Landmark Analyses Show Downside of Prolonged Antiplatelet Therapy

PARIS, France—After implantation of drug-eluting stents (DES), prolonging antiplatelet therapy beyond 4 months does not reduce ischemic events but does significantly increase bleeding. However, discontinuing dual antiplatelet therapy—but not a thienopyridine alone—is associated with an increased risk of adverse outcomes.

Tomohisa Tada, MD, of Kyoto University Hospital (Kyoto, Japan) presented the registry findings August 29, at the European Society of Cardiology Congress 2011.

Investigators looked at 6,802 patients from the CREDO-Kyoto PCI/CABG Registry Cohort-2 who received at least 1 DES, performing landmark analyses at 4 and 13 months.

Start Counting at 4 Months

In the 4-month cohort, 871 of 6,309 evaluable (13.8%) patients were no longer taking a thienopyridine. They differed in many ways from those who continued on the antiplatelet agents. For example, they were less likely to have prior MI or stroke or to have been treated for left main disease or chronic total occlusion. In addition, they were more likely to have taken ticlopidine as their original thienopyridine therapy (94% vs. 88%; P < 0.0001) and less likely to have taken clopidogrel (6.0% vs. 12%; P < 0.0001).

By 4 months, 14.0% of patients had discontinued clopidogrel; by 13 months, 30.8% had stopped; and by 3 years, 43.7% were no longer taking the antiplatelet agent.

Between 4 months and 1 year, the cumulative event rates for the primary efficacy outcome of death, MI, or stroke were virtually identical between those who were or were not on a thienopyridine. However, GUSTO moderate or severe bleeding, the primary safety endpoint, was substantially increased in those who were still using a thienopyridine (table 1).

Table 1. Adjusted Outcomes: 4-Month Landmark Analysis


On Thienopyridine
(n = 5,438)

Not on Thienopyridine
(n = 871)

P Value

Death, MI, Stroke








In addition, rates of gastrointestinal bleeding and TVR were higher among those taking a thienopyridine (1.8% vs. 0.6%; P = 0.02 and 14% vs. 11%; P = 0.008, respectively).

Unlucky 13 

In the 13-month landmark analysis 4,195 of 5,941 evaluable patients (71%) were still on dual antiplatelet therapy. Again, there were multiple clinical and angiographic differences between those who were or were not on a thienopyridine. The pattern of use of ticlopidine vs. clopidogrel between the 2 groups was also similar.

As in the 4-month analysis, patients who remained on a thienopyridine at 13 months had similar rates of the primary endpoint and increased bleeding compared with those who were no longer on such therapy (table 2).

Table 2. Adjusted Outcomes: 13-Month Landmark Analysis


On Thienopyridine
(n = 4,098)

Not on Thienopyridine
(n = 1,803)

P Value

Death, MI, Stroke








In addition, patients remaining on a thienopyridine had more strokes (2.8% vs. 2.4%; P = 0.007).

Patients who discontinued both aspirin and a thienopyridine at any time point up to 1 year had a higher incidence of the primary endpoint (eg, discontinuation between 31 and 120 days after implantation yielded a primary endpoint rate of 7.70% vs. 1.4% for those who did not stop dual therapy; P < 0.0001). Interestingly, however, those who stopped thienopyridine therapy alone did not increase their risk of ischemic events, suggesting that aspirin continued to provide protection.

Dr. Tada acknowledged certain limitations of the study, including the fact that decisions about the duration of clopidogrel therapy were left to the discretion of individual physicians, opening the analysis to unmeasured confounders. In addition, the landmark analyses may have underestimated the impact of thienopyridines by excluding events that occurred before the landmark time point. In addition, the 4-month analysis included a small number of patients who had discontinued a thienopyridine before the 4-month landmark, as well as a relatively large number of patients who discontinued a thienopyridine after the 4 months.

Nevertheless, “prolonged thienopyridine therapy after DES implantation either beyond 4 months or 13 months appeared not to be associated with risk reduction for serious cardiovascular events (death/MI/stroke), while it was associated with increased risk of bleeding,” he concluded.


Tada T. Long-term clinical outcomes and duration of dual antiplatelet therapy after drug-eluting stent implantation: Landmark analyses from CREDO-Kyoto Cohort-2 registry. Presented at: European Society of Cardiology Congress; August 29, 2011; Paris, France.



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  • Dr. Tada reports no relevant conflicts of interest.

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