Department of Pharmacy, New York Methodist Hospital, Brooklyn, New York 11215, USA.
Pharmacotherapy. 2010 Apr;30(4):390-404. doi: 10.1592/phco.30.4.390.
As a result of the multimechanistic pathology of pulmonary arterial hypertension (PAH), combination therapy is emerging as a potential treatment option. Recent guidelines from the American College of Chest Physicians and expert consensus from the American College of Cardiology Foundation and American Heart Association do not definitively support or disapprove of combination pharmacotherapy for the treatment of PAH. Published trials have investigated different combinations including endothelin receptor antagonists with prostanoids, prostanoids with phosphodiesterase inhibitors, and phosphodiesterase inhibitors with endothelin receptor antagonists. Pertinent trials on combination pharmacotherapy for PAH were identified through a MEDLINE search of literature from 1967-2009 in addition to a manual search of references from the articles retrieved. Search results identified 12 trials that evaluated combination therapy for PAH; some included an add-on agent for patients who failed treatment with monotherapy and others were placebo controlled. Even with the published data, the overall consensus is unclear. Well-designed, larger trials with validated end points are needed to further identify when to initiate combination therapy for the treatment of PAH. Meanwhile, perhaps the most appropriate situation for using combination pharmacotherapy may be in the setting of a lack of clinical improvement or deterioration.
由于肺动脉高压（PAH）的多机制病理，联合治疗作为一种潜在的治疗选择正在出现。美国胸科医师学会的最新指南和美国心脏病学会基金会及美国心脏协会的专家共识并未明确支持或反对联合药物治疗 PAH。已发表的试验研究了不同的联合治疗方案，包括内皮素受体拮抗剂与前列腺素、前列腺素与磷酸二酯酶抑制剂、以及磷酸二酯酶抑制剂与内皮素受体拮抗剂的联合治疗。通过对 1967 年至 2009 年文献的 MEDLINE 搜索，并对检索到的文章的参考文献进行手动搜索，确定了有关 PAH 联合药物治疗的相关试验。搜索结果确定了 12 项评估 PAH 联合治疗的试验；有些试验包括对单药治疗失败的患者加用辅助药物，而其他试验则为安慰剂对照。即使有了已发表的数据，总体共识仍不明确。需要进行设计良好、规模更大的具有验证终点的试验，以进一步确定何时开始联合治疗 PAH。同时，在缺乏临床改善或病情恶化的情况下，联合药物治疗可能是最合适的情况。
