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Legacy effects of statins on cardiovascular and all-cause mortality: a meta-analysis
Agnish Nayak1, Andrew Hayen2, Lin Zhu2
1UNSW Medicine, University of New South Wales, Sydney, New South Wales, Australia.
Insights
This meta-analysis found no overall legacy effect of statins on cardiovascular disease mortality but suggested a legacy effect on all-cause mortality, particularly in primary prevention trials.
Area of Science:
- Cardiovascular Medicine
- Pharmacology
- Epidemiology
Background:
- Statins are widely prescribed for cardiovascular disease (CVD) prevention.
- Understanding long-term 'legacy' effects after treatment cessation is crucial for optimizing therapeutic strategies.
- Previous research has primarily focused on in-trial effects, with limited data on post-trial outcomes.
Purpose of the Study:
- To evaluate the evidence for legacy effects of statin therapy on cardiovascular disease (CVD) mortality and all-cause mortality.
- To assess these effects in adult participants of placebo-controlled randomized controlled trials (RCTs).
Main Methods:
- A meta-analysis of aggregate data from placebo-controlled statin RCTs for primary and secondary CVD prevention.
- Searched PubMed and Embase for relevant RCT follow-up reports with ≥1000 participants.
- Extracted data on cardiovascular and all-cause mortality according to PRISMA guidelines.
Main Results:
- Eight trials with a mean post-trial follow-up of 1.6 to 15.1 years were included, encompassing 13,781 post-trial deaths.
- No overall legacy effect of statins was observed on CVD mortality.
- Some evidence suggested a legacy effect on all-cause mortality (p=0.01), potentially driven by primary prevention studies.
Conclusions:
- Post-trial legacy effects on all-cause mortality may be linked to primary prevention statin trials.
- While relative benefits were smaller post-trial, absolute benefits might be comparable to in-trial effects.
- Further analysis of individual patient data in lower-risk populations is warranted to confirm benefits of early atherosclerosis treatment.
Objectives:
To assess evidence for 'legacy' (post-trial) effects on cardiovascular disease (CVD) mortality and all-cause mortality among adult participants of placebo-controlled randomised controlled trials (RCTs) of statins.
Design:
Meta-analysis of aggregate data.
Setting/Participants:
Placebo-controlled statin RCTS for primary and secondary CVD prevention.
Methods:
Data sources: PubMed, Embase from inception and forward citations of Cholesterol Treatment Trialists' Collaborators RCTs to 16 June 2016.
Study Selection:
Two independent reviewers identified all statin RCT follow-up reports including ≥1000 participants, and cardiovascular and all-cause mortality.
Data Extraction And Synthesis:
Two independent reviewers extracted data in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.
Main Outcomes:
Post-trial CVD and all-cause mortality.
Results:
We included eight trials, with mean post-trial follow-up ranging from 1.6 to 15.1 years, and including 13 781 post-trial deaths (6685 CVD). Direct effects of statins within trials were greater than legacy effects post-trials. The pooled data from all eight studies showed no evidence overall of legacy effects on CVD mortality, but some evidence of legacy effects on all-cause mortality (p=0.01). Exploratory subgroup analysis found possible differences in legacy effect for primary prevention trials compared with secondary prevention trials for both CVD mortality (p=0.15) and all-cause mortality (p=0.02). Pooled post-trial HR for the three primary prevention studies demonstrated possible post-trial legacy effects on CVD mortality (HR=0.87; 95% CI 0.79 to 0.95) and on all-cause mortality (HR=0.90; 95% CI 0.85 to 0.96).
Conclusions:
Possible post-trial statin legacy effects on all-cause mortality appear to be driven by the primary prevention studies. Although these relative benefits were smaller than those observed within the trial, the absolute benefits may be similar for the two time periods. Analysis of individual patient data from follow-up studies after placebo-controlled statin RCTs in lower-risk populations may provide more definitive evidence on whether early treatment of subclinical atherosclerosis is likely to be beneficial.
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