What are the recommendations for using diclofenac (Non-Steroidal Anti-Inflammatory Drug (NSAID)) given the recent increase in cardiac arrest after its injection?

Diclofenac Should Be Avoided in Patients with Cardiac Disease Due to Substantially Elevated Risk of Cardiac Arrest and Death

Diclofenac carries a 2.4-fold increased risk of cardiovascular death (HR 2.40,95% CI 2.09-2.80) and a 1.5-fold increased risk of out-of-hospital cardiac arrest in patients with established cardiovascular disease, making it one of the most dangerous NSAIDs for cardiac patients. 1, 2, 3

Magnitude of Cardiac Risk with Diclofenac

The cardiovascular dangers of diclofenac are comparable to rofecoxib (Vioxx), which was withdrawn from the market:

• Mortality risk: 2.4-fold increase in cardiovascular death among post-MI patients 1, 2
• Recurrent MI risk: 1.54-fold increase (HR 1.54,95% CI 1.23-1.93) 4
• Out-of-hospital cardiac arrest: 1.50-fold increase (OR 1.50,95% CI 1.23-1.82) 3
• Overall vascular events: 1.63-fold increase (HR 1.63,95% CI 1.12-2.37) 4

These risks are dose-dependent and appear early after initiation of therapy. 1, 2

Why Diclofenac Is Particularly Dangerous

Diclofenac's high COX-2 selectivity causes loss of protective COX-2 upregulation during myocardial ischemia, resulting in larger infarct size and greater left ventricular wall thinning. 4 Additionally, diclofenac can trigger Kounis syndrome (allergic acute coronary syndrome), leading to coronary vasospasm, myocardial infarction, and cardiac arrest even in patients with normal coronary arteries. 5, 6

Absolute Contraindications for Diclofenac

Class III (Harm) recommendation: Diclofenac should NOT be used in patients with: 1

• History of myocardial infarction
• Unstable angina or acute coronary syndrome
• Established cardiovascular disease
• Heart failure
• Uncontrolled hypertension
• Patients on anticoagulation (3-6 fold increased bleeding risk) 4

Recommended Stepped-Care Approach for Pain Management

Class I recommendation: Use the following algorithm for musculoskeletal pain in cardiac patients: 1

First-Line Options:

• Acetaminophen (up to 4g/day in patients with normal liver function) 1
• Non-acetylated salicylates (e.g., salsalate) 1
• Tramadol 1
• Small doses of narcotics (short-term use) 1

Second-Line (Class IIa - Reasonable):

• Naproxen (if first-line insufficient) - appears safest among NSAIDs with RR 0.92 for vascular events 1, 4, 7
• Use lowest effective dose for shortest duration 1
• Add proton pump inhibitor for GI protection 1

Third-Line (Class IIb - May Consider):

• Other nonselective NSAIDs with lower COX-2 selectivity 1
• Ibuprofen ≤1200 mg/day (doses ≥2400 mg/day carry similar risk to diclofenac) 7
• Only if intolerable discomfort persists despite stepped-care 1

Never Use (Class III - Harm):

• Diclofenac 1, 4
• Rofecoxib 1
• High-dose ibuprofen (≥2400 mg/day) 7
• Selective COX-2 inhibitors (celecoxib, rofecoxib) in patients with established CVD 1

Critical Monitoring Requirements

If any NSAID must be used in a cardiac patient: 1

• Monitor blood pressure regularly (NSAIDs increase BP by average 5 mm Hg) 1
• Assess for new or worsening edema 1
• Monitor renal function (baseline creatinine, then weekly for 3 weeks if high-risk) 1
• Screen for GI bleeding 1
• Continue aspirin 81 mg daily with PPI 1
• Discontinue immediately if cardiovascular symptoms develop 1

Special Populations Requiring Extra Caution

Avoid all NSAIDs including diclofenac in: 1

• Preexisting renal disease (2% develop renal complications requiring discontinuation) 1
• Congestive heart failure (all NSAIDs double heart failure risk) 7
• Cirrhosis 1
• Patients on ACE inhibitors or ARBs (increased renal failure risk) 1
• Perioperative period (stop 2-3 days before surgery for naproxen, 2 days for ibuprofen) 1

Common Pitfalls to Avoid

• Do not assume intramuscular/IV diclofenac is safer than oral - cardiac arrest has been reported with IM injection 6
• Do not use diclofenac for "just one dose" - cardiac events can occur within hours of administration 3, 6
• Do not combine COX-2 inhibitors with nonselective NSAIDs - increases MI incidence and renal dysfunction 1
• Do not believe revascularization eliminates need for NSAID avoidance - post-PCI and post-CABG patients remain high-risk 1