The Ischemia–Plaque Paradox: A Mechanistic Framework for Chronic Coronary Syndromes

Percutaneous coronary intervention relieves angina in chronic coronary syndromes, yet contemporary randomized trials have not shown that relieving ischemia reduces death or myocardial infarction when added to optimal medical therapy. This discordance requires a mechanistic reevaluation. Inducible ischemia identifies obstructive coronary disease and the likelihood of angina but does not reliably identify plaques that will rupture. Fractional flow reserve-guided percutaneous intervention reduces urgent revascularization without reducing death or infarction. Most spontaneous infarctions arise from lesions that were not severely obstructive before rupture. Coronary artery bypass grafting reduces spontaneous infarction in complex multivessel and left main disease, plausibly through more complete revascularization and through placement of grafts distal to long diseased segments that preserve perfusion if proximal plaque rupture occurs. Advances in intracoronary imaging and coronary computed tomography angiography can identify high-risk plaque features, but trials of focal treatment of non-flow-limiting vulnerable plaques have not shown benefit. Modern medical therapy with high-intensity lipid lowering, icosapent ethyl in selected patients, anti-inflammatory approaches, and therapies for diabetes and chronic kidney disease has lowered overall event rates. Chronic coronary syndromes comprise 2 overlapping but distinct pathophysiological mechanisms. Flow-limiting stenoses cause angina and are effectively treated by percutaneous coronary intervention. Plaque instability causes infarction and is modified by systemic therapy. Bypass surgery in selected patients with complex coronary anatomy addresses both mechanisms by relieving flow limitation and protecting myocardium against future plaque events.