Comparison of two P2Y12 inhibitors in ACS patients with diabetes

Ticagrelor or Prasugrel in Patients With Acute Coronary Syndromes and Diabetes Mellitus

Literature - Ndrepepa G, Kastrati A, Menichelli M, et al. - JACC Cardiovasc Interv 2020, 13:2238-2247.doi: 10.1016/j.jcin.2020.07.032

Introduction and methods

Patients with diabetes (DM) who present themselves with acute coronary syndrome (ACS) and in whom invasive therapy is planned, have increased platelet reactivity, reduced response to antiplatelet drugs resulting in higher risk for subsequent thrombotic events and higher mortality risk when compared to patients without diabetes [1-5]. Even after increasing clopidogrel maintenance dose in patients with DM in the OPTIMUS trial, 60% of patients did not respond optimal [6], indicating the need for better strategies of platelet inhibition in patients with DM.

The TRITON-TIMI trial and PLATO trial demonstrated superiority of either prasugrel or ticagrelor respectively over clopidogrel in DM patients. But head-to-head comparisons of ticagrelor vs. prasugrel in DM patients are lacking and the trials enrolled different patient populations. Therefore, it is not known which antiplatelet drug is preferred in DM patients presenting with ACS and planned invasive therapy.

The ISAR-REACT (Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Actions for Coronary Treatment) 5 trial demonstrated superiority of prasugrel over ticagrelor in reduction the composite endpoint of death, MI, or stroke, without increasing risk of major bleeding in ACS patients undergoing PCI [7]. A prespecified analysis according to DM status was planned.

In the ISAR-REACT 5 trial, patients hospitalized for ACS with planned invasive treatment were enrolled and randomized to ticagrelor (a loading dose of 180 mg as soon as possible after randomization and continued at a maintenance dose of 90 mg twice daily) or to prasugrel (a loading dose of 60 mg after coronary angiography and continued at maintenance dose of 10 mg once daily). Information on DM was available in 4016 patients: 892 had DM and 3124 had no DM. Efficacy endpoint was a composite of death, MI, or stroke at 12 months. Safety endpoint was incidence of bleeding types 3 to 5 defined by BARC at 12 months.

Main results

  • Primary endpoint occurred in 51 patients in the ticagrelor group and 55 patients in the prasugrel group (11.2% vs. 13.0%, respectively; HR 0.84, 95%CI: 0.58-1.24, P=0.383). In those without DM, primary endpoint occurred more often in those on ticagrelor compared to those on prasugrel (HR 1.70, 95%CI: 1.29 to 2.24, P<0.001). There was a significant interaction between treatment arm and DM status on efficacy outcome (Pinteraction=0.0035).
  • In patients with DM, there were no differences according to study drug for any of the individual efficacy endpoints or incidence of stent thrombosis, whereas there was significant lower risk of MI and definite stent thrombosis with prasugrel compared to ticagrelor in those without DM.
  • In patients with DM, safety endpoint occurred in 27 patients in the ticagrelor group and 19 patients in the prasugrel group (6.9% vs. 5.5%, HR 1.27, 95%I: 0.70-2.29, P=0.425). In patients without DM, the safety endpoint occurred in 68 patients in the ticagrelor group and 60 patients in the prasugrel group (5.2% vs. 4.6%, HR 1.13, 95%CI: 0.80-1.60, P=0.500).

Conclusion

In this prespecified analysis of ISAR-REACT 5 trial, there was no difference between ticagrelor and prasugrel with regard to efficacy in ACS patients with DM. In addition, safety of ticagrelor was comparable with that of prasugrel in DM patients.

References

1. Angiolillo DJ, Fernandez-Ortiz A, Bernardo E, et al. Platelet function profiles in patients with type 2 diabetes and coronary artery disease on combined aspirin and clopidogrel treatment. Diabetes 2005;54:2430–5.

2. Angiolillo DJ, Jakubowski JA, Ferreiro JL, et al. Impaired responsiveness to the platelet P2Y12 receptor antagonist clopidogrel in patients with type 2 diabetes and coronary artery disease. J Am

Coll Cardiol 2014;64:1005–14.

3. Haffner SM, Lehto S, Ronnemaa T, Pyorala K, Laakso M. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med 1998;339:229–34.

4. Donahoe SM, Stewart GC, McCabe CH, et al. Diabetes and mortality following acute coronary syndromes. JAMA 2007;298:765–75.

5. Roffi M, Topol EJ. Percutaneous coronary intervention in diabetic patients with non-STsegment

elevation acute coronary syndromes. Eur Heart J 2004;25:190–8.

6. Angiolillo DJ, Shoemaker SB, Desai B, et al. Randomized comparison of a high clopidogrel maintenance dose in patients with diabetes mellitus and coronary artery disease: results of the Optimizing Antiplatelet Therapy in Diabetes Mellitus (OPTIMUS) study. Circulation 2007;115: 708–16.

7. Schupke S, Neumann FJ, Menichelli M, et al. Ticagrelor or prasugrel in patients with acute coronary syndromes. N Engl J Med 2019;381:1524–34.

Find this article online at JACC Cardiovasc Interv 2020

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