Angiotensin Receptor Blockers Versus Calcium Channel Blockers for First‐Line Antihypertensive Therapy and Survival in Adults Aged 75 Years or Older

BACKGROUND: Evidence guiding first-line antihypertensive drug choice in adults aged 75 years or older is limited, despite widespread use of angiotensin receptor blockers (ARBs) and calcium channel blockers (CCBs) in late older age. METHODS: We conducted a target trial emulation using a new-user design in a nationwide linked healthcare claims database in Japan. Adults aged ≥ 75 years who had no prescription of either drug class in the preceding 12 months and initiated an ARB (n = 10,037) or a CCB (n = 19,785) were followed from treatment initiation. The primary outcome was all-cause mortality; secondary outcomes included hospitalization for heart failure, myocardial infarction, stroke, and major adverse cardiovascular events (MACE). Intention-to-treat effects were estimated using inverse probability of treatment and censoring weighting with pooled logistic regression models. RESULTS: Among 29,822 patients, median follow-up was 4.0 years. During follow-up, 3487 deaths occurred. ARB therapy was associated with lower all-cause mortality than CCB therapy (hazard ratio [HR], 0.885; 95% CI, 0.823-0.951). The estimated 5-year risk of death was 12.7% for ARB users and 14.8% for CCB users (absolute risk difference, -2.1 percentage points; 95% CI, -3.1 to -1.0). ARB therapy was also associated with lower risks of heart failure hospitalization (HR, 0.843; 95% CI, 0.774-0.918), myocardial infarction (HR, 0.867; 95% CI, 0.795-0.945), stroke (HR, 0.931; 95% CI, 0.869-0.998), and MACE (HR, 0.889; 95% CI, 0.848-0.931). Associations were consistent across age subgroups, including adults aged ≥ 85 years. CONCLUSION: In adults aged 75 years or older, ARB-based antihypertensive therapy was associated with lower risks of mortality and cardiovascular events compared with CCB-based therapy. These findings suggest that first-line antihypertensive drug choice may have prognostic implications in late older age.