Antithrombotic Medication and Major Complications After Mechanical Aortic Valve Replacement

The risk for major bleeding after aortic valve replacement was 5-fold compared with major stroke.Early bleeding was associated with the use of triple antithrombotic medication.During the long-term follow-up, 1/6 of the major bleeding events were intracranial hemorrhages.A total of 1/10 of the patients died within 30 days after their first major bleeding event. Patients with mechanical aortic valve replacement (AVR) require lifelong vitamin K antagonist (VKA) therapy for stroke and systemic embolism prevention. However, VKA treatment predisposes patients to various types of bleeding. In the present study, we sought to assess the success of antithrombotic therapy and the occurrence and timing of strokes and bleeding events after mechanical AVR. A total of 308 patients who underwent isolated mechanical AVR were included in the study, and follow-up data were completed for 306 patients (99.4%). The median follow-up time was 7.3 (interquartile range 4.2 to 10.9) years. The risk for major bleeding was 5-fold compared with major stroke (6.2% vs 1.3% and 20.9% vs 4.0%, respectively; events rates 3.1 vs 0.5 per 100 patient-years, respectively) at 30-day and long-term follow-up, indicating good efficacy but inadequate safety of stroke prevention. At the time of the early postoperative major bleeding, the international normalized ratio was under the therapeutic range in 73.7% of the patients. However, most patients were on triple antithrombotic treatment consisting of subcutaneous enoxaparin, VKA, and a tail effect of discontinued aspirin. During the long-term follow-up, the most common site of bleeding was gastrointestinal (41.7%), followed by genitourinary bleeding (23.3%) and intracranial hemorrhage (18.3%). Furthermore, mortality was relatively high, with a 10-year survival estimate of 78.3%. In conclusion, although ischemic stroke is a well-identified adverse event after mechanical AVR, it seems that major bleeding is a frequent clinically relevant complication during perioperative and long-term follow-up. This finding underscores the recognition and management of modifiable bleeding risk factors. Patients with mechanical aortic valve replacement (AVR) require lifelong vitamin K antagonist (VKA) therapy for stroke and systemic embolism prevention. However, VKA treatment predisposes patients to various types of bleeding. In the present study, we sought to assess the success of antithrombotic therapy and the occurrence and timing of strokes and bleeding events after mechanical AVR. A total of 308 patients who underwent isolated mechanical AVR were included in the study, and follow-up data were completed for 306 patients (99.4%). The median follow-up time was 7.3 (interquartile range 4.2 to 10.9) years. The risk for major bleeding was 5-fold compared with major stroke (6.2% vs 1.3% and 20.9% vs 4.0%, respectively; events rates 3.1 vs 0.5 per 100 patient-years, respectively) at 30-day and long-term follow-up, indicating good efficacy but inadequate safety of stroke prevention. At the time of the early postoperative major bleeding, the international normalized ratio was under the therapeutic range in 73.7% of the patients. However, most patients were on triple antithrombotic treatment consisting of subcutaneous enoxaparin, VKA, and a tail effect of discontinued aspirin. During the long-term follow-up, the most common site of bleeding was gastrointestinal (41.7%), followed by genitourinary bleeding (23.3%) and intracranial hemorrhage (18.3%). Furthermore, mortality was relatively high, with a 10-year survival estimate of 78.3%. In conclusion, although ischemic stroke is a well-identified adverse event after mechanical AVR, it seems that major bleeding is a frequent clinically relevant complication during perioperative and long-term follow-up. This finding underscores the recognition and management of modifiable bleeding risk factors. The latest international guidelines for the management of valvular heart disease (VHD) suggest that in patients aged under 60 years requiring aortic valve replacement (AVR), mechanical AVR should be considered instead of biologic AVR.1Vahanian A Beyersdorf F Praz F Milojevic M Baldus S Bauersachs J Capodanno D Conradi L Bonis M De Paulis R De Delgado V Freemantle N Gilard M Haugaa KH Jeppsson A Jüni P Pierard L Prendergast BD Sádaba JR Tribouilloy C Wojakowski W ESC/EACTS Guidelines for the management of valvular heart disease: developed by the Task Force for the management of valvular heart disease of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS).Rev Esp Cardiol (Engl Ed). 2022; 75: 524PubMed Google Scholar,2Otto CM Nishimura RA Bonow RO Carabello BA Erwin JP Gentile F Jneid H Krieger EV Mack M McLeod C O'Gara PT Rigolin VH Sundt TM Thompson A Toly C 2020 ACC/AHA guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association joint committee on clinical practice guidelines.Circulation. 2021; 143: e35-e71PubMed Google Scholar Although mechanical valves usually offer a lifelong duration of the prosthesis, they come with increased risks of blood clotting, thus requiring permanent vitamin K antagonist (VKA) therapy guided by the international normalized ratio (INR). Because of the potential disabling and even fatal thromboembolic complications ensuing from inadequate anticoagulation, the focus of VKA therapy has been on preventing thromboembolic events. However, the VKA therapy also increases the risk of major bleeding events. Although ischemic stroke is a well-identified adverse event after mechanical AVR, many studies have shown that during long-term follow-up, the risk of major bleeding could be even higher than that of major stroke.3Torella M Torella D Chiodini P Franciulli M Romano G Santo L De Feo M De Amarelli C Sasso FC Salvatore T Ellison GM Indolfi C Cotrufo M Nappi G LOWERing the INtensity of oral anticoagulant therapy in patients with bileaflet mechanical aortic valve replacement: results from the “lOWERING-IT” Trial.Am Heart J. 2010; 160: 171-178Crossref PubMed Scopus (92) Google Scholar, 4Labaf A Svensson PJ Renlund H Jeppsson A Själander A. Incidence and risk factors for thromboembolism and major bleeding in patients with mechanical valve prosthesis: A nationwide population-based study.Am Heart J. 2016; 181: 1-9Crossref PubMed Scopus (16) Google Scholar, 5Puskas JD Gerdisch M Nichols D Fermin L Rhenman B Kapoor D Copeland J Quinn R Hughes GC Azar H McGrath M Wait M Kong B Martin T Douville EC Meyer S Ye J Jamieson WRE Landvater L Hagberg R Trotter T Armitage J Askew J Accola K Levy P Duncan D Yanagawa B Ely J Graeve A Puskas J Gerdisch M Nichols D Graeve A PROACT InvestigatorsAnticoagulation and antiplatelet strategies after On-X mechanical aortic valve replacement.J Am Coll Cardiol. 2018; 71: 2717-2726Crossref PubMed Scopus (83) Google Scholar, 6Ram E Amunts S Zuroff E Peled Y Kogan A Raanani E Sternik L. Outcomes of isolated surgical aortic valve replacement in the era of transcatheter aortic valve implantation.J Card Surg. 2020; 35: 1452-1457Crossref PubMed Scopus (9) Google Scholar, 7Kytö V Sipilä J Ahtela E Rautava P Gunn J. Mechanical versus biologic prostheses for surgical aortic valve replacement in patients aged 50 to 70.Ann Thorac Surg. 2020; 110: 102-110Abstract Full Text Full Text PDF PubMed Scopus (23) Google Scholar, 8Vogt F Santarpino G Fujita B Frerker C Bauer T Beckmann A Bekeredjian R Bleiziffer S Möllmann H Walther T Beyersdorf F Hamm C Böning A Baldus S Ensminger S Fischlein T Eckner D GARY Executive BoardSurgical aortic valve replacement in patients aged 50–69 years—insights from the German Aortic Valve Registry (GARY).Eur J Cardiothorac Surg. 2022; 62: 1-8Crossref Scopus (5) Google Scholar, 9Chiang YP Chikwe J Moskowitz AJ Itagaki S Adams DH Egorova NN. Survival and long-term outcomes following bioprosthetic vs mechanical aortic valve replacement in patients aged 50 to 69 years.JAMA. 2014; 312: 1323-1329Crossref PubMed Scopus (217) Google Scholar, 10Bouhout I Stevens LM Mazine A Poirier N R P outcomes after isolated mechanical aortic valve replacement in Thorac Surg. 2014; Full Text Full Text PDF PubMed Scopus Google Scholar, P M B Mechanical biologic prostheses for and J PubMed Scopus Google Scholar, P Mack M Svensson AJ K R complications after surgical aortic valve replacement compared with transcatheter aortic valve replacement: from the of Aortic transcatheter Am Coll Cardiol. 2014; PubMed Scopus Google Scholar Although the risk of bleeding events is to with in patients on VKA W D L S P D J R S M vitamin K versus to in patients a PubMed Scopus Google Scholar is and range and bleeding events associated in patients with mechanical aortic A Svensson PJ Renlund H Jeppsson A Själander A. Incidence and risk factors for thromboembolism and major bleeding in patients with mechanical valve prosthesis: A nationwide population-based study.Am Heart J. 2016; 181: 1-9Crossref PubMed Scopus (16) Google JD Gerdisch M Nichols D Fermin L Rhenman B Kapoor D Copeland J Quinn R Hughes GC Azar H McGrath M Wait M Kong B Martin T Douville EC Meyer S Ye J Jamieson WRE Landvater L Hagberg R Trotter T Armitage J Askew J Accola K Levy P Duncan D Yanagawa B Ely J Graeve A Puskas J Gerdisch M Nichols D Graeve A PROACT InvestigatorsAnticoagulation and antiplatelet strategies after On-X mechanical aortic valve replacement.J Am Coll Cardiol. 2018; 71: 2717-2726Crossref PubMed Scopus (83) Google Scholar the risk of early perioperative complications after mechanical AVR the success of the early treatment is This to assess the antithrombotic treatment and the success of VKA treatment at the time of major and complications after mechanical AVR, during the 30-day perioperative and long-term follow-up. 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The of were disease and aortic valve Patients who major bleeding events a for survival than although it to The of the present the the risk for major bleeding is 5-fold compared with major stroke during the early postoperative and long-term postoperative bleeding with the use of triple antithrombotic consisting of subcutaneous enoxaparin, oral VKA, and the tail of discontinued and the mortality is high, patients to the time of biologic valve is to of bioprosthetic heart Am Heart 2020; PubMed Scopus Google Scholar This a of major complications during the 30-day perioperative after isolated AVR During the perioperative major bleeding was common than early major and the bleeding were during triple antithrombotic therapy consisting of oral VKA, and the tail effect of to aspirin. 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Outcomes of isolated surgical aortic valve replacement in the era of transcatheter aortic valve implantation.J Card Surg. 2020; 35: 1452-1457Crossref PubMed Scopus (9) Google I Stevens LM Mazine A Poirier N R P outcomes after isolated mechanical aortic valve replacement in Thorac Surg. 2014; Full Text Full Text PDF PubMed Scopus Google Scholar In the of I Stevens LM Mazine A Poirier N R P outcomes after isolated mechanical aortic valve replacement in Thorac Surg. 2014; Full Text Full Text PDF PubMed Scopus Google Scholar of the patients mechanical AVR early major bleeding and early major in the of E Amunts S Zuroff E Peled Y Kogan A Raanani E Sternik L. Outcomes of isolated surgical aortic valve replacement in the era of transcatheter aortic valve implantation.J Card Surg. 2020; 35: 1452-1457Crossref PubMed Scopus (9) Google Scholar mechanical and biologic surgical AVR, of the patients early major bleeding, but early stroke were In to and the the perioperative stroke was higher than perioperative bleeding the of major bleeding was In the of ischemic stroke was within 30 postoperative V Sipilä J Ahtela E Rautava P Gunn J. Mechanical versus biologic prostheses for surgical aortic valve replacement in patients aged 50 to 70.Ann Thorac Surg. 2020; 110: 102-110Abstract Full Text Full Text PDF PubMed Scopus (23) Google Scholar During the long-term follow-up, of the patients who underwent mechanical AVR a major In a major stroke were during the follow-up The ratio of major bleeding to major strokes was in patients with relatively of to The most common for major bleeding was gastrointestinal bleeding, with V Sipilä J Ahtela E Rautava P Gunn J. 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Survival and long-term outcomes following bioprosthetic vs mechanical aortic valve replacement in patients aged 50 to 69 years.JAMA. 2014; 312: 1323-1329Crossref PubMed Scopus (217) Google Scholar, 10Bouhout I Stevens LM Mazine A Poirier N R P outcomes after isolated mechanical aortic valve replacement in Thorac Surg. 2014; Full Text Full Text PDF PubMed Scopus Google Scholar, P M B Mechanical biologic prostheses for and J PubMed Scopus Google Scholar mechanical AVR with follow-up than in the present with studies by YP Chikwe J Moskowitz AJ Itagaki S Adams DH Egorova NN. Survival and long-term outcomes following bioprosthetic vs mechanical aortic valve replacement in patients aged 50 to 69 years.JAMA. 2014; 312: 1323-1329Crossref PubMed Scopus (217) Google Scholar and I Stevens LM Mazine A Poirier N R P outcomes after isolated mechanical aortic valve replacement in Thorac Surg. 2014; Full Text Full Text PDF PubMed Scopus Google Scholar the estimate for major bleeding was higher in the present to vs This is most by the of follow-up data in the present in the first to the of the In in the of P M B Mechanical biologic prostheses for and J PubMed Scopus Google Scholar the estimate for major bleeding was to to the in the present study, the rates of major bleeding events were higher than of major although the of was to the of major strokes in the present study, higher than strokes in the clinical of oral the present ratio seems Although ischemic stroke is a complication after mechanical AVR, major bleeding to be a clinically relevant complication during long-term follow-up. results a should patients biologic AVR at a to the bleeding complications to data the of antithrombotic during the early postoperative the relatively of early perioperative bleeding from a during the tail effect of a of of at to days the should be Patients mechanical AVR require lifelong treatment with VKA guided by the has been shown that in patients VKA, bleeding increases with W D L S P D J R S M vitamin K versus to in patients a PubMed Scopus Google Scholar The international guidelines for a median than a therapeutic A Beyersdorf F Praz F Milojevic M Baldus S Bauersachs J Capodanno D Conradi L Bonis M De Paulis R De Delgado V Freemantle N Gilard M Haugaa KH Jeppsson A Jüni P Pierard L Prendergast BD Sádaba JR Tribouilloy C Wojakowski W ESC/EACTS Guidelines for the management of valvular heart disease: developed by the Task Force for the management of valvular heart disease of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS).Rev Esp Cardiol (Engl Ed). 2022; 75: 524PubMed Google Scholar,2Otto CM Nishimura RA Bonow RO Carabello BA Erwin JP Gentile F Jneid H Krieger EV Mack M McLeod C O'Gara PT Rigolin VH Sundt TM Thompson A Toly C 2020 ACC/AHA guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association joint committee on clinical practice guidelines.Circulation. 2021; 143: e35-e71PubMed Google Scholar on and risk the median with mechanical aortic valve from to studies therapeutic range have a to be associated with bleeding the risk of thromboembolic events is A Svensson PJ Renlund H Jeppsson A Själander A. Incidence and risk factors for thromboembolism and major bleeding in patients with mechanical valve prosthesis: A nationwide population-based study.Am Heart J. 2016; 181: 1-9Crossref PubMed Scopus (16) Google JD Gerdisch M Nichols D Fermin L Rhenman B Kapoor D Copeland J Quinn R Hughes GC Azar H McGrath M Wait M Kong B Martin T Douville EC Meyer S Ye J Jamieson WRE Landvater L Hagberg R Trotter T Armitage J Askew J Accola K Levy P Duncan D Yanagawa B Ely J Graeve A Puskas J Gerdisch M Nichols D Graeve A PROACT InvestigatorsAnticoagulation and antiplatelet strategies after On-X mechanical aortic valve replacement.J Am Coll Cardiol. 2018; 71: 2717-2726Crossref PubMed Scopus (83) Google M The of mechanical valves in the aortic in the era of and and focus on the On-X 2022; PubMed Scopus (5) Google Scholar the present that of the bleeding events during the long-term follow-up is higher than the therapeutic range In most of stroke events is in the therapeutic it seems that a of the adverse events could be by the VKA the bleeding it that the VKA treatment is the for increased bleeding risk in patients with mechanical aortic This of major bleeding. outcomes for patients who and after have also been in VH Puskas JD The of on and and long-term mortality in valvular Thorac Surg. Full Text Full Text PDF PubMed Scopus Google S A D R R De F M R K A M A G F M J J F N A P T G of on outcomes in patients transcatheter aortic valve 2021; Full Text Full Text PDF PubMed Scopus (5) Google Scholar However, most studies have on and transcatheter AVR data on the of on postoperative bleeding after surgical AVR the to bleeding, report that were to early to a higher and adverse events A J Gunn J A E T J M of in J 2022; PubMed Scopus Google Scholar results the for treatment for A total of of the patients died during the follow-up The mortality was that patients relatively and to the time of surgical and transcatheter biologic valve is to of bioprosthetic heart Am Heart 2020; PubMed Scopus Google Scholar with the studies by V Sipilä J Ahtela E Rautava P Gunn J. Mechanical versus biologic prostheses for surgical aortic valve replacement in patients aged 50 to 70.Ann Thorac Surg. 2020; 110: 102-110Abstract Full Text Full Text PDF PubMed Scopus (23) Google Scholar and I Stevens LM Mazine A Poirier N R P outcomes after isolated mechanical aortic valve replacement in Thorac Surg. 2014; Full Text Full Text PDF PubMed Scopus Google Scholar the 10-year survival in the present was to vs In compared with the of YP Chikwe J Moskowitz AJ Itagaki S Adams DH Egorova NN. Survival and long-term outcomes following bioprosthetic vs mechanical aortic valve replacement in patients aged 50 to 69 years.JAMA. 2014; 312: 1323-1329Crossref PubMed Scopus (217) Google Scholar the 10-year survival was higher in the present vs Although major bleeding was bleeding was a of during the long-term follow-up. 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