The year in cardiovascular medicine 2025: the top 10 papers in thrombosis and antithrombotic therapy

Inquadramento

1. Byrne RA, Valgimigli M, Bhatt DL, et al. Great debate: default duration of dual antiplatelet treatment after percutaneous coronary intervention in acute coronary syndrome should be 12 months. Eur Heart J 2025;46: 1965–78. doi.org/10.1093/ eurheartj/ehaf070. The evidence analysis summarized above provides a rationale as to why 12-month DAPT was maintained as the default strategy in preference to abbreviated durations of DAPT in patients with ACS.2 Given the conflicting evidence in the literature, Class II recommendations for DAPT abbreviation are appropriate. This approach is safer for patients than changing the default strategy to one that has not yet been adequately tested in higher-risk, more representative ACS populations.

2. Tarantini G, Honton B, Paradies V, et al. Early discontinuation of aspirin after PCI in low-risk acute myocardial infarction. N Engl J Med 2025;393:2083–94. An appropriate duration of dual antiplatelet therapy after percutaneous coronary intervention for acute myocardial infarction that has been treated with guidelinerecommended complete revascularization and a contemporary drug-eluting stent remains unclear. Among low-risk patients with acute myocardial infarction who had undergone early complete revascularization and had completed 1 month of dual antiplatelet therapy without complications, P2Y12-inhibitor monotherapy was noninferior to continued dual antiplatelet therapy with respect to the occurrence of adverse cardiovascular and cerebrovascular events and resulted in a lower incidence of bleeding events.

3. Guimaraes PO, Franken M, Tavares CAM, et al. Early withdrawal of aspirin after PCI in acute coronary syndromes. N Engl JMed 2025;393:2095–106. Whether potent P2Y12 inhibitor monotherapy without ASA initiated shortly after successful percutaneous coronary intervention (PCI) is effective and safe for patients with acute coronary syndromes is unclear. Among patients who had undergone successful PCI for acute coronary syndromes, potent P2Y12 inhibitor monotherapy was not found to be noninferior to dual antiplatelet therapy with respect to a composite of death or ischemic events at 12 months.

4. Jeppsson A, James S, Moller CH, Malm CJ, Dalén M, Vanky F, et al. Ticagrelor and aspirin or aspirin alone after coronary surgery for acute coronary syndrome. N Engl J Med 2025; 393:2313–23.   Patients benefit from antiplatelet therapy after coronary-artery bypass grafting (CABG) for an acute coronary syndrome. Whether the addition of ticagrelor to ASA, as compared with ASA alone, further reduces the risk of adverse cardiovascular outcomes is unclear. Among patients who underwent CABG for an acute coronary syndrome, ticagrelor plus ASA did not result in a lower incidence of death, myocardial infarction, stroke, or repeat coronary revascularization than ASA alone at 1 year.

5. Van’t Hof AWJ, Gibson CM, Rikken SAOF, et al. Zalunfiban at first medical contact for ST-elevation myocardial infarction. NEJM Evid 2025;5:EVIDoa2500268. Zalunfiban is a glycoprotein IIb/IIIa (integrin αIIbβ3) inhibitor designed for subcutaneous administration on first medical contact with patients with suspected ST-segment elevation myocardial infarction (STEMI). In patients with STEMI, zalunfiban administered at first medical contact significantly improved preintervention infarct-related patency and reduced the likelihood of a worse 30-day multicomponent hierarchical clinical end point. Zalunfiban was not associated with increased severe or life-threatening bleeding but was associated with increased mild to moderate bleeding.

6. Rashedi S, Keykhaei M, Sato A, et al. Anticoagulation and antiplatelet therapy for atrial fibrillation and stable coronary disease: meta-analysis of randomized trials. J Am Coll Cardiol 2025;85:1189–203.   The optimal long-term antithrombotic strategy in patients with atrial fibrillation (AF) and stable coronary artery disease (CAD) remains uncertain. Individual randomized controlled trials (RCTs) had variations in their reported results and were not powered for effectiveness outcomes. In patients with AF and stable CAD, OAC monotherapy, compared with OAC plus SAPT, was not associated with a statistically significant increased risk of ischemic events but resulted in a significantly reduced risk of bleeding.

7. Lemesle G, Didier R, Steg PG, et al. Aspirin in patients with chronic coronary syndrome receiving oral anticoagulation. N Engl J Med 2025;393:1578–88. The appropriate antithrombotic regimen for patients with chronic coronary syndrome who are at high atherothrombotic risk and receiving long-term oral anticoagulation remains unknown. Among patients with chronic coronary syndrome at high atherothrombotic risk who were receiving an oral anticoagulant, the addition of ASA led to a higher risk of cardiovascular death, myocardial infarction, stroke, systemic embolism, coronary revascularization, or acute limb ischemia than placebo, as well as higher risks of death from any cause and major bleeding.

8. Lee SJ, Yu HT, Lee YJ, et al. Therapy for atrial fibrillation in patients with drug eluting stents. N Engl J Med 2025. https://doi.org/10.1056/NEJMoa2512091. Despite guideline recommendations, evidence for the use of non–vitamin K antagonist oral anticoagulant (NOAC) monotherapy in patients with atrial fibrillation after implantation of a drug-eluting stent remains limited. Among patients with atrial fibrillation who had undergone implantation of a drug-eluting stent at least 1 year earlier, NOAC monotherapy was noninferior to combination therapy for net adverse clinical events.

9. Joosten LPT, van Doorn S, van de Ven PM, et al. Safety of switching from a vitamin K antagonist to a non-vitamin K antagonist oral anticoagulant in frail older patients with atrial fibrillation: results of the FRAIL AF randomized controlled trial. Circulation 2024;149:279–89. https://doi.org/10.1161/ CIRCULATIONAHA.123.066485. There is ambiguity whether frail patients with atrial fibrillation managed with vitamin K antagonists (VKAs) should be switched to a non vitamin K oral anticoagulant (NOAC). Switching international normalized ratio–guided VKA treatment to an NOAC in frail older patients with atrial fibrillation was associated with more bleeding complications compared with continuing VKA treatment, without an associated reduction in thromboembolic complications.

10. Nicolau AM, Giugliano RP, Zimerman A, et al. Outcomes in older patients after switching to a newer anticoagulant or remaining on warfarin: the COMBINE-AF substudy. J Am Coll Cardiol 2025;86:426–39. Whether frail, elderly patients with atrial fibrillation (AF) on a vitamin K antagonist (VKA) should switch to a direct-acting oral anticoagulant (DOAC) was studied in the FRAIL-AF trial and remains controversial. Frail, elderly, VKA-experienced patients with AF switched to SD-DOAC experienced significant reductions in stroke or systemic embolism, fatal and intracranial bleeding, and death. Gastrointestinal bleeding was increased with SD-DOAC, while major bleeding and the primary net clinical outcome were similar. Based on these findings, SD-DOAC is a reasonable choice for frail, elderly, VKA-experienced patients to reduce stroke and systemic embolism, death, and the most serious types of bleeding.

11. Veltkamp R, Korompoki E, Harvey KH, et al. Direct oral anticoagulants versus no anticoagulation for the prevention of stroke in survivors of intracerebral haemorrhage with atrial fibrillation (PRESTIGE-AF): a multicentre, openlabel, randomised, phase 3 trial. Lancet 2025;405:927–36. Direct oral anticoagulants (DOACs) reduce the rate of thromboembolism in patients with atrial fibrillation but the benefits and risks in survivors of intracerebral haemorrhage are uncertain. We aimed to determine whether DOACs reduce the risk of ischaemic stroke without substantially increasing the risk of recurrent intracerebral haemorrhage. DOACs effectively prevent ischaemic strokes in survivors of intracerebral haemorrhage with atrial fibrillation but a part of this benefit is offset by a substantially increased risk of recurrent intracerebral haemorrhage. To optimise stroke prevention in these vulnerable patients, further evidence from ongoing trials and a meta-analysis of randomised data is needed, as well as the evaluation of safer medical or mechanical alternatives for selected patients.

12. Karthikeyan G, Rajashekar P, Devasenapathy N, et al. Urgent surgery vs fibrinolytic therapy for left-sided prosthetic valve thrombosis: a randomized trial. Eur Heart J 2025;46:3373–81. https://doi. org/10.1093/eurheartj/ ehaf391. Left-sided mechanical prosthetic valve thrombosis (PVT) is common in lowresource settings. Treatment is either by fibrinolytic therapy (FT) or urgent surgery. This is the first randomized controlled trial (RCT) comparing urgent surgery with FT for symptomatic left-sided PVT. In symptomatic left-sided PVT, urgent surgery is not more efficacious than FT. Surgery is associated with a higher risk of complications, including death, while FT is more often associated with residual valve dysfunction.