PHARMACOEPIDEMIOLOGY AND PRESCRIPTION Use of calcium antagonists and worsening renal function in patients receiving angiotensin-converting-enzyme inhibitors Received: 9 October 2002 / Accepted: 11 December 2002 / Published online: 31 January 2003 Ó Springer-Verlag 2003 Abstract 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-con- verting enzyme (ACE) inhibitors. Methods: We explored the association between use of calcium antagonists and incident increases in serum creatinine in 780 elderly pa- tients with baseline creatinine levels <1.2 mg/dL (106.19 lmol/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, medica- tions, 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 an- tagonists, and in 31% of other patients (P=0.005). In the summary regression model, use of calcium antago- nists was associated with a decreased risk of worsening renal function (RR 0.56, 95% CI 0.37–0.84). The ad- justed 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 inhibi- tors. Conclusion: ACE inhibitors are underused in older subjects, mainly because of the higher incidence of renal damage among geriatric populations. Our results indi- cate that among elderly patients receiving ACE inhibi- tors, 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 al- low the use of ACE inhibitors in clinical practice to be expanded to the elderly population. Keywords Angiotensin-converting enzyme inhibitors Æ Calcium antagonists Æ Renal failure Æ Elderly Abbreviations ACE angiotensin-converting enzyme Æ RR relative risk Æ CI confidence interval Æ ATC Anatomic–Therapeutic–Chemical Æ OR odds ratio Introduction Treatment with angiotensin converting enzyme (ACE) inhibitors is associated with decreased morbidity and mortality in patients with heart failure, hypertension, or previous myocardial infarction [1, 2, 3]. However, all available literature indicates that this therapy is still underused in older patients [4, 5]. The fear of side effects, chiefly renal failure, represents a major barrier to the use of ACE inhibitors in clinical practice [6]. Indeed, these agents have been causally implicated in a relevant pro- portion of hospital admissions for renal failure among older subjects [7], probably because of a significant prevalence of occult renovascular disease in such pa- tients [8]. Noticeably, the frequency of this side effect is not reduced by the adoption of angiotensin II receptor blockers [9]. Several studies indicated that calcium antagonists yield several effects on glomerular function, chiefly vasodilation of the afferent glomerular arteriole [10]. Eur J Clin Pharmacol (2003) 58: 695–699 DOI 10.1007/s00228-002-0555-1 Giuseppe Zuccala` Æ Graziano Onder Æ Claudio Pedone Matteo Cesari Æ Emanuele Marzetti Æ Alberto Cocchi Pierugo Carbonin Æ Roberto Bernabei G. Zuccala` (&) Æ M. Cesari Æ E. Marzetti Æ A. Cocchi P. Carbonin Æ R. Bernabei Chair of Gerontology, Catholic University of the Sacred Heart, L.go F. Vito 1, 00168, Rome, Italy E-mail: giuseppe_zuccala@rm.unicatt.it Tel.: +39-06-3051190 Fax: +39-06-3051911 G. Onder Sticht Center on Aging, Department of Internal Medicine, Wake Forest University, Winston Salem, USA C. Pedone Center for Gerontology and Health Care Research, Brown University, Providence, USA