Dihydropyridine Calcium Channel Blockers and Risk of Pancreatic Cancer: A Population-Based Cohort Study

Abstract

Background Recent studies have reported that dihydropyridine calcium channel blockers (dCCBs) may increase the risk of pancreatic cancer, but these studies had methodological limitations. We thus aimed to determine whether dCCBs are associated with an increased risk of pancreatic cancer compared with thiazide diuretics, a clinically relevant comparator. Methods and Results We conducted a new user, active comparator, population-based cohort study using the UK Clinical Practice Research Datalink. We identified new users of dCCBs and new users of thiazide diuretics between 1990 and 2018, with follow-up until 2019. Cox proportional hazards models were used to estimate hazard ratios (HRs) with 95% CIs for pancreatic cancer, comparing dCCBs with thiazide diuretics. Models were weighted using standardized morbidity ratio weights based on calendar time-specific propensity scores. We also conducted secondary analyses by cumulative duration of use, time since initiation, and individual drugs and assessed for the presence of effect modification by age, sex, smoking status, body mass index, history of chronic pancreatitis, and diabetes. The cohort included 344 480 initiators of dCCBs and 357 968 initiators of thiazide diuretics, generating 3 360 745 person-years of follow-up. After a median follow-up of 4.5 years, the weighted incidence rate per 100 000 person-years was 37.2 (95% CI, 34.1-40.4) for dCCBs and 39.4 (95% CI, 36.1-42.9) for thiazide diuretics. Overall, dCCBs were not associated with an increased risk of pancreatic cancer (weighted HR, 0.93; 95% CI, 0.80-1.09). Similar results were observed in secondary analyses. Conclusions In this large, population-based cohort study, dCCBs were not associated with an increased risk of pancreatic cancer compared with thiazide diuretics. These findings provide reassurance regarding the long-term pancreatic cancer safety of these drugs.

Keywords: antihypertensive drugs; calcium channel blockers; cancer; cohort study; pancreatic cancer; propensity score; thiazide diuretics.

Figure 1. Study flow diagram of patients initiating dihydropyridine calcium channel blockers and thiazide diuretics in the Clinical Practice Research Datalink between January 1, 1990, and March 31, 2018.

dCCB indicates dihydropyridine calcium channel blocker; FAMM, familial atypical multiple mole and melanoma syndrome; MEN‐1, multiple endocrine neoplasia type 1; and PS, propensity score.

Figure 2. Forest plot presenting weighted hazard ratios and 95% CIs for the primary and sensitivity analyses.

HR indicates hazard ratio.