Kidney medicine · 2026
Dihydropyridine Calcium Channel Blocker Therapy and Risk of CKD Progression in Type 2 Diabetes Treated With Renin Angiotensin System Inhibitors and SGLT2 Inhibitors: A Real-World Retrospective Cohort Study.
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Agur Timna, Steinmetz Tali, Goldman Shira, Zingerman Boris, Bielopolski Dana, Nesher Eviatar, Fattal Ittai, Meisel Eshcar, Rozen-Zvi Benaya
Аннотация
RATIONALE & OBJECTIVE: Optimal antihypertensive therapy with renoprotective effects is essential to slow diabetic kidney disease progression. We evaluated the impact of dihydropyridine calcium channel blockers on kidney outcomes in patients with type 2 diabetes receiving guideline-directed renin angiotensin system inhibitors and sodium/glucose cotransporter 2 inhibitors.
STUDY DESIGN PARTICIPANTS & SETTINGS: A retrospective cohort study using Clalit Health Services (2016-2021).
EXPOSURE: Adults with type 2 diabetes treated with both renin angiotensin system inhibitors and sodium/glucose cotransporter 2 inhibitors were categorized into dihydropyridine calcium channel blockers group (renin angiotensin system inhibitors + dihydropyridine calcium channel blockers, with or without other agents) or a dihydropyridine calcium channel blocker-free group (renin angiotensin system inhibitors ± other antihypertensives excluding dihydropyridine calcium channel blockers).
OUTCOMES: The primary outcome was a major adverse kidney event (MAKE; defined as ≥40% estimated glomerular filtration rate decline or progression to kidney failure). Secondary outcomes included initiation of renal replacement therapy and all-cause mortality. Safety outcomes included hospitalizations and acute kidney injury.
ANALYTICAL APPROACH: Inverse probability of treatment weighting was applied to balance baseline characteristics.
RESULTS: We included 31,031 patients with type 2 diabetes treated with both sodium/glucose cotransporter 2 inhibitors and renin angiotensin system inhibitors. A total of 12,172 (60.8%) received dihydropyridine calcium channel blockers, and 18,859 (39.2%) received dihydropyridine calcium channel blocker-free therapy. Median follow-up was 1,260 days. Overall, 482 patients experienced MAKE, and 2,064 patients died. Dihydropyridine calcium channel blocker use was associated with a higher risk of MAKE compared with dihydropyridine calcium channel blocker-free therapy (weighted HR, 1.33; 95% CI, 1.03-1.73; P = 0.03), which remained significant after accounting for competing risk of death (HR, 1.39; 95% CI, 1.13-1.7; P = 0.002). Dihydropyridine calcium channel blocker use was not significantly associated with all-cause mortality or safety outcomes.
LIMITATIONS: The observational design is subject to residual confounding and did not allow for full characterization of medication exposure.
CONCLUSIONS: In patients with type 2 diabetes treated with renin angiotensin system inhibitors and sodium/glucose cotransporter 2 inhibitors, concomitant therapy with dihydropyridine calcium channel blockers was associated with a higher risk of adverse kidney outcomes. These findings may help inform clinicians when weighing the potential risks and benefits of second-line antihypertensive therapy in this population.
STUDY DESIGN PARTICIPANTS & SETTINGS: A retrospective cohort study using Clalit Health Services (2016-2021).
EXPOSURE: Adults with type 2 diabetes treated with both renin angiotensin system inhibitors and sodium/glucose cotransporter 2 inhibitors were categorized into dihydropyridine calcium channel blockers group (renin angiotensin system inhibitors + dihydropyridine calcium channel blockers, with or without other agents) or a dihydropyridine calcium channel blocker-free group (renin angiotensin system inhibitors ± other antihypertensives excluding dihydropyridine calcium channel blockers).
OUTCOMES: The primary outcome was a major adverse kidney event (MAKE; defined as ≥40% estimated glomerular filtration rate decline or progression to kidney failure). Secondary outcomes included initiation of renal replacement therapy and all-cause mortality. Safety outcomes included hospitalizations and acute kidney injury.
ANALYTICAL APPROACH: Inverse probability of treatment weighting was applied to balance baseline characteristics.
RESULTS: We included 31,031 patients with type 2 diabetes treated with both sodium/glucose cotransporter 2 inhibitors and renin angiotensin system inhibitors. A total of 12,172 (60.8%) received dihydropyridine calcium channel blockers, and 18,859 (39.2%) received dihydropyridine calcium channel blocker-free therapy. Median follow-up was 1,260 days. Overall, 482 patients experienced MAKE, and 2,064 patients died. Dihydropyridine calcium channel blocker use was associated with a higher risk of MAKE compared with dihydropyridine calcium channel blocker-free therapy (weighted HR, 1.33; 95% CI, 1.03-1.73; P = 0.03), which remained significant after accounting for competing risk of death (HR, 1.39; 95% CI, 1.13-1.7; P = 0.002). Dihydropyridine calcium channel blocker use was not significantly associated with all-cause mortality or safety outcomes.
LIMITATIONS: The observational design is subject to residual confounding and did not allow for full characterization of medication exposure.
CONCLUSIONS: In patients with type 2 diabetes treated with renin angiotensin system inhibitors and sodium/glucose cotransporter 2 inhibitors, concomitant therapy with dihydropyridine calcium channel blockers was associated with a higher risk of adverse kidney outcomes. These findings may help inform clinicians when weighing the potential risks and benefits of second-line antihypertensive therapy in this population.