New Studies Support Dropping Long-term Aspirin After Stenting

March 28, 2019

NEW ORLEANS — Two new studies from Asia provide more evidence that extended monotherapy with clopidogrel (Plavix, Sanofi) or another P2Y12 inhibitor antiplatelet, rather than either dual antiplatelet therapy with aspirin plus a P2Y12 inhibitor or aspirin alone, may be the preferred strategy after placement of a drug-eluting stent in patients with heart disease.

In the Japanese STOPDAPT-2 study, 1-month dual antiplatelet therapy followed by clopidogrel monotherapy provided a net clinical benefit with respect to ischemic and bleeding events compared with 12-month dual antiplatelet therapy with aspirin and clopidogrel after implantation of cobalt-chromium everolimus-eluting stents. The benefit was driven by a significant reduction in bleeding events without an increase in ischemic events.

And in the Korean SMART-CHOICE study, extended P2Y12 inhibitor monotherapy after 3-month dual antiplatelet therapy was noninferior to 12-month dual antiplatelet therapy in terms of ischemic events at 12 months, and it was associated with less bleeding.

Both studies were presented at the recent American College of Cardiology 68th Annual Scientific Session (ACC) 2019.

"Both these trials are very interesting, but neither is definitive," Martin Leon, MD, New York–Presbyterian/Columbia University Irving Medical Center, co-chair of the late-breaking clinical trial session at which the two studies were reported, commented to theheart.org | Medscape Cardiology.

"The trend towards monotherapy with a P2Y12 inhibitor is fascinating, and we are getting closer to believing that this may become a definitive therapy," he added. "But I do not think either of these current trials or even the combination of them both together gives us enough evidence for us to say that this should be current clinical practice at present. However, this is a very important trend, and I would not be surprised if in the next 3 to 5 years this does become the more standard therapy to use with a broad range of drug-eluting stents."

Leon noted that these are two of the largest trials so far of the strategy of replacing long-term aspirin monotherapy with long-term P2Y12 inhibitor monotherapy after a short period of dual antiplatelet therapy. But he said the generalizability of the results is questionable.

He explained that these studies included intravascular imaging, which is standard practice in Japan and Korea. "When this is incorporated into the study, it is often possible to make better decisions about whether to implant a stent and how large the stent should be — and this can lead to lower events rates," Leon said. "This affects the power of the study — both these studies had low event rates — and it can also neutralize the benefits of pharmacotherapy."

During the panel discussion of the study, Jeffrey Berger, MD, New York University Langone Health, New York City, pointed out that the thrombotic risk of the patients included in these two studies was lower than would be expected in patients in the United States who undergo stenting. "For this reason, the potential ramification of stopping aspirin in a higher-risk population cannot be understood from these data," he said.

"Dropping aspirin has been under discussion for the last few years, and interest in this idea is increasing," Berger commented to theheart.org | Medscape Cardiology. "Now these two studies together with some previous data suggest that dropping aspirin is potentially a very smart strategy in certain individuals. There are further studies underway — including some from the US — and I think we need to wait for those to know more."

STOPDAPT-2

The STOPDAPT-2 study was presented by Hirotoshi Watanabe, MD, Kyoto University Graduate School of Medicine, Japan.

The study included 3009 patients who received a drug-eluting stent at 89 centers in Japan. Of these, 38% had acute coronary syndrome. They were randomly assigned to receive either standard dual antiplatelet therapy for 1 year or dual antiplatelet therapy for the first month followed by clopidogrel alone after that.

The primary endpoint — a composite of cardiovascular death, myocardial infarction (MI), definite stent thrombosis, stroke, or TIMI (thrombolysis in myocardial infarction) major/minor bleeding at 12 months — occurred in 2.4% of the patients who stopped taking aspirin after 1 month compared with 3.7% of those who took dual antiplatelet therapy for the whole year (hazard ratio [HR], 0.64; 95% confidence interval [CI], 0.42 – 0.98; P = .04).

The key ischemic endpoint — the rate of cardiovascular death, MI, definite stent thrombosis, and stroke — was similar in the two groups: 2.0% in the group that stopped taking aspirin after 1 month vs 2.5% in those who received dual antiplatelet therapy for a year (HR, 0.79; 95% CI, 0.49 – 1.29).

TIMI major/minor bleeding occurred in 0.4% of those who stopped taking aspirin after 1 month, vs 1.5% of those taking dual antiplatelet therapy for the year (HR, 0.26; 95% CI, 0.11 – 0.64; P = .004).

"According to our findings, 1-month dual antiplatelet therapy followed by clopidogrel monotherapy could be a good option after drug-eluting stent implantation with an advantage of fewer bleeding events," Watanabe concluded.

SMARTCHOICE

The SMARTCHOICE trial was presented by Joo-Yong Hahn, MD, Sungkyunkwan University School of Medicine, Seoul, South Korea.

The trial enrolled 2993 patients who underwent percutaneous coronary intervention (PCI) and received a drug-eluting stent at 33 medical centers in South Korea. They were randomly assigned to receive either standard dual antiplatelet therapy for a year or aspirin plus a P2Y12 inhibitor for 3 months and to continue with only the P2Y12 inhibitor for 9 more months after that.

Of the different P2Y12 inhibitors, 77% of the patients took clopidogrel, and 23% took either prasugrel (Effient, Eli Lilly) or ticagrelor (Brilenta, AstraZeneca).

Results showed that stopping aspirin early was not inferior to dual antiplatelet therapy in terms of preventing ischemic events.

After 1 year, the primary ischemic endpoint — a composite of death from any cause, MI, or stroke — had occurred in 2.9% of patients who stopped taking aspirin, vs 2.5% of those who took standard dual antiplatelet therapy for a year (P = .007 for noninferiority).

In addition, bleeding events were significantly reduced in the group who stopped taking aspirin early. Bleeding (BARC type 2–5) occurred in 2% of the those who stopped taking aspirin at 3 months compared to 3.4% of those who received dual antiplatelet therapy for a whole year (HR, 0.58; 95% CI, 0.36 – 0.92; P = .02).

Taken together, the net rate of all adverse clinical events (death from any cause, MI, stroke, or bleeding) was not significantly different between the two groups.

One limitation of the study is that a considerable proportion of patients in the group assigned to stop taking aspirin early in fact received aspirin after 3 months, although a more detailed analysis suggested that this discrepancy did not undermine the overall findings, Hahn reported.

"The SMART-CHOICE trial suggests that P2Y12 inhibitor monotherapy after short duration of dual antiplatelet therapy is a novel antiplatelet strategy balancing ischemic and bleeding risk in patients undergoing PCI," he concluded.

The STOPDAPT-2 study was funded by Abbott Vascular Japan. The SMART-CHOICE study was funded by the Korean Society of Interventional Cardiology, Abbott Vascular, Biotronik, and Boston Scientific.

American College of Cardiology 68th Annual Scientific Session (ACC) 2019. Presented March 18, 2019.

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