CMAJ Readers' Forum

Primary prevention of heart disease and stroke

Online posting: Nov. 18, 1997
Published in print: January 13, 1998 (CMAJ 1998;158:24)
Re: Primary prevention of heart disease and stroke: a simplified approach to estimating risk of events and making drug treatment decisions, by James P. McCormack and associates, CMAJ 1997;157[4]:422-8 [full text / résumé]

See response from: J.P. McCormack and associates

I would like to comment on the use of meta-analyses of short-term intervention trials to estimate the potential benefits of antihypertensive therapy.

Although randomized clinical trials are the gold standard for evaluating the efficacy of most interventions, recent data from the Framingham Study1 suggest that the hypertension trials may underestimate the long-term benefits of antihypertensive therapy. These trials were designed to test the effect of short-term interventions (3 to 6 years) on end-points such as stroke, myocardial infarction and death. In young or middle-aged patients, the risk of these end-points occurring within 5 years (the time frame of most of the studies) is low, and the goal of antihypertensive therapy "is not to prevent an unlikely hypertension-related event . . . but rather to prevent or retard the development of cardiovascular lesions and help the subject attain their full life span."2 These trials may also have systematically underestimated the degree of any short-term treatment effects as a result of administration of active treatment to high-risk individuals in the placebo arms of the trials, recruitment of low-risk subjects into the trials, greater loss to follow-up of high-risk subjects and lack of statistical power in many of these trials.3 Finally, the relative risk reductions published in the meta-analyses represent the average treatment benefits for modest decreases in blood pressure (5 to 6 mm Hg diastolic, 10 mm Hg systolic) and, as such, probably underestimate the potential benefits for the individual in whom greater reductions in blood pressure may be achieved.

These limitations raise the question of how best to assess the potential long-term benefits of antihypertensive therapy. Although randomized clinical trials with long-term follow-up (on the order of 20 to 30 years) would be ideal, it is highly unlikely that these will be carried out. The use of actuarial data2 and observational outcomes research4 have recently been advocated, but these techniques are imperfect. Although the nomograms presented in the paper by McCormack and associates are a useful first step in estimating risk, we must now focus our attention on developing better estimates of the long-term benefits of preventive therapies.

Finlay A. McAlister, MD
Division of General Internal Medicine
Ottawa Civic Hospital
Ottawa, Ont.
finlay@ceu.uottawa.ca

References

  1. Sytkowski PA, D'Agostino RB, Belanger AJ, Kannel WB. Secular trends in long-term sustained hypertension, long-term treatment, and cardiovascular mortality. The Framingham Heart Study 1950 to 1990. Circulation 1996;93:697-703.
  2. Zanchetti A, Mancia G. Benefits and cost-effectiveness of antihypertensive therapy. The actuarial versus the intervention trial approach. J Hypertens 1996;14:809-11.
  3. Linjer E, Hansson L. Underestimation of the true benefits of antihypertensive treatment: an assessment of some important sources of error. J Hypertens 1997;15:221-5.
  4. Psaty BM, Siscovick DS, Wiess NS, et al. Hypertension and outcomes research: from clinical trials to clinical epidemiology. Am J Hypertens 1996;9:178-83.
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