"Take a Statin and Call Me in the Morning"- Are Statins the New Aspirin?
As we hear about the many wonders of statin therapy-most recently blood pressure reduction-it recalls the past 30 years of debate about the benefits of daily aspirin.
Joanne LaFleur is an assistant professor in the department of pharmacotherapy at the University of Utah College of Pharmacy.
When Heart Protection Study researchers unveiled their findings at the American Heart Association meeting in 2001, in their enthusiasm for the mortality benefits they found, they declared statins to be the new aspirin.1 Since then, the years have brought us frequent reports in the scientific literature about the many beneficial pleiotropic (nonlipid) effects of statin therapy (Table2-61). As we hear about these many wonders of statin therapy—most recently blood pressure reduction—it recalls to mind the past 30 years of debate about the benefits of daily aspirin for preventing everything from cardiovascular disease to cancer, and even dementia.62
Although the benefits of aspirin therapy are well-documented, particularly for cardiovascular disease prevention, we also now know that the risks of daily aspirin therapy may outweigh the benefits in several important subsets of the population.63 That is why we should carefully consider the evidence showing beneficial pleiotropic effects of the statin class before we similarly begin to regard it as a panacea. As a case in point, let us consider the evidence of the statin’s effects on blood pressure, which was the subject of a recent clinical trial.64
Statin Effects on Blood Pressure
Between 1999 and 2005, many observational studies showed small blood pressure reductions in hypertensive patients who were receiving statins.39-43 Some small-scale randomized controlled trials also studied blood pressure changes in statin recipients, but many showed conflicting results.44-47 Following these reports, clinicians and researchers remained uncertain about the effect of statins on blood pressure. The observational studies were conducted in widely differing patient populations, among whom numerous confounders were present; most of the randomized controlled trials were not designed to evaluate blood pressure as a primary end point; and above all, the effect sizes were very small.
Better data were soon forthcoming. A meta-analysis, published last year, concluded, on the basis of data from 563 patients from more than 20 randomized controlled trials, that statins reduced systolic blood pressure an average of 1.9 mm Hg.48 That was rather an underwhelming effect size, but the reduction was a little bit greater—4.0 mm Hg—in the subset of patients with baseline systolic blood pressure >130 mm Hg. Researchers found no effect on diastolic blood pressure. Following that analysis, the largest randomized controlled clinical trial to date (which included more patients than all the studies in the meta-analysis combined) showed in 973 men and women that statins reduced systolic blood pressure by 2.2 mm Hg and diastolic blood pressure by 2.4 mm Hg.64
Could the effects reported by these researchers be a result of chance or error? After all, an effect size of 2 mm Hg could easily be attributable to measurement error. Measurement error would not be a plausible explanation, however, unless we thought systematic differences existed in the blood pressure measurement methods between patients who received statins compared with those who did not. And, although random chance cannot be completely ruled out, it is an unlikely explanation. The statistics reported in these studies tell us that the likelihood that findings were due to random chance was less than 1 in 100 for the meta-analysis and less than 1 in 1000 for the clinical trial. These probabilities are well below established thresholds for determining “statistical” significance.
The impact of statins on blood pressure may be a real effect, but undoubtedly, the effect size is small—so small, in fact, that it may be safely disregarded. Findings from the recent clinical trial and meta-analysis suggest that any blood pressure effect of statins is certainly lower than the average effect of antihypertensive drugs. Therefore, statins should continue to be used for patients with dyslipidemias, particularly low-density lipoprotein elevations, and in patients with established coronary artery disease or risk equivalents (such as diabetes). Statins should not be considered as a means of reducing blood pressure. â–
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