美国加利福尼亚大学Marc A Suchard课题组近日取得一项新成果。经过不懈努力，他们综合比较了一线抗高血压药物的疗效和安全性。相关论文10月24日在线发表在《柳叶刀》杂志上。

关于高血压的最佳单一疗法仍未明确。现有指南推荐在没有共病指征的情况下，可使用一线药物中的任何主要药物，如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、二氢吡啶类钙通道阻滞剂和非二氢吡啶类钙通道阻断剂来进行治疗，但仍缺乏随机试验的验证与完善。

研究组开发了一个综合框架，以便更客观地评价药物的有效性和安全性。利用这个框架，研究组在一个新用户队列设计中进行了这项系统的大规模研究，评估了一线抗高血压药物治疗后三种主要结局的风险，即急性心肌梗死、心力衰竭住院和中风。

研究组共分析了490万名患者的临床数据，对所有类别与结局进行统计比较，发现不同类别之间并没有很大的疗效差异。但噻嗪类或噻嗪类利尿剂治疗后，三种主要结局的风险显著低于血管紧张素转换酶抑制剂，其中急性心肌梗死的风险比为0.84，心力衰竭住院为0.83，中风为0.83。与血管紧张素转换酶抑制剂相比，噻嗪类利尿剂的安全性更高。而非二氢吡啶类钙通道阻滞剂的疗效明显劣于其他四类。

该综合框架为大规模开展观察性保健科学提供了一种新的途径。研究结果支持现行指南，即不同类别药物单一治疗高血压的疗效大致相当，但噻嗪类或噻嗪类利尿剂优于血管紧张素转换酶抑制剂，而非二氢吡啶类钙通道阻滞剂的疗效最差。

附：英文原文

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

Author: Marc A Suchard, Martijn J Schuemie, Harlan M Krumholz, Seng Chan You, RuiJun Chen, Nicole Pratt, Christian G Reich, Jon Duke, David Madigan, George Hripcsak, Patrick B Ryan

Issue&Volume: 2019/10/24

Abstract: 

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.

DOI: 10.1016/S0140-6736(19)32317-7

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)32317-7/fulltext