Reducing microvascular injury in myocardial infarction.
Ticagrelor potentially mitigates the process of microvascular injury in ST-elevation myocardial infarction (STEMI) patients by exerting additional adenosine-mediated effects. The REDUCE-MVI study aimed to determine whether ticagrelor was associated with a better microvascular function compared to prasugrel maintenance therapy after STEMI. The study was conducted internationally in 6 different hospitals, the VU Medical Center, Amsterdam; Erasmus Medical Center, Rotterdam; Medisch Spectrum Twente, Enschede; Hospital Clínico San Carlos, Madrid; Academic Medical Centre, Amsterdam and Radboud University Medical Center, Nijmegen.
Microvascular injury is present in a large proportion of patients with ST-elevation myocardial infarction (STEMI) despite successful revascularization. In the coming years, more insight into the biochemical mechanisms involved in STEMI may be expected, which may hopefully lead to the development of more specific drugs for microvascular preservation. Along this line, the REDUCE-MVI study focused in more detail on current therapeutic options to retain microvascular integrity and function in patients with STEMI. Ticagrelor has been reported to increase plasma adenosine levels, which might have a protective effect on the microcirculation. The REDUCE-MVI study investigated if ticagrelor maintenance therapy after revascularized STEMI was associated with less MVI compared to prasugrel maintenance therapy.
A total of 110 STEMI patients with an additional stenosis in another coronary artery, received a loading dose of ticagrelor and were randomized to 1 year maintenance therapy of ticagrelor (n=56) or prasugrel (n=54), after successful percutaneous coronary intervention (PCI) of the infarct-related artery. FFR-guided PCI of the non-infarct-related artery was performed at 1 month. The primary outcome was MVI at 1 month, as determined with the index of microcirculatory resistance (IMR) in the infarct-related artery. Cardiovascular magnetic resonance imaging was performed during the acute phase and at one month to assess infarct size, microvascular obstruction and intramyocardial hemorrhage.
The primary outcome of IMR was not superior in ticagrelor or prasugrel treated patients (21 versus 18 U, respectively). Recovery of microcirculatory resistance over time was not better in patients with ticagrelor versus prasugrel. Intramyocardial hemorrhage was observed less frequently in patients with ticagrelor compared to prasugrel (23% versus 43%, respectively). At one month no between-group difference in infarct size (8 versus 10 grams, respectively) was observed. The occurrence of microvascular obstruction was not different in patients on ticagrelor (28%) or prasugrel (41%). Plasma adenosine concentrations were not different during the index procedure and during maintenance therapy with ticagrelor or prasugrel.
In summary, in patients with STEMI, ticagrelor maintenance therapy was not superior to prasugrel in preventing microvascular injury in the infarct-related territory as assessed by IMR and this resulted in a comparable infarct size at one month.
The main results of the REDUCE-MVI study have been published in Circulation, van Leeuwen et al. 2019 Jan 29;139(5):636-646. doi: 10.1161/CIRCULATIONAHA.118.035931.
In a sub-study of the REDUCE-MVI trial, we investigated the value of hemodynamic indices in non-culprit vessels of STEMI patients from the index event to 1 month follow-up. We related changes to cardiac magnetic resonance derived infarct characteristics.
Percutaneous coronary intervention of non-culprit vessels in STEMI patients is associated with improved clinical outcome compared to culprit vessel only PCI. Fractional flow reserve (FFR) and coronary flow reserve (CFR) are hyperemic indices used to guide revascularization. Recently, instantaneous wave-free ratio (iFR) was introduced as a non-hyperemic alternative to FFR. We investigated whether these indices can be used in the acute setting of STEMI.
Following successful primary PCI, non-culprit intracoronary hemodynamic measurements were performed and repeated at 1-month follow-up. Cardiac magnetic resonance imaging was performed 2-7 days and 1 month after primary PCI. A total of 73 STEMI patients with a mean age of 60.8±9.9 years were included. iFR did not change significantly and there was no change in Pd/Pa from acute to follow-up. FFR decreased, whereas CFR increased. IMR decreased and BMR increased from acute to follow-up. The drop in distal pressure from rest to hyperemia was smaller at the acute moment versus at follow-up with an accompanying decrease of FFR. This blunted acute hyperemic response correlated to final infarct size.
In summary, in the acute setting of STEMI, non-culprit CFR was reduced and FFR augmented, while iFR was not altered. This could be explained by an increased hyperemic microvascular resistance and a blunted adenosine responsiveness at the acute moment which was related to infarct size.
The results of the study have been published in JAMA Cardiology, van der Hoeven et al. 2019 Jul 3. doi: 10.1001/jamacardio.2019.2138.
Publications:
Reducing Micro Vascular Dysfunction in Acute Myocardial Infarction by Ticagrelor (REDUCE-MVI)
