McGavin Jane K, Keating Gillian M
Adis International Limited, Mairangi Bay, Auckland, New Zealand.
Drugs. 2002;62(18):2677-96. doi: 10.2165/00003495-200262180-00017.
Bisoprolol is a highly selective beta(1)-adrenoceptor antagonist. Administration of bisoprolol to patients with chronic heart failure is associated with increases in left ventricular function and reductions in heart rate; increases in heart rate variability are also seen. Two major randomised, double-blind, placebo-controlled, multicentre trials have examined the clinical efficacy of bisoprolol in combination with ACE inhibitors and diuretics in patients with stable chronic heart failure (New York Heart Association class III or IV): the Cardiac Insufficiency Bisoprolol Study (CIBIS; n = 641) and CIBIS II (n = 2 647). All-cause mortality (primary endpoint) was significantly lower in bisoprolol than in placebo recipients in CIBIS II (11.8 vs 17.3%) and was reduced by bisoprolol regardless of dosage. All-cause mortality was also lower in CIBIS (16.6 vs 20.9%) although the difference did not achieve statistical significance. In a meta-analysis of CIBIS and CIBIS II (n = 3 288), a relative reduction of 29% in the incidence of all-cause mortality was seen in bisoprolol versus placebo recipients; this analysis also demonstrated that bisoprolol reduces mortality in patients with chronic heart failure regardless of aetiology or severity. In CIBIS II, there were significantly fewer cardiovascular deaths, admissions to hospital for any reason, or cardiovascular deaths or cardiovascular hospitalisations (combined endpoint) in bisoprolol, compared with placebo, recipients (secondary endpoints). Compared with standard treatment alone, the addition of bisoprolol was a cost-effective option in chronic heart failure in UK, French, German and Swedish pharmacoeconomic studies. Bisoprolol is generally well tolerated in patients with chronic heart failure. In CIBIS II, adverse events occurring more commonly in bisoprolol than placebo recipients, regardless of causal relationship with the study medication, included dizziness, bradycardia, hypotension and fatigue. Bisoprolol recipients were less likely than placebo recipients to experience worsening of heart failure, dyspnoea or tachycardia. In both CIBIS and CIBIS II there was no significant difference between bisoprolol and placebo recipients in the incidence of permanent treatment withdrawal. In conclusion, adding the highly selective beta(1)-blocker bisoprolol to a treatment regimen comprising an ACE inhibitor and a diuretic significantly improves survival in patients with stable chronic heart failure and reduces the need for hospitalisation. The use of bisoprolol in this disorder is generally well tolerated and is cost effective. Thus, bisoprolol should be considered a standard treatment option when selecting a beta-blocker for use in combination with ACE inhibitors and diuretics in patients with stable, moderate to severe chronic heart failure.
比索洛尔是一种高度选择性的β1肾上腺素能受体拮抗剂。给慢性心力衰竭患者使用比索洛尔可使左心室功能增强、心率降低,心率变异性也增加。两项主要的随机、双盲、安慰剂对照、多中心试验研究了比索洛尔联合血管紧张素转换酶(ACE)抑制剂和利尿剂用于稳定型慢性心力衰竭(纽约心脏协会III或IV级)患者的临床疗效:心脏不全比索洛尔研究(CIBIS;n = 641)和CIBIS II(n = 2647)。在CIBIS II中,比索洛尔组的全因死亡率(主要终点)显著低于安慰剂组(11.8%对17.3%),且无论剂量如何,比索洛尔均能降低全因死亡率。CIBIS中全因死亡率也较低(16.6%对20.9%),尽管差异未达到统计学显著性。在对CIBIS和CIBIS II(n = 3288)的荟萃分析中,与安慰剂组相比,比索洛尔组全因死亡率发生率相对降低了29%;该分析还表明,无论病因或严重程度如何,比索洛尔均可降低慢性心力衰竭患者的死亡率。在CIBIS II中,与安慰剂组相比,比索洛尔组心血管死亡、因任何原因住院或心血管死亡或心血管住院(联合终点)的情况显著减少(次要终点)。在英国、法国、德国和瑞典的药物经济学研究中,与单独的标准治疗相比,加用比索洛尔是慢性心力衰竭治疗中具有成本效益的选择。慢性心力衰竭患者对比索洛尔一般耐受性良好。在CIBIS II中,如果不考虑与研究药物的因果关系,比索洛尔组比安慰剂组更常出现的不良事件包括头晕、心动过缓、低血压和疲劳。与安慰剂组相比,比索洛尔组患者心力衰竭、呼吸困难或心动过速恶化的可能性更小。在CIBIS和CIBIS II中,比索洛尔组和安慰剂组在永久停药发生率方面均无显著差异。总之,在包含ACE抑制剂和利尿剂的治疗方案中加用高度选择性的β1阻滞剂比索洛尔可显著提高稳定型慢性心力衰竭患者的生存率,并减少住院需求。在这种疾病中使用比索洛尔一般耐受性良好且具有成本效益。因此,在为稳定的中重度慢性心力衰竭患者选择与ACE抑制剂和利尿剂联合使用的β阻滞剂时,应将比索洛尔视为标准治疗选择。