The safety of combining angiotensin-converting- enzyme inhibitors with angiotensin-receptor blockers in elderly patients: a population-based longitudinal analysis

McAlister, Finlay A.; Jianguo Zhang; Tonelli, Marcello; Klarenbach, Scott; Manns, Braden J.; Hemmelgarn, Brenda R.
April 2011
CMAJ: Canadian Medical Association Journal;4/5/2011, Vol. 183 Issue 6, p655
Academic Journal
Background: The risks associated with using an angiotensin-converting-enzyme (ACE) inhibitor and an angiotensin-receptor blocker together are unclear. This study was designed to determine the safety of combination therapy with these two drugs in clinical practice. Methods: We conducted a population-based longitudinal analysis using linked administrative and laboratory data for elderly patients who were new users of an ACE inhibitor, an angiotensin-receptor blocker or a combination of both medications between May 1, 2002, and Dec. 31, 2006. We compared outcomes in patients given combination therapy versus patients given monotherapy using Cox proportional hazards analyses with adjustment for baseline characteristics. Results: Of the 32 312 new users of either medication (mean age 76.1 years, median creatinine level 92 µmol/L), 1750 (5.4%) received combination therapy. However, 1512 (86.4%) of the patients who were given combination therapy did not have trial-established indications such as heart failure or proteinuria. Renal dysfunction was more common among patients given combination therapy (5.2 [95% confidence interval (CI) 3.4 to 7.9] events per 1000 patients per month) than among patients given monotherapy (2.4 [95% CI 2.2 to 2.7] events per 1000 patients per month) (adjusted hazard ratio [HR] 2.36, 95% CI 1.51 to 3.71). Hyperkalemia was also more common among patients given combination therapy (2.5 [95% CI 1.4 to 4.3] events per 1000 patients per month) than among patients given monotherapy (0.9 [95% CI 0.8 to 1.0] events per 1000 patients per month) (adjusted HR 2.42, 95% CI 1.36 to 4.32). Most patients took combination therapy for only a short time (median three months before at least one agent was stopped). Interpretation: Combination therapy was frequently prescribed for patients without established indications and was associated with an increased risk of adverse renal outcomes when compared with monotherapy. These results mirrored data from randomized controlled trials.


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