Identifying optimal primary prevention interventions for major cardiovascular disease events and all-cause mortality: a systematic review and hierarchical network meta-analysis of RCTs.

Background: Cardiovascular disease accounts for substantial mortality and healthcare costs worldwide. Numerous interventions exist for primary prevention but lack head-to-head comparisons on long-term impacts.

Objective: To determine the comparative effectiveness of interventions for primary cardiovascular disease prevention through network meta-analysis of randomised trials.

Data sources: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, conference abstracts and trial registries from inception to March 2021.

Review methods: Randomised controlled trials of pharmacologic therapies, nutritional supplements, lifestyle changes, behavioural approaches and health policies with at least 6 months' follow-up were included. Pairwise and network meta-analyses were conducted for all-cause mortality, cardiovascular disease events, coronary heart disease and cardiovascular disease mortality.

Results: Data from 139 randomised trials, including 1,053,772 participants, proved suitable for quantitative synthesis. Blood pressure-lowering medications (risk ratio 0.82, 95% confidence interval 0.71 to 0.94), tight blood pressure control (risk ratio 0.66, 95% confidence interval 0.46 to 0.96), statins (risk ratio 0.81, 95% confidence interval 0.71 to 0.91) and multifactorial lifestyle interventions (risk ratio 0.75, 95% confidence interval 0.61 to 0.92) reduced composite cardiovascular events and mortality.

Limitations: Residual confounding may exist. Few direct head-to-head comparisons limited differentiation between some specific modalities.

Conclusions: We found evidence that blood pressure treatments, intense blood pressure targets, statins when appropriate and multifactorial lifestyle changes are the most effective strategies for primary prevention of cardiovascular disease, with unclear effects from other interventions. These findings can inform clinical guidelines and health policies prioritising interventions.

Funding: This research article presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number 17/148/05.