The Efficacy and Tolerability of ‘Polypills’: Meta-Analysis of Randomised Controlled Trials

BackgroundTo assess the blood pressure and lipid-lowering efficacy and tolerability of ‘polypills’ used in cardiovascular disease prevention trials. Methodology/Principal FindingsSystematic review and meta-analysis. Search strategy: The Cochrane Central Register of Controlled Trials, Medline, and PubMed databases were searched for eligible trials. Study inclusion criteria: Randomised controlled trials of at least six weeks duration, which compared a ‘polypill’ (that included at least one anti-hypertensive and one lipid-lowering medication) with a placebo (or one active component). Outcome measures: Change from baseline in systolic and diastolic blood pressures, and total and LDL-cholesterol; discontinuation of study medication and reported adverse effects. Of 44 potentially eligible studies, six trials (including 2,218 patients without previous cardiovascular disease) fulfilled the inclusion criteria. Compared with placebo, ‘polypills’ reduced systolic blood pressure by −9.2 mmHg (95% confidence interval (CI): −13.4, −5.0) diastolic blood pressure by −5.0 mmHg (95%CI: −7.4, −2.6), total cholesterol by −1.22 mmol/L (95%CI: −1.60, −0.84) and LDL-cholesterol by −1.02 mmol/L (95%CI: −1.37, −0.67). However, those taking a ‘polypill’ (vs. placebo or component) were more likely to discontinue medication (20% vs 14%) (Odds ratio: 1.5 (95% CI: 1.2, 1.9)). There was no significant difference in reported adverse effects amongst those on a ‘polypill’ (36% vs. 28%) (OR: 1.3 (95%CI: 0.7, 2.5)). There was high statistical heterogeneity in comparisons for blood pressure and lipid-lowering but use of random-effects and quality-effects models produced very similar results. Conclusions/SignificanceCompared with placebo, the ‘polypills’ reduced blood pressure and lipids. Tolerability was lower amongst those on ‘polypills’ than those on placebo or one component, but differences were moderate. Effectiveness trials are needed to help clarify the status of ‘polypills’ in primary care and prevention strategies.研究背景：本研究旨在评估心血管疾病预防试验中所用复方制剂（polypill）的降压、调脂疗效与耐受性。 研究方法与主要结果：本研究为系统评价与Meta分析。 检索策略：检索Cochrane对照试验中心注册库（Cochrane Central Register of Controlled Trials）、Medline及PubMed数据库，以获取符合纳入标准的试验。 研究纳入标准：纳入持续时长至少6周的随机对照试验，对比复方制剂（至少包含1种降压药物与1种调脂药物）与安慰剂（或单种活性成分）的干预效果。 结局指标：收缩压、舒张压及总胆固醇、低密度脂蛋白胆固醇（LDL-cholesterol）相较于基线的变化值；研究药物停药率与报告的不良反应。 在44项潜在符合条件的研究中，共6项试验（纳入2218名无既往心血管疾病史的患者）满足纳入标准。与安慰剂组相比，复方制剂可使收缩压降低9.2 mmHg（95%置信区间(CI)：-13.4，-5.0），舒张压降低5.0 mmHg（95%CI：-7.4，-2.6），总胆固醇降低1.22 mmol/L（95%CI：-1.60，-0.84），低密度脂蛋白胆固醇降低1.02 mmol/L（95%CI：-1.37，-0.67）。然而，服用复方制剂的受试者（相较于安慰剂组或单药组）更易停药（20% vs 14%），优势比（Odds ratio，OR）为1.5（95% CI：1.2，1.9）。两组报告的不良反应发生率无显著差异（36% vs. 28%）（OR：1.3（95%CI：0.7，2.5））。在降压与调脂的比较中存在较高的统计学异质性，但采用随机效应模型与质量效应模型所得结果极为相似。 研究结论与意义：与安慰剂相比，复方制剂可降低血压与血脂水平。服用复方制剂受试者的耐受性较安慰剂组或单药组更低，但差异幅度中等。尚需开展有效性试验，以明确复方制剂在基层医疗与预防策略中的应用定位。