Cochrane for Clinicians: Putting Evidence into Practice

Should We Use Multiple Risk Factor Interventions for the Primary Prevention of Coronary Heart Disease?

Am Fam Physician. 2002 Jul 15;66(2):245-246.

Clinical Scenario

A 45-year-old asymptomatic woman with hypertension, hypercholesterolemia, obesity, a history of smoking, and a family history of myocardial infarction presents for a complete physical examination. Her medications include atenolol and hydrochlorothiazide.

Clinical Question

Do multiple risk factor reduction interventions reduce the risk of morbidity or mortality from coronary artery disease?

Evidence-Based Answer

In hypertensive patients at high risk for coronary artery disease, multiple risk factor reduction interventions reduce risk factors and mortality. In other patients, multiple risk factor reduction interventions reduce total cholesterol levels, blood pressure (systolic and diastolic) levels, and smoking rates. However, risk factor reduction does not dramatically reduce mortality among low-risk patients. The review did not have sufficient power to demonstrate a small reduction in mortality (less than 10 percent). Therefore, it is possible that there is a small reduction in mortality in low-risk patients.

Cochrane Abstract

Background. Primary prevention programs in many countries attempt to reduce mortality and morbidity caused by coronary heart disease through risk factor modification. It is widely believed that multiple risk factor reduction interventions using counseling and educational methods are efficacious and cost-effective, and should be expanded. Recent trials examining risk factor changes have cast considerable doubt on the effectiveness of these multiple risk factor interventions.

Objectives. To assess the effects of multiple risk factor interventions in reducing cardiovascular risk factors, total mortality, and mortality from coronary heart disease among adults without clinical evidence of established cardiovascular disease.1

Search Strategy. The authors searched MEDLINE using a standard randomized trial filter. Date of the most recent search was April 1995. A substantive update to this search was performed in 1999.

Selection Criteria. Intervention studies using counseling or education to modify more than one cardiovascular risk factor in adults from general populations, occupational groups, or high-risk groups. Trials of less than six months' duration were excluded.

Data Collection and Analysis. Both reviewers independently extracted data. Investigators were contacted to obtain missing information.

Primary Results. A total of 18 trials were found, of which 10 reported clinical event data. Net changes in systolic and diastolic blood pressure levels, smoking prevalence, and serum cholesterol levels were −3.9 mm Hg (95 percent confidence interval [CI], −4.2, −3.6 mm Hg), −2.9 mm Hg (95 percent CI, −3.1, −2.7 mm Hg), −4.2 percent (95 percent CI, −4.8, −3.6 percent), and −0.08 mmol per L (95 percent CI −0.1, −0.06 mmol per L), respectively. In the 10 trials with clinical event end points, the pooled odds ratios for total and coronary heart disease mortality were 0.97 (95 percent CI, 0.92 to 1.02) and 0.97 (95 percent CI, 0.88 to 1.04), respectively.

Statistical heterogeneity between the studies with respect to mortality and risk factor changes was due to trials focusing on hypertensive participants and participants using considerable amounts of drug treatment. Only these trials demonstrated significant reductions in mortality.

Reviewers' Conclusions. The pooled effects suggest multiple risk factor intervention has no effect on mortality. However, a small but potentially important benefit of treatment (about a 10 percent reduction in coronary heart disease mortality) may have been missed. Risk factor changes were relatively modest and related to the amount of pharmacologic treatment used, and, in some cases, may have been over-estimated because of regression to the mean effects, lack of intention-to-treat analyses, habituation to blood pressure measurement, and use of self-reports of smoking. Interventions using personal or family counseling and education with or without pharmacologic treatment appear to be more effective in achieving risk factor reduction and consequent reductions in mortality in high-risk hypertensive populations. The evidence suggests that such interventions have limited utility in the general population.


These summaries have been derived from Cochrane reviews published in the Cochrane Database of Systematic Reviews in the Cochrane Library. Their content has, as far as possible, been checked with the authors of the original reviews, but the summaries should not be regarded as an official product of the Cochrane Collaboration; minor editing changes have been made to the text (http://www.cochrane.org)

Cochrane Critique

Did the authors address a focused clinical question? No. This review assessed a wide array of interventions (including counseling and educational approaches with or without pharmacologic interventions) on multiple outcomes (reducing systolic and diastolic blood pressure, total cholesterol levels, smoking rates, and coronary artery disease mortality among adults 40 years and older). Pooling these studies is highly questionable.

Were the criteria used to select articles for inclusion appropriate? The inclusion criteria were inappropriately broad.

Is it likely that important relevant articles were missed? No.

Was the validity of the individual articles appraised? Yes. Validation of quitting-smoking outcomes using biochemical assay of serum cotinine levels was used in only one trial.

Were the assessments of studies reproducible? Yes.

Were the results similar from study to study? Yes.

How precise were the results? The inclusion of studies with and without biochemical validation of quitting-smoking outcomes raises concern about ascertainment bias of smoking status.

Can the results be applied to patient care? Yes.

Do the conclusions make biologic and clinical sense? Yes.

Are the benefits worth the harms and cost? There is insufficient information to assess this question.

Practice Pointers

This review provides evidence from randomized controlled trials that multiple risk factor reduction interventions in adults are effective in reducing blood pressure levels, total cholesterol levels, and smoking rates. On the surface, this may not seem like new information, given the large body of epidemiologic evidence supporting the benefits on mortality of lowering cholesterol levels, blood pressure, and smoking prevalence. However, the U.S. Preventive Services Task Force2 has given counseling by primary care physicians to promote physical activity and a healthy diet a class C level of evidence. Class C evidence indicates that there is insufficient evidence that an intervention is effective in improving outcomes.

Reading the Numbers

The review noted that evidence of “statistical heterogeneity” was apparent in the pooled odds ratios for total mortality, but that removal of trials including hypertensive patients reduced the heterogeneity for total mortality. To pool studies with subjects recruited from different populations, it is important to determine whether the outcomes of interest (in this case, mortality) are different (heterogenous) or similar (homogenous) between strata. In other words, if mortality benefits are realized among hypertensive patients who receive multiple risk factor modification but not among normotensive patients, there is evidence of statistical heterogeneity between strata. If statistical heterogeneity exists, it is not valid to pool strata of hypertensive and normotensive patients because the outcome is confounded by the factor of hypertension. In this case, hypertension would be considered a control variable. This phenomenon is also referred to as interaction between the control variable(s) with respect to mortality, or as “effect modification.”3

Reading the Numbers

The review noted that evidence of “statistical heterogeneity” was apparent in the pooled odds ratios for total mortality, but that removal of trials including hypertensive patients reduced the heterogeneity for total mortality. To pool studies with subjects recruited from different populations, it is important to determine whether the outcomes of interest (in this case, mortality) are different (heterogenous) or similar (homogenous) between strata. In other words, if mortality benefits are realized among hypertensive patients who receive multiple risk factor modification but not among normotensive patients, there is evidence of statistical heterogeneity between strata. If statistical heterogeneity exists, it is not valid to pool strata of hypertensive and normotensive patients because the outcome is confounded by the factor of hypertension. In this case, hypertension would be considered a control variable. This phenomenon is also referred to as interaction between the control variable(s) with respect to mortality, or as “effect modification.”3

This review indicates that multiple risk factor intervention is effective in improving cardiac risk factors among populations of patients and that these interventions are also effective in reducing cardiovascular mortality among patients with high blood pressure. Although this review did not show a reduction in mortality in low-risk patients, there may be a small but clinically significant reduction in mortality among patients at all levels of risk. The bottom line for physicians is that risk factor identification and counseling, with or without pharmacologic therapy, has its intended effects on blood pressure and cholesterol levels, and on smoking rates, and should be included as part of standard preventive services, especially in high-risk patients.

Sean P. David, M.D., S.M., is assistant professor of family medicine at Brown University Medical School, Pawtucket, R.I. He is a visiting fellow in primary health care at the University of Oxford, Oxford, U.K.

Address correspondence to Sean P. David, M.D., S.M., Brown University Center for Primary Care and Prevention, 111 Brewster St., Pawtucket, RI (e-mail: sean_david@brown.edu). Reprints are not available from the author.

REFERENCES

1. Ebrahim S, Davey Smith G. Multiple risk factor interventions for primary prevention of coronary heart disease (Cochrane Review). Cochrane Database Syst Rev. 2000;2:CD001561.

2. U.S. Preventive Services Task Force. Guide to clinical preventive services: report of the U.S. Preventive Services Task Force. 2d ed. Baltimore: Williams & Wilkins, 1996:877–8.

3. MacMahon B, Trichopoulos D. Epidemiology: principles and methods. 2d ed. Boston: Little, Brown, 1996:196–7.

The Cochrane Abstract is a summary of a review from the Cochrane Library. It is accompanied by an interpretation that will help clinicians put evidence into practice. Sean P. David, M.D., S.M., presents a clinical scenario and question based on the Cochrane Abstract, along with the evidence-based answer and a full critique of the abstract.


Copyright © 2002 by the American Academy of Family Physicians.
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