Reducing Microvascular Dysfunction in Revascularized Patients with ST-Elevation Myocardial Infarction by Off-Target Properties of Ticagrelor versus Prasugrel. Rationale and Design of the REDUCE-MVI Study

Abstract

Microvascular injury is present in a large proportion of patients with ST-elevation myocardial infarction (STEMI) despite successful revascularization. Ticagrelor potentially mitigates this process by exerting additional adenosine-mediated effects. This study aims to determine whether ticagrelor is associated with a better microvascular function compared to prasugrel as maintenance therapy after STEMI. A total of 110 patients presenting with STEMI and additional intermediate stenosis in another coronary artery will be studied after successful percutaneous coronary intervention (PCI) of the infarct-related artery. Patients will be randomized to treatment with ticagrelor or prasugrel for 1 year. FFR-guided PCI of the non-infarct-related artery will be performed at 1 month. Microvascular function will be assessed by measurement of the index of microcirculatory resistance (IMR) in the infarct-related artery and non-infarct-related artery, immediately after primary PCI and after 1 month. The REDUCE-MVI study will establish whether ticagrelor as a maintenance therapy may improve microvascular function in patients after revascularized STEMI.

Comparative Prognostic Utility of Indexes of Microvascular Function Alone or in Combination in Patients With an Acute ST-Segment–Elevation Myocardial Infarction

“…53 In the setting of acute STEMI, a randomized trial of initial antiplatelet therapy in 76 patients undergoing primary PCI disclosed that, compared with an oral loading dose of 600 mg clopidogrel, an oral loading dose of 180 mg ticagrelor was associated with a lower IMR at the end of the procedure (22.2±18.0 versus 34.4±18.8 U; P =0.005). 54 In other randomized, controlled trials in acute MI, IMR is being used to assess the comparative efficacy of antiplatelet therapies 55 (NCT0273334), vasodilator therapy, 56 and low-dose intracoronary thrombolysis (T-TIME [A Trial of Low-Dose Adjunctive alteplase During Primary PCI]; NCT02257294).…”

Temporal Changes in Coronary Hyperemic and Resting Hemodynamic Indices in Nonculprit Vessels of Patients With ST-Segment Elevation Myocardial Infarction

“…This study was a predefined substudy of the Reducing Micro Vascular Dysfunction in Revascularized STEMI Patients by Off-target Properties of Ticagrelor (REDUCE-MVI) trial . The primary end point of the REDUCE-MVI study was microvascular resistance at 30 days in patients with ticagrelor vs prasugrel, measured by the index of microcirculatory resistance (IMR), which was similar in both groups.…”

Evaluation of Microvascular Injury in Revascularized Patients With ST-Segment–Elevation Myocardial Infarction Treated With Ticagrelor Versus Prasugrel

“…Upon request, the analytic methods will be made available to other researchers for purposes of reproducing the results or replicating the procedure, the data and study materials will not be made available. The trial was conducted in 6 centres in the Netherlands and Spain and the study design has been published previously 14 . In brief, patients were eligible for study participation when they presented with STEMI 1 <12 hours after onset of symptoms, received a loading dose of ticagrelor (180mg), underwent successful pPCI of the infarct-related artery with a drug eluting stent and had a concomitant intermediate lesion in the non-infarct related vessel(s).…”

“…IMR during the index procedure was not lower in the ticagrelor-compared to the prasugrel group (Figure 2). After a mean follow-up of 31±7 days, the primary endpoint of IMR was not superior in the ticagrelor group (ticagrelor 21 U, prasugrel 18 [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] U, p=0.08). Improvement of microvascular function over time was also non-superior between both groups (IMR ticagrelor -13.9 U vs. prasugrel -13.5 U, p=0.54).…”