ADAPT-DES: Poor Clopidogrel Response Not Predictive of 1-Year Mortality

MIAMI BEACH, FLA.—Patients found hyporesponsive to clopidogrel after DES implantation are more likely to experience stent thrombosis or MI at 1 year but less likely to have major bleeding events. However, on-treatment clopidogrel hyporesponsiveness appears to have no bearing on 1-year mortality when possible confounders are taken into account, according to findings from the ADAPT-DES registry announced at TCT 2012.

Referring to data presented at TCT 2011 in San Francisco, ADAPT-DES previously demonstrated a strong relationship between platelet responsiveness to clopidogrel, but not aspirin, and subsequent stent thrombosis to 30 days, said principal investigator Gregg W. Stone, MD, of Columbia University Medical Center in New York.

The registry prospectively enrolled an all-comers population of 8,543 patients at 11 sites in the United States and Germany from January 2008 to September 2010. All had successful and uncomplicated PCI with at least 1 noninvestigational DES (64.5% Xience V/Promus; Abbott Vascular/Boston Scientific). Patients then underwent platelet function testing for aspirin and clopidogrel response using the VerifyNow assay (Accumetrics). Overall, 42.7% were found to have high on-clopidogrel platelet reactivity using the cutoff of 208 PRU and 5.6% had poor response to aspirin. Most patients remained on a thienopyridine (79.6%) or aspirin (87.2%) daily through 1 year without any discontinuation.

At 1-year follow-up, there were 74 cases of definite or probable stent thrombosis  in 70 patients (0.84%). Forty of those events (57.1%) occurred within 30 days. Patients with poor clopidogrel response had higher risk of stent thrombosis, MI and mortality but lower risk of major bleeding (see Table).

Multivariable propensity score adjustment, however, attenuated the link between clopidogrel hyporesponsiven ess and 1-year mortality (adjusted HR 1.20; 95% CI 0.85-1.70; P=.30). Additional calculations taking into account time-adjusted adverse events found that MI, definite stent thrombosis, major bleeding and premature cessation of dual antiplatelet therapy within 6 months all increased the risk of death. Importantly, clopidogrel hyporesponsiveness showed no such association, Stone said. “That is because there is an offsetting relationship between the stent thrombosis, MI, and bleeding.”

Good response to aspirin, meanwhile, had no effect on stent thrombosis, MI or all-cause death but did increase the risk of major bleeding, thereby “questioning the utility of aspirin in patients treated with DES,” he said.

Based on the results of ADAPT-DES, Stone concluded, “Overcoming clopidogrel hyporesponsiveness with more potent antiplatelet agents is therefore unlikely to improve survival unless the beneficial effects of reducing stent thrombosis and MI can be uncoupled from the likely increase in bleeding with greater platelet inhibition.”