The efficacy of ticagrelor is maintained in women with acute coronary syndromes participating in the prospective, randomized, PLATelet inhibition and patient Outcomes (PLATO) trial

Abstract

Aims: The aim of this study was to assess the relationship between sex and clinical outcomes and treatment-related complications in patients with ST-elevation or non-ST-elevation acute coronary syndromes (ACS) randomized to treatment with ticagrelor or clopidogrel in the PLATelet inhibition and patient Outcomes (PLATO) trial.

Methods: The associations between sex subgroup and the primary composite outcomes, secondary outcomes, and major bleeding endpoints as well as interaction of sex subgroup with treatment effects were analysed using Cox proportional-hazards models.

Results: Sex was not significantly associated with the probability of the primary composite endpoint [adjusted hazard ratio (HR): 1.02 (0.91-1.16)], or other adverse cardiovascular endpoints. Ticagrelor was similarly more effective than clopidogrel in reducing rates of the primary endpoint in women 11.2 vs. 13.2% [adjusted HR: 0.88 (0.74-1.06)] and men 9.4 vs. 11.1% [adjusted HR: 0.86 (0.76-0.97)] (interaction P-value 0.78), all-cause death in women 5.8 vs. 6.8% [adjusted HR: 0.90 (0.69-1.16)] and men 4.0 vs. 5.7% [adjusted HR: 0.80 (0.67-0.96)] (interaction P-value 0.49), and definite stent thrombosis in women 1.2 vs. 1.4% [adjusted HR: 0.71 (0.36-1.38)] and men 1.4 vs. 2.1% [adjusted HR: 0.63 (0.45-0.89)] (interaction P-value 0.78). The treatments did not differ for PLATO-defined overall major bleeding complications in women [adjusted HR: 1.01 (0.83-1.23)] or men [adjusted HR: 1.10 (0.98-1.24)]. Sex had no significant association with these outcomes (interactions P = 0.43-0.88).

Conclusion: Female sex is not an independent risk factor for adverse clinical outcomes in moderate-to-high risk ACS patients. Ticagrelor has a similar efficacy and safety profile in men and women.

Trial registration: ClinicalTrials.gov NCT00391872.

Keywords: Acute coronary syndromes; P2Y12 receptor; Platelets; Sex; Thrombosis; Ticagrelor.

Figure 1

Association between sex and clinical outcome. *n = 5288. ^†n = 13 336. ^‡Adjustment variables selected from the following: age, weight, height, body mass index, waist circumference, race, smoking status, diabetes, hypertension, heart rate, systolic blood pressure, changes in electrocardiogram at entry, electrocardiogram depression, killip class at entry, age, haemoglobin, white blood cells, dyslipidaemia, creatinine, angina pectoris, prior myocardial infarction, congestive heart failure, prior GI bleeding, prior percutaneous coronary intervention, prior coronary artery bypass grafting, prior transient ischaemic attack, prior non-haemorrhagic stroke, peripheral arterial disease, renal disease, chronic obstructive pulmonary disease, final diagnosis, onset of symptoms to randomized treatment, glycoprotein IIb/IIIa inhibitors at randomization, randomized treatment, treatment approach, and region. ^§PLATO-defined and adjudicated. ^††Any bleeding includes major, minor, and minimal bleedings. CABG, coronary artery bypass grafting; CI, confidence interval; COPD, chronic obstructive pulmonary disease; CV death, death from cardiovascular causes; ECG, electrocardiogram; GI, gastrointestinal bleeding; HR, hazard ratio; KM, Kaplan–Meier analysis; MI, myocardial infarction; PAD, peripheral artery disease; PCI, percutaneous coronary intervention; TIA, transient ischaemic stroke.

Figure 2

Association between sex and treatment, and clinical outcome. *Tic = ticagrelor (n = 9333). ^†Clop = clopidogrel (n = 9291). ^‡Adjustment variables selected from the following: age, weight, waist circumference, smoking status, diabetes, hypertension, heart rate, systolic blood pressure, changes in electrocardiogram at entry, killip class at entry, haemoglobin, white blood cells, dyslipidaemia, angina pectoris, prior myocardial infarction, congestive heart failure, prior GI bleeding, prior percutaneous coronary intervention, prior coronary artery bypass grafting, prior transient ischaemic attack, non-haemorrhagic stroke, peripheral arterial disease, chronic renal disease, chronic obstructive pulmonary disease, final diagnosis, onset of symptoms to randomized treatment, GP Iib/IIIa inhibitors at randomization, randomized treatment, treatment approach, and region. ^§PLATO-defined and adjudicated. ^††Any bleeding includes major, minor, and minimal bleedings. CABG, coronary artery bypass grafting; CI, confidence interval; COPD, chronic obstructive pulmonary disease; CV death, death from cardiovascular causes; ECG, electrocardiogram; GI, gastrointestinal bleeding; HR, hazard ratio; KM, Kaplan–Meier analysis; MI, myocardial infarction; PCI, percutaneous coronary intervention; TIA, transient ischaemic stroke.

Figure 3

Cumulative Kaplan–Meier estimates of the incidence of the primary composite outcome—cardiovascular death/myocardial infarction/stroke, by sex and treatment (ticagrelor vs. clopidogrel). Estimated event rate at 12 months, ticagrelor vs. clopidogrel, interaction P = 0.88. CV death, death from cardiovascular causes; MI, myocardial infarction.

Figure 4

Cumulative Kaplan–Meier estimates of incidence of all-cause death, by sex and treatment (ticagrelor vs. clopidogrel). Estimated event rate at 12 months ticagrelor vs. clopidogrel, interaction P = 0.50.

Figure 5

Cumulative Kaplan–Meier estimates of incidence of overall major bleeding complications (PLATO-defined), by sex and treatment (ticagrelor vs. clopidogrel). Estimated event rate at 12 months ticagrelor vs. clopidogrel, interaction P = 0.43. CABG, coronary artery bypass.