Author + information
- Fabio Mangiacapra, MD, PhD,
- Giuseppe Di Gioia, MD,
- Mariano Pellicano, MD,
- Luigi Di Serafino, MD, PhD,
- Edoardo Bressi, MD,
- Aaron J. Peace, MD, PhD,
- Jozef Bartunek, MD, PhD,
- William Wijns, MD, PhD,
- Bernard De Bruyne, MD, PhD and
- Emanuele Barbato, MD, PhD∗ ()
- ↵∗Cardiovascular Center, Aalst OLV Clinic, Moorselbaan, 164, B-9300 Aalst, Belgium
Microvascular impairment has been reported in patients on clopidogrel undergoing elective percutaneous coronary intervention (PCI) (1). The related potential mechanisms might include the high residual platelet reactivity observed in a substantial proportion of these patients pretreated with clopidogrel at the time of PCI (2,3). Alternatively, microvascular constriction could occur possibly as consequence of transient endothelial dysfunction related to impaired platelet response to clopidogrel (4). It is unknown whether prasugrel might exert a protective effect on microcirculation during elective PCI in patients with stable coronary artery disease (CAD) scheduled for elective PCI.
The prospective randomized double-blind controlled PROMICRO-2 (PROtecting MICROcirculation during coronary angioplasty) trial enrolled thienopyridine-naive patients with stable CAD referred to elective PCI of an isolated, functionally significant (as confirmed by fractional flow reserve [FFR] <0.80) lesion located in the proximal two-thirds of a major coronary artery. Patients were randomized to either prasugrel (60 mg) or clopidogrel (600 mg) at least 12 h before PCI. All patients received a 500-mg loading dose of aspirin the day before the procedure. Coronary flow reserve (CFR), index of microvascular resistance (IMR), and FFR were measured in each patient before and after PCI, as previously described (1). High-sensitivity troponin T (hs-TnT) (Roche Diagnostics, Mannheim, Germany) was assessed in blood samples before, and 8 and 24 h after PCI. All procedures were performed via the femoral approach.
Forty patients were enrolled: 20 randomized to the prasugrel and 20 to the clopidogrel groups. Baseline clinical and procedural characteristics were similar in the 2 groups. At baseline, FFR, CFR, and IMR were similar in the 2 study groups (Table 1). Patients in the prasugrel group showed significantly lower post-PCI IMR values compared with those in the clopidogrel group. Compared with baseline, IMR increased post-PCI in the clopidogrel group (p = 0.009), but not in the prasugrel group (p = 0.299). Repeated measures 2-way analysis of variance (ANOVA) showed a significant interaction between treatment (i.e., prasugrel vs. clopidogrel) and time in determining IMR values (p = 0.047). Consistently, post-PCI CFR was significantly higher in the prasugrel compared with the clopidogrel group. Compared with baseline, CFR remained unchanged post-PCI in the clopidogrel group (p = 0.563), whereas increased in the prasugrel group (p = 0.036). Repeated-measures 2-way ANOVA showed a nonsignificant interaction between treatment (i.e., prasugrel vs. clopidogrel) and time in determining CFR values (p = 0.053). Baseline Hs-TnT was 4.8 (IQR: 3.2 to 10.1) ng/ml in the prasugrel group versus 5.1 (IQR: 3.0 to 12.8) ng/ml in the clopidogrel group (p = 0.845). Post-PCI Hs-TnT was 12.8 (IQR: 7.7 to 23.6) ng/ml in the prasugrel group versus 25.6 (11.8 to 50.6) ng/ml in the clopidogrel group (p = 0.032). Repeated-measures 2-way ANOVA showed a significant interaction between treatment and time in determining log-transformed Hs-TnT values (p = 0.044). Periprocedural Hs-TnT increase (i.e., difference between baseline and highest post-procedural values) was significantly lower in the prasugrel group compared with the clopidogrel group (6.6 [2.5 to 9.7] ng/ml vs. 15.8 [5.9 to 38.0] ng/ml; p = 0.034).
In this study, we hypothesized that suboptimal platelet inhibition before, and further platelet activation occurring during PCI could be, at least in part, responsible for the microvascular impairment reported in patients undergoing elective PCI (1). The results of the PROMICRO-2 study suggest that a single loading dose of prasugrel is able to prevent microvascular impairment and ischemic complications in the setting of elective PCI. A more potent platelet inhibition is expected to be of particular benefit at the occasion of coronary interventions that might potentially injure the endothelium, creating high thrombogenic milieu. An adequate platelet inhibition is even more important during complex interventions with extensive vascular damage (5). In these patients, strategies aimed at optimizing the immediate procedural outcome by preventing microvascular impairment and myocardial damage might positively affect long-term outcome. Moreover, the administration of a single dose of prasugrel (followed by clopidogrel) may also prevent the potential risk of bleeding possibly occurring during the maintenance phase of the treatment.
Despite limitations including relatively small sample size, measurement of IMR at a single time point post-PCI, and the lack of intracoronary imaging for assessment of plaque burden, the results of the PROMICRO-2 trial suggest that more intensive antiplatelet regimens might offer additional benefit compared with clopidogrel also in the setting of elective PCI. Larger randomized clinical trials, such as the ongoing ALPHEUS (Assessment of Loading With the P2Y12 Inhibitor Ticagrelor or Clopidogrel to Halt Ischemic Events in Patients Undergoing Elective Coronary Stenting) trial (NCT02617290), will help to clarify this issue.
Please note: Dr. Pellicano has been supported by a research grant provided by the Cardiopath PhD program. Dr. De Bruyne is a consultant for St. Jude Medical, Boston Scientific, and Opsens. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- American College of Cardiology Foundation
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