Dynamic perioperative platelet activity and cardiovascular events in peripheral artery disease

Objective: Patients with peripheral artery disease (PAD) undergo lower extremity revascularization (LER) for symptomatic relief or limb salvage. Despite LER, patients remain at increased risk of platelet-mediated complications, such as major adverse cardiac and limb events (MACLEs). Platelet activity is associated with cardiovascular events, yet little is known about the dynamic nature of platelet activity over time. We, therefore, investigated the change in platelet activity over time and its association with long-term cardiovascular risk.

Methods: Patients with PAD undergoing LER were enrolled into the multicenter, prospective Platelet Activity and Cardiovascular Events study. Platelet aggregation was assessed by light transmission aggregometry to submaximal epinephrine (0.4 μmol/L) immediately before LER, and on postoperative day 1 or 2 (POD1 or POD2) and 30 (POD30). A hyperreactive platelet phenotype was defined as >60% aggregation. Patients were followed longitudinally for MACLEs, defined as the composite of death, myocardial infarction, stroke, major lower extremity amputation, or acute limb ischemia leading to reintervention.

Results: Among 287 patients undergoing LER, the mean age was 70 ± 11 years, 33% were female, 61% were White, and 89% were on baseline antiplatelet therapy. Platelet aggregation to submaximal epinephrine induced a bimodal response; 15.5%, 16.8%, and 16.4% of patients demonstrated a hyperreactive platelet phenotype at baseline, POD1, and POD30, respectively. Platelet aggregation increased by 18.5% (P = .001) from baseline to POD1, which subsequently returned to baseline at POD30. After a median follow-up of 19 months, MACLEs occurred in 165 patients (57%). After adjustment for demographics, clinical risk factors, procedure type, and antiplatelet therapy, platelet hyperreactivity at POD1 was associated with a significant hazard of long-term MACLE (adjusted hazard ratio, 4.61; 95% confidence interval, 2.08-10.20; P < .001).

Conclusions: Among patients with severe PAD, platelet activity increases after LER. Platelet hyperreactivity to submaximal epinephrine on POD1 is associated with long-term MACLE. Platelet activity after LER may represent a modifiable biomarker associated with excess cardiovascular risk.