Обзор американских кардиологических журналов за неделю (ссылки)

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Title: Waist Circumference and All-Cause Mortality in a Large US Cohort
Date Posted: August 9, 2010
Authors: Jacobs EJ, Newton CC, Wang Y, et al.
Citation: Arch Intern Med 2010;170:1293-1301.

Study Question:
Is waist circumference associated with risk of death within body mass index (BMI) categories?
Methods:
Data from the Cancer Prevention Study II (CPS-II) Nutrition Cohort (established in 1992) were used for the current study. The CPS-II Nutrition Cohort is a subset of the CPS-II cohort established by the American Cancer Society in 1982. Subjects enrolled between 1992 and 1993 and were mailed questionnaires in 1997, in which they were asked to measure their waist circumference. Validity of self-report was not completed. Body mass index (BMI) was calculated from reported weight on the 1997 survey, and height was reported in the 1982 survey. Subjects who had lost ≥10 lbs or gained more than 25 lbs between 1992 and 1997 were excluded. Subjects with missing data on waist circumference or BMI were also excluded. Mortality was assessed through the National Death Index through December 31, 2006.
Results:
A total of 48,500 men and 56,343 women, 50 years or older, were included in this analysis. Median age at baseline was 69 years for men and 67 years for women. The cohort was predominately white. Subjects in the highest category of waist circumference were more likely to be less educated, have a high BMI, be sedentary, and were former smokers compared to subjects with lower waist circumference. This group was also more likely to have a history of cardiovascular disease, cancer, or respiratory disease. Between 1997 and 2006, 9,315 men and 5,332 women had died. After adjustment for BMI and other risk factors, increased waist circumference (≥120 cm compared to <90 cm) was associated with a twofold higher risk of mortality among men (relative risk [RR], 2.20; 95% confidence interval [CI], 1.71-2.39). For women, a waist circumference ≥110 cm compared to <75 cm was also associated with increased risk of death (RR, 2.36; 95% CI, 1.98-2.82). Waist circumference was positively associated with mortality in all categories of BMI. In men, a 10 cm increase in waist circumference was associated with RRs of 1.16 (95% CI, 1.09-1.23) for normal (18.5 to <25) BMI, 1.18 (95% CI, 1.12-1.24) for overweight (25 to <30) BMI, and 1.21 (95% CI, 1.13-1.30) for obese (≥30) BMI. In women, corresponding RRs were 1.25 (95% CI, 1.18-1.32), 1.15 (95% CI, 1.08-1.22), and 1.13 (95% CI, 1.06-1.20).
Conclusions:
The investigators concluded that waist circumference is important as a risk factor for mortality among older adults, regardless of BMI.
Perspective:
These data highlight the clinical significance of waist circumference. Clinicians may want to consider making waist circumference part of the vital signs for each patient, and to make clear to patients the potential benefits of preventing abdominal obesity.

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Long-Term Safety and Efficacy of Stenting Versus Coronary Artery Bypass Grafting for Unprotected Left Main Coronary Artery Disease: 5-Year Results From the MAIN-COMPARE (Revascularization for Unprotected Left Main Coronary Artery Stenosis: Comparison of Percutaneous Coronary Angioplasty Versus Surgical Revascularization) Registry
Park DW, Seung KB, Kim YH, et al.
J Am Coll Cardiol 2010;56:117-124.
Study Question: What is the long-term outcome of patients undergoing unprotected left main coronary artery (LMCA) stenting compared with those treated with coronary artery bypass grafting (CABG)?

Case Volume, Quality of Care, and Care Efficiency in Coronary Artery Bypass Surgery
Auerbach AD, Hilton JF, Maselli J, Pekow PS, Rothberg MB, Lindenauer PK.
Arch Intern Med 2010;170:1202-1208.
Study Question: What are the relationships between surgeon and hospital volume, and between case volume and costs and length of stay (LOS) after adjusting for individual measures of care quality, as well as overall care quality?

Long-Term (5- to 20-year) Patency of the Radial Artery for Coronary Bypass Grafting
Achouh P, Boutekadjirt R, Toledano D, et al.
J Thorac Cardiovasc Surg 2010;140:73-9.
Study Question: What are the angiographic results after use of the radial artery as a conduit for coronary artery bypass grafting (CABG)?

Endovascular Repair of Aortic Arch Lesions in High-Risk Patients or After Previous Aortic Surgery: Midterm Results
Canaud L, Hireche K, Berthet JP, Branchereau P, Marty-Ané C, Alric P.
J Thorac Cardiovasc Surg 2010;140:52-58.
Study Question: What are the midterm results after thoracic aortic endovascular repair of the aortic arch in high-risk patients or after previous aortic surgery?

Short- and Medium-Term Outcomes After Transcatheter Pulmonary Valve Placement in the Expanded Multicenter US Melody Valve Trial
McElhinney DB, Hellenbrand WE, Zahn EM, et al.
Circulation 2010;122:507-516.
Study Question: What are the procedural, short-term, and limited mid-term results with transcatheter pulmonary valve placement for pulmonary regurgitation and right ventricular outflow tract (RVOT) obstruction?

Cardiac Outcomes in Young Adult Survivors of the Arterial Switch Operation for Transposition of the Great Arteries
Tobler D, Williams WG, Jegatheeswaran A, et al.
J Am Coll Cardiol 2010;56:58-64.
Study Question: What are the outcomes of young adults with transposition of the great arteries after arterial switch operation (ASO)?

Biomarkers in Acute Myocardial Infarction
Chan D, Ng LL.
BMC Medicine 2010;8:34.
Perspective: The following are 10 points to remember about biomarkers in acute myocardial infarction (MI)

Risk of Acute Myocardial Infarction, Stroke, Heart Failure, and Death in Elderly Medicare Patients Treated With Rosiglitazone or Pioglitazone
Graham DJ, Ouellet-Hellstrom R, MaCurdy TE, et al.
JAMA 2010;304:411-418.
Study Question: What is the risk of serious cardiovascular harm with rosiglitazone, as compared with pioglitazone?

Long-Term Results After a Telephone Intervention in Chronic Heart Failure: DIAL (Randomized Trial of Phone Intervention in Chronic Heart Failure) Follow-Up
Ferrante D, Varini S, Macchia A, et al., on behalf of the GESICA Investigators.
J Am Coll Cardiol 2010;56:372-378.
Study Question: Does telephone intervention lead to a sustained improvement in heart failure (HF) outcomes?

Fractional Flow Reserve Versus Angiography for Guiding Percutaneous Coronary Intervention in Patients With Multivessel Coronary Artery Disease: 2-Year Follow-Up of the FAME (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation) Study
Pijls NH, Fearon WF, Tonino PA, et al., on behalf of the FAME Study Investigators.
J Am Coll Cardiol 2010;56:177-184.
Study Question: What is the 2-year outcome of patients undergoing percutaneous coronary intervention (PCI) guided by angiography versus those undergoing functional flow reserve (FFR)-guided coronary intervention?

Correlates of Echocardiographic Indices of Cardiac Remodeling Over the Adult Life Course. Longitudinal Observations From the Framingham Heart Study
Cheng S, Xanthakis V, Sullivan LM, et al.
Circulation 2010;122:570-578.
Study Question: In what ways does the heart remodel with age?

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IMPROVE HF: Implementation of practice-specific improvement programs linked with better care for patients with HF
Fonarow G. Circulation. 2010;doi: 10.1161/CIRCULATIONAHA.109.934471.
By
The implementation of practice-specific performance improvement interventions was associated with improved use of guideline-recommended therapies for patients with chronic HF, primary results from the IMPROVE HF trial suggested.
“Despite compelling scientific evidence and readily accessible national guidelines, beneficial therapies for HF remain underused in many care settings,” the researchers wrote in their study. “IMPROVE HF is the first large-scale outpatient performance improvement initiative designed to assess the effects of a practice-specific, process-of-care improvement intervention on HF patient care.”
Researchers collected data on 34,810 participants with HF or post-MI and reduced ejection fraction (≤35%) from 167 U.S. outpatient cardiology practices. Participants were followed longitudinally for intervention at 12 and 24 months, including single-point-in-time cohorts measured at 6 and 18 months. The researchers then measured adherence to a set of practice-specific guideline-recommended performance improvement interventions designed to improve the quality of HF care delivery.
According to the study results, the performance improvement interventions were associated with improvement in five of seven quality measures at 24 months after implementation (P<.001). The researchers reported that adherence to evidence-based, guideline-recommended care among practices was associated with an absolute increase of 25.1% for aldosterone antagonist use, a 29.9% increase for cardiac resynchronization therapy use and a 27.4% increase in the use of implantable cardioverter defibrillators vs. baseline (P<.001). The use of beta-blockers (6.2%) and HF education tools (12.6%) also increased after implementation.
The use of anticoagulation in patients with permanent, paroxysmal or persistent atrial fibrillation, however, decreased, and the increased use of ACE inhibitors and angiotensin receptor blockers was not statistically significant. When analyzed at an aggregate level, improvements in six of seven improvement measures were reported. The 20% or more absolute improvement in at least three of the seven quality measures met the study’s primary endpoint, according to the researchers.
“The results of this study suggest a favorable impact of applying performance improvement techniques of clinical decision support, reminder systems, guideline-driven care improvement tools, educational outreach, collaborative support, performance profiling and feedback in real-world cardiology practices,” they concluded. “Implementation of this defined and scalable practice-specific intervention may enhance use of guideline-recommended HF therapies previously demonstrated to improve outcomes.”
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ARMYDA-5 PRELOAD: Clopidogrel administered in advance of PCI yielded similar outcomes to cath lab administration
Di Sciascio G. J Am Coll Cardiol. 2010;56:550–557.
By
Dosage of clopidogrel in the catheterization lab was shown to produce similar clinical outcomes as the standard 4- and 8-hour preloads in patients who underwent percutaneous coronary intervention, according to results of the ARMYDA-5 PRELOAD trial.
The Italian researchers enrolled 409 patients in the study and randomly assigned them to receive either a 600 mg clopidogrel loading dose 4 to 8 hours prior to PCI (n=204) or a 600 mg loading dose given in the catheterization lab after coronary angiography, but prior to PCI (n=205). The primary endpoint was the 30-day incidence of the following major adverse cardiac events: cardiac death, MI or unplanned target vessel revascularization.
Researchers reported no significant difference in the primary endpoint between the two arms (8.8% in-lab vs. 10.3% pre-load), which was driven mainly by periprocedural MI. There was a minor increased risk of bleeding or vascular complications in the pre-load arm (7.8%) vs. the in-lab arm (5.4%). Additional findings showed that patients in the in-lab group showed higher platelet reactivity during PCI (P=.043) and 2 hours after intervention (P=.01) vs. those in the pre-load group, but the levels became similar at 8 and 24 hours.
The trial, the researchers wrote, “indicates that a strategy of 600-mg in-lab clopidogrel load pre-PCI may have similar clinical outcomes as routine 4- to 8-hour pre-load. Thus, when indicated, in-lab clopidogrel administration can be a safe alternative to routine pre-treatment given before knowing patients’ coronary anatomy.”
Goran Stankovic, MD, PhD, and Milorad Zivkovic, MD, both with the Medical School of Belgrade in Belgrade, Serbia, explained in an accompanying editorial that the study addresses a clinically relevant question with a randomized controlled trial, and that the results support the in-lab administration of clopidogrel as a safe alternative to routine pre-treatment given before knowing a patient’s anatomy.
“This study serves the purpose of stimulating more and larger efforts to study the issue of clopidogrel platelet reactivity by developing either new regimens of the same drug or new drugs that have different, more predictable and more powerful effects on platelet function, such as prasugrel or ticagrelor,” they concluded.

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Title: Clopidogrel Loading Dose Adjustment According to Platelet Reactivity Monitoring in Patients Carrying the 2C19 2* Loss of Function Polymorphism
Date Posted: August 11, 2010
Authors: Bonello L, Armero S, Mokhtar OA, et al.
Citation: J Am Coll Cardiol 2010;Aug 11:[Epub ahead of print].

Study Question:
What is the biological impact of a tailored clopidogrel loading dose (LD) according to platelet reactivity monitoring in carriers of the cytochrome (CYP) 2C19 2* loss-of-function polymorphism undergoing percutaneous coronary intervention (PCI) for an acute coronary syndrome?
Methods:
A prospective multicenter study enrolling 411 patients with non–ST-segment elevation acute coronary syndrome undergoing PCI was performed. Platelet reactivity was measured using the vasodilator-stimulated phosphoprotein (VASP) index, and a cutoff value of ≥50% was used to define high on-treatment platelet reactivity (HTPR). The genetic polymorphism of CYP 2C19 was determined by allele-specific polymerase chain reaction. In patients carrying CYP 2C19 2* and exhibiting HTPR after a first 600-mg LD of clopidogrel, dose adjustment was performed by using up to three additional 600 mg LDs to obtain a VASP index <50%.
Results:
One hundred thirty-four patients (35.3%) carried at least one 2C19 2* allele (11 homozygotes [2.7%] and 123 heterozygotes [32.6%]). The mean ± standard deviation (SD) VASP index in these patients was significantly higher than in homozygotic patients for the wild-type alleles (61.7 ± 18.4 vs. 49.2 ± 24.2%; p < 0.001). Of the 134 carriers of the loss-of-function polymorphism, 103 were considered to have HTPR. After a second clopidogrel LD, the mean ± SD VASP index was significantly decreased in these patients (69.7 ± 10.1% vs. 50.6 ± 17.6%; p < 0.0001). Finally, dose adjustment according to platelet reactivity monitoring, enabled 88% of 2C19 2* carriers exhibiting HTPR to reach a VASP index <50%.
Conclusions:
The authors concluded that increased and tailored clopidogrel LD according to platelet reactivity monitoring overcomes HTPR in carriers of the loss-of-function CYP 2C19 2* polymorphism.
Perspective:
This study reports that despite having reduced clopidogrel metabolism, most carriers of the loss-of-function CYP 2C19 2* polymorphism can reach optimal platelet inhibition using a strategy of tailored LD according to platelet reactivity monitoring. Furthermore, the data suggest that genetic polymorphism is not required to enable optimal platelet reactivity inhibition to be reached in patients exhibiting HTPR because a dose-adjustment strategy according to platelet reactivity monitoring may be efficient regardless of genetic status. The results of this relatively small study need to be confirmed in larger studies with clinical endpoints.
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Title: Increased Glucose Uptake in Visceral Versus Subcutaneous Adipose Tissue Revealed by PET Imaging
Date Posted: August 9, 2010
Authors: Christen T, Sheikine Y, Rocha VZ, et al.
Citation: J Am Coll Cardiol Img 2010;3:843-851.

Study Question:
Does glucose utilization differ between subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT)?
Methods:
This was a retrospective analysis of tissue-specific glucose uptake based on whole-body fluorodeoxyglucose positron emission tomography (FDG-PET) scans in humans. Glucose uptake was also assessed in vitro, using stromal vascular cells isolated from SAT and VAT of diet-induced obese C57BL/6 mice. Quantitative polymerase chain reaction (PCR) was performed to analyze expression of candidate genes involved in glucose metabolism in SAT and VAT of obese C57BL/6 mice.
Results:
FDG-PET scans from 31 obese and 26 lean patients were analyzed. VAT exhibited higher FDG uptake compared with SAT (p < 0.0001) independent of age, sex, body mass index, comorbidities, and medications. Glucose uptake was also studied in the stromal vascular cell fraction of AT, which is rich in inflammatory cells. Stromal vascular cells from VAT of diet-induced obese C57BL/6 mice exhibited higher glucose uptake than those from SAT (p < 0.01). Evaluation of expression of glucose transporters (GLUT-1, -3, and -4) and hexokinases (HK-1 and -2) revealed increased expression of HK-1 in VAT-derived compared with SAT-derived stromal vascular cells, and also in visceral versus subcutaneous unfractionated AT.
Conclusions:
In humans, VAT has increased glucose uptake compared with SAT, as determined noninvasively with FDG-PET imaging. Differential stromal metabolic activity may be one mechanism underlying differences in metabolic activity of visceral and subcutaneous AT.
Perspective:
Obesity is associated with increased cardiovascular risk and the associated risk is particularly related to excess visceral adiposity. The mechanism for this association remains unclear. Better methods to determine the risks associated with obesity, in addition to mechanistic underpinnings, are needed. In addition to circulating biomarkers, the current study suggests that imaging techniques to characterize metabolic activity of adipose tissue may be revealing since differences are observed between visceral and subcutaneous depots. Further studies are necessary to determine the clinical implications of these results.

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Trial Summary
CRESCENDO Title: Comprehensive Rimonabant Evaluation Study of Cardiovascular Endpoints and Outcomes
Trial Sponsor: Sanofi-Aventis
Year Published: 2010
Topic(s): General Cardiology, Prevention/Vascular
Summary Posted: 08/12/2010
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: BMS, Novartis, Alnylam EQUITY INTERESTS: Automedics Medical Systems RESEARCH/RESEARCH GRANTS: Sanofi-aventis/Bristol-Myers Squibb Parnership, Merck, AstraZeneca , Accumetrics Takeda, Glaxo Smith Kline, Intekrin OTHER FINANCIAL BENEFIT: Pfizer

Description:

The goal of the trial was to evaluate treatment with the endocannabinoid receptor rimonabant compared with placebo in patients with overt vascular disease or increased risk for vascular disease.
Hypothesis:

Rimonabant has been shown to reduce obesity and have favorable effects on several cardiovascular risk factors. The hypothesis was that rimonabant would in turn be effective in preventing cardiovascular death, myocardial infarction, or stroke.
Drugs/Procedures Used:
Patients with abdominal obesity, ages 55 or older, with overt vascular disease or increased risk for vascular disease were randomized to rimonabant 20 mg (n = 9,381) versus placebo (n = 9,314).

Concomitant Medications:

Antiplatelet and lipid-lowering therapy were used in 81% and 82%, respectively, and were balanced in the two groups.
Principal Findings:
Overall, 18,695 patients were randomized. In the rimonabant group, the mean age was 64 years, 36% were women, 12% were current smokers, mean body mass index was 33 kg/m2, 61% had diabetes, 88% had hypertension, 36% had prior myocardial infarction, 17% had prior stroke, and 7.6% had prior transient ischemic attack. The mean exposure to study drug was 13.8 months.



The primary outcome, cardiovascular death, myocardial infarction, or stroke, occurred in 3.9% of the rimonabant group versus 4.0% of the placebo group (p = 0.68). The primary outcome was similar between treatment groups among those with overt vascular disease or with just cardiovascular risk factors. All-cause mortality occurred in 2.1% versus 2.2% (p = 0.96), cardiovascular mortality in 1.3% versus 1.3% (p = 0.95), myocardial infarction in 1.5% versus 1.5% (p = 0.72), and stroke in 1.4% versus 1.6% (p = 0.50), respectively.


Gastrointestinal side effects occurred in 33% versus 22% (p < 0.05) in the rimonabant versus placebo groups, respectively; neuropsychiatric side effects in 32% versus 21% (p < 0.0001); serious psychiatric side effects in 2.5% versus 1.3% (p < 0.0001); and suicide in four patients versus one patient.
Interpretation:
Among patients with abdominal obesity, rimonabant was not effective at reducing the primary outcome of cardiovascular death, myocardial infarction, or stroke at 13.8 months of follow-up either for primary or secondary prevention. Rimonabant increased gastrointestinal, neuropsychiatric, and serious psychiatric side effects.


Four patients committed suicide in the rimonabant group compared with one in the placebo group. These excess side effects led regulatory authorities to terminate the CRESCENDO trial prematurely. The drug was not approved for use in the United States, and the drug was withdrawn from the market worldwide. Safe and effective weight loss agents are urgently needed.
Conditions:
Prevention
Therapies:
Medical
Study Design:
Placebo Controlled. Blinded. Randomized. Parallel. Stratified.
Primary Endpoints:
Cardiovascular death, myocardial infarction, or stroke
Secondary Endpoints:
Adverse events
Other Design Considerations:


Patient Population:
Patients at least 55 years of age with abdominal obesity, defined as waist circumference >88 cm (35 inches) in women and >102 cm (40 inches) in men
Documented vascular disease in the last 3 years (coronary, cerebrovascular, or peripheral arterial disease) or two or more cardiovascular disease risk factors (type 2 diabetes, renal artery disease, advanced age, asymptomatic cerebrovascular or peripheral arterial disease, or elevated high-sensitivity C-reactive protein)



Number of enrollees: 18,695

Duration of follow-up: mean 13.8 months

Age: mean 64 years

Percentage female: 36%
Exclusions:
Obesity due to endocrine disorder
Pregnancy
Surgical procedure for weight loss or a very low calorie diet in the last 6 months
Previous suicide attempt
Limited life span
References:
Topol EJ, Bousser MG, Fox KA, et al., on behalf of the CRESCENDO Investigators. Rimonabant for prevention of cardiovascular events (CRESCENDO): a randomized, multicentre, placebo-controlled trial. Lancet 2010;376:517-23.

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Title: Earlier Intervention in the Management of Hypercholesterolemia: What Are We Waiting For?
Date Posted: August 9, 2010
Authors: Steinberg D.
Citation: J Am Coll Cardiol 2010;56:627-629.

Study Question:
Should we be treating hypercholesterolemia earlier in life?

Should we be treating some patients’ hypercholesterolemia earlier than currently indicated? Clinicians rely on Adult Treatment Panel (ATP) guidelines to assist in determining if and when to start treating hypercholesterolemia with medications—mainly statins. The ATP guidelines use Framingham risk scores to determine a 10-year risk. These scores provide a method for determining risk level, which in turn assists clinicians to identify target goals for low-density lipoprotein (LDL) levels and use of pharmacologic therapy. The author points out that younger patients often have 10-year risk levels, which suggest interventions are not recommended. However, the lifetime risk for cardiovascular (CV) events is often much higher than the calculated 10-year risk. The hypothesis of this article being treatment at an earlier age would translate into years of lower LDL levels, which would significantly reduce CV disease (CVD) events. As the author correctly points out, a randomized study to examine this premise is not feasible. In looking at the literature related to the PCSK9 gene, a lifetime low LDL level (28% lower) suggests a benefit of an 88% drop in coronary heart disease risk. Given this observation, perhaps several decades of LDL levels would translate into significant reductions in CVD events. However, all drugs carry some degree of risk, and the long-term use of statins is not clear.

So do we place more weight on the lifetime risk for CVD and aggressively treat lipids at a younger age than currently recommended, or do we proceed with caution given the unknown risk of long-term pharmacologic intervention? Dr. Steinberg proposes that the benefits outweigh the risks for many people.
Perspective:
Most clinicians and patients would agree that more years of controlled risk factors are optimal for decreasing risk for CVD. All clinicians should celebrate each decade in which cardiac risk factors remain absent in patients. The balance between pharmacologic treatment for long-term lipid control versus potential adverse effects of such therapy is not clear. Use of more novel risk factors such as C-reactive protein and coronary artery calcium can assist in determining who would benefit the most from more aggressive therapies. Clinicians need to outline the current understanding of guidelines for risk factor management as well as more recent knowledge on the lifetime risk for CVD events. Each patient is ultimately the one who decides what is best for him/her.

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Postmarketing Drug Safety Surveillance – Is Enough Being Done?
By Rhonda Cooper-DeHoff, PharmD, MS

Lately, there has been much in the news regarding new and ongoing safety concerns related to a variety of sometimes very commonly used drugs. For example, based on data from a meta-analysis, angiotensin receptor blockers (ARBs) have recently been associated with a modest increase in the risk for a new cancer diagnosis. Similarly, since its approval in 2009, additional information regarding prasugrel’s (Effient, Daiichi Sankyo/Eli Lilly and Company) association with new and worse malignancies has recently become available. During the last few years, there have been mounting concerns regarding rosiglitazone (Avandia, GlaxoSmithKline) and an association with increased risk for CV events, culminating with the FDA’s review of the safety issues associated with rosiglitazone in a joint meeting of the Endocrinological and Metabolic Drugs and the Drug Safety and Risk Management advisory committees on July 13 and 14. After a thorough review of the data available to the advisory committee members, there was a clear lack of consensus as to where to go from here with regard to the status of rosiglitazone. One third of members suggested the safety signal is too strong to allow rosiglitazone to stay on the market, while the other two third felt the drug should stay on the market with additional warnings.

During the last decade alone, there have been more than 20 drugs withdrawn from the market (either voluntarily or at the request of authorities) in the United States, Canada and Europe. These withdrawals are usually for issues related to serious adverse effects which were unexpected or more serious than expected based on data from phase-III clinical trials. In most cases, these serious adverse effects only became apparent from postmarketing surveillance data from the wider patient community. Postmarketing surveillance currently occurs in a variety of forms, including postmarketing clinical trials which generate new data; reanalysis of existing clinical trial data; and the FDA’s MedWatch program.

Based on the known limitations of clinical trials that include patients who have limited comorbid conditions and concomitant medications, the MedWatch program provides education about the importance of postmarketing surveillance, facilitates the reporting of adverse events and disseminates new, clinically useful safety information to providers and patients. However, because the MedWatch program is a passive system that relies on voluntary reporting of adverse events by physicians and other health care providers, these events are often underreported, making it impossible to calculate reliable estimates of adverse event rates. Additionally, reports often contain inadequate documentation and detail. Perhaps most pointedly, the MedWatch system relies primarily on drug manufacturers for the majority of collection, evaluation, and reporting of data from postmarketing studies of their own products.
Recognizing that the MedWatch program alone was insufficient to systematically and rapidly identify potentially severe adverse events after a drug had been approved, the FDA implemented additional programs to help facilitate adverse event reporting and drug safety data assimilation. Created in 2005 and mandated by law in the FDA Amendments Act of 2007, the Drug Safety Oversight Board (DSB), advises the Center for Drug Evaluation and Research on the handling and communication of important and often emerging drug safety issues. Comprised of members from three FDA Centers and six other federal government agencies, one of the most important roles of the DSB is to help the FDA assess the impact of its safety decisions on the health care systems of its federal partners.

Another aspect of the FDA Amendments Act (this one implemented in 2008) gave the FDA the authority to require a Risk Evaluation and Mitigation Strategy (REMS) from manufacturers to ensure that the benefits of a drug or biological product outweigh its risks. Dronedarone (Multaq, Sanofi Aventis) is an example of a drug approved in July 2009, which required a REMS. The goals of the dronedarone REMS is to prevent use in patients with NYHA Class IV, or unstable Class III HF, and to inform patients about the serious risks of dronedarone, including increased mortality in patients with severe unstable HF. Elements of the dronedarone REMS include medication and communication guides, as well as a formal assessment of the REMS performance to be provided to the FDA annually for the first 5 years after launch, with the first assessment due in August 2010.

Another REMS, this one associated with darbepoeitin (Aranesp, Amgen), includes a certification process whereby those who prescribe and dispense the product must be certified by completing a specific training program and attest to statements indicating that they understand the risks of the product. In addition, prescribers must agree to prescribe it only in accordance with approved indications and must agree to share the required and appropriate information with all patients for whom the medication is prescribed. The patient signs a form indicating acknowledgment and understanding of the information, and the prescriber signs indicating compliance with the required provision of information to the patient.

The newest aspect of the FDA’s drug safety assessment program is the Sentinel Initiative, a national electronic system that the FDA hopes will transform its ability to track the safety of drugs, biologics and medical devices. Launched in March 2008, the Sentinel Initiative aims to develop and implement a proactive system that will complement existing systems already in place to track reports of adverse events linked to use of an FDA-regulated product. Stemming from elements of the 2007 FDA Amendments Act, which required the development of methods to obtain access to disparate data sources and established a postmarket risk identification and analysis system to link and analyze health care data from multiple sources, the Sentinel Initiative will enable the FDA to actively query diverse automated health care data holders to evaluate possible medical product safety issues quickly and securely. Sources will include electronic health record systems, administrative databases, insurance claims databases and registries. The Sentinel Initiative will be developed and implemented in stages, and while it is a long way from being fully functional, the FDA has begun to develop the scientific operations needed for the Initiative, including plans for the creation of a coordinating center which will have continuous access to the automated health care data systems.

The REMS program is still a work in progress, and whether the implementation of REMS, which are now in place for more than 100 FDA-approved medications, will improve the long term safe use of medication in this country is unknown, especially since the responsibility for implementation and reporting continues to lie with the manufacturers. Perhaps coupled with the Sentinel Initiative, together these programs will improve the overall safe use of medications in the United States.

In the meantime, we continue to be faced with issues like whether or not rosiglitazone is associated with increased risk for CV events. Rosiglitazone has been on the market since 1999, and prior to the first broad reports in 2007 associating its use with increased risk of adverse outcomes, it ranked 28th amongst the top brand-name drugs prescribed, with over 11 million prescriptions in 2006. In 2009, it had fallen to 103rd with 2.3 million prescriptions. While use has dropped significantly, likely based on safety concerns, prescriptions written in 2009 exposed almost as many patients to a drug with a questionable risk-benefit profile. Until we have fully functioning programs and systems in place to consistently and uniformly assess medication safety after a drug is approved, we will continue to be faced with scenarios such as this.

Rhonda M. Cooper-DeHoff, PharmD, MS, is an associate professor at the University of Florida College of Pharmacy in Gainesville, Fla. and is the column editor for Cardiology Today’s Pharmacology Consult.

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Waist circumference in older adults shown important risk factor for mortality
Jacobs E. Arch Intern Med. 2010;170:1293-1301.
By

Waist circumference regardless of BMI proved to be an important risk factor for mortality in older adults, according to a study appearing in Archives of Internal Medicine.

The study featured patients (n=104,843, 53.7% women) at least 50 years of age from the Cancer Prevention Study II Nutrition Cohort. BMI categories were defined as normal (18.5 to <25), overweight (25 to <30) and obese (≥30). Patients were excluded if they had missing information regarding waist circumference or BMI, waist circumference values determined extreme or implausible, BMI determined underweight or extreme, or unknown smoking status.

According to study results, high levels of waist circumference correlated with a roughly twofold higher risk for mortality in patients (men, RR=2.02; 95% CI, 1.71-2.39 for waist circumference ≥120 cm vs. <90 cm; women, RR=2.36; 95% CI, 1.98-2.82 for waist circumference ≥110 cm vs. <75 cm). Further, researchers found that waist circumference was associated with mortality within all BMI categories
Additional findings indicated that a 10-cm increase in waist circumference for men was associated with the following RRs: 1.16 (95% CI, 1.09-1.23) for normal BMI, 1.18 (95% CI, 1.12-1.24) for overweight BMI and 1.21 (95% CI, 1.13-1.30) for obese BMI. This same incremental increase in women corresponded with RRs of 1.25 (95% CI, 1.18-1.32) for normal BMI, 1.15 (95% CI, 1.08-1.22) for overweight and 1.13 (95% CI, 1.06-1.20) for obese.

“Results from this large, prospective study emphasize the importance of waist circumference as a risk factor for mortality in older adults, regardless of whether the BMI is categorized as normal, overweight or obese,” the researchers concluded. “Our results suggest that, regardless of weight, avoiding gains in waist circumference may reduce risk of premature mortality.”
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Acute, hospital-acquired anemia found common in patients with acute MI
Salisbury AC. Circ Cardiovasc Qual Outcomes. 2010;3:337-346.
By

Nearly half of the patients with acute MI who were treated medically or with percutaneous coronary intervention developed acute, hospital-acquired anemia, according to the outcomes of a new study.

Researchers identified patients (≥18 years, n=2,909) with acute MI who had normal hemoglobin on admission in the TRIUMPH multicenter registry. They used criteria proposed by Beutler and Waalen to define acute, hospital-acquired anemia (HAA), and they identified independent correlates of HAA and multivariable proportional hazards regression to identify the relationship between HAA and mortality and health status.

Of the study patients, 1,321 (45.4%) had HAA, with 348 (26.3%) developing moderate-severe HAA (hemoglobin <11 g/dL). Incidence of HAA varied across hospitals (range, 33%-69%; median rate ratio for HAA, 1.13; 95% CI, 1.07-1.23). Fewer than half of the patients with moderate-severe HAA had documented bleeding, although documented bleeding was more frequent with more severe HAA.
Researchers determined the following as independent correlates of HAA: age, female sex, white race, STEMI, chronic kidney disease, acute renal failure, use of glycoprotein IIb/IIIa inhibitors, in-hospital complications and length of stay.

“We found that HAA is common in acute MI patients who are treated medically or with PCI and varies significantly across hospitals,” the researcher concluded. “Development of moderate-severe HAA is associated with higher mortality and worse health status in the first year after acute MI, independent of documented in-hospital bleeding. Better understanding of whether prevention of HAA is feasible and can improve patient outcomes is needed.”

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Research group proposes serving statins with some fast foods
Ferenczi EM. Am J Cardiol. 2010; doi:10.1016/j.amjcard.2010.03.077.
By

The provision of statins along with a hamburger with cheese and a small milkshake is being proposed as a way to potentially offset the increased relative risk of CV disease resulting from the total fat and trans fat content of this popular fast-food meal option.

This approach, suggested by the authors of an article published in the American Journal of Cardiology, was proposed as as a viable condiment alternative to counter the backlash of an unhealthy, fast-food influenced lifestyle.

“The risk reduction associated with the daily consumption of most statins, with the exception of pravastatin (Pravachol, Teva Pharmaceuticals), is more powerful than the risk increase caused by the daily extra fat intake associated with a 7-oz. hamburger with cheese and a small milkshake,” the researchers wrote. “Fast food outlets already offer free condiments to supplement meals. A free statin-containing accompaniment would offer CV benefits, opposite to the effects of equally available salt, sugar and high-fat condiments.”
Their analysis consisted of seven randomized controlled trials that included a total of 42,848 patients. The primary outcome measure was the relative risk for a major CV event, including nonfatal MI and CAD death.

Most of the primary prevention stain regimes the researchers analyzed, including lovastatin (Mevacor, Merck), atorvastatin (Lipitor, Pfizer) and simvastatin (Zocor, Merck), were able to counteract the increased risk caused by an unhealthy diet or eating an additional 36 g of fat and 2.8 g of trans fat per day—the approximate fat content of a 7-oz. hamburger with cheese and a small milkshake.

“This does not mean that we should disregard nutritional education in prevention of CV disease,” the researchers commented in their study. “But it should be recognized that nonpharmacologic measures alone may sometimes be insufficient, thereby prompting us to move toward incorporating dietary advice and pharmacotherapy into a coherent strategy for primary prevention.”
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Exercise increased cardiac output, pulmonary artery pressure among patients with LVADs
Andersen M. J Am Coll Cardiol Img. 2010;3:854-859.
By

Patients with a left ventricular assist device who underwent exercise experienced increases in cardiac output and systolic/diastolic pulmonary artery pressure but little increase in filling pressure, study data suggested.

The study included 12 patients (>18 years of age) who had a history of severe HF. Each of the patients had continuous-flow LVAD (HeartMate II, Thoratec) implanted 2 months before enrollment and were in stable condition.

The researchers performed a resting study that was deemed optimal for the individual patient and then a bicycle exercise test. All patients underwent 2-D and Doppler echocardiographic examinations using a cardiac ultrasound system. Researchers compared echocardiographic indices of contraction and filling pressure with invasive measures, including right heart catheterization, and performed analyses blinded to all invasive measurements.
According to study results, exercise induced an increase in cardiac output, systolic pulmonary artery pressure and diastolic pulmonary artery pressure. Although researchers did not see any changes in LV dimensions or fractional shortening on echocardiography, systolic mitral annular motion increased — parallel to cardiac output — from 4.1 ± 1.3 cm/s to 8.7 ± 3.7 cm/s (P=.007) and diastolic E/e' ratio decreased from 11.2 ± 2.5 to 7.8 ± 1.7 (P=.01).

“The present study demonstrates a hemodynamic response to exercise in patients with continuous flow LVADs characterized by a considerable increase in cardiac output with little concomitant increase in filling pressure,” the researchers wrote. “These findings emphasize the potential role of exercise echocardiography in studying exercise hemodynamics in LVAD patients.”

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Title: Impact of Bivalirudin Therapy in High-Risk Patients With Acute Myocardial Infarction: 1-Year Results From the HORIZONS-AMI (Harmonizing Outcomes with RevasculariZatiON and Stents in Acute Myocardial Infarction) Trial
Date Posted: August 16, 2010
Authors: Parodi G, Antoniucci D, Nikolsky E, et al.
Citation: J Am Coll Cardiol Intv 2010;3:796-802.

Study Question:
How does baseline risk impact relative outcome of patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) and treated with bivalirudin versus those treated with unfractionated heparin (UFH) and platelet glycoprotein IIb/IIIa inhibitors (GPIs)?
Methods:
The authors evaluated the outcome of patients randomized to the HORIZONS-AMI (Harmonizing Outcomes with RevasculariZatiON and Stents in Acute Myocardial Infarction) trial by categorizing them by the CADILLAC (Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications) risk score into low, intermediate, and high risk.
Results:
The CADILLAC score could be calculated for 2,530 of the 3,602 patients enrolled in the trial. The majority (n = 1,522, 60%) were classified as low risk, 531 (21%) as intermediate risk, and 477 (19%) were classified as high risk. The 1-year mortality rates tended to be lower with bivalirudin compared with UFH + GPI in the low- (0.4% vs. 1.2%, p = 0.09) and high-risk (8.4% vs. 15.9%, p = 0.01) groups, and similar in the intermediate-risk group (4.2% vs. 4.1%, p = 0.99). Bivalirudin was associated with a reduction in noncoronary artery bypass grafting (CABG)–associated major bleeding in low-risk patients (3% vs. 6.9%, p = 0.0005), whereas no difference was seen in the intermediate- (7.2% vs. 9.8%) and the high-risk patients (12.9 % vs. 17.9%). A reduction in recurrent MI was also seen with bivalirudin in high-risk patients (3.6% vs. 7.9%, p = 0.04).
Conclusions:
Bivalirudin is associated with a reduction in 1-year mortality in high-risk patients undergoing primary PCI.
Perspective:
There was no interaction between the randomization arm and the CADILLAC risk category, suggesting that the benefit of bivalirudin was preserved irrespective of the baseline risk. GPI use in primary PCI is widespread despite any evidence supporting a survival benefit in this group of patients. Further trials are warranted to define the optimal pharmacotherapeutic choices in this patient population.

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Gender Differences in Clinical Outcome and Primary Prevention Defibrillator Benefit in Patients With Severe Left Ventricular Dysfunction: A Systematic Review and Meta-Analysis
Santangeli P, Pelargonio G, Dello Russo A, et al.
Heart Rhythm 2010;7:876-882.
Study Question: Do women sustain the same benefit as men following implantable cardioverter-defibrillator (ICD) implant for primary prevention in cardiomyopathy?

Effects of Cardiac Resynchronisation Therapy in Patients With Heart Failure Having a Narrow QRS Complex Enrolled in PROSPECT
Van Bommel RJ, Gorcsan J 3rd, Chung ES, et al.
Heart 2010;96:1107-1113.
Study Question: Will cardiac resynchronization therapy (CRT) benefit subjects with advanced heart failure who have a narrow QRS?

Prevalence of Fracture and Fragment Embolization of Bard Retrievable Vena Cava Filters and Clinical Implications Including Cardiac Perforation and Tamponade
Nicholson W, Nicholson WJ, Tolerico P, et al.
Arch Intern Med 2010;Aug 9:[Epub ahead of print].
Study Question: What is the prevalence of fracture and fragment embolization of Bard Recovery (first generation) and the Bard G2 (second generation) vena cava filters?

Predictors of Pregnancy Complications in Women With Congenital Heart Disease
Drenthen W, Boersma E, Balci, A, et al.
Eur Heart J 2010;Jun 28: [Epub ahead of print].
Study Question: What are the pregnancy outcomes of women with congenital heart disease?

Biological, Clinical and Population Relevance of 95 Loci for Blood Lipids
Teslovich TM, Musunuru K, Smith AV, et al.
Nature 2010;466:707-713.
Study Question: What common sequence variants in the human genome regulate blood lipid levels?

Prevalence and Clinical Significance of Aortic Root Dilation in Highly Trained Competitive Athletes
Pelliccia A, Di Paolo FM, De Blasiis E, et al.
Circulation 2010;122:698-706.
Study Question: What constitutes the upper limits of normal aortic root size, and what is the prevalence and significance of aortic dilation in a large cohort of competitive athletes?

Clopidogrel Loading Dose Adjustment According to Platelet Reactivity Monitoring in Patients Carrying the 2C19 2* Loss of Function Polymorphism
Bonello L, Armero S, Mokhtar OA, et al.
J Am Coll Cardiol 2010;Aug 11:[Epub ahead of print].
Study Question: What is the biological impact of a tailored clopidogrel loading dose (LD) according to platelet reactivity monitoring in carriers of the cytochrome (CYP) 2C19 2* loss-of-function polymorphism undergoing percutaneous coronary intervention (PCI) for an acute coronary syndrome?

Simplification of the Pulmonary Embolism Severity Index for Prognostication in Patients With Acute Symptomatic Pulmonary Embolism
Jiménez D, Aujesky D, Moores L, et al., on behalf of the RIETE Investigators.
Arch Intern Med 2010;170:1383-1389.
Study Question: Will a simplified version of the Pulmonary Embolism Severity Index (PESI) estimate the risk of 30-day mortality in patients with acute pulmonary embolism (PE) as well as the original tool?

Recommendations for the Use of Cardiac Troponin Measurement in Acute Cardiac Care
Thygesen K, Mair J, Katus H, et al., on behalf of the Study Group on Biomarkers in Cardiology of the ESC Working Group on Acute Cardiac Care.
Eur Heart J 2010;Aug 3:[Epub ahead of print].
Perspective: The following are 10 points to remember from this article.

Exercise-Induced Changes in Degenerative Mitral Regurgitation
Magne J, Lancellotti P, Piérard LA.
J Am Coll Cardiol 2010;56:300-309.
Study Question: In patients with degenerative mitral regurgitation (MR), is there a relationship between exercise-induced changes in MR severity and either exercise systolic pulmonary artery pressure or symptom-free survival?

Weight and Metabolic Outcomes After 2 Years on a Low-Carbohydrate Versus Low-Fat Diet: A Randomized Trial
Foster GD, Wyatt WR, Hill JO, et al.
Ann Intern Med 2010;153:147-157.
Study Question: Does a low-carbohydrate diet improve weight loss and metabolic parameters better than a low-fat diet?

A Longitudinal Study of Serum Lipoproteins in Relation to Endogenous Reproductive Hormones During the Menstrual Cycle: Findings From the BioCycle Study
Mumford SL, Schisterman EF, Siega-Riz AM, et al.
J Clin Endocrinol Metab 2010;Jun 9:[Epub ahead of print].
Study Question: Are endogenous estrogens associated with levels of serum lipoproteins across the menstrual cycle?

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High-risk residential areas identified for defibrillator placement
Folke F. Circulation. 2010;122:623-630.

Researchers were able to identify high-risk residential areas suitable for the placement of an automated external defibrillator by using simple demographic characteristics of a city center, according to a new study published in Circulation.

“According to the recommendations from the American Heart Association, 13 AEDs should be placed where there is a high likelihood of sudden cardiac arrest (≥one arrest every 5 years). Whereas a tremendous amount of resources has focused on deployment of AEDs in public locations, the majority of out-of-hospital cardiac arrests (OHCAs) take place in residential areas and remain not covered by publicly placed AEDs,” the researchers commented in their study. “Furthermore, little is known about how to identify residential areas with the highest risk of OHCA, let alone the possible cost of public access defibrillation in such areas.”


This led the group of Danish researchers to examine OHCAs (n=4,828) in Copenhagen from 1994 to 2005. They analyzed the incidence and characteristics of OCHAs in every 100-m × 100-m residential area, according to the demographic characteristics of the grid cells, information about age, level of education, population density and household income.

By combining at least two demographic characteristics, they determined 100-m × 100-m areas with at least one arrest every 5.6 years (characteristics included >300 people per area, lowest income) to one arrest every 4.3 years (characteristics included >300 people, lowest income, low education, highest age). The area with at least one arrest every 5.6 years covered 9% of all residential OCHAs, whereas the area of one arrest every 4.3 years covered 0.8%.

Additional data showed that individuals with OCHAs in residential locations differed from those in public areas in the following ways: patients were older (70.6 vs. 60.6 years), had less frequent ventricular fibrillation (12.8% vs. 38.1%) and had a worse 30-day survival rate (3.2% vs. 13.9%); the ambulance response interval was longer (6 vs. 5 minutes); and the arrests occurred more often at night (21.2% vs. 11.2%; P<.0001 for all comparisons).

“Using simple demographic characteristics of a city center, we were able to identify residential high-risk areas of OHCA suitable for AED placement. Such areas comprised 3% of all residential quarters, but included up to 9% of all residential OHCA,” researchers wrote. “However, individuals with OHCA in residential locations were more likely to have characteristics associated with a poor outcome, a finding emphasizing the necessity for strategic placement of AEDs if future public access defibrillation programs in residential areas are to succeed without excessive costs.”

As a way to overcome the obstacles impeding the success of public access defibrillations in residential areas, the researchers suggested, in addition to strategic placement and providing potential rescuers training in CPR and AED use, the establishment of local AED registries with information on location and availability of AEDs in the community to allow the emergency dispatcher to direct a rescuer to the nearest AED.
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Lead integrity alert algorithm linked with decrease in inappropriate shocks from ICD leads
Kallinen L. Heart Rhythm. 2010;7:1048-1055.

The use of lead integrity monitoring software was associated with an improvement in the number of inappropriate shocks delivered to patients implanted with Medtronic’s Sprint Fidelis implantable cardioverter defibrillator leads, results from a study suggested.

The Sprint Fidelis leads were formally recalled by the manufacturer in October 2007 after reports of lead failures. The manufacturer sent safety advisories to more than 250,000 patients and their physicians regarding the recall and continued impedance monitoring of patients who had received the leads. Although researchers had studied the use of audible alerts intended to identify impending lead fractures, the results of their studies suggested that the alerts did not reliably forewarn patients of impending fracture, nor substantially reduce inappropriate shocks to the patients. After the release of lead integrity alert software by the manufacturer in August 2008, researchers for the current study sought to evaluate an algorithm-based alert system.


Researchers for the single-center study included patients who had received Sprint Fidelis high-voltage ICD leads, which are prone to fracture, at the Minneapolis Heart Institute. Two models of the leads (6949 and 6931) were included for analysis.

Fifty-two (11.3%) of 461 leads failed in the study population between October 2004 and January 2010, with an annual failure rate of 3.6%. Fracture of the pace-sense conductor occurred in 49 of the 52 lead failures (94.2%); the remaining three device failures affected high-voltage conductors. The average time to lead failure was 34.2 ± 12 months.

Inappropriate shocks, according to the researchers, were the first indication of lead failure in more patients without the lead integrity alert software (n=18, 69%) vs. those with the lead integrity alert software (n=4, 17%; P=.0004). The patients who received inappropriate shocks and who did not have the lead integrity alert software had an average of 13.2 ± 13.6 shocks vs. those with the lead integrity alert software (3 ± 2 shocks, P=.017 for comparison). In addition, the audible alert was effective in 70% of patients with the software and 36% of those without the software and whose audible alerts were programmed ON (P=.053).

“The audible alert is problematic for some patients, and manufacturers should improve the ability of ICDs to automatically recognize device problems and to notify caregivers without delay,” the researchers wrote. “Patients who have Sprint Fidelis leads should have lead integrity alert monitoring.”

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Coumadin 1 mg tablet blister packs recalled

Bristol-Myers Squibb has announced a voluntary recall of three lots of physician sample blister packs of Coumadin 1 mg tablets and five lots of Coumadin 1 mg tablet hospital unit dose blister packs. According to the FDA, this recall does not involve Coumadin 1 mg supplied in bottles or any other strengths and dosage forms of the product.

The manufacturer has not received any reports of adverse events, but issued the recall as a precautionary measure based on its determination that some of the tablets, over time, may not meet specifications for isopropanol. Isopropanol is used to maintain the active ingredient, Coumadin, in the crystalline state and could affect the therapeutic levels of the active ingredient.

The following lot numbers are included in this recall:
Physician sample blister packs: Lot# 9A48931A, 9A48931B, 9A48931C, expiration January 2012.
Hospital unit dose blister packs: Lot# 8F34006B, 8K44272A, 8K46168A, 9F44437A and 9K58012B with expiry dates between June 2011 and November 2012.

Any adverse reactions may also be reported to the FDA’s MedWatch Program.
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Title: Safety and Efficacy of Sertraline for Depression in Patients With Heart Failure: Results of the SADHART-CHF (Sertraline Against Depression and Heart Disease in Chronic Heart Failure) Trial
Date Posted: August 18, 2010
Authors: O’Connor CM, Jiang W, Kuchibhartla M, et al.
Citation: J Am Coll Cardiol 2010;56:692-699.

Study Question:
Is sertraline effective for treatment of depression in patients with heart failure?
Methods:
The Sertraline Against Depression and Heart Disease in Chronic Heart Failure (SADHART-CHF) study was a randomized, double-blind, controlled trial comparing sertraline 50 to 200 mg/day to matching placebo among heart failure patients. Subjects were 45 years or older with a left ventricular ejection fraction ≤45% and New York Heart Association functional class II-IV. Clinical major depression was diagnosed by the Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition criteria. Patients with significant cognitive impairment, psychosis, recent alcohol or drug dependence, bipolar or severe personality disorder, active suicidal ideation, and current antipsychotic or antidepressant medication use were excluded. Both treatment arms received nurse-facilitated support. Primary outcomes of interest were change in depression severity measured by the Hamilton Depression Rating Scale total score and composite cardiovascular status at 12 weeks.
Results:
A total of 469 patients were included in the study (234 randomized to sertraline and 235 randomized to placebo). The mean ± SE change in depression score from baseline to 12 weeks was –7.1 ± 0.5 for those in the sertraline groups and –6.8 ± 0.5 for those in the placebo group. The difference between groups was not significant (p = 0.89). The proportion of subjects whose composite cardiovascular score worsened, improved, or was unchanged were 29.9%, 40.6%, and 29.5%, respectively for the sertraline group and 31.1%, 43.8%, and 25.1%, respectively in the placebo group. These proportions were similar between the two groups (p = 0.078).
Conclusions:
The investigators concluded that sertraline was safe for use in heart failure patients with depression; however, reduction in depression compared with the control group was not statistically different. Improved cardiovascular status was also similar between patients randomized to sertraline, as compared to placebo.
Perspective:
Depression among patients with heart failure is an important concern for clinicians. It is likely that the nonsignificant difference between the intervention (i.e., sertraline) and control groups was in part due to the nurse-facilitated support provided to both groups in addition to the types of patients who would enroll in such a study, less severe depression, and dosing of sertraline.

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Title: System Delay and Mortality Among Patients With STEMI Treated With Primary Percutaneous Coronary Intervention
Date Posted: August 17, 2010
Authors: Terkelsen CJ, Sørensen JT, Maeng M, et al.
Citation: JAMA 2010;30:763-771.

Study Question:
What is the impact of delay from the first contact with the health care system to the initiation of reperfusion therapy (system delay) on outcome of patients undergoing primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI)?
Methods:
The authors evaluated the long-term outcome of 6,209 patients who underwent primary PCI for STEMI at three high-volume PCI centers in Western Denmark from January 1, 2002, to December 31, 2008. All patients in the study were transported by emergency medical services.
Results:
The median follow-up was 3.4 years. Over 35% of patients were triaged in the field and transported directly to PCI hospitals with the proportion of patients being directly transferred increasing over the study time period. An increase in long-term mortality was seen with increasingly longer system delay. The long-term mortality among patients with a system delay of 60 minutes or less was 15.4%; for a delay of 61-120 minutes, it was 23.3%, and rose to 28.1% among those with a system delay of 121-180 minutes and 30.8% in those with a delay of 181- 360 minutes. After adjusting for baseline confounders, system delay was an independent predictor of long-term mortality (adjusted hazard ratio for 1-hour delay, 1.10; 95% confidence interval, 1.04-1.16). Increasing mortality was seen with both prehospital delay and prolonged door-to-balloon time.
Conclusions:
Prolonged delay between first contact with health care and reperfusion is associated with an increased risk of long-term mortality.
Perspective:
Although the importance of rapid reperfusion in STEMI has been recognized for a long time, most of the effort to translate this into clinical practice has focused on reducing door-to-balloon time. This study invokes the need to focus on the total delay and to develop systems of care to minimize both prehospital and hospital delays to reperfusion.
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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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Women and Heart Disease: A report from the 2010 World Congress of Cardiology in Beijing
by Nanette K. Wenger, MD

Incorporated within the World Congress of Cardiology Scientific Sessions 2010 in Beijing was the Third International Conference on Women, Heart Disease and Stroke, the first time this latter meeting has been held in Asia.
Fifteen sessions addressing women and CHD were held during the course of the Congress, including meetings on therapeutic interventions and case discussions; CVD and pharmacology in pregnancy; gender differences and international trends; mobilizing communities to reduce the effect of tobacco in women; and examination of the Heart Health Tool Kit, highlighting the needs and opportunities in every decade of a woman’s life for coronary prevention.
At the conference, Dong Zhao, MD, PhD, co-chair of the World Congress of Cardiology 2010 Scientific Program and chair of the Third International Conference on Women, Heart Disease and Stroke, said worldwide, more women than men die from CVD. In fact, CVD is the No. 1 killer worldwide for women, killing more women than all cancers, HIV/AIDS, tuberculosis and malaria combined. Eighty percent of CV deaths in women occur in developing countries. CVD is the major killer of women in China, both urban and rural, surpassing cancer and respiratory disease. Because CVD has been considered erroneously to be predominantly a disease of men, a disturbing gap exists in the knowledge, understanding and general awareness of CVD in women worldwide.

Online survey

Before this conference, the World Heart Federation conducted an online survey of 1,017 Chinese women, widely distributed throughout the provinces of China, to ascertain their knowledge about CVD. Ten percent said they believed that heart disease and stroke were leading causes of death in Chinese women, but 82% said cancer was the major killer of women in China. Ten percent and 3% of women considered heart disease and stroke, respectively, to be their primary health concerns; but 72% of women thought that men were more likely than women to have a heart attack or stroke. Approximately one-third of the women surveyed did not believe that smoking (34%) or lack of exercise (29%) placed women at greater risk for heart disease and stroke.

This survey highlights the potential gap in relating behavioral modifications to reduction of risk, and that Chinese women are often at increased risk for heart disease and stroke because they are unaware of CV risk factors. Not that this is sex-specific in the region — China consumes one-quarter of all the cigarettes smoked worldwide, with smoking highly prevalent among male Chinese cardiologists. Hypertension and hyperlipidemia are rampant in both sexes, and obesity is increasing.

These data in the survey of Chinese women are not dissimilar from those in the United States during the mid-1990s, when the American Heart Association undertook the Go Red for Women campaign, designed to increase awareness and consequent action by women to prevent CVD. The goal is that this AHA program can be exported to developing countries worldwide, and the initial approaches in China show that this is highly feasible and relevant.

Global campaign

Among the aspects currently being adapted within China are those that were enunciated in the 2005 Second International Conference on Women, Heart Disease and Stroke in Orlando, Fla. The campaign emphasizes motivating health professionals to appropriately care for women by recognizing differing symptoms of heart disease and stroke between the sexes and providing treatment accordingly. It also encourages more research into sex-specific heart health issues, but perhaps more importantly, appeals to policymakers to include heart health for women and their families in governmental health policies and programs.

The promotion for the Go Red for Women campaign in China, designed to improve the prevention, diagnosis and treatment of CVD in women by raising awareness, emphasizes in its promotional illustrations that the campaign’s primary symbol is not just a “Red Dress,” but “a Red Alert,” signifying the need for increased awareness that the woman’s heart is vulnerable to heart disease and that prevention strategies are available and appropriate.

Dr. Zhao said the Third International Conference on Women, Heart Disease and Stroke “will definitely increase the awareness of the importance of heart disease and stroke to the scientific community and the public, especially in Asia, where over 60% of women in the world live.”

It was my privilege to have been involved in the planning and chairing of a number of these sessions, and I cherish the participation with my Chinese professional colleagues in this important scientific and public policy endeavor.