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.

• Authors: Pontus Andell, Stefan K James, Christopher P Cannon, Derek D Cyr, Anders Himmelmann, Steen Husted, Matyas Keltai, Sasha Koul, Anwar Santoso, Ph Gabriel Steg, Robert F Storey, Lars Wallentin, David Erlinge, PLATO Investigators
• Journal: Journal of the American Heart Association (J Am Heart Assoc) Vol. 4 Issue 10 Pg. e002490 (Oct 09 2015) ISSN: 2047-9980 [Electronic] England
• PMID: 26452988 (Publication Type: Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Chemical References

• Platelet Aggregation Inhibitors
• Clopidogrel
• Ticagrelor
• Adenosine
• Ticlopidine

Topics

• Acute Coronary Syndrome (complications, diagnosis, drug therapy, mortality)
• Adenosine (adverse effects, analogs & derivatives, therapeutic use)
• Aged
• Clopidogrel
• Dyspnea (chemically induced)
• Female
• Hemorrhage (chemically induced)
• Humans
• Kaplan-Meier Estimate
• Male
• Middle Aged
• Platelet Aggregation Inhibitors (adverse effects, therapeutic use)
• Proportional Hazards Models
• Pulmonary Disease, Chronic Obstructive (complications, diagnosis, mortality)
• Risk Assessment
• Risk Factors
• Ticagrelor
• Ticlopidine (adverse effects, analogs & derivatives, therapeutic use)
• Time Factors
• Treatment Outcome