Prevalence of Risk of Thrombosis and of Bleeding and Antithrombotic Treatment in Patients with Heart Failure

Patients with heart failure (HF), both in sinus rhythm and not, have an increased risk of thromboembolic and bleeding events, both of which considerably contribute to their mortality, morbidity and long-term disabilities.1 However, data on the current clinical use of oral anticoagulants and antiplatelets in these patients are scant and, particularly in patients in sinus rhythm, the net benefit of these medications is still unproven. The risks of thromboembolism and haemorrhage in a ‘real-world’ population of HF patients with and without sinus rhythm are also unclear, as is the current use of antithrombotic therapy in relation to such risks.2 We, therefore, analysed data from a cohort of patients with HF enrolled in 211 Cardiology centres of 21 European and Mediterranean countries participating in a prospective, observational study conducted by the European Society of Cardiology EURObservational Research Programme (EORP) (see Appendix).3 This registry aimed to describe the diagnostic and therapeutic approaches used in these patients, who are representative of the generality of HF patients seen in daily practice. The study population consisted of 7448 patients with HF, of whom 5515 (74.0%) were in sinus rhythm and the remaining 1933 (26.0%) were with atrial fibrillation/flutter (AF/AFL). Decisions on prescribing antithrombotic therapy were made by the attending physicians on a patient-by-patient basis without a formal assessment of thromboembolic and bleeding risk scores. Thus, using data obtained from the database, we assessed the thromboembolic and bleeding risk profiles by retrospectively calculating for each patient the CHA2DS2-VASc and HAS-BLED scores.4, 5 We defined a high thromboembolic risk as CHA2DS2-VASc score > 2 and a high bleeding risk as HAS-BLED score ≥ 2. In terms of demographic and clinical characteristics, patients in sinus rhythm had a lower prevalence of each of the components of both CHA2DS2-VASc and HAS-BLED, with the exception of diabetes and vascular disease. In fact, within the sinus rhythm group, there were fewer elderly patients, females, and patients with hypertension than in the AF/AFL group. Furthermore, patients in sinus rhythm were less likely to have experienced stroke/transient ischaemic attack and to have renal or hepatic dysfunction. Conversely, patients with AF/AFL had more frequently a high thromboembolic risk and high bleeding risk than patients in sinus rhythm. Still, even amongst the 5515 patients in sinus rhythm, the risk of thromboembolism or of bleeding was high, in 4631 (84%) and 2245 (41%) patients, respectively. High risk of both thromboembolism and bleeding coexisted in 2237 patients (41%). As shown in Figure 1, only 6% of patients with AF/AFL and 26% of those in sinus rhythm were not receiving any antithrombotic medication. As expected, the prescription of oral anticoagulants was more common in AF/AFL patients, while antiplatelet agents prevailed in patients who were in sinus rhythm. As many as 57% of the latter group were being treated with antiplatelet agents, although only a fraction had an ischaemic aetiology and a clear indication for this therapy. A total of 1377 (25%) received oral anticoagulants, either alone (17%) or in combination with antiplatelet agents (8%) (Figure 1). Table 1 shows the distribution of antithrombotic treatments according to the CHA2DS2-VASc and HAS-BLED risk scores, in sinus rhythm and AF/AFL patients. A similar proportion of patients in sinus rhythm were prescribed oral anticoagulants, regardless of their thromboembolic or bleeding risk. In fact, the use of oral anticoagulants (either alone or in association with antiplatelets) was not greater in patients with a high thromboembolic risk (CHA2DS2-VASc ≥2), nor was it lower in those with a high bleeding risk (HAS-BLED ≥2). As expected, the proportion of patients treated with oral anticoagulants was far higher in the AF/AFL group (Table 1) than in the sinus rhythm group, but again it appeared not to be affected by either the CHA2DS2-VASc or HAS-BLED score. The predictive value of CHA2DS2-VASc and HAS-BLED scores was originally validated only in patients with AF/AFL. However, more recent data indicate that these risk scores can be used to predict thromboembolic and haemorrhagic events also in HF patients in sinus rhythm,4, 6 suggesting that the combined scores may be useful as well in this patient category for establishing a personalized thromboprophylaxis regimen. The present study shows that the current use of antithrombotic therapy is frequent in all groups of patients with HF and appears not to be related to these scores. Most patients with AF/AFL were treated with anticoagulants regardless of their bleeding risk, suggesting that, when high thromboembolic and bleeding risks coexist, the former tends to prevail and has a greater impact on physicians' decision-making. It is worth noting that as many as 17% of AF/AFL patients received a combination of anticoagulant and antiplatelet agents despite the fact that this regimen may increase the risk of bleeding events and is not recommended by current guidelines in patients with AF/AFL and stable coronary artery disease.7 For patients in sinus rhythm, there are no clear guideline recommendations on how to manage thromboembolic therapy8 and, hence, the treatment decision is even less dependent on risk score criteria. It seems, rather, to be based on a case-by-case evaluation in which the clinician takes into account many other factors including age, aetiology of HF, severity of functional impairment, cardiac remodelling including the left atrial dimension, and the risk of drug non-adherence. The effectiveness of anticoagulation and the international normalized ratio variability, information not available in the registry, may also have influenced the clinicians' therapeutic decision. Our results suggest that, in the ‘real world’ of HF patients, both those in sinus rhythm and those with AF/AFL, a high risk of thromboembolism and bleeding often coexists and most patients are treated with antithrombotic medications regardless of their bleeding risk. In the decision making whether or not to prescribe antithrombotic medications (and what type and dosage) in an individual patient, clinicians should be guided by an assessment of these competing risks and carefully weigh up the advantages vs. disadvantages of different antithrombotic treatments. This would require the application of more refined thromboembolic and bleeding risk scores and the development of well calibrated and prospectively validated prediction models. EORP Oversight Committee, Registry Executive and Steering Committees of the EURObservational Research Programme (EORP). Data collection was conducted by the EORP department from the ESC by Emanuela Fiorucci as Project Officer, Gerard Gracia and Maryna Andarala as Data Managers, and Cécile Laroche as Statistician. Overall activities were coordinated and supervised by Doctor Aldo P. Maggioni (EORP Scientific Coordinator). Since the start of EORP, the following companies have supported the programme: Abbott Vascular Int. (2011–2021), Amgen Cardiovascular (2009–2018), AstraZeneca (2014–2021), Bayer AG (2009–2018), Boehringer Ingelheim (2009–2019), Boston Scientific (2009–2012), The Bristol Myers Squibb and Pfizer Alliance (2011–2019), The Alliance Daiichi Sankyo Europe GmbH and Eli Lilly and Company (2011–2017), Daiichi Sankyo Europe (2012–2020), Edwards (2016–2019), Gedeon Richter Plc. (2014–2017), Menarini Int. Op. (2009–2012), MSD–Merck & Co. (2011–2014), Novartis Pharma AG (2014–2020), ResMed (2014–2016), Sanofi (2009–2011), Servier (2009–2021), Vifor (2019–2022). Conflict of interest: L.T. reports personal fees from Servier and CVIE Therapeutics, outside the submitted work. A.M. reports personal fees from Cardiorentis, during the conduct of the study; reports personal fees from Novartis, Orion, Roche, Servier, Cardiorentis, Zs Pharma and Neuro Tronik, grants and personal fees from Adrenomed, Abbott and Sphyngotec, grants from MyCartis and Critical diagnostics, outside the submitted work. A.P.M. reports personal fees from Bayer, Cardiorentis and Novartis, outside the submitted work . J.G.C. reports grants from Servier, during the conduct of the study. M.C.G.L. reports grants and personal fees from Novartis, personal fees from Abbott, grants and other from Astra Zeneka, grants from Vifor, Servier and Medtronic, outside the submitted work. S.D.A. reports personal fees from Bayer, Vifor, Boehringer Ingelheim, Servier and Novartis, outside the submitted work. G.F. reports he was Committee member of trials and registries sponsored from Bayer, Novartis, Servier, Vifor, outside the submitted work. All other authors have nothing to disclose. EORP Oversight Committee: Christopher Peter Gale, Chair, GB, Branko Beleslin, RS, Andrzej Budaj, PL, Ovidiu Chioncel, RO, Nikolaos Dagres, DE, Nicolas Danchin, FR, David Erlinge, SE, Jonathan Emberson, GB, Michael Glikson, IL, Alastair Gray, GB, Meral Kayikcioglu, TR, Aldo Maggioni, IT, Klaudia Vivien Nagy, HU, Aleksandr Nedoshivin, RU, Anna-Sonia Petronio, IT, Jolien Roos-Hesselink, NL, Lars Wallentin, SE, Uwe Zeymer, DE. Executive Committee: M. Crespo-Leiro, S. Anker, A. Mebazaa, A. Coats, G. Filippatos, R. Ferrari, A.P. Maggioni, M.F. Piepoli Steering Committee (National Coordinators): A. Goda, AL; M. Diez, AR; A. Fernandez, AR; F. Fruhwald, AT; E. Fazlibegovic, BA; P. Gatzov, BG; A. Kurlianskaya, BY; R. Hullin, CH; T. Christodoulides, CY; J. Hradec, CZ; O. Wendelboe Nielsen, DK; R. Nedjar, DZ; T. Uuetoa, EE; M. Hassanein, EG; J. F. Delgado Jimenez, ES; V-P. Harjola, FI; D. Logeart, FR; V. Chumburidze, GE; D. Tousoulis, GR; D. Milicic, HR; B. Merkely, HU; E. O'Donoghue, IE; O. Amir, IL; A. Shotan, IL; D. Shafie, IR; M. Metra, IT; A. Matsumori, JP; E. Mirrakhimov, KG; A. Kavoliuniene, LT; A. Erglis, LV; E. Vataman, MD; M. Otljanska, MK; E. Srbinovska Kostovska, MK; D. Cassar DeMarco, MT; J. Drozdz, PL; C. Fonseca, PT; O. Chioncel, RO; M. Dekleva, RS; E. Shkolnik, RU; U. Dahlstrom, SE; M. Lainscak, SI; E. Goncalvesova, SK; A. Temizhan, TR; V. Estrago, UY; G. Bajraktari, XK. Austria Braunau: J. Auer; Graz: K. Ablasser, F. Fruhwald, T. Dolze, K. Brandner; Innsbruck: S. Gstrein, G. Poelzl; Sankt Poelten: D. Moertl; Vienna: S. Reiter, A. Podczeck-Schweighofer; Bosnia Herzegovina Mostar: A. Muslibegovic, M. Vasilj, E. Fazlibegovic, M. Cesko, D. Zelenika, B. Palic, D. Pravdic, D. Cuk; Bulgaria Sofia: K. Vitlianova, T. Katova, T. Velikov, T. Kurteva, P. Gatzov; Vidin: D. 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