Oral activated factor XI (FXIa) inhibitors may modulate coagulation to prevent thromboembolic events without substantially increasing bleeding. We explored the pharmacodynamics, safety, and efficacy of the oral FXIa inhibitor asundexian for secondary prevention after acute myocardial infarction (MI).We randomized 1601 patients with recent acute MI to oral asundexian 10, 20, or 50 mg or placebo once daily for 6 to 12 months in a double-blind, placebo-controlled, phase 2, dose-ranging trial. Patients were randomized within 5 days of their qualifying MI and received dual antiplatelet therapy with aspirin plus a P2Y12 inhibitor. The effect of asundexian on FXIa inhibition was assessed at 4 weeks. The prespecified main safety outcome was Bleeding Academic Research Consortium type 2, 3, or 5 bleeding comparing all pooled asundexian doses with placebo. The prespecified efficacy outcome was a composite of cardiovascular death, MI, stroke, or stent thrombosis comparing pooled asundexian 20 and 50 mg doses with placebo.The median age was 68 years, 23% of participants were women, 51% had ST-segment-elevation MI, 80% were treated with aspirin plus ticagrelor or prasugrel, and 99% underwent percutaneous coronary intervention before randomization. Asundexian caused dose-related inhibition of FXIa activity, with 50 mg resulting in >90% inhibition. Over a median follow-up of 368 days, the main safety outcome occurred in 30 (7.6%), 32 (8.1%), 42 (10.5%), and 36 (9.0%) patients receiving asundexian 10 mg, 20 mg, or 50 mg, or placebo, respectively (pooled asundexian versus placebo: hazard ratio, 0.98 [90% CI, 0.71-1.35]). The efficacy outcome occurred in 27 (6.8%), 24 (6.0%), 22 (5.5%), and 22 (5.5%) patients assigned asundexian 10 mg, 20 mg, or 50 mg, or placebo, respectively (pooled asundexian 20 and 50 mg versus placebo: hazard ratio, 1.05 [90% CI, 0.69-1.61]).In patients with recent acute MI, 3 doses of asundexian, when added to aspirin plus a P2Y12 inhibitor, resulted in dose-dependent, near-complete inhibition of FXIa activity without a significant increase in bleeding and a low rate of ischemic events. These data support the investigation of asundexian at a dose of 50 mg daily in an adequately powered clinical trial of patients who experienced acute MI.URL: https://www.gov; Unique identifier: NCT04304534; URL: https://www.clinicaltrialsregister.eu/ctr-search/search; Unique identifier: 2019-003244-79.

10.1161/circulationaha.122.061612

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Citations (109)

468Vulnerability for cardiac arrest in patients with ST elevation myocardial infarction: Is it time or patient dependent? Results from a nationwide observational study

European Heart Journal (2018)

Mahadi Salah Sofie Gevaert Patrick Coussement Christophe Beauloye Peter Sinnaeve

10.1093/eurheartj/ehy564.468

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Presentation, care, and outcomes of patients with NSTEMI according to World Bank country income classification: the ACVC-EAPCI EORP NSTEMI Registry of the European Society of Cardiology

European Heart Journal - Quality of Care and Clinical Outcomes (2023)

Ramesh Nadarajah Peter Ludman Cécile Laroche Yolande Appelman Salvatore Brugaletta

The majority of NSTEMI burden resides outside high-income countries (HICs). We describe presentation, care, and outcomes of NSTEMI by country income classification.

Presentation (obstetrics)

10.1093/ehjqcco/qcad008

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Feasibility and cost of FH cascade screening in Belgium (BEL-CASCADE) including a novel rapid rule-out strategy

Acta Cardiologica (2020)

Olivier Descamps Ernst Rietzschel Anja Laporte Ian Buysschaert Herbert De Raedt

Familial hypercholesterolaemia (FH) is underdiagnosed in most countries. We report our first experience from a national pilot project of cascade screening in relatives of FH patients.Participating specialists recruited consecutive index patients (IP) with Dutch Lipid Clinic Network (DLCN) score ≥6. After informed consent, the relatives were visited by the nurses to collect relevant clinical data and perform blood sampling for lipid profile measurement. FH diagnosis in the relatives was based on the DLCN and/or MEDPED FH (Make-Early-Diagnosis-to-Prevent-Early-Deaths-in-FH) criteria.In a period of 18 months, a total of 127 IP (90 with definite FH and 37 with probable FH) were enrolled in 15 centres. Out of the 270 relatives visited by the nurses, 105 were suspected of having FH: 31 with DCLN score >8, 33 with DLCN score 5-8 and 41 with MEDPED FH criteria. In a post-hoc analysis, another set of MEDPED FH criteria established in the Netherlands and adapted to Belgium allowed to detect FH in 51 additional relatives.In a country with no national FH screening program, our pilot project demonstrated that implementing a simple phenotypical FH cascade screening strategy using the collaboration of motivated specialists and two nurses, allowed to diagnose FH in 127 index patients and an additional 105 of their relatives over the two-year period. Newly developed MEDPED FH cut-offs, easily applicable by a nurse with a single blood sample, might further improve the sensitivity of detecting FH within families.

10.1080/00015385.2020.1820683

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84 Left ventricular force frequency relationship in heart failure patients before and after cardiac resynchronisation therapy

European Journal of Heart Failure Supplements (2006)

Wilfried Müllens Jozef Bartúnek Marc Goethals Sofie Verstreken P Geelen

10.1016/s1567-4215(06)80050-0

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Vulnerability to cardiac arrest in patients with ST elevation myocardial infarction: Is it time or patient dependent? Results from a nationwide observational study

European Heart Journal Acute Cardiovascular Care (2019)

Mahadi Salah Sofie Gevaert Patrick Coussement Christophe Beauloye Peter Sinnaeve

Aim: Cardiac arrest is a common complication of ST elevation myocardial infarction and is associated with high mortality. We evaluated whether vulnerability to cardiac arrest follows a circadian rhythm and whether it is related to specific patient characteristics. Methods: A total of 24,164 ST elevation myocardial infarction patients who were admitted to 60 Belgian hospitals between 2008–2017 were analysed. The proportion of patients with cardiac arrest before initiation of reperfusion therapy was calculated for different time periods (hour of the day, months, seasons) and related to patient characteristics using stepwise logistic regression analysis. Results: Cardiac arrest occurred in 10.8% of the ST elevation myocardial infarction patients at a median of 65 min (interquartile range 33–138 min) after onset of pain. ST elevation myocardial infarction patients with cardiac arrest showed a biphasic pattern with one peak in the morning and one peak in the late afternoon. Multivariate analysis identified the following independent factors associated with cardiac arrest: cardiogenic shock (odds ratio=28), left bundle branch block (odds ratio=3.7), short (<180 min) ischaemic period (odds ratio=2.2), post-meridiem daytime presentation (odds ratio=1.4), anterior infarction (odds ratio=1.3). Overall in-hospital mortality was 30% for cardiac arrest patients versus 3.7% for non-cardiac arrest patients (p<0.0001). Conclusion: In the present study population, cardiac arrest in ST elevation myocardial infarction showed an atypical circadian rhythm with not only a morning peak but also a second peak in the late afternoon, suggesting that cardiac arrest and ST elevation myocardial infarction triggers are, at least partially, different. In addition, specific patient characteristics, such as short ischaemic period, cardiogenic shock and left bundle branch block, increase the vulnerability to cardiac arrest.

Interquartile range

ST elevation

10.1177/2048872619872127

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Mode of admission and its effect on adherence to reperfusion therapy guidelines in Belgian STEMI patients

European Heart Journal Acute Cardiovascular Care (2016)

Céline Rousseaux Pierre Mols Peter Sinnaeve Carl Convens Philippe Dubois

Emergency medical services play a key role in the recognition and treatment of ST-segment elevation myocardial infarction (STEMI). This study evaluates the effect of emergency medical services use on adherence to reperfusion therapy guidelines in Belgian STEMI patients and on in-hospital mortality. The mode of admission with against without emergency medical services was associated with baseline risk profile, reperfusion modalities and in-hospital mortality in 5692 consecutive STEMI patients from 2012 to 2014. A total of 3896 STEMI patients (68%) were transported to the hospital by emergency medical services, and 1796 patients (32%) arrived at the hospital using their own transport (self-referral). Emergency medical services patients were older than self-referral patients (64 vs. 62 years) and more frequently presented with cardiac arrest (14% vs. 5%) and with cardiogenic shock (10% vs. 4%). Emergency medical services patients received primary percutaneous coronary intervention more often (95% vs. 91%, P<0.0001) and more frequently within 90 minutes (72% vs. 65%, P<0.001). Moreover, the time interval between symptom onset and reperfusion therapy was shorter in the emergency medical services group (median of 195 vs. 255 minutes, P<0.001). Crude in-hospital mortality was higher in the emergency medical services group (7.7% vs. 3.8%, P<0.0001) and was mainly driven by the high prevalence of cardiogenic shock and cardiac arrest in the emergency medical services group. After adjustment, the impact on mortality was no longer significantly different. Emergency medical services are used by two-thirds of Belgian STEMI patients and are associated with a better adherence to STEMI reperfusion guidelines. These data favour the use of emergency medical services as the preferred transfer system for patients with chest pain suspicious for STEMI.

Reperfusion Therapy

10.1177/2048872616647708

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Citations (5)