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. 2025 Jul;29(37):1–65. doi: 10.3310/RLDH7432

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

Olalekan A Uthman, Rachel Court, Jodie Enderby, Chidozie Nduka, Lena Al-Khudairy, Seun Anjorin, Hema Mistry, G J Melendez-Torres, Sian Taylor-Phillips, Aileen Clarke
PMCID: PMC12376007  PMID: 40611785

Abstract

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.

Plain language summary

Heart disease is a leading cause of death worldwide, and preventing it is a major health priority. Our study aimed to compare different ways to prevent heart disease, such as medicines, diet supplements, lifestyle changes and health policies, by looking at a large number of clinical trials. We searched through medical databases up to March 2021 to find studies that tested these prevention methods. We specifically looked for studies that followed participants for at least 6 months to see how well these methods worked in preventing death from heart disease or heart disease events like heart attacks. Our review included data from 139 studies involving over one million people. We found that taking medication to lower blood pressure, aiming for lower blood pressure targets, using statins (a type of cholesterol-lowering medication) and making several lifestyle changes at once (like eating healthier, exercising more and quitting smoking) were the most effective ways to prevent heart disease and reduce the risk of dying from it. However, it was hard to tell exactly how some specific methods compared directly to each other because there were not many studies directly comparing them. Also, there’s always a chance that other factors we didn’t account for could affect our results. In conclusion, our research supports the use of blood pressure management, statins and comprehensive lifestyle changes as key strategies for preventing heart disease. This information could help doctors and policy-makers decide which prevention methods to recommend or support.

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