Lafeber Melvin, Webster Ruth, Visseren Frank Lj, Bots Michiel L, Grobbee Diederick E, Spiering W, Rodgers Anthony
Julius Center for Health Sciences and Primary Care, the Netherlands Department of Vascular Medicine, University Medical Center Utrecht, the Netherlands.
George Institute for Global Health, Australia.
Eur J Prev Cardiol. 2016 Aug;23(12):1289-97. doi: 10.1177/2047487315624523. Epub 2016 Jan 7.
Recent data indicate that fixed-dose combination (FDC) pills, polypills, can produce sizeable risk factor reductions. There are very few published data on the consistency of the effects of a polypill in different patient populations. It is unclear for example whether the effects of the polypill are mainly driven by the individuals with high individual risk factor levels. The aim of the present study is to examine whether baseline risk factor levels modify the effect of polypill treatment on low-density lipoprotein (LDL)-cholesterol, blood pressure (BP), calculated cardiovascular relative risk reduction and adverse events.
This paper describes a post-hoc analysis of a randomised, placebo-controlled trial of a polypill (containing aspirin 75 mg, simvastatin 20 mg, lisinopril 10 mg and hydrochlorothiazide 12.5 mg) in 378 individuals without an indication for any component of the polypill, but who had an estimated five-year risk for cardiovascular disease ≥7.5%. The outcomes considered were effect modification by baseline risk factor levels on change in LDL-cholesterol, systolic BP, calculated cardiovascular relative risk reduction and adverse events.
The mean LDL-cholesterol in the polypill group was 0.9 mmol/l (95% confidence interval (CI): 0.8-1.0) lower compared with the placebo group during follow-up. Those with a baseline LDL-cholesterol >3.6 mmol/l achieved a greater absolute LDL-cholesterol reduction with the polypill compared with placebo, than patients with an LDL-cholesterol ≤3.6 mmol/l (-1.1 versus -0.6 mmol/l, respectively). The mean systolic BP was 10 mm Hg (95% CI: 8-12) lower in the polypill group. In participants with a baseline systolic BP >135 mm Hg the polypill resulted in a greater absolute systolic BP reduction with the polypill compared with placebo, than participants with a systolic BP ≤ 135 mm Hg (-12 versus -7 mm Hg, respectively). Calculated from individual risk factor reductions, the mean cardiovascular relative risk reduction was 48% (95% CI: 43-52) in the polypill group. Both baseline LDL-cholesterol and estimated cardiovascular risk were significant modifiers of the estimated cardiovascular relative risk reduction caused by the polypill. Adverse events did not appear to be related to baseline risk factor levels or the estimated cardiovascular risk.
This study demonstrated that the effect of a cardiovascular polypill on risk factor levels is modified by the level of these risk factors. Groups defined by baseline LDL-cholesterol or systolic BP had large differences in risk factor reductions but only moderate differences in estimated cardiovascular relative risk reduction, suggesting also that patients with mildly increased risk factor levels but an overall raised cardiovascular risk benefit from being treated with a polypill.
近期数据表明，固定剂量复方（FDC）药丸，即多效药丸，可显著降低风险因素。关于多效药丸在不同患者群体中效果一致性的已发表数据非常少。例如，尚不清楚多效药丸的效果是否主要由个体风险因素水平较高者驱动。本研究的目的是检验基线风险因素水平是否会改变多效药丸治疗对低密度脂蛋白（LDL）胆固醇、血压（BP）、计算得出的心血管相对风险降低以及不良事件的影响。
本文描述了一项对多效药丸（含75毫克阿司匹林、20毫克辛伐他汀、10毫克赖诺普利和12.5毫克氢氯噻嗪）进行的随机、安慰剂对照试验的事后分析，该试验纳入了378名无多效药丸任何成分用药指征但估计心血管疾病五年风险≥7.5%的个体。所考虑的结局是基线风险因素水平对LDL胆固醇变化、收缩压、计算得出的心血管相对风险降低以及不良事件的效应修正。
在随访期间，多效药丸组的平均LDL胆固醇比安慰剂组低0.9毫摩尔/升（95%置信区间（CI）：0.8 - 1.0）。与LDL胆固醇≤3.6毫摩尔/升的患者相比，基线LDL胆固醇>3.6毫摩尔/升的患者服用多效药丸后LDL胆固醇的绝对降低幅度更大（分别为-1.1与-0.6毫摩尔/升）。多效药丸组的平均收缩压比安慰剂组低10毫米汞柱（95% CI：8 - 12）。与收缩压≤135毫米汞柱的参与者相比，基线收缩压>135毫米汞柱的参与者服用多效药丸后收缩压的绝对降低幅度更大（分别为-12与-7毫米汞柱）。根据个体风险因素降低情况计算，多效药丸组的平均心血管相对风险降低为48%（95% CI：43 - 52）。基线LDL胆固醇和估计的心血管风险都是多效药丸导致的估计心血管相对风险降低的显著效应修饰因素。不良事件似乎与基线风险因素水平或估计的心血管风险无关。
本研究表明，心血管多效药丸对风险因素水平的影响会因这些风险因素的水平而改变。由基线LDL胆固醇或收缩压定义的组在风险因素降低方面存在很大差异，但在估计的心血管相对风险降低方面仅存在中等差异，这也表明风险因素水平轻度升高但总体心血管风险升高的患者可从多效药丸治疗中获益。
