Ticagrelor Versus Clopidogrel in Patients With Acute Coronary Syndromes and Chronic Obstructive Pulmonary Disease: An Analysis From the Platelet Inhibition and Patient Outcomes (PLATO) Trial

Abstract

Background: Patients with chronic obstructive pulmonary disease (COPD) experiencing acute coronary syndromes (ACS) are at high risk for clinical events. In the Platelet Inhibition and Patient Outcomes (PLATO) trial, ticagrelor versus clopidogrel reduced the primary endpoint of death from vascular causes, myocardial infarction, or stroke after ACS, but increased the incidence of dyspnea, which may lead clinicians to withhold ticagrelor from COPD patients.

Methods and results: In 18 624 patients with ACS randomized to treatment with ticagrelor or clopidogrel, history of COPD was recorded in 1085 (5.8%). At 1 year, the primary endpoint occurred in 17.7% of patients with COPD versus 10.4% in those without COPD (P<0.001). The 1-year event rate for the primary endpoint in COPD patients treated with ticagrelor versus clopidogrel was 14.8% versus 20.6% (hazard ratio [HR]=0.72; 95% confidence interval [CI]: 0.54 to 0.97), for death from any cause 8.4% versus 12.4% (HR=0.70; 95% CI: 0.47 to 1.04), and for PLATO-defined major bleeding rates at 1 year 14.6% versus 16.6% (HR=0.85; 95% CI: 0.61 to 1.17). Dyspnea occurred more frequently with ticagrelor (26.1% vs. 16.3%; HR=1.71; 95% CI: 1.28 to 2.30). There was no differential increase in the relative risk of dyspnea compared to non-COPD patients (HR=1.85). No COPD status-by-treatment interactions were found, showing consistency with the main trial results.

Conclusions: In this post-hoc analysis, COPD patients experienced high rates of ischemic events. Ticagrelor versus clopidogrel reduced and substantially decreased the absolute risk of ischemic events (5.8%) in COPD patients, without increasing overall major bleeding events. The benefit-risk profile supports the use of ticagrelor in patients with ACS and concomitant COPD.

Clinical trial registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00391872.

Keywords: cardiovascular diseases; lung; myocardial infarction.

Figure 1

The percentages are Kaplan–Meier (K‐M) estimates of the rate of the endpoint at 12 months. CABG indicates coronary artery bypass graft; CI, confidence interval; COPD, chronic obstructive pulmonary disease; MI, myocardial infarction; TIMI, thrombolysis in myocardial infarction study group.

Figure 2

Cumulative Kaplan–Meier estimates of the time to first adjudicated occurrence of the primary efficacy endpoint (a composite of death from vascular causes, myocardial infarction, or stroke). Chronic obstructive pulmonary disease (COPD) patients randomized to ticagrelor or clopidogrel are represented by solid blue and red lines, respectively, and non‐COPD patients randomized to ticagrelor or clopidogrel are represented by dashed blue and red lines, respectively. K‐M indicates Kaplan–Meier.

Figure 3

Cumulative Kaplan–Meier estimates of the time to first PLATO‐defined major bleeding event. COPD patients randomized to ticagrelor or clopidogrel are represented by solid blue and red lines, respectively, and non‐COPD patients randomized to ticagrelor or clopidogrel are represented by dashed blue and red lines, respectively. COPD indicates chronic obstructive pulmonary disease; K‐M, Kaplan–Meier; PLATO, Platelet Inhibition and Patient Outcomes.