Clinical Pharmacology and Pharmacy, Department of Public Health, University of Southern Denmark, Odense, Denmark; Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Odense, Denmark; Department of Clinical Pharmacology, Aarhus University Hospital, Aarhus, Denmark.
Center for Evidence-Based Medicine, Odense University Hospital, Odense, Denmark; Department of Clinical Research, University of Southern Denmark, Odense, Denmark; Odense Explorative Patient Data Network (OPEN), Odense University Hospital, Odense, Denmark.
Am J Med. 2020 Jun;133(6):e280-e289. doi: 10.1016/j.amjmed.2019.11.015. Epub 2020 Mar 13.
Outcome postponement has been proposed as an effect measure for preventive drug treatment. It describes the average delay of the investigated unwanted clinical event, achieved by taking medication. The objective was to estimate postponement of death for the following heart failure medications compared to placebo: beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), ARB added to ACE inhibitors, aldosterone antagonists, ivabradine, and renin antagonists.
We searched Medline and Embase from inception of databases until October 2017. Eligibility criteria were randomized placebo-controlled heart failure trials, including at least 1000 participants, with survival as a prespecified outcome and a minimum trial duration of 1 year. We calculated the outcome postponement by modeling the area between survival curves. This area was modeled on the basis of the hazard ratio or relative risk, the rate of mortality in the placebo group, and the trial duration. All results were standardized to a 3-year trial duration to ensure comparability between treatments.
We identified 14 eligible trials, with a total of 52,014 patients. The results in terms of postponement of all-cause mortality was: beta-blockers 43.7 days (95% confidence interval [95% CI], 20.8-66.5), ACE inhibitors 41.0 days (95% CI, 18.8-63.3), and aldosterone-antagonists 41.3 days (95% CI, 14.3,68.4).
The modeled outcome postponement estimates reiterate beta-blockers, ACE inhibitors, and aldosterone antagonists as the mainstay of heart failure treatment. Furthermore, ivabradine or ARBs added to ACE inhibitors results in no statistically significant gain in survival.
结果推迟被提议作为预防药物治疗的一种效应测量方法。它描述了通过服用药物实现的所研究的不良临床事件的平均延迟。目的是估计以下心力衰竭药物与安慰剂相比，死亡推迟的情况：β受体阻滞剂、血管紧张素转换酶（ACE）抑制剂、血管紧张素 II 受体阻滞剂（ARB）、ACE 抑制剂加用 ARB、醛固酮拮抗剂、伊伐布雷定和肾素拮抗剂。
我们检索了从数据库建立到 2017 年 10 月的 Medline 和 Embase。纳入标准为随机安慰剂对照心力衰竭试验，包括至少 1000 名参与者，生存为预设结局，试验持续时间至少 1 年。我们通过模拟生存曲线之间的区域来计算结果推迟。该区域是基于危险比或相对风险、安慰剂组的死亡率和试验持续时间来建模的。所有结果均标准化为 3 年试验持续时间，以确保治疗之间的可比性。
我们确定了 14 项符合条件的试验，共 52014 名患者。所有原因死亡率推迟的结果是：β受体阻滞剂 43.7 天（95%置信区间[95%CI]，20.8-66.5）、ACE 抑制剂 41.0 天（95%CI，18.8-63.3）和醛固酮拮抗剂 41.3 天（95%CI，14.3，68.4）。
模型化的结果推迟估计重申了β受体阻滞剂、ACE 抑制剂和醛固酮拮抗剂是心力衰竭治疗的主要方法。此外，伊伐布雷定或 ACE 抑制剂加用 ARB 并没有在生存方面带来统计学上的显著获益。
