Major
acetylsalicylic acid × enalapril
Antiplatelet agents (low dose) / NSAIDs (analgesic dose)×Angiotensin-converting enzyme inhibitors (ACEi)
Mechanism
Aspirin's COX inhibition reduces renal prostaglandin-mediated vasodilation. In patients with already-compromised renal perfusion (HF, dehydration, CKD) combined with an ACE inhibitor, acute kidney injury and loss of antihypertensive effect can occur. The effect is clearly dose-dependent. Antiplatelet aspirin doses of 75–100 mg predominantly inhibit platelet COX-1 and barely affect renal prostaglandins. Analgesic and antipyretic doses of 500–1000 mg inhibit COX-1 and COX-2 systemically and are comparable to other nonselective NSAIDs in their effect on renal hemodynamics and BP (FDA Drug Safety Communication, July 2015; AHA Scientific Statement on NSAIDs and CV risk, Circulation 2007).
Management
Antiplatelet aspirin doses of 75–100 mg are compatible with ACE inhibitors – no adjustment needed. Analgesic and antipyretic doses of 500–1000 mg, when required, should be limited to the shortest possible course (3–5 days) and ideally replaced with paracetamol. For NSAID courses longer than 5 days, check creatinine, potassium, and BP at 7–10 days. In patients with eGFR below 60 mL/min and/or aged over 75, analgesic-dose aspirin should be avoided altogether.
Sources
- FDA: FDA Drug Safety Communication: FDA strengthens warning that non-aspirin NSAIDs can cause heart attacks or strokes (2015)— FDA Drug Safety Communication, July 9, 2015
- AHA: Use of Nonsteroidal Antiinflammatory Drugs: An Update for Clinicians. A Scientific Statement From the American Heart Association (2007)— Circulation 2007;115(12):1634–1642
- AGS: American Geriatrics Society 2023 Updated AGS Beers Criteria for Potentially Inappropriate Medication Use in Older Adults (2023)— J Am Geriatr Soc 2023;71(7):2052–2081