The efficacy and tolerability of 'polypills': meta-analysis of randomised controlled trials

C Raina Elley, Ajay K Gupta, Ruth Webster, Vanessa Selak, Min Jun, Anushka Patel, Anthony Rodgers, Simon Thom, C Raina Elley, Ajay K Gupta, Ruth Webster, Vanessa Selak, Min Jun, Anushka Patel, Anthony Rodgers, Simon Thom

Abstract

Background: To assess the blood pressure and lipid-lowering efficacy and tolerability of 'polypills' used in cardiovascular disease prevention trials.

Methodology/principal findings: Systematic 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/significance: Compared 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.

Conflict of interest statement

Competing Interests: The authors have read the journal's policy and have the following conflicts: AR and RW have received a grant from Dr Reddy's Ltd (DRL) for the SPACE collaboration centre but this is unrelated to the current meta-analysis. DRL also provided a fixed dose combination formulation free of charge for four randomized controlled trials to assess the effectiveness of a “polypill-based strategy.” CRE, VS, AP, ST and AR are investigators or are on the steering committee of at least one of these trials. The George Institute for Global Health is now negotiating a global license for these products, following a decision by DRL not to proceed with taking the products to market because of existing regulatory requirements. DRL has provided travel assistance to meetings on “polypills” for CRE, RW, VS, AP, ST and AR in the past. AKG has received travel assistance to attend a conference from Pfizer. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.

Figures

Figure 1. Polypills Meta-analysis ‘PRISMA’ Flow Diagram.
Figure 1. Polypills Meta-analysis ‘PRISMA’ Flow Diagram.
Figure 2. Forest Plots of Polypills versus…
Figure 2. Forest Plots of Polypills versus Control for Change in Systolic and Diastolic Blood Pressure.
Figure 3. Forest Plots of Polypills versus…
Figure 3. Forest Plots of Polypills versus Control for Change in Total Cholesterol and LDL-cholesterol.
Figure 4. Forest Plots of Polypills versus…
Figure 4. Forest Plots of Polypills versus Control for Change in Discontinuation of Study Medication and Side Effects.

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