Unit of Cardiology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden2Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden.
Department of Clinical Science and Education, Karolinska Institutet, South Hospital, Stockholm, Sweden.
JAMA. 2014 Nov 19;312(19):2008-18. doi: 10.1001/jama.2014.15241.
Heart failure with preserved ejection fraction (HFPEF) may be as common and may have similar mortality as heart failure with reduced ejection fraction (HFREF). β-Blockers reduce mortality in HFREF but are inadequately studied in HFPEF.
To test the hypothesis that β-blockers are associated with reduced all-cause mortality in HFPEF.
Propensity score-matched cohort study using the Swedish Heart Failure Registry. Propensity scores for β-blocker use were derived from 52 baseline clinical and socioeconomic variables.
Nationwide registry of 67 hospitals with inpatient and outpatient units and 95 outpatient primary care clinics in Sweden with patients entered into the registry between July 1, 2005, and December 30, 2012, and followed up until December 31, 2012.
From a consecutive sample of 41,976 patients, 19,083 patients with HFPEF (mean [SD] age, 76 [12] years; 46% women). Of these, 8244 were matched 2:1 based on age and propensity score for β-blocker use, yielding 5496 treated and 2748 untreated patients with HFPEF. Also we conducted a positive-control consistency analysis involving 22,893 patients with HFREF, of whom 6081 were matched yielding 4054 treated and 2027 untreated patients.
β-Blockers prescribed at discharge from the hospital or during an outpatient visit, analyzed 2 ways: without consideration of crossover and per-protocol analysis with censoring at crossover, if applicable.
The prespecified primary outcome was all-cause mortality and the secondary outcome was combined all-cause mortality or heart failure hospitalization.
Median follow-up in HFPEF was 755 days, overall; 709 days in the matched cohort; no patients were lost to follow-up. In the matched HFPEF cohort, 1-year survival was 80% vs 79% for treated vs untreated patients, and 5-year survival was 45% vs 42%, with 2279 (41%) vs 1244 (45%) total deaths and 177 vs 191 deaths per 1000 patient-years (hazard ratio [HR], 0.93; 95% CI, 0.86-0.996; P = .04). β-Blockers were not associated with reduced combined mortality or heart failure hospitalizations: 3368 (61%) vs 1753 (64%) total for first events, with 371 vs 378 first events per 1000 patient-years (HR, 0.98; 95% CI, 0.92-1.04; P = .46). In the matched HFREF cohort, β-blockers were associated with reduced mortality (HR, 0.89; 95% CI, 0.82-0.97, P=.005) and also with reduced combined mortality or heart failure hospitalization (HR, 0.89; 95% CI, 0.84-0.95; P = .001).
In patients with HFPEF, use of β-blockers was associated with lower all-cause mortality but not with combined all-cause mortality or heart failure hospitalization. β-Blockers in HFPEF should be examined in a large randomized clinical trial.
重要性：射血分数保留型心力衰竭（HFPEF）可能与射血分数降低型心力衰竭（HFREF）一样常见，且死亡率可能相似。β-受体阻滞剂可降低 HFREF 的死亡率，但在 HFPEF 中的研究尚不充分。
目的：检验β-受体阻滞剂与 HFPEF 患者全因死亡率降低相关的假设。
设计：利用瑞典心力衰竭注册研究进行倾向评分匹配队列研究。使用 52 项基线临床和社会经济变量得出β-受体阻滞剂使用的倾向评分。
设置：在瑞典，全国有 67 家医院的住院和门诊单位，以及 95 家门诊初级保健诊所，患者在 2005 年 7 月 1 日至 2012 年 12 月 30 日期间被纳入该注册中心，并随访至 2012 年 12 月 31 日。
参与者：从连续的 41976 例患者中，筛选出 19083 例 HFPEF 患者（平均年龄 76[12]岁，46%为女性）。其中，8244 例患者按照年龄和β-受体阻滞剂使用的倾向评分进行了 2:1 的匹配，产生了 5496 例接受治疗和 2748 例未接受治疗的 HFPEF 患者。我们还进行了一项阳性对照一致性分析，涉及 22893 例 HFREF 患者，其中 6081 例进行了匹配，产生了 4054 例接受治疗和 2027 例未接受治疗的患者。
暴露情况：出院或门诊就诊时开具的β-受体阻滞剂，分析了 2 种方法：不考虑交叉情况和按方案分析（如有交叉，以交叉为终点）。
主要结果和措施：主要结局是全因死亡率，次要结局是全因死亡率或心力衰竭住院的复合结局。
结果：HFPEF 的中位随访时间为 755 天，总体；匹配队列为 709 天；无患者失访。在匹配的 HFPEF 队列中，1 年生存率为治疗组 80% vs 未治疗组 79%，5 年生存率为治疗组 45% vs 未治疗组 42%，共有 2279 例（41%）和 1244 例（45%）患者死亡，每 1000 患者年有 177 例和 191 例死亡（风险比[HR]，0.93；95%CI，0.86-0.996；P=0.04）。β-受体阻滞剂与降低复合死亡率或心力衰竭住院率无关：首次事件中，3368 例（61%）和 1753 例（64%）为首次事件，每 1000 患者年有 371 例和 378 例首次事件（HR，0.98；95%CI，0.92-1.04；P=0.46）。在匹配的 HFREF 队列中，β-受体阻滞剂与死亡率降低相关（HR，0.89；95%CI，0.82-0.97，P=0.005），也与降低复合死亡率或心力衰竭住院率相关（HR，0.89；95%CI，0.84-0.95，P=0.001）。
结论和相关性：在 HFPEF 患者中，β-受体阻滞剂的使用与较低的全因死亡率相关，但与全因死亡率或心力衰竭住院的复合结局无关。HFPEF 中的β-受体阻滞剂应在大型随机临床试验中进行检验。
