Why the study?
ACEi and ARB are first-line treatment for hypertension in CKD, but guidelines do not recommend specific subsequent medication classes when additional blood pressure lowering is needed.
Does adding a thiazide diuretic compared to a calcium channel blocker, β-blocker, or loop diuretic reduce composite cardiovascular and kidney outcomes in adults with non-dialysis CKD on ACEi/ARB therapy?
Cohort (n=150,369)
Yes
Does adding a thiazide diuretic compared to a calcium channel blocker, β-blocker, or loop diuretic reduce composite cardiovascular and kidney outcomes in adults with non-dialysis CKD on ACEi/ARB therapy?
Answers are grounded in this paper and cite their sources.
In patients with non-dialysis CKD on baseline ACEi/ARB therapy, adding a thiazide diuretic as a second-line antihypertensive agent is associated with lower risks of composite cardiovascular and kidney outcomes compared to adding a calcium channel blocker, β-blocker, or loop diuretic.
Background: Angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) are first-line treatment for hypertension in chronic kidney disease (CKD). However, guidelines do not recommend subsequent medication classes if additional blood pressure-lowering effect is desired. Methods: This target trial emulation using national outpatient data from the Veterans Health Administration from January 1, 2010, to December 31, 2016, included adults with non-dialysis CKD stages G1-G5 on an ACEi/ARB who initiated treatment with a second antihypertensive medication, classified as a thiazide diuretic, loop diuretic, calcium channel blocker, or β-blocker. Outcomes included composite cardiovascular events (fatal or nonfatal myocardial infarction or stroke, hospitalization for heart failure, coronary revascularization), all-cause death, and composite kidney outcomes (dialysis initiation, kidney transplantation, sustained creatinine doubling). Clinically important characteristics were included as covariates in the analysis. Results: Of 150,369 individuals already on ACEi/ARB treatment, 45,836 (30%) were prescribed a thiazide diuretic, 17,589 (12%) a loop diuretic, 33,172 (22%) a calcium channel blocker, and 53,772 (36%) a β-blocker. Those receiving thiazide diuretics and calcium channel blockers had the highest baseline blood pressure. Those receiving loop diuretics were more likely to have more advanced CKD or heart failure. Over a median (IQR) follow-up of 1282 (621, 1979) days, compared to thiazide diuretics, cardiovascular event risk was higher for calcium channel blockers, aHR 1.18 (95% CI 1.15-1.22), β-blockers, aHR 1.63 (95% CI 1.58-1.67), and loop diuretics, aHR 1.97 (95% CI 1.90-2.04). Composite kidney outcomes were also higher with calcium channel blockers, aHR 1.42 (95% CI 1.33-1.52), β-blockers, aHR 1.13 (95% CI 1.06-1.21), and loop diuretics, aHR 1.98 (95% CI 1.83-2.15). Conclusions: Adding a thiazide diuretic rather than a calcium channel blocker, β-blocker, or loop diuretic on top of ACEi/ARB treatment was associated with favorable clinical outcomes among people with CKD.
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Gregg et al. (2026) conducted a cohort in Hypertension and non-dialysis chronic kidney disease (CKD stages G1-G5) (n=150,369). Calcium channel blocker, beta-blocker, or loop diuretic added to ACEi/ARB vs. Thiazide diuretic added to ACEi/ARB was evaluated on Composite cardiovascular events (fatal or nonfatal myocardial infarction or stroke, hospitalization for heart failure, coronary revascularization) (aHR 1.18, 95% CI 1.15-1.22).
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