Olalekan A Uthman, Louise Hartley, Karen Rees, Fiona Taylor, Shah Ebrahim, Aileen Clarke

In many low- and middle-income countries (LMICs) morbidity and mortality associated with cardiovascular diseases (CVDs) have grown exponentially over recent years. It is estimated that about 80% of CVD deaths occur in LMICs. People in LMICs are more exposed to cardiovascular risk factors such as tobacco, and often do not have access to effective and equitable healthcare services (including early detection services). Evidence from high-income countries indicates that multiple risk factor intervention programmes do not result in reductions in CVD events. Given the increasing incidence of CVDs and lower CVD health awareness in LMICs it is possible that such programmes may have beneficial effects. To determine the effectiveness of multiple risk factor interventions (with or without pharmacological treatment) aimed at modifying major cardiovascular risk factors for the primary prevention of CVD in LMICs. We searched (from inception to 27 June 2014) the Cochrane Library (CENTRAL, HTA, DARE, EED), MEDLINE, EMBASE, Global Health and three other databases on 27 June 2014. We also searched two clinical trial registers and conducted reference checking to identify additional studies. We applied no language limits. We included randomised controlled trials (RCTs) of health promotion interventions to achieve behaviour change (i.e. smoking cessation, dietary advice, increasing activity levels) with or without pharmacological treatments, which aim to alter more than one cardiovascular risk factor (i.e. diet, reduce blood pressure, smoking, total blood cholesterol or increase physical activity) of at least six months duration of follow-up conducted in LMICs. Two authors independently assessed trial eligibility and risk of bias, and extracted data. We combined dichotomous data using risk ratios (RRs) and continuous data using mean differences (MDs), and presented all results with a 95% confidence interval (CI). The primary outcome was combined fatal and non-fatal cardiovascular disease events. 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.