National Heart Centre Singapore, Singapore, Singapore; School of Population and Global Health, University of Western Australia, WA, Australia.
National Heart Centre Singapore, Singapore, Singapore; Department of Cardiology, University Medical Center Groningen, Groningen, Netherlands.
Lancet Glob Health. 2018 Sep;6(9):e1008-e1018. doi: 10.1016/S2214-109X(18)30306-1.
Angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs), β blockers, and mineralocorticoid receptor antagonists (MRAs) are of proven benefit and are recommended by guidelines for management of patients with heart failure and reduced ejection fraction (HFrEF). We aimed to examine the first prospective multinational data from Asia on prescribing patterns of guideline-directed medical therapies and analyse its effect on outcomes.
In the prospective multinational ASIAN-HF registry (with enrolment from 46 centres in 11 countries in Asia), we enrolled patients aged 18 years or older, with symptomatic heart failure (stage C, with at least one episode of decompensated heart failure in the past 6 months that resulted in admission to hospital or was treated in an outpatient clinic) and left ventricular systolic dysfunction (ejection fraction ≤40% on baseline echocardiography, consistent with 2016 European Society of Cardiology guidelines). We excluded patients with heart failure caused by severe valvular heart disease, life-threatening comorbidity with a life expectancy of less than 1 year, who were unable or unwilling to give consent, or who had concurrent participation in a clinical trial. Patients were followed up for 3 years for the outcomes of death and cause-specific admittance to hospital. Primary outcomes were uptake of guideline-directed medical therapies (as proportions) by therapeutic class, achieved doses as proportions of guideline-recommended doses, and their association with 1-year composite outcome of all-cause death or admittance to hospital because of heart failure. This study is registered with ClinicalTrials.gov, number NCT01633398.
Between Oct 1, 2012, and Dec 31, 2015, we enrolled 5276 patients with HFrEF (mean age 59·6 years [SD 13·2], 77% men, body-mass index 24·9 kg/m [5·1], 33% New York Heart Association class III or IV). Follow-up data were available for 4544 (90%) of 5061 eligible patients taking medication for heart failure, with median follow-up of 417 days (IQR 214-735). ACE inhibitors or ARBs were prescribed to 3868 (77%) of 5005 patients, β blockers to 3975 (79%) of 5061, and MRAs to 2998 (58%) of 5205, with substantial regional variation. Guideline-recommended dose was achieved in only 17% of cases for ACE inhibitors or ARB, 13% for β blockers, and 29% for MRAs. Country (all three drug classes), increasing body-mass index (ACE inhibitors or ARBs and MRAs), and in-patient recruitment (ACE inhibitors or ARBs and β blockers) were associated with attainment of guideline-recommended dose (all p<0·05). When adjusted for indication bias, increasing drug doses, from low dose (1-<25% of guideline-recommended dose) upwards were associated with lower hazards of a 1-year composite outcome for ACE inhibitors or ARBs and β blockers compared with non-users. The lowest adjusted hazards were in the group that attained guideline-recommended doses above 50% (hazard ratio [HR] 0·54, 95% CI 0·50-0·58 for ACE inhibitors or ARBs [50-99·9%]; HR 0·47, 0·46-0·50 for β blockers, and HR 0·77, 0·72-0·81 for MRAs [≥100%]).
Guideline-directed medical therapies at recommended doses are underutilised in patients with HFrEF. Improved uptake and uptitration of guideline-directed medical therapies are needed for better patient outcomes.
National Medical Research Council (Singapore), A*STAR Biomedical Research Council ATTRaCT program, Boston Scientific Investigator Sponsored Research program, and Bayer.
血管紧张素转换酶（ACE）抑制剂或血管紧张素 II 受体阻滞剂（ARB）、β受体阻滞剂和盐皮质激素受体拮抗剂（MRA）已被证明具有益处，并且被心力衰竭和射血分数降低（HFrEF）患者管理指南推荐。我们旨在研究亚洲首个来自亚洲的前瞻性多国数据，了解指南指导的药物治疗方案的处方模式，并分析其对结局的影响。
在这项前瞻性多国亚洲心力衰竭注册研究（在亚洲 11 个国家的 46 个中心进行招募）中，我们招募了年龄在 18 岁及以上、有症状性心力衰竭（C 期，过去 6 个月至少有一次失代偿性心力衰竭发作，导致住院或在门诊治疗）和左心室收缩功能障碍（基线超声心动图射血分数≤40%，符合 2016 年欧洲心脏病学会指南）的患者。我们排除了因严重瓣膜性心脏病、有预期寿命不到 1 年的危及生命的合并症、无法或不愿同意、或同时参加临床试验而导致的心力衰竭患者。患者在 3 年内接受死亡和因心力衰竭特定原因住院的结局随访。主要结局是按治疗类别报告指南指导的药物治疗的使用率（作为比例）、达到指南推荐剂量的比例以及它们与所有原因死亡或因心力衰竭住院的 1 年复合结局的相关性。本研究在 ClinicalTrials.gov 上注册，编号为 NCT01633398。
在 2012 年 10 月 1 日至 2015 年 12 月 31 日期间，我们招募了 5276 例 HFrEF 患者（平均年龄 59.6 岁[标准差 13.2]，77%为男性，体重指数 24.9kg/m[5.1]，33%为纽约心脏协会心功能分级 III 或 IV 级）。我们获得了 5061 名有心力衰竭用药记录的合格患者中 4544 名（90%）的随访数据，中位随访时间为 417 天（IQR 214-735）。5005 例患者中有 3868 例（77%）使用 ACE 抑制剂或 ARB，5061 例中有 3975 例（79%）使用β受体阻滞剂，5205 例中有 2998 例（58%）使用 MRA，存在显著的区域差异。ACE 抑制剂或 ARB 的推荐剂量仅在 17%的病例中达到，β受体阻滞剂为 13%，MRA 为 29%。国家（所有三种药物类别）、体重指数增加（ACE 抑制剂或 ARB 和 MRA）和住院招募（ACE 抑制剂或 ARB 和β受体阻滞剂）与达到指南推荐剂量相关（所有 p<0.05）。在调整适应证偏倚后，与未使用者相比，从低剂量（ACE 抑制剂或 ARB 和 MRA 的 1-<25%推荐剂量）增加药物剂量与 ACE 抑制剂或 ARB 和β受体阻滞剂的 1 年复合结局风险降低相关。最低的调整风险是达到指南推荐剂量 50%以上的组（ACE 抑制剂或 ARB 的危险比[HR]为 0.54，95%CI 为 0.50-0.58[50-99.9%]；β受体阻滞剂为 0.47，0.46-0.50；MRA 为 0.77，0.72-0.81[≥100%]）。
在射血分数降低的心力衰竭患者中，指南指导的药物治疗方案在推荐剂量下的使用率较低。需要提高和增加指南指导的药物治疗方案的使用率，以改善患者的结局。
新加坡国家医学研究委员会、A*STAR 生物医学研究理事会 ATTRaCT 计划、波士顿科学公司研究者发起的研究计划和拜耳公司。
