Top POEMs of 2012: Cardiovascular Disease

ASA: Not for Primary Prevention

Clinical question: Is regular aspirin useful to prevent cardiovascular events in patients without cardiovascular disease?

Bottom line: The shine is off the aspirin-for-primary-prevention apple -- it no longer looks as though an aspirin a day keeps the heart disease away. Based on 9 studies of more than 100,000 patients, including 3 fairly recent studies, a total of 254 patients without cardiovascular disease have to take aspirin for 7 years to prevent 1 additional person from having a cardiovascular event. And there will be one more major bleed in the same group. (LOE = 1a)

Reference: Berger JS, Lala A, Krantz MJ, Baker GS, Hiatt WR. Aspirin for the prevention of cardiovascular events in patients without clinical cardiovascular disease: A meta-analysis of randomized trials. Am Heart J 2011;162(1):115-124.e2.

Study design: Meta-analysis (randomized controlled trials)

Funding source: Government

Setting: Various (meta-analysis)

Synopsis: This meta-analysis is an update from a previous analysis, including the results of 3 new studies. Together, these studies evaluated 102,621 patients without clinically apparent cardiovascular disease. The majority of the studies enrolled a significant proportion of women and 2 studies enrolled only patients with diabetes. Doses of aspirin ranged from 100 mg every other day to 500 mg daily. The authors did not explain how they selected the studies, extracted the data, or evaluated the quality of the research. They found no heterogeneity in the outcomes, except for the end point of myocardial infarction.The composite outcome of major cardiovascular events occurred in 3.86% of patients treated with aspirin as compared with 4.16% treated with placebo (relative risk = 0.9; 95% CI, 0.85 - 0.96). In other words, one event was prevented in 1 of 253 patients treated for almost 7 years. However, none of the individual outcomes -- myocardial infarction, stroke, or death -- were signficantly reduced, making the actual estimate of benefit suspect. Aspirin use was associated with significantly higher risk of hemorrhagic stroke and major bleeding, leading to a number needed to treat to harm of 261 (182-476). The lack of benefit seems not to be related to baseline risk or sex.

Allen F. Shaughnessy, PharmD, MMedEd
Professor of Family Medicine
Tufts University
Boston, MA

Treatment for Mild Hypertension Is Ineffective

Clinical question: Does the treatment of mild hypertension decrease morbidity or mortality in patients without cardiovascular disease?

Bottom line: Dogma dashed? The treatment of mild hypertension (defined as 140-159/90-99 mmHg) in patients without cardiovascular disease does not decrease mortality, coronary heart disease, stroke, or total cardiovascular events. We can stop worrying about patients who have these mildly elevated numbers without symptoms or signs of heart disease. (LOE = 1a)

Reference: Diao D, Wright JM, Cundiff DK, Gueyffier F. Pharmacotherapy for mild hypertension. Cochrane Database Syst Rev 2012 Aug 15;8:CD006742.

Study design: Meta-analysis (randomized controlled trials)

Funding source: Self-funded or unfunded

Setting: Various (meta-analysis)

Synopsis: This Cochrane Review was conducted in, well, the usual Cochrane Review manner, which assures good search, review, and data-analysis techniques. The process doesn't control all decisions regarding study inclusion, though it requires authors to explain how they selected and used data. In this analysis, the authors selected studies evaluating active treatment of mild hypertension (defined as systolic blood pressure 140-159 mmHg, diastolic blood pressure 90-99 mmHg, or both) compared with placebo, in patients without overt cardiovascular disease. The authors excluded 3 big studies that didn't include a placebo group and excluded 3 more studies for which they were unable to obtain the primary data to tease out patients with mild hypertension from other patients. The final analysis included 4 studies with a total of 8912 participants. Most of the patients were from a single study (the Medical Research Council Study of mild hypertension), which treated half the patients with a diuretic and half with a beta-blocker. Risk of bias was high for most of the studies, which makes any difference between treatment and placebo suspect -- but there wasn't any difference. Treatment for 4 to 5 years did not reduce total mortality, coronary heart disease, stroke, or total cardiovascular events. The problem? It's a good one to have: low rates of death, heart disease, or stroke in untreated patients, making it hard to show further benefit of diuresing or beta-blocking. The glass-half-full crowd will point out a nonsignificant decrease in stroke (relative risk [RR] = .51; 95% CI, .24-1.08) and mortality (RR = .85; .63 - 1.15); the glass-half-empty response is to point out a nonsignificant increase in heart disease (RR = 1.12; .8 - 1.57).

Allen F. Shaughnessy, PharmD, MMedEd
Professor of Family Medicine
Tufts University
Boston, MA

Statins of Modest Benefit for Low- to Moderate-Risk Persons (NNT ~ 80)

Clinical question: To what extent are statins effective for primary prevention in persons at low to moderate cardiovascular risk?

Bottom line: The title of this study is somewhat misleading: It is actually a report of patients who are at low to moderate risk (an average 10-year risk of cardiovascular death or myocardial infarction [MI] of 6.2%). What does a patient like this look like? Checking the mirror, I found that a 50-year-old male nonsmoker who takes antihypertensives, has a total cholesterol level of 210 mg/dL, an HDL level of 50 mg/dL, and systolic blood pressure of 130 mm Hg has a 6% 10-year risk. Gulp! The question is whether it is worth taking a medication for 10 years to be the 1 in 80 people who will benefit from it. And, these fairly high numbers needed to treat for primary prevention in moderate-risk persons incorporate some of the biases of the underlying studies, so they are probably on the optimistic side. (LOE = 1a)

Reference: Tonelli M, Lloyd A, Clement F, et al, for the Alberta Kidney Disease Network. Efficacy of statins for primary prevention in people at low cardiovascular risk: a meta-analysis. CMAJ 2011;183(16):E1189-1202.

Study design: Meta-analysis (randomized controlled trials)

Funding source: Government

Setting: Various (meta-analysis)

Synopsis: There is still considerable controversy about the extent to which statins reduce key patient-oriented outcomes as primary prevention. In this meta-analysis, the authors did a thorough search to identify all randomized controlled trials that compared a statin with placebo or no treatment in low-risk adults and reported at least one patient-oriented outcome. "Low risk" was defined as a 10-year risk of cardiovascular death or nonfatal MI of less than 20%. Some patients actually had known coronary heart disease, and the mean 10-year risk of cardiovascular death or MI was 6.2%, with a range of 0 to 18%. A total of 29 studies with 80,711 patients met their inclusion criteria; the median age of participants was 58 years. Perhaps the most interesting table in the entire article is a list of the 21 acronyms used by the trialists, including such gems as ASTRONOMER, PHYLLIS (My mother-in-law! Who knew?), METEOR, and ESPLANADE. The authors reported relative and absolute risk reduction for key outcomes, as well as the number needed to treat (NNT). However, NNT requires a context: an NNT of 100 over 10 years to prevent 1 death is very different from an NNT of 100 over 3 years to prevent 1 death. I therefore used data from their appendix to calculate a mean duration of follow-up across all studies of 3.4 years. The NNT for all-cause mortality was 239, for any MI was 216, and for any stroke was 291. These benefits were statistically significant. If one assumed that the benefit was linear and extrapolated to 10 years, the NNTs were 80, 72, and 97, respectively. There was no difference in the all-cause mortality benefit between low-potency and high-potency statins (relative risk = 0.90 for both).

Mark H. Ebell, MD, MS
Associate Professor
University of Georgia
Athens, GA

POEMs are provided by Essential Evidence Plus, a point-of-care clinical decision support system published by Wiley-Blackwell. For more information, please see http://www.essentialevidenceplus.com(www.essentialevidenceplus.com).

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