A more potent P2Y12 inhibitor was not better for the prevention of ischemic complications in elective percutaneous coronary intervention (PCI), according to the ALPHEUS trial.
Ticagrelor (Brilinta) did not reduce the incidence of PCI-related MI or major myocardial injury at 48 hours (or discharge if earlier) compared with clopidogrel (Plavix) in stable but complex patients undergoing elective PCI (35.5% vs 36.2%, OR 0.97, 95% CI 0.80-1.17).
Moreover, rates of the individual endpoint components (MI type 4a, MI type 4b, or major myocardial injury) were similar between groups, reported Johanne Silvain, MD, PhD, of Sorbonne University and The Pitié-Salpêtrière Hospital in Paris, at the American Heart Association (AHA) virtual meeting. Full trial results were published simultaneously in the Lancet.
The secondary outcome of periprocedural MI and any myocardial injury also favored neither group (77.6% vs 76.8%, OR 1.05, 95% CI 0.84-1.30).
These findings remained unchanged out to 30 days, according to Silvain.
As for safety, major bleeding (BARC 3 or 5) stayed similarly infrequent between ticagrelor and clopidogrel arms. However, ticagrelor was associated with more minor bleeds (BARC 1 or 2) at 30 days (11% vs 8%, OR 1.54, 95% CI 1.12-2.11).
Dyspnea was numerically more common in the ticagrelor group (11.2% vs 0.5%), and it contributed to a higher frequency of study drug discontinuation (2.2% vs 0.4%), Silvain reported.
“These results support the use of clopidogrel as the standard of care for elective PCI,” he concluded.
“Clopidogrel provides sufficient antithrombotic protection at a lower risk of bleeding, and that is reassuring,” according to H. Vernon Anderson, MD, of McGovern Medical School at UTHealth in Houston, who was not involved with the trial.
This stands in contrast with the demonstrated benefit of ticagrelor over clopidogrel in acute coronary syndrome (ACS), where the reduced thrombotic events outweigh the increase in bleeding.
“The U.S. and European guidelines recommend dual antiplatelet therapy, including either ticagrelor or clopidogrel, and have emphasized that the evidence for ticagrelor over clopidogrel in stable patients is weak. Now we have the stronger evidence we need,” Anderson told MedPage Today.
ALPHEUS was an open-label trial conducted at 44 centers in France and five in the Czech Republic.
Silvain and colleagues included 1,883 adult patients, scheduled for non-emergent PCI with at least one high risk feature (multivessel disease, diabetes status), who were troponin-negative (or had modestly positive and decreasing troponin results).
People with ACS were excluded, as were those who needed chronic oral anticoagulation and others with planned coronary revascularization within 30 days.
The resulting cohort had a mean age of about 66, and women accounted for approximately one in five patients.
Study participants were already on clopidogrel in more than 40% of cases, and on aspirin in more than 85%. More than 60% had multivessel disease.
Patients randomized to the ticagrelor group got a loading dose of 180 mg and a maintenance dose of 90 mg twice a day after PCI. Meanwhile, the clopidogrel group had loading doses of either 300 or 600 mg (depending on physician’s discretion) and a maintenance dose of 75-mg daily.
PCI was performed with radial access in nearly all cases.
Pharmacodynamic data from ALPHEUS showed ticagrelor to be more potent than clopidogrel both 4 hours after the loading dose, and the next day after PCI, in line with previous studies.
“Our study supports the safety of elective percutaneous revascularisation, with low rates of complications. By contrast, periprocedural myonecrosis was frequent in this study … but could be more related to mechanical rather than thrombotic causes,” Silvain’s group wrote.
“In stable patients, troponin elevation may be more related to atherosclerosis and technical factors than platelet activation and thrombosis,” suggested Stephen Wiviott, MD, of Mass General Brigham in Boston, during an AHA press briefing.
A lingering question is whether stronger and more rapid platelet inhibition is needed to reduce periprocedural myonecrosis in PCI.
“Previous trials have shown a reduction in cardiac marker release and periprocedural events when using intravenous drugs such as glycoprotein IIb/IIIa inhibitors or cangrelor [Kengreal]. These drugs immediately provide a more potent effect than that obtained with oral P2Y12 inhibitors,” according to Silvain’s group.
One limitation of ALPHEUS was that it was not powered to evaluate hard outcomes — spontaneous MI, death, or stroke — or stent thrombosis, cautioned Roxana Mehran, MD, of Mount Sinai School of Medicine in New York City, who was not involved with the trial.
In addition, there may be some heterogeneity in troponin testing given that all troponin assays were allowed in the trial, the authors acknowledged.
“Finally, whether a similar strategy would have resulted in a different outcome in a population of patients with poor response to clopidogrel with high platelet reactivity is unknown,” they stated.
ALPHEUS was funded by the ACTION Study Group and AstraZeneca.
Silvain disclosed support from, and/or relevant relationships with, AstraZeneca, Bayer, Boehringer Ingelheim, BPI France, CSL Behring, Gilead, Sanofi-Aventis, Zoll, and Pharmaseeds.