背景:在COAPT(MitraClip经皮治疗伴功能性二尖瓣反流的心力衰竭患者的心血管结果评估)试验中,中央心力衰竭委员会(HF)专家优化了指南指导的药物治疗(GDMT),并记录了患者入组前的用药和目标剂量不耐受.
目的:作者试图评估这些比率,原因,以及COAPT试验中GDMT不耐受的预测因子。
方法:基线使用,剂量,和血管紧张素转换酶抑制剂(ACEI)血管紧张素II受体阻滞剂(ARB)的不耐受,血管紧张素受体脑啡肽抑制剂(ARNIs),β受体阻滞剂,和盐皮质激素受体拮抗剂(MRA)分析左心室射血分数(LVEF)≤40%的患者,在纳入之前,需要由独立HF专家评估的这些药物的最大耐受剂量.
结果:共有464例患者LVEF≤40%,且用药信息完整。在基线,38.8%,39.4%,19.8%的患者耐受3、2和1个GDMT类别,分别(任何剂量);只有1.9%不能耐受任何GDMT。β受体阻滞剂是最常见的耐受GDMT(93.1%),其次是ACEI/ARB/ARNI(68.5%),然后是MRA(55.0%)。不公差因GDMT类别而异,但低血压和肾功能障碍是最常见的。由于不耐受限制滴定,β受体阻滞剂(32.3%)和ACEI/ARBs/ARNI(10.2%)的目标剂量不常见。只有2.2%的患者耐受所有3个GDMT类别的目标剂量。
结论:在患有HF的当代试验人群中,重度二尖瓣反流,和系统的HF专家指导的GDMT优化,大多数患者存在医学不耐受,禁止1个或更多GDMT类别并达到目标剂量.注意到的特定不耐受性和用于GDMT优化的方法为在未来的临床试验中实施GDMT优化提供了重要的经验教训。(功能性二尖瓣反流心力衰竭患者的MitraClip经皮治疗的心血管结果评估[COAPT试验][COAPT];NCT01626079)。
In the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation) trial, a central committee of heart failure (HF) specialists optimized
guideline-directed medical therapies (GDMT) and documented medication and goal dose intolerances before patient enrollment.
The authors sought to assess the rates, reasons, and predictors of GDMT intolerance in the COAPT trial.
Baseline use, dose, and intolerances of angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), angiotensin receptor neprilysin inhibitors (ARNIs), beta-blockers, and mineralocorticoid receptor antagonists (MRAs) were analyzed in patients with left ventricular ejection fraction (LVEF) ≤40%, in whom maximally tolerated doses of these agents as assessed by an independent HF specialist were required before enrollment.
A total of 464 patients had LVEF ≤40% and complete medication information. At baseline, 38.8%, 39.4%, and 19.8% of patients tolerated 3, 2, and 1 GDMT classes, respectively (any dose); only 1.9% could not tolerate any GDMT. Beta-blockers were the most frequently tolerated GDMT (93.1%), followed by ACEIs/ARBs/ARNIs (68.5%), and then MRAs (55.0%). Intolerances differed by GDMT class, but hypotension and kidney dysfunction were most common. Goal doses were uncommonly achieved for beta-blockers (32.3%) and ACEIs/ARBs/ARNIs (10.2%) due to intolerances limiting titration. Only 2.2% of patients tolerated goal doses of all 3 GDMT classes.
In a contemporary trial population with HF, severe mitral regurgitation, and systematic HF specialist-directed GDMT optimization, most patients had medical intolerances prohibiting 1 or more GDMT classes and achieving goal doses. The specific intolerances noted and methods used for GDMT optimization provide important lessons for the implementation of GDMT optimization in future clinical trials. (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation [The COAPT Trial] [COAPT]; NCT01626079).