Response to Combination Treatment to Prevent Atherosclerosis
In his letter, Koh1 focused on the significant heterogeneity in the blood pressure (BP) effects of statins observed in the studies included in our meta-analysis2 and correctly identified a number of reasons that explain this large variability. Also, it should be underscored that very few of the trials available had the effect on BP as a specific outcome. In addition, Koh mentions the use of secondary sources, ie, published articles instead of primary data sets, as a potential source of bias. One may agree on this view in principle, but the difficulty of obtaining access to the original data sets and making appropriate use of them should not be underestimated. More specifically, reference is made to a study by Koh et al3 that was quoted in our work and included in the meta-analysis. Koh1 remarks that, in contrast with our report that treatment with simvastatin was associated in their study with a BP rise, there was actually a fall in BP of as much as 3/3 mm Hg, which was marginally statistically significant. Indeed, in this case, the problem does not arise from the use of the published data but from a different approach to the data. The putative 3/3 mm Hg BP fall claimed by Koh1 was the difference between baseline and final BP in the simvastatin plus placebo arm of the study. We chose not to use this finding because there was actually no control in this analysis. The trial by Koh et al3 included 2 other parallel treatment arms with administration of losartan plus placebo and losartan plus simvastatin, respectively, and, indeed, the objective of the study was to investigate the additive beneficial effects of losartan combined with simvastatin in the treatment of hypercholesterolemic, hypertensive patients. Thus, in our opinion, the proper comparison was the one between the losartan plus simvastatin treatment (difference between final and baseline BP) and that with losartan plus placebo. In this comparison, as the authors acknowledged, no additive effect of the statin was observed. As far as the additional work by Koh et al4 in diabetic patients, we regret that our search strategy failed to detect this work, which was unable to demonstrate an effect of statins on BP in normotensive participants.
We share the view that patients with hypertension and a combination of risk factors may be the best candidates to experience a fall in BP while taking a statin. We also would agree that probably the more marked the endothelial dysfunction the greater the BP effect; this, however, awaits direct demonstration.
Koh KK. Combination treatment to prevent atherosclerosis. Hypertension. 2007; 50: e67.
Strazzullo P, Kerry SM, Barbato A, Versiero M, D’Elia L, Cappuccio FP. Do statins reduce blood pressure? A meta-analysis of randomized, controlled trials. Hypertension. 2007; 49: 792–798.
Koh KK, Quon MJ, Han SH, Chung WJ, Ahn JY, Seo YH, Kang MH, Ahn TH, Choi IS, Shin EK. Additive beneficial effects of losartan combined with simvastatin in the treatment of hypercholesterolemic, hypertensive patients. Circulation. 2004; 110: 3687–3692.
Koh KK, Quon MJ, Han SH, Ahn JY, Jin DK, Kim HS, Kim DS, Shin EK. Vascular and metabolic effects of combined therapy with ramipril and simvastatin in patients with type 2 diabetes. Hypertension. 2005; 45: 1088–1093.