Blood pressure-lowering and risk of cancer: an individual participant-level data meta-analysis and Mendelian randomisation studies

BACKGROUND Pharmacological blood pressure (BP)-lowering is typically a lifelong treatment, and both clinicians and patients may have concerns about the long-term use of antihypertensives and the risk of cancer. However, evidence from randomised controlled trials (RCTs) regarding the effect of long-term pharmacological BP-lowering on the risk of new-onset cancer is limited, with most knowledge derived from observational studies. OBJECTIVES This study aimed to assess whether long-term BP-lowering affects the risk of new-onset cancer, cause-specific cancer death, and selected site-specific cancers. METHODS Individual-level data from 42 RCTs were pooled using a one-stage individual participant data (IPD) meta-analysis. The primary outcome was incident cancer of all types, and secondary outcomes were cause-specific cancer death and selected site-specific cancers. Pre-specified subgroup analyses were conducted to assess the heterogeneity of the BP-lowering effect by baseline variables and also over follow-up time. Cox proportional hazards regression, stratified by trial, was used for the statistical analysis. For site-specific cancers, analyses were complemented with Mendelian randomisation, using naturally randomised genetic variants associated with BP-lowering to mimic the design of a long-term RCT. RESULTS Data from 314,016 randomly allocated participants without known cancer at baseline were analysed. Over a median follow-up of four years (25th-75th percentiles 3–5), 17,954 participants (5.7%) developed cancer, and 4,878 (1.5%) died from cancer. In the IPD meta-analysis, no associations were found between reductions in systolic or diastolic BP and cancer risk (hazard ratio [HR] per 5 mmHg reduction in systolic BP: 1.03 [95% CI 0.99-1.06]; per 3 mmHg reduction in diastolic BP: 1.03 [95% CI 0.98-1.07]). No changes in relative risk for incident cancer was observed over follow-up time, nor was there evidence of heterogeneity in treatment effects across baseline subgroups. No effect on cause-specific cancer death was found. For site-specific cancers, no evidence of effect was observed, except a possible link with lung cancer risk (HR for systolic BP reduction: 1.17 [99.5% CI 1.02-1.32]). Mendelian randomisation studies showed no association between systolic or diastolic BP reduction and site-specific cancers, including overall lung cancer and its subtypes. CONCLUSIONS Randomised data analysis provided no evidence to indicate that pharmacological BP-lowering has a substantial impact—either increasing or decreasing—on the risk of incident cancer, cause-specific cancer death, or selected site-specific cancers.