Hjalmarson A, Goldstein S, Fagerberg B, Wedel H, Waagstein F, Kjekshus J, Wikstrand J, El Allaf D, Vítovec J, Aldershvile J, Halinen M, Dietz R, Neuhaus K L, Jánosi A, Thorgeirsson G, Dunselman P H, Gullestad L, Kuch J, Herlitz J, Rickenbacher P, Ball S, Gottlieb S, Deedwania P
Department of Cardiology, Sahlgrenska University Hospital, Göteborg, Sweden.
JAMA. 2000 Mar 8;283(10):1295-302. doi: 10.1001/jama.283.10.1295.
Results from recent studies on the effects of beta1-blockade in patients with heart failure demonstrated a 34% reduction in total mortality. However, the effect of beta1-blockade on the frequency of hospitalizations, symptoms, and quality of life in patients with heart failure has not been fully explored.
To examine the effects of the beta1-blocker controlled-release/extended-release metoprolol succinate (metoprolol CR/XL) on mortality, hospitalization, symptoms, and quality of life in patients with heart failure.
Randomized, double-blind controlled trial, preceded by a 2-week single-blind placebo run-in period, conducted from February 14, 1997, to October 31, 1998, with a mean follow-up of 1 year.
Three hundred thirteen sites in 14 countries.
Patients (n = 3991) with chronic heart failure, New York Heart Association (NYHA) functional class II to IV, and ejection fraction of 0.40 or less who were stabilized with optimum standard therapy.
Patients were randomized to metoprolol CR/XL, 25 mg once per day (NYHA class II), or 12.5 mg once per day (NYHA class III or IV), titrated for 6 to 8 weeks up to a target dosage of 200 mg once per day (n = 1990); or matching placebo (n = 2001).
Total mortality or any hospitalization (time to first event), number of hospitalizations for worsening heart failure, and change in NYHA class, by intervention group; quality of life was assessed in a substudy of 741 patients.
The incidence of all predefined end points was lower in the metoprolol CR/XL group than in the placebo group, including total mortality or all-cause hospitalizations (the prespecified second primary end point; 641 vs 767 events; risk reduction, 19%; 95% confidence interval [CI], 10%-27%; P<.001); total mortality or hospitalizations due to worsening heart failure (311 vs 439 events; risk reduction, 31%; 95% CI, 20%-40%; P<.001), number of hospitalizations due to worsening heart failure (317 vs 451; P<.001); and number of days in hospital due to worsening heart failure (3401 vs 5303 days; P<.001). NYHA functional class, assessed by physicians, and McMaster Overall Treatment Evaluation score, assessed by patients, both improved in the metoprolol CR/XL group compared with the placebo group (P = .003 and P = .009, respectively).
In this study of patients with symptomatic heartfailure, metoprolol CR/XL improved survival, reduced the need for hospitalizations due to worsening heart failure, improved NYHA functional class, and had beneficial effects on patient well-being.
近期关于β1受体阻滞剂对心力衰竭患者影响的研究结果显示，总死亡率降低了34%。然而，β1受体阻滞剂对心力衰竭患者住院频率、症状及生活质量的影响尚未得到充分研究。
探讨β1受体阻滞剂琥珀酸美托洛尔控释/缓释片（美托洛尔CR/XL）对心力衰竭患者死亡率、住院率、症状及生活质量的影响。
随机、双盲对照试验，在1997年2月14日至1998年10月31日进行，为期2周的单盲安慰剂导入期，平均随访1年。
14个国家的313个研究点。
3991例慢性心力衰竭患者，纽约心脏协会（NYHA）心功能分级为II至IV级，射血分数为0.40或更低，且已通过最佳标准治疗稳定病情。
患者被随机分为美托洛尔CR/XL组，NYHA II级患者每日1次服用25mg，NYHA III或IV级患者每日1次服用12.5mg，滴定6至8周，直至目标剂量为每日1次200mg（n = 1990）；或匹配的安慰剂组（n = 2001）。
按干预组划分的总死亡率或任何住院情况（首次事件发生时间）、因心力衰竭恶化导致的住院次数、NYHA分级变化；在741例患者的子研究中评估生活质量。
美托洛尔CR/XL组所有预定义终点的发生率均低于安慰剂组，包括总死亡率或全因住院率（预先指定的第二个主要终点；641例对767例事件；风险降低19%；95%置信区间[CI]，10% - 27%；P <.001）；总死亡率或因心力衰竭恶化导致的住院率（311例对439例事件；风险降低31%；95% CI，20% - 40%；P <.001），因心力衰竭恶化导致的住院次数（317次对451次；P <.001）；以及因心力衰竭恶化导致的住院天数（3401天对5303天；P <.001）。与安慰剂组相比，美托洛尔CR/XL组经医生评估的NYHA功能分级和经患者评估的麦克马斯特总体治疗评价得分均有所改善（分别为P =.003和P =.009）。
在这项对有症状心力衰竭患者的研究中，美托洛尔CR/XL改善了生存率，减少了因心力衰竭恶化导致的住院需求，改善了NYHA功能分级，并对患者的健康状况产生了有益影响。
