Can too much ibuprofen cause high blood pressure

Ibuprofen is associated with increased blood pressure and hypertension compared to celecoxib in patients with osteoarthritis or rheumatoid arthritis and increased risk of cardiovascular disease, according to late-breaking results from the PRECISION-ABPM study presented today in a Hot Line Session at ESC Congress1 and published in EHJ.

Nonsteroidal anti-inflammatory drugs (NSAIDs), both non-selective and selective cyclooxygenase-2 (COX-2) inhibitors, are among the most widely prescribed drugs worldwide, but are linked with increased blood pressure and adverse cardiovascular events. Indeed, 19% of the US population use at least one NSAID on a regular basis, including 30 million Americans with osteoarthritis, of whom more than 40% also have hypertension.

NSAID labels include warnings about potential increases in blood pressure but there is little data on the effects of individual drugs. Maintaining or achieving blood pressure control in patients with arthritis and concomitant hypertension (treated or untreated) could avoid more than 70,000 deaths from stroke and 60,000 deaths from coronary heart disease each year,2 making it important to investigate the effects of various NSAIDs on blood pressure.

PRECISION-ABPM,3 a pre-specified four month substudy of the landmark PRECISION trial,4 was designed to determine the blood pressure effects of the selective COX-2 inhibitor celecoxib compared to the non-selective NSAIDs naproxen and ibuprofen.

PRECISION-ABPM was a prospective, double-blind, randomised, non-inferiority cardiovascular safety trial. The study was conducted at 60 sites in the US and included 444 patients, of whom 408 (92%) had osteoarthritis and 36 (8%) had rheumatoid arthritis. All patients had evidence of, or were at increased risk for, coronary artery disease.

Patients were randomised in a 1:1:1 fashion to receive celecoxib (100-200 mg twice a day), ibuprofen (600-800 mg three times a day), or naproxen (375-500 mg twice a day) with matching placebos. The primary endpoint was the change from baseline in 24-hour ambulatory blood pressure after four months.

The investigators found that celecoxib decreased the average systolic blood pressure measured over 24 hours by -0.3 mmHg while ibuprofen and naproxen increased it by 3.7 and 1.6 mmHg, respectively. The resulting difference of -3.9 mmHg between celecoxib and ibuprofen was significant (p=0.009).

Principal investigator Professor Frank Ruschitzka, professor of cardiology and co-head, Department of Cardiology, University Heart Centre, Zurich, Switzerland, said: "PRECISION-ABPM showed differential blood pressure effects between the different NSAIDs, ibuprofen and naproxen, and the COX-2 inhibitor celecoxib. While celecoxib and naproxen produced either a slight decrease (celecoxib) or a relatively small increase (naproxen) in blood pressure, ibuprofen was associated with a significant increase in ambulatory systolic blood pressure of more than 3 mmHg."

An additional analysis showed that the percentage of patients with normal baseline blood pressure who developed hypertension5 was 23.2% for ibuprofen, 19.0% for naproxen and 10.3% for celecoxib (odds ratio [OR] 0.39, p=0.004 and OR 0.49, p=0.03 for celecoxib versus ibuprofen and naproxen, respectively).

"Patients receiving ibuprofen had a 61% higher incidence of de novo hypertension compared to those receiving celecoxib," said Professor Ruschitzka.

These results support and extend the findings of the PRECISION trial, demonstrating noninferiority for the primary cardiovascular outcomes for moderate doses of celecoxib compared with naproxen or ibuprofen.6 These findings may have the greatest clinical significance in the elderly, who have a high prevalence of arthritis and hypertension.

Professor Ruschitzka said: "The current findings suggest that the elevated cardiovascular risk with NSAIDs may be partly due to drug-specific increases in blood pressure. This challenges the widely advocated belief that conventional NSAIDs, like naproxen and ibuprofen, with their higher COX-1 (and thromboxane reducing) effects would provide greater cardiovascular safety than other more COX-2 selective agents, particularly celecoxib."

He concluded: "PRECISION-ABPM clearly demonstrates that NSAIDs, particularly ibuprofen, may be not as safe as previously thought. Patients should continue to consult their doctor before taking NSAIDs or coxibs and clinicians need to weigh the potential hazards of worsening blood pressure control when considering the use of these agents."

Many common over-the-counter (OTC) pain relievers have been shown to increase blood pressure. This effect can occur in both people with normal blood pressure and in those with already diagnosed high blood pressure (hypertension). Many common medications, not just pain relievers, can affect blood pressure because of the way that they affect signaling systems within the body. It is not commonly appreciated that pain relief drugs can have side effects that involve changes in blood pressure.

Non-steroidal anti-inflammatory drugs (NSAIDs)

NSAIDs like aspirin, ibuprofen, naproxen, and others all have the capacity to increase blood pressure. The average increase is small, but the actual amount of increase can vary widely from individual to individual. This effect occurs at doses that are typically used for pain relief and reduction of inflammation. Moreover, these drugs can reduce the effect of many types of drugs used to treat elevated blood pressure. The effect on blood pressure seems to be due to a reduction in excretion of sodium and increased retention of water. Studies of NSAIDs showed that only low-dose aspirin (81 mg a day) did not have measurable effects on blood pressure.

Acetaminophen

Acetaminophen, the active ingredient in Tylenol and other drugs, has been shown in some studies to cause a mild increase in blood pressure, but it hasn't been associated with stroke or heart attack. Still, this medication has its own side effects and poses a risk of liver damage when taken in overly large doses. Prolonged use at high doses can also cause kidney failure.

Options for people with high blood pressure

If you have high blood pressure or heart conditions and would like to take pain control medications, discuss your options with your doctor beforehand. Most experts agree that acetaminophen and aspirin are the safest pain relief choices for people with high blood pressure. However, not everyone should use aspirin. Ask your doctor if aspirin is safe for you if you take medications for high blood pressure. Aspirin may also cause ulcers, heartburn, and upset stomach, and it can be dangerous to take if you have gout, liver disease, rheumatic fever, or if used in children. Pregnant women also should not take aspirin as it can be unsafe for both mother and baby.

Alternatives for pain relief

If you do not want to take pain medications for relief of headache or other mild aches and pains, there are other alternatives. Many people find that ice packs (for acute injuries) and heating pads (for chronic overuse injuries) can bring relief. Relaxation techniques like meditation, imagery, or yoga can be used to help manage pain. Physical activity may help with some kinds of pain, like that of arthritis. Finally, acupuncture and other nontraditional techniques can help some people with mild to moderate pain.

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References

Medically reviewed by Robert J. Bryg, MD; Board Certified Internal Medicine with subspecialty in Cardiovascular Disease

REFERENCES:

Dawson, J. et al. "Acetaminophen use and change in blood pressure in a hypertensive population." Journal of Hypertension 2013.

Dedier, J. et al. "Nonnarcotic analgesic use and the risk of hypertension in U.S. women." Hypertension 40.5 (2002): 604-608.

Radack, K. L. et al. "Ibuprofen interferes with the efficacy of antihypertensive drugs. A randomized, double-blind, placebo-controlled trial of ibuprofen compared with acetaminophen." Annals of Internal Medicine 107.5 (1987): 628-635.

Sudano, I. et al. "Acetaminophen increases blood pressure in patients with coronary artery disease." Circulation 122.18 (2010) 1789-1796.

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