曲前列尼尔注射液联合治疗肺动脉高压的疗效及安全性观察

Clinical efficacy and safety of treprostinil combination treatment for pulmonary hypertension

目的观察曲前列尼尔注射液(瑞莫杜林)治疗肺动脉高压的远期疗效、安全性及用药方法。方法选取2014年11月—2015年11月明确诊断为肺动脉高压患者32例,按设定的治疗策略随机分为治疗组和对照组,各16例。对照组口服波生坦片62.5 mg,2次/d,服用2周后调整为125 mg,2次/d。治疗组在对照组基础上联合曲前列尼尔注射液,采用输注泵经插入式皮下导管连续输注方式给药,根据患者体质量计算初始给药剂量,开始剂量每天0.625 ng/(kg·min),根据病情及不良反应调整用药剂量,最低减少至0.3 ng/(kg·min),最高增加至8.75 ng/(kg·min)维持量。观察用药24周后肺动脉收缩压、WHO心功能分级、6 min步行距离(6-minute walk distance,6MWD)等临床指标的变化及用药期间的药物不良反应。结果治疗组患者联合应用曲前列尼尔药物后WHO心功能分级、6MWD、Borg呼吸困难评分、外周氧饱和度都得到明显改善,差异有统计学意义(P<0.05),肺动脉收缩压力及N末端脑钠肽前体(NT-proBNP)较前略有降低,但差异无统计学意义(P>0.05)。治疗组与对照组总不良反应发生率分别为31.3%、25.0%,差异无统计学意义(P>0.05)。结论对于肺动脉高压危重患者波生坦联合使用曲前列尼尔治疗,能够有效改善患者心功能,提高运动能力,且安全性好。

Objective To observe the long-term effects and safety of treprostinil combined with bosentan in treating pulmonary hypertension. Methods Thirty-two patients who were hospitalized for pulmonary hypertension between November 2014 and November 2015 were selected and divided into 2 groups： the combined group （16 cases） and the control group （16 cases）. For the control group treatment, bosentan 62.5 mg bid was taken orally, and was increased to 125 mg bid in two weeks. For the combined therapy group, the patients were given Remodulin by subcutaneous injection combined with bosentan. The initial drug dose was 0.625 ng/（kg·min） calculated according to a patient＇s weight, and the dose was adjusted according to the condition of the patient and adverse reactions. The dose ranged from 0.3 ng/（kg·min） to 8.75 ng/（kg·min）. Then, the changes of some of the clinical indexes, such as pulmonary artery systolic pressure （PASP）, 6-minute walk distance （6MWD） and the WHO functional class, were evaluated after 24 weeks of treatment. Results The WHO functional class, 6MWD, Borg dyspnea score and mixed venous oxygen saturation were improved significantly （P〈0.05）. The PASP and N-terminal pro-brain natriuretic peptide were decreased, but without statistically significant difference （P〉0.05）. There was no significant difference in the incidence of adverse reactions between the combined group and the control group （P〉0.05）. Conclusion Remodulin combined with bosentan for severe pulmonary hypertension can not only improve the heart function and the ability to move about, but is safe.