TRILOGY’s subplot: Fewer adverse events with angiography + prasugrel

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 - clinical trial

In a subanalysis of TRILOGY ACS patients who had angiography, the prasugrel group had fewer adverse events than the clopidogrel group. Overall, patients who had angiography fared better than those who did not, a finding that editorial writers attributed to patient selection.

The study and editorial were published Aug. 17 in The Lancet.

TRILOGY ACS (Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage Acute Coronary Syndromes) was generally a neutral trial. Results from the phase III randomized study found Prasugrel (Effient) was not superior to clopidogrel (Plavix) for reducing the rate of major cardiovascular events in patients with acute coronary syndrome (ACS) who did not undergo revascularization. Patients in the prasugrel group had higher rates of minor and moderate bleeding, but there was no significant increase in the rate of severe, major or life-threatening bleeding.

Before randomization, patients enrolled in the trial could have undergone angiography. Stephen D. Wiviott, MD, of Brigham and Women’s Hospital in Boston, and colleagues wanted to determine if the patients who had angiography had different characteristics and outcomes than those who did not have angiography, and to compare the prasugrel and clopidogrel angiography subgroups.

Of the more than 7,000 patients enrolled in TRILOGY ACS, 43 percent had angiography before medical treatment. Those who did not have angiography were more likely to be older, women and have unstable angina rather than non-STEMI and to have been treated in facilities in Latin America, east Asia, India and central and eastern Europe.

Patients who had angiography before treatment had fewer adverse events as defined by the primary endpoint, a composite of cardiovascular death, MI or stroke at 30 months, compared with those who did not (12.8 percent vs. 16.5 percent). Within the group that had angiography, the prasugrel subset had fewer adverse events than the clopidogrel subset (10.7 percent vs. 14.9 percent). For patients who did not have angiography, type of antiplatelet therapy made no difference in adverse events.

“These data may have implications for patient care, since the patients who seem to benefit most from intensified antiplatelet treatment are those with confirmed coronary artery disease,” Wiviott said in a release. “However, these data would need to be verified in another study before making such a recommendation.”

The Wiviott team and editorial writers Rajesh V. Swaminathan, MD, and Dmitry N. Feldman, MD, both of NewYork Presbyterian Hospital in New York City, described the results as hypothesis generating.

Swaminathan and Feldman reasoned that patient selection accounted for the difference in outcomes between the patients who had angiography and those who did not. “[P]atients with more comorbidities were more likely to be treated without angiography. Regional selection bias also played a part. Patients who enrolled without angiography were more likely to have been enrolled … where access to angiography might have been limited.”

They pointed out that angiography would have helped to exclude patients with modest coronary disease and those who would benefit from PCI or CABG. “Therefore, most patients enrolled after angiography had moderate or severe coronary disease probably not suitable for percutaneous coronary intervention  or were in centres without access to percutaneous coronary intervention and had a definitive cause of acute coronary syndrome. Coupled with favourable characteristics for reduced bleeding … with prasugrel, these patients would probably benefit from more intense P2Y12 inhibition.”

They added that the results offer “compelling but inconclusive evidence for the use of prasugrel in this heterogeneous and often undertreated population.”

Daiichi Sankyo and Eli Lilly provided funding for the study.