Pub Date : 2024-08-26DOI: 10.1016/j.jacc.2024.07.003
{"title":"The Post–Left Atrial Appendage Occlusion Antithrombotic Selection Conundrum","authors":"","doi":"10.1016/j.jacc.2024.07.003","DOIUrl":"10.1016/j.jacc.2024.07.003","url":null,"abstract":"","PeriodicalId":17187,"journal":{"name":"Journal of the American College of Cardiology","volume":null,"pages":null},"PeriodicalIF":21.7,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142077302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-26DOI: 10.1016/j.jacc.2024.07.008
{"title":"Bleeding and Thrombosis in Patients With Atrial Fibrillation After Acute Coronary Syndrome or Percutaneous Coronary Intervention","authors":"","doi":"10.1016/j.jacc.2024.07.008","DOIUrl":"10.1016/j.jacc.2024.07.008","url":null,"abstract":"","PeriodicalId":17187,"journal":{"name":"Journal of the American College of Cardiology","volume":null,"pages":null},"PeriodicalIF":21.7,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142077300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-26DOI: 10.1016/j.jacc.2024.06.022
Background
The optimal antithrombotic regimen for patients with atrial fibrillation (AF) who had an acute coronary syndrome (ACS) or have undergone percutaneous coronary intervention (PCI) is not known.
Objectives
The authors sought to determine which antithrombotic regimen best balances safety and efficacy.
Methods
AUGUSTUS, a multicenter 2 × 2 factorial design randomized trial compared apixaban with vitamin K antagonist (VKA) and aspirin with placebo in patients with AF with recent ACS and/or PCI treated with a P2Y12 inhibitor. We conducted a 4-way analysis comparing safety and efficacy outcomes in the 4 randomized groups. The primary outcome was a composite of all-cause death, major or clinically relevant nonmajor bleeding, or hospitalization for cardiovascular causes over 6-month follow-up. Secondary outcomes included individual components of the primary endpoint.
Results
A total of 4,614 patients were enrolled. All patients were treated with a P2Y12 inhibitor. The primary endpoint occurred in 21.9% of patients randomized to apixaban plus placebo, 27.3% randomized to apixaban plus aspirin, 28.0% randomized to VKA plus placebo, and 33.3% randomized to VKA plus aspirin. Rates of major or clinically relevant nonmajor bleeding and hospitalization for cardiovascular causes were lower with apixaban and placebo compared with the other 3 antithrombotic strategies. There was no difference between the 4 randomized groups with respect to all-cause death.
Conclusions
In patients with AF and a recent ACS and/or PCI, an antithrombotic regimen that included a P2Y12 inhibitor and apixaban without aspirin resulted in a lower incidence of the composite of death, bleeding, or cardiovascular hospitalization than regimens including VKA, aspirin, or both. (An Open-label, 2 x 2 Factorial, Randomized Controlled, Clinical Trial to Evaluate the Safety of Apixaban vs. Vitamin K Antagonist and Aspirin vs. Aspirin Placebo in Patients with Atrial Fibrillation and Acute Coronary Syndrome or Percutaneous Coronary Intervention; NCT02415400)
{"title":"Antithrombotic Strategies in Atrial Fibrillation After ACS and/or PCI","authors":"","doi":"10.1016/j.jacc.2024.06.022","DOIUrl":"10.1016/j.jacc.2024.06.022","url":null,"abstract":"<div><h3>Background</h3><p>The optimal antithrombotic regimen for patients with atrial fibrillation (AF) who had an acute coronary syndrome (ACS) or have undergone percutaneous coronary intervention (PCI) is not known.</p></div><div><h3>Objectives</h3><p>The authors sought to determine which antithrombotic regimen best balances safety and efficacy.</p></div><div><h3>Methods</h3><p>AUGUSTUS, a multicenter 2 × 2 factorial design randomized trial compared apixaban with vitamin K antagonist (VKA) and aspirin with placebo in patients with AF with recent ACS and/or PCI treated with a P2Y<sub>12</sub> inhibitor. We conducted a 4-way analysis comparing safety and efficacy outcomes in the 4 randomized groups. The primary outcome was a composite of all-cause death, major or clinically relevant nonmajor bleeding, or hospitalization for cardiovascular causes over 6-month follow-up. Secondary outcomes included individual components of the primary endpoint.</p></div><div><h3>Results</h3><p>A total of 4,614 patients were enrolled. All patients were treated with a P2Y<sub>12</sub> inhibitor. The primary endpoint occurred in 21.9% of patients randomized to apixaban plus placebo, 27.3% randomized to apixaban plus aspirin, 28.0% randomized to VKA plus placebo, and 33.3% randomized to VKA plus aspirin. Rates of major or clinically relevant nonmajor bleeding and hospitalization for cardiovascular causes were lower with apixaban and placebo compared with the other 3 antithrombotic strategies. There was no difference between the 4 randomized groups with respect to all-cause death.</p></div><div><h3>Conclusions</h3><p>In patients with AF and a recent ACS and/or PCI, an antithrombotic regimen that included a P2Y<sub>12</sub> inhibitor and apixaban without aspirin resulted in a lower incidence of the composite of death, bleeding, or cardiovascular hospitalization than regimens including VKA, aspirin, or both. (An Open-label, 2 x 2 Factorial, Randomized Controlled, Clinical Trial to Evaluate the Safety of Apixaban vs. Vitamin K Antagonist and Aspirin vs. Aspirin Placebo in Patients with Atrial Fibrillation and Acute Coronary Syndrome or Percutaneous Coronary Intervention; <span><span>NCT02415400</span><svg><path></path></svg></span>)</p></div>","PeriodicalId":17187,"journal":{"name":"Journal of the American College of Cardiology","volume":null,"pages":null},"PeriodicalIF":21.7,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142077299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-26DOI: 10.1016/j.jacc.2024.06.027
Patients with peripheral artery disease (PAD) experience major cardiovascular and limb events. Antithrombotic strategies including antiplatelets and anticoagulants remain a cornerstone of treatment and prevention. Recent trials have shown heterogeneity in the response to antithrombotic therapies in patients presenting primarily with PAD when compared to those presenting primarily with coronary artery disease. In addition, there is observed heterogeneity with regards to the effects of antiplatelets and anticoagulants with respect to different outcomes including cardiovascular and major adverse limb events. This, coupled with risks of bleeding, requires a patient-centered and holistic assessment of benefit-risk when selecting antithrombotic strategies for patients with PAD. A global multidisciplinary work group was convened to evaluate antithrombotic strategies in PAD and to summarize the current state of the art. Common clinical scenarios around antithrombotic decision making were provided. Finally, insights with regard to implementation future investigation were described.
外周动脉疾病（PAD）患者会发生重大心血管和肢体事件。包括抗血小板和抗凝剂在内的抗血栓策略仍然是治疗和预防的基石。最近的试验表明，与主要患有冠状动脉疾病的患者相比，主要患有 PAD 的患者对抗血栓疗法的反应存在异质性。此外，还观察到抗血小板和抗凝剂对不同结果（包括心血管和肢体重大不良事件）的影响存在异质性。再加上出血风险，在为 PAD 患者选择抗血栓策略时，需要以患者为中心，全面评估获益与风险。我们召集了一个全球多学科工作组，以评估 PAD 的抗血栓策略并总结当前的技术水平。工作小组还提供了有关抗血栓决策的常见临床情景。最后，介绍了对未来调查实施的见解。
{"title":"Antithrombotic Strategies for Patients With Peripheral Artery Disease","authors":"","doi":"10.1016/j.jacc.2024.06.027","DOIUrl":"10.1016/j.jacc.2024.06.027","url":null,"abstract":"<div><p>Patients with peripheral artery disease (PAD) experience major cardiovascular and limb events. Antithrombotic strategies including antiplatelets and anticoagulants remain a cornerstone of treatment and prevention. Recent trials have shown heterogeneity in the response to antithrombotic therapies in patients presenting primarily with PAD when compared to those presenting primarily with coronary artery disease. In addition, there is observed heterogeneity with regards to the effects of antiplatelets and anticoagulants with respect to different outcomes including cardiovascular and major adverse limb events. This, coupled with risks of bleeding, requires a patient-centered and holistic assessment of benefit-risk when selecting antithrombotic strategies for patients with PAD. A global multidisciplinary work group was convened to evaluate antithrombotic strategies in PAD and to summarize the current state of the art. Common clinical scenarios around antithrombotic decision making were provided. Finally, insights with regard to implementation future investigation were described.</p></div>","PeriodicalId":17187,"journal":{"name":"Journal of the American College of Cardiology","volume":null,"pages":null},"PeriodicalIF":21.7,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142077250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-26DOI: 10.1016/j.jacc.2024.08.006
Brendon L Neuen, John W Ostrominski, Brian Claggett, Iris E Beldhuis, Safia Chatur, Finnian R McCausland, Sunil V Badve, Clare Arnott, Hiddo J L Heerspink, Min Jun, Michael Falster, Juliana de Oliveira Costa, Carol Pollock, Meg J Jardine, Kenneth W Mahaffey, Vlado Perkovic, Scott D Solomon, Muthiah Vaduganathan
{"title":"Bidirectional Relationship Between Kidney Disease Progression and Cardiovascular Events in Type 2 Diabetes.","authors":"Brendon L Neuen, John W Ostrominski, Brian Claggett, Iris E Beldhuis, Safia Chatur, Finnian R McCausland, Sunil V Badve, Clare Arnott, Hiddo J L Heerspink, Min Jun, Michael Falster, Juliana de Oliveira Costa, Carol Pollock, Meg J Jardine, Kenneth W Mahaffey, Vlado Perkovic, Scott D Solomon, Muthiah Vaduganathan","doi":"10.1016/j.jacc.2024.08.006","DOIUrl":"https://doi.org/10.1016/j.jacc.2024.08.006","url":null,"abstract":"","PeriodicalId":17187,"journal":{"name":"Journal of the American College of Cardiology","volume":null,"pages":null},"PeriodicalIF":21.7,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142108642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-26DOI: 10.1016/S0735-1097(24)07988-9
{"title":"Audio Summary","authors":"","doi":"10.1016/S0735-1097(24)07988-9","DOIUrl":"10.1016/S0735-1097(24)07988-9","url":null,"abstract":"","PeriodicalId":17187,"journal":{"name":"Journal of the American College of Cardiology","volume":null,"pages":null},"PeriodicalIF":21.7,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142077297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-26DOI: 10.1016/j.jacc.2024.06.028
{"title":"Finding Truth in Observational and Interventional Studies in Diabetes and Cardiovascular Disease","authors":"","doi":"10.1016/j.jacc.2024.06.028","DOIUrl":"10.1016/j.jacc.2024.06.028","url":null,"abstract":"","PeriodicalId":17187,"journal":{"name":"Journal of the American College of Cardiology","volume":null,"pages":null},"PeriodicalIF":21.7,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142077304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-26DOI: 10.1016/j.jacc.2024.08.046
Michael J Blaha, Andrew P DeFilippis
{"title":"Exploring the Need for Precise MI Adjudication in Clinical Trials.","authors":"Michael J Blaha, Andrew P DeFilippis","doi":"10.1016/j.jacc.2024.08.046","DOIUrl":"https://doi.org/10.1016/j.jacc.2024.08.046","url":null,"abstract":"","PeriodicalId":17187,"journal":{"name":"Journal of the American College of Cardiology","volume":null,"pages":null},"PeriodicalIF":21.7,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142133012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-25DOI: 10.1016/j.jacc.2024.07.028
Marta Cocco, Gianluca Campo, Vincenzo Guiducci, Gianni Casella, Caterina Cavazza, Enrico Cerrato, Giorgio Sacchetta, Raul Moreno, Alberto Menozzi, Ignacio Amat Santos, José Luis Díez Gil, Roberto Scarsini, Andrea Picchi, Giuseppe Vadalà, Gerlando Pilato, Iginio Colaiori, Marco Barbierato, Manfredi Arioti, Rita Pavasini, Valerio Lanzilotti, Mila Menozzi, Ferdinando Varbella, Andrea Erriquez, Simone Biscaglia
Background: The effectiveness of complete revascularization is well established in patients with ST-segment elevation myocardial infarction (STEMI), but it is less investigated in those with non-ST-segment elevation myocardial infarction (NSTEMI).
Objectives: This study aimed to assess whether complete revascularization, compared with culprit-only revascularization, was associated with consistent outcomes in older patients with STEMI and NSTEMI.
Methods: In the FIRE (Functional Assessment in Elderly MI Patients with Multivessel Disease) trial, 1,445 older patients with myocardial infarction (MI) were randomized to culprit-only or physiology-guided complete revascularization, stratified by STEMI (n = 256 culprit-only vs n = 253 complete) and NSTEMI (n = 469 culprit-only vs n = 467 complete). The primary outcome comprised a composite of death, MI, stroke, or revascularization at 1 year. The key secondary outcome included a composite of cardiovascular death or MI at 1 year.
Results: In the overall study population, physiology-guided complete revascularization reduced both primary and key secondary outcomes. The primary outcome occurred in 54 (21.1%) STEMI patients randomized to culprit-only vs 41 (16.2%) STEMI patients of the complete group (HR: 0.75; 95% CI: 0.50-1.13) and in 98 (20.9%) NSTEMI patients randomized to culprit-only vs 72 (15.4%) NSTEMI patients of the complete group (HR: 0.71; 95% CI: 0.53-0.97), with negative interaction testing (P for interaction, 0.846). Similarly, no signal of heterogeneity with respect to the initial clinical presentation was observed for the key secondary endpoint (P for interaction, 0.654).
Conclusions: Physiology-guided complete revascularization, compared with culprit-only revascularization, provided consistent benefit across the whole spectrum of patients with MI. (FIRE [Functional Assessment in Elderly MI Patients With Multivessel Disease]; NCT03772743).
背景：完全血运重建对ST段抬高型心肌梗死（STEMI）患者的有效性已得到公认，但对非ST段抬高型心肌梗死（NSTEMI）患者的研究较少：本研究旨在评估在 STEMI 和 NSTEMI 老年患者中，完全血运重建与单纯罪魁祸首血运重建相比，是否具有一致的预后：在FIRE（多血管疾病老年心肌梗死患者功能评估）试验中，1,445名老年心肌梗死（MI）患者被随机分配接受单纯死因再通术或生理学指导下的完全再通术，按STEMI（n = 256例单纯死因再通术 vs n = 253例完全再通术）和NSTEMI（n = 469例单纯死因再通术 vs n = 467例完全再通术）进行分层。主要结果包括1年内死亡、心肌梗死、中风或血管再通的复合结果。主要次要结果包括 1 年后心血管死亡或心肌梗死的复合结果：在整个研究人群中，生理学指导下的完全血管再通减少了主要和关键次要结果。54例（21.1%）STEMI患者随机接受了单纯罪魁祸首再通术，41例（16.2%）STEMI患者接受了完全再通术（HR：0.75；95% CI：0.50-1.13），98例（20.9%）NSTEMI患者随机接受了单纯罪魁祸首再通术，72例（15.4%）NSTEMI患者接受了完全再通术（HR：0.71；95% CI：0.53-0.97）。同样，在关键的次要终点方面，也没有观察到与初始临床表现有关的异质性信号（交互检验的P值为0.654）：结论：生理学指导下的完全血运重建与单纯罪魁祸首血运重建相比，能为所有心肌梗死患者带来一致的获益。(FIRE[多血管疾病老年 MI 患者功能评估]；NCT03772743）。
{"title":"Complete vs Culprit-Only Revascularization in Older Patients With Myocardial Infarction With or Without ST-Segment Elevation.","authors":"Marta Cocco, Gianluca Campo, Vincenzo Guiducci, Gianni Casella, Caterina Cavazza, Enrico Cerrato, Giorgio Sacchetta, Raul Moreno, Alberto Menozzi, Ignacio Amat Santos, José Luis Díez Gil, Roberto Scarsini, Andrea Picchi, Giuseppe Vadalà, Gerlando Pilato, Iginio Colaiori, Marco Barbierato, Manfredi Arioti, Rita Pavasini, Valerio Lanzilotti, Mila Menozzi, Ferdinando Varbella, Andrea Erriquez, Simone Biscaglia","doi":"10.1016/j.jacc.2024.07.028","DOIUrl":"https://doi.org/10.1016/j.jacc.2024.07.028","url":null,"abstract":"<p><strong>Background: </strong>The effectiveness of complete revascularization is well established in patients with ST-segment elevation myocardial infarction (STEMI), but it is less investigated in those with non-ST-segment elevation myocardial infarction (NSTEMI).</p><p><strong>Objectives: </strong>This study aimed to assess whether complete revascularization, compared with culprit-only revascularization, was associated with consistent outcomes in older patients with STEMI and NSTEMI.</p><p><strong>Methods: </strong>In the FIRE (Functional Assessment in Elderly MI Patients with Multivessel Disease) trial, 1,445 older patients with myocardial infarction (MI) were randomized to culprit-only or physiology-guided complete revascularization, stratified by STEMI (n = 256 culprit-only vs n = 253 complete) and NSTEMI (n = 469 culprit-only vs n = 467 complete). The primary outcome comprised a composite of death, MI, stroke, or revascularization at 1 year. The key secondary outcome included a composite of cardiovascular death or MI at 1 year.</p><p><strong>Results: </strong>In the overall study population, physiology-guided complete revascularization reduced both primary and key secondary outcomes. The primary outcome occurred in 54 (21.1%) STEMI patients randomized to culprit-only vs 41 (16.2%) STEMI patients of the complete group (HR: 0.75; 95% CI: 0.50-1.13) and in 98 (20.9%) NSTEMI patients randomized to culprit-only vs 72 (15.4%) NSTEMI patients of the complete group (HR: 0.71; 95% CI: 0.53-0.97), with negative interaction testing (P for interaction, 0.846). Similarly, no signal of heterogeneity with respect to the initial clinical presentation was observed for the key secondary endpoint (P for interaction, 0.654).</p><p><strong>Conclusions: </strong>Physiology-guided complete revascularization, compared with culprit-only revascularization, provided consistent benefit across the whole spectrum of patients with MI. (FIRE [Functional Assessment in Elderly MI Patients With Multivessel Disease]; NCT03772743).</p>","PeriodicalId":17187,"journal":{"name":"Journal of the American College of Cardiology","volume":null,"pages":null},"PeriodicalIF":21.7,"publicationDate":"2024-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142108643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-24DOI: 10.1016/j.jacc.2024.08.002
Sheila M Hegde, Brian L Claggett, Xiaowen Wang, Karola Jering, Narayana Prasad, Farideh Roshanali, Ahmad Masri, Michael E Nassif, Roberto Barriales-Villa, Theodore P Abraham, Nuno Cardim, Caroline J Coats, Christopher M Kramer, Martin S Maron, Michelle Michels, Iacopo Olivotto, Sara Saberi, Daniel L Jacoby, Stephen B Heitner, Stuart Kupfer, Lisa Meng, Amy Wohltman, Fady I Malik, Scott D Solomon
Background: Aficamten, a next-in-class cardiac myosin inhibitor, improved peak oxygen uptake (pVO2) and lowered resting and Valsalva left ventricular outflow (LVOT) gradients in adults with symptomatic obstructive hypertrophic cardiomyopathy (oHCM) in SEQUOIA-HCM (Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Placebo in Adults With Symptomatic oHCM), a phase 3, multicenter, randomized, double-blinded, placebo-controlled study.
Objectives: The authors sought to evaluate the effect of aficamten on echocardiographic measures of cardiac structure and function in SEQUOIA-HCM.
Methods: Serial echocardiograms were performed over 28 weeks in patients randomized to receive placebo or aficamten in up to 4 individually titrated escalating doses (5-20 mg daily) over 24 weeks based on Valsalva LVOT gradients and left ventricular ejection fraction (LVEF).
Results: Among 282 patients (mean age 59 ± 13 years; 41% female, 79% White, 19% Asian), mean LVEF was 75% ± 6% with resting and Valsalva LVOT gradients of 55 ± 30 mm Hg and 83 ± 32 mm Hg, respectively. Over 24 weeks, aficamten significantly lowered resting and Valsalva LVOT gradients, and improved left atrial volume index, lateral and septal e' velocities, and lateral and septal E/e' (all P ≤ 0.001). LV end-systolic volume increased and wall thickness decreased (all P ≤ 0.003). Aficamten resulted in a mild reversible decrease in LVEF (-4.8% [95% CI: -6.4 to -3.3]; P < 0.001) and absolute LV global circumferential strain (-3.7% [95% CI: 1.8-5.6]; P < 0.0010), whereas LV global longitudinal strain was unchanged. Several measures, including LVEF, LVOT gradients, and E/e' returned to baseline following washout. Among those treated with aficamten, improved pVO2 and reduction in N-terminal pro-B-type natriuretic peptide (NT-proBNP) were associated with improvement in lateral e' velocity and septal and lateral E/e' (all P < 0.03), whereas improvement in Kansas City Cardiomyopathy Questionnaire Clinical Summary Scores (KCCQ-CSS) was associated with a decrease in both LVOT gradients (all P < 0.001).
Conclusions: Compared with placebo, patients receiving aficamten demonstrated significant improvement in LVOT gradients and measures of LV diastolic function, and several of these measures were associated with improvements in pVO2, KCCQ-CSS, and NT-proBNP. A modest decrease in LVEF occurred yet remained within normal range. These findings suggest aficamten improved multiple structural and physiological parameters in oHCM without significant adverse changes in LV systolic function. (Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Placebo in Adults With Symptomatic oHCM [SEQUOIA-HCM]; NCT05186818).
研究背景Aficamten是一种新型心肌酶抑制剂，在SEQUOIA-HCM（评估Aficamten与安慰剂相比在症状性肥厚型心肌病（oHCM）成人中的疗效和安全性的3期试验）中，Aficamten改善了无症状阻塞性肥厚型心肌病（oHCM）成人的峰值摄氧量（pVO2），降低了静息和Valsalva左心室流出量（LVOT）梯度、这是一项多中心、随机、双盲、安慰剂对照的 3 期研究。研究目的作者试图评估阿菲康坦对 SEQUOIA-HCM 患者心脏结构和功能的超声心动图测量的影响：根据 Valsalva LVOT 梯度和左心室射血分数 (LVEF)，对随机接受安慰剂或阿菲康定的患者进行为期 28 周的连续超声心动图检查，阿菲康定剂量最多为 4 个单独滴定递增剂量（每天 5-20 毫克），持续 24 周：282名患者（平均年龄59±13岁，女性占41%，白人占79%，亚洲人占19%）的平均左心室射血分数（LVEF）为75%±6%，静息和Valsalva左心室出口梯度分别为55±30毫米汞柱和83±32毫米汞柱。在24周的时间里，阿非坎顿明显降低了静息和Valsalva LVOT梯度，改善了左心房容积指数、侧壁和室间隔e'速度以及侧壁和室间隔E/e'（所有P均≤0.001）。左心室收缩末期容积增大，室壁厚度减小（均 P ≤ 0.003）。阿菲康坦导致 LVEF 轻度可逆性下降（-4.8% [95% CI: -6.4 to -3.3]；P 2 和 N 端前 B 型钠尿肽（NT-proBNP）的降低与侧向 e'速度及室间隔和侧向 E/e' 的改善有关（均 P < 0.03），而堪萨斯城心肌病问卷临床总结评分（KCCQ-CSS）的改善与左心室出口梯度的降低有关（均P < 0.001）：与安慰剂相比，接受阿非坎顿治疗的患者左心室出口梯度和左心室舒张功能指标均有显著改善，其中一些指标与pVO2、KCCQ-CSS和NT-proBNP的改善有关。LVEF 略有下降，但仍保持在正常范围内。这些研究结果表明，阿非坎顿可改善 oHCM 的多个结构和生理参数，而不会对左心室收缩功能造成显著的不良影响。(评估阿菲康坦与安慰剂相比在有症状 oHCM 成人中的疗效和安全性的 3 期试验 [SEQUOIA-HCM]；NCT05186818）。
{"title":"Impact of Aficamten on Echocardiographic Cardiac Structure and Function in Symptomatic Obstructive Hypertrophic Cardiomyopathy.","authors":"Sheila M Hegde, Brian L Claggett, Xiaowen Wang, Karola Jering, Narayana Prasad, Farideh Roshanali, Ahmad Masri, Michael E Nassif, Roberto Barriales-Villa, Theodore P Abraham, Nuno Cardim, Caroline J Coats, Christopher M Kramer, Martin S Maron, Michelle Michels, Iacopo Olivotto, Sara Saberi, Daniel L Jacoby, Stephen B Heitner, Stuart Kupfer, Lisa Meng, Amy Wohltman, Fady I Malik, Scott D Solomon","doi":"10.1016/j.jacc.2024.08.002","DOIUrl":"https://doi.org/10.1016/j.jacc.2024.08.002","url":null,"abstract":"<p><strong>Background: </strong>Aficamten, a next-in-class cardiac myosin inhibitor, improved peak oxygen uptake (pVO<sub>2</sub>) and lowered resting and Valsalva left ventricular outflow (LVOT) gradients in adults with symptomatic obstructive hypertrophic cardiomyopathy (oHCM) in SEQUOIA-HCM (Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Placebo in Adults With Symptomatic oHCM), a phase 3, multicenter, randomized, double-blinded, placebo-controlled study.</p><p><strong>Objectives: </strong>The authors sought to evaluate the effect of aficamten on echocardiographic measures of cardiac structure and function in SEQUOIA-HCM.</p><p><strong>Methods: </strong>Serial echocardiograms were performed over 28 weeks in patients randomized to receive placebo or aficamten in up to 4 individually titrated escalating doses (5-20 mg daily) over 24 weeks based on Valsalva LVOT gradients and left ventricular ejection fraction (LVEF).</p><p><strong>Results: </strong>Among 282 patients (mean age 59 ± 13 years; 41% female, 79% White, 19% Asian), mean LVEF was 75% ± 6% with resting and Valsalva LVOT gradients of 55 ± 30 mm Hg and 83 ± 32 mm Hg, respectively. Over 24 weeks, aficamten significantly lowered resting and Valsalva LVOT gradients, and improved left atrial volume index, lateral and septal e' velocities, and lateral and septal E/e' (all P ≤ 0.001). LV end-systolic volume increased and wall thickness decreased (all P ≤ 0.003). Aficamten resulted in a mild reversible decrease in LVEF (-4.8% [95% CI: -6.4 to -3.3]; P < 0.001) and absolute LV global circumferential strain (-3.7% [95% CI: 1.8-5.6]; P < 0.0010), whereas LV global longitudinal strain was unchanged. Several measures, including LVEF, LVOT gradients, and E/e' returned to baseline following washout. Among those treated with aficamten, improved pVO<sub>2</sub> and reduction in N-terminal pro-B-type natriuretic peptide (NT-proBNP) were associated with improvement in lateral e' velocity and septal and lateral E/e' (all P < 0.03), whereas improvement in Kansas City Cardiomyopathy Questionnaire Clinical Summary Scores (KCCQ-CSS) was associated with a decrease in both LVOT gradients (all P < 0.001).</p><p><strong>Conclusions: </strong>Compared with placebo, patients receiving aficamten demonstrated significant improvement in LVOT gradients and measures of LV diastolic function, and several of these measures were associated with improvements in pVO<sub>2</sub>, KCCQ-CSS, and NT-proBNP. A modest decrease in LVEF occurred yet remained within normal range. These findings suggest aficamten improved multiple structural and physiological parameters in oHCM without significant adverse changes in LV systolic function. (Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Placebo in Adults With Symptomatic oHCM [SEQUOIA-HCM]; NCT05186818).</p>","PeriodicalId":17187,"journal":{"name":"Journal of the American College of Cardiology","volume":null,"pages":null},"PeriodicalIF":21.7,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142108652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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