NSAIDs Boost CV, Bleeding Risks in Post-MI Patients

All NSAIDs are associated with risk, but celecoxib and meloxicam appear to be safest, a South Korean study suggests.

NSAIDs Boost CV, Bleeding Risks in Post-MI Patients

Among patients on antithrombotic therapy after an MI, nonsteroidal anti-inflammatory drugs (NSAIDs) should be used cautiously, Korean data affirm.

Overall, NSAID use was associated with heightened risks of thromboembolic cardiovascular events (HR 6.96; 95% CI 6.24-7.77) and clinically relevant bleeding events (HR 4.08; 95% CI 3.51-4.73), according to researchers led by Dong Oh Kang, MD, and Hyonggin An, PhD (both from Korea University College of Medicine, Seoul, South Korea).

All individual NSAIDs carried risks, although the hazards appeared to be lowest with celecoxib and meloxicam, they report in a study published online ahead of the August 4, 2020, issue of the Journal of the American College of Cardiology.

“On the basis of the contemporary guidelines, NSAIDs should generally be avoided after MI because their use is associated with increased risk for ischemic and bleeding events,” senior author Cheol Ung Choi, MD, PhD (Korea University College of Medicine), told TCTMD in an email.

He added, however, that “when NSAIDs prescription is unavoidable (eg, [for] osteoarthritis or rheumatoid arthritis), either celecoxib or meloxicam may be preferred over other NSAIDs given their relative safety.”

Commenting for TCTMD, Deepak Bhatt, MD (Brigham and Women’s Hospital, Boston, MA), said the study is a good reminder that NSAIDs are not benign medicines, particularly among patients taking antithrombotic therapy for a cardiovascular condition. “I think many times doctors—and patients, of course, since these can be obtained over the counter—forget that there is a risk to NSAID use having to do with cardiovascular risks, but also bleeding risks, that sometimes are not appreciated.”

Risk Seen Even With Short Duration

Indeed, cardiovascular and bleeding risks have long been a concern with NSAIDs, and professional societies have discouraged their use in patients with established CVD. They’re still commonly used by CV patients with other comorbidities, however, because of their anti-inflammatory and pain-killing effects.

Much of the literature on NSAIDs and cardiovascular risk is based on Western populations, the Korean investigators note. “Considering the ethnic variations observed in post-MI antithrombotic therapy, studies from different populations with concomitant NSAID treatment after MI are imperative to produce global evidence that encompasses diverse population groups,” they say.

I think many times doctors—and patients, of course, since these can be obtained over the counter—forget that there is a risk to NSAID use having to do with cardiovascular risks, but also bleeding risks, that sometimes are not appreciated. Deepak Bhatt

For the current study, the researchers used the Health Insurance Review and Assessment Service database in South Korea, which contains claims data from the country’s National Health Insurance Service covering more than 98% of residents. The analysis included 108,232 patients (mean age 64.2 years; 72.1% men) with a first diagnosed MI between 2009 and 2013. Most patients (87.9%) were prescribed dual antiplatelet therapy after discharge, with some receiving other types of antiplatelet and/or anticoagulant therapy.

Few patients—1.8% for the analysis of CV events and 1.9% for the analysis of bleeding events—were prescribed an NSAID for at least four consecutive weeks. Diclofenac was the most frequently prescribed NSAID in both analyses (71.8% and 68.9%, respectively), with celecoxib making up roughly 13% of prescriptions. The database did not capture over-the-counter use.

The primary outcome of thromboembolic CV events, including recurrent MI, ischemic stroke/TIA, and systemic arterial embolism, occurred at a rate of 24.2% through a mean follow-up of 2.3 years in the entire study cohort. Clinically relevant bleeding events, including GI, intracranial, respiratory, or urinary tract bleeding plus posthemorrhagic anemia, occurred in 23.4%.

Risks of both outcomes were higher in patients taking NSAIDs, in the overall cohort as well as across groups defined by antithrombotic treatment.

Risks also were elevated with each individual NSAID type compared with no NSAID use, although CV and bleeding risks were lowest with celecoxib (HRs 4.65 and 3.44, respectively) and meloxicam (HRs 3.03 and 2.80, respectively). Using celecoxib as the reference, all NSAIDs other than meloxicam were associated with a higher CV risk; only naproxen was associated with an elevated bleeding risk (HR 2.90; 95% CI 1.02-8.22).

The researchers found that even a shorter duration of NSAID use (at least 1 week) was associated with heightened risks of cardiovascular events and bleeding. “These findings provide additional evidence that there is no definite [safe] therapeutic window for concomitant NSAID treatment in patients with MI,” they write. “Intensive monitoring should be conducted throughout the whole treatment duration with concomitant NSAID treatment, if NSAID use is unavoidable after MI.”

The Price of Pain

Asked whether NSAIDs should be avoided altogether in patients who have had an MI, Bhatt said that is not a practical option. “If one is just looking at risk, that would be good advice, but the reality is that for some patients who have bad pains, in particular arthritis, some just don’t find relief from anything else. So I think it would just be unrealistic advice to say, ‘You can’t use an NSAID,’ especially since it’s over the counter and there’s really no way to stop it.”

That said, it’s best to try other ways of treating pain before opting for an NSAID, Bhatt advised, offering a basic algorithm.

In a patient with osteoarthritis, for example, doctors can try physical therapy or topical creams to combat pain. If medication is required, acetaminophen might be a safer option than NSAIDs. “And in those patients who have to take NSAIDs because there’s nothing else that works for their particular type of pain, try to limit the dose and the quantity and the duration of NSAID use,” he said.

As for selecting among the NSAIDs when one is required, Bhatt said that’s a tricky question, with conflicting results coming from observational studies over the years. “I don’t know that I would necessarily say that this study really points us in one direction or another in terms of which NSAID is safer to use,” he commented. “That remains a very controversial area.”

In an accompanying editorial Juan Badimon, PhD, and Carlos Santos-Gallego, MD (both Icahn School of Medicine at Mount Sinai, New York, NY), say that despite some limitations, “this important study confirms that NSAID use post-MI significantly increased cardiovascular and bleeding risks, expands this fact to the Asian population, and provides information guiding treatment decisions.”

They appear to accept that celecoxib and meloxicam are safer options on the basis of these data, saying “they may deserve a more central place in the anti-inflammatory armamentarium.”

As Badimon and Santos-Gallego conclude: “There is no free lunch in medicine, so if NSAID therapy in patients post-MI is inevitable, we have to understand which price we are paying for pain relief.”

Sources
Disclosures
  • An, Badimon, Choi, Kang, and Santos-Gallego report no relevant conflicts of interest.
  • Bhatt reports receiving research funding or unfunded research support from Abbott, Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Chiesi, Eisai, Ethicon, Forest Laboratories, Idorsia, Ironwood, Ischemix, Lilly, Medtronic, PhaseBio, Pfizer, Regeneron, Roche, Sanofi, Synaptic, The Medicines Company, FlowCo, Merck, Novo Nordisk, PLx Pharma, and Takeda; being a site co-investigator for Biotronik, Boston Scientific, St. Jude Medical, and Svelte; being a trustee for ACC; serving as an advisory board member, director, or chair for Cardax, Elsevier Practice Update Cardiology, Medscape Cardiology, Regado Biosciences; the Boston VA Research Institute, the Society of Cardiovascular Patient Care, TobeSoft; the American Heart Association Quality Oversight Committee; serving on a range of data safety monitoring committees; receiving honoraria for editorial or committee activities for a range of publications and organizations; and receiving royalties from Elsevier.

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