Which Drugs Have Truly Safe and Effective Effects?

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Meta-Analysis Shows Statins Do Lower Blood Pressure

The question remains open as to whether the effect of statins on cardiovascular morbidity and mortality may in some way be linked to an ability to lower blood pressure, as well as lowering low-density lipoprotein (LDL) cholesterol. Statins have been linked to benefits in hypertension because of their effects on endothelial function, their interactions with the renin-angiotensin system, and their influence on large artery compliance. However, few studies have been carried out on the antihypertensive effects of statins in patients with hypertension and hypercholesterolemia, and those studies that have were usually limited by small sample size, short treatment period, and/or inappropriate study design. In an analysis of clinical trial data presented at the ESH meeting, European investigators showed that statin therapy has a small but statistically significant effect on blood pressure, especially systolic blood pressure (SBP).^[6]

Pasquale Strazzullo, MD (Federico II University Medical School, Naples, Italy), reported the results of a meta-analysis performed with colleagues at the University of London and Warwick Medical School, Coventry, UK, of all studies that reported blood pressure data during treatment with statins. The 20 randomized controlled trials included in the meta-analysis were all published, in English, up to 2005. Each reported on a number of prespecified variables, including blood pressure values at the start and end of the study, and per meta-analysis protocol, patients on concomitant antihypertensive medication had to have remained on a fixed regimen throughout the trials. Eighteen trials were placebo-controlled, 1 compared a statin with probucol, and 1 compared a statin plus orlistat vs orlistat. The statins involved in the trials were pravastatin (8 trials), simvastatin (6 trials), fluvastatin (3 trials), atorvastatin (2 trials), cerivastatin (2 trials), and lovastatin (1 trial). In 18 trials, patients were hypercholesterolemic and in 11 trials they were hypertensive. A total of 889 patients participated, and the length of the studies ranged from 4 weeks to 1 year.

In 14 trials, SBP was lower in patients on a statin than on placebo or control drug. Overall, SBP was lower by a mean of -1.9 mm Hg (-3.8 to 0.1), approaching statistical significance. Diastolic blood pressure (DBP) was lower on statins vs control in 14 trials. In 3 of these trials, this difference was statistically significant, but overall, the effect on DBP was not significant. Higher blood pressure at baseline appeared to be a significant predictor of the blood pressure response with statin treatment (P = .06 for SBP and P = .02 for DBP).

A larger effect of the statins on SBP was seen when the analysis was restricted to studies in which average follow-up SBP was > 130 mm Hg, with a highly significant mean reduction of 4.0 mm Hg. Analysis restricted to studies with mean DBP > 80 mm Hg also showed a greater reduction with statins at 1.2 mm Hg. The effects of statins appeared to be greater in the 4 trials in diabetic patients, with an average 6 mm Hg reduction in SBP and 3 mm Hg reduction in DBP. No significant relationship was found between blood pressure response to statin treatment and age, diabetic status, change in serum cholesterol due to treatment, and concomitant antihypertensive treatment. The relationship with diabetes is suggestive, although not statistically significant, and it is not clear whether this is a class effect or a property of 1 or more single drugs, Prof. Strazzullo pointed out. He suggested that a possible mechanism of action might be that patients who have a greater degree of endothelial dysfunction might have a larger blood pressure response to statins.