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Determining Optimal Strategies for Primary Prevention of Cardiovascular Disease: Systematic Review, Network Meta-Analysis and Cost-Effectiveness Review

Leads: Dr Olalekan Uthman, Prof Aileen Clarke, Dr Lena Al-Khudairy, Dr Amy Grove (Public Health), Dr Nick Parsons (Meths)

Public contributors reviewed the protocol and will be involved in dissemination of the findings.

Dates: February 2019 – July 2021


Despite recent reductions in the burden of cardiovascular disease (CVD) in the UK, deaths from CVD are relatively high compared with other high-income countries. An estimated 7 million people in the UK are living with CVD, and the healthcare cost is approximately £11 billion annually. In more than 90% of cases, the risk of a first heart attack is thought to be related to modifiable risk factors including smoking, poor diet, lipidemia, high blood pressure, inactivity, obesity and excess alcohol consumption.

Others have looked at different risk factors e.g. medical, physical activity, dietary, mental wellbeing, and policy and structural interventions However, the problem is that there is no overarching systematic review with a network meta analysis able to tell us the hierarchy of the relative effectiveness of the interventions showing us how to prioritise among the many possible CVD primary prevention interventions, what the most important measures to take really are and where maximal effort should be directed by policy makers.

Policy and Practice Partners:

Desk-based study - see below.

Co-Funding Partners:


Aims and Objectives:

Aim is to comprehensively synthesise the evidence on strategies and interventions, including combinations of strategies and interventions, for primary prevention of cardiovascular disease in order to develop a hierarchy of interventions. The specific objectives are as follows:

  1. To use comprehensive searches and to describe the scale and range of interventions that have been conducted and to categorise interventions and their components.
  2. To determine which interventions, have the greatest probability of effectiveness for the primary prevention of CVD.
  3. To identify which intervention components are associated with the greatest effectiveness for the primary prevention of CVD.
  4. To examine reliability and conclusiveness of the available evidence on interventions for the primary prevention of CVD and to identify the areas with most potential benefit for future research.
  5. To identify, appraise and synthesise any published economic evaluations and economic models of interventions for the primary prevention of CVD.
  6. To determine the applicability and generalisability of interventions and the assessments of their cost-effectiveness to the UK NHS setting.


We will systematically search databases (for example, MEDLINE (Ovid), Embase (Ovid), Cochrane Library) and the reference lists of previous systematic reviews for randomised controlled trials that assess the effectiveness and cost-effectiveness of any form of intervention aimed at adult populations for the primary prevention of CVD, including but not limited to lipid lowering medications, blood pressure lowering medications, antiplatelet agents, nutritional supplements, dietary interventions, health promotion programmes, physical activity interventions or structural and policy interventions. Interventions may or may not be targeted at high-risk groups. Publications from any year will be considered for inclusion. The primary outcome will be all cause mortality. Secondary outcomes will be cardiovascular diseases related mortality, major cardiovascular events, coronary heart disease, incremental costs per quality-adjusted life years gained. If data permits, we will use network meta-analysis to compare and rank effectiveness of different interventions, and test effect modification of intervention effectiveness using subgroup analyses and meta-regression analyses.

Main Results:

We completed updating the scoping review of existing systematic reviews. We identified and extracted data from 94 existing systematic reviews. Most of the reviews examined pharmacological interventions (n=84, 82%). Only 18 examined lifestyle interventions (n=18, 18%).

Conclusion and Implications for Implementation:

The results will be important for policymakers when making decisions between multiple possible alternative strategies to prevent CVD.