Prior chronic clopidogrel therapy is associated with increased adverse events and early stent thrombosis: Are patients better off without clopidogrel?

Clopidogrel is indicated for treatment of patients with atherothrombotic disease. However, clopidogrel seems to be associated with higher rates of post PCI (percutaneous coronary intervention) complications, stent thromboses, death and heart attacks in several trials. Study results have shown that up to 40% of patients with an acute coronary syndrome are non-responsive to clopidogrel and may experience major adverse cardiovascular events.

Therefore, are certain patients better off without clopidogrel? To answer this question, a recent study in Thrombosis and Haemostasis found that patients sustaining an acute coronary syndrome while on chronic clopidogrel treatment are at higher risk for in-hospital and 30-day adverse outcomes and a more than 2-fold increase of stent thrombosis than treatment-naïve patients.

5,386 patients were followed for 30 days

Study investigator Elad Asher, M.D, M.H.A, Leviev Heart Center, Sheba Medical Center, Tel Hashomer, Israel, explained that "our aim was to determine whether patients sustaining an acute coronary syndrome while on chronic clopidogrel therapy have a worse prognosis than clopidogrel-naïve patients." For this reason, 5,386 patients suffering from acute coronary syndromes - 12.6% of whom had been treated with clopidogrel prior to the index event - were followed for 30 days.

In Asher's trial, patients receiving chronic clopidogrel therapy had a worse prognosis and a higher rate of stent thrombosis. The study results showed that chronic clopidogrel treatment was associated with worse major adverse cardiovascular events, defined as death, recurrent acute coronary syndrome, stroke and/or stent thrombosis. Prior clopidogrel therapy was associated with a higher risk of in-hospital and 30-day adverse outcomes, including stent thromboses.

monitor patients on chronic clopidogrel treatment

The authors suggest that clopidogrel failure is more than just a marker for higher-risk patients, but is also associated with pharmacologic resistance to its antiplatelet effect. Chronic clopidogrel treatment failure may also be of prognostic significance, and physicians should consider this when choosing an anti-aggregation treatment. Thus, Asher urges that cardiologists and primary care physicians should closely monitor patients on chronic clopidogrel treatment. "We think that 'prior aspirin or clopidogrel treatment' as a risk factor might replace the classical 'prior aspirin treatment' risk factor in the TIMI risk score."

Nonetheless, further studies are needed to examine the long-term major adverse cardiovascular events of these patients and whether newer P2Y12 inhibitors would be more beneficial in this group of high-risk patients. This issue needs to be further investigated in large randomised control trials. Especially since the current study is subject to limitations due to its observational non-randomised design and the duration of the follow-up period. Moreover, the type of acute coronary syndrome (STEMI versus unstable angina/NSTEMI) has different effects on short- and long-term prognosis, and the recent study results regarding clinical outcomes can be applied only to short-term prognosis. Because pre-treated patients often received clopidogrel plus aspirin, it might be possible that an aspirin-clopidogrel interaction - rather than clopidogrel alone - may have influenced outcomes.

Werner Zwick, M.A., Munich, Germany

Asher E et al.: Opens external link in new windowPrior Chronic Clopidogrel Therapy is Associated with Increased Adverse Events and Early Stent Thrombosis. Thromb Haemost 2016; 115: 433-438.

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