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Evolution of antiplatelet therapy in Japan for the management of cerebrovascular and cardiovascular disease: a survey using data from an insurance claims data information service. 日本用于治疗脑血管和心血管疾病的抗血小板疗法的演变:一项利用保险理赔数据信息服务数据进行的调查。
IF 3.2 3区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-09-18 DOI: 10.1080/14656566.2024.2404108
Kosuke Miyake,Shuhei Ikeda,Yu Sadachi,Masako Sugimoto,Taketoshi Furugori,Tetsuya Kimura,Yusuke Yakushiji
BACKGROUNDNon-cardioembolic ischemic stroke (NCIS) and ischemic heart disease (IHD) require secondary prevention with antiplatelet therapy (APT). We investigated APT prescription status for patients with NCIS and IHD.RESEARCH DESIGN AND METHODSThis retrospective study utilized claims data from patients with NCIS and those who underwent percutaneous coronary intervention for IHD and received antiplatelet drugs. The study included Phases A (2015-2016), B (2017-2018), and C (2019-2020). We evaluated patient characteristics, APT prescription rates (dual [DAPT] and single [SAPT]), and prescriptions by NCIS subtype.RESULTSIn the NCIS cohort, the initial DAPT prescription rate increased over time (Phase A: 14.9%, B: 19.2%, C: 28.0%), but decreased to 6% after 3 months. Subsequently, 25% of patients did not receive APT. For IHD, DAPT duration decreased over time, with 12-month prescription rates of 48.0%, 43.1%, and 32.6% for Phases A, B, and C, respectively. SAPT prescriptions, predominantly aspirin, increased, and use of P2Y12 inhibitors also rose. Few patients (10%) did not receive APT.CONCLUSIONSShorter DAPT duration/earlier switching to SAPT for NCIS and IHD have gained acceptance in regional medical care. A higher proportion of NCIS vs IHD patients did not receive APT in the chronic phase.TRIAL REGISTRATIONUMIN000052198.
背景非心肌栓塞性缺血性中风(NCIS)和缺血性心脏病(IHD)需要使用抗血小板疗法(APT)进行二级预防。我们对 NCIS 和 IHD 患者的 APT 处方情况进行了调查。研究设计和方法这项回顾性研究利用了 NCIS 患者和因 IHD 接受经皮冠状动脉介入治疗并接受抗血小板药物治疗的患者的索赔数据。研究包括 A 阶段(2015-2016 年)、B 阶段(2017-2018 年)和 C 阶段(2019-2020 年)。我们评估了患者特征、APT处方率(双联 [DAPT]和单联 [SAPT])以及按NCIS亚型划分的处方情况。结果在NCIS队列中,初始DAPT处方率随时间推移而增加(A期:14.9%,B期:19.2%,C期:28.0%),但3个月后降至6%。随后,25% 的患者没有接受 APT。对于 IHD 患者,DAPT 持续时间随着时间的推移而缩短,A、B 和 C 阶段的 12 个月处方率分别为 48.0%、43.1% 和 32.6%。SAPT 处方(主要是阿司匹林)有所增加,P2Y12 抑制剂的使用也有所增加。结论NCIS和IHD患者缩短DAPT持续时间/提早改用SAPT已被地区医疗机构接受。NCIS与IHD患者在慢性期未接受APT治疗的比例更高。
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引用次数: 0
Expanding therapeutic options: overview of novel pharmacotherapies for dyslipidemia. 扩大治疗选择:血脂异常新型药物疗法概述。
IF 3.2 3区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-09-17 DOI: 10.1080/14656566.2024.2406270
Naif Saad ALGhasab,Federica Fogacci,Ashot Avagimyan,Arrigo F G Cicero
INTRODUCTIONDyslipidemia plays a crucial role in the development of atherosclerotic cardiovascular diseases.AREAS COVEREDThis article explores the emerging therapeutic targets for the treatment of dyslipidemia and provides novel insights into this field. Thus, it aims to contribute to the understanding and advancement of therapeutic options for managing dyslipidemia.EXPERT OPINIONOptimizing the use of available first- and second-line lipid-lowering drugs allows us to adequately control low-density lipoprotein cholesterol (LDL-C) levels, even in statin-intolerant individuals and in patients at high and very high risk of developing cardiovascular diseases who must reach more aggressive LDL-C targets. The drugs under development will further improve our ability to manage the overall lipid-related cardiovascular disease risk and target other dyslipidemia biomarkers.
简介血脂异常在动脉粥样硬化性心血管疾病的发生发展中起着至关重要的作用。专家观点优化现有一线和二线降脂药物的使用可使我们充分控制低密度脂蛋白胆固醇(LDL-C)水平,即使是对他汀类药物不耐受的患者以及必须达到更严格的 LDL-C 目标的心血管疾病高风险和极高风险患者也不例外。正在开发的药物将进一步提高我们管理总体血脂相关心血管疾病风险和针对其他血脂异常生物标志物的能力。
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引用次数: 0
Pharmacogenomics and pediatric drug development: science and political power. A narrative review 药物基因组学与儿科药物开发:科学与政治权力。叙述性综述
IF 3.2 3区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-09-13 DOI: 10.1080/14656566.2024.2401429
Earl B. Ettienne, Jane M. Grant-Kels, Pasquale Striano, Emilio Russo, David Neubauer, Klaus Rose
Pharmacogenomics (PGx) investigates how genomes control enzyme expression. Developmental pharmacology (DP) describes the temporal sequence of enzymes impacting absorption, distribution, metabolism,...
药物基因组学(PGx)研究基因组如何控制酶的表达。发育药理学(DP)描述了影响药物吸收、分布、代谢和代谢的酶的时间序列。
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引用次数: 0
Current approaches to the pharmacological management of metastatic breast cancer in older women. 目前对老年妇女转移性乳腺癌的药物治疗方法。
IF 2.5 3区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-09-01 Epub Date: 2024-09-16 DOI: 10.1080/14656566.2024.2402022
Carlos A Carmona-Gonzalez, Sudhir Kumar, Ines B Menjak

Introduction: A substantial majority of patients diagnosed with metastatic breast cancer consists of individuals 65-year-old or above. Emerging treatment approaches, which utilize genomics-guided therapy and innovative biomarkers, are currently in development. Given the numerous choices in the metastatic context, it is necessary to adopt a personalized approach to decision-making for these patients.

Areas covered: The authors provide a comprehensive analysis of the existing literature on the use of systemic anticancer treatments in older women, specifically those aged 65 and above, who have metastatic breast cancer, focusing on the reported effectiveness and adverse effects of these treatments in this population.

Expert opinion: The evidence to treat older patients with metastatic breast cancer primarily relies on subgroup analyses, whose interpretation should be approached with caution. In several clinical trials subgroup analysis, it has been observed that this population seem to have comparable benefits and toxicities to younger patients, but real-world data have showed older women exhibit worse rates of survival compared to younger women. Multiple factors are likely involved in this, but we postulate this is related to lower rates of guideline concordant, and factors such as comorbidity, lack of social supports, malnutrition, and geriatric factors like frailty and/or vulnerability. This underscores the importance of a broader assessment for patients with a geriatric perspective and involvement of multi-disciplinary team.

导言在确诊的转移性乳腺癌患者中,绝大多数是 65 岁或以上的老人。利用基因组学指导治疗和创新生物标志物的新兴治疗方法目前正在开发中。鉴于转移性乳腺癌患者的选择众多,有必要对这些患者采取个性化的决策方法:作者全面分析了现有文献中关于转移性乳腺癌老年妇女(特别是 65 岁及以上的老年妇女)使用全身抗癌治疗的情况,重点分析了这些治疗方法在这一人群中的有效性和不良反应:治疗老年转移性乳腺癌患者的证据主要依赖于亚组分析,对亚组分析的解释应谨慎。在几项临床试验的亚组分析中,观察到这一人群的获益和毒性似乎与年轻患者相当,但实际数据显示,老年妇女的生存率比年轻妇女低。这可能涉及多种因素,但我们推测这与较低的指南符合率以及合并症、缺乏社会支持、营养不良和老年病因素(如虚弱和/或脆弱)有关。这凸显了从老年医学角度对患者进行更广泛评估以及多学科团队参与的重要性。
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引用次数: 0
Revisiting PPAR agonists: novel perspectives in the treatment of primary biliary cholangitis. 重温 PPAR 激动剂:治疗原发性胆汁性胆管炎的新视角。
IF 2.5 3区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-09-01 Epub Date: 2024-10-04 DOI: 10.1080/14656566.2024.2406268
Yiran Chen, Kunyu Zheng, Gahu Da, Xu Wang, Yi Wei, Guochun Wang, Fengchun Zhang, Li Wang

Introduction: In primary biliary cholangitis (PBC), approximately 40% of the patients respond incompletely to first-line treatment with ursodeoxycholic acid (UDCA), resulting in a poorer prognosis. Although obeticholic acid (OCA) is approved as a second-line therapy, it is not well-tolerated by patients with significant itching or advanced cirrhosis. Peroxisome proliferator-activated receptor (PPAR) agonists, including fibrates traditionally known as antihyperlipidemic agents, have emerged as potent alternatives for treating PBC patients with an incomplete response to UDCA.

Areas covered: This article provides a detailed overview of the mechanisms of PPAR agonists and evaluates their efficacy and adverse events, focusing on findings from recent phase III clinical trials.

Expert opinion: PPAR agonists are significant alternatives in the treatment of PBC, showing the potential to enhance biochemical responses, reduce mortality, and alleviate pruritus. Long-term outcomes for PBC patients, particularly those with advanced disease, and longitudinal data on the antipruritic effects of PPAR agonists require further investigation. Combining PPAR agonists with other treatments and advancing personalized approaches may enhance therapeutic efficacy and patient outcomes. This study provides future perspectives on the roles of PPAR agonists in PBC management.

简介:在原发性胆汁性胆管炎(PBC)患者中,约 40% 的患者对熊去氧胆酸(UDCA)的一线治疗反应不完全,导致预后较差。尽管顺苯乙醇酸(OCA)已被批准作为二线疗法,但有明显瘙痒或肝硬化晚期的患者对其耐受性不佳。过氧化物酶体增殖激活受体(PPAR)激动剂,包括传统上被称为降血脂药的纤维酸盐,已成为治疗对 UDCA 反应不完全的 PBC 患者的有效替代药物:本文详细概述了 PPAR 激动剂的作用机制,并评估了它们的疗效和不良反应,重点关注近期 III 期临床试验的结果:PPAR激动剂是治疗PBC的重要替代药物,具有增强生化反应、降低死亡率和减轻瘙痒的潜力。PBC患者(尤其是晚期患者)的长期疗效以及PPAR激动剂止痒效果的纵向数据需要进一步研究。将 PPAR 激动剂与其他治疗方法相结合并推进个性化治疗方法可能会提高疗效和患者预后。本研究为 PPAR 激动剂在 PBC 治疗中的作用提供了未来展望。
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引用次数: 0
Navigating the pharmacotherapeutic management of comorbid inflammatory bowel disease and primary sclerosing cholangitis. 为合并炎症性肠病和原发性硬化性胆管炎的药物治疗导航。
IF 2.5 3区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-09-01 Epub Date: 2024-10-11 DOI: 10.1080/14656566.2024.2407022
Brigid Pinnuck, Kate D Lynch

Introduction: Primary sclerosing cholangitis (PSC) is the most specific hepatobiliary extraintestinal manifestation in inflammatory bowel disease (IBD). PSC ultimately has a poor prognosis, with disease progression resulting in liver cirrhosis and subsequent liver failure. While there is current data for the medical management of IBD, the optimal approach for concurrent PSC-IBD is unclear.

Areas covered: This review focuses on the current literature of pharmacotherapy in the PSC-IBD population including anti-tumor necrosis factor agents, vedolizumab, JAK inhibitors, IL-12/23 inhibitors, and thiopurines. Regarding PSC-IBD, it focuses on effectiveness of IBD therapies on liver biochemistry and IBD activity as well as the advent of clinically relevant liver outcomes and safety. The authors also address the need for further advances in research.

Expert opinion: The longer-term data for pharmacological management for IBD is well established. In the concomitant PSC-IBD population there is no drug to date that has effectively reduced disease related morbidity and mortality outcomes. There are limitations in the current, mostly retrospective data on IBD drugs in PSC-IBD with respect to samples sizes, heterogenous outcomes, and lack of a high-quality surrogate endpoint in PSC. However, current data for adalimumab offers encouraging results which require further exploration with larger prospective studies.

简介:原发性硬化性胆管炎(PSC原发性硬化性胆管炎(PSC)是炎症性肠病(IBD)中最特殊的肝胆肠外表现。原发性硬化性胆管炎的预后很差,病情发展会导致肝硬化和随后的肝功能衰竭。虽然目前有关于 IBD 药物治疗的数据,但并发 PSC-IBD 的最佳治疗方法尚不明确:本综述重点关注目前针对 PSC-IBD 患者的药物治疗文献,包括抗肿瘤坏死因子药物、维多珠单抗、JAK 抑制剂、IL-12/23 抑制剂和硫嘌呤类药物。关于PSC-IBD,该书重点讨论了IBD疗法对肝脏生化和IBD活动的影响,以及临床相关肝脏结果和安全性的出现。作者还谈到了进一步推进研究的必要性:IBD药物治疗的长期数据已经得到证实。在同时患有 PSC-IBD 的人群中,迄今还没有一种药物能有效降低与疾病相关的发病率和死亡率。目前,PSC-IBD 中有关 IBD 药物的数据大多是回顾性的,这些数据在样本大小、异质性结果以及缺乏高质量的 PSC 代用终点等方面存在局限性。不过,阿达木单抗的现有数据提供了令人鼓舞的结果,需要通过更大规模的前瞻性研究进行进一步探索。
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引用次数: 0
Pharmacological management of chronic lymphocytic leukemia: current and emerging therapies. 慢性淋巴细胞白血病的药物治疗:现有疗法和新兴疗法。
IF 2.5 3区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-09-01 Epub Date: 2024-09-08 DOI: 10.1080/14656566.2024.2398603
Ivan J Huang, Grace T Baek, Chloe Siu, Mazyar Shadman

Introduction: Chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), characterized by its monoclonal lymphoproliferative nature, is an indolent but incurable malignancy. The treatment landscape of CLL/SLL has drastically transformed in the last decade since the introduction of targeted therapy and immune-effector T-cell therapy. The paradigm shift from chemoimmunotherapy to targeted and cellular therapies was largely driven by improved efficacy and safety. With the success of targeted therapies, novel agents and combinations are rapidly emerging on the horizon.

Areas covered: In this review, we will summarize clinical evidence supporting current and emerging therapies with emphasis on investigational therapies and novel combinations of commercial agents. Clinical trials were identified via clinicaltrials.gov, and a PubMed literature search was last performed in June 2024.

Expert opinion: With the availability of more effective and better-tolerated treatments for CLL/SLL, the role of early intervention should be further investigated due to its potential to alter disease course, delay progression, and improve overall survival rates. With many highly effective agents and combinations expected to become commercially available, attention to safety profiles and careful selection of patients for each treatment will be critical, with consideration of comorbidities, logistical issues, and financial burden of treatment.

简介慢性淋巴细胞白血病(CLL)或小淋巴细胞淋巴瘤(SLL)以单克隆淋巴细胞增生为特征,是一种不活跃但无法治愈的恶性肿瘤。自靶向疗法和免疫效应 T 细胞疗法问世以来,CLL/SLL 的治疗格局在过去十年中发生了翻天覆地的变化。从化学免疫疗法到靶向疗法和细胞疗法的模式转变,主要是由于疗效和安全性的提高。随着靶向疗法的成功,新型药物和组合疗法正迅速出现在人们的视野中:在这篇综述中,我们将总结支持当前和新兴疗法的临床证据,重点是研究性疗法和商业药物的新型组合。临床试验通过 clinicaltrials.gov 确定,PubMed 文献检索最后一次进行是在 2024 年 6 月:专家意见:随着CLL/SLL的治疗方法越来越有效、耐受性越来越好,应进一步研究早期干预的作用,因为它有可能改变病程、延缓病情恶化并提高总生存率。随着许多高效药物和组合有望投入市场,对安全性的关注和每种治疗方法对患者的精心选择将至关重要,同时还要考虑合并症、后勤问题和治疗的经济负担。
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引用次数: 0
Which therapy in biliary tract cancer? Review of main concerns in diagnosis and choice of therapy in advanced setting, current standard, and new options. 胆道癌的治疗方法有哪些?回顾晚期诊断和治疗选择的主要问题、现行标准和新选择。
IF 2.5 3区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-09-01 Epub Date: 2024-09-30 DOI: 10.1080/14656566.2024.2406287
Ester Oneda, Serena Astore, Laura Gandolfi, Laura Melocchi, Alberto Zaniboni

The incidence of biliary tract cancer is increasing in developed countries and is generating renewed interest in the scientific community due to the evidence of a high percentage (approximately 40%) of potentially targetable molecular alterations. However, to date, patient selection and the development of therapeutic approaches remain challenging due to the need for accurate diagnosis, adequate sampling, a specialized team for molecular analysis, centralization of patients in high-volume centers capable of supporting the high cost of these methods, and the feasibility of clinical studies on diseases with aggressive onset and poor prognosis. In this article, we would like to provide a detailed overview of the necessary tools for diagnostic framing and the various therapeutic scenarios being investigated concerning the most frequently detected molecular alterations.

在发达国家,胆道癌的发病率正在上升,而且由于有证据表明存在高比例(约 40%)的潜在靶向分子改变,胆道癌再次引起了科学界的关注。然而,迄今为止,由于需要准确的诊断、充分的取样、专业的分子分析团队、将患者集中到能够支持这些方法高昂费用的高容量中心,以及对发病凶险、预后不良的疾病进行临床研究的可行性,患者的选择和治疗方法的开发仍具有挑战性。在本文中,我们将详细介绍诊断框架所需的必要工具,以及就最常检测到的分子改变进行研究的各种治疗方案。
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引用次数: 0
Talazoparib for the treatment of prostate cancer. 用于治疗前列腺癌的 Talazoparib。
IF 2.5 3区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-09-01 Epub Date: 2024-08-29 DOI: 10.1080/14656566.2024.2397002
Arshit Narang, Chadi Hage Chehade, Zeynep Irem Ozay, Blake Nordblad, Umang Swami, Neeraj Agarwal

Introduction: Around 25% of patients with advanced prostate cancer harbor alterations in the homologous recombination/DNA damage repair (HRR) pathway. Inhibiting poly (ADP-ribose) polymerase (PARP) in these patients leads to synthetic lethality, making PARP inhibitors (PARPi), including talazoparib, a promising treatment for metastatic castration-resistant prostate cancer (mCRPC) and potentially for metastatic hormone-sensitive prostate cancer (mHSPC).

Areas covered: This article examines the mechanism of action, chemical properties, pharmacokinetics, pharmacodynamics, and clinical safety and efficacy data of different PARPis, including talazoparib in prostate cancer. It reviews the TALAPRO-1 and TALAPRO-2 clinical trials and the ongoing TALAPRO-3 trial.

Expert opinion: Despite recent therapeutic advancements, mCRPC remains a lethal disease. Androgen receptor pathway inhibitors (ARPIs) are approved for patients with mCRPC and mHSPC, yet most patients first receive these agents in the castration-resistant setting. Real-world data indicate that around half of patients with mCRPC do not receive subsequent lines of therapy, underscoring the efficacy of upfront combination therapies. The combinations of ARPI plus PARPi are indicated for patients with mCRPC harboring HRR mutations, though identifying these patients is challenging due to limited genomic testing. Further research and improved access to genomic testing are essential to optimize treatment strategies.

前言:约25%的晚期前列腺癌患者存在同源重组/DNA损伤修复(HRR)途径的改变。在这些患者中抑制多聚(ADP-核糖)聚合酶(PARP)会导致合成致死,这使得包括talazoparib在内的PARP抑制剂(PARPi)成为治疗转移性阉割耐药前列腺癌(mCRPC)和潜在的转移性激素敏感性前列腺癌(mHSPC)的一种很有前景的疗法:本文探讨了不同PARPis(包括talazoparib)在前列腺癌中的作用机制、化学特性、药代动力学、药效学以及临床安全性和有效性数据。文章回顾了TALAPRO-1和TALAPRO-2临床试验以及正在进行的TALAPRO-3试验:尽管近期治疗取得了进展,但mCRPC仍是一种致命疾病。雄激素受体通路抑制剂(ARPIs)已被批准用于治疗mCRPC和mHSPC患者,但大多数患者首先是在阉割耐药的情况下接受这些药物治疗。真实世界的数据表明,约有一半的 mCRPC 患者没有接受后续治疗,这突出表明了前期联合疗法的疗效。ARPI 加 PARPi 组合适用于携带 HRR 突变的 mCRPC 患者,但由于基因组检测有限,确定这些患者具有挑战性。要优化治疗策略,就必须开展进一步的研究并提高基因组检测的可及性。
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引用次数: 0
Pharmacotherapeutic options for the treatment of hypertension in pregnancy. 治疗妊娠高血压的药物治疗方案。
IF 2.5 3区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-09-01 Epub Date: 2024-09-09 DOI: 10.1080/14656566.2024.2398602
Frances Conti-Ramsden, Antonio de Marvao, Lucy C Chappell

Introduction: Hypertensive disorders of pregnancy affect approximately one in 10 pregnancies and are associated with increased risk of adverse fetal, neonatal and maternal outcomes. There is strong evidence that effective treatment of hypertension (blood pressure ≥ 140/90 mmHg), and enhanced monitoring throughout pregnancy reduces these risks.

Areas covered: This article provides a contemporaneous review of treatment of hypertension in pregnancy with antihypertensive agents. We completed a systematic search and review of all meta-analyses and systematic reviews of studies comparing antihypertensives for treatment of pregnancy hypertension in the last five years. We provide a clinically focused summary of when to treat hypertension in pregnancy and which antihypertensive agents can be offered. Special scenarios reviewed include treatment-resistant hypertension and pre-pregnancy antihypertensive optimization.

Expert opinion: Several antihypertensives are considered safe and are known to be effective for treatment of hypertension in pregnancy. Given the current uncertainty as to which antihypertensive(s) are superior for treatment of hypertension in pregnancy, women should be counselled and offered a range of antihypertensive options in keeping with evidence on clinical effectiveness, local context and availability of antihypertensive(s), potential side effect profile, and women's preference. Further research is required to help guide clinical decision making, and move toward personalized treatment.

导言:妊娠期高血压疾病影响着大约十分之一的妊娠,并与胎儿、新生儿和孕产妇不良结局的风险增加有关。有确凿证据表明,有效治疗高血压(血压≥ 140/90 mmHg)并在整个孕期加强监测可降低这些风险:本文对使用降压药物治疗妊娠期高血压进行了同期综述。我们对过去五年中所有比较抗高血压药物治疗妊娠高血压的荟萃分析和系统综述研究进行了系统检索和综述。我们以临床为重点,总结了何时治疗妊娠高血压以及可提供哪些降压药物。专家意见:专家意见:有几种降压药被认为是安全的,并且对治疗妊娠期高血压有效。鉴于目前尚不确定哪种降压药更适合治疗妊娠期高血压,因此应根据临床疗效证据、当地情况和降压药的可用性、潜在的副作用以及妇女的偏好,为妇女提供一系列降压药选择。需要开展进一步的研究,以帮助指导临床决策,实现个性化治疗。
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引用次数: 0
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