From the Unit of Cardiology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; Heart and Vascular Theme, Karolinska University Hospital, Stockholm, Sweden.
From the Unit of Cardiology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
J Card Fail. 2022 Jul;28(7):1050-1062. doi: 10.1016/j.cardfail.2022.04.011. Epub 2022 May 10.
We investigated eligibility for dapagliflozin and empagliflozin in a real-world heart failure (HF) cohort based on selection criteria of DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure), DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients with Preserved Ejection Fraction Heart Failure), and EMPEROR (Empagliflozin Outcome Trial in Patients with Chronic Heart Failure with Reduced Ejection Fraction and Empagliflozin Outcome Trial in Patients with Chronic Heart Failure with APreserved Ejection Fraction) trials.
Selection criteria were applied to the Swedish HF registry outpatient population according to 3 scenarios: (i) a "trial scenario" applying all selection criteria; (ii) a "pragmatic scenario" applying the most clinically relevant criteria; and (iii) a "label scenario" following the regulatory agencies labels. Of the 49,317 patients, 55% had an ejection fraction of less than 40% and were assessed for eligibility based on DAPA-HF and EMPEROR-Reduced, 45% had ejection fraction of 40% or greater and were assessed based on EMPEROR-Preserved and DELIVER. Eligibility using trial, pragmatic, and label scenarios was 35%, 61%, and 80% for DAPA-HF; 31%, 55%, and 81% for EMPEROR-Reduced; 30%, 61%, and 74% for DELIVER; and 32%, 59%, and 75% for EMPEROR-Preserved, respectively. The main selection criteria limiting eligibility were HF duration and N-terminal pro-B type natriuretic peptide levels. Eligible patients had more severe HF, more comorbidities, higher use of HF treatments and higher mortality and morbidity.Clinical Highlights: Large clinical trials for the approval of new drugs in heart failure often apply numerous selection criteria, limiting the generalizability of trial findings to real-world populations. We assessed eligibility for dapagliflozin and empagliflozin according to trial criteria, the more practical criteria usually applied in daily practice for treatment selection, and the criteria mandated by regulatory agencies, in a real-word heart failure population. Our results from the Swedish Heart Failure Registry show that a great number of patients with heart failure might be candidates for these therapies, which have been shown to significantly decrease morbidity and mortality; therefore, their use should be implemented in clinical practice.
When strictly applying selection criteria used in clinical trials, only one-third of a real-world heart failure population is eligible for treatment with empagliflozin and dapagliflozin. Adopting approaches that consider the most meaningful criteria, that is, those most clinically relevant or those mandated by regulatory agencies, significantly broadened eligibility. These results might contribute to future trial design taking into consideration the characteristics of real-world populations, feasibility, and potential cost benefits.
In a real-world HF setting, eligibility for sodium glucose co-transporter-2 inhibitors was similar whether selection criteria from DAPA-HF or EMPEROR-Reduced were applied in HFrEF, or EMPEROR-Preserved or DELIVER in HFpEF. These data might help stakeholders assessing the consequences of future trial eligibility.
我们根据 DAPA-HF（达格列净预防心力衰竭不良结局）、DELIVER（达格列净对射血分数保留心力衰竭患者的疗效评估）和 EMPEROR（恩格列净在射血分数降低的慢性心力衰竭患者中的疗效试验和恩格列净在射血分数保留的慢性心力衰竭患者中的疗效试验）试验的入选标准，在真实世界心力衰竭（HF）队列中调查了达格列净和恩格列净的入选情况。
根据 3 种情况，将入选标准应用于瑞典 HF 登记处的门诊人群：（i）“试验方案”，适用于所有入选标准；（ii）“实用方案”，适用于最具临床相关性的标准；（iii）“标签方案”，遵循监管机构的标签。在 49317 名患者中，55%的患者射血分数<40%，根据 DAPA-HF 和 EMPEROR-Reduced 评估其入选资格，45%的患者射血分数为 40%或更高，根据 EMPEROR-Preserved 和 DELIVER 进行评估。根据试验、实用和标签方案，DAPA-HF 的入选率分别为 35%、61%和 80%；EMPEROR-Reduced 的入选率分别为 31%、55%和 81%；DELIVER 的入选率分别为 30%、61%和 74%；EMPEROR-Preserved 的入选率分别为 32%、59%和 75%。限制入选资格的主要入选标准是心力衰竭持续时间和 N 端脑钠肽前体水平。入选患者的心力衰竭更严重，合并症更多，心力衰竭治疗使用率更高，死亡率和发病率更高。
新药批准的大型临床试验通常应用大量的入选标准，将试验结果的普遍性限制在真实世界人群中。我们根据试验标准、日常治疗选择中通常应用的更实用的标准以及监管机构规定的标准，对达格列净和恩格列净在真实世界心力衰竭人群中的入选情况进行了评估。我们从瑞典心力衰竭登记处获得的结果表明，大量心力衰竭患者可能是这些疗法的候选者，这些疗法已被证明能显著降低发病率和死亡率；因此，应在临床实践中应用这些疗法。
当严格应用临床试验中的入选标准时，只有三分之一的真实世界心力衰竭患者有资格接受恩格列净和达格列净治疗。采用考虑最有意义的标准的方法，即最具临床相关性的标准或监管机构规定的标准，显著扩大了入选范围。这些结果可能有助于未来的临床试验设计考虑真实世界人群的特征、可行性和潜在的成本效益。
在真实世界的 HF 环境中，在 HFrEF 中应用 DAPA-HF 或 EMPEROR-Reduced 的入选标准，或在 HFpEF 中应用 EMPEROR-Preserved 或 DELIVER 的入选标准，对钠-葡萄糖共转运蛋白 2 抑制剂的入选情况相似。这些数据可能有助于利益相关者评估未来试验入选的结果。
