Advertisement

Association of intravenous heparin administration with in-hospital clinical outcomes among hospitalized patients with acute heart failure

Published:November 11, 2022DOI:https://doi.org/10.1016/j.ijcard.2022.11.018

      Highlights

      • Heparin was not associated with a lower risk of death and ischemic stroke in AHF.
      • Heparin was associated with a higher risk of major bleeding in AHF.
      • These results were consistent across major subgroups in AHF.

      Abstract

      Backgrounds

      Patients with acute heart failure (AHF) possess a high risk for thromboembolism, and thromboembolism prophylaxis using heparin has been recommended by the guidelines.

      Methods

      Among 4056 patients enrolled in the KCHF Registry, the current study population consisted of 2525 patients after excluding patients with acute coronary syndrome and oral anticoagulants on admission and those with mechanical circulatory supports. There were 789 patients (31%) with heparin administration within 24 h after admission, and 1736 patients (69%) without.

      Results

      The baseline characteristics included mean age: 78 ± 13 years, New York Heart Association class IV: 51%, ischemic etiology: 30%, atrial fibrillation: 31% and mean left ventricular ejection fraction: 45%. During median hospitalization length of 16 days, 161 patients had all-cause death, 34 patients developed ischemic stroke, and 48 patients developed major bleeding. Multivariable logistic regression analyses demonstrated that heparin administration compared with no heparin administration was not associated with a lower risk for all-cause death (OR: 1.39, 95%CI: 0.90–2.15; P = 0.14), nor for ischemic stroke (OR: 1.14, 95%CI: 0.53–2.43; P = 0.74), but was associated with a higher risk for major bleeding (OR: 2.88, 95%CI: 1.54–5.41; P < 0.001).

      Conclusions

      In patients with AHF, heparin administration within 24 h after admission was not associated with a lower risk of all-cause death and ischemic stroke, but was associated with a higher risk of major bleeding during hospitalization. Our study raises questions about the routine use of heparin for thromboembolism prophylaxis in hospitalized patients with AHF. Further studies are warranted to address the utility of anticoagulant therapy in these patients.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to International Journal of Cardiology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Iguchi M.
        • Kato T.
        • Yaku H.
        • Morimoto T.
        • Inuzuka Y.
        • Tamaki Y.
        • et al.
        Ischemic stroke in acute decompensated heart failure: from the KCHF registry.
        J. Am. Heart Assoc. 2021; 10e022525
        • Hamatani Y.
        • Iguchi M.
        • Nakamura M.
        • Ohtani R.
        • Yamashita Y.
        • Takagi D.
        • et al.
        Incidence and predictors of ischemic stroke during hospitalization for congestive heart failure.
        Heart Vessel. 2016; 31: 1154-1161
        • Wolf P.A.
        • Abbott R.D.
        • Kannel W.B.
        Atrial fibrillation as an independent risk factor for stroke: the Framingham study.
        Stroke. 1991; 22: 983-988
        • Adelborg K.
        • Szépligeti S.
        • Sundbøll J.
        • Horváth-Puhó E.
        • Henderson V.W.
        • Ording A.
        • et al.
        Risk of stroke in patients with heart failure: a population-based 30-year cohort study.
        Stroke. 2017; 48: 1161-1168
        • Lip G.Y.
        • Gibbs C.R.
        Does heart failure confer a hypercoagulable state? Virchow’s triad revisited.
        J. Am. Coll. Cardiol. 1999; 33: 1424-1426
        • Hindricks G.
        • Potpara T.
        • Dagres N.
        • Arbelo E.
        • Bax J.J.
        • Blomstrom-Lundqvist C.
        • et al.
        ESC guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS): the task force for the diagnosis and management of atrial fibrillation of the European Society of Cardiology (ESC) developed with the special contribution of the European heart rhythm association (EHRA) of the ESC.
        Eur. Heart J. 2021; 42: 373-498
        • Lin A.Y.
        • Dinatolo E.
        • Metra M.
        • Sbolli M.
        • Dasseni N.
        • Butler J.
        • et al.
        Thromboembolism in heart failure patients in sinus rhythm: epidemiology, pathophysiology, clinical trials, and future direction.
        JACC Heart Fail. 2021; 9: 243-253
        • Schafer A.
        • Flierl U.
        • Bauersachs J.
        Anticoagulants for stroke prevention in heart failure with reduced ejection fraction.
        Clin. Res. Cardiol. 2022; 111: 1-13
        • Rivas A.
        • Lauw M.N.
        • Schnabel R.B.
        • Crowther M.
        • Van Spall H.G.C.
        Stroke and thromboembolism in patients with heart failure and sinus rhythm: a matter of risk stratification?.
        Thromb. Haemost. 2022; 122: 871-878
        • Chung I.
        • Choudhury A.
        • Lip G.Y.
        Platelet activation in acute, decompensated congestive heart failure.
        Thromb. Res. 2007; 120: 709-713
        • Colombo P.C.
        • Onat D.
        • Sabbah H.N.
        Acute heart failure as “acute endothelitis”--Interaction of fluid overload and endothelial dysfunction.
        Eur. J. Heart Fail. 2008; 10: 170-175
        • Hamatani Y.
        • Nagai T.
        • Nakai M.
        • Nishimura K.
        • Honda Y.
        • Nakano H.
        • et al.
        Elevated plasma D-dimer level is associated with short-term risk of ischemic stroke in patients with acute heart failure.
        Stroke. 2018; 49: 1737-1740
        • Iguchi M.
        • Tezuka Y.
        • Ogawa H.
        • Hamatani Y.
        • Takagi D.
        • An Y.
        • et al.
        Incidence and risk factors of stroke or systemic embolism in patients with atrial fibrillation and heart failure - the Fushimi AF registry.
        Circ. J. 2018; 82: 1327-1335
        • McDonagh T.A.
        • Metra M.
        • Adamo M.
        • Gardner R.S.
        • Baumbach A.
        • Bohm M.
        • et al.
        ESC guidelines for the diagnosis and treatment of acute and chronic heart failure.
        Eur. Heart J. 2021; 42: 3599-3726
        • Nakano H.
        • Hamatani Y.
        • Nagai T.
        • Nakai M.
        • Nishimura K.
        • Sumita Y.
        • et al.
        Current practice and effects of intravenous anticoagulant therapy in hospitalized acute heart failure patients with sinus rhythm.
        Sci. Rep. 2021; 11: 1202
        • Yamamoto E.
        • Kato T.
        • Ozasa N.
        • Yaku H.
        • Inuzuka Y.
        • Tamaki Y.
        • et al.
        Kyoto congestive heart failure (KCHF) study: rationale and design.
        ESC Heart Fail. 2017; 4: 216-223
        • Yaku H.
        • Ozasa N.
        • Morimoto T.
        • Inuzuka Y.
        • Tamaki Y.
        • Yamamoto E.
        • et al.
        Demographics, management, and in-hospital outcome of hospitalized acute heart failure syndrome patients in contemporary real clinical practice in Japan - observations from the prospective, multicenter Kyoto congestive heart failure (KCHF) registry.
        Circ. J. 2018; 82: 2811-2819
        • Nutritional anaemias
        Report of a WHO scientific group.
        World Health Organ. Tech. Rep. Ser. 1968; 405: 5-37
      1. An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction.
        N. Engl. J. Med. 1993; 329: 673-682
        • Tamaki Y.
        • Yaku H.
        • Morimoto T.
        • Inuzuka Y.
        • Ozasa N.
        • Yamamoto E.
        • et al.
        Lower in-hospital mortality with Beta-blocker use at admission in patients with acute decompensated heart failure.
        J. Am. Heart Assoc. 2021; 10e020012
        • Yaku H.
        • Kato T.
        • Morimoto T.
        • Inuzuka Y.
        • Tamaki Y.
        • Ozasa N.
        • et al.
        Association of mineralocorticoid receptor antagonist use with all-cause mortality and hospital readmission in older adults with acute decompensated heart failure.
        JAMA Netw. Open. 2019; 2e195892
        • Homma S.
        • Thompson J.L.
        • Pullicino P.M.
        • Levin B.
        • Freudenberger R.S.
        • Teerlink J.R.
        • et al.
        Warfarin and aspirin in patients with heart failure and sinus rhythm.
        N. Engl. J. Med. 2012; 366: 1859-1869
        • Zannad F.
        • Anker S.D.
        • Byra W.M.
        • Cleland J.G.F.
        • Fu M.
        • Gheorghiade M.
        • et al.
        Rivaroxaban in patients with heart failure, sinus rhythm, and coronary disease.
        N. Engl. J. Med. 2018; 379: 1332-1342
        • Zhang J.
        • Shantsila E.
        • Lip G.Y.H.
        Heart failure with sinus rhythm: does anticoagulation reduce stroke at all?.
        J. Card. Fail. 2021; 27: 865-868
        • Kociol R.D.
        • Hammill B.G.
        • Hernandez A.F.
        • Klaskala W.
        • Mills R.M.
        • Curtis L.H.
        • et al.
        Pharmacologic prophylaxis for venous thromboembolism and 30-day outcomes among older patients hospitalized with heart failure: an analysis from the ADHERE national registry linked to Medicare claims.
        Clin. Cardiol. 2011; 34: 682-688
        • Jois-Bilowich P.
        • Michota F.
        • Bartholomew J.R.
        • Glauser J.
        • Diercks D.
        • Weber J.
        • et al.
        Venous thromboembolism prophylaxis in hospitalized heart failure patients.
        J. Card. Fail. 2008; 14: 127-132
        • Douketis J.D.
        • Spyropoulos A.C.
        • Kaatz S.
        • Becker R.C.
        • Caprini J.A.
        • Dunn A.S.
        • et al.
        Perioperative bridging anticoagulation in patients with atrial fibrillation.
        N. Engl. J. Med. 2015; 373: 823-833
        • Urban P.
        • Mehran R.
        • Colleran R.
        • Angiolillo D.J.
        • Byrne R.A.
        • Capodanno D.
        • et al.
        Defining high bleeding risk in patients undergoing percutaneous coronary intervention.
        Circulation. 2019; 140: 240-261
        • O’Brien E.C.
        • Simon D.N.
        • Thomas L.E.
        • Hylek E.M.
        • Gersh B.J.
        • Ansell J.E.
        • et al.
        The ORBIT bleeding score: a simple bedside score to assess bleeding risk in atrial fibrillation.
        Eur. Heart J. 2015; 36: 3258-3264
        • Fang M.C.
        • Go A.S.
        • Chang Y.
        • Borowsky L.H.
        • Pomernacki N.K.
        • Udaltsova N.
        • et al.
        A new risk scheme to predict warfarin-associated hemorrhage: the ATRIA (anticoagulation and risk factors in atrial fibrillation) study.
        J. Am. Coll. Cardiol. 2011; 58: 395-401
        • Li W.
        • Seo J.
        • Kokkinidis D.G.
        • Palaiodimos L.
        • Nagraj S.
        • Korompoki E.
        • et al.
        Efficacy and safety of vitamin-K antagonists and direct oral anticoagulants for stroke prevention in patients with heart failure and sinus rhythm: An updated systematic review and meta-analysis of randomized clinical trials.
        Int. J. Stroke. 2022; (in press)
        • Bonnet-Zamponi D.
        • Aumont M.C.
        • Comets E.
        • Bruhat C.
        • Chauveheid M.P.
        • Duval X.
        • et al.
        Heparin bridging therapy and bleeding events in octogenarian inpatients with atrial fibrillation starting anticoagulation: results of an ancillary study.
        J. Am. Geriatr. Soc. 2011; 59: 2174-2178
        • Saeed O.
        • Zhang S.
        • Patel S.R.
        • Jorde U.P.
        • Garcia M.J.
        • Bulcha N.
        • et al.
        Oral anticoagulation and adverse outcomes after ischemic stroke in heart failure patients without atrial fibrillation.
        J. Card. Fail. 2021; 27: 857-864
        • Hernandez A.F.
        • Hammill B.G.
        • Kociol R.D.
        • Eapen Z.J.
        • Fonarow G.C.
        • Klaskala W.
        • et al.
        Clinical effectiveness of anticoagulation therapy among older patients with heart failure and without atrial fibrillation: findings from the ADHERE registry linked to Medicare claims.
        J. Card. Fail. 2013; 19: 401-407
        • Mehra M.R.
        • Vaduganathan M.
        • Fu M.
        • Ferreira J.P.
        • Anker S.D.
        • Cleland J.G.F.
        • et al.
        A comprehensive analysis of the effects of rivaroxaban on stroke or transient ischaemic attack in patients with heart failure, coronary artery disease, and sinus rhythm: the COMMANDER HF trial.
        Eur. Heart J. 2019; 40: 3593-3602
        • Greenberg B.
        • Neaton J.D.
        • Anker S.D.
        • Byra W.M.
        • Cleland J.G.F.
        • Deng H.
        • et al.
        Association of Rivaroxaban with Thromboembolic Events in patients with heart failure, coronary disease, and sinus rhythm: a post hoc analysis of the COMMANDER HF trial.
        JAMA Cardiol. 2019; 4: 515-523
        • Tsutsui H.
        • Isobe M.
        • Ito H.
        • Ito H.
        • Okumura K.
        • Ono M.
        • et al.
        JCS 2017/JHFS 2017 Guideline on diagnosis and treatment of acute and chronic heart failure- digest version.
        Circ. J. 2019; 83: 2084-2184