Anton Pottegård, Lars Ulrik Gerdes, Jakob Langballe Wetche, Wade Thompson
Aims: Examine whether low-density lipoprotein cholesterol (LDL-C) determination method influences the rate of statin initiation for primary prevention of cardiovascular disease.
Methods and results: We conducted a register-based retrospective study in the Region of Southern Denmark. Two hospital-based laboratories in the Region directly measure LDL-C whereas four laboratories calculate LDL-C using Friedewald's formula. Physicians do not choose which method is used. We included all statin-naïve patients ≥40 years with no history of cardiovascular disease, diabetes, or chronic kidney disease, who had their LDL-C determined during 2018-2019. There were 202,807 people who had LDL-C determined during the study period (median age 59 years, 44% women) of which 37% had a direct LDL-C measurement. The median reported LDL-C was 3.40 mmol/L (IQR 2.90 to 4.00) for those with a direct measurement versus 3.00 mmol/L (IQR 2.40 to 3.50) for those with calculated LDL-C. For those with direct measurement, re-calculated LDL-C (using Friedewald's formula) was 0.35 mmol/L lower than the reported direct LDL-C measurement. Among those with directly measured LDL-C, 3.6% initiated statins compared with 2.7% of those with a calculated LDL-C. Direct LDL-C measurement led to higher odds of having a statin initiated compared to calculated LDL-C (adjusted odds ratio 1.23, 95% CI 1.17 to 1.30); for those with triglycerides > 1.7 mmol/L the adjusted odds ratio was 1.41 (95% CI 1.30 to 1.52).
Conclusion: Differences in the reporting of LDL-C from laboratories using different methods have a substantial influence on physician's decisions to prescribe statins.
{"title":"Does LDL-C determination method affect statin prescribing for primary prevention? A register-based study in Southern Denmark.","authors":"Anton Pottegård, Lars Ulrik Gerdes, Jakob Langballe Wetche, Wade Thompson","doi":"10.1093/ehjcvp/pvae043","DOIUrl":"https://doi.org/10.1093/ehjcvp/pvae043","url":null,"abstract":"<p><strong>Aims: </strong>Examine whether low-density lipoprotein cholesterol (LDL-C) determination method influences the rate of statin initiation for primary prevention of cardiovascular disease.</p><p><strong>Methods and results: </strong>We conducted a register-based retrospective study in the Region of Southern Denmark. Two hospital-based laboratories in the Region directly measure LDL-C whereas four laboratories calculate LDL-C using Friedewald's formula. Physicians do not choose which method is used. We included all statin-naïve patients ≥40 years with no history of cardiovascular disease, diabetes, or chronic kidney disease, who had their LDL-C determined during 2018-2019. There were 202,807 people who had LDL-C determined during the study period (median age 59 years, 44% women) of which 37% had a direct LDL-C measurement. The median reported LDL-C was 3.40 mmol/L (IQR 2.90 to 4.00) for those with a direct measurement versus 3.00 mmol/L (IQR 2.40 to 3.50) for those with calculated LDL-C. For those with direct measurement, re-calculated LDL-C (using Friedewald's formula) was 0.35 mmol/L lower than the reported direct LDL-C measurement. Among those with directly measured LDL-C, 3.6% initiated statins compared with 2.7% of those with a calculated LDL-C. Direct LDL-C measurement led to higher odds of having a statin initiated compared to calculated LDL-C (adjusted odds ratio 1.23, 95% CI 1.17 to 1.30); for those with triglycerides > 1.7 mmol/L the adjusted odds ratio was 1.41 (95% CI 1.30 to 1.52).</p><p><strong>Conclusion: </strong>Differences in the reporting of LDL-C from laboratories using different methods have a substantial influence on physician's decisions to prescribe statins.</p>","PeriodicalId":11982,"journal":{"name":"European Heart Journal - Cardiovascular Pharmacotherapy","volume":null,"pages":null},"PeriodicalIF":7.1,"publicationDate":"2024-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141179172","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}
Background: Antihypertensive drugs are known to lower cardiovascular mortality, but the role of different types of antihypertensive drugs in lifespan has not been clarified. Moreover, the underlying mechanisms remain unclear.
Methods: To minimize confounding, we used Mendelian randomization to assess the role of different antihypertensive drug classes in longevity and examined the pathways via proteins. Genetic variants associated with systolic blood pressure (SBP) corresponding to drug target genes were used as genetic instruments. The genetic associations with lifespan were obtained from a large genome-wide association study including 1 million European participants from UK Biobank and LifeGen. For significant antihypertensive drug classes, we performed sex-specific analysis, drug-target analysis and colocalization. To examine the mediation pathways, we assessed the associations of 2291 plasma proteins with lifespan, and examined the associations of drug classes with the proteins affecting lifespan.
Results: After correcting for multiple testing, genetically proxied beta-blockers (BBs), calcium channel blockers (CCBs) and vasodilators were related to longer life years (BBs: 2.03, 95% CI 0.78 to 3.28 per 5-mmHg reduction in SBP, CCBs: 3.40, 95% CI 1.47 to 5.33, and vasodilators: 2.92, 95% CI 1.08 to 4.77). The beneficial effects of BBs and CCBs were more obvious in men. ADRB1, CACNA2D2, CACNB3, CPT1A, CPT2, and EDNRA genes were related to extended lifespan with CPT2 further supported by colocalization evidence. 86 proteins were related to lifespan, of which 4 proteins were affected by CCBs. CDH1 may mediate the association between CCBs and lifespan.
Conclusions: BBs, CCBs and vasodilators may prolong lifespan, with potential sex differences for BBs and CCBs. The role of CCBs in lifespan is partly mediated by CDH1. Prioritizing the potential protein targets can provide new insights into healthy aging.
背景:众所周知,降压药可降低心血管疾病死亡率,但不同类型的降压药在寿命中的作用尚未明确。此外,其潜在机制仍不清楚:为了最大限度地减少混杂因素,我们采用孟德尔随机法评估了不同类型的降压药对长寿的作用,并通过蛋白质研究了其作用途径。与药物靶基因相对应的收缩压(SBP)相关基因变异被用作遗传工具。与寿命相关的遗传变异来自一项大型全基因组关联研究,其中包括来自英国生物库和 LifeGen 的 100 万欧洲参与者。对于重要的抗高血压药物类别,我们进行了性别特异性分析、药物靶标分析和共定位分析。为了研究中介途径,我们评估了2291种血浆蛋白与寿命的关联,并研究了药物类别与影响寿命的蛋白的关联:经多重检验校正后,基因替代的β受体阻滞剂(BBs)、钙通道阻滞剂(CCBs)和血管扩张剂与延长寿命有关(BBs:SBP每降低5 mmHg,BBs的寿命为2.03,95% CI为0.78-3.28;CCBs:SBP每降低5 mmHg,CCBs的寿命为3.40,95% CI为1.28):3.40,95% CI 1.47 至 5.33,血管扩张剂:2.92,95% CI 1.08 至 4.77)。BB类和CCB类药物对男性的益处更为明显。ADRB1、CACNA2D2、CACNB3、CPT1A、CPT2和EDNRA基因与延长寿命有关,其中CPT2得到了共定位证据的进一步支持。86种蛋白质与寿命有关,其中4种蛋白质受CCB影响。CDH1可能介导了CCBs与寿命之间的关联:结论:BBs、CCBs和血管扩张剂可延长寿命,其中BBs和CCBs可能存在性别差异。CCBs对寿命的作用部分由CDH1介导。对潜在的蛋白质靶点进行优先排序可为健康老龄化提供新的见解。
{"title":"Utilizing genetics and proteomics to assess the role of antihypertensive drugs in human longevity and the underlying pathways: a Mendelian randomization study.","authors":"Bohan Fan, Jie V Zhao","doi":"10.1093/ehjcvp/pvae038","DOIUrl":"https://doi.org/10.1093/ehjcvp/pvae038","url":null,"abstract":"<p><strong>Background: </strong>Antihypertensive drugs are known to lower cardiovascular mortality, but the role of different types of antihypertensive drugs in lifespan has not been clarified. Moreover, the underlying mechanisms remain unclear.</p><p><strong>Methods: </strong>To minimize confounding, we used Mendelian randomization to assess the role of different antihypertensive drug classes in longevity and examined the pathways via proteins. Genetic variants associated with systolic blood pressure (SBP) corresponding to drug target genes were used as genetic instruments. The genetic associations with lifespan were obtained from a large genome-wide association study including 1 million European participants from UK Biobank and LifeGen. For significant antihypertensive drug classes, we performed sex-specific analysis, drug-target analysis and colocalization. To examine the mediation pathways, we assessed the associations of 2291 plasma proteins with lifespan, and examined the associations of drug classes with the proteins affecting lifespan.</p><p><strong>Results: </strong>After correcting for multiple testing, genetically proxied beta-blockers (BBs), calcium channel blockers (CCBs) and vasodilators were related to longer life years (BBs: 2.03, 95% CI 0.78 to 3.28 per 5-mmHg reduction in SBP, CCBs: 3.40, 95% CI 1.47 to 5.33, and vasodilators: 2.92, 95% CI 1.08 to 4.77). The beneficial effects of BBs and CCBs were more obvious in men. ADRB1, CACNA2D2, CACNB3, CPT1A, CPT2, and EDNRA genes were related to extended lifespan with CPT2 further supported by colocalization evidence. 86 proteins were related to lifespan, of which 4 proteins were affected by CCBs. CDH1 may mediate the association between CCBs and lifespan.</p><p><strong>Conclusions: </strong>BBs, CCBs and vasodilators may prolong lifespan, with potential sex differences for BBs and CCBs. The role of CCBs in lifespan is partly mediated by CDH1. Prioritizing the potential protein targets can provide new insights into healthy aging.</p>","PeriodicalId":11982,"journal":{"name":"European Heart Journal - Cardiovascular Pharmacotherapy","volume":null,"pages":null},"PeriodicalIF":7.1,"publicationDate":"2024-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141070135","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}
Mattia Galli, Giovanni Occhipinti, Stefano Benenati, Renzo Laborante, Luis Ortega-Paz, Francesco Franchi, Domenico D'Amario, Roberto Nerla, Fausto Castriota, Giacomo Frati, Giuseppe Biondi-Zoccai, Sebastiano Sciarretta, Dominick J Angiolillo
Background: Carriers of cytochrome 2C19 (CYP2C19) loss of function (LoF) alleles treated with clopidogrel have impaired drug metabolism resulting in reduced active metabolite levels, high platelet reactivity (HPR), and an increased risk of thrombotic events. Several alternative antiplatelet therapies have been proposed to overcome HPR in these patients, but their comparative effects remain poorly explored.
Methods: Randomized controlled trials (RCTs) comparing different oral antiplatelet therapies in carriers of CYP2C19 LoF alleles undergoing percutaneous coronary interventions (PCI) were included. A frequentist network meta-analysis was conducted to estimate mean difference (MD) or odds ratios (OR) and 95% confidence intervals (CI). The primary outcome was platelet reactivity assessed by VerifyNow and reported as P2Y12 reaction unit (PRU). The secondary outcome was the rate of HPR. Standard-dose of clopidogrel (75 mg daily) was used as reference treatment.
Results: A total of 12 RCTs testing 6 alternative strategies (i.e., clopidogrel 150 mg, prasugrel 3.75 mg, 5 mg, and 10 mg, ticagrelor 90 mg bid, and adjunctive cilostazol 100 mg bid) were included in the network. Compared with standard-dose clopidogrel, the greatest reduction in PRU was observed with prasugrel 10 mg (MD -127.91; 95% CI -141.04; -114.78) and ticagrelor 90 mg bid (MD -124.91; 95% CI -161.78; -88.04), followed by prasugrel 5 mg (MD -76.33; 95% CI -98.01; -54.65) and prasugrel 3.75 mg (MD -73.00; 95% CI -100.28; -45.72). Among other strategies, adjunctive cilostazol (MD-42.64; 95% CI -64.72; -20.57) and high-dose clopidogrel (MD -32.11; 95% CI -51.33; -12.90) were associated with a modest reduction in PRU compared with standard-dose clopidogrel.
Conclusion: Among carriers of CYP2C19 LoF alleles undergoing PCI, standard-dose prasugrel or ticagrelor are most effective in reducing platelet reactivity, while double-dose clopidogrel and additional cilostazol showed modest effects. Reduced-dose of prasugrel may represent a balanced strategy to overcome HPR without a significant increase in bleeding. The clinical implications of these pharmacodynamic findings warrant further investigation.
{"title":"Comparative effects of different antiplatelet strategies in carriers of CYP2C19 loss-of-function alleles: a network meta-analysis.","authors":"Mattia Galli, Giovanni Occhipinti, Stefano Benenati, Renzo Laborante, Luis Ortega-Paz, Francesco Franchi, Domenico D'Amario, Roberto Nerla, Fausto Castriota, Giacomo Frati, Giuseppe Biondi-Zoccai, Sebastiano Sciarretta, Dominick J Angiolillo","doi":"10.1093/ehjcvp/pvae036","DOIUrl":"https://doi.org/10.1093/ehjcvp/pvae036","url":null,"abstract":"<p><strong>Background: </strong>Carriers of cytochrome 2C19 (CYP2C19) loss of function (LoF) alleles treated with clopidogrel have impaired drug metabolism resulting in reduced active metabolite levels, high platelet reactivity (HPR), and an increased risk of thrombotic events. Several alternative antiplatelet therapies have been proposed to overcome HPR in these patients, but their comparative effects remain poorly explored.</p><p><strong>Methods: </strong>Randomized controlled trials (RCTs) comparing different oral antiplatelet therapies in carriers of CYP2C19 LoF alleles undergoing percutaneous coronary interventions (PCI) were included. A frequentist network meta-analysis was conducted to estimate mean difference (MD) or odds ratios (OR) and 95% confidence intervals (CI). The primary outcome was platelet reactivity assessed by VerifyNow and reported as P2Y12 reaction unit (PRU). The secondary outcome was the rate of HPR. Standard-dose of clopidogrel (75 mg daily) was used as reference treatment.</p><p><strong>Results: </strong>A total of 12 RCTs testing 6 alternative strategies (i.e., clopidogrel 150 mg, prasugrel 3.75 mg, 5 mg, and 10 mg, ticagrelor 90 mg bid, and adjunctive cilostazol 100 mg bid) were included in the network. Compared with standard-dose clopidogrel, the greatest reduction in PRU was observed with prasugrel 10 mg (MD -127.91; 95% CI -141.04; -114.78) and ticagrelor 90 mg bid (MD -124.91; 95% CI -161.78; -88.04), followed by prasugrel 5 mg (MD -76.33; 95% CI -98.01; -54.65) and prasugrel 3.75 mg (MD -73.00; 95% CI -100.28; -45.72). Among other strategies, adjunctive cilostazol (MD-42.64; 95% CI -64.72; -20.57) and high-dose clopidogrel (MD -32.11; 95% CI -51.33; -12.90) were associated with a modest reduction in PRU compared with standard-dose clopidogrel.</p><p><strong>Conclusion: </strong>Among carriers of CYP2C19 LoF alleles undergoing PCI, standard-dose prasugrel or ticagrelor are most effective in reducing platelet reactivity, while double-dose clopidogrel and additional cilostazol showed modest effects. Reduced-dose of prasugrel may represent a balanced strategy to overcome HPR without a significant increase in bleeding. The clinical implications of these pharmacodynamic findings warrant further investigation.</p>","PeriodicalId":11982,"journal":{"name":"European Heart Journal - Cardiovascular Pharmacotherapy","volume":null,"pages":null},"PeriodicalIF":7.1,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140956801","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}
{"title":"Reply: subcutaneous furosemide patch: heart failure decongestion 'from the comfort of your home'.","authors":"Joanna Osmanska, Mark C Petrie, Ross T Campbell","doi":"10.1093/ehjcvp/pvae015","DOIUrl":"10.1093/ehjcvp/pvae015","url":null,"abstract":"","PeriodicalId":11982,"journal":{"name":"European Heart Journal - Cardiovascular Pharmacotherapy","volume":null,"pages":null},"PeriodicalIF":7.1,"publicationDate":"2024-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139746419","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}
{"title":"Letter to the editor: 1-year clinical outcomes of bivalirudin vs. unfractionated heparin in patients with type 2 diabetes undergoing elective percutaneous coronary intervention.","authors":"Fatima Rajab, Aleena Mujahid, Bisal Naseer","doi":"10.1093/ehjcvp/pvae010","DOIUrl":"10.1093/ehjcvp/pvae010","url":null,"abstract":"","PeriodicalId":11982,"journal":{"name":"European Heart Journal - Cardiovascular Pharmacotherapy","volume":null,"pages":null},"PeriodicalIF":7.1,"publicationDate":"2024-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139574387","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}
Domenico D'Amario, Mattia Galli, Attilio Restivo, Francesco Canonico, Rocco Vergallo, Stefano Migliaro, Carlo Trani, Francesco Burzotta, Cristina Aurigemma, Renzo Laborante, Enrico Romagnoli, Francesca Francese, Ilaria Ceccarelli, Josip A Borovac, Dominick J Angiolillo, Barbara Tavazzi, Antonio M Leone, Filippo Crea, Giuseppe Patti, Italo Porto
Background: Ticagrelor improves clinical outcomes in patients with acute coronary syndromes compared with clopidogrel. Ticagrelor also inhibits cell uptake of adenosine and has been associated with cardioprotective effects in animal models. We sought to investigate the potential cardioprotective effects of ticagrelor, as compared with clopidogrel, in stable patients undergoing percutaneous coronary intervention (PCI).
Methods and results: This was a Prospective Randomized Open Blinded End-points (PROBE) trial enrolling stable patients with coronary artery disease (CAD) requiring fractional flow reserve-guided PCI of intermediate epicardial coronary lesions. ST-segment elevation at intracoronary electrocardiogram (IC-ECG) during a two-step sequential coronary balloon inflations in the reference vessel during PCI was used as an indirect marker of cardioprotection induced by ischemic preconditioning (IPC). The primary endpoint of the study was the comparison of the delta (Δ) (difference) ST-segment elevation measured by IC-ECG during two-step sequential coronary balloon inflations.
Results: Fifty-three patients were randomized to either clopidogrel or ticagrelor. The study was stopped earlier because the primary endpoint was met at a pre-specified interim analysis. ΔST-segment elevation was significantly higher in ticagrelor as compared to clopidogrel arms (P < 0.0001). Ticagrelor was associated with lower angina score during coronary balloon inflations. There was no difference in coronary microvascular resistance between groups. Adenosine serum concentrations were increased in patients treated with ticagrelor as compared to those treated with clopidogrel.
Conclusions: Ticagrelor enhances the cardioprotective effects of IPC compared with clopidogrel in stable patients with CAD undergoing PCI. Further studies are warranted to fully elucidate the mechanisms through which ticagrelor may exert cardioprotective effects in humans.
{"title":"Ticagrelor enhances the cardioprotective effects of ischemic preconditioning in stable patients undergoing percutaneous coronary intervention: the TAPER-S randomized study.","authors":"Domenico D'Amario, Mattia Galli, Attilio Restivo, Francesco Canonico, Rocco Vergallo, Stefano Migliaro, Carlo Trani, Francesco Burzotta, Cristina Aurigemma, Renzo Laborante, Enrico Romagnoli, Francesca Francese, Ilaria Ceccarelli, Josip A Borovac, Dominick J Angiolillo, Barbara Tavazzi, Antonio M Leone, Filippo Crea, Giuseppe Patti, Italo Porto","doi":"10.1093/ehjcvp/pvad092","DOIUrl":"10.1093/ehjcvp/pvad092","url":null,"abstract":"<p><strong>Background: </strong>Ticagrelor improves clinical outcomes in patients with acute coronary syndromes compared with clopidogrel. Ticagrelor also inhibits cell uptake of adenosine and has been associated with cardioprotective effects in animal models. We sought to investigate the potential cardioprotective effects of ticagrelor, as compared with clopidogrel, in stable patients undergoing percutaneous coronary intervention (PCI).</p><p><strong>Methods and results: </strong>This was a Prospective Randomized Open Blinded End-points (PROBE) trial enrolling stable patients with coronary artery disease (CAD) requiring fractional flow reserve-guided PCI of intermediate epicardial coronary lesions. ST-segment elevation at intracoronary electrocardiogram (IC-ECG) during a two-step sequential coronary balloon inflations in the reference vessel during PCI was used as an indirect marker of cardioprotection induced by ischemic preconditioning (IPC). The primary endpoint of the study was the comparison of the delta (Δ) (difference) ST-segment elevation measured by IC-ECG during two-step sequential coronary balloon inflations.</p><p><strong>Results: </strong>Fifty-three patients were randomized to either clopidogrel or ticagrelor. The study was stopped earlier because the primary endpoint was met at a pre-specified interim analysis. ΔST-segment elevation was significantly higher in ticagrelor as compared to clopidogrel arms (P < 0.0001). Ticagrelor was associated with lower angina score during coronary balloon inflations. There was no difference in coronary microvascular resistance between groups. Adenosine serum concentrations were increased in patients treated with ticagrelor as compared to those treated with clopidogrel.</p><p><strong>Conclusions: </strong>Ticagrelor enhances the cardioprotective effects of IPC compared with clopidogrel in stable patients with CAD undergoing PCI. Further studies are warranted to fully elucidate the mechanisms through which ticagrelor may exert cardioprotective effects in humans.</p><p><strong>Clinical trial registration: </strong>http://www.clinicaltrials.gov. Unique Identifier: NCT02701140.</p>","PeriodicalId":11982,"journal":{"name":"European Heart Journal - Cardiovascular Pharmacotherapy","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138433593","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}
{"title":"Oral anticoagulants and antiplatelet treatment in different settings.","authors":"","doi":"10.1093/ehjcvp/pvae021","DOIUrl":"10.1093/ehjcvp/pvae021","url":null,"abstract":"","PeriodicalId":11982,"journal":{"name":"European Heart Journal - Cardiovascular Pharmacotherapy","volume":null,"pages":null},"PeriodicalIF":7.1,"publicationDate":"2024-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140335272","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}
Marie Hauguel-Moreau, Paul Guedeney, Claire Dauphin, Vincent Auffret, Eloi Marijon, Philippe Aldebert, Jean-Michel Clerc, Farzin Beygui, Meyer Elbaz, Wissam Abi Khalil, Antoine Da Costa, Jean-Christophe Macia, Simon Elhadad, Guillaume Cayla, Delphine Brugier, Johanne Silvain, Nadjib Hammoudi, Guillaume Duthoit, Eric Vicaut, Gilles Montalescot
Introduction: Atrial arrhythmia is the most common complication of patent foramen ovale (PFO) closure. The real incidence of post-PFO closure atrial arrhytmia and whether this complication can be prevented is unknown.
Methods/design: The Assessment of Flecainide to Lower the PFO closure risk of Atrial fibrillation or Tachycardia (AFLOAT) trial is a prospective, national, multicentre, randomized, open-label, superiority trial with a blind evaluation of all the endpoints (PROBE design). A total of 186 patients are randomized in a 1:1:1 ratio immediately after PFO closure to receive Flecainide (150 mg per day in a single sustained-release (SR) dose) for 6 months (Group 1), Flecainide (150 mg per day in a single SR dose) for 3 months (Group 2), or no additional treatment (standard of care) for 6 months (Group 3). The primary endpoint is the percentage of patients with at least one episode of symptomatic or asymptomatic atrial arrhythmia episode (≥30 s) recorded within 3 months after PFO closure on long-term monitoring with an insertable cardiac monitor. Whether 3 months of treatment is sufficient compared to 6 months will be analysed as a secondary objective of the study.
Conclusion: AFLOAT is the first trial to test the hypothesis that a short treatment with oral Flecainide can prevent the new-onset of atrial arrhythmia after PFO closure.
{"title":"Flecainide to prevent atrial arrhythmia after patent foramen ovale closure, Rationale and design of the randomized AFLOAT study.","authors":"Marie Hauguel-Moreau, Paul Guedeney, Claire Dauphin, Vincent Auffret, Eloi Marijon, Philippe Aldebert, Jean-Michel Clerc, Farzin Beygui, Meyer Elbaz, Wissam Abi Khalil, Antoine Da Costa, Jean-Christophe Macia, Simon Elhadad, Guillaume Cayla, Delphine Brugier, Johanne Silvain, Nadjib Hammoudi, Guillaume Duthoit, Eric Vicaut, Gilles Montalescot","doi":"10.1093/ehjcvp/pvad100","DOIUrl":"10.1093/ehjcvp/pvad100","url":null,"abstract":"<p><strong>Introduction: </strong>Atrial arrhythmia is the most common complication of patent foramen ovale (PFO) closure. The real incidence of post-PFO closure atrial arrhytmia and whether this complication can be prevented is unknown.</p><p><strong>Methods/design: </strong>The Assessment of Flecainide to Lower the PFO closure risk of Atrial fibrillation or Tachycardia (AFLOAT) trial is a prospective, national, multicentre, randomized, open-label, superiority trial with a blind evaluation of all the endpoints (PROBE design). A total of 186 patients are randomized in a 1:1:1 ratio immediately after PFO closure to receive Flecainide (150 mg per day in a single sustained-release (SR) dose) for 6 months (Group 1), Flecainide (150 mg per day in a single SR dose) for 3 months (Group 2), or no additional treatment (standard of care) for 6 months (Group 3). The primary endpoint is the percentage of patients with at least one episode of symptomatic or asymptomatic atrial arrhythmia episode (≥30 s) recorded within 3 months after PFO closure on long-term monitoring with an insertable cardiac monitor. Whether 3 months of treatment is sufficient compared to 6 months will be analysed as a secondary objective of the study.</p><p><strong>Conclusion: </strong>AFLOAT is the first trial to test the hypothesis that a short treatment with oral Flecainide can prevent the new-onset of atrial arrhythmia after PFO closure.</p><p><strong>Clinical trial registration: </strong>NCT05213104 (clinicaltrials.gov).</p>","PeriodicalId":11982,"journal":{"name":"European Heart Journal - Cardiovascular Pharmacotherapy","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139432353","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}
Juan Tamargo, Stefan Agewall, Claudio Borghi, Claudio Ceconi, Elisabetta Cerbai, Gheorghe A Dan, Péter Ferdinandy, Erik Lerkevang Grove, Bianca Rocca, Emma Magavern, Patrick Sulzgruber, Anne Grete Semb, Samuel Sossalla, Alexander Niessner, Juan Carlos Kaski, Dobromir Dobrev
Although cardiovascular diseases (CVDs) are the leading cause of death worldwide, their pharmacotherapy remains suboptimal. Thus, there is a clear unmet need to develop more effective and safer pharmacological strategies. In this review, we summarize the most relevant advances in cardiovascular pharmacology in 2023, including the approval of first-in-class drugs that open new avenues for the treatment of atherosclerotic CVD and heart failure (HF). The new indications of drugs already marketed (repurposing) for the treatment of obstructive hypertrophic cardiomyopathy, hypercholesterolaemia, type 2 diabetes, obesity, and HF; the impact of polypharmacy on guideline-directed drug use is highlighted as well as results from negative clinical trials. Finally, we end with a summary of the most important phase 2 and 3 clinical trials assessing the efficacy and safety of cardiovascular drugs under development for the prevention and treatment of CVDs.
{"title":"New pharmacological agents and novel cardiovascular pharmacotherapy strategies in 2023.","authors":"Juan Tamargo, Stefan Agewall, Claudio Borghi, Claudio Ceconi, Elisabetta Cerbai, Gheorghe A Dan, Péter Ferdinandy, Erik Lerkevang Grove, Bianca Rocca, Emma Magavern, Patrick Sulzgruber, Anne Grete Semb, Samuel Sossalla, Alexander Niessner, Juan Carlos Kaski, Dobromir Dobrev","doi":"10.1093/ehjcvp/pvae013","DOIUrl":"10.1093/ehjcvp/pvae013","url":null,"abstract":"<p><p>Although cardiovascular diseases (CVDs) are the leading cause of death worldwide, their pharmacotherapy remains suboptimal. Thus, there is a clear unmet need to develop more effective and safer pharmacological strategies. In this review, we summarize the most relevant advances in cardiovascular pharmacology in 2023, including the approval of first-in-class drugs that open new avenues for the treatment of atherosclerotic CVD and heart failure (HF). The new indications of drugs already marketed (repurposing) for the treatment of obstructive hypertrophic cardiomyopathy, hypercholesterolaemia, type 2 diabetes, obesity, and HF; the impact of polypharmacy on guideline-directed drug use is highlighted as well as results from negative clinical trials. Finally, we end with a summary of the most important phase 2 and 3 clinical trials assessing the efficacy and safety of cardiovascular drugs under development for the prevention and treatment of CVDs.</p>","PeriodicalId":11982,"journal":{"name":"European Heart Journal - Cardiovascular Pharmacotherapy","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11121198/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139912378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anna Meta Dyrvig Kristensen, John Munkhaugen, Sigrun Halvorsen, Michael Hecht Olsen, Arnhild Bakken, Thomas Steen Gyldenstierne Sehested, Vidar Ruddox, Theis Lange, Morten Wang Fagerland, Christian Torp-Pedersen, Eva Prescott, Dan Atar
Background and aims: The evidence for beta-blocker therapy after myocardial infarction (MI) is randomized trials conducted more than 30 years ago, and the continued efficacy has been questioned.
Design and methods: The ongoing Danish (DANBLOCK) and Norwegian (BETAMI) randomized beta-blocker trials are joined to evaluate the effectiveness and risks of long-term beta-blocker therapy after MI. Patients with normal or mildly reduced left ventricular ejection fraction (LVEF ≥ 40%) will be randomized to open-label treatment with beta-blockers or no such therapy. The event-driven trial will randomize ∼5700 patients and continue until 950 primary endpoints have occurred. As of July 2023, 5228 patients have been randomized. Of the first 4000 patients randomized, median age was 62 years, 79% were men, 48% had a ST-segment elevation myocardial infarction (STEMI), and 84% had a normal LVEF. The primary endpoint is a composite of adjudicated recurrent MI, incident heart failure (HF), coronary revascularization, ischaemic stroke, all-cause mortality, malignant ventricular arrhythmia, or resuscitated cardiac arrest. The primary safety endpoint includes a composite of recurrent MI, HF, all-cause mortality, malignant ventricular arrhythmia, or resuscitated cardiac arrest 30 days after randomization. Secondary endpoints include each of the components of the primary endpoint, patient-reported outcomes, and other clinical outcomes linked to beta-blocker therapy. The primary analysis will be conducted according to the intention-to-treat principle using a Cox proportional hazards regression model. End of follow-up is expected in December 2024.
Conclusion: The combined BETAMI-DANBLOCK trial will have the potential to affect current clinical practice for beta-blocker therapy in patients with normal or mildly reduced LVEF after MI.
{"title":"The Danish-Norwegian randomized trial on beta-blocker therapy after myocardial infarction: Design, rationale, and baseline characteristics.","authors":"Anna Meta Dyrvig Kristensen, John Munkhaugen, Sigrun Halvorsen, Michael Hecht Olsen, Arnhild Bakken, Thomas Steen Gyldenstierne Sehested, Vidar Ruddox, Theis Lange, Morten Wang Fagerland, Christian Torp-Pedersen, Eva Prescott, Dan Atar","doi":"10.1093/ehjcvp/pvad093","DOIUrl":"10.1093/ehjcvp/pvad093","url":null,"abstract":"<p><strong>Background and aims: </strong>The evidence for beta-blocker therapy after myocardial infarction (MI) is randomized trials conducted more than 30 years ago, and the continued efficacy has been questioned.</p><p><strong>Design and methods: </strong>The ongoing Danish (DANBLOCK) and Norwegian (BETAMI) randomized beta-blocker trials are joined to evaluate the effectiveness and risks of long-term beta-blocker therapy after MI. Patients with normal or mildly reduced left ventricular ejection fraction (LVEF ≥ 40%) will be randomized to open-label treatment with beta-blockers or no such therapy. The event-driven trial will randomize ∼5700 patients and continue until 950 primary endpoints have occurred. As of July 2023, 5228 patients have been randomized. Of the first 4000 patients randomized, median age was 62 years, 79% were men, 48% had a ST-segment elevation myocardial infarction (STEMI), and 84% had a normal LVEF. The primary endpoint is a composite of adjudicated recurrent MI, incident heart failure (HF), coronary revascularization, ischaemic stroke, all-cause mortality, malignant ventricular arrhythmia, or resuscitated cardiac arrest. The primary safety endpoint includes a composite of recurrent MI, HF, all-cause mortality, malignant ventricular arrhythmia, or resuscitated cardiac arrest 30 days after randomization. Secondary endpoints include each of the components of the primary endpoint, patient-reported outcomes, and other clinical outcomes linked to beta-blocker therapy. The primary analysis will be conducted according to the intention-to-treat principle using a Cox proportional hazards regression model. End of follow-up is expected in December 2024.</p><p><strong>Conclusion: </strong>The combined BETAMI-DANBLOCK trial will have the potential to affect current clinical practice for beta-blocker therapy in patients with normal or mildly reduced LVEF after MI.</p>","PeriodicalId":11982,"journal":{"name":"European Heart Journal - Cardiovascular Pharmacotherapy","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138451204","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}