Settembre 8, 2026

Great debate: preventive percutaneous coronary intervention added to optimal medical treatment should be the default treatment for non-flow-limiting vulnerable plaques

Nell’introduzione, Barbato e Gallinoro dell’Ospedale Sant’Andrea di Roma osservano come alla base delle sindromi coronariche acute (ACS) vi sia una rottura o erosione di una placca vulnerabile, generalmente non limitante il flusso. Negli ultimi anni, una considerevole mole di dati, ottenuti soprattutto con l’utilizzo dell’imaging intra-coronarico, ha cercato di individuare le caratteristiche morfologiche di tali placche così da poter mettere in atto terapie preventive riguardo alla loro potenziale instabilizzazione. Inoltre, recenti studi….

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Trombosi del ventricolo sinistro nei pazienti STEMI: quale terapia antitrombotica?

Inquadramento La trombosi del ventricolo sinistro (LVT) è evenienza non rara nell’infarto miocardico acuto, soprattutto a sede anteriore, anche con il trattamento interventistico attuale che ne ha comunque ridotto l’incidenza. Infatti, alla risonanza magnetica (RMN), che ha una sensibilità superiore rispetto all’ecocardiografia transtoracica, l’incidenza è compresa, per l’infarto anteriore, tra il 15% e il 25%[1]McCarthy CP, Vaduganathan M, McCarthy KJ, et al. Left ventricular thrombus after acute myocardial infarction: screening, prevention, and treatment. JAMA Cardiol. 2018;3:642-649. … Continua a leggere. Uno studio del 2022 ha mostrato una riduzione marcata (pari al 92%) del rischio di LVT in pazienti STEMI, trattati con PCI primaria utilizzando una terapia composta da rivaroxaban a bassa dose associata a una doppia terapia antipiastrinica (DAPT)[2]Zhang Z, Si D, Zhang Q, et al. Prophylactic rivaroxaban therapy for left ventricular thrombus after anterior ST-segment elevation myocardial infarction. JACC Cardiovasc Interv. 2022;15:861-872. … Continua a leggere. Tuttavia, la casistica limitata dello studio non ha permesso di raggiungere risultati definitivi. Lo studio in esame Lo studio APERITIF (Low-Dose Rivaroxaban for Prevention of Left Ventricular Thrombosis After Anterior Acute Myocardial Infarction) è uno studio policentrico randomizzato, inserito su un registro permanente (French Cohort of Myocardial Infarction Evaluation -FRENCHIE-) di pazienti con infarto acuto ricoverati in UTIC. Il trial, condotto in 29 centri francesi, ha arruolato 560 pazienti con STEMI anteriore (età media 61 anni, 21% rappresentato da donne, LVEF media 45%), randomizzandoli a ricevere per 4 settimane dall’evento acuto rivaroxaban 2,5 mg due volte al dì associato a DAPT (“gruppo triplice terapia antitrombotica”, n=277, ticagrelor associato ad ASA nel 69% dei casi), oppure a una sola DAPT (“gruppo sola DAPT” – n=283 – ticagrelor associato ad ASA nell’87% dei casi). Rivaroxaban è stato sospeso prematuramente in 42 pazienti nel gruppo con triplice terapia antitrombotica. La numerosità di campione (560 pazienti) è stata calcolata sulla base di una incidenza di eventi attesi nell’11% dei pazienti del gruppo “triplice terapia antitrombotica” versus 20% nel gruppo DAPT. A un mese (−5/+15 giorni) è stata eseguita una RMN per verificare la presenza di LVT (outcome primario), individuato in 38 pazienti del gruppo “triplice terapia antitrombotica” (13.7%) e in 47 pazienti del gruppo “sola DAPT” (16.6%) con una differenza di −2.9%; 95% CI, da −8.9% a +3.2%; P=.34).  Tra i pazienti in DAPT, la trombosi era apparentemente più elevata (29%) nei pazienti in DAPT con ASA che in quelli con ASA e ticagrelor (6.9%). Il diametro del trombo non era significativamente differente tra gruppo in triplice (9 mm) versus sola DAPT (11 mm), così come i MACE (mortalità per ogni causa, infarto miocardico, stroke: 0.7% versus 1.1%). Il BARC bleeding ≥2 era non significativamente differente nel gruppo in triplice terapia versus sola DAPT (1.5% vs 0.7%). Solo il BARC bleeding 1 era più elevato nel gruppo in triplice terapia antitrombotica (Tabella). Take home message Nei pazienti con STEMI anteriore, una triplice terapia antitrombotica (DAPT + rivaroxaban a bassa dose) non ha significativamente ridotto l’incidenza di trombosi del ventricolo sinistro rispetto alla sola DAPT. La potenza limitata dello studio non permette di escludere un potenziale effetto benefico. Interpretazione dei dati L’incidenza di trombosi del ventricolo sinistro in questo studio, che ha incluso solo pazienti con infarto STEMI a sede anteriore, è stata globalmente del 15%, un dato inferiore rispetto a quanto osservato in alcune casistiche riportate in letteratura in popolazioni analoghe[3]McCarthy CP, Vaduganathan M, McCarthy KJ, et al. Left ventricular thrombus after acute myocardial infarction: screening, prevention, and treatment. JAMA Cardiol. 2018;3:642-649. … Continua a leggere. Questa è una problematica che ha progressivamente perso il suo impatto clinico per l’affermarsi nel tempo del trattamento con PCI primaria dell’infarto acuto, dell’utilizzo di farmaci che contrastano il rimodellamento ventricolare e di una terapia antiaggregante potente. Ne è prova che tale tematica non è affrontata nelle Linee Guida ESC del 2023[4]Byrne RA, Rossello X, Coughlan JJ, et al. ESC Scientific Document Group. 2023 ESC guidelines for the management of acute coronary syndromes. Eur Heart J 2023;44:3720-3826.doi:10.1093/eurheartj/ehad191, mentre era discussa e oggetto di raccomandazioni sull’utilizzo della terapia anticoagulante nelle Linee Guida più datate[5]Van de Werf F, Ardissino D, Betriu A, et al. for the Task Force on the Management of Acute Myocardial Infarction of the European Society of Cardiology. Management of acute myocardial infarction … Continua a leggere. Gli Autori attribuiscono la minore frequenza della trombosi ventricolare osservata nel gruppo randomizzato a DAPT, rispetto a quanto atteso (globalmente 16.6% in confronto all’ipotesi iniziale del 20% nel disegno dello studio), all’utilizzo di ticagrelor rispetto a clopidogrel nella maggioranza dei pazienti STEMI. In effetti, nello studio APERITIF (anche se questi dati non derivano da un confronto diretto tra uso di clopidogrel e uso di ticagrelor) l’incidenza di trombosi ventricolare è stata osservata con minor frequenza nei pazienti in DAPT che assumevano ticagrelor (7%), rispetto ai pazienti in DAPT basata su clopidogrel (29%). Un esperienza analoga è stata riportata in letteratura[6]Altıntaş B, Altındağ R, Bilge Ö, et al. The effectmof ticagrelor based dual antiplatelet therapy on development of late left ventricular thrombus after acute anterior ST elevation myocardial … Continua a leggere. Benchè questa osservazione sia interessante, il suo peso pratico risulta molto modesto. Nello studio PLATO, che ha confrontato ticagrelor con clopidogrel nelle sindromi coronariche acute, l’ictus ischemico si è verificato nell’1.1% di entrambi i gruppi, mentre i TIA sono stati osservati in percentuali ancora più ridotte (0.2% con ticagrelor versus 0.4% con clopidogrel). Bibliografia[+] Bibliografia ↑1 McCarthy CP, Vaduganathan M, McCarthy KJ, et al. Left ventricular thrombus after acute myocardial infarction: screening, prevention, and treatment. JAMA Cardiol. 2018;3:642-649. doi:10.1001/jamacardio.2018.1086 ↑2 Zhang Z, Si D, Zhang Q, et al. Prophylactic rivaroxaban therapy for left ventricular thrombus after anterior ST-segment elevation myocardial infarction. JACC Cardiovasc Interv. 2022;15:861-872. doi:10.1016/j.jcin.2022.01.28. ↑3 McCarthy CP, Vaduganathan M, McCarthy KJ, et al. Left ventricular thrombus after acute myocardial infarction: screening, prevention, and treatment. JAMA Cardiol. 2018;3:642-649. doi:10.1001/jamacardio.2018.1086. ↑4 Byrne RA, Rossello X, Coughlan JJ, et al. ESC Scientific Document Group. 2023 ESC guidelines for the management of acute coronary syndromes. Eur Heart J 2023;44:3720-3826.doi:10.1093/eurheartj/ehad191 ↑5 Van de Werf F, Ardissino D, Betriu A,

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Effetti favorevoli della rivascolarizzazione nella cardiomiopatia ischemica: in quali pazienti?

Lo studio ha incluso 941 pazienti (età media 65 anni, 81% erano maschi, 49% con anamnesi di infarto miocardico e il 18% con fibrillazione atriale) con ICM (coronaropatia ostruttiva documentata alla coronarografia e associata a disfunzione FE definita in base a FE <50%). Tutti pazienti avevano eseguito una risonanza magnetica (RMN) per evidenziare aree cicatriziali in base alla presenza di “late gadolinium enhancement - LGE - tra il 2015 e il 2022. Di questi, 193 avevano eseguito un intervento di rivascolarizzazione (CABG n=117, PCI n=76) entro 90 giorni dalla RMN (“early revascularization group), con una rivascolarizzazione completa nel 76% dei casi, mentre 748 erano stati rivascolarizzati dopo 90 giorni o mai rivascolarizzati (“no early revascularization group”). La FE era del 33% nei pazienti rivascolarizzati precocemente e 36% nel gruppo non rivascolarizzato (P =0.01). Alla RMN un segmento di miocardio è stato considerato vitale se la transmuralità della cicatrice era ≤50%. Utilizzando il software CARAT gli operatori interagivano con un diagramma coronarico personalizzato per indicare severità, lunghezza e sede delle stenosi coronariche. Per ogni segmento miocardico...

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Bisoprololo o verapamil nella cardiomiopatia ipertrofica non ostruttiva

Lo studio è il primo, relativamente ampio, di confronto tra farmaci in pazienti con cardiomiopatia ipertrofica non ostruttiva. Il messaggio è clinicamente rilevante in quanto conferisce una superiorità a verapamil rispetto a bisoprololo sulla base dei risultati del test cardiopolmonare che ha mostrato una riduzione del picco di VO2 con il betabloccante, mentre è stata osservata alcuna variazione significativa di tale parametro durante la terapia con il calcio-antagonista non diidropiridinico. Poichè il picco di VO2 è correlato alla portata cardiaca (ed è predittore di eventi in questa patologia) è verisimile che la differenza osservata tra i due farmaci sia dipendente dal diverso effetto sulla frequenza cardiaca di picco, decisamente inferiore con bisoprololo rispetto a verapamil. L’aumentato volume telediastolico, osservato durante trattamento con bisoprololo, riflette verosimilmente…

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Efficacia e complicanze della “ross procedure”: importanza dell’esperienza dell’operatore

Lo studio presenta notevoli elementi di interesse. Da un lato la crescita degli interventi negli ultimi anni sottolinea i dati favorevoli di outcome associati alla procedura di Ross. La mortalità operatoria più bassa è stata osservata negli anni 2019/2020, quando i centri che effettuavano questo tipo di intervento erano meno di 30 (27 nel 2019 e 29 nel 2020) e la procedura di Ross rappresentava meno del 3% delle sostituzioni valvolari aortiche chirurgiche (112 procedure nel 2019, pari al 2.3% e 149 nel 2020, pari al 2.9%). A partire da quegli anni, un numero crescente di centri ha iniziato a effettuare tale intervento…

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The year in cardiovascular medicine 2025: the top 10 papers in valvular heart disease

1. Poterucha TJ, Jing L, Ricart RP, et al. Detecting structural heart disease from electrocardiograms using AI. Nature 2025; 644:221–30. doi.org/10.1038/s41586-025-09227-0. We introduce a deep learning model, EchoNext, trained on more than 1 million heart rhythm and imaging records across a large and diverse health system to detect many forms of structural heart disease. These findings support the potential of artificial intelligence to expand access to heart disease screening at scale. To enable further development and transparency, we have publicly released model weights and a large, annotated dataset linking heart rhythm data to imaging-based diagnoses. 2. Long A, Finer J, Hartman H, et al. Deep learning for echocardiographic assessment and risk stratification of aortic, mitral, and tricuspid regurgitation: the DELINEATEregurgitation study. Eur Heart J 2025;46: 2780–91. Classification and risk stratification in aortic (AR), mitral (MR), and tricuspid regurgitation (TR) remains a significant clinical challenge. This study aimed to develop an artificial intelligence (AI) system to assess valvular regurgitation and stratify MR-progression risk. An AI system can accurately classify AR, MR, and TR and predict MR progression beyond currently known risk factors. 3. Généreux P, Banovic M, Kang D, et al. Aortic valve replacement vs clinical surveillance in asymptomatic severe aortic stenosis: a systematic review and meta-analysis. J Am Coll Cardiol 2025;85:912–22. doi.org/ 10.1016/j.jacc.2024.11.006.   Current guidelines recommend a strategy of clinical surveillance (CS) for patients with asymptomatic severe aortic stenosis (AS) and a normal left ventricular ejection fraction. In this meta-analysis of 4 randomized trials, early aortic valve replacement was associated with a significant reduction in unplanned cardiovascular or heart failure hospitalization and stroke and no differences in all-cause and cardiovascular mortality compared with CS. 4. Leon MB, Mack MJ, Pibarot P, et al. Transcatheter or surgical aortic-valve replacement in low-risk patients at 7 years. N Engl J Med 2025. doi.org/10.1056/NEJM oa2509766. Five-year data from the PARTNER 3 trial showed that among low-risk patients with severe, symptomatic aortic stenosis, outcomes were similar among patients who had undergone transcatheter aortic-valve replacement (TAVR) and those who had undergone surgical aortic-valve replacement. Longer-term assessments of clinical outcomes and valve durability are needed. Among low-risk patients with severe, symptomatic aortic stenosis, no significant differences with respect to two primary composite end points involving death, stroke, and rehospitalization were observed at 7 years between those who had undergone TAVR and those who had undergone surgery. 5. Jørgensen TH, Savontaus M, Willemen Y, et al. Three-year follow-up of the NOTION-2 trial: TAVR versus SAVR to treat younger low-risk patients with tricuspid or bicuspid aortic stenosis. Circulation 2025;152: 1326–37.   Transcatheter aortic valve replacement (TAVR) is increasingly performed in younger, low surgical risk patients. The NOTION-2 study (The Nordic Aortic Valve Intervention) reports midterm outcomes in low-risk patients age 60 to 75 years with severe tricuspid or bicuspid aortic stenosis undergoing TAVR or surgical valve replacement. For patients age 60 to 75 years with severe aortic stenosis who are at low surgical risk, 3-year clinical outcomes are similar between TAVR and surgery. Both procedures are associated with low rates of structural valve deterioration and need for reintervention. 6. Raposeiras-Roubin S, Amat-Santos IJ, Rossello X, et al. Dapagliflozin in patients undergoing transcatheter aortic-valve implantation. N Engl J Med 2025;392:1396–405. https://doi.org/10.1056/ NEJMoa2500366. Sodium–glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of heart-failure admission among high-risk patients. However, most patients with valvular heart disease, including those undergoing transcatheter aortic-valve implantation (TAVI), have been excluded from randomized trials. Among older adults with aortic stenosis undergoing TAVI who were at high risk for heart failure events, dapagliflozin resulted in a significantly lower incidence of death from any cause or worsening of heart failure than standard care alone.  7. Messika-Zeitoun D, Chu MWA, Bouchard D, et al. Clinical presentation and outcomes after surgery for mitral regurgitation: real- world insights from the MITRACURE international registry. Circulation 2025;152: 927–38.  Comprehensive knowledge of the clinical presentation, contemporary management, and outcomes on “all-comer” patients referred for mitral valve surgery (MVS) are critical to evaluate current practice and adherence to guidelines, understand selection biases, and inform key stakeholders on quality improvement. MITRACURE provides a contemporary, multicenter, “real-world” picture of the clinical presentation, management, and in-hospital outcomes of MVS for MR in two Western countries. Patients were often referred late in the disease process, with few patients undergoing early intervention. The higher mortality and lower repair rates reported may be more reflective of an unselected MR patient population but have room for improvement. Our results underline the need to develop strategies to improve management and outcomes of patients with MR.  8. Kaneko T, Kagiyama N, Okazaki S, et al. Transcatheter edge-to-edge repair vs medical therapy in atrial functional mitral regurgitation: a propensity score-based comparison from the OCEAN-Mitral and REVEAL-AFMR registries. Eur Heart J 2025. Epub ahead of print. doi.org/10.1093/ eurheartj/ehaf511. Atrial functional mitral regurgitation (AFMR) commonly affects elderly and frail individuals. The prognostic impact of transcatheter edgeto-edge repair (TEER) for AFMR has not been. investigated. In real-world data, TEER for patients with moderate or severe AFMR were associated with a lower incidence of adverse events compared with medical treatment.  9. Guerrero ME, Daniels DV, Makkar RR, et al. Percutaneous transcatheter valve replacement in individuals with mitral regurgitation unsuitable for surgery or transcatheter edge-to-edge repair: a prospective, multicountry, single-arm trial. Lancet 2025;406:2541–50. https://doi.org/ 10.1016/S0140- 6736(25)02073-2. Patients with severe mitral regurgitation are frequently not candidates for surgery or transcatheter edge-to-edge repair (TEER). We aimed to evaluate 1-year outcomes of a novel percutaneous transseptal transcatheter mitral valve replacement (TMVR) system in patients unsuitable for surgery or TEER. Percutaneous transseptal TMVR with the SAPIEN M3 system effectively reduced mitral regurgitation with low rates of complications and mortality. These findings support percutaneous TMVR with the SAPIEN M3 system as a therapeutic option for patients who are unsuitable for surgery or TEER. 10. Kar S, Makkar RR, Whisenant BK, Hamid N, Naik H, Tadros P, et al. Two-year outcomes of transcatheter edge-to-edge repair for severe tricuspid regurgitation: the TRILUMINATE pivotal randomized controlled trial. Circulation 2025;151:1630–8. One-year outcomes of TRILUMINATE Pivotal (Trial to Evaluate Cardiovascular

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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.

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