Risk of Thromboembolic Events without Oral Anticoagulation at 90 Days after Surgical Aortic Valve Replacement with a Bioprosthesis

Thromboembolism, including systemic emboli and prosthetic valve thrombosis, is among the most dreaded complications after aortic valve replacement (AVR). However, in contrast to the lifelong necessity of oral anticoagulation (OAC) with mechanical valves, the optimal antithrombotic regimen and duration of treatment after implantation of a bioprosthesis remain controversial. Despite low long-term thromboembolic risk, it has been anticipated that patients with bioprosthetic valves are at moderate risk for thromboembolic complications in the first 3 months after surgery, until the sewing ring is fully endothelialized.[1] [2] [3]

For patients at high risk for thromboembolic events (atrial fibrillation, venous thromboembolism, hypercoagulable state or severely impaired left ventricular function), current guidelines recommend OAC.[4] [5] However, the optimal antithrombotic therapy is still debated for the majority of patients after bioprosthetic AVR. This is reflected in the most recent North American and European guidelines, which recommend low dose aspirin (evidence level IIa), or warfarin therapy (evidence level IIa and IIb, respectively) for 3 months after surgery.[4] [5] Of note, these guidelines are supported by weak evidence. The initial support for post-operative OAC came from Heras et al in 1995, reporting that OAC was associated with lower thromboembolic risk after implantation of a bioprosthesis. However, this observational study examined early generation bioprosthetic valves implanted in the 1970s and included both aortic and mitral valve implantations.[2] To date, only two randomized trials have compared anticoagulation versus antiplatelet treatment after bioprosthetic AVR.[6] [7] Both trials did not demonstrate superiority of anticoagulation over antiplatelet treatment for thromboprophylaxis. None of them focused on patients with no condition associated with high-risk of thromboembolism. As a consequence, there remains great variability in the current clinical practice. The ACTION Registry including 48 European centres reported that after bioprosthetic AVR, 43% of centres prescribe anticoagulation with warfarin only, 33% with aspirin only, 20% with both aspirin and warfarin and no antithrombotic therapy at all in 4% of the centres.[8]

In patients undergoing surgical AVR with a bioprosthesis and no condition with a high-risk of thromboembolism, we compared the 3-month outcomes with a post-operative management with no OAC and with or without aspirin 75 mg once daily. From 1984 to 2011, a total of 2,981 consecutive patients undergoing bioprosthetic AVR at our institution were identified. They all received the same model of bovine pericardial bioprosthesis (PERIMOUNT valve, Edwards Lifesciences, Irvine, California, United States). Exclusion criteria were: associated surgery on another valve; history of atrial fibrillation, thromboembolism, venous thrombosis and/or pulmonary embolus; and left ventricular ejection fraction inferior to 30%. Patients with prior use of anticoagulants and high risk of bleeding like history of cerebral bleeding were also excluded. Finally, patients who developed post-operative atrial fibrillation before hospital discharge were also excluded from the study.

At the time of discharge, 2,282 patients met the inclusion criteria (n = 699 exclusions). For all these patients with no condition associated with a high thromboembolic risk, a strategy with no post-operative OAC was systematically chosen. Low-molecular weight heparin 4,000 IU was administered for 10 days post-operatively. The administration of aspirin was at the discretion of the clinician and was started on day 2 after operation. Group A (n = 1,194 patients) received no post-operative OAC and no aspirin, while group B (n = 1,088 patients) received no OAC but a low-dose aspirin (75 mg once daily) during the first 3 months. Hospital charts of all patients were reviewed for in-hospital events. For 90-day follow-up, clinical questionnaires were mailed to patients and those not responding were contacted by phone. Information concerning post-operative treatment, bleeding and thromboembolic events were collected. The 90-day-follow-up was 100% complete. Definition of events followed guidelines for reporting morbidity after cardiac intervention.[9]

At baseline, the only significant difference between the two groups was a higher prevalence of coronary artery disease and coronary artery bypass graft in the group treated with aspirin (26.5% vs. 15.1%; p < 0.01) ([Table 1]). There was no significant difference concerning operative mortality or the mean hospital stay, around 7 days.

Table 1 Baseline characteristics and outcomes in patients with bioprosthetic aortic valve replacement

Patients, n = 2,282	No VKA, no aspirin (n = 1,194)	No VKA with aspirin (n = 1,088)	p-Value
Male, n (%)	812 (68)	740 (68)	0.99
Age, y	70.1 ± 11.0	70.2 ± 11.0	0.75
History of
• Hypertension	609 (51%)	566 (52%)	0.46
• Diabetes	196 (16%)	207 (19%)	0.21
• Peripheral vascular disease	251 (21%)	283 (26%	0.12
• Myocardial infarction	24 (2%)	44 (4%)	0.17
• Coronary artery disease	84 (7%)	250 (23%)	< 0.01
LVEF, %	59 ± 11	58 ± 12	0.71
NYHA class III–IV	394 (33%)	392 (36%)	0.55
Creatinine clearance < 50 mL/min	11 (1%)	10 (1%)	0.91
Euroscore II	1.81 ± 1.2	1.75 ± 1.2	0.67
CHA2DS2VASc score	2.41 ± 1.1	2.49 ± 1.1	0.77
Redo, n (%)	48 (4)	49 (4)	0.8
Operative mortality (30 d), n (%)	24 (2.0)	20 (1.8)	0.76
90-d mortality, n (%)	34 2.8)	30 (2.8)	0.96
90-d thromboembolism, n (%)	15 (1.3)	12 (1.1)	0.71
90-d valve thrombosis, n (%)	0	0	–
90-d bleeding, n (%)	2 (0.2)	3 0.3)	0.88
90-d readmission, n (%)	47(3.9)	51 (4.7)	0.52

Abbreviations: LVEF, left ventricular ejection fraction; NYHA, New York Heart Association; VKA, vitamin K antagonist.

Note: p-Value = 0.009.

At 3 months, thromboembolic and bleeding events were rare and we report no case of valve thrombosis. More precisely, 27 thromboembolic events were reported at 3 months: 15 strokes (4 leading to death), 7 transient ischaemic attack and 5 non-cerebral thromboembolic events. In multivariate analysis, use of aspirin was not associated with a lower risk of thromboembolism (odds ratio [OR] = 0.96; p = 0.91). Interestingly, 78% (n = 21) of thromboembolic events occurred in the first week and only 6 events were described after hospital discharge. Five bleeding events were reported: 4 of them occurred during the first month and 2 led to death. Localization of bleeding was respiratory, orthopaedic, gastrointestinal or gynaecological. In multivariate analysis, use of aspirin was not associated with a higher risk of bleeding (OR = 1.03; p = 0.88).

Authors' Contributions

All authors confirm they had full access to data and contributed to drafting of the article.

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