Fewer major bleeds with prasugrel as default antiplatelet after PCI

When prasugrel is the default antiplatelet choice for patients with acute coronary syndromes (ACS) undergoing PCI*, fewer major bleeds occur than when ticagrelor is the default, according to the SWITCH-SWEDEHEART study presented at ESC 2026. This benefit is not accompanied by increased ischaemic events.

“Prasugrel and ticagrelor have been recommended over clopidogrel for years,” said Dr Elmir Omerovic from Sahlgrenska University Hospital and University of Gothenburg, Sweden at the ESC press conference. However, with the arrival of the ISAR-REACT 5 trial in 2020, which showed prasugrel as superior to ticagrelor, European guidelines for ACS management were updated to reflect that shift.

But whether the findings from the ISAR-REACT 5 trial are generalisable to routine practice is uncertain, said Omerovic. Thus, his team investigated which of the two P2Y12 inhibitors yielded better outcomes when the default medication was switched.

Not a head-to-head comparison

He clarified, however, that SWITCH-SWEDEHEART was not a direct comparison with ticagrelor but a policy-level perspective that, by design, offers insight into how much clinical recommendations influence practice.

The researchers used the Swedish healthcare system to compare the two medications. Seven of 21 regions participated, covering roughly half of the population. Initially, local regulators recommended ticagrelor as the first choice; then, between 2021 and 2024, patients were switched to prasugrel policy in a random order.

Recommended maintenance doses were 90 mg twice daily for ticagrelor and 10 mg daily for prasugrel (reduced to 5 mg in patients aged >70 years and those weighing <60 kg).

“By randomizing the default policy rather than individual drug assignment, the trial preserved the protection of randomization while incorporating clinician-directed exceptions, contraindications, and treatment selection as they occur in practice,” the researchers said.

Subsequently, they analysed national registry data for 17,095 patients (mean age 69.8 years, 27.8 percent female) undergoing PCI for ACS during the study period. Fifty-five percent received ticagrelor as default and 45 percent prasugrel. Nearly four in 10 presented with STEMI, 43.7 percent with NSTEMI, and 16.8 percent with unstable angina. Angiographic and procedural characteristics were similar between groups.

After excluding patients who died within a week of admission without receiving post-discharge medications, 93.5 percent of those treated with ticagrelor as a default and 94.2 percent of those treated with prasugrel received a P2Y12 inhibitor.

Drug choice did not always follow policy: 75.8 percent of patients received prasugrel as recommended and 60.6 percent received ticagrelor as recommended. Most patients treated in contrast to policy received clopidogrel, though 10 percent treated during the prasugrel policy eras received ticagrelor. Some patients also switched agents after starting: 12.7 percent of those who received ticagrelor as recommended and 8.7 percent of those who received prasugrel as recommended ultimately shifted to another P2Y12 inhibitor.

At 1-year follow-up, the primary endpoint of death, MI, or stroke had occurred in 11.1 percent of the prasugrel-policy group and 11.8 percent of the ticagrelor-policy group (adjusted OR 0.90; 95% CI 0.77-1.06). Major bleeding occurred in 4.2 percent and 4.4 percent of patients, respectively (adjusted OR 0.80, 95 percent CI, 0.64-0.99).

“With equal protection against major events and less major bleeding, the overall balance favours prasugrel as the first-choice recommendation for routine care,” Omerovic concluded. The researchers noted that the findings from the SWITCH-SWEDEHEART trial “refine, rather than contradict,” the existing evidence.

Beneficial idea

Discussant Dr Roxana Mehran from the Icahn School of Medicine at Mount Sinai, New York, New York, US, however, said the results must be interpreted with nuance because it was the policy, not the treatment, that was randomized.

“The question I would keep in mind is not whether this was well done, as it clearly was, but whether it allows comparison between the two agents,” Mehran commented.