Calcium Channel Blocker Versus Renin-Angiotensin System Inhibitor in Risk of Kidney Cancer Among Patients With Hypertension: A Propensity Score-Matched Cohort Study

Abstract

Background: Use of antihypertensive medications could be associated with an increased risk of kidney cancer. Despite their various mechanisms of action, whether this association differs between different classes of medications remains unclear.

Objective: The objective of this study is to compare the risk of kidney cancer between first-line treatment options of antihypertensive medications in a hypertensive population.

Method: In this retrospective cohort study, we used the MarketScan Databases (2007-2021). We included individuals older than 30 years of age with a diagnosis of hypertension who received first-line medications for hypertension, which included three classes: angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB), and dihydropyridine calcium channel blockers (dCCB). We applied a propensity score matching method and created three separate cohorts: (1) ARB versus ACEI, (2) dCCB versus ACEI, and (3) dCCB versus ACEI. For non-dCCB, we repeated the analyses. The primary outcome was kidney cancer incidence. To assess kidney cancer risk, we applied multivariable conditional Cox proportional hazards models.

Results: In the first cohort, ARB use was associated with an increased risk of kidney cancer compared to ACEI use (hazard ratio [HR] 1.10, 95% confidence interval [CI] 1.02-1.18). In the second cohort, dCCB use was associated with an increased risk of kidney cancer compared to ACEI use (HR 1.29, 95% CI 1.18-1.40). In the third cohort, dCCB use was associated with a higher risk of kidney cancer compared to ARB use (HR 1.17, 95% CI 1.08-1.28). Null association was shown when comparing non-dCCB with ACEI or ARB use.

Conclusion: Use of dCCB showed a higher risk of kidney cancer compared to ACEI or ARB use in patients with hypertension.

Keywords: antihypertensive drugs; calcium channel blocker; hypertension; kidney cancer; renin–angiotensin system inhibitor.

FIGURE 1

Forest plots of subgroup analyses for kidney cancer risk associated with ACEI, ARB, and dCCB. Across the three cohorts, results from the subgroup analyses generally supported the main findings. In the second and third cohorts, a greater risk was observed among patients without renal failure/COPD than those with renal failure/COPD. The model was adjusted for Charlson comorbidity index. ACEI, angiotensin‐converting enzyme inhibitor; ARB, angiotensin receptor blocker; CI, confidence interval; COPD, chronic obstructive pulmonary disease; dCCB, dihydropyridine calcium channel blocker; DM, diabetes mellitus; HR, hazard ratio; PVD, peripheral vascular disease; TIA, transient ischemic attack.

FIGURE 2

Plots of exposure to antihypertensive medications with the risk of kidney cancer. According to the medication exposure, consistent trends supporting the main finding were shown. Stronger hazard ratios were observed in the highest exposure group across the three study cohorts. The hazard ratios were adjusted for Charlson comorbidity index. ACEI, angiotensin‐converting enzyme inhibitor; ARB, angiotensin receptor blocker; cDDD, cumulative defined daily dose; CI, confidence interval; dCCB, dihydropyridine calcium channel blocker; HR, hazard ratio.