What is the safety of naproxen (nonsteroidal anti-inflammatory drug, NSAID) in patients with hypertension?

From the Guidelines

Naproxen should be used with caution in patients with hypertension as it can raise blood pressure and potentially interfere with antihypertensive medications. For hypertensive patients who require pain relief, acetaminophen (Tylenol) is generally a safer first choice. If naproxen is necessary, it should be used at the lowest effective dose (typically 220-500 mg) for the shortest duration possible, and blood pressure should be monitored regularly during treatment 1. Patients should be advised to take naproxen with food to reduce gastrointestinal side effects. Those on blood pressure medications should be particularly vigilant about monitoring their blood pressure when starting naproxen. The blood pressure-raising effect occurs because naproxen, like other NSAIDs, inhibits prostaglandin synthesis, which can lead to sodium and fluid retention and increased peripheral vascular resistance. Additionally, NSAIDs can directly interfere with the effectiveness of certain antihypertensive medications, particularly ACE inhibitors, ARBs, and diuretics. If a patient notices sustained blood pressure elevation while taking naproxen, they should contact their healthcare provider to discuss alternative pain management strategies.

Some key points to consider when using naproxen in patients with hypertension include:

• Monitoring blood pressure regularly during treatment with naproxen 1
• Using the lowest effective dose of naproxen for the shortest duration possible 1
• Advising patients to take naproxen with food to reduce gastrointestinal side effects
• Being aware of the potential for naproxen to interfere with antihypertensive medications, particularly ACE inhibitors, ARBs, and diuretics 1

It's also important to note that the American Heart Association recommends avoiding or withdrawing NSAIDs, including naproxen, in patients with resistant hypertension whenever possible 1. However, if naproxen is necessary, close monitoring of blood pressure and adjustments to the antihypertensive regimen may be necessary.

From the FDA Drug Label

WARNINGS CARDIOVASCULAR EFFECTS Cardiovascular Thrombotic Events Clinical trials of several COX-2 selective and nonselective NSAIDs of up to three years duration have shown an increased risk of serious cardiovascular (CV) thrombotic events, myocardial infarction, and stroke, which can be fatal. All NSAIDs, both COX-2 selective and nonselective, may have a similar risk Patients with known CV disease or risk factors for CV disease may be at greater risk. To minimize the potential risk for an adverse CV event in patients treated with an NSAID, the lowest effective dose should be used for the shortest duration possible. Physicians and patients should remain alert for the development of such events, even in the absence of previous CV symptoms Patients should be informed about the signs and/or symptoms of serious CV events and the steps to take if they occur. There is no consistent evidence that concurrent use of aspirin mitigates the increased risk of serious CV thrombotic events associated with NSAID use The concurrent use of aspirin and an NSAID does increase the risk of serious GI events (see Gastrointestinal Effects - Risk of Ulceration, Bleeding, and Perforation). Two large, controlled, clinical trials of a COX-2 selective NSAID for the treatment of pain in the first 10-14 days following CABG surgery found an increased incidence of myocardial infarction and stroke (see CONTRAINDICATIONS) Hypertension NSAIDs, including naproxen, can lead to onset of new hypertension or worsening of pre-existing hypertension, either of which may contribute to the increased incidence of CV events. Patients taking thiazides or loop diuretics may have impaired response to these therapies when taking NSAIDs. NSAIDs, including naproxen, should be used with caution in patients with hypertension Blood pressure (BP) should be monitored closely during the initiation of NSAID treatment and throughout the course of therapy.

The safety of naproxen in patients with hypertension is a concern, as NSAIDs, including naproxen, can lead to the onset of new hypertension or worsening of pre-existing hypertension.

• Key points:
  • Naproxen should be used with caution in patients with hypertension.
  • Blood pressure (BP) should be monitored closely during the initiation of NSAID treatment and throughout the course of therapy.
  • Patients taking thiazides or loop diuretics may have impaired response to these therapies when taking NSAIDs.
  • The lowest effective dose of naproxen should be used for the shortest duration possible to minimize the potential risk for an adverse CV event 2.

From the Research

Safety of Naproxen in Hypertension

• The safety of naproxen in hypertension has been studied in several clinical trials, with varying results 3, 4, 5, 6, 7.
• A study published in 2013 found that naproxen significantly increased clinic and ambulatory systolic/diastolic blood pressure values in patients treated with ramipril or valsartan, but did not affect aliskiren effects 3.
• Another study published in 2017 found that ibuprofen, compared with celecoxib, was associated with a significant increase in systolic blood pressure and a higher incidence of new-onset hypertension, while naproxen had a smaller effect on blood pressure compared to ibuprofen 4.
• A study published in 2011 found that naproxcinod, a nitric oxide-donating naproxen, had a smaller effect on blood pressure compared to naproxen, and may be a beneficial alternative for patients with osteoarthritis requiring nonsteroidal anti-inflammatory drugs 5.
• A more recent study published in 2024 found that naproxen inhibited COX-2 activity to a greater degree than celecoxib, and significantly increased blood pressure compared to celecoxib, with the difference in systolic blood pressure relative to placebo associated with the degree of COX-2 inhibition 6.
• An older study published in 1997 found that nonsteroidal anti-inflammatory drugs, including naproxen, can induce an increase in blood pressure and may potentially reduce the efficacy of several antihypertensive drugs, particularly those that act through the increase of prostaglandin formation, such as diuretics, beta-blockers, and ACE inhibitors 7.

Mechanisms of Action

• The mechanisms of action of naproxen and other nonsteroidal anti-inflammatory drugs on blood pressure are complex and involve the inhibition of prostaglandin synthesis, which can lead to vasoconstriction and sodium retention 3, 7.
• The degree of COX-2 inhibition may also play a role in the blood pressure effects of naproxen and other nonsteroidal anti-inflammatory drugs, with greater inhibition associated with greater increases in blood pressure 6.

Clinical Implications

• The use of naproxen and other nonsteroidal anti-inflammatory drugs in patients with hypertension requires careful consideration of the potential effects on blood pressure and the efficacy of antihypertensive medications 3, 4, 7.
• Alternative treatments, such as calcium antagonists, may be preferable for patients with hypertension who require nonsteroidal anti-inflammatory drug therapy 7.