Fixed-dose combination pills reduced SBP and LDL-C in patients with, or at high risk for, cardiovascular disease

摘要

Commentary That C V outcomes could be improved by the widespread use of a fixed-dose pill containing several medications individually known to be beneficial goes back to at least 2003, when Wald and Law used modeling to estimate that a "polypill" containing aspirin, a statin, an angiotensin-converting enzyme inhibitor, a P-blocker, a thiazide, and folic acid might achieve a relative risk reduction of 88% in incident CVD events (1). Since then, the concept has been the subject of numerous commentaries and meta-analyses of trials of the individual components. However, until the UMPIRE trial, there had not been a direct comparison of a polypill and usual care for patients at risk for CV events. In the trial by Thorn and colleagues, use of the polypill (without folic acid after the collapse of the homocysteine hypothesis) improved patient compliance according to self-report in an unblinded trial, which increases the possibility of bias. Surrogate CVD outcomes (SBP and LDL-C) also improved, but by small amounts: 2 to 3 mm Hg of blood pressure and 4 mg/dL of LDL-C. Given these small changes in surrogate outcomes, an 88% reduction in CVD events is not possible. The authors calculate that these reductions "might" result in a relative risk reduction of about 15%. Further, attributing any benefits to the polypill alone is problematic in this trial: It was provided free to participants in the intervention group, whereas control group participants had to pay out of pocket or provide their own insurance coverage for the individual-component medications. In addition, despite its name, the UMPIRE trial was not powered to detect differences in actual cardiac events, which occurred in 5% in the polypill group and 3.5% in the usual care group. While not statistically different, these results indicate that studies of actual CVD outcomes are needed before widespread use of-the polypill can be advocated. In the debate about which strategy is better "one size fits all, which will increase compliance" vs "individualized drugs and doses to personalize treatment," the UMPIRE trial falls short of deciding a winner.