PLATO Substudy: Ticagrelor Doesn't Hurt the Lungs

October 13, 2011

October 12, 2011 (Dallas, Texas) — Daily treatment with ticagrelor (Brilinta, AstraZeneca) in patients with acute coronary syndromes (ACS) doesn't have an adverse effect on pulmonary function compared with clopidogrel (Plavix, Bristol-Myers Squibb/Sanofi-Aventis), suggests a small, prospectively defined substudy of the Platelet Inhibition and Patient Outcomes (PLATO) trial [1].

The finding argues against a direct influence on the lungs as the mechanism behind a well-documented side effect of the newer antiplatelet, mild to moderate dyspnea that is usually self-limiting, which despite the pulmonary-study results had been observed with ticagrelor in the overall PLATO population.

It also represents "one strand of a body of evidence suggesting that ticagrelor-induced dyspnea is a benign phenomenon," lead author Dr Robert F Storey (University of Sheffield, UK), told heartwire by email.

As described in an American Journal of Cardiology report published online September 3, 2011, the pulmonary substudy included 199 PLATO subjects who were without "advanced lung disease" or congestive heart failure and hadn't undergone CABG after their qualifying ACS event. They completed pulmonary-function studies on three occasions: 30 to 40 days after the start and within 10 days of the end of randomized therapy (which was, on average, after 211 days) and again about a month later.

On none of the three occasions was there a difference between the two treatment groups in tests of pulse oximetry, forced expiratory volume in one second, forced vital capacity, lung volumes, or diffusion capacity.

The PLATO investigators note that baseline pulmonary-function testing wasn't possible in the trial as it would have interfered with prompt treatment.

"Although there were unavoidable limitations in the pulmonary-substudy design related to studying an ACS population, it should be noted that this work complements the previous analysis of the ONSET/OFFSET study [2], in which we found no evidence, on prospective assessment, of any pulmonary or cardiac pathology associated with ticagrelor-related dyspnea," according to Storey.

The international PLATO trial had randomized 18 624 patients with ACS to receive either ticagrelor (180-mg loading dose followed by 90 mg twice daily) or clopidogrel (300- to 600-mg loading dose followed by 75 mg/day thereafter) on top of aspirin, as previously reported by heartwire .

The ticagrelor group showed a 16% reduction in the primary end point of CV death, MI, or stroke (p<0.001) compared with those who received clopidogrel over the average follow-up of 190 days.

The pulmonary-substudy publication closely follows release of a post hoc analysis of the entire PLATO population shedding more light on ticagrelor-associated dyspnea [3].

"Interestingly," Storey said, "the ticagrelor patients developing dyspnea in the first 30 days had no increase in mortality compared with the patients without dyspnea in this time period, despite having higher frequencies of high-risk characteristics, raising the hypothesis that ticagrelor-related dyspnea is not associated with reduced efficacy in terms of mortality reduction compared with clopidogrel treatment."

 "Funding and statistical support were provided by AstraZeneca," from which Storey reports receiving "honoraria, consultant fees, and/or research grants." Two coauthors on the report "are employees of and have equity ownership in AstraZeneca."