title: Antithrombotic effects of losartan in patients with hypertension complicated by atrial fibrillation: 4A (Angiotensin II Antagonist of platelet Aggregation in patients with Atrial fibrillation), a pilot study.
abstract: Angiotensin receptor blockers (ARBs) are widely used for the treatment of hypertension. It has been reported that the ARB losartan has antiplatelet, anticoagulant and profibrinolytic effects experimentally. These properties could be desirable to treat hypertensive patients with high atherothrombotic and/or thromboembolic risk. To examine the antithrombotic effects of losartan in hypertension, 20 consecutive patients with hypertension complicated by atrial fibrillation (AF) were enrolled in this study. The patients were treated with losartan 50 mg for 8 weeks followed by 100 mg for 4 weeks. Blood samples were obtained from each patient at 0 (pretreatment), 8 and 12 weeks after initiating treatment. Platelet aggregability, plasma levels of tissue factor (TF) and type 1 plasminogen activator inhibitor (PAI-1) activity levels were measured. The area under the curve for small platelet aggregability decreased from 100 to 42.8% at 12 weeks (P<0.0001). TF levels (ng ml(-1)) and PAI-1 activity (IU ml(-1); mean±s.d.) also changed from 14.2±3.6 to 10.9±4.5 at 12 weeks (P=0.0299) and from 11.7±3.6 to 8.5±3.1 at 12 weeks (P=0.0122), respectively. Losartan inhibited platelet activity and coagulation factors in a dose- and time-dependent manner in patients with hypertension complicated by AF, whereas the fibrinolytic capacity was increased. The use of losartan could be advantageous in the treatment of hypertensive patients with high atherothrombotic risk.
authors.affiliation: Division of Cardiology, Saiseikai Kumamoto Hospital Cardiovascular Center, Kumamoto, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Sakamoto
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kudoh
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Sakamoto
authors.affiliation: Department of General Medicine, Yamaguchi University Hospital, Ube, Japan.
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Matsui
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Hisao
authors.initials: H
authors.lastname: Ogawa
mesh_terms: D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000097:blood / Q000188:drug therapy* / Q000209:etiology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005343:Fibrinolytic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000150:complications* / Q000188:drug therapy*; D019808:Losartan / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D010974:Platelet Aggregation / Q000187:drug effects; D012307:Risk Factors; D013923:Thromboembolism / Q000453:epidemiology; D013925:Thromboplastin / Q000378:metabolism; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D005343:Fibrinolytic Agents; D017395:Plasminogen Activator Inhibitor 1; D013925:Thromboplastin; D019808:Losartan