Stent thrombosis relationship to discontinuation of antiplatelet therapy

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Incidence of premature discontinuation of antiplatelet therapy

In a prospective study analyzing 1622 patients who received at least one DES, 14.4% discontinued at least 1 antiplatelet drug, predominantly clopidogrel with an incidence of 11.8% for at least five consecutive days during the first year post-implantation.

Predictors of premature discontinuation of antiplatelet therapy

According to a prospective study analyzing 1622 patients, the following observations were made as the reason for discontinuation of one or both antiplatelet therapy:

• Bleeding events or invasive procedures:
  • Nearly 50% patients had interventions or minor bleeding that did not require discontinuation.
  • In patients who discontinued due to bleeding events/invasive procedures, predictors included renal impairment, prior major hemorrhage, or peripheral artery disease

• Medical decisions: 32% patients were either undergoing procedures in a private hospital or did not receive instructions in whom medical decision was the cause.

• Patient decision: 18% patients stopped antiplatelet therapy on their own accord or were on psychotropic drugs.

According to the results evaluated in the PREMIER registry of MI patients, predictors of premature thienopyridine discontinuation included:

• Older age,
• Lower level of education,
• Avoidance of healthcare because of cost,
• Unmarried,
• Anemia,
• Preexisting cardiovascular disease,
• Absence of discharge instructions about the medication, and
• Lack of referral to a cardiac rehabilitation program.

Risk associated with premature discontinuation of antiplatelet therapy

In patients with DES , the most important risk factor for late ST (>30days to 1year) was premature cessation (less than 6 months) of antiplatelet therapy.

Clinical trial data:

• In a prospective observational cohort study followed for 18 months analyzing 3021 patients, thienopyridine was discontinued during the first six months which was the major determinant of ST(hazard ratio 13.7). However there is insufficient information available on the benefit of continuing thienopyridine beyond 6 months.

• From a total cohort of 2974 consecutive patients treated with DES, 38 patients presented with angiographic evidence of ST. Acute ST occurred in 5 patients, subacute ST in 25 patients and late ST in 8 patients. Individuals who discontinued clopidogrel more likely had late ST (36.8% versus 10.7% percent in those without stent thrombosis). The mean duration between cessation of clopidogrel and stent thrombosis was 153 days.

• Drug-eluting stents significantly reduce restenosis, but require 3 to 6 months of thienopyridine therapy to prevent stent thrombosis. The rate and consequences of prematurely discontinuing thienopyridine therapy were also evaluated in the PREMIER registry of MI patients. Almost 14% MI patients treated with DES discontinued thienopyridine therapy at 30 days. Those who discontinued medication were more likely to die during the next 11 months (7.5% versus 0.7%).

• In the aggregate the above studies suggest that thienopyridine therapy for at least six months, in addition to aspirin, reduces the likelihood of ST during the first year after DES placement. However, these studies do not inform us as to the optimal time to stop thienopyridine. It is possible that the benefit of dual antiplatelet therapy, particularly considering the bleeding risk, may become small after six months. In the absence of better evidence, however, we recommend dual antiplatelet therapy for at least one year after DES.