Use of calcium antagonists and worsening renal function in patients receiving angiotensin-converting-enzyme inhibitors

Objective: The objective of this study was to assess whether calcium antagonists, which have been proven to dilate the afferent glomerular arteriole, might prevent increases in serum creatinine levels among older subjects who started treatment with angiotensin-converting enzyme (ACE) inhibitors. Methods: We explored the association between use of calcium antagonists and incident increases in serum creatinine in 780 elderly patients with baseline creatinine levels < 1.2 mg/dL (106.19 μmol/L), who were enrolled in a multicenter pharmacoepidemiology study, and who started using ACE inhibitors during their hospital stay. Among these participants, 279 also started using calcium antagonists. Demographic variables, comorbid conditions, medications, and objective tests, which were associated with increasing serum creatinine levels in separate regression models, were examined as potential confounders in a summary model. Results: Among patients receiving ACE inhibitors, serum creatinine levels increased in 22% of participants who were dispensed calcium antagonists, and in 31% of other patients (P=0.005). In the summary regression model, use of calcium antagonists was associated with a decreased risk of worsening renal function (RR 0.56, 95% CI 0.37-0.84). The adjusted risk of increasing serum creatinine was lower (RR 0.25, 95% CI 0.05-0.95) in participants receiving higher calcium antagonists dosages than in those taking lower dosages. This protective effect of calcium antagonists was not detected in patients not dispensed ACE inhibitors. Conclusion: ACE inhibitors are underused in older subjects, mainly because of the higher incidence of renal damage among geriatric populations. Our results indicate that among elderly patients receiving ACE inhibitors, the use of calcium antagonists is associated with a reduced risk of worsening renal function. Thus, these results warrant trials aiming at establishing whether combined treatment with calcium antagonists might allow the use of ACE inhibitors in clinical practice to be expanded to the elderly population.