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Angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers and the risk of major adverse cardiac events in patients with diabetes and prior stroke

a nationwide study

Shih, Chia-Jen; Chen, Hung-Ta; Chao, Pei-Wen; Kuo, Shu-Chen; Li, Szu-Yuan; Yang, Chih-Yu; Tarng, Der-Cherng; Ou, Shuo-Ming; Chen, Yung-Tai

doi: 10.1097/HJH.0000000000000804
ORIGINAL PAPERS: Therapeutic aspects

Objective: Renin–angiotensin–aldosterone system blockers are the preferred antihypertensive medications in patients with diabetes and prior stroke. This study aimed to compare the effects of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) in terms of major adverse cardiac events (MACEs) in patients with diabetes who survived ischemic stroke.

Methods: We conducted an observational, nationwide, propensity score-matched cohort study using Taiwan's National Health Insurance Research Database. Patients aged at least 20 years with type 2 diabetes who initiated ACEI (n = 15 959) or ARB (n = 23 929) use within 90 days after discharge for first ischemic stroke between January 2000 and December 2011 were allocated to ACEI and ARB groups, respectively. The primary outcomes were MACEs (myocardial infarction, ischemic stroke, and cardiovascular mortality). The secondary outcomes were hospitalization for acute kidney injury and hyperkalemia. Intention-to-treat and as-treated models were used.

Results: Intention-to-treat analysis showed no significant difference between the ACEI and ARB groups in the outcomes of MACEs [hazard ratio (HR), 0.99; 95% confidence interval (CI), 0.95–1.04], including ischemic stroke (HR, 1.01; 95% CI, 0.97–1.06), myocardial infarction (HR, 1.06; 95% CI, 0.95–1.18), and cardiovascular mortality (HR, 0.98; 95% CI, 0.91–1.06). As-treated analysis produced similar results. Additionally, the groups showed no difference in the risk of hospitalization for acute kidney injury or hyperkalemia.

Conclusion: Our study supports the hypothesis that the risks of MACEs and two additional secondary outcomes in patients with diabetes who survived ischemic stroke did not differ according to ACEI versus ARB use.

aSchool of Medicine, National Yang-Ming University, Taipei

bDepartment of Medicine, Taipei Veterans General Hospital, Yuanshan Branch, Yilan

cDeran Clinic, Yilan

dDivision of Endocrinology and Metabolism, Department of Medicine, Taipei City Hospital, Heping Fuyou Branch

eDepartment of Anesthesiology, Wan Fang Hospital, Taipei Medical University

fSchool of Medicine, Taipei Medical University, Taipei

gNational Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli County

hDivision of Infectious Diseases, Taipei Veterans General Hospital

iDivision of Nephrology, Department of Medicine, Taipei Veterans General Hospital

jDivision of Nephrology, Department of Medicine, Taipei City Hospital, Heping Fuyou Branch, Taipei, Taiwan

*Chia-Jen Shiha and Hung-Ta Chen contributed equally to the writing of this article.

Yung-Tai Chen and Shuo-Ming Ou contributed equally as corresponding authors to this work.

Correspondence to Yung-Tai Chen, MD, Department of Nephrology, Taipei City Hospital Heping Fuyou Branch, Taipei 112, Taiwan. Tel: +886 2 2388 9595; fax: +886 2 2876 5215; e-mail:

Abbreviations: ACEI, angiotensin-converting enzyme inhibitors; ARB, angiotensin II receptor blockers; AT, as-treated; ICD-9-CM, International Classification of Diseases, Ninth Revision, Clinical Modification; ITT, intention-to-treat; MACEs, major adverse cardiac events; NHIRD, National Health Insurance Research Database; RAAS, renin–angiotensin–aldosterone system; RCTs, randomized controlled trials

Received 13 August, 2015

Revised 28 September, 2015

Accepted 16 October, 2015

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