β受体阻滞剂的心脏保护作用 课件.ppt

COPERNICUS试验 Months 0 3 6 9 18 15 12 21 50 80 70 60 90 100 Survival (%) Months 0 3 6 9 18 15 12 21 0 60 40 20 80 100 Event-free survival (%) All-cause mortality and hospitalization for any reason 35% relative risk reduction (95% CI 19 – 48%) P=0.00013 P=0.0014 adjusted for interim analysis 24% relative risk reduction (95% CI 13 – 33%) P0.001 Placebo Carvedilol Packer et al. N Engl J Med.2001;344:1651-8 0 250 随访（月） 死亡率 (%) 0 3 6 9 12 15 18 21 20 15 10 5 0 安慰剂 美托洛尔CR/XL MERIT-HF CIBIS II 生存率 300 150 卡维地洛 (n=696) 安慰剂 (n=398) 时间(天) 50 100 200 350 400 1.0 0.9 0.8 0.7 0.6 0.5 USCP 死亡率的早期获益优于ACEI 总 结 β受体阻滞剂在心血管疾病链的不同环节均发挥心脏保护作用 β1受体阻滞是发挥治疗作用的关键 比索洛尔是目前选择性最高的β1受体阻滞剂，对于有β受体阻滞剂的强适应证的心血管病患者，比索洛尔不仅可以改善症状，还能改善预后。 * 如果早期通过控制心血管病危险因素、逆转靶器官损害，阻止或逆转病程的进展，就会使病人心血管事件发生的风险降到很低的水平。 * * * * ?受体阻滞剂经历了不断的发展阶段,从60年代非选择性(普萘洛尔-心得安/心得静)?80年代选择性(阿替洛尔,贝他洛尔) ?90年代更高选择性比索洛尔即康忻，其选择比率(?1 /?2)为75:1，阿替洛尔为35:1，美托洛尔为20:1，普萘洛尔为1:1.8. 康忻，化学名为富马酸比索洛尔：是具有最高?1选择性的?受体阻滞剂. Receptor occupancy detected by an in vitro incubation of plasma samples with a ?-adrenoceptor preparation allows for a prediction of the relative extent of ?-adrenoceptor antagonistic effects in man. In this study the time course of plasma concentration after a single oral dose of 100 mg of bisoprolol – a dosage far beyond the therapeutic dose range – was compared with the ?-adrenoceptor occupancy of the two adrenoceptor subtypes in an ex-vivo/in-vitro assay. 24 hours after the administration of 100 mg bisoprolol, there was no longer any ?2-adrenoceptor occupancy detected in the plasma samples. Up to that time, plasma levels far exceeded the normal therapeutic range. Therefore an occupancy of the ?2-receptors is practically not to be expected under therapeutic conditions. 36 to 60 hours after a single oral dose of 100 mg of bisoprolol, plasma concentrations similar to a steady state condition after once daily dosage of 10 mg were found. At an 80 % occupancy of ?1-receptors, there was no occupancy of ?2-receptors seen wi