title: Dual phosphodiesterase type 5 inhibitor therapy for refractory pulmonary arterial hypertension: a pilot study.
abstract: BACKGROUND
  Recent vasodilating drugs have improved prognosis of Pulmonary arterial hypertension (PAH). Some reports describe the merits of combination therapies for PAH, and this study evaluated the efficacy and safety of phosphodiesterase type 5 inhibitors (PDE5i) combination therapy, using sildenafil and tadalafil, for multi-drug-resistant PAH.
  
  
  METHODS
  We retrospectively analyzed 7 consecutive refractory patients with PAH administered either sildenafil 60 mg or tadalafil 40 mg as well as both ERA and prostanoid as combination therapies. All were started on the dual PDE5i (sildenafil and tadalafil at maximum dose).
  
  
  RESULTS
  Treatment was generally well tolerated without severe adverse events. On completion of the study, the seven patients received right heart catheterization and the 6-minute walk test (6WMT) 9.6 ± 1.4 months after initiation of the dual PDE5i therapy, showing significant improvements in hemodynamic parameters and exercise tolerance. Mean pulmonary arterial pressure and pulmonary vascular resistance decreased from 47.9 ± 9.7 to 41.7 ± 9.2 mmHg (P = 0.004) and 9.3 ± 2.7 to 6.7 ± 2.9 mmHg (P = 0.018), respectively. Cardiac index and 6MWT also increased from 2.8 ± 0.9 to 3.1 ± 0.8 L/min/m(2) (P = 0.026) and 353 ± 60 to 382 ± 62 m (P = 0.014), respectively.
  
  
  CONCLUSIONS
  The findings support dual PDE5i therapy as a new treatment option for refractory PAH.
authors.affiliation: Department of Cardiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan. keyten2003@hotmail.com.
authors.forename: Mai
authors.initials: M
authors.lastname: Kimura
authors.affiliation: Department of Cardiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan. u1@ta-mu.net.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Tamura
authors.affiliation: Department of Cardiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan. makoto_tk@hotmail.com.
authors.forename: Makoto
authors.initials: M
authors.lastname: Takei
authors.affiliation: Department of Cardiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan. tsunetsune0625@a8.keio.jp.
authors.forename: Tsunehisa
authors.initials: T
authors.lastname: Yamamoto
authors.affiliation: Department of Cardiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan. tomohiko@a6.keio.jp.
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Ono
authors.affiliation: Department of Cardiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan. jfujita@a6.keio.jp.
authors.forename: Jun
authors.initials: J
authors.lastname: Fujita
authors.affiliation: Department of Cardiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan. m.kataoka09@gmail.com.
authors.forename: Masaharu
authors.initials: M
authors.lastname: Kataoka
authors.affiliation: Department of Allergy and Rheumatology, Nippon Medical School, Tokyo, Japan. kuwanam@nms.ac.jp.
authors.forename: Masataka
authors.initials: M
authors.lastname: Kuwana
authors.affiliation: Department of Cardiology, Kyorin University School of Medicine, Tokyo, Japan. tsatoh2008@me.com.
authors.forename: Toru
authors.initials: T
authors.lastname: Satoh
authors.affiliation: Department of Cardiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan. kfukuda@a2.keio.jp.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Fukuda
mesh_terms: D000328:Adult; D000959:Antihypertensive Agents / Q000627:therapeutic use; D000077300:Bosentan; D006328:Cardiac Catheterization; D004359:Drug Therapy, Combination; D065128:Endothelin Receptor Antagonists / Q000627:therapeutic use; D011464:Epoprostenol / Q000031:analogs & derivatives / Q000627:therapeutic use; D005080:Exercise Test; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy*; D008875:Middle Aged; D010666:Phenylpropionates / Q000627:therapeutic use; D058986:Phosphodiesterase 5 Inhibitors / Q000627:therapeutic use*; D010865:Pilot Projects; D011453:Prostaglandins / Q000627:therapeutic use; D011669:Pulmonary Wedge Pressure; D011724:Pyridazines / Q000627:therapeutic use; D012189:Retrospective Studies; D000068677:Sildenafil Citrate / Q000627:therapeutic use*; D013449:Sulfonamides / Q000627:therapeutic use; D000068581:Tadalafil / Q000627:therapeutic use*; D016896:Treatment Outcome; D014655:Vascular Resistance; D055815:Young Adult
chemical_list: D000959:Antihypertensive Agents; D065128:Endothelin Receptor Antagonists; D010666:Phenylpropionates; D058986:Phosphodiesterase 5 Inhibitors; D011453:Prostaglandins; D011724:Pyridazines; D013449:Sulfonamides; C048081:beraprost; D000068581:Tadalafil; D000068677:Sildenafil Citrate; D011464:Epoprostenol; C467894:ambrisentan; D000077300:Bosentan