Abstract: Thirteen trials met the inclusion criteria and are included in the review. All studies had at least one domain with unclear risk of bias. Some studies were at high risk of bias for random sequence generation (two trials), allocation concealment (two trials), blinding of outcome assessors (one trial) and incomplete outcome data (one trial). Duration and content of multiple risk factor interventions varied across the trials. Two trials recruited healthy participants and the other 11 trials recruited people with varying risks of CVD, such as participants with known hypertension and type 2 diabetes. Only one study reported CVD outcomes and multiple risk factor interventions did not reduce the incidence of cardiovascular events (RR 0.57, 95% CI 0.11 to 3.07, 232 participants, low-quality evidence); the result is imprecise (a wide confidence interval and small sample size) and makes it difficult to draw a reliable conclusion. None of the included trials reported all-cause mortality. The pooled effect indicated a reduction in systolic blood pressure (MD -6.72 mmHg, 95% CI -9.82 to -3.61, I² = 91%, 4868 participants, low-quality evidence), diastolic blood pressure (MD -4.40 mmHg, 95% CI -6.47 to -2.34, I² = 92%, 4701 participants, low-quality evidence), body mass index (MD -0.76 kg/m², 95% CI -1.29 to -0.22, I² = 80%, 2984 participants, low-quality evidence) and waist circumference (MD -3.31, 95% CI -4.77 to -1.86, I² = 55%, 393 participants, moderate-quality evidence) in favour of multiple risk factor interventions, but there was substantial heterogeneity. There was insufficient evidence to determine the effect of these interventions on consumption of fruit or vegetables, smoking cessation, glycated haemoglobin, fasting blood sugar, high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol and total cholesterol. None of the included trials reported on adverse events. Due to the limited evidence currently available, we can draw no conclusions as to the effectiveness of multiple risk factor interventions on combined CVD events and mortality. There is some evidence that multiple risk factor interventions may lower blood pressure levels, body mass index and waist circumference in populations in LMIC settings at high risk of hypertension and diabetes. There was considerable heterogeneity between the trials, the trials were small, and at some risk of bias. Larger studies with longer follow-up periods are required to confirm whether multiple risk factor interventions lead to reduced CVD events and mortality in LMIC settings.

Plain-language summary: We performed a thorough search of the medical literature up to June 2014. We identified 13 trials that recruited 7310 participants. Two trials recruited healthy participants and the other 11 trials recruited people at varying risk of CVD, such as participants with known hypertension("high blood pressure") and type 2 diabetes, and randomly assigned them to either a multiple risk factor intervention or to no intervention. The trials were conducted between 2001 and 2010, and published between 2004 and 2012. Three trials were conducted in Turkey. Two trials each were conducted in China and Mexico. One trial recruited participants from both China and Nigeria. The other trials were conducted in Brazil, India, Pakistan, Romania and Jordan. The content of the interventions varied across the trials; most of the trials included dietary advice and advice on physical activity. The trials follow-up the participants between six months to 30 months (average follow-up period was 13.3 months). We found that evidence for effects on cardiovascular disease events was scarce, with only one trial reporting these. None of the included trials reported deaths from any cause. Multiple risk factors interventions may lower systolic blood pressure, diastolic blood pressure, body mass index and waist circumference. We found no difference for eating more fruit and vegetables, rates of smoking cessation, measure of blood glucose sugar was for the past two to three months, fasting blood sugar, high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol and total cholesterol. None of the included trials reported on harms. Overall, the studies included in this review were at some risk of bias and there was variation between the results of the studies when we analysed the data. Our findings should be treated with some caution.