Ticagrelor vs. clopidogrel in patients with non-ST-elevation acute coronary syndrome with or without revascularization: results from the PLATO trial

Abstract

AimsThe optimal platelet inhibition strategy for ACS patients managed without revascularization is unknown.We aimed to evaluate efficacy and safety of ticagrelor vs. clopidogrel in the non-ST-elevation acute coronary syndrome (NSTE-ACS) subgroup of the PLATO trial, in the total cohort, and in the subgroups managed with and without revascularization within 10 days of randomization.Methods and resultsWe performed a retrospective analysis of the primary endpoint of cardiovascular death/myocardial infarction/stroke. Among 18 624 PLATO patients, 11 080 (59%) were categorized as NSTE-ACS at randomization. During the initial 10 days, 74% had angiography, 46% PCI, and 5% CABG. In NSTE-ACS patients, the primary endpoint was reduced with ticagrelor vs. clopidogrel [10.0 vs. 12.3%; hazard ratio (HR) 0.83; 95% confidence interval (CI) = 0.74–0.93], as was myocardial infarction (6.6 vs. 7.7%; HR 0.86; 95% CI = 0.74–0.99), cardiovascular death (3.7 vs. 4.9%; HR 0.77; 95% CI = 0.64–0.93), and all-cause death (4.3 vs. 5.8%; HR 0.76; 95% CI = 0.64–0.90). Major bleeding rate was similar between treatment groups (13.4 vs. 12.6%; HR 1.07; 95% CI = 0.95–1.19), but ticagrelor was associated with an increase in non-CABG major bleeding (4.8 vs. 3.8%; HR 1.28; 95% CI = 1.05–1.56). Within the first 10 days, 5366 (48.4%) patients were managed without revascularization. Regardless of revascularization or not, ticagrelor consistently reduced the primary outcome (HR 0.86 vs. 0.85, interaction P = 0.93), and all-cause death (HR 0.75 vs. 0.73, interaction P = 0.89) with no significant increase in overall major bleeding.ConclusionIn patients with NSTE-ACS, benefit of ticagrelor over clopidogrel in reducing ischaemic events and total mortality was consistent with the overall PLATO trial, independent of actually performed revascularization during the initial 10 days.

Trials Evaluating Ticagrelor in Cardiovascular Disease: Will It Reign Supreme in the Anti-Platelet World?

“…With unstable coronary disease there is usually a coronary culprit lesion and potentially other active non-culprit vascular segments. The PLATO findings [4,9] might also suggest protection from ticagrelor on non-culprit, non-stented coronary segments. Whether ticagrelor benefited patients with stable coronary disease was tested in PEGASUS-a 3-arm 21162 patient trial comparing long-term therapy with ticagrelor (2 randomized doses) versus placebo on top of low-dose aspirin.…”

“…In PLATO, the benefit from dual aspirin-ticagrelor therapy over aspirin-clopidogrel was observed in both invasively managed and noninvasively managed patients [4,9]. With unstable coronary disease there is usually a coronary culprit lesion and potentially other active non-culprit vascular segments.…”

Acute Coronary Syndrome: Focus on Antiplatelet Therapy

“…21 No significant differences in the rate of major bleeding were found, either overall or in patients undergoing a coronary artery bypass graft (CABG) in whom clopidogrel and ticagrelor were discontinued according to the study protocol before the procedure (5 days and 24-72 hours before surgery, respectively) in the overall PLATO population 20 or the NSTE-ACS population. 21 However, ticagrelor demonstrated significantly increased rates of major bleeding that were not related to CABG (4.5% vs 3.8%, P = .03 overall; 4.8% vs 3.8%, P = .01 for NSTE-ACS), 20,21 dyspnea (13.8% vs 7.8%, P < .001 overall; although only 0.9% of ticagrelor recipients and 0.1% of clopidogrel recipients discontinued treatment because of dyspnea), 20 and ventricular pauses of 3 seconds or longer during treatment week 1 that were not associated with syncope or with pacemaker implantation (5.8% vs 3.6%, P < .01 overall). 20 In the overall PLATO population, ticagrelor effi cacy (primary composite end point) was apparently lower in patients weighing less than the median weight (for their sex) and in patients who were not receiving lipidlowering medication when randomized.…”

“…Similar to guidelines for patients with STEMI, the recommendations for use of ticagrelor in patients with NSTE-ACS are primarily derived from the results of the pivotal Platelet Inhibition and Patient Outcomes (PLATO) study, which enrolled 18 624 patients with ACS 20 (NSTE-ACS, n = 11 080) 21 and compared cardiovascular outcomes in patients taking ticagrelor (180-mg loading dose, 90-mg twice-daily maintenance dose) with those taking clopidogrel (300-to 600-mg loading dose, 75-mg daily maintenance dose). 20 An aspirin loading dose of 325 mg and a maintenance dose of 75 to 100 mg daily (325 mg daily in patients with stents was permitted up to 6 months) were recommended in the study protocol.…”

Antiplatelet Therapy Changes for Patients With Myocardial Infarction With Recurrent Ischemic Events: Insights Into Contemporary Practice From the TRANSLATE‐ACS (Treatment With ADP Receptor Inhibitors: Longitudinal Assessment of Treatment Patterns and Events After Acute Coronary Syndrome) Study

“…Compared with clopidogrel, the higher‐potency P2Y 12 inhibitors, ticagrelor and prasugrel, reduce the incidence of recurrent cardiovascular events in patients with ACS undergoing percutaneous coronary intervention (PCI), but uptake of these agents into clinical practice in the United States has been tempered by concerns about increased bleeding risk and higher out‐of‐pocket patient costs 5, 6, 7, 8…”