Davis Barry R, Kostis John B, Simpson Lara M, Black Henry R, Cushman William C, Einhorn Paula T, Farber Michael A, Ford Charles E, Levy Daniel, Massie Barry M, Nawaz Shah
University of Texas Health Science Center School of Public Health, Houston, TX 77030, USA.
Circulation. 2008 Nov 25;118(22):2259-67. doi: 10.1161/CIRCULATIONAHA.107.762229. Epub 2008 Nov 10.
Heart failure (HF) developing in hypertensive patients may occur with preserved or reduced left ventricular ejection fraction (PEF [>or=50%] or REF [<50%]). In the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), 42 418 high-risk hypertensive patients were randomized to chlorthalidone, amlodipine, lisinopril, or doxazosin, providing an opportunity to compare these treatments with regard to occurrence of hospitalized HFPEF or HFREF.
HF diagnostic criteria were prespecified in the ALLHAT protocol. EF estimated by contrast ventriculography, echocardiography, or radionuclide study was available in 910 of 1367 patients (66.6%) with hospitalized events meeting ALLHAT criteria. Cox regression models adjusted for baseline characteristics were used to examine treatment differences for HF (overall and by PEF and REF). HF case fatality rates were examined. Of those with EF data, 44.4% had HFPEF and 55.6% had HFREF. Chlorthalidone reduced the risk of HFPEF compared with amlodipine, lisinopril, or doxazosin; the hazard ratios were 0.69 (95% confidence interval [CI], 0.53 to 0.91; P=0.009), 0.74 (95% CI, 0.56 to 0.97; P=0.032), and 0.53 (95% CI, 0.38 to 0.73; P<0.001), respectively. Chlorthalidone reduced the risk of HFREF compared with amlodipine or doxazosin; the hazard ratios were 0.74 (95% CI, 0.59 to 0.94; P=0.013) and 0.61 (95% CI, 0.47 to 0.79; P<0.001), respectively. Chlorthalidone was similar to lisinopril with regard to incidence of HFREF (hazard ratio, 1.07; 95% CI, 0.82 to 1.40; P=0.596). After HF onset, death occurred in 29.2% of participants (chlorthalidone/amlodipine/lisinopril) with new-onset HFPEF versus 41.9% in those with HFREF (P<0.001; median follow-up, 1.74 years); and in the chlorthalidone/doxazosin comparison that was terminated early, 20.0% of HFPEF and 26.0% of HFREF patients died (P=0.185; median follow-up, 1.55 years).
In ALLHAT, with adjudicated outcomes, chlorthalidone significantly reduced the occurrence of new-onset hospitalized HFPEF and HFREF compared with amlodipine and doxazosin. Chlorthalidone also reduced the incidence of new-onset HFPEF compared with lisinopril. Among high-risk hypertensive men and women, HFPEF has a better prognosis than HFREF.
高血压患者发生的心力衰竭（HF）可能伴有左心室射血分数保留或降低（PEF[≥50%]或REF[<50%]）。在抗高血压和降脂治疗预防心脏病发作试验（ALLHAT）中，42418例高危高血压患者被随机分配接受氯噻酮、氨氯地平、赖诺普利或多沙唑嗪治疗，从而有机会比较这些治疗在住院HFPEF或HFREF发生方面的差异。
ALLHAT方案预先规定了HF诊断标准。在1367例符合ALLHAT标准的住院事件患者中，910例（66.6%）可获得通过造影剂心室造影、超声心动图或放射性核素研究估算的EF。采用针对基线特征进行调整的Cox回归模型来检验HF（总体以及按PEF和REF）的治疗差异。对HF病死率进行了检查。在有EF数据的患者中，44.4%患有HFPEF，55.6%患有HFREF。与氨氯地平、赖诺普利或多沙唑嗪相比，氯噻酮降低了HFPEF的风险；风险比分别为0.69（95%置信区间[CI]，0.53至0.91；P=0.009）、0.74（95%CI，0.56至0.97；P=0.032）和0.53（95%CI，0.38至0.73；P<0.001）。与氨氯地平或多沙唑嗪相比，氯噻酮降低了HFREF的风险；风险比分别为0.74（95%CI，0.59至0.94；P=0.013）和0.61（95%CI，0.47至0.79；P<0.001）。氯噻酮在HFREF发生率方面与赖诺普利相似（风险比，1.07；95%CI，0.82至1.40；P=0.596）。HF发作后，新发HFPEF的参与者中有29.2%（氯噻酮/氨氯地平/赖诺普利）死亡，而HFREF患者中为41.9%（P<0.001；中位随访时间，1.74年）；在提前终止的氯噻酮/多沙唑嗪比较中，20.0%的HFPEF患者和26.0%的HFREF患者死亡（P=0.185；中位随访时间，1.55年）。
在ALLHAT中，经判定的结果显示，与氨氯地平和多沙唑嗪相比，氯噻酮显著降低了新发住院HFPEF和HFREF的发生率。与赖诺普利相比，氯噻酮也降低了新发HFPEF的发生率。在高危高血压男性和女性中，HFPEF的预后优于HFREF。
