No Increase in Adverse Events During Aliskiren Use Among Ontario Patients Receiving Angiotensin-Converting Enzyme Inhibitors or Angiotensin-Receptor Blockers

• Published in: Canadian journal of cardiology 2013-05, Vol.29 (5), p.586-591
• Main Authors: Gilbert, Cameron J., MD, MSc, Gomes, Tara, MHSc, Mamdani, Muhammad M., PharmD, MPH, Hellings, Chelsea, MSc, Yao, Zhan, MD, MSc, Garg, Amit X., MD, PhD, Wald, Ron, MD, Harel, Ziv, MD, MSc, Juurlink, David N., MD, PhD
• Format: Article
• Language: English
• Subjects: Acute Kidney Injury - chemically induced; Acute Kidney Injury - epidemiology; Aged; Aged, 80 and over; Amides - adverse effects; Amides - therapeutic use; Angiotensin Receptor Antagonists - therapeutic use; Angiotensin-Converting Enzyme Inhibitors - therapeutic use; Cardiovascular; Case-Control Studies; Cohort Studies; Drug Therapy, Combination; Female; Fumarates - adverse effects; Fumarates - therapeutic use; Hospitalization; Humans; Hyperkalemia - chemically induced; Hyperkalemia - epidemiology; Logistic Models; Male; Ontario - epidemiology; Renin - adverse effects; Renin - antagonists & inhibitors; Renin - therapeutic use; Risk Factors; Stroke - chemically induced; Stroke - epidemiology
• ISSN: 0828-282X; 1916-7075
• DOI: 10.1016/j.cjca.2013.02.015

Abstract Background Some evidence suggests that the direct renin inhibitor aliskiren may increase the risk of severe hyperkalemia, stroke, or acute kidney injury (AKI) when prescribed with angiotensin-converting enzyme inhibitors (ACEi's) or angiotensin-receptor blockers (ARBs). The extent to which concomitant treatment increases the risk of these outcomes in routine clinical practice is unknown. We addressed this issue with the use of administrative databases. Methods We established a cohort of Ontarians treated with an ACEi or an ARB. Within this cohort, we conducted 3 case-control studies. Cases were patients hospitalized with 1 of 3 outcomes (hyperkalemia, AKI, or stroke). In each analysis, we identified up to 5 matched control subjects for each case. Conditional logistic regression was used to examine the association between hospitalization for each outcome and the use of aliskiren in the preceding 60 days. Results Among 903,346 patients aged 66 years and older treated with an ACEi or ARB during the 28-month study period, we identified 4235 hospitalized with hyperkalemia, 18,231 hospitalized with AKI, and 8283 hospitalized with stroke. After extensive multivariable adjustment, aliskiren therapy was not associated with a significant increase in the risk of hospitalization for hyperkalemia, AKI, or stroke. We found similar results in stratified analyses of patients with and without a history of chronic kidney disease, diabetes, or heart failure. Conclusions Among community-dwelling patients aged 66 years and older receiving therapy with an ACEi or an ARB, aliskiren use was not associated with hospitalization for hyperkalemia, AKI, or stroke.