Extended Dual Antiplatelet Therapy Lowers Death, MI Rates in DES Patients

Patients taking clopidogrel and aspirin 1 to 2 years after drug-eluting stent (DES) implantation have lower long-term rates of death and myocardial infarction (MI) than those who discontinue at 12 or 24 months. The results, published online December 3, 2012, ahead of print in the American Journal of Cardiology, run counter to recent studies showing that a shorter course of dual antiplatelet therapy may be just as safe—and sometimes safer—than a longer duration.

Researchers led by Suresh R. Mulukutla, MD, of the University of Pittsburgh (Pittsburgh, PA), looked at 3,130 patients from the National Heart, Lung, and Blood Institute Dynamic Registry who received at least 1 DES during 2 different time periods (2004 and 2006) and were discharged on dual therapy. In patients analyzed at the 1-year mark (n = 2,157), almost a third (31%; n = 673) had stopped taking clopidogrel. And in patients analyzed at 2 years (n = 1,918), almost half (47%; n = 911) had discontinued the antiplatelet agent.

Overall, 4-year rates of death, MI, repeat revascularization, and stent thrombosis were 9.1%, 7.5%, 18.8%, and 1.4%, respectively. At both the 1- and 2-year landmarks, patients who remained on dual antiplatelet therapy showed lower 4-year rates of death, MI, and repeat revascularization (tables 1 and 2).

Table 1. Four-Year Outcomes by Dual Therapy Status at 1 Year After DES

 

Table 2. Four-Year Outcomes by Dual Therapy Status at 2 Years After DES

Propensity adjustment confirmed the reductions in mortality risk in patients still taking dual antiplatelet therapy at 12 months (HR 0.77; 95% CI 0.57-1.04; P = 0.09) and 2 years (adjusted HR 0.57; 95% CI 0.38-0.87; P = 0.009) compared with patients who had stopped therapy at those time points, although the 1-year reduction missed statistical significance.

Propensity adjusted risk reductions were also shown for the combined endpoint of death or MI in patients still on clopidogrel and aspirin at 1 (HR 0.74; 95% CI 0.57-0.97; P = 0.03) and 2 years (HR 0.64; 95% CI 0.44-0.91; P = 0.01). There were no subgroups in which longer duration of dual therapy was hazardous.

“Our study showed that in patients treated with DES, there was a significant benefit in all-cause mortality and the combined outcome of death and MI associated with continued use of [dual antiplatelet therapy] compared to the discontinuation of [dual therapy] at the 12- and 24-month landmark time points,” the authors conclude.

Duration Debate Has Data on Both Sides

The findings come despite several recent studies such as PRODIGY and EXCELLENT suggesting that shorter dual therapy duration may be safe, if not safer. Still, “[o]ur patient sample is derived from unrestricted DES use and may be more reflective of general clinical practice,” the authors said.

They acknowledge that a possible rationale for extended dual antiplatelet therapy is to prevent stent thrombosis, though no protective effect was observed in the current study despite the reduction in death and MI. However, the authors point out that the study was not powered to detect differences in stent thrombosis given the rarity of the complication.

According to Ajay J. Kirtane, MD, SM, of Columbia University Medical Center (New York, NY), the jury is still out regarding the appropriate length of dual therapy in DES patients. “We just don’t know,” he told TCTMD in a telephone interview. “On the basis of this study or other observational studies, I don’t think we can make recommendations one way or the other.”

Why Ask Why?

Dr. Kirtane noted that a key issue with the current study and similar reports is determining why patients discontinued clopidogrel. “If you were to take two identical patients, one of whom continued and one of whom stopped, both treated by the same doctor, there might be other things that led the doctor to stop treatment that would obviously influence their outcomes,” he said. “Maybe they’re a bleeder, or don’t have insurance so they can’t pay for it, who knows?”

In the study, reasons for discontinuation were available for patients enrolled in 2006. In these patients, discontinuation of clopidogrel was “physician mediated” in about 90%, while noncompliance was the reason in about 5%.

Dr. Kirtane agreed with the authors that prevention of stent thrombosis is probably not the reason for the reductions in death and MI with continued dual therapy given the low rates of the complication in the study. “Even if it’s not driven by stent thrombosis, there could be some plausible explanation, because maybe you’re reducing MIs in other [coronary] distributions in patients who we know have coronary disease because they have a stent,” he said. “So there’s a mechanistic argument, but on the other hand, we all know bleeding causes events as well, and that’s why most people aren’t sure what to do.”

Dr. Kirtane noted that a key drawback of the study is that the stent types used were mostly older DES. “The NHLBI Dynamic Registry does for the most part take into account patients treated with first generation DES,” he said. “They’re recruited before approval of the newer ones, which have data demonstrating you can do shorter duration dual antiplatelet therapy.”

 

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Source:
Mulukutla SR, Marroquin OC, Vlachos HA, et al. Benefit of long-term dual anti-platelet therapy in patients treated with drug-eluting stents: From the NHLBI Dynamic Registry. Am J Cardiol. 2012;Epub ahead of print.

 

 

Related Stories:

• PRODIGY Published: No Advantage to Long-term Clopidogrel
• Long-term Antiplatelet Therapy: All Risk, No Benefit
• Early Discontinuation of DAPT May Increase Risk of Stent Thrombosis