https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(13)62105-4.pdf

[Global health 2035: a world converging within a generation].

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(14)61464-1.pdf

Macroeconomic implications of population ageing and selected policy responses

Importance Most patients with cardiovascular disease (CVD) do not take recommended medications long-term. The use of fixed-dose combinations (FDCs) improves adherence in several clinical areas. Previous trials of cardiovascular FDCs have assessed short-term effects compared with placebo or no treatment. Objective To assess whether FDC delivery of aspirin, statin, and 2 blood pressure–lowering agents vs usual care improves long-term adherence to indicated therapy and 2 major CVD risk factors, systolic blood pressure (SBP) and low-density lipoprotein cholesterol (LDL-C). Design, Setting, and Participants The UMPIRE trial, a randomized, open-label, blinded-end-point trial among 2004 participants with established CVD or at risk of CVD enrolled July 2010–July 2011 in India and Europe. The trial follow-up concluded in July 2012. Interventions Participants were randomly assigned (1:1) to an FDC-based strategy (n=1002) containing either (1) 75 mg aspirin, 40 mg simvastatin, 10 mg lisinopril, and 50 mg atenolol or (2) 75 mg aspirin, 40 mg simvastatin, 10 mg lisinopril, and 12.5 mg hydrochlorothiazide or to usual care (n=1002). Main Outcomes and Measures Adherence to medication (defined as self-reported use of antiplatelet, statin, and ≥2 BP-lowering medications) and changes in SBP and LDL-C from baseline. Results At baseline, mean BP was 137/78 mm Hg, LDL-C was 91.5 mg/dL, and 1233 (61.5%) of 2004 participants reported use of antiplatelet, statin, and 2 or more BP-lowering medications. Median follow-up was 15 months (interquartile range, 12-18 months). The FDC group had improved adherence vs usual care (86% vs 65%; relative risk [RR] of being adherent, 1.33; 95% CI, 1.26-1.41; P P P P P  = .01 for interaction), and LDL-C was reduced by 6.7 mg/dL (95% CI, 10.5-2.8 mg/dL; P  = .11 for interaction). There were no significant differences in serious adverse events or cardiovascular events (50 [5%] in the FDC group and 35 [3.5%] in the usual care group; RR, 1.45; 95% CI, 0.94-2.24; P =.09) between the groups. Conclusions and Relevance Among patients with or at high risk of CVD, use of an FDC strategy for blood pressure, cholesterol, and platelet control vs usual care resulted in significantly improved medication adherence at 15 months and statistically significant but small improvements in SBP and LDL-C. Trial Registration clinicaltrials.gov Identifier:NCT01057537

https://jamanetwork.com/journals/jama/articlepdf/1734704/joi130052.pdf

Effects of a Fixed-Dose Combination Strategy on Adherence and Risk Factors in Patients With or at High Risk of CVD: The UMPIRE Randomized Clinical Trial

An International Atherosclerosis Society Position Paper: Global recommendations for the management of dyslipidemia

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(12)61127-1.pdf

Technologies for global health

Background There has been widespread interest in the potential of combination cardiovascular medications containing aspirin and agents to lower blood pressure and cholesterol ('polypills') to reduce cardiovascular disease. However, no reliable placebo-controlled data are available on both efficacy and tolerability. Methods We conducted a randomised, double-blind placebo-controlled trial of a polypill (containing aspirin 75 mg, lisinopril 10 mg, hydrochlorothiazide 12.5 mg and simvastatin 20 mg) in 378 individuals without an indication for any component of the polypill, but who had an estimated 5-year cardiovascular disease risk over 7.5%. The primary outcomes were systolic blood pressure (SBP), LDL-cholesterol and tolerability (proportion discontinued randomised therapy) at 12 weeks follow-up. Findings At baseline, mean BP was 134/81 mmHg and mean LDL-cholesterol was 3.7 mmol/L. Over 12 weeks, polypill treatment reduced SBP by 9.9 (95% CI: 7.7 to 12.1) mmHg and LDL-cholesterol by 0.8 (95% CI 0.6 to 0.9) mmol/L. The discontinuation rates in the polypill group compared to placebo were 23% vs 18% (RR 1.33, 95% CI 0.89 to 2.00, p = 0.2). There was an excess of side effects known to the component medicines (58% vs 42%, p = 0.001), which was mostly apparent within a few weeks, and usually did not warrant cessation of trial treatment. Conclusions This polypill achieved sizeable reductions in SBP and LDL-cholesterol but caused side effects in about 1 in 6 people. The halving in predicted cardiovascular risk is moderately lower than previous estimates and the side effect rate is moderately higher. Nonetheless, substantial net benefits would be expected among patients at high risk. Trial registration Australian New Zealand Clinical Trials Registry ACTRN12607000099426.

/pdf/an-international-randomised-placebo-controlled-trial-of-a-4m7ura5sdr.pdf

An international randomised placebo-controlled trial of a four-component combination pill ("polypill") in people with raised cardiovascular risk.

Objectives To determine levels of cardiovascular disease (CVD) prevention and to model the potential impact of improved prevention strategies for a large rural Indian region. Design A cross-sectional study with modelling of coronary heart disease (CHD) events over 10 years. Setting Rural Andhra Pradesh, India. Participants A stratified random sample of 1079 adults 30 years and older. Main outcome measures Proportion on medical and behavioural treatments for prevention of CVD; estimated number of CHD events using a locally recalibrated Framingham risk equation. Results Among the 3.5% (95% CI 2.1% to 4.9%) with existing CVD, 49.3% (95% CI 28.8% to 69.8%) were on blood pressure (BP)-lowering medication, 4.7% (95% CI 0 to 10.4%) were on cholesterol-lowering medication, 24.6% (95% CI 9% to 40.3%) had increased exercise and 26.9% (95% CI 2.6% to 51.1%) attempted to quit smoking. Among the 7.6% (95% CI 6.2% to 8.9%) with a high global CHD risk (>20% over 10 years), 29.5% (95% CI 19.5 to 39.5%) were on BP-lowering medication, 2.8% (95% CI 0 to 6.7%) were on cholesterol-lowering medication, 19.4% (95% CI 10.9% to 28%) had increased exercise and 24.8% (95% CI 15.8% to 33.8%) attempted to quit smoking. If confirmed drug therapies were provided to all individuals at high risk there would be a 28% reduction in cardiovascular events over 10 years at an approximate annual treatment cost of US$533 per event avoided. Conclusions There are serious deficiencies in CVD prevention in rural areas of India. Addressing these with simple confirmed drug treatments could produce a large reduction in the future cardiovascular burden in India.

https://heart.bmj.com/content/heartjnl/early/2011/07/19/hrt.2011.225987.full.pdf

P. K. Raju

Papers

An international randomised placebo-controlled trial of a four-component combination pill ("polypill") in people with raised cardiovascular risk.

Prevention of cardiovascular disease in a rural region of India and strategies to address the unmet need

The prevalence and management of diabetes in rural Indian adults