MIAMI—Physicians should weigh the benefits and risks of more intensive antiplatelet therapy for patients in whom angiography is performed and coronary disease is confirmed, whether the patient receives medical therapy or PCI, according to the lead investigator of the late-breaking TRILOGY ACS trial presented Oct. 24 at the Transcatheter Cardiovascular Therapeutics (TCT) conference. However, because the overall TRILOGY trial was negative, the results of the trial are only hypothesis generating.
The proportion of acute coronary syndrome (ACS) patients globally who are managed medically without revascularization (PCI or CABG) is 40 to 60 percent, which includes two distinct sets of patients:
- Those who are triaged to medical therapy after angiography; and
- Those in whom angiography is not performed.
Prasugrel, a thienopyridine P2Y12 inhibitor, improved ischemic outcomes in ACS patients undergoing PCI in the TRITON-TIMI 38 trial, with an increase in major bleeding, explained lead investigator Stephen D. Wiviott, MD, of Brigham and Women’s Hospital in Boston.
The researchers included 7,243 patients less than 75 years old in the study. The primary population was broken into two groups: 43 percent of whom were triaged after angiography and 57 percent of whom were triaged without angiography.
In the angiography group, 1,524 patients were randomized to prasugrel and 1,561 patients were randomized to clopidogrel. In the non-angiography group, 2,096 patients were randomized to prasugrel and 2,602 were randomized to clopidogrel.
Overall adverse event rates were higher among patients treated with medical therapy who were triaged without angiography (16.5 vs. 12.8 percent), reported Wiviott. “This difference was largely driven by higher rates of cardiovascular death, while the rates of stroke and MI were relatively similar.”
One finding Wiviott highlighted was that the rates of bleeding were “somewhat higher” among patients who had angiography (2 vs. 1.6 percent TIMI major bleeds and 3.2 vs. 2.3 percent in TIMI major/minor bleeds).
For the primary efficacy endpoint at 30 months, patients who received angiography and had confirmed coronary artery disease had a 22 percent risk reduction with prasugrel compared with clopidogrel. This finding was statistically significant. In patients who did not have angiography, there was “absolutely no difference in the outcomes among patients treated with prasugrel compared with clopidogrel,” Wiviott said.
Also, there was a 26 percent relative reduction in MI seen among patients who were triaged to angiography after medical therapy, and no difference in MI in patients who had no angiogram.
“Substantial differences exist among patients triaged for medical therapy with or without angiography from TRILOGY ACS,” he said. “There were geographic differences discovered, with subjects from North America, Western Europe and the Mediterranean tending to have angiography pre-randomization.” As an example, in North America, about 85 percent of the patients received angiography before entry in the trial, but in Central and Eastern Europe, it was only about 25 percent. “However, we did not think the regional differences impacted the outcomes.”
He added that patients with angiography had lower overall events rates, particularly cardiovascular death.
When treated with prasugrel compared with clopidogrel, patients triaged to medical therapy following angiography tended to have: lower rates of the combined endpoint of cardiovascular death, MI or stroke; lower rates of MI, stroke alone and recurrent ischemic events; and higher rates of bleeding.
Finally, prasugrel did not reduce cardiovascular events among patients managed medically for acute coronary syndrome.
When asked for his interpretation of these findings, Wiviott said that even if a physician chooses to medically manage patients who have angiography with confirmed coronary disease, there is benefit to more intensive antiplatelet therapy. “It’s likely that these are just different populations of patients, both in their demographics and the likelihood that the ACS event was related to coronary plaque rupture, and therefore amenable to antiplatelet therapy,” he added.
“Though this is hypothesis generating, these results are consistent with previous trials and suggest when angiography is performed and coronary disease is confirmed, the benefits and risks of intensive antiplatelet therapy exist whether medical therapy or PCI is elected,” Wiviott reported.
On the physician panel, Roxana Mehran, MD, stressed that “the overall trial was a negative trial, and whenever you examine a subgroup of that trial, even if those results are positive, it can only be hypothesis generating. Although you’re seeing some benefit the p value interaction was never statistically significant.”
However, based on the results, she asked: Should these patients for whom medical therapy is being considered at least have their anatomy checked, because maybe physicians can tease out which patients may benefit from more potent antiplatelet agents?
“When we see a patient in the clinic and it is determined that he or she has coronary disease, we typically send them for angiography [in North America],” Wiviott responded. “However, if the coronary anatomy is complex—whether or not they receive medical therapy or PCI—there is some suggestion that there is some benefit for stronger antiplatelet options.”