Pharmaceutical interventions for the management of no-reflow

Abstract

A common complication of percutaneous coronary intervention (PCI), no-reflow is predominantly encountered during interventions in degenerated saphenous vein grafts and is associated with a marked increase in short-term mortality risk. Etiologically, no-reflow is complex and multifactorial. Microembolic debris from dilated target sites, sustained diffuse microvascular spasm, and pathophysiologic alterations from initial ischemic insults and subsequent reperfusion injuries result in persistence of myocardial ischemia despite angiographic evidence of restored vessel patency. Treatments to prevent or reverse no-reflow include antiplatelet medications to interfere with platelet aggregation. However, insufficient evidence exists demonstrating benefits with their prophylactic use in humans. Distal protection devices target microemboli, but soluble vasoactive factors may elude capture, contributing to downstream vasospasm. Intracoronary administration of vasodilators during PCI address a root cause of no-reflow. Adenosine, nitroprusside, verapamil, nicardipine and others have been evaluated clinically, showing improvements across a range of surrogate TIMI flow grade and frame count and real endpoints (wall motion indices and elevated CPK). Nicardipine may be particularly well-suited for prevention or reversal of no-reflow, demonstrating pharmacologic protection equal or superior to mechanical distal protection devices. The consistent and often dramatic mitigation of no-reflow by adjunctive use of vasodilators supports the role of microvascular spasm as a major, modifiable cause of the syndrome and a critical therapeutic target. A further large-scale, prospective, randomized, controlled clinical study is warranted to confirm prior findings, determine the optimal dosing regimen, and whether treatment or prevention of no-reflow confers clinically relevant outcome benefits.