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Renin-angiotensin-aldosterone system inhibitors and major cardiovascular events and acute kidney injury in patients with coronary artery disease

Sud M, Ko DT, Chong A, Koh M, Azizi P, Austin PC, Stukel T, Jackevicius CA. Pharmacotherapy. 2021 Sep 8 [Epub ahead of print]. DOI: https://doi.org/10.1002/phar.2624


Background — Renin-angiotensin-aldosterone system inhibitors (RAASIs) are recommended for most patients with coronary artery disease (CAD). However, there is debate across guidelines as to which patients with CAD benefit the most from these agents. This study investigated the association between RAASIs and cardiovascular outcomes and acute kidney injury in a contemporary cohort of patients with CAD.

Methods — Patients ≥65 years of age with CAD alive on April 1st, 2012 in Ontario, Canada were included. Outcomes included major adverse cardiovascular events (MACE: cardiovascular death, myocardial infarction (MI), unstable angina, stroke or coronary revascularization) and acute kidney injury (AKI) hospitalizations at 4 years. Inverse probability of treatment-weighted Cox proportional hazards regression models were used to compare the rates of each outcome in patients treated with and without RAASIs (angiotensin converting-enzyme inhibitors or angiotensin II receptor blockers).

Results — There were 165,058 patients with CAD identified (mean age 75 years, 65.5% male, 64.7% prescribed RAASIs). After inverse-probability weighting, treatment with RAASIs was associated with a lower rate of MACE compared to treatment without RAASIs (17.6% vs. 18.2%, hazard ratio [HR]: 0.96, 95% CI: 0.89-0.96 respectively). However, treatment with RAASIs was associated with a higher rate of AKI compared to treatment without RAASIs (1.7% vs. 1.5%, HR: 1.14, 95% CI: 1.02-1.29, respectively). The reduction in MACE was greater in patients with prior MI (HR: 0.87, 95% CI: 0.82-0.92) compared to patients without prior MI (HR: 1.00, 95% CI: 0.97-1.04, interaction p<0.01). The increase in AKI was lower in patients with prior MI (HR: 0.82, 95% CI: 0.66-1.00) compared to patients without prior MI (HR: 1.37, 95% CI: 1.19-1.57, interaction p<0.01).

Conclusions — This study supports the continued use of RAASIs in patients with CAD, although the benefit appears smaller in magnitude than observed in prior trials. High-risk patients, particularly those with prior MI, appear to benefit the most from RAASIs.

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