Comprehensive comparative effectiveness and safety of first-line antihypertensive drug classes: a systematic, multinational, large-scale analysis.,The Lancet

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Comprehensive comparative effectiveness and safety of first-line antihypertensive drug classes: a systematic, multinational, large-scale analysis.
The Lancet ( IF 98.4 ) Pub Date : 2019-10-24 , DOI: 10.1016/s0140-6736(19)32317-7
Marc A Suchard ₁ , Martijn J Schuemie ₂ , Harlan M Krumholz ₃ , Seng Chan You ₄ , RuiJun Chen ₅ , Nicole Pratt ₆ , Christian G Reich ₇ , Jon Duke ₈ , David Madigan ₉ , George Hripcsak ₁₀ , Patrick B Ryan ₁₁

Affiliation

Department of Biostatistics, Fielding School of Public Health, University of California, Los Angeles, CA, USA; Department of Biomathematics, David Geffen School of Medicine at UCLA, University of California, Los Angeles, CA, USA.
Department of Biostatistics, Fielding School of Public Health, University of California, Los Angeles, CA, USA; Epidemiology Analytics, Janssen Research & Development, Titusville, NJ, USA.
Department of Medicine, Yale University School of Medicine, New Haven, CA, USA.
Department of Biomedical Informatics, Ajou University School of Medicine, Suwon, South Korea.
Department of Medicine, Weill Cornell Medical College, New York, NY, USA; Department of Biomedical Informatics, Columbia University Medical Center, New York, NY, USA.
Quality Use of Medicines and Pharmacy Research Centre, Sansom Institute, University of South Australia, Adelaide, SA, Australia.
Real World Analytics Solutions, IQVIA, Durham, NC, USA.
Georgia Tech Research Institute, Georgia Tech College of Computing, Atlanta, GA, USA.
Department of Statistics, Columbia University, New York, NY, USA.
Department of Biomedical Informatics, Columbia University Medical Center, New York, NY, USA; Medical Informatics Services, New York-Presbyterian Hospital, New York, NY, USA.
Epidemiology Analytics, Janssen Research & Development, Titusville, NJ, USA; Department of Biomedical Informatics, Columbia University Medical Center, New York, NY, USA.

BACKGROUND Uncertainty remains about the optimal monotherapy for hypertension, with current guidelines recommending any primary agent among the first-line drug classes thiazide or thiazide-like diuretics, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, dihydropyridine calcium channel blockers, and non-dihydropyridine calcium channel blockers, in the absence of comorbid indications. Randomised trials have not further refined this choice. METHODS We developed a comprehensive framework for real-world evidence that enables comparative effectiveness and safety evaluation across many drugs and outcomes from observational data encompassing millions of patients, while minimising inherent bias. Using this framework, we did a systematic, large-scale study under a new-user cohort design to estimate the relative risks of three primary (acute myocardial infarction, hospitalisation for heart failure, and stroke) and six secondary effectiveness and 46 safety outcomes comparing all first-line classes across a global network of six administrative claims and three electronic health record databases. The framework addressed residual confounding, publication bias, and p-hacking using large-scale propensity adjustment, a large set of control outcomes, and full disclosure of hypotheses tested. FINDINGS Using 4·9 million patients, we generated 22 000 calibrated, propensity-score-adjusted hazard ratios (HRs) comparing all classes and outcomes across databases. Most estimates revealed no effectiveness differences between classes; however, thiazide or thiazide-like diuretics showed better primary effectiveness than angiotensin-converting enzyme inhibitors: acute myocardial infarction (HR 0·84, 95% CI 0·75-0·95), hospitalisation for heart failure (0·83, 0·74-0·95), and stroke (0·83, 0·74-0·95) risk while on initial treatment. Safety profiles also favoured thiazide or thiazide-like diuretics over angiotensin-converting enzyme inhibitors. The non-dihydropyridine calcium channel blockers were significantly inferior to the other four classes. INTERPRETATION This comprehensive framework introduces a new way of doing observational health-care science at scale. The approach supports equivalence between drug classes for initiating monotherapy for hypertension-in keeping with current guidelines, with the exception of thiazide or thiazide-like diuretics superiority to angiotensin-converting enzyme inhibitors and the inferiority of non-dihydropyridine calcium channel blockers. FUNDING US National Science Foundation, US National Institutes of Health, Janssen Research & Development, IQVIA, South Korean Ministry of Health & Welfare, Australian National Health and Medical Research Council.

中文翻译：

一线抗高血压药物类别的综合有效性和安全性比较：系统性、跨国性、大规模分析。

背景对于高血压的最佳单一疗法仍然存在不确定性，目前的指南推荐一线药物类噻嗪类或噻嗪类利尿剂、血管紧张素转换酶抑制剂、血管紧张素受体阻滞剂、二氢吡啶钙通道阻滞剂和非二氢吡啶中的任何主要药物钙通道阻滞剂，在没有合并症的情况下。随机试验尚未进一步完善这一选择。方法我们为现实世界的证据开发了一个全面的框架，可以对多种药物的有效性和安全性进行比较以及来自数百万患者的观察数据的结果，同时最大限度地减少固有偏差。使用这个框架，我们在新用户队列设计下进行了一项系统的大规模研究，以评估三种主要（急性心肌梗塞、心力衰竭住院和中风）和六种次要有效性和 46 种安全性结局的相对风险，比较涵盖六个行政索赔和三个电子健康记录数据库的全球网络中的所有一线课程。该框架使用大规模倾向调整、大量控制结果和全面披露所测试的假设来解决残余混杂、发表偏差和 p-hacking。结果我们使用 4·900 万患者，生成了 22 000 个经过校准、倾向评分调整的风险比 (HR)，比较了数据库中的所有类别和结果。大多数估计显示不同类别之间的有效性没有差异；然而，噻嗪类或噻嗪类利尿剂比血管紧张素转换酶抑制剂表现出更好的主要疗效：急性心肌梗死（HR 0·84，95％CI 0·75-0·95），心力衰竭住院（0·83，0 ·74-0·95) 和中风 (0·83, 0·74-0·95) 风险在初始治疗期间。与血管紧张素转换酶抑制剂相比，安全性也更倾向于噻嗪类利尿剂或噻嗪类利尿剂。非二氢吡啶类钙通道阻滞剂明显劣于其他四类药物。解释这一综合框架引入了一种大规模开展观察性医疗保健科学的新方法。该方法支持用于高血压单一疗法的药物类别之间的等效性，符合当前指南，但噻嗪类或噻嗪类利尿剂优于血管紧张素转换酶抑制剂以及非二氢吡啶类钙通道阻滞剂较差。资助美国国家科学基金会、美国国立卫生研究院、杨森研发中心、IQVIA、韩国卫生和福利部、澳大利亚国家健康和医学研究委员会。

更新日期：2019-11-15

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