RAAS Inhibitors in Patients With Coronary Artery Disease

Quick Takes

  • Use of renin-angiotensin-aldosterone system inhibitors (RAASi) is associated with a lower risk of MACE, although the benefit appears to be smaller than observed in prior trials.
  • Patients with a prior MI had a lower risk of MACE than those with no prior MI.
  • Rate of acute kidney injury was higher in patients treated with a RAASi compared to treatment without a RAASi.

Study Questions:

Is there a benefit of renin-angiotensin-aldosterone system inhibitor (RAASi) treatment in patients with coronary artery disease (CAD)?


Patients aged 65-105 years for whom prescription data were available from one of six Canadian databases were included. Patients with a CAD diagnosis were identified using ICD codes for chronic ischemic heart disease, angina, myocardial infarction (MI), percutaneous coronary intervention (PCI), and coronary artery bypass grafting (CABG). Patients residing in nursing homes or on chronic dialysis were excluded along with patients with moderate-to-severe liver disease, prior transplant, dementia, metastatic cancer, prior heart failure hospitalizations, acute kidney injury (AKI) hospitalization within 100 days, and dual renin-angiotensin blockade (angiotensin-converting enzyme [ACE] plus angiotensin receptor blockade). RAASi exposure was defined as use of an ACE inhibitor or angiotensin receptor blocker within the past 100 days. The primary outcomes were major adverse cardiovascular events (MACE) and AKI hospitalizations at 4 years of follow-up. MACE was defined as cardiovascular death, hospitalization for MI or unstable angina, hospitalizations for cerebrovascular events, or need for PCI or CABG. A validated algorithm was used to identify AKI hospitalizations.


A total of 165,058 were included, of which 106,743 (64.7%) were receiving a RAASi. Baseline characteristics were well balanced between patients receiving and not receiving a RAASi. At follow-up of 4 years, treatment with a RAASi was associated with a lower risk of MACE compared with treatment without a RAASi (17.6% vs. 18.2%, hazard ratio [HR], 0.96; 95% confidence interval [CI], 0.93-0.99). Patients receiving a RAASi had significantly lower hazards of cardiovascular death (HR, 0.92; 95% CI, 0.87-0.98) and MI or unstable angina (HR, 0.94; 95% CI, 0.89-0.99). There were no significant differences observed in risk of stroke or transient ischemic attack, revascularization with PCI or CABG, or heart failure hospitalizations. Treatment with a RAASi was associated with a higher hazard of AKI (HR, 1.14; 95% CI, 1.02-1.29) compared to treatment without a RAASi.

In subgroup analyses, the reduction in MACE was found to be greater in patients with a prior MI (HR, 0.87 95% CI, 0.82-0.92 with prior MI vs. HR, 1.00; 95% CI, 0.97-1.04 with no prior MI; p < 0.01). The increased risk of AKI was lower in patients with a prior MI (HR, 0.82; 95% CI, 0.66-1.00 with prior MI vs. HR, 1.37; 95% CI, 1.19-1.57 with no prior MI, p < 0.01).


The use of RAASi in elderly patients is associated with a small reduction in MACE and an increase in AKI at 4 years. Although the reduction in MACE is smaller in magnitude than previous trials, the absolute risk reduction still outweighs the increase in AKI. Patients with prior MI appear to obtain the greatest benefit from use of RAASi.


Prior clinical trials have demonstrated reduced cardiovascular events in high-risk patients but not in lower-risk patients with CAD, which has led to uncertainty regarding which subgroups benefit the most. This study supports the continued use of RAASi in patients with CAD, particularly in those with a prior MI.

Keywords: Acute Coronary Syndrome, Acute Kidney Injury, Angina, Unstable, Angiotensin Receptor Antagonists, Angiotensin-Converting Enzyme Inhibitors, Angiotensins, Coronary Artery Bypass, Coronary Artery Disease, Geriatrics, Heart Failure, Ischemic Attack, Transient, Myocardial Infarction, Myocardial Ischemia, Myocardial Revascularization, Receptors, Angiotensin, Renin, Renin-Angiotensin System, Secondary Prevention, Stroke

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