statistically independent of race, age, and other characteristics.
Conclusions:
The authors concluded that plasma renin activity and pretreatment BP level predict BP responses to atenolol and hydrochlorothiazide.
Perspective:
The primary finding of this study is that measurements of plasma renin activity, which were previously shown to predict BP responses to beta-blocker and thiazide diuretic monotherapies, also predict responses to add-on therapy with each drug. For both mono- and add-on therapy responses, the predictive effects of pretreatment plasma renin activity were statistically independent of and not subsumed by age, race, pretreatment BP, or other participant characteristics. Based on available data, it seems reasonable to measure renin in those not well controlled with standard antihypertensive therapies rather than routinely measure renin in all hypertensive patients, the majority of whom are controlled with standard therapies.

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Trial Summary
ATOLL Title: Acute STEMI Treated With Primary PCI and Intravenous Enoxaparin or UFH to Lower Ischemic and Bleeding Events at Short- and Long-Term Follow-Up
Trial Sponsor: Assistance Publique-Hopitaux de Paris
Year Presented: 2010
Topic(s): Interventional Cardiology, General Cardiology, Prevention/Vascular
Summary Posted: 08/30/2010
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, Heartscape, Eisai, Sanofi Aventis, The Medicines Company, Ethicon, Bristol Myers Squibb Cogentus, PLx Pharma, Takeda

Description:

The goal of the trial was to evaluate treatment with enoxaparin compared with unfractionated heparin (UFH) among patients undergoing primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI).
Hypothesis:

Enoxaparin will be more effective in reducing ischemic and bleeding events.
Drugs/Procedures Used:

Prior to coronary angiography, STEMI patients were randomized to enoxaparin 0.5 mg/kg intravenous, (n = 450) versus UFH 50-70 U/kg intravenous with a glycoprotein inhibitor or 70-100 U/kg without a glycoprotein inhibitor (n = 460).
Concomitant Medications:

In the enoxaparin group, during hospitalization, the use of aspirin was 96%, clopidogrel 94%, beta-blocker 88%, angiotensin-converting enzyme inhibitor 75%, and statin 87%.
Principal Findings:
Overall, 910 patients were randomized. In the enoxaparin group, the median age was 59 years, 22% were women, diabetics were 14%, shock and/or cardiac arrest prior to procedure was 4%, time from symptom onset to randomization was 2 hours 33 minutes, radial access was used in 69%, stenting was performed in 96%, and glycoprotein inhibitor was used in 71%.

The primary outcome, all-cause death, complications of MI, procedural failure, or non-coronary artery bypass graft (CABG) major bleeding occurred in 28% of the enoxaparin group versus 34% of the UFH group (p = 0.07).

For secondary outcomes: death, MI, or revascularization occurred in 5.1% versus 8.5% (p = 0.04); death, complications of MI, or major bleeding occurred in 10.2% versus 15.0% (p = 0.03); death or complications of myocardial infarction occurred in 7.8% versus 12.4% (p = 0.02); all-cause mortality occurred in 3.8% versus 6.3% (p = 0.08); and death or resuscitated cardiac arrest occurred in 4% versus 7% (p = 0.049).

Non-CABG major bleeding occurred in 4.5% versus 4.9% (p = NS), and TIMI major bleeding occurred in 2.9% versus 2.4% (p = NS).
Interpretation:
Among patients with STEMI, the use of enoxaparin compared with UFH during primary PCI is feasible. Currently, there are relatively limited data to support the use of low molecular weight heparin during primary PCI. Enoxaparin did not reduce the primary outcome, although secondary ischemic outcomes were reduced, and bleeding was similar between the groups.

This trial studied an unusual primary outcome, which consisted of 12 individual components. The benefit seen in secondary outcomes will need to be explored in future larger studies with more standardized definitions of ischemic and bleeding events.
Conditions:
Coronary heart disease
Coronary heart disease / Angina pectoris
Coronary heart disease / Silent ischemia
Prevention
Therapies:
Anticoagulant / Enoxaparin
Anticoagulant / Heparin
Anticoagulant
Medical
Study Design:
Randomized. Parallel.
Primary Endpoints:
All-cause death, complications of MI, procedural failure, or non-CABG major bleeding
Complications of MI defined as resuscitated cardiac arrest, recurrent MI, urgent revascularization, stroke, peripheral or pulmonary embolism
Procedural failure defined as stent thrombosis, bailout use of glycoprotein IIb/IIIa inhibitor, non-TIMI 3 flow post-PCI, ST-resolution <50% post-PCI
Major bleeding according to STEEPLE definition
Secondary Endpoints:
All-cause death, recurrent MI, or urgent revascularization
Non-CABG major bleeding
Death or complications of MI
Death or resuscitated cardiac arrest
Major or minor bleeding
Death, complications of MI, or major bleeding
Patient Population:
STEMI patients

Number of enrollees: 910
Duration of follow-up: 30 days
Mean patient age: median 59 years
Percentage female: 22%
Exclusions:
Use of antithrombin or lytic therapy prior to randomization
References:

Presented by Dr. Gilles Montalescot at the European Society of Cardiology Congress, Stockholm, Sweden, August 2010.

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Trial Summary
J-LANCELOT Title: Japanese-Lesson from Antagonizing the Cellular Effect of Thrombin
Trial Sponsor: Eisai
Year Presented: 2010
Topic(s): General Cardiology, Interventional Cardiology, Prevention/Vascular
Summary Posted: 08/30/2010
Writer: Anthony A. Bavry, M.D., M.P.H., F.A.C.C.
Author Disclosure: NOTHING TO DISCLOSE
Reviewer: Christopher P. Cannon, M.D., F.A.C.C.
Reviewer Disclosure: CONSULTING FEES/HONORARIA: Novartis, Alnylam, BMS EQUITY INTERESTS: Automedics Medical Systems RESEARCH/RESEARCH GRANTS: Merck, Accumetrics , Sanofi-aventis/Bristol-Myers Squibb Parnership, AstraZeneca Takeda, Glaxo Smith Kline, Intekrin OTHER FINANCIAL BENEFIT: Pfizer

Description:

The goal of the trial was to evaluate treatment with the novel protease-activated receptor-1 (PAR-1) antagonist E5555 (atopaxar) compared with placebo among Japanese patients with an acute coronary syndrome (ACS) or coronary artery disease (CAD). PAR-1 binding inhibits platelet activation.
Hypothesis:

E5555 will be associated with an acceptable rate of bleeding.
Drugs/Procedures Used:
Eligible Japanese patients were randomized to one of four treatment groups: 1) E5555 200 mg daily (n = 129), 2) E5555 100 mg daily (n = 131), 3) E5555 50 mg daily (n = 117), or 4) placebo (n = 127). Patients initially received a loading dose of E5555 400 mg or placebo on day 1.

ACS patients were treated with study drug for 12 weeks, whereas the other patients were treated for 24 weeks.
Concomitant Medications:

All patients received aspirin 75-325 mg daily.
Principal Findings:
In the ACS E5555 200 mg cohort, mean age was 64 years, 26% were women, mean weight was 65 kg, 36% had diabetes, and 75% had hypertension. The use of aspirin was 98%, and thienopyridine 89%.

There were no Thrombolysis in Myocardial Infarction (TIMI) major bleeds in any group. In the ACS cohort, any TIMI bleed (major, minor, or minimal) was 23.0% with the E5555 200 mg dose versus 16.4% with placebo (p = 0.40), and in the CAD cohort, any TIMI bleed was 13.2% versus 4.5% (p = 0.081), respectively.

In the ACS cohort, major adverse cardiac events (MACE) were 5.0% in the combined E5555 group versus 6.6% with placebo (p = 0.73), and in the CAD cohort, MACE were 1.0% versus 4.5% (p = 0.066), respectively.

In the ACS cohort, treatment-related adverse events were 44% in the combined E5555 group versus 28% with placebo (p = 0.024), and in the CAD cohort, treatment-related adverse events were 32% versus 14% (p = 0.003), respectively. This was mainly due to a dose-dependent increase in liver function abnormalities. Platelet aggregation was more than 90% with 100 mg and 200 mg E5555, and 20-60% with 50 mg E5555.
Interpretation:

Among patients with ACS, CAD, or high-risk clinical characteristics, the use of E5555 (atopaxar) on a background of aspirin and clopidogrel may be effective. This novel agent prevented platelet activation in a dose-dependent manner by blocking the PAR-1 receptor. Nonmajor bleeding events were nonsignificantly increased with E5555, whereas MACE were nonsignificantly decreased. Liver enzyme abnormalities were increased with this experimental agent. Further study is needed to more precisely characterize the efficacy and safety of E5555.
Conditions:
Coronary heart disease
Coronary heart disease / Acute MI
Coronary heart disease / Angina pectoris
Coronary heart disease / Angina pectoris / Stable
Diabetes mellitus
Peripheral vascular disease
Coronary heart disease / Acute MI / Non-Q-Wave
Coronary heart disease / Angina pectoris / Unstable
Therapies:
Medical
Study Design:
Placebo Controlled. Randomized. Blinded. Parallel.
Primary Endpoints:
Bleeding events
Secondary Endpoints:
MACE defined as cardiovascular death, myocardial infarction, stroke, or recurrent ischemia
Platelet aggregation induced by thrombin receptor-activating peptide (TRAP)
Patient Population:
Patients with CAD or recent/current ACS
Documented CAD defined as percutaneous coronary intervention (>4 weeks prior to enrollment), coronary artery bypass grafting (>12 weeks prior to enrollment), or stable CAD
Patients with diabetes, peripheral arterial disease, or prior stroke/transient ischemic attack were also eligible for enrollment

Number of enrollees: 504
Duration of follow-up: 12 weeks
Age range: mean 64-67 years across different groups
Percentage female: 12-20% across different groups
Exclusions:
ST-elevation myocardial infarction
References:

Presented by Dr. Shinya Goto at the European Society of Cardiology Congress, Stockholm, Sweden, August 2010

[Chevychelov]

Trial Summary
ART Title: Arterial Revascularization Trial
Trial Sponsor: UK Medical Research Council, British Heart Foundation
Year Presented: 2010
Topic(s): Cardiovascular Surgery, General Cardiology, Prevention/Vascular
Summary Posted: 08/30/2010
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, Heartscape, Eisai, Sanofi Aventis, The Medicines Company, Ethicon, Bristol Myers Squibb Cogentus, PLx Pharma, Takeda

Description:

The goal of the trial was to evaluate the use of bilateral internal mammary arteries (BIMA) versus a single internal mammary artery (SIMA) during coronary artery bypass grafting (CABG).
Hypothesis:

CABG with BIMA will improve long-term survival.
Drugs/Procedures Used:

Patients undergoing CABG were randomized to BIMA (n = 1,548) versus SIMA (n = 1,554). Patients in either group could receive saphenous vein and/or radial artery grafts, and on-pump or off-pump surgery as needed.
Principal Findings:
Overall, 3,102 patients were randomized. In the BIMA group, the mean age was 64 years, 15% were women, 24% were diabetic, and 40% had prior myocardial infarction. Off-pump surgery was performed in 42%.

Three grafts were used in 50%, whereas four or more grafts were used in 31%. Duration of surgery was 222 minutes in the BIMA group versus 199 minutes in the SIMA group. Duration of ventilatory support was 968 minutes versus 863 minutes, duration of intensive care unit support was 41 hours versus 38 hours, and duration of postoperative care was 8 days versus 7.5 days, respectively, for BIMA versus SIMA groups.

At 1 year, mortality was 2.5% in the BIMA group versus 2.1% in the SIMA group. Stroke was 1.5% versus 1.8%, myocardial infarction was 2.0% versus 2.0%, and revascularization was 1.8% versus 1.3%, respectively.

At 30 days, mortality was 1.2% in the BIMA group versus 1.2% in the SIMA group. Stroke was 1.0% versus 1.2%, myocardial infarction was 1.4% versus 1.5%, revascularization was 0.7% versus 0.4%, and sternal wound reconstruction was 1.9% versus 0.6% (p < 0.05), respectively.
Interpretation:
Among patients with multi-vessel coronary artery disease, the use of BIMA during CABG is feasible. Interim results reveal that this operative technique is associated with slightly increased surgical time, duration of ventilatory support, and duration of hospitalization; however, mortality, stroke, myocardial infarction, and need for revascularization are similar at 1 year. These outcomes were also similar at 30 days, except BIMA patients experienced a 1.3% absolute increase in need for sternal wound reconstruction.

A difference in these surgical techniques may not become evident until 10 years, during which time >95% of IMAs remain patent, in contrast to only 25-50% of saphenous veins. Regarding sternal wound reconstruction, secondary analysis may reveal certain characteristics such as diabetes or obesity that increase the hazard for this outcome.
Conditions:
Coronary heart disease / Saphenous vein grafts
Coronary heart disease
Coronary heart disease / Angina pectoris
Diabetes mellitus
Prevention
Therapies:
CABG
Study Design:
Randomized. Parallel.
Primary Endpoints:
Survival at 10 years
Secondary Endpoints:
30-day mortality
Reintervention
Clinical events
Quality of life
Cost-effectiveness
Patient Population:
Patients undergoing CABG

Number of enrollees: 3,102
Duration of follow-up: Reported to 1 year, anticipated to 10 years
Age range: Mean 64 years
Percentage female: 15%
References:

Presented by Dr. David P. Taggart at the European Society of Cardiology Congress, Stockholm, Sweden, August 2010.

[Chevychelov]

Title: Euro Heart Survey Acute Coronary Syndromes III Registry: Significant Improvement Reported in STEMI Care
Event: ESC Congress 2010
Topic(s):
Presenter: Francois Schiele, MD, PhD
Writer(s):
Date Posted: 08/30/2010


In the Euro Heart Survey Acute Coronary Syndromes (ACS) III registry, over a period of 2 years, use of clopidogrel, coronary angiography, and reperfusion by primary angioplasty significantly increased with a concomitant decrease in major acute coronary events (MACE), specifically in-hospital mortality, major bleeding, re-infarction, or stroke.
Background

Since 1999, the ESC has implemented an international clinical research program known as the Euro Heart Survey & Registry (EHS/R). The purpose of the EHS/R is to evaluate the extent to which clinical practice uses existing guidelines as well as to identify differences in population profiles, patient management, and outcome across Europe.

The first survey on (ACS-I) included 10,484 patients with a discharge diagnosis of ACS and enrolled during 2000-2001 in 103 hospitals from 25 countries.1 Euro Heart Survey ACS II was carried out in 2004 and included 6,385 patients from 190 hospitals in 32 countries.2

These surveys revealed an increasing use of primary reperfusion therapy in patients with ST elevation myocardial infarction (STEMI) in ACS-II (64% vs. 56% in ACS-I), with a larger proportion receiving primary percutaneous coronary intervention (PCI) (37% of patients; 59% of reperfusion therapy). Time between symptom onset and arrival at the emergency room (ER) was shorter in ACS-II (145 vs. 176 minutes in ACS-I), and also the time period between ER and reperfusion by primary PCI was shorter in ACS-II (70 minutes vs. 93 in ACS-I). The major reasons for not providing primary reperfusion therapy in 36% of ACS-II patients were late arrival (30%), uncertain diagnosis (11%), early resolution of ST-elevation (12%), and contraindications (7%).

Coronary angiography was performed in 70% of ACS-II patients compared to 56% in ACS-I. Among the increasing number of patients who underwent PCI, the proportion of patients receiving stents increased from 31% in ACS-I to 52% in ACS-II.
Acute Coronary Syndromes III

At the 2010 ESC Scientific Sessions, Schiele et al. presented data for STEMI patients eligible for reperfusion. Over the 2-year period studied, there was no major change in patient characteristics and no change in the use of aspirin, oral beta-blockers, and ACE-inhibitors.

However, there was a significant increase in the use of clopidogrel, coronary angiography, and reperfusion (more primary angioplasty, less use of thrombolysis). Overall, among patients eligible for reperfusion according to guidelines-based criteria, about 20% were treated by fibrinolytic therapy, 60% by primary PCI, and 20% did not undergo any reperfusion.

Door-to-needle time and door-to-balloon time decreased significantly, too, during the study period, from 20 to 5 min (p = 0.01) and from 60 to 45 min (p <0.0001) respectively, an impressive 25% reduction. For comparison, in ACS-1, median time from arrival in the ER to reperfusion therapy was 59 minutes to the initiation of fibrinolytic therapy and 93 minutes to first balloon inflation.

With similar baseline characteristics for patients treated across the four 6-month periods comprising the ACS-III study period, in-hospital mortality and the combined MACE endpoint decreased significantly (8.1 to 6.6%, p = 0.047 and 13.3 to 10.0%, p = 0.006 for trend, respectively) from the first 6-month period to the last.

Overall, the results reported at ESC are markedly better than ACS-I, published in 2002, in which the authors wrote that their data “clearly demonstrate the discordance between existing guidelines for the treatment of ACS and current practice in this region.” Moreover, the results in the original ACS-I analysis were substantially different from those reported by large clinical trials of the time, including a 50% greater 30-day mortality rate in the survey than the large GUSTO trial, for example.
Drivers of Change

Dr. Francois Schiele said it is unclear what is driving the significant improvements over a short period of time. Unlike in the U.S., there are no specific programs across Europe targeting reduced times to reperfusion. However, Dr. Schiele wonders whether being enrolled in the EHS/R is having affects similar to U.S. quality improvement programs.

“We have similar results without any specific program. And the question is, did we see that because we have in this registry only centers that are very aware on the quality of care, or can just participating in such a survey act like a program because people know that we’ll be checking the result, we’ll make some benchmarking, we will look at the time for reperfusion.”

[Chevychelov]

Title: REACH Registry: An International Pandemic of Cardiovascular Disease
Event: ESC Congress 2010
Topic(s): PreventionVascular
Presenter: Deepak L. Bhatt, MD, FACC
Writer(s):
Date Posted: 08/30/2010


New analysis of 4-year event rates of The REACH Registry of stable outpatienst with known atherothrombotic disease or multiple risk factors found four simple criteria for identifying patients at higher risk for CV events: polyvascular disease, a recent ischemic event, a prior ischemic event at any time, and diabetes.

In addition, according to Dr. Deepak Bhatt, “For a variety of reasons, there’s still a lot of undertreatment of common risk factors, which are highly prevalent throughout the world.” Consequently, registry data show high rates of ischemic events in areas such as Japan, Taiwan, the Middle East, and Eastern Europe; places, he said, where widespread atherothrombotic disease was much less common just a generation ago.
Background

Atherothrombosis is the leading cause of CV morbidity and mortality, and the Reduction of Atherothrombosis for Continued Health (REACH) Registry is a single international database designed to characterize patterns in atherosclerosis risk factor profiles and treatment intensity of these patients. To this end, investigators followed 68,236 stable outpatients (typically treated in nonacademic centers) from 44 countries. All participants had coronary artery disease (CAD), cerebrovascular disease (CVD), peripheral arterial disease (PAD), or three or more risk factors for atherothrombosis.

The baseline publication reported that classic CV risk factors are consistent and common but largely undertreated and undercontrolled in most parts of the world.1 One-year results demonstrated a strong increased risk that was dependent on the number of arterial beds affected (so-called polyvascular disease):
5% event rate for patients with risk factors only
13% for patients with risk factors + 1 diseased vascular bed
22% for patients with risk factors + 2 diseased vascular beds
26% for patients with risk factors + 3 diseased vascular beds2

(Polyvascular disease refers to disease in different arterial beds and should not be confused with multivessel disease.)

Extrapolating from the REACH data, in the U.S. alone, up to 1.75 million CV events would be expected annually in patients with multiple arterial diseases. That’s a high event rate for a stable outpatient population treated with contemporary therapy. It was surprisingly high, too, for individuals without a history of CAD, CVD, or PAD but only multiple risk factors for these conditions (a 5% risk of hospitalization for atherothrombosis during 12 months of follow-up).
4-Year Results

The initial follow-up period was 2 years, but enrolling centers were invited to participate in a project extension lasting an additional 2 years. Follow-up data were available for 45,227 patients enrolled in 3,647 centers in 29 countries and will be published simultaneously in JAMA to coincide with Dr. Bhatt’s presentation at ESC Congress 2010.

Key results at 4 years:

The risk continuum for future CV events showed that patients with prior ischemic events at baseline were at greater risk than patients with stable atherosclerosis at baseline who were likewise at greater risk than individuals with risk factors only.

Polyvascular disease remained the strongest independent predictor of future CV events.

In patients with prior ischemic events, an event ≤1 year prior to enrollment was a strong predictor for CV events (vs. >1 year prior to enrollment).

Diabetes increased the risk of CV events in all populations but to a lesser extent than polyvascular disease or established atherosclerosis.
Diabetes – Not a CHD Equivalent?

One interesting observation from the REACH registry: diabetic patients without established atherothrombosis are at much lower risk than nondiabetic patients who did have atherothrombosis. This contradicts a classic study by Haffner et al. indicating that the presence of type 2 diabetes may confer the same degree of risk as preexisting coronary heart disease.3

“But the REACH dataset actually doesn’t show that,” said Dr. Bhatt. “I don’t want to downplay the importance of diabetes, but whether you actually have plaque in your arteries is a better predictor of whether you’re going to have a (cardiac event) than just having diabetes.”

Specifically, diabetic patients with risk factors only had a lower major adverse cardiac event rate than nondiabetic subjects or diabetic patients both with established atherothrombotic disease (2.2% vs 4.0% vs 6.0%, respectively; p <0.001 for the two comparisons).4
Take Home Messages
The REACH Registry analysis provides simple criteria for assessing risk for CV events in stable outpatients: polyvascular disease, a recent ischemic event, a prior ischemic event at any time, and diabetes.
Individuals with type 2 diabetes who pay careful attention to risk factor management have significantly less risk than a person with diabetes plus atherothrombotic disease.
The findings should help clinicians identify patients at very high risk of atherothrombotic events and adapt their treatment strategies accordingly.

[Chevychelov]

Trial Summary
INNOVATE PCI Title: Intravenous and Oral Elinogrel, a Selective and Reversible P2Y12 Receptor Inhibitor in Patients Undergoing Nonurgent PCI
Trial Sponsor: Portola Pharmaceuticals
Year Presented: 2010
Topic(s): Interventional Cardiology, General Cardiology
Summary Posted: 08/30/2010
Writer: Anthony A. Bavry, M.D., M.P.H., F.A.C.C.
Author Disclosure: NOTHING TO DISCLOSE
Reviewer: Christopher P. Cannon, M.D., F.A.C.C.
Reviewer Disclosure: CONSULTING FEES/HONORARIA: Novartis, Alnylam, BMS EQUITY INTERESTS: Automedics Medical Systems RESEARCH/RESEARCH GRANTS: Merck, Accumetrics , Sanofi-aventis/Bristol-Myers Squibb Parnership, AstraZeneca Takeda, Glaxo Smith Kline, Intekrin OTHER FINANCIAL BENEFIT: Pfizer

Description:
The goal of the trial was to evaluate treatment with the intravenous (IV) and oral P2Y12 receptor inhibitor PRT060128 (elinogrel) compared with clopidogrel during nonurgent percutaneous coronary intervention (PCI). Elinogrel is a direct acting agent, which competitively binds to the P2Y12 receptor.
Hypothesis:

This is a phase II dose-finding study for elinogrel.
Drugs/Procedures Used:
Patients undergoing nonurgent PCI were randomized to one of four groups prior to PCI: 1) elinogrel 80 mg IV, then 50 mg oral twice daily; 2) elinogrel 80 mg IV, then 100 mg oral twice daily; 3) elinogrel 80 mg IV, then 150 mg oral twice daily; or 4) clopidogrel 300-600 mg, then 75 mg daily.

After the trial began, the Data Safety and Monitoring Board recommended increasing the IV dose of elinogrel from 80 mg to 120 mg and discontinuing the 50 mg twice daily arm. The chronic phase was also extended from 2 to 4 months.
Principal Findings:
Overall, 616 patients were randomized. In the pooled elinogrel 150 mg group, the median age was 61 years, 22% were women, body mass index was 29 kg/m2, 40% were diabetics, 45% were on chronic clopidogrel therapy, and femoral access was used in 75%.

Inhibition of platelet aggregation was greater with elinogrel versus clopidogrel.

There were no TIMI major bleeds in any group. There was a numerical increase in access bleeds requiring medical attention with higher doses of elinogrel compared with clopidogrel. Ischemic outcomes are similar across the study groups. Death, MI, stroke, or revascularization occurred in approximately 2.8% of the elinogrel 150 mg group, 4% of the elinogrel 100 mg group, and 1.5% of the clopidogrel group (p = NS).

Any serious adverse event occurred in 12.6% of the elinogrel 150 mg group, 14.9% of the elinogrel 100 mg group, and 11.1% of the clopidogrel group. Dyspnea occurred in 12.1%, 15.4%, and 4.3%, whereas alanine aminotransferase (ALT)/aspartate aminotransferase (AST) >3 x upper limit of normal occurred in 4.8%, 4.0%, and 1.0%, respectively.
Interpretation:

Among patients undergoing nonurgent PCI, elinogrel resulted in greater antiplatelet effect compared with clopidogrel. There were no TIMI major bleeds in any group, although access site bleeds that required medical attention were numerically higher with increasing doses of elinogrel. Similar to ticagrelor, dyspnea was more common with the study drug. Certain properties of elinogrel are attractive such as the IV and oral formulations, which can be used for acute and chronic settings; however, the increase in liver enzymes will need to be carefully monitored during future phase III studies.
Conditions:
Coronary heart disease
Coronary heart disease / Angina pectoris
Coronary heart disease / Angina pectoris / Stable
Prevention
Therapies:
Antiplatelet agent
Medical
Study Design:
Parallel. Randomized.
Primary Endpoints:
TIMI major/minor bleeding
Bleeding requiring medical attention
Clinically relevant major/minor/nuisance bleeding
Secondary Endpoints:
Troponin elevation >2 x upper limit of normal at 24 hours
Death, MI, stroke, revascularization, bailout glycoprotein IIb/IIIa inhibitor use, or stent thrombosis at 24 hours
Death, MI, stroke, or revascularization at 4 months
Death, MI, stroke, revascularization, or stent thrombosis at 4 months
Patient Population:
Patients undergoing nonurgent PCI of at least one coronary lesion

Number of enrollees: 616
Duration of follow-up: 4 months
Mean patient age: median 61 years
Percentage female: 22%
Exclusions:
Anemia/thrombocytopenia
Recent trauma/bleeding
Stroke or transient ischemic attack within the last 5 years
Clopidogrel load within the last 7 days
Use of thrombolytics, anticoagulates, or fondaparinux
Age >75 years
Weight <55 kg
Creatinine clearance <45 cc/min
Allergy to study medication
References:

Presented by Dr. Sunil Rao at the European Society of Cardiology Congress, Stockholm, Sweden, August 2010.

[Chevychelov]

Trial Summary
EINSTEIN DVT Title: Oral Rivaroxaban Versus Standard Therapy in the Initial Treatment of Symptomatic Deep Vein Thrombosis and Long-Term Prevention of Recurrent Venous Thromboembolism
Trial Sponsor: Bayer Schering Pharma
Year Presented: 2010
Topic(s): General Cardiology, Prevention/Vascular
Summary Posted: 08/31/2010
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, Heartscape, Eisai, Sanofi Aventis, The Medicines Company, Ethicon, Bristol Myers Squibb Cogentus, PLx Pharma, Takeda

Description:

The goal of the trial was to evaluate treatment with the oral direct factor Xa inhibitor rivaroxaban compared with enoxaparin among patients with acute deep venous thromboembolism.
Hypothesis:

Rivaroxaban will be noninferior to enoxaparin in preventing recurrent symptomatic venous thromboembolism.
Drugs/Procedures Used:

Patients with acute deep venous thromboembolism were randomized to oral rivaroxaban 15 mg twice daily for 3 weeks, then 20 mg daily (n = 1,731) versus enoxaparin 1 mg/kg twice daily ≥5 days, then warfarin with target international normalized ratio (INR) 2-3 (n = 1,718). Physicians could decide on treatment duration (3, 6, or 12 months).
Principal Findings:
Overall, 3,449 patients were randomized. In the rivaroxaban group, the mean age was 56 years, 43% were women, body mass index was 28 kg/m2, and intended treatment duration of 6 months was selected in 63%. In the enoxaparin group, 58% of patients were at target INR.

The primary efficacy outcome, recurrent symptomatic venous thromboembolism, occurred in 2.1% of the rivaroxaban group versus 3.0% of the enoxaparin group (p < 0.0001 for noninferiority, p = 0.076 for superiority). Recurrent deep venous thromboembolism occurred in 0.8% versus 1.6%, and nonfatal pulmonary embolism occurred in 1.2% versus 1.0%, respectively.

The primary safety outcome, major and clinically relevant nonmajor bleeding, occurred in 8.1% of the rivaroxaban group versus 8.1% of the enoxaparin group.

Alanine aminotransferase >3x ULN/bilirubin >2x ULN occurred in 0.1% versus 0.2%, respectively.
Interpretation:

Among patients with acute deep venous thromboembolism, the use of oral rivaroxaban was effective. This therapy was noninferior to subcutaneous enoxaparin with transition to warfarin in the prevention of recurrent symptomatic venous thromboembolism. Both nondisabling and disabling strokes are prevented by the use of rivaroxaban. Beeding was similar between the groups and there was no evidence for an increase in hepatic toxicity. This single drug regimen without need for INR monitoring may simplify the treatment of acute deep venous thromboembolism.
Conditions:
Prevention
Prevention/Secondary
Therapies:
Anticoagulant
Anticoagulant / Enoxaparin
Anticoagulant / Warfarin
Medical
Study Design:
Randomized. Parallel.
Primary Endpoints:
Recurrent symptomatic venous thromboembolism (recurrent deep venous thromboembolism, or nonfatal or fatal pulmonary embolism)
Major and clinically relevant nonmajor bleeding
Secondary Endpoints:
Net clinical benefit
Total mortality
Cardiovascular events
Liver enzyme monitoring
Patient Population:
Patients with acute symptomatic deep venous thromboembolism

Number of enrollees: 3,449
Mean patient age: 56 years
Percentage female: 43%
Exclusions:
Acute pulmonary embolism
References:

Presented by Dr. Harry Buller at the European Society of Cardiology Congress, Stockholm, Sweden, August 2010.

[Chevychelov]

AVERROES Title: Apixaban Versus Acetylsalicylic Acid to Prevent Strokes
Trial Sponsor: Bristol-Myers Squibb, Pfizer
Year Presented: 2010
Topic(s): Arrhythmias, General Cardiology, Prevention/Vascular
Summary Posted: 08/31/2010
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, Heartscape, Eisai, Sanofi Aventis, The Medicines Company, Ethicon, Bristol Myers Squibb Cogentus, PLx Pharma, Takeda

Description:

The goal of the trial was to evaluate treatment with the oral direct factor Xa inhibitor apixaban compared with acetylsalicylic acid (aspirin) among patients with atrial fibrillation who are unsuitable for warfarin therapy.
Hypothesis:

Apixaban will be more effective in preventing stroke.
Drugs/Procedures Used:

Patients with atrial fibrillation unsuitable for warfarin therapy were randomized to apixaban 5 mg twice daily (n = 2,809) versus aspirin 81-324 mg daily (n = 2,791).
Concomitant Medications:

At baseline, in the apixiban group, 76% of participants were on aspirin therapy.
Principal Findings:
Overall, 5,600 patients were randomized. In the apixaban group, the mean age was 70, 41% were women, mean CHADS2 score was 2.1, 27% had a CHADS2 score ≥3, 14% had a prior stroke or transient ischemic attack, 19% were diabetics, and 40% had congestive heart failure. In the aspirin group, 91% of patients received a dose of 81-162 mg daily.

The primary outcome, stroke or systemic embolism, occurred at an annual rate of 1.6% in the apixiban group compared with 3.6% in the aspirin group (relative risk [RR] 0.46, p < 0.001). Stroke was 1.5 versus 3.3 (p < 0.001), respectively. Apixiban reduced nondisabling strokes (modified Rankin score 0-2; p = 0.04) and disabling strokes (modified Rankin score 3-6; p < 0.001).

The annual event rate of stroke, systemic embolism, myocardial infarction (MI), or vascular death was 4.1 in the apixiban group versus 6.2 in the aspirin group (p < 0.001). MI was 0.7 versus 0.8 (p = 0.57), vascular death was 2.5 versus 2.9 (p = 0.33), cardiovascular hospitalization was 11.8 versus 14.9 (p < 0.001), and all-cause mortality was 3.4 versus 4.4 (p = 0.07), respectively.

Major bleeding was similar between the groups (RR 1.14, p = 0.56). The annual event rate of clinically relevant nonmajor bleeding was 3.0 in the apixiban group versus 2.6 in the aspirin group (p = 0.28). Fatal bleeding was 0.1 versus 0.1 (p = 0.77), and intracranial hemorrhage was 0.4 versus 0.3 (p = 0.83), respectively.

Termination of study drug was reduced with apixaban (RR 0.88, p = 0.04). Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >3x upper limit of normal occurred in 0.7% versus 1% (p = 0.12), respectively.
Interpretation:
Among patients with atrial fibrillation with elevated risk for stroke and not suitable for warfarin therapy, apixaban was beneficial and well tolerated. This therapy reduced the risk for the primary outcome of stroke or systemic embolism compared with aspirin. Apixaban did not increase the risk for major bleeding. This represents an important new agent in stroke prophylaxis among atrial fibrillation patients. The need for twice daily dosing may represent a challenge for some patients.

The ongoing ARISTOTLE trial will compare apixaban against warfarin in patients with atrial fibrillation.
Conditions:
Arrhythmias / Atrial fibrillation
Prevention
Therapies:
Antiplatelet agent / Aspirin
Study Design:
Blinded. Parallel. Randomized.
Primary Endpoints:
Stroke or systemic embolism
Patient Population:
Patients with atrial fibrillation and at least one high-risk factor
Unsuitability for warfarin therapy due to inability to control international normalized ratio, increased risk for bleeding, patient refusal, or intermediate risk for stroke

Number of enrollees: 5,600
Duration of follow-up: maximum 21 months
Mean patient age: 70 years
Percentage female: 41%
References:

Presented by Dr. Stuart Connolly at the European Society of Cardiology Congress, Stockholm, Sweden, August 2010.