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Front. Neurol. | doi: 10.3389/fneur.2018.01003

The Dipyridamole Added to Dual Antiplatelet Therapy in Cerebral Infarction after First Acute Myocardial Infarction: A Nationwide, Case-control Study

 Mei-Tzu Wang1, Cheng Ken Tsai2, 3, Shu-Hung Kuo1,  Wei-Chun Huang1, 3, 4, 5, 6*, Kun-Chang Lin1, Wang-Ting Hung1, Chin-Chang Cheng1, 4, 5, Pei-Ling Tang1, Cheng Chung Hung1, Jin-Shiou Yang5, Hsin-Li Liang1, Guang-Yuan Mar1 and Chun-Peng Liu1, 3
  • 1Kaohsiung Veterans General Hospital, Taiwan
  • 2Zuoying Branch of Kaohsiung Armed Forces General Hospital, Taiwan
  • 3National Defense Medical Center, Taiwan
  • 4National Yang-Ming University, Taiwan
  • 5Fooyin University, Taiwan
  • 6Kaohsiung Medical University, Taiwan

Background and Purpose: No previous study has compared the impact of dipyridamole-based triple antiplatelet therapy on secondary stroke prevention and long-term outcomes to that of dual antiplatelet therapy (DAPT) in patients with acute myocardial infarction (AMI) and previous stroke. This study aimed to evaluate the impact of dipyridamole added to DAPT on stroke prevention and long-term outcomes in patients with cerebral infarction after first AMI.
Methods: This nationwide, case-control study included 75,789 patients with cerebral infarction after first AMI. A 1:4 propensity score matching ratio was adopted based on multiple variables. Finally, the data of 4,468 patients included in the DAPT group and 1,117 patients included in the Dipyridamole-DAPT group were analyzed. Primary outcome was overall survival. Secondary outcomes were cumulative event rate of recurrent MI or stroke, and cumulative intracerebral haemorrhage (ICH) and gastrointestinal bleeding rate.
Results: Long-term survival rate was comparable between the two groups (log-rank P = .1117), regardless of sex analyses. However, after first year, DAPT subgroup revealed better survival over DAPT-dipyridamole subgroup (log-rank P = .0188). In age subgroup analysis, a lower survival rate was detected in younger patients from the Dipyridamole-DAPT group after first year (log-rank P = .0151), but no survival difference for older patients. No benefit of Dipyridamole-DAPT was detected for patients after AMI, regardless of the myocardial infarction type. DAPT was superior to Dipyridamole-DAPT in patients who underwent percutaneous coronary intervention (PCI) (log-rank P = .0153) and ST elevation myocardial infarction after first year (log-rank P = .0019). Dipyridamole-DAPT did not reduce cumulative event rate of recurrent MI or stroke in patients after AMI. Moreover, Dipyridamole-DAPT increased the cumulative ICH rate (log-rank P = .0026), but did not affect the cumulative event rate of gastrointestinal bleeding. In Cox analysis, dipyridamole did not improve long-term survival.
Conclusions: This nationwide study showed that Dipyridamole-DAPT, compared with DAPT, did not improve long-term survival in patients with stroke after AMI, and was related to poor outcomes after one year. Dipyridamole-DAPT did not reduce recurrent rate of MI or stroke, but increased the ICH rate without impacting the incidence of gastrointestinal bleeding.

Keywords: acute myocardial infarction, Antiplatelet agent, Dipyridamole, Stroke, Dual antiplatelet therapy

Received: 18 Aug 2018; Accepted: 06 Nov 2018.

Edited by:

Linxin Li, University of Oxford, United Kingdom

Reviewed by:

AMELIA FILIPPELLI, University of Salerno, Italy
Michele Romoli, University of Perugia, Italy
Sang-Hyun Kim, Seoul Boramae Hospital, South Korea  

Copyright: © 2018 Wang, Tsai, Kuo, Huang, Lin, Hung, Cheng, Tang, Hung, Yang, Liang, Mar and Liu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Wei-Chun Huang, Kaohsiung Veterans General Hospital, Kaohsiung City, Taiwan,