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Meta-Analysis
. 2024 Feb 8;19(2):e0297852.
doi: 10.1371/journal.pone.0297852. eCollection 2024.

Is there a shift from cardiovascular to cancer death in lipid-lowering trials? A systematic review and meta-analysis

Lucy Bolt  1   2 , Alexandre Speierer  1   2 , Sylvain Bétrisey  1   2 , Martina Aeschbacher-Germann  1   2 , Manuel R Blum  1   2 , Baris Gencer  1   3 , Cinzia Del Giovane  1 , Drahomir Aujseky  2 , Elisavet Moutzouri  1   2 , Nicolas Rodondi  1   2
Affiliations
Meta-Analysis

Is there a shift from cardiovascular to cancer death in lipid-lowering trials? A systematic review and meta-analysis

Lucy Bolt et al. PLoS One. .

Abstract

Background: Lipid-lowering therapy (LLT) reduces cardiovascular (CV) events, but data are conflicting on all-cause mortality, especially among older adults. Though LLT does not induce cancer, some randomized clinical trials (RCTs) found a pattern of increased cancer death under LLT. Our objective was to assess a possible shift from CV to cancer death in LLT trials (i.e. an increase in cancer and decrease in CV death) and to investigate potential subgroups at risk.

Methods: We performed a systematic review and meta-analysis. We retrieved RCTs from MEDLINE, Embase, and Cochrane Central until 08/2023. We extracted the number of CV and cancer deaths in the treatment vs. in the control arm, calculated the relative risk (RR) by dividing the risk of death in the treatment over the risk of death in the control group and then pooled them using random-effect meta-analysis. We performed subgroup analyses on primary and secondary prevention, and according to different age cut-offs.

Results: We included 27 trials with 188'259 participants (23 statin; 4 ezetimibe trials). The trials reported 4056 cancer deaths, 2061 under LLT and 1995 in control groups. Overall, there was no increased risk of cancer mortality (RR 1.03, 95% confidence interval 0.97-1.10), with no difference between primary and secondary prevention. In the subgroup analyses for RCTs with ≥15% of participants aged ≥75 years, the RR of cancer death was 1.11 (1.00-1.23), while the RR for CV death was 0.96 (0.91-1.01). For RCTs with a mean age ≥ 70 years, the RR for cancer death was 1.21 (0.99-1.47).

Conclusion: LLT does not lead to a shift from CV to cancer death. However, there might be a possible shift with a pattern of increased cancer deaths in trials with more older adults, particularly ≥75 years. Individual participant data from LLT trials should be made public to allow further investigations.

Prospero registration: CRD42021271658.

PubMed Disclaimer

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Flow chart of included trials.
CV = cardiovascular, RCT = randomized controlled trial, FUP = follow-up period, CTTC = Cholesterol Treatment Trialists’ Collaboration.
Fig 2
Fig 2. Relative risk for cancer mortality according to lipid-lowering therapy and prevention strategy.
pts = participants, CI = confidence interval.
Fig 3
Fig 3. Relative risk for cancer mortality according to lipid-lowering therapy and the prevalence of participants aged ≥75 years1 1.
The SPARCL and REPRIEVE trial did not report the prevalence of participants aged ≥75 years pts = participants, CI = confidence interval.
See this image and copyright information in PMC

References

    1. Armitage J, Baigent C, Barnes E, Betteridge DJ, Blackwell L, Blazing M, et al.. Efficacy and safety of statin therapy in older people: a meta-analysis of individual participant data from 28 randomised controlled trials. The Lancet. 2019;393(10170):407–15. doi: 10.1016/S0140-6736(18)31942-1 - DOI - PMC - PubMed
    1. Ouchi Y, Sasaki J, Arai H, Yokote K, Harada K, Katayama Y, et al.. Ezetimibe Lipid-Lowering Trial on Prevention of Atherosclerotic Cardiovascular Disease in 75 or Older (EWTOPIA 75): A Randomized, Controlled Trial. Circulation. 2019;140(12):992–1003. doi: 10.1161/CIRCULATIONAHA.118.039415 - DOI - PubMed
    1. Shepherd J, Blauw GJ, Murphy MB, Bollen EL, Buckley BM, Cobbe SM, et al.. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. The Lancet. 2002;360(9346):1623–30. - PubMed
    1. The ALLHAT Officers Coordinators for the ALLHAT Collaborative Research Group. Major Outcomes in Moderately Hypercholesterolemic, Hypertensive Patients Randomized to Pravastatin vs Usual CareThe Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT-LLT). JAMA. 2002;288(23):2998–3007. doi: 10.1001/jama.288.23.2998 - DOI - PubMed
    1. Han BH, Sutin D, Williamson JD, Davis BR, Piller LB, Pervin H, et al.. Effect of Statin Treatment vs Usual Care on Primary Cardiovascular Prevention Among Older Adults: The ALLHAT-LLT Randomized Clinical Trial. JAMA Intern Med. 2017;177(7):955–65. doi: 10.1001/jamainternmed.2017.1442 - DOI - PMC - PubMed

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