Short-Term Dual Antiplatelet Therapy Increases Risk of Heart Attack

The risk of myocardial infarction was 2.4-fold higher in patients on short-term P2Y12 inhibitors after 18 months and 5.1-fold higher from month 6 to month 18.

Hyeon Cheol Gwon, MD

The utilization of 6-month dual antiplatelet therapy (DAPT), while not inferior to 12-month or longer-term DAPT for major adverse cardiac and cerebrovascular events (MACCE), increases the risk of myocardial infarction (MI) 2.4-fold in patients with acute coronary syndrome (ACS).

In the SMART-DATE trial, at 18 months post angioplasty procedure, MI occurred in 1.8% (n = 24) of the short-term group compared with 0.8% (n = 10) of the long-term group (HR, 2.41; 95% CI, 1.15—5.05; P = .02). Between months 6 and 18, the risk of MI in the short-term group was 5.1 times higher, as well as a 69% higher risk of all-cause death, than the long-term group.

“Based on our findings, we can’t say that short-term DAPT is safe in patients with ACS who have received drug-eluting stents,” said Hyeon Cheol Gwon, MD, a professor in the Division of Cardiology at Sungkyunkwan University, director of the cardiac center at Samsung Medical Center in Seoul, South Korea, and principal investigator of the study. “We conclude that current guidelines that recommend prolonged DAPT in patients with ACS who are not at excessive risk for bleeding should continue to be followed.”

Limited evidence exists for the use of DAPT for 12 months or longer, Gwon noted, with 2 recent studies suggesting that short-term use of DAPT (6 months) could offer similar benefits in reducing the risk of adverse events such as death, MI or stroke, and bleeding.

However, those studies had small cohorts, which did not allow for definitive answers to be provided. “This is the largest trial to address the optimal duration of DAPT in patients with ACS,” Gwon said.

Presented at the 67th American College of Cardiology Scientific Sessions in Orlando, Florida, the trial randomized patients to either P2Y12 inhibitors for 6 months, coupled with indefinite aspirin (n = 1357), or P2Y12 inhibitors for 12 or more months, coupled with indefinite aspirin (n = 1355).

In the short-term group, 333 patients were on P2Y12 inhibitors for >240 days and 15 were on P2Y12 inhibitors for <120 days, with the median duration being 184 days. Adherence to P2Y12 inhibitors was 97.1% in the short-term group at 6 months, plummeting to 23.3% by month 9 and 15.0% by month 18. Adherence to aspirin was 96.1% by month 12 in the short-term group.

Comparatively, 43 patients were on P2Y12 inhibitors for <300 days in the long-term group, with median duration reported as 531 days. Adherence to P2Y12 inhibitors was 9.61% at month 12, dropping to 69.6% at month 18. Aspirin adherence remained above 90% up to 18 months.

The primary endpoint of MACCE occurred in 4.7% (n = 63) of the short-term group and 4.2% (n = 56) of the long-term group (HR, 1.13; 95% CI, 0.79—1.62; P = .51).

The study was limited in its lack of blinding and placebo control. However, the study did have statisticians and independent assessment of data.

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