Risk of NSAID Use in Patients Receiving Antithrombotic Therapy After Myocardial Infarction

By Harold L. Karpman, MD, FACC, FACP

Clinical Professor of Medicine, UCLA School of Medicine

Dr. Karpman reports no financial relationships related to this field of study.

SYNOPSIS: Among patients receiving antithrombotic therapy after MI, the use of NSAIDs was associated with increased risk of bleeding and excess thrombotic events, even after short-term treatment.

SOURCE: Schjerning Olsen AM, et al. Association of NSAID use with risk of bleeding and cardiovascular events in patients receiving antithrombotic therapy after myocardial infarction. JAMA 2015;313:805-814.

Numerous published studies have demonstrated an increased risk of thrombotic cardiovascular events associated with the use of anti-inflammatory drugs (NSAIDs).^1-3 Current guidelines discourage the use of NSAIDs in patients with cardiovascular disease,4 yet up to 44% of patients with a history of myocardial infarction (MI) are treated with these agents5,6 for a variety of clinical conditions. Current management guidelines also advise that all patients with MI should be prescribed dual antithrombotic therapy (aspirin and clopridogel) for up to 12 months, and since a substantial proportion of patients have additional indications for oral anticoagulants, adding NSAIDs to the treatment regimen may further increase bleeding risks in these patients and may also increase the risk of recurrent cardiovascular events. As a result, Olson and her associates⁷ mounted a prospective study to investigate the association of the concomitant use of NSAIDs with risk of bleeding and cardiovascular events in patients receiving antithrombotic treatment after suffering a MI.

A total of 61,971 patients who suffered a first MI in Denmark between 2002 and 2011 and who filled at least one NSAID prescription were included in this study. The number of deaths during a median follow-up of 3.5 years was 18,105 (29.2%). In addition, a total of 5288 bleeding events (8.5%) and 18,568 cardiovascular events (30%) also occurred. Bleeding events occurred in 4.2% of those patients receiving concomitant NSAID therapy and in only 2.2% of those patients not receiving NSAID therapy. The authors concluded that an increased risk of bleeding and cardiovascular events occured with concomitant use of NSAID therapy regardless of the type of antithrombotic treatment administered, the type of NSAID utilized, and/or the duration of NSAID use.

COMMENTARY

In this Danish nationwide study, the concomitant use of NSAIDs was associated with an increased risk of bleeding in patients who had experienced a first MI and were also being treated with antithrombotic drugs. The study facilitators observed an increased risk regardless of which antithrombotic drugs were used. The results of the Olson study⁷ support the guideline recommendations from the American Heart Association⁴ as well as published European guidelines.⁶ It is important to point out that the Olson study results are limited because of its observational design, and because only prescription data were utilized in reaching its conclusions. Therefore, one cannot avoid the uncertainty that exists about patient adherence to treatment recommendations in the individual patient, which obviously is important since the definition of NSAID therapy in this study was based only on prescription data. However, despite these limitations, it is important to recognize that in patients receiving antithrombotic therapy after MI, there is likely a significantly increased risk of bleeding and excess thrombotic events when NSAIDs are used, even after short-term treatment with these anti-inflammatory drugs.

In conclusion, clinicians should be aware of the increased risks of bleeding and/or thrombosis when using NSAIDs in patients following an acute or recent myocardial infarction. Physicians obviously need a properly controlled prospective research study not dependent only on prescription data to answer the important question about whether it is safe to prescribe NSAIDs to patients who recently have suffered a myocardial infarction.

REFERENCES

1. Brophy JM, et al. The coronary risk of cyclo-oxygenase-2 inhibitors in patients with a previous myocardial infarction. Heart 2007;93:189-194.
2. Gislason GH, et al. Risk of death or reinfarction associated with the use of selective cyclooxygenase-2 inhibitors and nonselective nonsteroidal anti-inflammatory drugs after acute myocardial infarction. Circulation 2006;113:2906-2913.
3. McGettigan P, Henry D. Cardiovascular risk with nonsteroidal anti-inflammatory drugs: Systematic review of population-based controlled observational studies. PLoS Med 2011;8:e1001098.
4. Antman EM, et al. Use of nonsteroidal anti-inflammatory drugs: An update for clinicians: A scientific statement from the American Heart Association. Circulation 2007;115:1634-1642.
5. Schjerning Olsen AM, et al. Duration of treatment with nonsteroidal anti-inflammatory drugs and impact on risk of death and recurrent myocardial infarction in patients with prior myocardial infarction: A nationwide cohort study. Circulation 2011;123:2226-2235.
6. European Medicines Agency. PRAC Recommends the Same Cardiovascular Precautions for Diclofenac as for Selective COX-2 inhibitors. Available at: http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/news/2013/06/news_detail_001816.jsp&mid=WC0b01ac058004d5c1. Accessed January 28, 2015.
7. Schjerning Olsen AM, et al. Association of NSAID use with risk of bleeding and cardiovascular events in patients receiving antithrombotic therapy after myocardial infarction. JAMA 2015;313:805-814.