Mineralocorticoid Receptor Antagonists

盐皮质激素受体拮抗剂
  • 文章类型: Journal Article
    背景:我们先前证明了较高的简单指导药物治疗(GDMT)评分(包括肾素-血管紧张素系统抑制剂,β-受体阻滞剂,盐皮质激素拮抗剂,出院时钠-葡萄糖协同转运蛋白2抑制剂)与心力衰竭(HF)患者预后改善相关。HF再入院与不良结果有关,强调需要加强GDMT的优化。方法和结果:使用简单的GDMT评分,我们评估了修订和修改院内GDMT对HF再入院患者预后的影响.在2,100例HF患者的回顾性分析中,我们集中于1,222例射血分数降低/射血分数中度降低的HF患者,排除射血分数保留的HF患者,透析时,或者是谁死在医院.较高的当前GDMT评分与较好的HF预后相关。在研究的1,222名患者中,我们分析了372例再次住院,计算入院和出院时的简单GDMT分数。根据评分改善情况分组。多变量分析显示,改善的院内简单GDMT评分与复合结局(HF再入院+全因死亡率;风险比0.459;95%置信区间0.257-0.820;P=0.008)之间存在显著关联。即使在倾向得分匹配以调整背景之后,在再次住院的患者中,住院简易GDMT评分改善的患者预后较好.
    结论:我们的结果强调了在住院期间采取强有力的干预措施和提高评分可改善预后的潜力。
    BACKGROUND: We previously demonstrated that higher simple guideline-directed medical therapy (GDMT) scores (comprising renin-angiotensin system inhibitors, β-blockers, mineralocorticoid antagonists, and sodium-glucose cotransporter 2 inhibitors) at discharge were correlated with improved prognosis in heart failure (HF) patients. HF readmissions are linked to adverse outcomes, emphasizing the need for enhanced optimization of GDMT.
    RESULTS: Using the simple GDMT score, we evaluated the effect of revising and modifying in-hospital GDMT on the prognosis of patients with HF readmissions. In this retrospective analysis of 2,100 HF patients, we concentrated on 1,222 patients with HF with reduced ejection/moderately reduced ejection fraction, excluding patients with HF with preserved ejection fraction, on dialysis, or who died in hospital. A higher current GDMT score was associated with better HF prognosis. Of the 1,222 patients in the study, we analyzed 372 cases of rehospitalization, calculating the simple GDMT scores at admission and discharge. Patients were divided into groups according to score improvement. Multivariate analysis showed a significant association between improved in-hospital simple GDMT score and the composite outcome (HF readmission+all-cause mortality; hazard ratio 0.459; 95% confidence interval 0.257-0.820; P=0.008). Even after propensity score matching to adjust for background, among rehospitalized patients, those with an improved in-hospital simple GDMT score had a better prognosis.
    CONCLUSIONS: Our results highlight the potential of robust interventions and score elevation during hospitalization leading to improved outcomes.
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  • 文章类型: Journal Article
    背景:指导医学治疗(GDMT)在改善心力衰竭患者的预后方面具有革命性意义。然而,随着更多的药物类别的增加,这些药物在美国医疗保健系统中的年度成本需要进一步评估.
    目标:我们的目标是使用Medicare-D部分数据库评估2013年至2021年GDMT的年度成本趋势。
    方法:使用MedicareD部分数据库(2013-2021),我们确定了接受这些药物的受益人的数量,每种药物的30天填充总数,以及这些药物的年度总支出。线性回归用于使用Python编程语言分析数据。P值小于0.05被认为具有统计学意义。
    结果:在2020年至2021年期间,估计的年度Medicare-D部分在empagliflozin的支出成本增加了50%,这可能归因于其FDA批准降低射血分数的心力衰竭。仅在2021年,Empagliflozin就花费了医疗保险37.3亿美元。此外,沙库巴曲-缬沙坦自2015年推向市场以来,其发展轨迹强劲。自2015年7月批准以来,Medicare花费了45.1亿美元。盐皮质激素受体拮抗剂类别是成本最低的GDMT类别。
    结论:GDMT的成本上升在不同类别的GDMT中不成比例。近年来,较新的药物类别给Medicare带来了巨大的成本。
    BACKGROUND: Guideline Directed Medical Therapy (GDMT) has been revolutionary in improving outcomes of heart failure patients. However, with the addition of more medication classes, the annual cost of these medications on the US healthcare system needs further evaluation.
    OBJECTIVE: We aim to evaluate the trend of annual cost of GDMT from 2013 to 2021 using the Medicare-part D Database.
    METHODS: Using Medicare Part D database (2013-2021), we determined the number of beneficiaries receiving these drugs, the total number of 30-day fills for each medication, and the total annual spending on these medications. Linear regression was used to analyze data using Python Programming Language. P value of less than 0.05 was considered to be statistically significant.
    RESULTS: The estimated annual Medicare- part D spending on empagliflozin had a 50 % increase in cost between 2020 and 2021, which could be attributed to its FDA approval for heart failure with reduced ejection fraction. Empagliflozin cost Medicare 3.73 billion USD in 2021 alone. In addition, sacubitril-valsartan had a strong trajectory since its introduction to the market in 2015. Since its approval in July 2015, it cost Medicare 4.51 billion USD. The Mineralocorticoid Receptor Antagonist class was the least costly class of GDMT.
    CONCLUSIONS: The rise in the cost of GDMT is not proportionate amongst the different classes of GDMT. Newer classes of medications cast a significant cost on Medicare in recent years.
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  • 文章类型: Editorial
    暂无摘要。
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  • 文章类型: Journal Article
    量化指南指导的药物治疗(GDMT)强度是改善心力衰竭(HF)护理的基础。现有措施降低剂量强度或使用不一致的权重。
    堪萨斯城医学优化(KCMO)评分是合格GDMT的每日总剂量与目标剂量百分比的平均值,反映规定的最佳GDMT的百分比(范围,0-100)。在改变HF患者的管理中,我们计算了KCMO,HF合作(0-7),和改良的HFCollaboratory(0-100)评分为每个患者的基线和1年时已建立的GDMT的变化(盐皮质激素受体拮抗剂,β-受体阻滞剂,ACE[血管紧张素转换酶]抑制剂/血管紧张素受体阻滞剂/血管紧张素受体脑啡肽酶抑制剂)。我们比较了基线和1年的变化分布以及分数之间的变异系数(SD/平均值)。
    在基线时的4532名患者中,意思是KCMO,HF合作,改良的HF校准评分为38.8分(SD,25.7),3.4(1.7)、和42.2(22.2),分别。KCMO的平均1年变化(n=4061)为-1.94(17.8);HF合作者,-0.11(1.32);和改进的HF协作,-1.35(19.8)。KCMO的变异系数最高(0.66),表明平均值比HF协作(0.49)和改良的HF协作(0.53)分数更大的变异性,反映了患者GDMT强度变异性的更高分辨率。
    KCMO通过纳入剂量和治疗资格来测量GDMT强度,提供比现有方法更多的粒度,很容易解释(理想GDMT的百分比),并且可以随着绩效指标的发展而调整。需要进一步研究其与结果的关联及其对质量评估和改进的有用性。
    UNASSIGNED: Quantifying guideline-directed medical therapy (GDMT) intensity is foundational for improving heart failure (HF) care. Existing measures discount dose intensity or use inconsistent weighting.
    UNASSIGNED: The Kansas City Medical Optimization (KCMO) score is the average of total daily to target dose percentages for eligible GDMT, reflecting the percentage of optimal GDMT prescribed (range, 0-100). In Change the Management of Patients With HF, we computed KCMO, HF collaboratory (0-7), and modified HF Collaboratory (0-100) scores for each patient at baseline and for 1-year change in established GDMT at the time (mineralocorticoid receptor antagonist, β-blocker, ACE [angiotensin-converting enzyme] inhibitor/angiotensin receptor blocker/angiotensin receptor neprilysin inhibitor). We compared baseline and 1-year change distributions and the coefficient of variation (SD/mean) across scores.
    UNASSIGNED: Among 4532 patients at baseline, mean KCMO, HF collaboratory, and modified HF Collaboratory scores were 38.8 (SD, 25.7), 3.4 (1.7), and 42.2 (22.2), respectively. The mean 1-year change (n=4061) for KCMO was -1.94 (17.8); HF collaborator, -0.11 (1.32); and modified HF Collaboratory, -1.35 (19.8). KCMO had the highest coefficient of variation (0.66), indicating greater variability around the mean than the HF collaboratory (0.49) and modified HF Collaboratory (0.53) scores, reflecting higher resolution of the variability in GDMT intensity across patients.
    UNASSIGNED: KCMO measures GDMT intensity by incorporating dosing and treatment eligibility, provides more granularity than existing methods, is easily interpretable (percentage of ideal GDMT), and can be adapted as performance measures evolve. Further study of its association with outcomes and its usefulness for quality assessment and improvement is needed.
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  • 文章类型: Journal Article
    背景:据推测,癌症阻碍了针对心力衰竭(HF)的指南指导药物治疗(GDMT)的实施。然而,这方面的数据很少。
    方法:我们对热诺瓦的IRCCSOspedalePoliclinicoSanMartino的HF门诊进行了回顾性分析,意大利。在2010年至2019年期间评估的所有HF患者,左心室射血分数<50%,并且至少两次间隔≥3个月的访问以及有关GDMT的完整信息被纳入研究。我们特别评估了GDMT的处方,β受体阻滞剂(BB),肾素-血管紧张素系统抑制剂(RASi),和盐皮质激素拮抗剂(MRA)-在最后一次HF评估时,并在有和无偶发癌症的患者之间进行比较。对于那些患有癌症的人来说,我们还评估了GDMT的修改,比较了癌症诊断前后的HF评估结果.
    结果:在464例HF患者中,39例(8%)有偶发癌。在最后一次评估中,有和没有偶然癌症的患者之间的GDMT没有统计学差异。在癌症诊断后的一年,在BB上的33例偶然癌症患者中,没有人停止治疗,但是有两个人的剂量低于50%;在RASi的27名患者中,两名患者停止了治疗,三名患者的剂量下降至<50%;在MRA的19名患者中,四个停止治疗。
    结论:尽管患有偶发癌症的HF患者在诊断癌症时可能需要进行GDMT的滴定,这似乎并未显著阻碍随访期间HF治疗的实施.
    BACKGROUND: It has been postulated that cancer hampers the delivery of guideline-directed medical therapy (GDMT) for heart failure (HF). However, few data are available in this regard.
    METHODS: We performed a retrospective analysis from the HF Outpatient Clinic of the IRCCS Ospedale Policlinico San Martino in Genova, Italy. All HF patients evaluated between 2010 and 2019, with a left ventricular ejection fraction <50% and at least two visits ≥3 months apart with complete information about GDMT were included in the study. We assessed the prescription of GDMT-in particular, beta-blockers (BB), renin-angiotensin system inhibitors (RASi), and mineralocorticoid antagonists (MRA)-at the time of the last HF evaluation and compared it between patients with and without incidental cancer. For those with incidental cancer, we also evaluated modifications of GDMT comparing the HF evaluations before and after cancer diagnosis.
    RESULTS: Of 464 HF patients, 39 (8%) had incidental cancer. There were no statistical differences in GDMT between patients with and without incidental cancer at last evaluation. In the year following cancer diagnosis, of 33 patients with incidental cancer on BB, none stopped therapy, but two had a down-titration to a dosage <50%; of 27 patients on RASi, two patients stopped therapy and three had a down-titration to a dosage <50%; of 19 patients on MRA, four stopped therapy.
    CONCLUSIONS: Although HF patients with incidental cancer may need to have GDMT down-titrated at the time of cancer diagnosis, this does not appear to significantly hinder the delivery of HF therapies during follow-up.
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  • 文章类型: Journal Article
    背景:推荐的心力衰竭(HF)药物的使用随着时间的推移而有所改善,但是妇女和农村医院仍然存在改善的机会。
    目的:本研究旨在描述美国退伍军人事务部(VA)医院在使用指南推荐的HF药物治疗方面的国家趋势,药物共付额适中。
    方法:在2013年1月1日至2019年12月31日期间从VA医院出院的HF患者中,评估了符合条件的患者接受所有指南推荐的HF药物治疗的情况。由循证β受体阻滞剂组成;血管紧张素转换酶抑制剂,血管紧张素受体阻滞剂,或血管紧张素受体脑啡肽抑制剂;盐皮质激素受体拮抗剂;和口服抗凝。
    结果:在122家医院的55,560名患者中,32,304(58.1%)接受了所有符合资格的指南推荐的HF药物。与2013年相比,2019年接受所有推荐药物的患者比例更高(OR:1.54;95%CI:1.44-1.65)。医院绩效中位数为59.1%(Q1-Q3:53.2%-66.2%),从2013年(中位数为56.4%;第一季度至第三季度:50.0%-62.0%)到2019年(中位数为65.7%;第一季度至第三季度:56.3%-73.5%),各站点之间存在较大差异。与男性相比,女性接受推荐治疗的可能性较低(校正OR[aOR]:0.84;95%CI:0.74-0.96)。与非西班牙裔白人患者相比,非西班牙裔黑人患者接受推荐治疗的可能性较小(aOR:0.83;95%CI:0.79~0.87).城市医院位置与较低的药物接收可能性相关(aOR:0.73;95%CI:0.59-0.92)。
    结论:42%的患者在出院时未接受所有推荐的HF药物治疗,尤其是女性,少数民族患者,以及那些在城市医院接受治疗的人。使用率随着时间的推移而增加,不同医院的表现各不相同。
    BACKGROUND: The use of recommended heart failure (HF) medications has improved over time, but opportunities for improvement persist among women and at rural hospitals.
    OBJECTIVE: This study aims to characterize national trends in performance in the use of guideline-recommended pharmacologic treatment for HF at U.S. Department of Veterans Affairs (VA) hospitals, at which medication copayments are modest.
    METHODS: Among patients discharged from VA hospitals with HF between January 1, 2013, and December 31, 2019, receipt of all guideline-recommended HF pharmacotherapy among eligible patients was assessed, consisting of evidence-based beta-blockers; angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or angiotensin receptor neprilysin inhibitors; mineralocorticoid receptor antagonists; and oral anticoagulation.
    RESULTS: Of 55,560 patients at 122 hospitals, 32,304 (58.1%) received all guideline-recommended HF medications for which they were eligible. The proportion of patients receiving all recommended medications was higher in 2019 relative to 2013 (OR: 1.54; 95% CI: 1.44-1.65). The median of hospital performance was 59.1% (Q1-Q3: 53.2%-66.2%), improving with substantial variation across sites from 2013 (median 56.4%; Q1-Q3: 50.0%-62.0%) to 2019 (median 65.7%; Q1-Q3: 56.3%-73.5%). Women were less likely to receive recommended therapies than men (adjusted OR [aOR]: 0.84; 95% CI: 0.74-0.96). Compared with non-Hispanic White patients, non-Hispanic Black patients were less likely to receive recommended therapies (aOR: 0.83; 95% CI: 0.79-0.87). Urban hospital location was associated with lower likelihood of medication receipt (aOR: 0.73; 95% CI: 0.59-0.92).
    CONCLUSIONS: Forty-two percent of patients did not receive all recommended HF medications at discharge, particularly women, minority patients, and those receiving care at urban hospitals. Rates of use increased over time, with variation in performance across hospitals.
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  • 文章类型: Journal Article
    2024年3月27日:本文错误地发表在《早期观点》上。该文章受到禁运,将在2024年5月11日之后重新发布。
    OBJECTIVE: Recent guidelines recommend four core drug classes (renin-angiotensin system inhibitor/angiotensin receptor-neprilysin inhibitor [RASi/ARNi], beta-blocker, mineralocorticoid receptor antagonist [MRA], and sodium-glucose cotransporter 2 inhibitor [SGLT2i]) for the pharmacological management of heart failure (HF) with reduced ejection fraction (HFrEF). We assessed physicians\' perceived (i) comfort with implementing the recent HFrEF guideline recommendations; (ii) status of guideline-directed medical therapy (GDMT) implementation; (iii) use of different GDMT sequencing strategies; and (iv) barriers and strategies for achieving implementation.
    RESULTS: A 26-question survey was disseminated via bulletin, e-mail and social channels directed to physicians with an interest in HF. Of 432 respondents representing 91 countries, 36% were female, 52% were aged <50 years, and 90% mainly practiced in cardiology (30% HF). Overall comfort with implementing quadruple therapy was high (87%). Only 12% estimated that >90% of patients with HFrEF without contraindications received quadruple therapy. The time required to initiate quadruple therapy was estimated at 1-2 weeks by 34% of respondents, 1 month by 36%, 3 months by 24%, and ≥6 months by 6%. The average respondent favoured traditional drug sequencing strategies (RASi/ARNi with/followed by beta-blocker, and then MRA with/followed by SGLT2i) over simultaneous initiation or SGLT2i-first sequences. The most frequently perceived clinical barriers to implementation were hypotension (70%), creatinine increase (47%), hyperkalaemia (45%) and patient adherence (42%).
    CONCLUSIONS: Although comfort with implementing all four core drug classes in patients with HFrEF was high among physicians, a majority estimated implementation of GDMT in HFrEF to be low. We identified several important perceived clinical and non-clinical barriers that can be targeted to improve implementation.
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  • 文章类型: Journal Article
    心力衰竭是一种慢性和无效综合征,影响全世界数千万人,对医疗保健系统产生重大的社会经济影响。在了解心力衰竭的病理生理学方面的重大进展已经允许逐步引入几种药物类别来管理此类患者。β受体阻滞剂,盐皮质激素受体拮抗剂,血管紧张素受体脑啡肽抑制剂,和钠-葡萄糖-协同转运蛋白2抑制剂都被认为是指导心力衰竭的指导药物治疗的支柱.尽管心力衰竭的发病率和死亡率显著改善,然而,许多患者在与这四个药物支柱联合治疗期间仍出现临床上显著的高钾血症.结果通常是一种或多种关键药物的滴定或停药,这反过来导致心血管事件的风险显著增加,透析,和全因死亡率。本文将探讨治疗心力衰竭高钾血症的新方法。包括更密切的钾水平监测,早期审查可能增加高钾血症风险的药物,和高钾血症的药物治疗,特别强调钠-葡萄糖-协同转运蛋白2抑制剂和钾结合剂,包括patiromer和环硅酸锆钠。
    Heart failure is a chronic and invalidating syndrome that affects tens of millions of people worldwide with significant socio-economic ramifications for the health care systems. Significant progress in the understanding of the pathophysiology of heart failure has allowed the gradual introduction of several drug classes for the management of such patients. Beta-blockers, mineralocorticoid receptor antagonists, angiotensin receptor neprilysin inhibitors, and sodium-glucose-cotransporter 2 inhibitors are all considered pillars of the guideline-directed medical therapy for heart failure. Despite remarkable improvements in the morbidity and mortality of heart failure, however, many patients still develop clinically significant hyperkalemia during combined treatment with those four pharmacological pillars. The consequence is often a down-titration or discontinuation of one or more crucial drugs, which in turns leads to a considerable increase in the risk of cardiovascular events, dialysis, and all-cause mortality. This paper will explore novel approaches for the management of hyperkalemia in heart failure, including closer monitoring of potassium levels, early review of drugs that might increase the risk of hyperkalemia, and pharmacological treatment of hyperkalemia, with a special emphasis on sodium-glucose-cotransporter 2 inhibitors and potassium-binding agents, including patiromer and sodium zirconium cyclosilicate.
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  • 文章类型: Journal Article
    背景:尽管一些指南建议射血分数降低(HFrEF)的心力衰竭患者接受血管紧张素转换酶抑制剂/血管紧张素II受体阻滞剂(ACEI/ARBs)或血管紧张素受体-脑啡肽抑制剂(ARNIs)治疗,β受体阻滞剂,盐皮质激素受体拮抗剂(MRA),和钠-葡萄糖协同转运蛋白-2抑制剂(SGLT2i),在哥伦比亚,他们的处方和剂量仍然存在一些差距。本研究旨在描述哥伦比亚心力衰竭登记处(RECOLFACA)中HFrEF治疗的使用模式。
    方法:纳入2017-2019年RECOLFACA的HFrEF患者。使用绝对数和比例评估心力衰竭(HF)药物处方和每日剂量。将内科专家治疗的患者的治疗方案与心脏病专家治疗的患者进行了比较。
    结果:在注册的2,528名患者中,1,384(54.7%)有HFrEF。在这些人中,88.9%的人是处方β受体阻滞剂,72.3%与ACEI/ARB,67.9%与MRA,和13.1%的ARNI。此外,只有不到三分之一的患者达到了欧洲HF指南推荐的目标剂量.在由内科专家或心脏病专家治疗的患者之间,未观察到治疗方案或目标剂量的显着差异。
    结论:哥伦比亚的处方率和目标剂量实现均不理想。然而,与一些最新的HF注册相比,RECOLFACA的β受体阻滞剂和MRA的处方率最高。然而,ARNI仍然被低估。持续的注册更新可以改善适合ARNI和SGLT2i治疗的患者的识别,以促进其在临床实践中的使用。
    BACKGROUND: Although several guidelines recommend that patients with heart failure with reduced ejection fraction (HFrEF) be treated with angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (ACEIs/ARBs) or angiotensin receptor-neprilysin inhibitors (ARNIs), beta-blockers, mineralocorticoid receptor antagonists (MRAs), and sodium-glucose cotransporter-2 inhibitor (SGLT2i), there are still several gaps in their prescription and dosage in Colombia. This study aimed to describe the use patterns of HFrEF treatments in the Colombian Heart Failure Registry (RECOLFACA).
    METHODS: Patients with HFrEF enrolled in RECOLFACA during 2017-2019 were included. Heart failure (HF) medication prescription and daily dose were assessed using absolute numbers and proportions. Therapeutic schemes of patients treated by internal medicine specialists were compared with those treated by cardiologists.
    RESULTS: Out of 2,528 patients in the registry, 1,384 (54.7%) had HFrEF. Among those individuals, 88.9% were prescribed beta-blockers, 72.3% with ACEI/ARBs, 67.9% with MRAs, and 13.1% with ARNIs. Moreover, less than a third of the total patients reached the target doses recommended by the European HF guidelines. No significant differences in the therapeutic schemes or target doses were observed between patients treated by internal medicine specialists or cardiologists.
    CONCLUSIONS: Prescription rates and target dose achievement are suboptimal in Colombia. Nevertheless, RECOLFACA had one of the highest prescription rates of beta-blockers and MRAs compared to some of the most recent HF registries. However, ARNIs remain underprescribed. Continuous registry updates can improve the identification of patients suitable for ARNI and SGLT2i therapy to promote their use in clinical practice.
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  • 文章类型: Journal Article
    背景:主要心力衰竭(HF)试验在评估临床特征差异方面仍然不足,生物标志物,由于女性的压抑不足,治疗效果和安全性。该研究旨在介绍HF管理中与性别相关的差异,包括人口统计学的差异,合并症,心脏生物标志物,处方药,和治疗结果。
    方法:该研究使用了2016年1月1日至2022年12月31日土耳其卫生部国家电子数据库的匿名数据。队列分析包括2,501,231例成人HF患者。使用Cox回归模型分析特定的治疗组合,以获得全因死亡的相对风险降低。主要终点是全因死亡率。
    结果:在队列中,48.7%(n=1218911)为男性,51.3%(n=1282320)为女性。女性患者的中位年龄较高(71岁vs.68岁),表现为糖尿病患病率较高,贫血,心房颤动,焦虑,和缺血性中风。男性患者先前的心肌梗塞发生率较高,血脂异常,慢性阻塞性肺疾病,和慢性肾病。在女性患者中观察到较高浓度的利钠肽。RASi,β受体阻滞剂,MRA,SGLT2i,伊伐布雷定更常见于男性患者,而环状利尿剂,地高辛,和羧基麦芽糖铁在女性中更常见。男性患者的CRT和ICD植入率较高。男性患者的全因死亡率和住院率较高。与单一疗法相比,所有组合,包括SGLT2i,对女性和男性HF患者的全因死亡率均有有益的影响。在住院的HF患者中,在RASi中加入地高辛,MRA,在女性HF患者的全因死亡率方面,与男性HF患者相比,β受体阻滞剂优于单药治疗.
    结论:结论:本研究强调,与单药治疗相比,对HF药物组合的性别特异性反应以及合并症的差异强调了量身定制管理策略的重要性.在住院后,地高辛对两性的全因死亡率有对比作用,而SGLT2i当添加到所有组合中时,在两种性别中都表现出一致的有益效果。
    Major heart failure (HF) trials remain insufficient in terms of assessing the differences in clinical characteristics, biomarkers, treatment efficacy, and safety because of the under-representation of women. The study aimed to present sex-related disparities in HF management, including differences in demographics, co-morbidities, cardiac biomarkers, prescribed medications, and treatment outcomes. The study utilized anonymized data from the Turkish Ministry of Health\'s National Electronic Database between January 1, 2016, and December 31, 2022. The cohort analysis included 2,501,231 adult patients with HF. Specific therapeutic combinations were analyzed using a Cox regression model to obtain relative risk reduction for all-cause death. The primary end point was all-cause mortality. In the cohort, 48.7% (n = 1,218,911) were male, whereas 51.3% (n = 1,282,320) were female. Female patients exhibited a higher median age (71 vs 68 years) and manifested higher prevalence of diabetes mellitus, anemia, atrial fibrillation, anxiety, and ischemic stroke. Male patients demonstrated higher rates of previous myocardial infarction, dyslipidemia, chronic obstructive pulmonary disease, and chronic kidney disease. Higher concentrations of natriuretic peptides were observed in female patients. Renin-angiotensin aldosterone inhibitor, β blockers, mineralocorticoid receptor antagonists, sodium/glucose cotransporter 2 inhibitor (SGLT2i), and ivabradine were more commonly prescribed in male patients, whereas loop diuretics, digoxin, and ferric carboxymaltose were more frequent in female patients. Male patients had higher rates of cardiac resynchronization therapy and implantable cardioverter defibrillator implantation rates. All-cause mortality and hospitalization rates were higher in male patients. Compared with monotherapy, all combinations, including SGLT2i, showed a beneficial effect on all-cause mortality in both female and male patients with HF. In hospitalized patients with HF, the addition of digoxin to renin-angiotensin aldosterone inhibitor, mineralocorticoid receptor antagonists, and β blockers was superior to monotherapy regarding all-cause mortality in female patients with HF compared with male patients with HF. In conclusion, this study highlights that sex-specific responses to HF medication combinations compared with monotherapy and differences in co-morbidities underscore the importance of tailored management strategies. Digoxin showed a contrasting effect on all-cause mortality between both sexes after hospitalization, whereas SGLT2i exhibited a consistent beneficial effect in both sexes when added to all combinations.
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