Clinical Trials and Evaluation Unit, School of Clinical Sciences, University of Bristol, Bristol, UK.
School of Social and Community Medicine, University of Bristol, Bristol, UK.
Health Technol Assess. 2017 Aug;21(40):1-150. doi: 10.3310/hta21400.
Heart failure (HF) affects around 500,000 people in the UK. HF medications are frequently underprescribed and B-type natriuretic peptide (BNP)-guided therapy may help to optimise treatment.
To evaluate the clinical effectiveness and cost-effectiveness of BNP-guided therapy compared with symptom-guided therapy in HF patients.
Systematic review, cohort study and cost-effectiveness model.
A literature review and usual care in the NHS.
(a) HF patients in randomised controlled trials (RCTs) of BNP-guided therapy; and (b) patients having usual care for HF in the NHS.
: BNP-guided therapy or symptom-guided therapy in primary or secondary care. : BNP monitored (≥ 6 months' follow-up three or more BNP tests two or more tests per year), BNP tested (≥ 1 tests but not BNP monitored) or never tested. : BNP-guided therapy in specialist clinics.
Mortality, hospital admission (all cause and HF related) and adverse events; and quality-adjusted life-years (QALYs) for the cost-effectiveness model.
: Individual participant or aggregate data from eligible RCTs. : The Clinical Practice Research Datalink, Hospital Episode Statistics and National Heart Failure Audit (NHFA).
A systematic literature search (five databases, trial registries, grey literature and reference lists of publications) for published and unpublished RCTs.
Five RCTs contributed individual participant data (IPD) and eight RCTs contributed aggregate data (1536 participants were randomised to BNP-guided therapy and 1538 participants were randomised to symptom-guided therapy). For all-cause mortality, the hazard ratio (HR) for BNP-guided therapy was 0.87 [95% confidence interval (CI) 0.73 to 1.04]. Patients who were aged < 75 years or who had heart failure with a reduced ejection fraction (HFrEF) received the most benefit [interactions ( = 0.03): < 75 years vs. ≥ 75 years: HR 0.70 (95% CI 0.53 to 0.92) vs. 1.07 (95% CI 0.84 to 1.37); HFrEF vs. heart failure with a preserved ejection fraction (HFpEF): HR 0.83 (95% CI 0.68 to 1.01) vs. 1.33 (95% CI 0.83 to 2.11)]. In the cohort study, incident HF patients (1 April 2005-31 March 2013) were never tested ( = 13,632), BNP tested ( = 3392) or BNP monitored ( = 71). Median survival was 5 years; all-cause mortality was 141.5 out of 1000 person-years (95% CI 138.5 to 144.6 person-years). All-cause mortality and hospital admission rate were highest in the BNP-monitored group, and median survival among 130,433 NHFA patients (1 January 2007-1 March 2013) was 2.2 years. The admission rate was 1.1 patients per year (interquartile range 0.5-3.5 patients). In the cost-effectiveness model, in patients aged < 75 years with HFrEF or HFpEF, BNP-guided therapy improves median survival (7.98 vs. 6.46 years) with a small QALY gain (5.68 vs. 5.02) but higher lifetime costs (£64,777 vs. £58,139). BNP-guided therapy is cost-effective at a threshold of £20,000 per QALY.
The limitations of the trial were a lack of IPD for most RCTs and heterogeneous interventions; the inability to identify BNP monitoring confidently, to determine medication doses or to distinguish between HFrEF and HFpEF; the use of a simplified two-state Markov model; a focus on health service costs and a paucity of data on HFpEF patients aged < 75 years and HFrEF patients aged ≥ 75 years.
The efficacy of BNP-guided therapy in specialist HF clinics is uncertain. If efficacious, it would be cost-effective for patients aged < 75 years with HFrEF. The evidence reviewed may not apply in the UK because care is delivered differently.
Identify an optimal BNP-monitoring strategy and how to optimise HF management in accordance with guidelines; update the IPD meta-analysis to include the Guiding Evidence Based Therapy Using Biomarker Intensified Treatment (GUIDE-IT) RCT; collect routine long-term outcome data for completed and ongoing RCTs.
Current Controlled Trials ISRCTN37248047 and PROSPERO CRD42013005335.
This project was funded by the NIHR Health Technology Assessment programme and will be published in full in ; Vol. 21, No. 40. See the NIHR Journals Library website for further project information. The British Heart Foundation paid for Chris A Rogers' and Maria Pufulete's time contributing to the study. Syed Mohiuddin's time is supported by the NIHR Collaboration for Leadership in Applied Health Research and Care West at University Hospitals Bristol NHS Foundation Trust. Rachel Maishman contributed to the study when she was in receipt of a NIHR Methodology Research Fellowship.
心力衰竭（HF）影响英国约 50 万人。HF 药物的处方常常不足，B 型利钠肽（BNP）指导的治疗可能有助于优化治疗。
评估 BNP 指导治疗与 HF 患者的症状指导治疗相比的临床效果和成本效益。
系统评价、队列研究和成本效益模型。
文献综述和 NHS 中的常规护理。
（a）BNP 指导治疗随机对照试验（RCT）中的 HF 患者；（b）NHS 中接受 HF 常规护理的患者。
初级或二级保健中的 BNP 指导治疗或症状指导治疗；BNP 监测（≥6 个月的随访 至少 3 次 BNP 测试 每年至少 2 次测试）、BNP 测试（至少 1 次测试但未进行 BNP 监测）或从未测试过。在专科诊所进行 BNP 指导治疗。
死亡率、住院（所有原因和 HF 相关）和不良事件；以及成本效益模型的质量调整生命年（QALYs）。
：合格 RCT 的个体参与者或汇总数据。：临床实践研究数据库、住院事件统计数据和国家心力衰竭审计（NHFA）。
对已发表和未发表的 RCT 进行系统文献检索（五个数据库、试验登记处、灰色文献和出版物的参考文献列表）。
五项 RCT 提供了个体参与者数据（IPD），八项 RCT 提供了汇总数据（1536 名参与者被随机分配到 BNP 指导治疗组，1538 名参与者被随机分配到症状指导治疗组）。全因死亡率的 BNP 指导治疗的危险比（HR）为 0.87 [95%置信区间（CI）0.73 至 1.04]。年龄<75 岁或射血分数降低性心力衰竭（HFrEF）的患者获益最大[交互项（ = 0.03）：<75 岁与≥75 岁：HR 0.70（95%CI 0.53 至 0.92）与 1.07（95%CI 0.84 至 1.37）；射血分数保留性心力衰竭（HFpEF）与 HFrEF：HR 0.83（95%CI 0.68 至 1.01）与 1.33（95%CI 0.83 至 2.11）]。在队列研究中，新诊断的 HF 患者（2005 年 4 月 1 日至 2013 年 3 月 31 日）从未接受过测试（ = 13632）、BNP 测试（ = 3392）或 BNP 监测（ = 71）。中位生存期为 5 年；全因死亡率为每 1000 人年 141.5 人（95%CI 138.5 至 144.6 人年）。BNP 监测组的全因死亡率和住院率最高，在 130433 名 NHFA 患者（2007 年 1 月 1 日至 2013 年 3 月 1 日）中，中位生存期为 2.2 年。住院率为每年 1.1 例（四分位距 0.5-3.5 例）。在成本效益模型中，在年龄<75 岁且有 HFrEF 或 HFpEF 的患者中，BNP 指导治疗可提高中位生存期（7.98 年与 6.46 年），但 QALY 获益较小（5.68 年与 5.02 年），但终生成本更高（£64777 与 £58139）。在 20000 英镑/QALY 的阈值下，BNP 指导治疗具有成本效益。
试验的局限性是大多数 RCT 缺乏 IPD，干预措施不同；无法确定 BNP 监测的置信度，无法确定药物剂量，也无法区分 HFrEF 和 HFpEF；使用简化的两状态马尔可夫模型；关注卫生服务成本，缺乏年龄<75 岁的 HFpEF 患者和年龄≥75 岁的 HFrEF 患者的数据。
HF 专科诊所中 BNP 指导治疗的疗效不确定。如果有效，对于年龄<75 岁且有 HFrEF 的患者，它将具有成本效益。审查的证据可能不适用于英国，因为护理方式不同。
确定最佳的 BNP 监测策略和如何根据指南优化 HF 管理；更新包含 Guiding Evidence Based Therapy Using Biomarker Intensified Treatment（GUIDE-IT）RCT 的 IPD 荟萃分析；为已完成和正在进行的 RCT 收集长期结局数据。
当前对照试验 ISRCTN37248047 和 PROSPERO CRD42013005335。
本项目由英国国家卫生与保健研究所卫生技术评估计划资助，将在 ；第 21 卷，第 40 期。欲了解该研究的更多项目信息，请访问英国国家卫生与保健研究所期刊库网站。英国心脏基金会支付 Chris A Rogers 和 Maria Pufulete 参与研究的时间。Syed Mohiuddin 的时间由英国国家卫生与保健研究所应用健康研究与护理西部合作组织在布里斯托尔大学医院 NHS 基金会信托基金的支持。Rachel Maishman 在她接受英国国家卫生与保健研究所方法论研究奖学金期间为该研究做出了贡献。
