Diclofenac Significantly Increases Risk of Cardiac Arrest and Death in Patients with Cardiac Pain
Diclofenac should be avoided in patients with cardiac pain due to substantially elevated risks of cardiac arrest, recurrent myocardial infarction, and cardiovascular mortality—risks that are among the highest of all NSAIDs and comparable to withdrawn drugs like rofecoxib. 1, 2
Magnitude of Risk in Cardiac Patients
The evidence demonstrates alarming cardiovascular risks specifically with diclofenac:
- Mortality risk increases 2.4-fold (RR 2.40,95% CI 2.09-2.80) in registry data 1
- Recurrent MI risk increases 1.54-fold (RR 1.54,95% CI 1.23-1.93) 1
- Overall vascular events increase 1.63-fold (RR 1.63,95% CI 1.12-2.37) in meta-analyses of randomized controlled trials 1
- Out-of-hospital cardiac arrest risk increases 1.50-fold (OR 1.50,95% CI 1.23-1.82) in a nationwide Danish study 3
These risks are substantially higher than other commonly used NSAIDs like ibuprofen and naproxen. 1
FDA Black Box Warning
The FDA mandates a black box warning stating that NSAIDs, including diclofenac, cause increased risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which can be fatal, with risk increasing with duration of use and being greater in patients with cardiovascular disease or risk factors. 2
Specific Contraindications and High-Risk Scenarios
Absolute avoidance is required in:
- Post-CABG surgery patients (FDA contraindication) 2
- Recent MI patients—observational studies show 20 deaths per 100 person-years in NSAID-treated post-MI patients versus 12 per 100 in non-exposed patients 2
Extreme caution or avoidance in:
- Patients on anticoagulants (3-6 fold increased bleeding risk) 4
- Patients taking aspirin for cardioprotection (though diclofenac does not block aspirin's antiplatelet effect like ibuprofen does) 1
- Patients with heart failure, hypertension, or renal impairment 2
Mechanism of Harm in Cardiac Ischemia
Diclofenac's high COX-2 inhibitory potency leads to:
- Loss of protective COX-2 upregulation during myocardial ischemia 1
- Larger infarct size and greater left ventricular wall thinning 1
- Increased tendency to myocardial rupture 1
- Sodium retention and blood pressure elevation 2
Risk Appears Early in Treatment
The increased cardiovascular risk begins as early as the first weeks of treatment and persists throughout therapy, even in short-term use (<90 days). 2, 3, 5 In patients recently hospitalized for serious coronary heart disease, short-term diclofenac use showed an incidence rate ratio of 1.86 (95% CI 1.18-2.92) for serious coronary events. 5
Safer Alternatives for Pain Management
The American College of Cardiology recommends a stepped-care approach: 4
First-line options:
- Acetaminophen
- Small doses of narcotics
- Non-acetylated salicylates
Second-line (if first-line insufficient):
If NSAIDs unavoidable in anticoagulated patients:
- Maximize non-NSAID analgesics
- Add proton pump inhibitor therapy
- Monitor closely for bleeding 4
Critical Clinical Pitfalls
- Do not assume "cardiac pain" means only angina—any patient with known cardiovascular disease, prior MI, or cardiac risk factors falls into this high-risk category 1, 2
- Do not rely on low doses for safety—while dose-dependent, even lower doses carry risk in cardiac patients 1, 2
- Do not use for chronic pain management—the mortality risk persists for at least 4 years of follow-up in post-MI patients 2
- Monitor blood pressure and renal function if diclofenac cannot be avoided, as these contribute to cardiovascular events 2
Comparative Risk Among NSAIDs
When compared directly to naproxen in patients with serious coronary heart disease, diclofenac showed significantly increased risk of serious cardiovascular disease/death (IRR 1.52,95% CI 1.22-1.89). 5 This makes diclofenac one of the highest-risk NSAIDs available, with cardiovascular toxicity similar to the withdrawn drug rofecoxib. 1