Best Antiplatelet Therapy in Real-World PCI? European Registries Fuel the Debate

PARIS, France—Numerous randomized trials have attempted to identify which antiplatelet therapy is best to pair with aspirin during PCI for acute coronary syndromes, particularly STEMI, but the question is far from settled in the real world. Two studies presented last week at EuroPCR 2017, one from the United Kingdom and the other from Sweden, provide insight into what happens outside the research setting.

Ticagrelor (Brilinta; AstraZeneca) did not come out ahead of clopidogrel in either study. And the British numbers showed that prasugrel (Effient; Eli Lilly) outperformed both of those drugs in terms of survival at 30 days and 1 year after primary PCI for STEMI.

Dual antiplatelet therapy (DAPT) “has really revolutionized PCI practice. It’s driven more complex procedures. . . , with marked reductions in stent thrombosis and improved ischemic outcomes,” said Mamas Mamas, BMBCh (Keele University, Stoke-on-Trent, England), who shared data from the British Cardiovascular Intervention Society (BCIS) registry.

The newer antiplatelet drugs, specifically prasugrel and ticagrelor, have swiftly moved into practice, Mamas said. But while prasugrel and ticagrelor were both supported by the findings of landmark trials, post hoc analyses of PLATO and TRITON-TIMI 38 did not show any statistically significant benefit for the drugs compared with clopidogrel for primary PCI. Only recently did the head-to-head comparison in PRAGUE-18 trial show short-term similarity between prasugrel and ticagrelor, he pointed out; however, that trial was stopped early for futility and lacked statistical power.

Prasugrel Stands Out

Mamas and colleagues looked at 89,067 PCI cases in which patients were prescribed clopidogrel, prasugrel, or ticagrelor in England and Wales. The choice of antiplatelet varied by region, with prasugrel being introduced earlier. Over time, the proportion of cases involving clopidogrel decreased and the use of the newer drugs increased, with ticagrelor now being most common.

Numerous baseline characteristics varied among the three antiplatelet groups; clopidogrel tended to be used in higher-risk patients. After multivariate logistic regression, prasugrel was associated with lower mortality than clopidogrel at 30 days and 1 year. Compared with prasugrel, ticagrelor was linked to higher mortality at both time points. The odds of death did not differ between ticagrelor and clopidogrel.

Mortality Risk of STEMI Patients Undergoing Primary PCI

Given that the analysis is observational, Mamas cautioned that its results should be considered hypothesis-generating.

Elmir Omerovic, MD, PhD (Sahlgrenska University Hospital, Gothenburg, Sweden), who was slated to present his data from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR) in the same session, asked Mamas for his thoughts on a potential mechanism for the findings.

“Ticagrelor has never been shown in primary PCI to have better mortality outcomes than clopidogrel,” Mamas replied. “I think in the real world there are much more multimorbid patients than in clinical trials. They potentially represent a complete different cohort.” Also, the drug discontinuation rate is higher in registries, he said.

Ticagrelor vs Clopidogrel

In his presentation, Omerovic shifted the conversation toward acute coronary syndromes, where the PLATO trial has shown that ticagrelor improves outcomes over clopidogrel. “European and American guidelines recommend ticagrelor and prasugrel as a ‘first-choice’ drug for treating these patients,” he noted, reporting that there’s been a rapid acceptance of ticagrelor in Sweden.

Omerovic and colleagues analyzed SCAAR data on 12,168 patients who had PCI for unstable angina, NSTEMI, and STEMI in Västra Götaland County between 2005 and 2015. Three-quarters of the patients received clopidogrel and the rest ticagrelor.

They adjusted for patient characteristics, procedural details, and other relevant clinical factors. At 30 days, risks of death or a composite of death or stent thrombosis were similar with the two antiplatelet therapies. Moreover, there was no difference in the mortality risk at 1 year. “In this observational study, treatment with ticagrelor was not superior to clopidogrel in patients with acute coronary syndrome treated with PCI,” Omerovic concluded.

One reason for ticagrelor’s lack of advantage, he suggested, may be poor compliance. Factors at play here are the risk of dyspnea and bleeding, as well as the inconvenience of twice-daily dosing.

Asked by an audience member how the findings might relate to those of the TOPIC trial, which studied the effects of switching from a more potent P2Y12 inhibitor to clopidogrel at 1 month after PCI, Omerovic said that practice is rare in Sweden.