Aspirin + clopidogrel therapy: how does your care compare to the evidence? Did you know that patients with drug-eluting stents should receive dual therapy for at least a year, and that dual therapy for stroke prevention may put patients at risk?

Journal of Family Practice, Jan, 2008 by B. Brent Simmons, Brooke E. Salzman

Practice recommendations

* Patients with drug-eluting stents should receive dual therapy (aspirin clopidogrel) for at least 12 months (B).

* For patients who have had an ischemic stroke or transient ischemic attack, adding aspirin to clopidogrel increases the risk of hemorrhage and is not routinely recommended (A).

* Adding clopidogrel to aspirin is not more effective than aspirin alone in the primary prevention of coronary artery disease in patients with multiple risk factors. In fact, it may actually cause harm in patients without established cardiovascular disease (B).

Strength of recommendation (SOR)

A Good-quality patient-oriented evidence

B Inconsistent or limited-quality patient-oriented evidence

C Consensus, usual practice, opinion, disease-oriented evidence, case series

Jessica is 72 years old and a new patient of yours, having recently moved to the area. She has a history of non-ST elevation myocardial infarction (NSTEMI) 8 months ago, hypertension, and hyperlipidemia. Her NSTEMI did not require stent placement. Upon reviewing her medications, you see she is taking aspirin 81 mg, clopidogrel 75 mg, simvastatin 80 mg, and metoprolol XL 100 mg. The patient isn't sure how long she has been on clopidogrel and wants to know if she still needs to take it because she has a high co-pay.

What would you tell her?

John is a 60-year-old patient of yours with a history of coronary artery disease, who had an elective catheterization 18 months ago at which time a sirolimus drug-eluting stent was placed. Also at that time, he was placed on aspirin 325 mg daily and clopidogrel 75 mg daily. The patient says he has a friend at work who also has a coronary stent, but his friend stopped taking clopidogre112 months after his stent was placed. The patient wants to know why he is still taking clopidogrel and when he can stop it.

What would you tell him?

Anna is a 68-year-old patient of yours who has uncontrolled type 2 diabetes. She still smokes a pack a day, as she has done for the last 53 years, her BMI is 43, and her LDL is 103 on 80 mg of simvastatin. Her additional meds include lisinopril, 70/30 insulin, and a daily aspirin. Despite her inability to quit smoking or lose weight, she is compliant with her medications. You are both very concerned about her future risk of cardiovascular disease. You consider whether she would benefit from adding clopidogrel to aspirin in order to prevent future coronary events.

Do you write a prescription for clopidogrel, 75 mg/day?

In your conversation with Jessica, you should have told her that she needs to take the clopidogrel for another 4 months (making it 1 year of therapy following her NSTEMI). 2007 guidelines from the American Heart Association and the American College of Cardiology support this approach.

In your discussion with John, you should have told him that for drug-eluting stents, recent studies have shown an additional benefit to continuing dual therapy longer than 1 year, and that consideration should be given to continuing clopidogrel indefinitely. (1,2)

In the case of Anna, your patient with multiple atherothrombotic risk factors, you should have opted against writing her a prescription for clopidogrel. The evidence suggests that putting her on clopidogrel might actually increase her risk of cardiovascular death. (3)

These 3 cases demonstrate how much our understanding of dual antiplatelet therapy (aspirin clopidogrel) has evolved over the past few years--and even months. Given the volume of information we must sift through daily, it is easy to occasionally miss a study or update. The result? You may be underutilizing combination antiplatelet therapy when treatment is indicated. Or, you may be combining aspirin and clopidogrel in situations where there is insufficient data to support its use--and possibly, in situations where it is associated with an increased incidence of adverse events.

This review can help.

Here we have summarized the latest trials and recommendations on dual antiplatelet therapy as they pertain to:

* acute coronary syndrome (ACS)

* coronary stents

* stroke

* the primary prevention and secondary prevention of distant cardiovascular events.

Should you need a quick reference tool for your office, we have also included an at-a-glance summary of current recommendations (TABLE).

* Dual therapy reduces future MI risk in ACS

The Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) trial in 2001 was one of the first combination trials published; it looked at combination antiplatelet therapy in ACS. (4) CURE enrolled patients with NSTEMI and randomized them to receive aspirin plus clopidogrel or aspirin plus placebo for 3 to 12 months. Out of the total number of patients, 9.3% of the dual therapy group reached the endpoint of cardiovascular death, MI, or stroke, compared with 11.4% of the aspirin-only group (relative risk [RR]=0.80 for dual therapy). Further, the rate of each component of the composite outcome tended to be lower in the combination-therapy group.

In particular, there was an RR of 0.77 for MI and, more specifically, an RR of 0.60 for Q-wave MI in the dual therapy group. There was, however, a 1.38 RR for major bleeding (defined as bleeding resulting in disability, vision loss, or transfusion of at least 2 units of blood) in the combination-therapy group vs the aspirin-only group (3.7% to 2.7%). However, neither rates of life-threatening bleeding nor hemorrhagic stroke were significantly different between the 2 groups.