Correspondence Article Type Letter by Bertoletti et al Regarding Article, “Anticoagulation and Survival in Pulmonary Arterial Hypertension: Results From the Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA)” To the Editor: Olsson and coworkers1 have to be warmly thanked for their important work on the debatable question of anticoagulant therapy in patients with pulmonary arterial hypertension (PAH). They make the paradox of anticoagulation for PAH patients quite apparent. Clinicians are making huge efforts to evaluate targeted therapies in well-designed, randomized, controlled trials, yet at the same time, we are prescribing potentially life-threatening drugs such as vitamin K antagonists (VKA), which are recommended with a low level of evidence2 but prescribed widely in clinical practice.3 In their study, Olsson et al found that VKA prescription was associated with a better prognosis in patients with idiopathic PAH. However, the potential impact of VKA on prognosis merely depends on their expected effect. In others words, it depends on their indication. VKAs are the cornerstone therapy in venous thromboembolism (VTE), as in atrial fibrillation (AF). They are associated with a reduction in mortality compared with placebo in both indications.4 It is worth noting that VTE and AF increase frequently after 60 years of age. Because the median age in the Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA) study was 70 years in the anticoagulant group, it is possible that a significant proportion of patients were also experiencing VTE or AF. It would therefore be important first to know whether VKAs were prescribed for a validated indication such as VTE or AF and second to evaluate whether their benefit remains according to the presence or absence of such an indication. If data limited to patients with PAH but without validated indications for VKA remain favorable to VKA therapy in PAH patients, it would then be timely to evaluate the risk-to-benefit ratio of antithrombotic therapy in patients with PAH. In line with this last point, it would be important to evaluate the pharmacological interactions between new oral anticoagulants (indicated for VTE and AF) and the treatment received by patients with PAH.5

Disclosures None. Laurent Bertoletti, MD, PhD Patrick Mismetti, MD, PhD Hervé Decousus, MD, PhD Université Jean-Monnet Thrombosis Research Group St. Etienne, France INSERM, CIC-CIE3 St. Etienne, France Centre Hospitalier Universitaire Service de Médecine Vasculaire et Thérapeutique St. Etienne, France

References 1. Olsson KM, Delcroix M, Ghofrani HA, Tiede H, Huscher D, Speich R, Grünig E, Staehler G, Rosenkranz S, Halank M, Held M, Lange TJ, Behr J, Klose H, Claussen M, Ewert R, Opitz CF, Vizza CD, Scelsi L, VonkNoordegraaf A, Kaemmerer H, Gibbs JS, Coghlan G, Pepke-Zaba J, Schulz U, Gorenflo M, Pittrow D, Hoeper MM. Anticoagulation and survival in pulmonary arterial hypertension: results from the Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA). Circulation. 2014;129:57–65. 2. Galiè N, Hoeper MM, Humbert M, Torbicki A, Vachiery J-L, Barbera J a, Beghetti M, Corris P, Gaine S, Gibbs JS, Gomez-Sanchez MA, Jondeau G, Klepetko W, Opitz C, Peacock A, Rubin L, Zellweger M, Simonneau G. Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Respir J. 2009; 34:1219–1263. 3. Humbert M, Sitbon O, Chaouat A, Bertocchi M, Habib G, Gressin V, Yaïci A, Weitzenblum E, Cordier JF, Chabot F, Dromer C, Pison C, ReynaudGaubert M, Haloun A, Laurent M, Hachulla E, Cottin V, Degano B, Jaïs X, Montani D, Souza R, Simonneau G. Survival in patients with idiopathic, familial, and anorexigen-associated pulmonary arterial hypertension in the modern management era. Circulation. 2010;122:156–163. 4. BAATAF Investigators. The effect of low-dose warfarin on the risk of stroke in patients with nonrheumatic atrial fibrillation: the Boston Area Anticoagulation Trial for Atrial Fibrillation Investigators. N. Engl. J. Med. 1990; 323:1505–1511. 5. Bertoletti L, Delavenne X, Montani D. Antithrombotics in pulmonary hypertension: more work needed before we turn to newer agents! Eur Respir J. 2013;41:775–777.

(Circulation. 2014;130:e108.) © 2014 American Heart Association, Inc. Circulation is available at http://circ.ahajournals.org

DOI: 10.1161/CIRCULATIONAHA.113.007143

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Letter by Bertoletti et al Regarding Article, ''Anticoagulation and Survival in Pulmonary Arterial Hypertension: Results From the Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA)'' Laurent Bertoletti, Patrick Mismetti and Hervé Decousus Circulation. 2014;130:e108 doi: 10.1161/CIRCULATIONAHA.113.007143 Circulation is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231 Copyright © 2014 American Heart Association, Inc. All rights reserved. Print ISSN: 0009-7322. Online ISSN: 1524-4539

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