Assessment of Limitations to Optimization of Guideline-Directed Medical Therapy in Heart Failure From the GUIDE-IT Trial A Secondary Analysis of a Randomized Clinical Trial
Assessment of Limitations to Optimization of Guideline-Directed Medical Therapy in Heart Failure From the GUIDE-IT Trial A Secondary Analysis of a Randomized Clinical Trial
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DOI：
10.1001/jamacardio.2020.0640
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发表时间：
2020-07-01
期刊：
影响因子：
24
通讯作者：
O'Connor, Christopher M.
中科院分区：
文献类型：
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作者：
Fiuzat, Mona;Ezekowitz, Justin;O'Connor, Christopher M.
问：在使用生物标志物强化治疗的指导性循证治疗研究中，使用了什么心力衰竭药物，没有进行滴定治疗的原因是什么？在一项随机临床试验的二次分析中，包括838名心力衰竭和射血分数降低的患者，在5218次合格的访问中，有2847人(54.6%)进行了药物调整。没有调整的最常见原因是“临床稳定”和“已经达到最大耐受性治疗”，在6个月时，只有130名患者(15.5%)获得了最佳指南指导的药物治疗(=β-受体阻滞剂、血管紧张素转换酶抑制剂或血管紧张素受体阻滞剂或任何剂量的盐皮质激素拮抗剂目标剂量的50%)。这些结果表明，在心力衰竭患者中存在滴定药物以获得最大益处的机会。这项随机临床试验的二次分析检查了使用Biomarker强化治疗的指导性循证治疗中的药物治疗和干预对心力衰竭患者无效的原因。尽管有证据表明指南指导的药物治疗(GDMT)改善了心力衰竭(HF)和射血分数降低的患者的预后，但许多患者仍未得到充分治疗。使用生物标记物强化治疗的指导性循证治疗(GUIDE-IT)试验测试了使用N末端脑利钠肽原(NT-proBNP)的目标浓度来指导GDMT优化的策略是否可以改善结果。目的了解GUIDE-IT对心力衰竭的药物治疗情况及干预措施未改善内科治疗效果的可能原因。设计、设置和参与者GUIDE-IT是一项在美国和加拿大的45个地点进行的随机临床试验，于2013年1月16日至2016年9月20日进行。共894例心衰患者，862例(96.4%)患者的射血分数降低(<1000pg/mL)。大多数调整发生在前6个月内，主要是前6周内。没有调整的最常见的原因是“临床稳定”和“已经接受了最大限度的治疗”。只有130名患者(15.5%)在6个月时达到最佳GDMT(=β-受体阻滞剂或血管紧张素转换酶抑制剂/血管紧张素受体阻滞剂或任何剂量的盐皮质激素拮抗剂目标剂量的50%)，较基线(891例中的79例[8.9%])有所增加，但治疗组没有差异。较高剂量的β-受体阻滞剂与心力衰竭住院和心血管死亡(危险比[HR]，0.98；95%CI，0.97-1.00；P=.008)和全原因死亡(HR，0.97；95%CI，0.95-0.99；P=.01)的综合结果风险降低相关。较高剂量的血管紧张素转换酶抑制剂(HR，0.84；95%CI，0.75-0.93；P<；.001)和血管紧张素受体阻滞剂(HR，0.84；95%CI，0.71-0.99；P=0.04)与降低全因死亡风险相关。增加盐皮质激素拮抗剂的剂量似乎与改善结果无关。结论和相关性尽管采用了方案驱动的方法，GUIDE-IT组的许多患者没有接受药物调整，也没有达到最佳的GDMT，包括那些已知NT-proBNP浓度升高的患者。这些结果表明，存在机会滴定药物，以最大限度地受益于心衰。GUIDE-IT可能由于临床实践中的治疗惰性而未能获得治疗益处，或者当前的GDMT目标可能不现实。
Question What heart failure medication was used and what were reasons for not titrating therapy in the Guiding Evidence-Based Therapy Using Biomarker Intensified Treatment study? Findings In this secondary analysis of a randomized clinical trial including 838 patients with heart failure and reduced ejection fraction, medication adjustments were made during 2847 of 5218 qualified visits (54.6%). The most common reasons for not adjusting were "clinically stable" and "already at maximally tolerated therapy," and at 6 months, only 130 patients (15.5%) achieved optimal guideline-directed medical therapy (>= 50% of the target dose of beta-blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, or any dose of mineralocorticoid antagonists). Meaning These results suggest that opportunities exist to titrate medications for maximal benefit in patients with heart failure.This secondary analysis of a randomized clinical trial examines medical therapy and reasons why an intervention did not work for patients with heart failure in the Guiding Evidence-Based Therapy Using Biomarker Intensified Treatment.Importance Despite evidence that guideline-directed medical therapy (GDMT) improves outcomes in patients with heart failure (HF) and reduced ejection fraction, many patients are undertreated. The Guiding Evidence-Based Therapy Using Biomarker Intensified Treatment (GUIDE-IT) trial tested whether a strategy of using target concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP) to guide optimization of GDMT could improve outcomes. Objective To examine medical therapy for HF in GUIDE-IT and potential reasons why the intervention did not produce improvements in medical therapy. Design, Setting, and Participants GUIDE-IT, a randomized clinical trial performed at 45 sites in the United States and Canada, was conducted from January 16, 2013, to September 20, 2016. A total of 894 patients with HF and reduced ejection fraction (= 1000 pg/mL) in 862 patients (96.4%). Most adjustments occurred within the first 6 months, primarily within the first 6 weeks. The most common reasons for not adjusting were "clinically stable" and "already at maximally tolerated therapy." Only 130 patients (15.5%) achieved optimal GDMT (>= 50% of the target dose of beta-blockers or angiotensin-converting enzyme inhibitors/angiotensin receptor blockers or any dose of mineralocorticoid antagonists) at 6 months, an increase from the baseline (79 of 891 [8.9%]) but not different by treatment arm. Higher doses of beta-blockers were associated with reduced risk of the composite outcome of HF hospitalization and cardiovascular death (hazard ratio [HR], 0.98; 95% CI, 0.97-1.00; P = .008) and of all-cause death (HR, 0.97; 95% CI, 0.95-0.99; P = .01). Higher doses of angiotensin-converting enzyme inhibitors (HR, 0.84; 95% CI, 0.75-0.93; P < .001) and angiotensin receptor blockers (HR, 0.84; 95% CI, 0.71-0.99; P = .04) were associated with reduced risk of all-cause death. Increasing doses of mineralocorticoid antagonists did not appear to be associated with improved outcomes. Conclusions and Relevance Despite a protocol-driven approach, many patients in GUIDE-IT did not receive medication adjustments and did not achieve optimal GDMT, including those with known elevated NT-proBNP concentrations. These results suggest that opportunities exist to titrate medications for maximal benefit in HF. GUIDE-IT may have failed to achieve treatment benefit because of therapeutic inertia in clinical practice, or current GDMT goals may be unrealistic.