When are Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) contraindicated?

When Are NSAIDs Contraindicated?

Absolute Contraindications

NSAIDs are absolutely contraindicated in the setting of coronary artery bypass graft (CABG) surgery for perioperative pain management 1, 2, 3. This represents a black box warning from the FDA, as two large controlled trials demonstrated increased incidence of myocardial infarction and stroke in the first 10-14 days following CABG 1.

Additional Absolute Contraindications:

• History of peptic ulcer disease or gastrointestinal bleeding - particularly in patients who must continue anticoagulation therapy 4
• Active gastrointestinal bleeding or perforation - NSAIDs should be discontinued immediately if peptic ulcer or GI hemorrhage develops 4
• Severe chronic kidney disease - NSAIDs should be avoided entirely in patients with pre-existing renal disease 5, 6
• Cirrhosis with ascites - the risk of acute renal failure, hyponatremia, and diuretic resistance is extremely high 5
• Decompensated heart failure - NSAIDs cause sodium and water retention, worsening renal function and precipitating acute decompensation 4, 5

High-Risk Situations Requiring Extreme Caution or Avoidance

Cardiovascular Contraindications:

• Recent myocardial infarction - observational studies show NSAID-treated patients had 20 deaths per 100 person-years versus 12 per 100 in non-NSAID users in the first year post-MI 1
• Known cardiovascular disease or high cardiovascular risk - NSAIDs increase risk of serious CV thrombotic events, MI, and stroke even with short-term use 4, 1
• Uncontrolled hypertension - NSAIDs should be discontinued if hypertension develops or worsens 4

Renal Contraindications:

NSAIDs must be prescribed with extreme caution or avoided in patients with:

• Age ≥60 years - this alone represents high risk for renal toxicity 4
• Compromised fluid status or volume depletion 4
• Concomitant nephrotoxic drugs - including cyclosporin, cisplatin, or renally excreted chemotherapy 4
• Congestive heart failure - prostaglandins are critical for maintaining renal perfusion in these patients 5

Discontinue NSAIDs immediately if:

• BUN or creatinine doubles from baseline 4
• Hypertension develops or worsens 4

Gastrointestinal Contraindications:

Avoid NSAIDs in patients with:

• Age ≥60 years combined with history of peptic ulcer disease 4
• Concurrent corticosteroid therapy - significantly increases upper GI bleeding risk 4
• Untreated H. pylori infection - increases GI bleeding risk with chronic NSAID use 4
• Significant alcohol use (≥2 alcoholic beverages per day) 4
• Major organ dysfunction including hepatic dysfunction 4

Hematologic Contraindications:

Oral NSAIDs should be avoided in:

• Therapeutic or prophylactic anticoagulation - NSAIDs with warfarin or heparin increase bleeding complications 3-6 fold 4, 6
• Thrombocytopenia or bleeding disorders 4
• Concurrent antiplatelet therapy - concomitant use with low-dose aspirin increases GI bleeding risk 4

Note: Topical NSAIDs (diclofenac gel or patch) may be considered as alternatives in anticoagulated patients 4.

Hepatic Contraindications:

• Discontinue NSAIDs if liver function studies increase to multiple times the upper limit of normal 4
• Advanced liver disease with coagulopathy - these patients are at increased risk for GI bleeding 1

Critical Drug Interactions Requiring Avoidance

The combination of NSAIDs with the following medications creates compounded risk:

• ACE inhibitors or ARBs - creates a "perfect storm" where the kidney loses both vasodilatory and pressure-maintaining mechanisms 5, 7
• Diuretics - NSAIDs directly reduce sodium excretion and blunt natriuretic response, causing fluid retention and edema 5
• Multiple nephrotoxic agents simultaneously - exponentially increases acute kidney injury risk 5

Common Pitfalls to Avoid

• COX-2 selective inhibitors produce identical sodium retention and renal effects as non-selective NSAIDs - they offer no renal safety advantage 5
• Even short-term NSAID use carries cardiovascular and GI risk - the increased risk begins as early as the first weeks of treatment 4
• Dyspeptic symptoms do not correlate with clinically significant ulcerations - only 1 in 5 patients who develop serious upper GI events are symptomatic 4, 1
• Over-the-counter NSAID use often goes unreported - always specifically ask patients about ibuprofen, naproxen, and aspirin use 5

Monitoring Requirements When NSAIDs Cannot Be Avoided

Baseline assessment required:

• Blood pressure, BUN, creatinine, liver function studies (alkaline phosphatase, LDH, SGOT, SGPT), CBC, and fecal occult blood 4

Repeat monitoring every 3 months to ensure lack of toxicity 4

For high-risk patients, some experts recommend weekly monitoring for the first three weeks after NSAID initiation 5