What nonsteroidal anti-inflammatory drugs (NSAIDs) are recommended for chest pain?

NSAIDs Should Be Avoided for Chest Pain in Cardiac Contexts

NSAIDs (except aspirin) must not be initiated and should be discontinued immediately in patients with chest pain related to acute coronary syndromes or suspected cardiac ischemia due to significantly increased risk of death, myocardial infarction, heart failure, and other major adverse cardiac events. 1

When NSAIDs Are Absolutely Contraindicated

Acute Coronary Syndromes (ACS)

• All non-aspirin NSAIDs are Class III: Harm in patients hospitalized for non-ST-elevation ACS (NSTE-ACS) and should be discontinued immediately. 1
• The 2025 ACC/AHA/ACEP guideline explicitly states that NSAIDs should be avoided for management of suspected or known ischemic pain, as they are associated with increased risk of major adverse cardiac events with no documented benefit. 1
• This prohibition applies to both traditional NSAIDs (ibuprofen, naproxen, diclofenac) and COX-2 selective inhibitors (celecoxib). 1

ST-Elevation Myocardial Infarction (STEMI)

• NSAIDs should not be given for pain relief in STEMI because of possible prothrombotic effects. 1
• Morphine 4-8 mg IV with additional 2 mg doses every 5-15 minutes is the recommended analgesic for cardiac chest pain. 1

Patients with Coronary Stents

• The American Heart Association warns that NSAIDs carry risks of mortality, reinfarction, heart failure, hypertension, and myocardial rupture in stent patients. 2
• Aspirin must be continued as cornerstone antiplatelet therapy and should never be discontinued. 2

When NSAIDs May Be Appropriate for Chest Pain

Pericarditis

Aspirin or NSAIDs are recommended as first-line therapy for acute pericarditis with gastroprotection (Class I, Level A). 1

• Aspirin 750-1000 mg every 8 hours for 1-2 weeks, tapered by 250-500 mg every 1-2 weeks. 1
• Ibuprofen 600 mg every 8 hours for 1-2 weeks, tapered by 200-400 mg every 1-2 weeks. 1
• Colchicine 0.5 mg once daily (<70 kg) or twice daily (≥70 kg) for 3 months is recommended as adjunct therapy to improve response and prevent recurrences (Class I, Level A). 1
• Treatment duration should be guided by symptoms and C-reactive protein normalization. 1

Non-Cardiac Chest Pain (Post-COVID, Musculoskeletal)

• For pleuritic chest pain or costochondritis without cardiac involvement, a 1-2 week trial of NSAIDs is reasonable, with addition of low-dose colchicine as needed. 1
• Acetaminophen 500 mg orally every 6 hours should be the first-line agent when cardiac issues cannot be excluded. 3, 2
• NSAIDs must be avoided entirely in patients with potential cardiac issues, as they can cause nephrotoxicity when combined with certain medications. 3

Critical Drug Interactions and Timing

Ibuprofen and Aspirin Interaction

• Ibuprofen interferes with aspirin's cardioprotective effects by blocking irreversible acetylation of platelet COX-1 enzyme. 1, 2
• Patients taking immediate-release low-dose aspirin and ibuprofen 400 mg should take ibuprofen at least 30 minutes after aspirin ingestion, or at least 8 hours before aspirin. 1
• Recommendations cannot be made for concomitant use with enteric-coated aspirin, as one study showed attenuation of antiplatelet effect when ibuprofen was dosed 2,7, and 12 hours after aspirin. 1

Other NSAIDs and Aspirin

• Rofecoxib (COX-2 inhibitor), acetaminophen, and diclofenac do not interfere with aspirin's antiplatelet effects. 1
• However, combining aspirin with a COX-2 inhibitor may eliminate the gastric mucosal protective effect of COX-2 inhibition. 1

Cardiovascular Risk Profile of Specific NSAIDs

Relative Safety Hierarchy

• Naproxen and low-dose ibuprofen (≤1200 mg/day) appear to have the lowest cardiovascular risk among NSAIDs. 4, 5
• COX-2 selective inhibitors have the highest cardiovascular risk in patients with prior myocardial infarction, with an estimated excess risk of 6 deaths per 100 person-years of treatment. 1
• Diclofenac carries significant cardiovascular risk even at doses below 100 mg daily. 5

Dose and Duration Considerations

• Cardiovascular risks are dose- and duration-dependent, with increased risk occurring within weeks of COX-2 inhibitor use. 4, 5
• At doses below maximal OTC limits (ibuprofen ≤1200 mg/day) and short durations typical of OTC use, there is no clear association with increased cardiovascular risk. 5
• Low-dose, short-term OTC ibuprofen has been used for over 30 years without major health issues. 6, 7

Safe Alternatives for Cardiac Chest Pain

First-Line Analgesics

• Morphine sulfate 2-4 mg IV, repeated every 5-15 minutes as needed (up to 10 mg total) for ischemic chest pain resistant to maximally tolerated anti-ischemic medications. 1
• Fentanyl 25-50 µg IV, repeated as needed (up to 100 µg total) is an alternative opioid. 1
• Both opioids may delay absorption of oral P2Y12 inhibitors, requiring close monitoring. 1

Nitroglycerin

• Sublingual nitroglycerin 0.3-0.4 mg every 5 minutes up to 3 doses for hemodynamically stable patients with systolic blood pressure ≥90 mmHg. 1
• IV nitroglycerin starting at 10 µg/min for persistent anginal pain, hypertension, or pulmonary edema. 1
• Contraindicated within 12 hours of avanafil, 24 hours of sildenafil/vardenafil, or 48 hours of tadalafil use. 1

Common Pitfalls to Avoid

• Never confuse local corticosteroid injections with systemic NSAIDs—local injections are not contraindicated in cardiac stent patients. 2
• Do not use NSAIDs to mask cardiac symptoms, as this delays appropriate diagnosis and treatment. 1
• Avoid immediate-release nifedipine without a beta-blocker in ACS patients (Class III: Harm). 1
• Do not substitute COX-2 inhibitors thinking they are safer in cardiac patients—they carry the highest cardiovascular risk. 1, 2
• Monitor blood pressure and renal function in all patients taking NSAIDs, especially those with hypertension, renal disease, or heart failure. 1