Ruth Webster, Anushka Patel, Vanessa Selak, Laurent Billot, Michiel L. Bots, Alex Brown, Chris Bullen, Alan Cass, Sue Crengle, C. Raina Elley, Diederick E. Grobbee, Bruce Neal, David Peiris, Neil Poulter, Dorairaj Prabhakaran, Natasha Rafter, Alice Stanton, Sandrine Stepien, Simon Thom, Tim Usherwood, Angela Wadham, Anthony Rodgers, on behalf of the SPACE Collaboration

To conduct a prospective, individual participant data (IPD) meta-analysis of randomised controlled trials comparing a polypill-based approach with usual care in high risk individuals. Three trials comparing polypill-based care with usual care in individuals with CVD or high calculated cardiovascular risk contributed IPD. Primary outcomes were self-reported adherence to combination therapy (anti-platelet, statin and ≥two blood pressure (BP) lowering agents), and difference in mean systolic BP (SBP) and LDL-cholesterol at 12months. Analyses used random effects models. Among 3140 patients from Australia, England, India, Ireland, New Zealand and The Netherlands (75% male, mean age 62years), median follow-up was 15months. At baseline, 84%, 87% and 61% respectively were taking a statin, anti-platelet agent and at least two BP lowering agents. At 12months, compared to usual care, participants in the polypill arm had higher adherence to combination therapy (80% vs. 50%, RR 1.58; 95% CI, 1.32 to 1.90; p<0.001), lower SBP (-2.5mmHg; 95% CI, -4.5 to -0.4; p=0.02) and lower LDL-cholesterol (-0.1mmol/L; 95% CI, -0.2 to 0.0; p=0.04). Baseline treatment levels were a major effect modifier for adherence and SBP (p-homog <0.0001 and 0.02 respectively) with greatest improvements seen among those under-treated at baseline. Polypill therapy significantly improved adherence, SBP and LDL-cholesterol in high risk patients compared with usual care, especially among those who were under-treated at baseline.