Antihypertensive Treatment and Cancer: Umbrella Review of Meta-Analyses of Randomized Controlled Trials and Observational Studies

Aghil   Rostami; Kazem  Rahimi; Haleh  Ashraf; Hesam  Mosavari; Noushin  Fahimfar

doi:10.18502/jthc.v21i2.21694

Aghil Rostami Non-Communicable Diseases Research Center, Ilam University of Medical Sciences, Ilam, Iran
Kazem Rahimi Nuffield Department of Women’s and Reproductive Health, Medical Science Division, University of Oxford, Oxford, UK.
Haleh Ashraf Tehran Heart Center, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
Hesam Mosavari Department of Surgery, Surgery Research Center, School of Medicine, Rasool E Akram Hospital, Iran University of Medical Sciences, Tehran, Iran
Noushin Fahimfar Non-Communicable Diseases Research Center, Ilam University of Medical Sciences, Ilam, Iran.

DOI: https://doi.org/10.18502/jthc.v21i2.21694

Keywords: Hypertension; Cancer; Risk; Mortality; Survival; Review

Abstract

Background: Data on the link between use of antihypertensive medications and the risk of developing or dying from cancer have uncertain credibility and certainty.

Objectives: We sought to evaluate the credibility of evidence from observational studies and the certainty of evidence from randomized controlled trials (RCTs) on the association between antihypertensive medication use and cancer risk, mortality, or survival outcomes.

Methods: Comprehensive searches were performed in PubMed, Embase, Scopus, and the Cochrane Database of Systematic Reviews from their creation through July 2024. The study included systematic reviews and meta-analyses of epidemiological research investigating the relationships between antihypertensive therapies and cancer risk, mortality, or survival outcomes. The credibility of evidence from observational studies was categorized as convincing, highly suggestive, suggestive, weak, or nonsignificant. Through the GRADE framework, the certainty of evidence from RCTs was categorized as high, moderate, low, or very low.

Results: A total of 109 meta-analyses were identified, with 90 originating from observational studies and 23 from RCTs. The observational studies provided highly suggestive evidence that calcium channel blockers (CCBs) and diuretics were associated with an increased cancer risk (equivalent odds ratio [eOR], 1.07; 95% CI, 1.04 to 1.10; and eOR, 1.15; 95% CI, 1.10 to 1.20, respectively). Evidence suggests that β-blockers are associated with an increase in cancer-specific survival (eOR, 0.78; 95% CI, 0.69 to 0.89). No association satisfied the standards for convincing evidence. Pooled analyses of RCTs determined that CCB use was associated with an increased cancer risk (eOR, 1.06; 95% CI, 1.01 to 1.12; moderate certainty).

Conclusions: No strong or consistent evidence was found to support a causal relationship between antihypertensive medications and cancer outcomes. The observed associations were of very small magnitude, suggesting limited clinical relevance.