Seoul St. Mary's Hospital Team Proposes Antiplatelet Dose Reduction Strategy to Lower Bleeding Risk After Cardiac Intervention

Favorable Outcomes with Reduced-Intensity Antiplatelet Strategy
for Acute Myocardial Infarction Patients with BMI Below 28

A new study published in an international journal reports that adjusting the intensity of antiplatelet therapy based on obesity levels during maintenance therapy after acute-phase treatment for patients with acute myocardial infarction can reduce the risk of bleeding without increasing the incidence of ischemic events.

According to Seoul St. Mary's Hospital of the Catholic University of Korea on March 16, a research team led by Jang Giyook (corresponding author) of the Department of Cardiology at Seoul St. Mary's Hospital and Bu Seonghyeon (first author), Professor of Cardiology at Uijeongbu St. Mary's Hospital, conducted this study based on the TALOS-AMI (Ticagrelor versus Clopidogrel in Antiplatelet Therapy) data published in 2021 in *The Lancet*, one of the world's most prestigious journals. The study included 2,686 patients from 32 centers in Korea.

Jang Gi-yook (left), Department of Cardiology, Seoul St. Mary's Hospital, and Professor Buseong Hyun, Department of Cardiology, Uijeongbu St. Mary's Hospital. Seoul St. Mary's Hospital

Acute myocardial infarction, commonly referred to as a heart attack, is a condition in which the coronary artery that supplies blood to the heart suddenly becomes blocked, resulting in the death of heart muscle. While rapid recanalization to reopen the blocked coronary artery is vital, patients are also required to continue taking antiplatelet drugs after treatment to prevent reocclusion. However, high-intensity antiplatelet drugs, which inhibit blood coagulation, have been associated with an increased risk of bleeding.

The key finding of the study is that for non-obese patients with a body mass index (BMI) of less than 28, reducing the intensity of antiplatelet therapy during the maintenance phase after the acute period offers the same efficacy with greater safety.

All patients in the study received a combination of aspirin and the high-intensity antiplatelet agent ticagrelor for the first month after percutaneous coronary intervention. Subsequently, stabilized patients continued on aspirin and were randomly assigned to either the "maintenance group," which continued the same medication, or the "switch group," which changed to the relatively lower-intensity antiplatelet agent clopidogrel, for an additional 11 months of treatment.

The primary endpoint was the composite rate of major events at 12 months after percutaneous coronary intervention, including cardiovascular death, myocardial infarction, stroke, and clinically significant bleeding classified as type 2, 3, or 5 by the Bleeding Academic Research Consortium (BARC).

The results showed that in non-obese patients with a BMI below 28, switching from ticagrelor to clopidogrel resulted in a clear safety advantage compared to maintaining high-intensity antiplatelet therapy.

Specifically, the group that reduced the medication experienced bleeding events at less than half the rate (a reduction of about 53%), and the incidence of major composite events (including cardiovascular death, myocardial infarction, stroke, and bleeding) was also about 46% lower. On the other hand, there was no significant difference in the incidence of ischemic events—such as reocclusion of the vessel—between the two groups, meaning efficacy was maintained while risk was reduced.

The background for these results lies in the characteristics of ticagrelor. While it has become the standard therapy during the acute phase of myocardial infarction due to its mechanism of directly binding to platelets and rapidly and powerfully inhibiting blood clotting, the downside of its potent effect is an increased risk of bleeding—making long-term use burdensome for both patients and healthcare providers.

This study is being recognized for providing the first clinical evidence that high-intensity antiplatelet therapy is not necessarily required during the stable phase for patients with lower obesity levels, potentially reducing the burden on clinical practice.

Bu Seonghyeon, Professor of Cardiology at Uijeongbu St. Mary's Hospital, stated, "This study offers new insight into the so-called 'obesity paradox' observed in acute myocardial infarction patients who have undergone percutaneous coronary intervention." He explained, "Until now, attention has focused on the phenomenon that patients with higher BMI have better outcomes, but our results show that patients with lower BMI have a relatively higher vulnerability to bleeding." He added, "Rather than simply interpreting 'obesity as protective,' the intensity of antiplatelet therapy after intervention should be tailored more precisely to each patient's BMI and risk of bleeding."

Jang Giyook, Professor of Cardiology at Seoul St. Mary's Hospital, who led the study, said, "The previously known 'East Asian paradox' has been interpreted as a racial difference—East Asians have lower rates of ischemic events but higher risks of bleeding compared to Westerners. However, our findings suggest that the risk of bleeding may be better explained by BMI differences rather than ethnicity." He continued, "As most dual antiplatelet therapy studies reported to date have been conducted on Western populations with higher BMI, this provides new clinical evidence that BMI should be considered when developing treatment strategies for Korean patients."

The results of this study have been published in the international journal *JAMA Network Open* (IF=10.5), the official journal of the American Medical Association.

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