What is Diclofenac?
Diclofenac is a nonsteroidal anti-inflammatory drug (NSAID) used to relieve pain, swelling, and joint stiffness from conditions like arthritis, menstrual cramps, and migraine attacks [1.2.3, 1.6.2]. It works by inhibiting the body's production of prostaglandins, substances that cause pain and inflammation [1.2.3]. While effective, its use, especially in oral form, has come under scrutiny, leading many healthcare professionals to prefer alternatives.
The Core Concern: Significant Cardiovascular Risks
The most compelling reason for medical caution surrounding diclofenac is its association with an increased risk of serious cardiovascular thrombotic events. All NSAIDs (except aspirin) carry a black box warning from the U.S. Food and Drug Administration (FDA) for this risk, but studies suggest diclofenac's risk profile is particularly concerning [1.6.1, 1.4.3].
A comprehensive series of nationwide cohort studies in Denmark revealed that starting diclofenac was associated with a 50% increased rate of major adverse cardiovascular events (MACE) compared with those not starting the drug [1.10.1]. This included a higher risk for:
- Myocardial infarction (heart attack) [1.10.1]
- Ischemic stroke [1.10.1]
- Heart failure [1.10.1]
- Cardiac death [1.10.1]
Compared to other common NSAIDs, diclofenac also fared poorly. The same research found the risk of MACE was 20% higher than for those starting ibuprofen or paracetamol (acetaminophen) and 30% higher than for those starting naproxen [1.3.1, 1.10.1]. The European Medicines Agency has also stated that data consistently points to this increased risk, particularly at high doses (150 mg daily) and with long-term treatment [1.2.1]. Due to these findings, diclofenac is often contraindicated in patients with established ischemic heart disease, heart failure, peripheral arterial disease, or cerebrovascular disease [1.2.1].
How its Mechanism Contributes to Risk
Diclofenac works by inhibiting cyclooxygenase (COX) enzymes. There are two main types: COX-1, which helps protect the stomach lining, and COX-2, which is more involved in inflammation [1.9.4]. While diclofenac is a non-selective inhibitor, it shows a preferential action against COX-2, similar to celecoxib [1.9.2]. This greater COX-2 selectivity is believed to contribute to the cardiovascular risk. It can disrupt the balance between pro-thrombotic substances (like thromboxane A2, a product of COX-1) and anti-thrombotic substances (like prostacyclin, a product of COX-2), potentially leading to a higher risk of blood clots [1.9.1].
Gastrointestinal Complications
Like all oral NSAIDs, diclofenac carries a risk of serious gastrointestinal (GI) side effects. The FDA includes a boxed warning for these issues, which include bleeding, ulceration, and perforation (holes) in the stomach or intestines [1.2.2, 1.6.3]. These events can occur at any time during treatment, may happen without warning symptoms, and can be fatal [1.6.3].
Studies show that initiating diclofenac can increase the risk of upper gastrointestinal bleeding by approximately 4.5 times compared to not taking it, and 2.5 times compared to taking ibuprofen or paracetamol [1.10.1]. The risk is higher for individuals who:
- Are older in age [1.6.3]
- Have a prior history of peptic ulcer disease or GI bleeding [1.4.3]
- Take the medication for a long duration [1.6.3]
- Consume alcohol [1.4.4]
- Take other medications like oral corticosteroids or anticoagulants ('blood thinners') [1.4.4]
Liver and Kidney Toxicity
Hepatotoxicity (Liver Damage)
Diclofenac is the NSAID most frequently implicated in causing liver injury [1.7.4]. Chronic use of oral diclofenac can cause elevated serum aminotransferase (liver enzyme) levels in up to 15% of patients [1.7.3]. While severe, symptomatic liver disease is rare (1 to 5 cases per 100,000 prescriptions), it can be serious and potentially fatal when it occurs [1.7.3]. The FDA recommends that physicians monitor liver enzymes within 4 to 8 weeks of starting long-term diclofenac therapy [1.6.1]. Signs of liver toxicity can include nausea, fatigue, jaundice (yellowing of the skin or eyes), and pain in the upper right abdomen [1.6.2].
Renal Toxicity (Kidney Damage)
NSAIDs can also impact kidney function. By inhibiting prostaglandins, which help dilate blood vessels in the kidneys to ensure proper blood flow, diclofenac can reduce renal perfusion [1.9.1]. This can lead to fluid retention, edema (swelling), and high blood pressure [1.2.2]. For most healthy individuals, this effect is temporary. However, for those with pre-existing kidney disease, heart failure, or dehydration, the risk of developing acute kidney injury is significantly higher [1.7.1, 1.9.1]. Long-term administration has been linked to renal papillary necrosis and other forms of kidney injury [1.6.1].
Comparison with Other NSAIDs
When choosing a pain reliever, doctors weigh the effectiveness against the safety profile for each individual patient. Here is how diclofenac generally compares to other common NSAIDs:
| Feature | Diclofenac | Ibuprofen | Naproxen |
|---|---|---|---|
| Cardiovascular Risk | Higher risk compared to ibuprofen and naproxen [1.10.1] | Lower cardiovascular risk than diclofenac, but still present [1.5.4] | Often considered to have the lowest cardiovascular risk among common NSAIDs [1.5.3, 1.5.5] |
| Gastrointestinal Risk | Higher risk than ibuprofen; similar to naproxen [1.10.1] | Generally considered to have a lower GI risk than diclofenac or naproxen [1.5.1] | Higher GI risk than ibuprofen; similar to diclofenac [1.5.1, 1.10.1] |
| Hepatotoxicity (Liver) | Higher risk of liver enzyme elevations than many other NSAIDs [1.7.3] | Lower risk than diclofenac | Lower risk than diclofenac |
| Common Use | Prescription for arthritis, severe pain [1.2.3] | Over-the-counter for mild to moderate pain, fever [1.8.4] | Over-the-counter for longer-lasting relief of mild to moderate pain [1.8.4] |
Safer Alternatives to Diclofenac
Given the risks, doctors often consider several alternatives:
- Naproxen: For patients with high cardiovascular risk, naproxen is often the preferred NSAID due to its more favorable cardiac safety profile [1.5.5].
- Topical Diclofenac: For localized pain, such as in a single arthritic joint, topical diclofenac (gels, patches) is a much safer option. Systemic absorption is minimal, which significantly reduces the risk of cardiovascular and GI side effects compared to oral diclofenac [1.8.3, 1.11.3].
- Acetaminophen (Tylenol): For pain relief without inflammation, acetaminophen is a common first-line alternative. It does not carry the cardiovascular or GI risks of NSAIDs, but overdose can cause severe liver damage [1.8.2].
- COX-2 Inhibitors (e.g., Celecoxib): These drugs were designed to be easier on the stomach than traditional NSAIDs. However, they still carry cardiovascular risks similar to diclofenac [1.2.1, 1.8.1].
Conclusion
While diclofenac is an effective anti-inflammatory and pain reliever, the reasons why do doctors not like diclofenac for first-line or long-term use are clear and backed by extensive research. Its notable association with a higher risk of heart attack, stroke, and gastrointestinal bleeding compared to other options like naproxen makes it a less favorable choice for many patients, especially those with pre-existing cardiovascular risk factors. The availability of safer alternatives, including the topical form of diclofenac itself, provides clinicians with better-tolerated options for managing pain and inflammation. Patient-specific risk factors must always be assessed before prescribing any NSAID.
Authoritative Link: Diclofenac Drug Information from the U.S. National Library of Medicine [1.6.3]
