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Dihydropyridine Calcium Channel Blocker Therapy and Risk of CKD Progression in Type 2 Diabetes Treated With Renin
Timna Agur1,2, Tali Steinmetz1,2, Shira Goldman1,2
1Department of Nephrology and Hypertension, Rabin Medical Center, Petah Tikva, Israel.
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.
Insights
Adding dihydropyridine calcium channel blockers to renin angiotensin system inhibitors and sodium/glucose cotransporter 2 inhibitors therapy increased adverse kidney outcomes in type 2 diabetes patients. This highlights potential risks of this combination antihypertensive therapy.
Area of Science:
- Nephrology
- Endocrinology
- Cardiology
Background:
- Diabetic kidney disease (DKD) progression necessitates optimal antihypertensive strategies with renoprotective effects.
- Guideline-directed therapy for type 2 diabetes often includes renin-angiotensin system inhibitors (RASi) and sodium/glucose cotransporter 2 inhibitors (SGLT2i).
Purpose of the Study:
- To evaluate the impact of dihydropyridine calcium channel blockers (DHPS) on kidney outcomes in type 2 diabetes patients already on RASi and SGLT2i.
- To assess the association between DHP use and major adverse kidney events (MAKE) in this specific patient population.
Main Methods:
- Retrospective cohort study of 31,031 adults with type 2 diabetes from 2016-2021.
- Patients were categorized into DHP or DHP-free groups, both receiving RASi and SGLT2i.
- Inverse probability of treatment weighting (IPTW) was used to adjust for baseline differences.
Main Results:
- DHP use was associated with a significantly higher risk of MAKE (weighted HR, 1.33; P=0.03), even after accounting for competing risk of death.
- No significant association was found between DHP use and all-cause mortality or safety outcomes like hospitalizations or acute kidney injury.
- The study included 12,172 patients on DHP and 18,859 patients without DHP, with a median follow-up of 1,260 days.
Conclusions:
- Concomitant use of DHP with RASi and SGLT2i in type 2 diabetes patients was linked to increased adverse kidney outcomes.
- These findings suggest caution when considering DHP as second-line antihypertensive therapy in this high-risk population.
- Further research is needed to fully understand the risks and benefits, given the observational nature and potential for residual confounding.
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