Intracoronary EnalaPrilat to Reduce MICROvascular Damage During Percutaneous Coronary Intervention (ProMicro) study

J Am Coll Cardiol. 2013 Feb 12;61(6):615-21. doi: 10.1016/j.jacc.2012.11.025. Epub 2013 Jan 2.

Abstract

Objectives: This study investigated the influence of intracoronary enalaprilat on coronary microvascular function and peri-procedural outcome measures in patients with stable angina undergoing percutaneous coronary intervention (PCI).

Background: Intracoronary angiotensin-converting enzyme inhibitors have been shown to relieve myocardial ischemia in stable patients and to improve epicardial flow in patients with ST-segment elevation myocardial infarction. Yet, it is still unclear whether these effects are mediated by a modulation of the coronary microcirculation.

Methods: We randomly assigned 40 patients to receive either an intracoronary bolus of enalaprilat (50 μg) or placebo before elective PCI. The index of microvascular resistance was measured at baseline, 10 minutes after study drug administration, and after PCI. High-sensitivity cardiac troponin T was measured as a marker of myocardial injury.

Results: Infusion of enalaprilat resulted in a significant reduction in index of microvascular resistance (27 ± 11 at baseline vs. 19 ± 9 after drug vs. 15 ± 8 after PCI), whereas a significant post-procedural increase in index of microvascular resistance levels was observed in the placebo group (24 ± 15 at baseline vs. 24 ± 15 after drug vs. 33 ± 19 after PCI). Index of microvascular resistance levels after PCI were significantly lower in the enalaprilat group (p < 0.001). Patients pre-treated with enalaprilat also showed lower peak values (mean: 21.7 ng/ml, range: 8.2 to 34.8 ng/ml vs. mean: 32.3 ng/ml, range: 12.6 to 65.2 ng/ml, p = 0.048) and peri-procedural increases of high-sensitivity cardiac troponin T (mean: 9.9 ng/ml, range: 2.7 to 19.0 ng/ml vs. mean: 26.6 ng/ml, range: 6.3 to 60.5 ng/ml, p = 0.025).

Conclusions: Intracoronary enalaprilat improves coronary microvascular function and protects myocardium from procedure-related injury in patients with coronary artery disease undergoing PCI. Larger studies are warranted to investigate whether these effects of enalaprilat could result into a significant clinical benefit.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Angina, Stable* / blood
  • Angina, Stable* / diagnosis
  • Angina, Stable* / physiopathology
  • Angina, Stable* / therapy
  • Angiotensin-Converting Enzyme Inhibitors / administration & dosage
  • Angiotensin-Converting Enzyme Inhibitors / pharmacokinetics
  • Biological Availability
  • Cardiotonic Agents / administration & dosage
  • Cardiotonic Agents / pharmacokinetics
  • Coronary Angiography
  • Coronary Circulation / drug effects
  • Drug Monitoring
  • Enalaprilat* / administration & dosage
  • Enalaprilat* / pharmacokinetics
  • Female
  • Humans
  • Injections, Intra-Arterial
  • Male
  • Microcirculation / drug effects
  • Microvessels / drug effects*
  • Microvessels / physiopathology
  • Middle Aged
  • Percutaneous Coronary Intervention / methods*
  • Perioperative Care / methods*
  • Treatment Outcome
  • Troponin T / blood
  • Vascular Resistance / drug effects

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Cardiotonic Agents
  • Troponin T
  • Enalaprilat