What is the preferred nonsteroidal anti-inflammatory drug (NSAID) between naproxen and ibuprofen for a patient with hypertension?

NSAID Selection in Hypertensive Patients

Neither naproxen nor ibuprofen is preferred—avoid both NSAIDs entirely in patients with hypertension and use acetaminophen (up to 3000 mg/day) as the first-line analgesic instead. 1

Primary Recommendation: Avoid NSAIDs

• Acetaminophen is the preferred first-line analgesic for hypertensive patients because it has minimal effects on blood pressure compared to traditional NSAIDs. 1
• The American College of Cardiology supports acetaminophen up to 3000 mg/day in divided doses, with monitoring for hepatic toxicity during long-term use. 1
• For localized pain requiring anti-inflammatory effects, topical NSAID preparations are recommended to minimize systemic absorption and cardiovascular effects. 1

If NSAIDs Are Absolutely Necessary: Comparative Evidence

When NSAIDs cannot be avoided, the evidence shows important differences between these agents:

Blood Pressure Effects

• Ibuprofen causes greater blood pressure elevation than naproxen. In the highest quality comparative study, ibuprofen increased systolic blood pressure by 3 mmHg more than naproxen and by 5 mmHg more than celecoxib. 2
• In hypertensive patients on hydrochlorothiazide, ibuprofen increased diastolic blood pressure by 2.6 mmHg at 2 weeks (statistically significant), while naproxen increased it by only 0.7 mmHg (not statistically significant). 3
• A dose-response relationship exists between naproxen and systolic blood pressure (7 mmHg increase with regular dosing), but this relationship was not found with ibuprofen or diclofenac. 4

Cardiovascular Risk Profile

• Ibuprofen carries substantially higher cardiovascular mortality risk. The American Heart Association found that ibuprofen users had a 25% increased risk of recurrent myocardial infarction and 50% increased mortality compared to non-users. 5
• Patients with existing cardiovascular disease face substantially greater risk of serious cardiovascular thrombotic events, myocardial infarction, stroke, and death with ibuprofen, with risk escalating with duration of use. 5

Critical Drug Interaction: Aspirin

• Ibuprofen interferes with aspirin's cardioprotective effects by blocking aspirin's ability to irreversibly acetylate platelet COX-1, which can eliminate aspirin's cardiovascular benefits. 5
• Patients taking immediate-release low-dose aspirin should take ibuprofen at least 30 minutes after aspirin ingestion or at least 8 hours before aspirin to avoid this interaction. 5
• This interaction is particularly problematic since many hypertensive patients are on aspirin for cardiovascular protection.

Antihypertensive Medication Interactions

• Both naproxen and acetaminophen significantly affect blood pressure control in patients treated with ramipril or valsartan, but naproxen did not affect aliskiren's antihypertensive effects. 6
• Most antihypertensive medications show decreased effects with concomitant NSAID administration, with the exception of calcium channel blockers. 7
• Blood pressure increases with NSAIDs are 3 mmHg in patients on ACE inhibitors or calcium channel blockers and 6 mmHg in those on beta-blockers. 2

Mandatory Monitoring Protocol

If an NSAID must be used despite these risks:

• Check blood pressure within 1-2 weeks of starting any NSAID and monitor renal function, especially in patients taking ACE inhibitors, ARBs, or diuretics. 1
• Monitor blood pressure, renal function, and liver function every 3 months if NSAIDs must be continued. 8
• Use the lowest effective dose for the shortest duration possible. 1
• Discontinue NSAIDs if blood pressure increases significantly, renal function worsens, or signs of fluid retention develop. 1

Absolute Contraindications

Avoid NSAIDs entirely in patients with: 1

• Uncontrolled hypertension
• Heart failure
• Chronic kidney disease
• Pre-existing cardiovascular disease

Clinical Decision Algorithm

If the patient requires analgesia:

1. Start with acetaminophen up to 3000 mg/day 1
2. Consider topical NSAIDs for localized pain 1
3. If systemic NSAID is unavoidable AND the patient is on aspirin, naproxen may be marginally preferable to avoid aspirin interaction 5
4. If systemic NSAID is unavoidable AND the patient is NOT on aspirin, neither agent is clearly superior, but ibuprofen shows higher cardiovascular mortality 5, 2
5. Avoid chronic use for more than 2 days/week to minimize cumulative toxicity 8

Common pitfall: Assuming acetaminophen is completely safe—it also slightly but significantly affects blood pressure in hypertensive patients and increases heart rate by approximately 3 beats per minute. 6 However, this effect is still substantially less than traditional NSAIDs.