Heart failure and renal outcomes with angiotensin receptor blockers compared with calcium channel blockers in patients with chronic kidney disease: a target trial emulation.

BACKGROUND

Hypertension is highly prevalent among patients with chronic kidney disease (CKD) and contributes substantially to cardiovascular complications and progression of kidney disease. Although angiotensin receptor blockers (ARBs) and calcium channel blockers (CCBs) are widely used antihypertensive agents in CKD, comparative evidence regarding their long-term effects on clinically important cardiorenal outcomes remains limited.

METHODS

We conducted a target trial emulation using nationwide-scale healthcare claims and health check-up data in Japan between April 2014 and September 2024. We emulated sequentially nested new-user trials and used a 1-month induction-period approach to compare ARB-based versus CCB-based antihypertensive treatment strategies. Intention-to-treat effects were estimated using discrete-time proportional hazards models with inverse probability of treatment and censoring weighting, accounting for competing risks.

RESULTS

Among 12 978 patients with CKD (4524 initiating ARB-based therapy and 8454 initiating CCB-based therapy), ARB-based strategies were associated with a directionally lower but not statistically significant risk of heart failure hospitalisation (HR 0.871, 95% CI 0.751 to 1.011). ARB-based therapy was also associated with lower risks of progression to end-stage renal disease (HR 0.533, 95% CI 0.317 to 0.898) and all-cause mortality (HR 0.825, 95% CI 0.706 to 0.963). No consistent differences were observed for myocardial infarction or stroke.

CONCLUSIONS

In this nationwide target trial emulation, ARB-based antihypertensive strategies were associated with lower risks of kidney failure and all-cause mortality, with a directionally lower but statistically uncertain risk of heart failure hospitalisation. These findings suggest that ARB-based antihypertensive strategies may confer clinically relevant cardiorenal benefits compared with CCB-based strategies in patients with CKD, although causal interpretation remains limited by the observational design.