British Heart Foundation Centre of Excellence and National Institute for Health Research Biomedical Research Centre at the School of Cardiovascular Medicine and Sciences (A.S., H.R., O.M.D., U.D., H.E., A.M.S., A.C., M.M., A.J.W., D.P.), King's College London, UK.
Department of Medical Statistics, School of Life Course & Population Sciences (A.D.), King's College London, UK.
Circulation. 2024 Jan 2;149(1):36-47. doi: 10.1161/CIRCULATIONAHA.123.066680. Epub 2023 Oct 31.
Angina with nonobstructive coronary arteries is a common condition for which no effective treatment has been established. We hypothesized that the measurement of coronary flow reserve (CFR) allows identification of patients with angina with nonobstructive coronary arteries who would benefit from anti-ischemic therapy.
Patients with angina with nonobstructive coronary arteries underwent blinded invasive CFR measurement and were randomly assigned to receive 4 weeks of amlodipine or ranolazine. After a 1-week washout, they crossed over to the other drug for 4 weeks; final assessment was after the cessation of study medication for another 4 weeks. The primary outcome was change in treadmill exercise time, and the secondary outcome was change in Seattle Angina Questionnaire summary score in response to anti-ischemic therapy. Analysis was on a per protocol basis according to the following classification: coronary microvascular disease (CMD group) if CFR<2.5 and reference group if CFR≥2.5. The study protocol was registered before the first patient was enrolled (International Standard Randomised Controlled Trial Number: ISRCTN94728379).
Eighty-seven patients (61±8 years of age; 62% women) underwent random assignment (57 CMD group and 30 reference group). Baseline exercise time and Seattle Angina Questionnaire summary scores were similar between groups. The CMD group had a greater increment (delta) in exercise time than the reference group in response to both amlodipine (difference in delta, 82 s [95% CI, 37-126 s]; <0.001) and ranolazine (difference in delta, 68 s [95% CI, 21-115 s]; =0.005). The CMD group reported a greater increment (delta) in Seattle Angina Questionnaire summary score than the reference group in response to ranolazine (difference in delta, 7 points [95% CI, 0-15]; =0.048), but not to amlodipine (difference in delta, 2 points [95% CI, -5 to 8]; =0.549).
Among phenotypically similar patients with angina with nonobstructive coronary arteries, only those with an impaired CFR derive benefit from anti-ischemic therapy. These findings support measurement of CFR to diagnose and guide management of this otherwise heterogeneous patient group.
伴有非阻塞性冠状动脉的心绞痛是一种常见病症，目前尚无有效的治疗方法。我们假设，冠状动脉血流储备（CFR）的测量可确定患有伴有非阻塞性冠状动脉的心绞痛并受益于抗缺血治疗的患者。
患有伴有非阻塞性冠状动脉的心绞痛的患者接受了盲法的侵入性 CFR 测量，并随机分配接受 4 周的氨氯地平或雷诺嗪治疗。在 1 周洗脱期后，他们交叉接受另一种药物治疗 4 周；最终评估是在停止研究药物治疗后的另外 4 周。主要结局是跑步机运动时间的变化，次要结局是抗缺血治疗后西雅图心绞痛问卷综合评分的变化。根据以下分类，按意向治疗进行分析：如果 CFR<2.5，则为冠状动脉微血管疾病（CMD 组），如果 CFR≥2.5，则为参考组。该研究方案在首位患者入组前进行了注册（国际标准随机对照试验编号：ISRCTN94728379）。
87 名患者（61±8 岁；62%为女性）接受了随机分组（57 名 CMD 组和 30 名参考组）。基线运动时间和西雅图心绞痛问卷综合评分在两组之间相似。CMD 组对氨氯地平和雷诺嗪的反应均表现出更大的运动时间增量（delta）（delta 的差异，分别为 82 秒[95%CI，37-126 秒]；<0.001）和 68 秒[95%CI，21-115 秒]；=0.005）。CMD 组在对雷诺嗪的反应中报告西雅图心绞痛问卷综合评分的增量（delta）大于参考组（delta 的差异，7 分[95%CI，0-15]；=0.048），而对氨氯地平无差异（delta 的差异，2 分[95%CI，-5 至 8]；=0.549）。
在表型相似的伴有非阻塞性冠状动脉的心绞痛患者中，只有那些 CFR 受损的患者才受益于抗缺血治疗。这些发现支持使用 CFR 测量来诊断和指导这一异质性患者群体的治疗。
