麻豆传媒

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CHICAGO -- Extending dual antiplatelet therapy for as long as 30 months after implantation of a drug-eluting stent (DES) reduced the risk of both stent thrombosis and myocardial infarction in native arteries compared with aspirin therapy alone.

Continued dual antiplatelet therapy was associated with a stent thrombosis rate of 0.4% versus 1.4% among patients who took aspirin alone for an extended period (hazard ratio 0.29, 95% CI 0.17-0.48, P<0.001), reported and colleagues online in the .

The rate of major adverse cardiovascular events -- myocardial infarction (MI) and stroke -- was also significantly reduced (4.3% versus 5.9%, HR 0.71, 95% CI 0.59-0.85, P<0.001).

Likewise the rate of MI was 2.1% versus 4.1% (HR 0.47, P<0.001) and the rate of death from any cause was borderline significant, 2.0% versus 1.5% (P=0.05).

All 9,961 patients in the Dual Antiplatelet Therapy (DAPT) trial had dual antiplatelet therapy with clopidogrel (Plavix) or prasugrel (Effient) plus aspirin for 12 months, and were then randomized to either a continuation of a dual antiplatelet regimen or to aspirin plus placebo for another 18 months.

The dual antiplatelet therapy was stopped at 30 months and patients were observed for another 3 months.

The DAPT results were also reported here as a late-breaking clinical trial at the American Heart Association Scientific Sessions.

That finding from the DAPT study was reassuring to cardiologists like , of Northwestern University in Chicago, because he has been routinely keeping patients on dual antiplatelet therapy for at least 12 months. He said he now feels confident in maintaining that regimen for longer periods.

Bonow, who is a former president of the American Heart Association, said that it was clear that discontinuation of thienopyridine "at any point does increase the risk of stent thrombosis for about 3 months," which is also a factor in guiding clinical decisions.

He told 麻豆传媒 that one worrisome sign was bleeding -- there were more bleeding events among patients maintained on dual antiplatelet therapy, "but these were not big bleeds and the overall risk was small." The rate of moderate or severe bleeding was 2.5% among patients in the dual antiplatelet group versus 1.6% in the control group (P=0.001).

The angst surrounding dual antiplatelet therapy has waxed and waned but never disappeared since the introduction of DES complicated what was once a simple issue: put in a bare metal stent and put the patient on dual antiplatelet therapy for 30 days, which was considered ample time for the stent to fully endothelialize.

DES, armed as they are with drugs specifically chosen for their anti-proliferative properties, complicated things. The first DES -- -- eluted sirolimus, and when first approved, the recommendation was for 3 months of dual antiplatelet therapy to follow implantation.

Cypher was followed by the paclitaxel-eluting stent, and the recommendation with it was for 6 months of dual antiplatelet therapy.

Those simple recommendations were upended in 2006, when a series of studies suggested that DES carried a very real risk of a catastrophic event in the form of very late stent thrombosis.

Those reports triggered 2 days of contentious public hearings by the FDA, which stopped short of mandating extended dual antiplatelet therapy, but made strong recommendations, and eventually guidelines were changed.

That begs the question: is the best way to reduce the risk of stent thrombosis, especially late stent thrombosis, to turn back the clock to the era of bare metal stents? That question was not, however, answered by the DAPT study.

Study Details

The average age of patients in the DAPT study was 61 and about a quarter of the patients were women. More than 90% of participants were white.

About one in 10 patients had stents placed following ST-elevation MI and roughly 15% had non-STEMI. About 17% of patients had unstable angina, whereas 38% had stable angina. Half of the patients had at least one risk factor for stent thrombosis. Patients were enrolled within 72 hours of percutaneous coronary intervention.

Unlike many large trials, most of the patients in DAPT were enrolled at centers in North America, with only 8% recruited at European centers and less than 3% were from Australia or New Zealand.

Clopidogrel was the thienopyridine used by most patients (65%).

A variety of DES were used: 47% to 48% received everolimus-eluting stents, 27% paclitaxel-eluting, 13% zotarolimus-eluting, and about 11% sirolimus-eluting stents.

Roughly half of the lesions were less than 3 mm, and most patients had one to two stents placed. The most common location for stented lesions was the left anterior descending artery (40%) followed by the right coronary artery (33%).

Mauri and colleagues concluded, that "among patients treated with drug-eluting stents, continuation of thienopyridine-plus-aspirin therapy, as compared with aspirin therapy alone, beyond 1 year reduced the risk of ischemic events."

How Long Should DAPT Continue?

In an accompanying editorial, Antonio Colombo, MD, and Alaide Chieffo, MD, of and EMO GVM Columbus Hospital in Milan, were less sanguine. They concluded that the "key message of the DAPT study is the suggestion that some patients who have been treated with a drug-eluting stent may benefit from extending dual antiplatelet therapy beyond 1 year, but also that the potential harm with this approach should not be overlooked."

Thus the study, Colombo and Chieffo contended, did not offer the definitive answer to the question: How long should dual antiplatelet therapy continue?

"The safest and most effective duration of dual antiplatelet therapy therefore remains uncertain and must be individualized for each patient," they wrote.

Meta-Analysis

Also published online today, a meta-analysis in , which had Mauri as a co-author, assessed outcomes for 69,644 patients from 14 trials that tested varying durations of dual antiplatelet therapy.

"Compared with aspirin alone or short duration antiplatelet therapy (≤6 months), continued treatment was not associated with a difference in all-cause mortality (HR 1.05, 95% credible interval 0.96-1.19, P=0.33)." They also detected no difference in either cardiovascular mortality or noncardiovascular mortality based on duration of dual antiplatelet therapy.

In a commentary in The Lancet, Giles Lemesle, MD, of the Hopital Cardiologique, Centre Hospitalier Regional et Universitaire de Lille in France, concluded that dual antiplatelet therapy proves one-size does not fit all stent patients, but he found three take-aways from the meta-analysis:

• Dual antiplatelet therapy does reduce the risk of ischemic events, but at the price of increased bleeding.
• Don't rush a decision about duration of therapy, but rather assess the patient at specified time points, say 6 and 12 months, to determine whether or not to continue dual antiplatelet therapy.
• The DAPT trial did not answer lingering questions about the risk of noncardiac mortality with long-term dual antiplatelet therapy.

From the American Heart Association: