Is Acetaminophen Really Safer Than NSAIDs in Heart Disease?

Megan Brooks

September 15, 2022

New research calls into question the assumption that acetaminophen is safer than non-steroidal anti-inflammatory drugs (NSAIDs) for patients with known cardiovascular disease (CVD) or CVD risk factors.

The analysis found a significant correlation between the use of acetaminophen and elevated systolic blood pressure.

While acetaminophen may still be safer than NSAIDs from a bleeding risk standpoint, or in patients with known kidney disease, "the gap may not be as large as once thought," Rahul Gupta, MD, cardiologist with Lehigh Valley Health Network, Allentown, Pennsylvania, told | Medscape Cardiology.

"Cautious use is recommended over the long term, especially in patients with pre-existing hypertension or cardiovascular risk factors," Gupta said.

The study was presented at the American Heart Association (AHA) Hypertension Scientific Sessions 2022 in San Diego, California.

Acetaminophen is one of the most widely used over-the-counter medications, as it is considered a safer medication for long-term use since it lacks the anti-inflammatory effects of NSAIDs, Gupta explained.

NSAIDs have been known to raise blood pressure, but the effect of acetaminophen in this regard has not been well studied. Observational studies have shown contradictory results in terms of its effect on blood pressure, he noted.

To investigate further, Gupta and colleagues did a meta-analysis of three studies that compared the effect of acetaminophen (3-4 g/day) vs placebo on systolic and diastolic ambulatory blood pressure in patients with heart disease or hypertension. Together, the studies included 172 adults (mean age, 60 years; 73% male). 

They found that patients receiving acetaminophen had significantly higher systolic blood pressure compared with those receiving placebo (standard mean difference [SMD] = 0.35; 95% CI, 0.08-0.63; P = .01).

Subgroup analysis of the effect on hypertensive patients showed significant change in systolic blood pressure as well (SMD = 0.38; 95% CI, 0.05-0.71; P = .02).

"Interestingly, there was no significant difference in the effect on diastolic blood pressure," Gupta commented.

Reached for comment, Timothy S. Anderson, MD, clinical investigator in the Division of General Medicine at Beth Israel Deaconess Medical Center and assistant professor of medicine at the Harvard Medical School in Boston, Massachusetts, said this is "an interesting and not particularly well-known issue."

"However, most of the trials look at very high doses of acetaminophen use (eg, six to eight of the 500-mg pills each day) so we don't really know whether the more common patterns of using one to two acetaminophen pills every once in a while is problematic," Anderson told | Medscape Cardiology.

"We also don't have data showing a direct harm from these medications with regards to strokes or heart attacks or other downstream consequences of high blood pressure. Ideally would need a head-to-head trial comparing ibuprofen-type medications to acetaminophen-type medications," Anderson said.

The study had no specific funding. Gupta and Anderson reported no relevant disclosures.

American Heart Association (AHA) Hypertension Scientific Sessions 2022. Poster 033. Presented September 7, 2022.

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