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

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, 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

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.

© 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Figures

Figure 1
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
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
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.

References

    1. Sidney S, Sorel M, Quesenberry CP Jr, DeLuise C, Lanes S, Eisner MD. COPD and incident cardiovascular disease hospitalizations and mortality: Kaiser Permanente Medical Care Program. Chest. 2005;128:2068–2075.
    1. Doll R, Peto R, Wheatley K, Gray R, Sutherland I. Mortality in relation to smoking: 40 years’ observations on male British doctors. BMJ. 1994;309:901–911.
    1. Sin DD, Man SF. Why are patients with chronic obstructive pulmonary disease at increased risk of cardiovascular diseases? The potential role of systemic inflammation in chronic obstructive pulmonary disease. Circulation. 2003;107:1514–1519.
    1. Friedman GD, Klatsky AL, Siegelaub AB. Lung function and risk of myocardial infarction and sudden cardiac death. N Engl J Med. 1976;294:1071–1075.
    1. Engstrom G, Wollmer P, Hedblad B, Juul‐Moller S, Valind S, Janzon L. Occurrence and prognostic significance of ventricular arrhythmia is related to pulmonary function: a study from “men born in 1914”, Malmo, Sweden. Circulation. 2001;103:3086–3091.
    1. Sin DD, Wu L, Man SF. The relationship between reduced lung function and cardiovascular mortality: a population‐based study and a systematic review of the literature. Chest. 2005;127:1952–1959.
    1. Hole DJ, Watt GC, Davey‐Smith G, Hart CL, Gillis CR, Hawthorne VM. Impaired lung function and mortality risk in men and women: findings from the Renfrew and Paisley prospective population study. BMJ. 1996;313:711–715; discussion 715‐6.
    1. Salisbury AC, Reid KJ, Spertus JA. Impact of chronic obstructive pulmonary disease on post‐myocardial infarction outcomes. Am J Cardiol. 2007;99:636–641.
    1. Bursi F, Vassallo R, Weston SA, Killian JM, Roger VL. Chronic obstructive pulmonary disease after myocardial infarction in the community. Am Heart J. 2010;160:95–101.
    1. Campo G, Guastaroba P, Marzocchi A, Santarelli A, Varani E, Vignali L, Sangiorgio P, Tondi S, Serenelli C, De Palma R, Saia F. Impact of COPD on long‐term outcome after ST‐segment elevation myocardial infarction receiving primary percutaneous coronary intervention. Chest. 2013;144:750–757.
    1. Andell P, Koul S, Martinsson A, Sundström J, Jernberg T, Smith JG, James S, Lindahl B, Erlinge D. Impact of chronic obstructive pulmonary disease on morbidity and mortality after myocardial infarction. Open Heart. 2014;1:e000002.
    1. Quint JK, Herrett E, Bhaskaran K, Timmis A, Hemingway H, Wedzicha JA, Smeeth L. Effect of beta blockers on mortality after myocardial infarction in adults with COPD: population based cohort study of UK electronic healthcare records. BMJ. 2013;347:f6650.
    1. Wallentin L, Becker RC, Budaj A, Cannon CP, Emanuelsson H, Held C, Horrow J, Husted S, James S, Katus H, Mahaffey KW, Scirica BM, Skene A, Steg PG, Storey RF, Harrington RA; Investigators P , Freij A, Thorsen M. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2009;361:1045–1057.
    1. Storey RF, Becker RC, Harrington RA, Husted S, James SK, Cools F, Steg PG, Khurmi NS, Emanuelsson H, Cooper A, Cairns R, Cannon CP, Wallentin L. Characterization of dyspnoea in PLATO study patients treated with ticagrelor or clopidogrel and its association with clinical outcomes. Eur Heart J. 2011;32:2945–2953.
    1. Storey RF, Becker RC, Harrington RA, Husted S, James SK, Cools F, Steg PG, Khurmi NS, Emanuelsson H, Lim ST, Cannon CP, Katus HA, Wallentin L. Pulmonary function in patients with acute coronary syndrome treated with ticagrelor or clopidogrel (from the Platelet Inhibition and Patient Outcomes [PLATO] pulmonary function substudy). Am J Cardiol. 2011;108:1542–1546.
    1. James S, Angiolillo DJ, Cornel JH, Erlinge D, Husted S, Kontny F, Maya J, Nicolau JC, Spinar J, Storey RF, Stevens SR, Wallentin L; Group PS . Ticagrelor vs. clopidogrel in patients with acute coronary syndromes and diabetes: a substudy from the PLATelet inhibition and patient Outcomes (PLATO) trial. Eur Heart J. 2010;31:3006–3016.
    1. James S, Budaj A, Aylward P, Buck KK, Cannon CP, Cornel JH, Harrington RA, Horrow J, Katus H, Keltai M, Lewis BS, Parikh K, Storey RF, Szummer K, Wojdyla D, Wallentin L. Ticagrelor versus clopidogrel in acute coronary syndromes in relation to renal function: results from the Platelet Inhibition and Patient Outcomes (PLATO) trial. Circulation. 2010;122:1056–1067.
    1. Husted S, James S, Becker RC, Horrow J, Katus H, Storey RF, Cannon CP, Heras M, Lopes RD, Morais J, Mahaffey KW, Bach RG, Wojdyla D, Wallentin L; Group PS . Ticagrelor versus clopidogrel in elderly patients with acute coronary syndromes: a substudy from the prospective randomized PLATelet inhibition and patient Outcomes (PLATO) trial. Circ Cardiovasc Qual Outcomes. 2012;5:680–688.
    1. Schomig A. Ticagrelor—is there need for a new player in the antiplatelet‐therapy field? N Engl J Med. 2009;361:1108–1111.
    1. European Medicines Agency E . European public assessment report (EPAR) for Brilique—product information. 2011.
    1. James S, Akerblom A, Cannon CP, Emanuelsson H, Husted S, Katus H, Skene A, Steg PG, Storey RF, Harrington R, Becker R, Wallentin L. Comparison of ticagrelor, the first reversible oral P2Y(12) receptor antagonist, with clopidogrel in patients with acute coronary syndromes: rationale, design, and baseline characteristics of the PLATelet inhibition and patient Outcomes (PLATO) trial. Am Heart J. 2009;157:599–605.
    1. Hadi HA, Zubaid M, Al Mahmeed W, El‐Menyar AA, Ridha M, Alsheikh‐Ali AA, Singh R, Assad N, Al Habib K, Al Suwaidi J. Prevalence and prognosis of chronic obstructive pulmonary disease among 8167 Middle Eastern patients with acute coronary syndrome. Clin Cardiol. 2010;33:228–235.
    1. Andell P, Erlinge D, Smith JG, Sundstrom J, Lindahl B, James S, Koul S. Blocker use and mortality in COPD patients after myocardial infarction a Swedish nationwide observational study. J Am Heart Assoc. 2015;4e001611.
    1. James SK, Storey RF, Khurmi NS, Husted S, Keltai M, Mahaffey KW, Maya J, Morais J, Lopes RD, Nicolau JC, Pais P, Raev D, Lopez‐Sendon JL, Stevens SR, Becker RC; Group PS . Ticagrelor versus clopidogrel in patients with acute coronary syndromes and a history of stroke or transient ischemic attack. Circulation. 2012;125:2914–2921.
    1. Storey RF, Bliden KP, Patil SB, Karunakaran A, Ecob R, Butler K, Teng R, Wei C, Tantry US, Gurbel PA; Investigators OO . Incidence of dyspnea and assessment of cardiac and pulmonary function in patients with stable coronary artery disease receiving ticagrelor, clopidogrel, or placebo in the ONSET/OFFSET study. J Am Coll Cardiol. 2010;56:185–193.

Source: PubMed

Sponsoren und Mitarbeiter

Krankheiten

Drogeninterventionen

3
Abonnieren