Intracoronary ACE Inhibitor Reduces Microvascular Damage in Elective PCI

Intracoronary enalaprilat, an angiotensin-converting enzyme (ACE) inhibitor, improves microvascular function and protects myocardium from procedure-related injury in patients with coronary artery disease (CAD) undergoing elective percutaneous coronary intervention (PCI), according to a study published online January 2, 2013, ahead of print in the Journal of the American College of Cardiology.

Investigators led by Emanuele Barbato, MD, PhD, of the Cardiovascular Care Center Aalst OLV Clinic (Aalst, Belgium), randomized 40 patients with stable CAD to receive either an intracoronary bolus of enalaprilat (50 µg) or placebo prior to elective PCI. Patients were treated at a single Belgian center from February 2011 to September 2011.

ACE Inhibitor Comes Out Ahead

Intracoronary infusion of enalaprilat resulted in a reduction in the index of microcirculatory resistance (IMR)—a measure of microvascular impairment—from baseline to 10 minutes after drug administration (27 ± 11 vs. 19 ± 9). IMR values were lower after PCI in the ACE inhibitor group compared with the placebo group (15 ± 8 vs. 33 ± 19; P < 0.001).

Likewise, levels of coronary flow reserve increased in the study group (2.2 ± 1.4 at baseline vs. 2.7 ± 1.3 after drug administration; P = 0.004) and not in the placebo group. In addition, fractional flow reserve (FFR) decreased after drug administration in the ACE inhibitor group (P = 0.023) but not in the placebo group.

Procedural success was achieved in all patients and FFR values increased to more than the ischemic threshold of 0.80 with no differences in FFR values after PCI between the 2 study arms. The enalaprilat treatment group showed lower peak values and lower periprocedural increases of high-sensitivity cardiac troponin T (table 1).

Table 1. Mean High-Sensitivity Cardiac Troponin T Levels

Promise for Enalaprilat in Stable Patients

The beneficial effect of enalaprilat on microcirculation translated into a reduced risk of PCI-related myocardial injury, Dr. Barbato and colleagues write. The moderate correlation between IMR after PCI and postprocedural troponin levels “suggests that the myocardial injury that occurs at the time of PCI is reflected by an immediate increase in IMR and a subsequent increase in [troponin]. This is in line with our previous findings demonstrating, in stable patients undergoing PCI, a correlation between post-procedural troponin T elevation and IMR values obtained in patients with conventional balloon dilatation followed by stent implantation versus a direct stenting technique.”

The current findings may be “clinically relevant if considering that even small elevations of troponin after PCI have been associated with subsequent adverse cardiovascular events. Even if the issue of periprocedural myocardial leakage is being reappraised, strategies aiming at reducing myocardial damage in the context of coronary intervention should be welcomed in patients undergoing coronary revascularization,” they write.

Because of this they suggest that “pretreatment with enalaprilat could be considered as an adjunctive treatment in patients with stable coronary artery disease undergoing PCI.”

Still, the researchers recommend further larger studies with long-term follow-up to investigate whether the effects of enalaprilat do, in fact, result in actual clinical benefit.

 

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Source:
Mangiacapra F, Peace AJ, Di Serafino L, et al. Intracoronary enalaprilat to reduce microvascular damage during percutaneous coronary intervention (ProMicro) study. J Am Coll Cardiol. 2013;Epub ahead of print.

 

 

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