Efficacy of Folic Acid Therapy in Primary Prevention of Stroke Among Adults With Hypertension in China The CSPPT Randomized Clinical Trial
Efficacy of Folic Acid Therapy in Primary Prevention of Stroke Among Adults With Hypertension in China The CSPPT Randomized Clinical Trial
复制标题
叶酸治疗对中国成人高血压患者脑卒中一级预防的疗效 CSPPT 随机临床试验
DOI：
10.1001/jama.2015.2274
复制
发表时间：
2015-04-07
影响因子：
120.7
通讯作者：
Hou, Fan Fan
中科院分区：
文献类型：
--
作者：
Huo, Yong;Li, Jianping;Hou, Fan Fan
由于数据有限和不一致，叶酸治疗卒中一级预防的有效性仍然存在重要的不确定性。目的检验依那普利联合叶酸治疗在中国成年高血压患者中比单用依那普利更有效地减少首次卒中的基本假设。设计、背景和参与者于2008年5月19日至2013年8月24日在江苏和安徽的32个社区进行的中国卒中一级预防试验是一项随机双盲临床试验。共有20702名无中风或心肌梗死(MI)病史的成人高血压患者参加了这项研究。干预符合条件的参与者按MTHFR C677T基因(CC、CT和TT)分层，随机分配到每天接受双盲治疗，单片含依那普利10 mg和叶酸0.8 mg(n=10348)，或单片含依那普利(10 Mg)(n=10354)。次要结果包括首次缺血性卒中；首次出血性卒中；心肌梗死；由心血管死亡、心肌梗死和卒中组成的心血管事件的组合；以及全因死亡。结果在4.5年的中位治疗期间，与单用依那普利组相比，依那普利-叶酸组首次卒中的风险显著降低(依那普利-叶酸组的2.7%与单用依那普利组的3.4%；危险比[HR]，0.79；95%CI，0.68-0.93)，首次缺血性中风(依那普利-叶酸治疗2.2%，依那普利单独治疗2.8%；HR，0.76；95%CI，0.64-0.91)，以及由心血管死亡、心肌梗死和中风组成的复合心血管事件(依那普利-叶酸治疗3.1%，单用依那普利3.9%；HR，0.80；95%CI，0.69-0.92)。出血性中风(HR，0.93；95%CI，0.65-1.34)、MI(HR，1.04；95%CI，0.60-1.82)和全因死亡(HR，0.94；95%CI，0.81-1.10)的风险在两组之间没有显著差异。两组不良事件发生率差异无统计学意义。结论在中国地区无卒中或心肌梗塞病史的成年高血压患者中，联合应用依那普利和叶酸较单用依那普利可显著降低首次卒中的风险。这些发现与在患有高血压和低基线叶酸水平的成年人中使用叶酸的好处是一致的。
IMPORTANCE Uncertainty remains about the efficacy of folic acid therapy for the primary prevention of stroke because of limited and inconsistent data.OBJECTIVE To test the primary hypothesis that therapy with enalapril and folic acid is more effective in reducing first stroke than enalapril alone among Chinese adults with hypertension.DESIGN, SETTING, AND PARTICIPANTS The China Stroke Primary Prevention Trial, a randomized, double-blind clinical trial conducted from May 19, 2008, to August 24, 2013, in 32 communities in Jiangsu and Anhui provinces in China. A total of 20 702 adults with hypertension without history of stroke or myocardial infarction (MI) participated in the study.INTERVENTIONS Eligible participants, stratified by MTHFR C677T genotypes (CC, CT, and TT), were randomly assigned to receive double-blind daily treatment with a single-pill combination containing enalapril, 10 mg, and folic acid, 0.8 mg (n = 10 348) or a tablet containing enalapril,10 mg, alone (n = 10 354).MAIN OUTCOMES AND MEASURES The primary outcome was first stroke. Secondary outcomes included first ischemic stroke; first hemorrhagic stroke; MI; a composite of cardiovascular events consisting of cardiovascular death, MI, and stroke; and all-cause death.RESULTS During a median treatment duration of 4.5 years, compared with the enalapril alone group, the enalapril-folic acid group had a significant risk reduction in first stroke (2.7% of participants in the enalapril-folic acid group vs 3.4% in the enalapril alone group; hazard ratio [HR], 0.79; 95% Cl, 0.68-0.93), first ischemic stroke (2.2% with enalapril-folic acid vs 2.8% with enalapril alone; HR, 0.76; 95% Cl, 0.64-0.91), and composite cardiovascular events consisting of cardiovascular death, MI, and stroke (3.1% with enalapril-folic acid vs 3.9% with enalapril alone; HR, 0.80; 95% Cl, 0.69-0.92). The risks of hemorrhagic stroke (HR, 0.93; 95% Cl, 0.65-1.34), MI (HR, 1.04; 95% Cl, 0.60-1.82), and all-cause deaths (HR, 0.94; 95% Cl, 0.81-1.10) did not differ significantly between the 2 treatment groups. There were no significant differences between the 2 treatment groups in the frequencies of adverse events.CONCLUSIONS AND RELEVANCE Among adults with hypertension in China without a history of stroke or MI, the combined use of enalapril and folic acid, compared with enalapril alone, significantly reduced the risk of first stroke. These findings are consistent with benefits from folate use among adults with hypertension and low baseline folate levels.