In patients on chronic angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs), does withholding the ACEI or ARB prior to non-cardiac surgery decrease the risk of cardiovascular events?
Withholding ACEIs and ARBs before major noncardiac surgery was associated with a lower risk of mortality and postoperative vascular events.
While guidelines from the American College of Cardiology and the American Heart Association have recommended continuing ACEIs and ARBs for major non-cardiac surgery, common practice among many anesthetic providers was to hold these medications to avoid intraoperative hypotension. This study performed a secondary analysis on a sample of patients from VISION (a multicenter international prospective cohort study) and found that withholding the ACEI or ARB the morning of surgery was associated with an 18% reduction in the relative risk of the composite outcome of death, stroke, or MINS (myocardial injury after non-cardiac surgery) as well as a 20% relative reduction in the risk of intraoperative hypotension.
- Multicenter, international, prospective, cohort study
- Patients on chronic ACEI or ARB (n=4,802)
- Patients not on chronic ACEI or ARB (n=9,885)
- Setting: 12 centers in 8 countries (throughout North and South America, Australia, Asia, and Europe)
- Enrollment: August 2000 to January 2011
- Mean Follow-up: 30 days
- Primary outcome: composite of 30 day all-cause death, stroke, and myocardial injury after non-cardiac surgery
- Age > 45 years
- Undergoing non-cardiac surgery
- Underwent general or regional anesthesia
- Required overnight hospital admission
- Unable to consent due to cognitive impairment
- Did not have post-operative blood pressures recorded
- Did not have a troponin assay measured after surgery
- Incomplete preoperative medication data
- Mean age: 64.8 years
- Mean preoperative systolic blood pressure: 139.7 mmHg
- Taking any preoperative anti-hypertensives (n): 6,856
- Taking preoperative ACEI or ARB (n): 4,802
Comparisons are withheld ACEI/ARB vs. continuing ACEI/ARB.
- Composite of 30-day all cause death, stroke, and MINS
- 12.0% vs 12.9% (aRR 0.82; 95% CI 0.70-0.96; P=0.01)
- Intraoperative hypotension
- 23.3% vs 28.6% (aRR 0.80; 95% CI, 0.73-0.88; P<0.001)
- Postoperative hypotension
- 19.4% vs 20.2% (aRR 0.92; 95% CI, 0.77-1.10; P=0.36)
Among all patients (regardless of ACEI/ARB use), those who experienced clinically significant hypotension during surgery were more likely to develop clinically important hypotension after surgery (aRR 1.65; 95% CI, 1.48-1.84; P<0.001). Adjusted for postoperative hypotension, intraoperative hypotension was not significantly associated with the composite outcome of death, MINS, or stroke within the 30 days after surgery (aRR 1.11; 95% CI, 0.98-1.25; P=0.09).
In total, 19.5% of all patients experienced at least one episode of clinically important postoperative hypotension. Postoperative hypotension occurred in the PACU in 3.4% of patients; in the hours immediately after transfer out of the PACU in 6.3%; and during the next day in 11.6% of patients. Patients who experienced clinically important hypotension by the third postoperative day were more likely to die or suffer a vascular event compared to their counterparts without postoperative hypotension (aRR 1.68; 95% CI, 1.53-1.85; P<0.001).
Residual confounding is possible in any observational study. In patients who had their ACEI/ARB withheld, they had similar baseline characteristics but were more likely to undergo urgent or emergency surgery. The authors could not account for the effects of holding other antihypertensive medications or starting new medications, and were unable to study subpopulations of patients with heart failure or known cardiovascular disease. An increased sample size could have improved the power of the study.
This study was coordinated by the Clinical Advances Through Research and Information Translation project office in the Department of Clinical Epidemiology and Biostatistics at McMaster University (Hamilton, Ontario, Canada) and the Population Health Research Institute at the Hamilton Health Sciences, McMaster University (Hamilton, Ontario, Canada). Dr. Devereaux received grants from Roche-Diagnostics (Mannheim, Germany) and Abbott-Diagnostics (Abbott Park, Illinois). The other authors declare no competing interests.
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