Effect of DAPT on Stent Thrombosis According to DES Type
Effect of DAPT on Stent Thrombosis According to DES Type
Aim. To investigate 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 and Results. Of 8709 patients in PROTECT, 4357 were randomized to E-ZES and 4352 to C-SES. Aspirin was to be given indefinitely, and clopidogrel/ticlopidine for ≥3 months or up to 12 months after implantation. 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. Dual antiplatelet therapy 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). We 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 vs. C-SES (adjusted hazard ratio 0.38, 95% confidence interval 0.19, 0.75; P = 0.0056). In the presence of DAPT, no difference was found (1.18; 0.79, 1.77; P = 0.43).
Conclusion. 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. These results suggest that the incidence of stent thrombosis in DES trials should not be evaluated independently of DAPT use, and the optimal duration of DAPT will likely depend upon stent type (Clinicaltrials.gov number NCT00476957).
The importance of dual antiplatelet therapy (DAPT) to prevent in-stent thrombotic events in patients implanted with a drug-eluting stent (DES) has been widely reported. Interruption of DAPT is also a major independent predictor of stent thrombosis, underscoring the importance of this therapy in the prevention of early and late thrombotic events after deployment of a DES.
The Patient Related OuTcomes with Endeavor vs. Cypher stenting Trial (PROTECT) was designed as a superiority trial comparing the incidence of stent thrombosis in a broad population of patients and involving two widely used DES with different potency profiles and nearly opposite healing characteristics: the Endeavor zotarolimus-eluting stent (E-ZES; Medtronic CardioVascular) and the Cypher sirolimus-eluting stent (C-SES; Cordis, Johnson & Johnson). Both devices prevent the occurrence of restenosis yet have different antiproliferative potencies due to drug, polymer, and drug-release characteristics. Therefore, the key design element of PROTECT was the selection of two DES systems with contrasting site-specific vascular healing responses, with E-ZES more closely mirroring the healing response following bare-metal stent implantation.
In PROTECT, the primary outcome of definite or probable stent thrombosis at 3 years did not differ between E-ZES and C-SES [1.42% (predicted 1.5%) vs. 1.79% (predicted 2.5%); log-rank P = 0.22], respectively. During the period from 1 to 3 years when the use of DAPT was low, however, a significant 0.75% difference emerged in the incidence of stent thrombosis (E-ZES 0.32% vs. C-SES 1.07%; log-rank P < 0.0001). We hypothesized that DAPT use influenced the rate of stent thrombosis to a different extent, depending upon the type of implanted DES.
Abstract and Introduction
Abstract
Aim. To investigate 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 and Results. Of 8709 patients in PROTECT, 4357 were randomized to E-ZES and 4352 to C-SES. Aspirin was to be given indefinitely, and clopidogrel/ticlopidine for ≥3 months or up to 12 months after implantation. 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. Dual antiplatelet therapy 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). We 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 vs. C-SES (adjusted hazard ratio 0.38, 95% confidence interval 0.19, 0.75; P = 0.0056). In the presence of DAPT, no difference was found (1.18; 0.79, 1.77; P = 0.43).
Conclusion. 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. These results suggest that the incidence of stent thrombosis in DES trials should not be evaluated independently of DAPT use, and the optimal duration of DAPT will likely depend upon stent type (Clinicaltrials.gov number NCT00476957).
Introduction
The importance of dual antiplatelet therapy (DAPT) to prevent in-stent thrombotic events in patients implanted with a drug-eluting stent (DES) has been widely reported. Interruption of DAPT is also a major independent predictor of stent thrombosis, underscoring the importance of this therapy in the prevention of early and late thrombotic events after deployment of a DES.
The Patient Related OuTcomes with Endeavor vs. Cypher stenting Trial (PROTECT) was designed as a superiority trial comparing the incidence of stent thrombosis in a broad population of patients and involving two widely used DES with different potency profiles and nearly opposite healing characteristics: the Endeavor zotarolimus-eluting stent (E-ZES; Medtronic CardioVascular) and the Cypher sirolimus-eluting stent (C-SES; Cordis, Johnson & Johnson). Both devices prevent the occurrence of restenosis yet have different antiproliferative potencies due to drug, polymer, and drug-release characteristics. Therefore, the key design element of PROTECT was the selection of two DES systems with contrasting site-specific vascular healing responses, with E-ZES more closely mirroring the healing response following bare-metal stent implantation.
In PROTECT, the primary outcome of definite or probable stent thrombosis at 3 years did not differ between E-ZES and C-SES [1.42% (predicted 1.5%) vs. 1.79% (predicted 2.5%); log-rank P = 0.22], respectively. During the period from 1 to 3 years when the use of DAPT was low, however, a significant 0.75% difference emerged in the incidence of stent thrombosis (E-ZES 0.32% vs. C-SES 1.07%; log-rank P < 0.0001). We hypothesized that DAPT use influenced the rate of stent thrombosis to a different extent, depending upon the type of implanted DES.