Influence of baseline anemia on long-term clinical outcomes in patients with venous thromboembolism: from the COMMAND VTE registry
- 27 Downloads
The influence of anemia on the long-term clinical outcomes has not been fully evaluated in patients with venous thromboembolism (VTE). We evaluated the influence of anemia among 3012 patients in the COMMAND VTE Registry with a median follow-up period of 1219 days. The outcomes measures were ISTH major bleeding, recurrent VTE and all-cause death. There were 1012 patients (34%) with moderate/severe anemia (Hb ≤ 10.9 g/dl), 615 patients (20%) with mild anemia (Hb 11.0–12.9 g/dl for men, and 11.0–11.9 g/dl for women), and 1385 patients (46%) without anemia. The cumulative 5-year incidence of major bleeding was significantly higher in patients with anemia (moderate/severe anemia: 17.6%, mild anemia: 12.1%, and no anemia: 8.7%, P < 0.001). After adjusting the confounders, the excess risk of mild and moderate/severe anemia, respectively, relative to no anemia for major bleeding remained significant (mild: adjusted HR 1.41: [95% CI 1.00–1.98], P = 0.048; moderate/severe: adjusted HR 1.91: [95% CI 1.42–2.58], P < 0.001, respectively). The excess risk of moderate/severe anemia relative to no anemia was also significant for mortality (adjusted HR 2.89: 95% CI 2.45–3.42, P < 0.001), but the risk was neutral for recurrent VTE (adjusted HR 1.05: 95% CI 0.76–1.45, P = 0.77). In conclusions, VTE patients with mild and moderate/severe anemia had higher risk for major bleeding events without significant excess risk for recurrent VTE events, and the risk for major bleeding events increased according to the severity of anemia. We should pay more attention to the optimal intensity and duration of anticoagulation in VTE patients with anemia.
KeywordsVenous thromboembolism Anemia Bleeding Recurrence Mortality
We appreciate the support and collaboration of the co-investigators participating in the COMMAND VTE Registry. We are indebted to the independent clinical research organization (Research Institute for Production Development, Kyoto, Japan) for technical support.
The COMMAND VTE Registry is supported by the independent clinical research organization (Research Institute for Production Development, Kyoto, Japan) and research funding from Mitsubishi Tanabe Pharma Corporation. The research funding had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript.
Compliance with ethical standards
Conflict of interest
Dr. Yamashita received lecture fees from Daiichi-Sankyo, Bristol-Myers Squibb, and Bayer Healthcare. Dr. Morimoto received lecture fees from Mitsubishi Tanabe Pharma and Pfizer Japan and consultant fees from Asahi Kasei, Bristol-Myers Squibb, and Boston Scientific. Dr. Akao received lecture fees from Pfizer, Bristol-Myers Squibb, Boehringer Ingelheim, Bayer Healthcare and Daiichi-Sankyo. Dr. Kimura serves as an advisory board member for Abbott Vascular and Terumo Company. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. For this type of retrospective study formal consent is not required.
- 1.Cohen AT, Agnelli G, Anderson FA, Arcelus JI, Bergqvist D, Brecht JG, Greer IA, Heit JA, Hutchinson JL, Kakkar AK, Mottier D, Oger E, Samama MM, Spannagl M (2007) Venous thromboembolism (VTE) in Europe. The number of VTE events and associated morbidity and mortality. Thromb Haemost 98:756–764CrossRefGoogle Scholar
- 3.Konstantinides SV, Torbicki A, Agnelli G, Danchin N, Fitzmaurice D, Galie N, Gibbs JS, Huisman MV, Humbert M, Kucher N, Lang I, Lankeit M, Lekakis J, Maack C, Mayer E, Meneveau N, Perrier A, Pruszczyk P, Rasmussen LH, Schindler TH, Svitil P, Vonk Noordegraaf A, Zamorano JL, Zompatori M (2014) 2014 ESC guidelines on the diagnosis and management of acute pulmonary embolism. Eur Heart J 35:3033–3069CrossRefGoogle Scholar
- 4.Jaff MR, McMurtry MS, Archer SL, Cushman M, Goldenberg N, Goldhaber SZ, Jenkins JS, Kline JA, Michaels AD, Thistlethwaite P, Vedantham S, White RJ, Zierler BK (2011) Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic thromboembolic pulmonary hypertension: a scientific statement from the American Heart Association. Circulation 123:1788–1830CrossRefGoogle Scholar
- 6.Ando M, Fukuda I, Ito M, Kobayashi T, Masuda M, Miyahara Y, Nakanishi N, Niwa A, Ohgi S, Tajima H, Ishibashi H, Kanaoka Y, Nakamura M, Sakuma M, Satoh T, Tanabe N, Yamada N, Yamashita M, Kuriyama T, Matsubara J, Nakano T, Ozaki Y, Sakata R (2011) Guidelines for the diagnosis, treatment and prevention of pulmonary thromboembolism and deep vein thrombosis (JCS 2009). Circ J 75:1258–1281CrossRefGoogle Scholar
- 10.Yamashita Y, Morimoto T, Amano H, Takase T, Hiramori S, Kim K, Konishi T, Akao M, Kobayashi Y, Inoue T, Oi M, Izumi T, Takahashi K, Tada T, Chen PM, Murata K, Tsuyuki Y, Sakai H, Saga S, Sasa T, Sakamoto J, Yamada C, Kinoshita M, Togi K, Ikeda T, Ishii K, Kaneda K, Mabuchi H, Otani H, Takabayashi K, Takahashi M, Shiomi H, Makiyama T, Ono K, Kimura T (2018) Anticoagulation therapy for venous thromboembolism in the real world-from the COMMAND VTE Registry. Circ J 82:1262–1270CrossRefGoogle Scholar
- 12.World Health Organization (1968) Nutritional anaemias. Report of a WHO scientific group. World Health Organ Tech Rep Ser 405:5–37Google Scholar
- 15.Faller N, Limacher A, Mean M, Righini M, Aschwanden M, Beer JH, Frauchiger B, Osterwalder J, Kucher N, Lammle B, Cornuz J, Angelillo-Scherrer A, Matter CM, Husmann M, Banyai M, Staub D, Mazzolai L, Hugli O, Rodondi N, Aujesky D (2017) Predictors and causes of long-term mortality in elderly patients with acute venous thromboembolism: a prospective cohort study. Am J Med 130:198–206CrossRefGoogle Scholar
- 16.Kimura T, Morimoto T, Nakagawa Y, Tamura T, Kadota K, Yasumoto H, Nishikawa H, Hiasa Y, Muramatsu T, Meguro T, Inoue N, Honda H, Hayashi Y, Miyazaki S, Oshima S, Honda T, Shiode N, Namura M, Sone T, Nobuyoshi M, Kita T, Mitsudo K (2009) Antiplatelet therapy and stent thrombosis after sirolimus-eluting stent implantation. Circulation 119:987–995CrossRefGoogle Scholar
- 19.Bauersachs R, Berkowitz SD, Brenner B, Buller HR, Decousus H, Gallus AS, Lensing AW, Misselwitz F, Prins MH, Raskob GE, Segers A, Verhamme P, Wells P, Agnelli G, Bounameaux H, Cohen A, Davidson BL, Piovella F, Schellong S (2010) Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med 363:2499–2510CrossRefGoogle Scholar
- 22.Buller HR, Prins MH, Lensin AW, Decousus H, Jacobson BF, Minar E, Chlumsky J, Verhamme P, Wells P, Agnelli G, Cohen A, Berkowitz SD, Bounameaux H, Davidson BL, Misselwitz F, Gallus AS, Raskob GE, Schellong S, Segers A (2012) Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med 366:1287–1297CrossRefGoogle Scholar
- 24.Weitz JI, Lensing AWA, Prins MH, Bauersachs R, Beyer-Westendorf J, Bounameaux H, Brighton TA, Cohen AT, Davidson BL, Decousus H, Freitas MCS, Holberg G, Kakkar AK, Haskell L, van Bellen B, Pap AF, Berkowitz SD, Verhamme P, Wells PS, Prandoni P (2017) Rivaroxaban or aspirin for extended treatment of venous thromboembolism. N Engl J Med 376:1211–1222CrossRefGoogle Scholar
- 25.Westenbrink BD, Alings M, Connolly SJ, Eikelboom J, Ezekowitz MD, Oldgren J, Yang S, Pongue J, Yusuf S, Wallentin L, van Gilst WH (2015) Anemia predicts thromboembolic events, bleeding complications and mortality in patients with atrial fibrillation: insights from the RE-LY trial. J Thromb Haemost 13:699–707CrossRefGoogle Scholar