Even short-term treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen increases the risk of bleeding in patients taking anti-clotting drugs after a heart attack, a study published in JAMA suggests.

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The risk of bleeding doubled even with just a few days of NSAID use by patients on anti-clotting drugs after a heart attack.

All patients who have had a myocardial infarction (MI) are recommended to take two antithrombotic drugs (aspirin and clopidogrel) as preventive treatment for up to a year after the heart attack, and to continue taking one of the anti-clotting pills thereafter.

Risk of bleeding is known to be increased by then adding the use of NSAIDs, and some – ibuprofen, for example – have a counter effect to the preventive heart drugs, inhibiting the antithrombotic effects of aspirin.

Guidelines from the American Heart Association, therefore, recommend against the use of NSAIDs in people with established heart disease.

However, in this study – led by Dr. Anne-Marie Schjerning Olsen from the Copenhagen University Hospital Gentofte, in Hellerup, Denmark – 34% of the 61,971 patients, all of whom had survived an MI, filled at least one prescription for an NSAID.

The study results “suggest that no safe treatment period exists.” The authors add:

Fewer than 3 days of NSAID use, together with dual antiplatelet therapy, was associated with a marked increase in the risk of bleeding.”

“These risks are of considerable public health concern, given the widespread use of NSAIDs,” the authors say.

Dr. Schjerning Olsen and her colleagues used nationwide administrative registries in Denmark for the years 2002 to 2011 to analyze patients aged 30 years or older admitted with a first-time heart attack and who were alive 30 days after discharge from hospital.

They determined subsequent treatment with aspirin, clopidogrel or other oral anticoagulants and their combinations, as well as ongoing concomitant NSAID use.

Compared with not having NSAID treatment, using the drugs – such as ibuprofen, diclofenac and naproxen – resulted in just over twice the risk of bleeding.

This extra risk was regardless of the antithrombotic treatment or type of NSAID used, and regardless of the duration of use. The risk of cardiovascular events was also increased.

Over a median follow-up of 3.5 years, the number of deaths was 18,105 (29%). There was a total of 5,288 bleeding events (9% – 799 of which were fatal) and 18,568 cardiovascular events (30%).

The rate of bleeding in every 100 person-years was 4.2 events when patients had concomitant NSAID treatment, and 2.2 events without, which equated to an adjusted increased risk of 2.02 times.

A bleeding event was defined as hospital admission or death from a diagnosis of:

  • Intracranial bleeding
  • Gastrointestinal bleeding – bleeding ulcer, hematemesis (vomiting blood), melena (passing black, tarry stools), and “unspecified”
  • Bleeding from the respiratory or urinary tract
  • Anemia caused by bleeding.

The rate in every 100 person-years of cardiovascular events was 11.2 events for people with ongoing NSAID treatment, compared with 8.3 events for those without NSAID treatment, which equated to an adjusted figure of 1.4 times increased risk. Cardiovascular events were:

  • Cardiovascular death
  • Non-fatal recurrent heart attack
  • Ischemic stroke (caused by a blocked artery to the brain)
  • Transient ischemic attack (mini-stroke)
  • Systemic arterial emboli (clots that travel to distant arteries).

The authors conclude: “More research is needed to confirm these findings; however, physicians should exercise appropriate caution when prescribing NSAIDs for patients who have recently experienced MI.”

Fast facts about NSAIDs
  • At low doses, NSAIDs work as painkillers, and reduce inflammation at higher doses
  • Side effects associated with NSAIDs include dyspepsia, stomach ulcers and anemia
  • Over-the-counter NSAIDs should not be added to prescribed ones.

Learn more about NSAIDs

An editorial article giving comment on the study says the danger of NSAID use alongside antiplatelet therapies may be even greater in many countries such as the US.

The study tracked the risks from NSAIDs given by prescription, but the drugs “are widely available as over-the-counter medications, and physicians may be unaware whether their patients are taking NSAIDs,” the editorial notes.

While there are limitations to the study noted by both its authors and the commentators, the editorial article points to evidence that will be reported in the coming year from a large prospective, randomized study examining the cardiovascular safety of NSAIDs.

“However, until the results from PRECISION are available,” says the article, “practitioners would do well to advise patients with cardiovascular disease against all NSAID use (except low-dose aspirin), especially patients with a recent acute coronary syndrome.”