80 70 60 50 40 30 20 10 0
No change Moderate improvement Large improvement
72 51
Patients (%)
12
17
13
19
Angina absent
Seattle Angina Questionnaire
Change in QOL score Angina present
CAD: 治疗的难点
老的抗心绞痛药物 许多病人不能耐受治疗剂量产生的副作 用 BP, lipid, and glucose goals 要求越 来越低 许多患者不适合进行
控制危险因素
PCI
生活方式的改善
患者依从性不佳导致长期效果不良
慢性稳定性心绞痛的药物治疗
ACC/AHA 指南 I IIa IIb III
CCB = calcium channel blocker DHP = dihydropyridine *Except amlodipine
抗心绞痛药物的副作用和禁忌症
Drug class β-blockers Asthma Severe bradycardia AV block Severe depression Raynaud’s syndrome Sick sinus syndrome Nitrates Severe aortic stenosis Hypertrophic obstructive cardiomyopathy Erectile dysfunction* Calcium channel blockers† AV block Bradycardia Heart failure Left ventricular dysfunction Sinus node dysfunction
稳定性心绞痛: PCI vs 药物保守治疗
Meta-analysis of 11 randomized trials; N = 2950
Favors PCI Death Cardiac death or MI Nonfatal MI CABG ement
↓ Vasodilator response to stress
Adapted from Abrams J. N Engl J Med. 2005;352:2524-33.
心内膜下的灌注不足与心绞痛症状发生相关
MRI of myocardium during first pass of gadolinium
Aspirin 有心梗史的患者使用β-blockers 无心梗史的患者使用β-blockers 可疑 CAD患者的降脂治疗： LDL-C >130 mg/dL (target LDL-C <100 mg/dL*) ACEI 应用于所有合并糖尿病和左室功能障碍的 患者
Gibbons RJ et al. ACC/AHA 2002 guidelines. /clinical/guidelines/stable/stable.pdf. Grundy SM et al. Circulation. 2004;110:227-39.
Previous coronary revascularization
No
Yes
Exercise imaging study
High risk
Treatment* Consider angiography
Resting ECG interpretable
Yes
No
Consider angiography/ revascularization
斑块和缺血
Normal Fatty streak Plaque Increased plaque Obstructive atherosclerotic plaque
Exertional angina
Noninvasive tests: normal
Noninvasive tests: abnormal
*Optional goal of <70 mg/dL in patients at very high risk (ATP III Update)
目前广泛使用的抗心绞痛药物: 药理作用
O2 Supply Drug class β-blockers DHP CCBs Non-DHP CCBs Long-acting nitrates Coronary blood flow Heart rate O2 Demand Arterial pressure Venous return Myocardial contractility
*If adequate information on diagnosis/prognosis available
ACC/AHA 指南: 慢性稳定性心绞痛的治疗
Sublingual NTG
Yes
Patient education CCB, Long-acting nitrate
Prinzmetal angina?
Add/substitute CCB
Serious contraindication or unsuccessful treatment
Consider revascularization
Add long-acting nitrate
Unsuccessful treatment
Gibbons RJ et al. ACC/AHA 2002 guidelines. /clinical/guidelines/stable/stable.pdf.
PCI术后患者仍存在心绞痛症状
入选1620名PCI术后患者，跟踪随访1年
100 80 Patients (%) 60 40 20 0
Nitrates CCBs β-blockers ≥1 antianginal 27.9 29.9 78.6 60.9
仍有26%患者发生心 绞痛
Antianginal therapy
Spertus JA et al. Circulation. 2004;110:3789-94.
再次血管成形术受到限制：
• 高龄 • 左室功能障碍 • 多次血管成形术后 • 血管不适合再次血管成形术 • 弥漫病变或远端血管病变（如：糖尿病患者） • 多种合并疾病增加了围术期和术中的并发症
Mannheimer C et al. Eur Heart J. 2002;23:355-70.
*
/
Boden WE et al. Clin Cardiol. 2001;24:73-9. Gibbons RJ et al. ACC/AHA 2002 guidelines. /clinical/guidelines/stable/stable.pdf Kerins DM et al. In: Goodman and Gilman’s The Pharmacological Basis of Therapeutics. 10th ed.
心肌缺血可影响患者的生活质量
N = 1957; 7 months post-discharge following MI/UA
50 40 38 26 19 43
发生抑郁比例* (%)
30 20 10 0 None
Monthly
Weekly
Daily
发生心绞痛频率
*Seattle Angina Questionnaire Rumsfeld JS et al. Am Heart J. 2003;145:493-9.
P 0.68 0.28 0.12 0.82 0.34
Risk ratio (95% Cl)
1
2
Katritsis DG et al. Circulation. 2005;111:2906-12.
PCI的主要优点：缓解心绞痛症状
N = 1020 undergoing elective PCI; 1 year follow-up
存在药物难以缓解的心绞痛
• 目前所使用的传统治疗心绞痛的药物包括：β受体阻滞剂、钙离子拮抗 剂、硝酸酯类药物等，据统计，冠心病患者平均每周发生2次心绞痛 • 有一部分患者不能耐受服用治疗剂量的β受体阻滞剂、钙离子拮抗剂、 硝酸酯类 • Β受体阻滞剂和许多钙离子拮抗剂等药物有明显影响心率、血压以及房 室结传导的副作用 • 需要研发新的抗心绞痛药物
心肌缺血：基础研究
供氧不足的原因
冠状动脉血流受阻 • 血管粥样病变 • 内皮功能受损使得血管的顺应性下降
– 扩张功能受损 – 血管收缩
冠状动脉微血管血流储备能力下降 • 阻力血管（指直径小于200ug的小血管）功能障碍
– – – – 血管平滑肌细胞功能损伤 活动性异常 生长异常 炎症反应
血管外压迫作用
No Yes
Consider angiography
Symptoms/clinical findings Yes warrant angiography
No
Patient able to exercise
Yes
No
Pharmacologic imaging study
Low/intermediate risk
Medications/conditions that provoke/exacerbate angina?
No
Yes
Treat appropriately
β-blocker
Serious contraindication or unsuccessful treatment
Routine follow-up
Healthy control
A. At rest B. During stress (adenosine infusion)
Patient with chest pain and angiographically normal coronary arteries