Modifying Effect of Dual Antiplatelet Therapy on Incidence of Stent Thrombosis According to Implanted Drug-Eluting Stent Type

Study Questions:

What is the putative modifying effect of dual antiplatelet therapy (DAPT) use on the incidence of stent thrombosis at 3 years in patients randomized to Endeavor zotarolimus-eluting stent (E-ZES) or Cypher sirolimus-eluting stent (C-SES)?

Methods:

Of 8,709 patients in the PROTECT study, 4,357 were randomized to E-ZES and 4,352 to C-SES. Aspirin was to be given indefinitely, and clopidogrel/ticlopidine was to be given for ≥3 months or up to 12 months after implantation. The main outcome measures were definite or probable stent thrombosis at 3 years. Multivariable Cox regression analysis was applied, with stent type, DAPT, and their interaction as the main outcome determinants.

Results:

DAPT adherence remained the same in the E-ZES and C-SES groups (79.6% at 1 year, 32.8% at 2 years, and 21.6% at 3 years). The investigators observed a statistically significant (p = 0.0052) heterogeneity in treatment effect of stent type in relation to DAPT. In the absence of DAPT, stent thrombosis was lower with E-ZES versus C-SES (adjusted hazard ratio [HR], 0.38; 95% confidence interval [CI], 0.19-0.75; p = 0.0056). In the presence of DAPT, no difference was found (adjusted HR, 1.18; 95% CI, 0.79-1.77; p = 0.43).

Conclusions:

The authors concluded that a strong interaction was observed between drug-eluting stent type and DAPT use, most likely prompted by the vascular healing response induced by the implanted DES system.

Perspective:

These data from the PROTECT trial suggest that adherence to DAPT modifies the outcome of stent thrombosis to a greater extent after C-SES deployment than after E-ZES deployment, most likely due to differential healing characteristics. These findings suggest that DAPT use should be taken into consideration when interpreting the incidence of stent thrombosis in studies evaluating different DES. The results of the Dual Antiplatelet Therapy Study, if analyzed according to stent type, may help elucidate whether conceptual technological modifications in stent design have translated into a long-term decrease of thrombotic events. It is quite possible that in the future, the optimal duration of DAPT will depend upon stent type.

Clinical Topics: Invasive Cardiovascular Angiography and Intervention

Keywords: Outcome Assessment (Health Care), Thrombosis, Drug-Eluting Stents, Ticlopidine, Sirolimus, Stents


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