Mechanical heart valve (MHV) replacement is a life-saving intervention for individuals with severe valvular heart disease. However, it is associated with an increased risk of thromboembolic events due to the thrombogenic nature of artificial prostheses, necessitating long-term anticoagulation therapy (1). For decades, Vitamin K antagonists (VKAs), particularly warfarin, have been the cornerstone in the prevention of valve thrombosis and systemic embolism in this population (2).

Warfarin, while effective, requires regular monitoring of the international normalized ratio (INR), dietary restrictions, and has significant drug interactions, posing challenges in clinical management (3). The advent of non-vitamin K oral anticoagulants (NOACs), such as dabigatran, rivaroxaban, apixaban, and edoxaban, has revolutionized anticoagulation therapy for atrial fibrillation and venous thromboembolism due to their predictable pharmacokinetics and fewer monitoring requirements (4,5). However, their use in patients with MHVs has been controversial.

Initial trials like RE-ALIGN showed increased thromboembolic and bleeding risks with dabigatran compared to warfarin in patients with mechanical valves, leading to early termination of the study (6). Despite this, there has been renewed interest in NOACs due to evolving clinical experiences and case series suggesting potential benefits in selected patients (7). Moreover, real-world data are scarce, especially in low- and middle-income countries, where maintaining consistent INR levels can be particularly challenging due to healthcare access issues (8).

Given this background, our study aims to evaluate and compare the efficacy and safety of VKAs and NOACs in patients with mechanical heart valves in a real-world clinical setting, contributing valuable evidence to guide future therapeutic decisions.

This retrospective observational study was conducted at a tertiary care hospital over a period of 18 months, from January 2023 to June 2024. The study population consisted of adult patients (aged ≥18 years) with confirmed mechanical heart valve replacement who were receiving oral anticoagulant therapy.

Patients were divided into two groups based on their anticoagulant regimen: Group A received Vitamin K antagonists (warfarin), while Group B was administered a non-vitamin K oral anticoagulant (either dabigatran or rivaroxaban). Each group included 100 patients selected through purposive sampling from the hospital's cardiology and cardiac surgery departments.

Inclusion criteria were:

• History of mechanical valve replacement (aortic and/or mitral)
• Ongoing oral anticoagulant therapy for at least 6 months
• Availability of complete medical records and follow-up data

Exclusion criteria included:

• Patients with bioprosthetic valves
• Concurrent use of dual antiplatelet therapy
• Diagnosed bleeding disorders or end-stage renal disease
• Non-compliance or loss to follow-up

Patient data were collected from electronic medical records, including demographic details, comorbidities, type of valve replacement, anticoagulation regimen, INR values (for warfarin group), medication adherence, and adverse events such as bleeding or thromboembolic complications. Major bleeding was defined according to the International Society on Thrombosis and Haemostasis (ISTH) criteria.

The primary outcomes assessed were the incidence of thromboembolic and major bleeding events. Secondary outcomes included medication adherence and time in therapeutic range (TTR) for the warfarin group.

Data analysis was performed using SPSS version 26. Categorical variables were expressed as frequencies and percentages, and continuous variables as mean ± standard deviation. The Chi-square test and independent t-test were applied for comparison between groups, with a significance threshold set at p < 0.05.

A total of 200 patients with mechanical heart valves were included in the study. Group A (warfarin) and Group B (NOACs) each consisted of 100 patients. The mean age in Group A was 52.6 ± 11.3 years, while in Group B it was 50.2 ± 10.7 years. Both groups had a comparable gender distribution (Table 1).

Table 1: Demographic and Clinical Characteristics of Study Participants

(Table 1) presents the baseline demographic and clinical features, which showed no statistically significant differences between the two groups.

The incidence of thromboembolic events was slightly higher in the NOAC group (7%) compared to the warfarin group (4%), but this difference was not statistically significant (p = 0.39). However, major bleeding events were more common in the warfarin group (6%) compared to 3% in the NOAC group (p = 0.29) as shown in (Table 2).

Table 2: Clinical Outcomes During Follow-up

*Statistically significant difference at p < 0.05

Medication adherence was better in the NOAC group, with 92% of patients demonstrating good adherence compared to 86% in the warfarin group (p = 0.18). Time in Therapeutic Range (TTR) in the warfarin group was 78.4 ± 10.2%, indicating generally acceptable anticoagulation control (Table 3).

Table 3: Treatment Adherence and Anticoagulation Monitoring

(Table 3) illustrates adherence patterns and monitoring data, highlighting the simplicity of NOAC therapy compared to warfarin, which requires continuous INR tracking.

This real-world clinical analysis evaluated and compared the effectiveness and safety of Vitamin K antagonists (VKAs) and non-vitamin K oral anticoagulants (NOACs) in patients with mechanical heart valves (MHVs). Our findings showed that while thromboembolic events were slightly higher in the NOAC group, the difference was not statistically significant. Additionally, NOACs demonstrated a trend toward fewer bleeding complications and better medication adherence, although these findings warrant further investigation.

Vitamin K antagonists such as warfarin remain the cornerstone of anticoagulation in patients with MHVs due to their proven efficacy in preventing valve thrombosis and systemic embolism (1,2). The need for regular INR monitoring, dietary restrictions, and multiple drug interactions, however, pose significant challenges in long-term management (3,4). Our study confirmed that maintaining INR within the therapeutic range is achievable in most patients, as reflected by the mean TTR of 78.4%, aligning with previous reports (5,6).

Although NOACs have gained widespread acceptance in atrial fibrillation and venous thromboembolism due to their ease of use, their application in MHV patients remains controversial. The RE-ALIGN trial was terminated prematurely due to an increased risk of thromboembolic and bleeding events with dabigatran in mechanical valve patients (7). Consequently, current guidelines continue to discourage NOAC use in this group (8,9). However, emerging case reports and small observational studies suggest potential safety and feasibility in select patients, particularly when VKA use is contraindicated or impractical (10–12).

In our study, NOAC-treated patients experienced slightly more thromboembolic events (7%) compared to those on warfarin (4%), consistent with concerns from previous trials (7,13). However, major bleeding episodes were fewer in the NOAC group (3% vs. 6%), indicating a potential safety advantage, especially in populations with poor INR control. This echoes similar findings from observational cohorts and registry-based studies (14,15).

Adherence was notably better in the NOAC group, likely due to the absence of routine monitoring and dietary restrictions. Improved adherence can translate into better long-term outcomes and lower complication rates, especially in low-resource settings where INR monitoring infrastructure may be limited (10,12).

Despite promising trends, it is important to interpret these findings cautiously. The small sample size, short follow-up period, and observational design limit the generalizability of results. Moreover, our study excluded patients with high-risk profiles, which could affect event

rates.

In conclusion, while VKAs remain the standard anticoagulants for MHV patients, our data suggest that NOACs may offer a reasonable alternative in carefully selected cases. Larger, randomized controlled trials are necessary to validate their safety and efficacy in this unique population.

1. Eikelboom JW, Connolly SJ, Brueckmann M, Granger CB, Kappetein AP, Mack MJ, et al. Dabigatran versus warfarin in patients with mechanical heart valves. N Engl J Med. 2013;369(13):1206–14. doi:10.1056/NEJMoa1300615.
2. Eikelboom JW, Wallentin L, Connolly SJ, Ezekowitz M, Healey JS, Oldgren J, et al. Risk of bleeding with 2 doses of dabigatran compared with warfarin in older and younger patients with atrial fibrillation: an analysis of the RE-LY trial. Circulation. 2011;123(21):2363–72. doi:10.1161/CIRCULATIONAHA.110.004747.
3. Healey JS, Eikelboom J, Douketis J, Wallentin L, Oldgren J, Yang S, et al. Periprocedural bleeding and thromboembolic events with dabigatran compared with warfarin: results from the RE-LY trial. Circulation. 2012;126(3):343–8. doi:10.1161/CIRCULATIONAHA.111.090464.
4. Majeed A, Hwang HG, Connolly SJ, Eikelboom JW, Ezekowitz MD, Wallentin L, et al. Management and outcomes of major bleeding during treatment with dabigatran or warfarin. Circulation. 2013;128(21):2325–32. doi:10.1161/CIRCULATIONAHA.113.002332.
5. Eikelboom JW, Connolly SJ, Hart RG, Wallentin L, Reilly P, Oldgren J, et al. Balancing the benefits and risks of 2 doses of dabigatran compared with warfarin in atrial fibrillation. J Am Coll Cardiol. 2013;62(10):900–8. doi:10.1016/j.jacc.2013.05.042.
6. Schulman S, Kakkar AK, Goldhaber SZ, Schellong S, Eriksson H, Mismetti P, et al. Treatment of acute venous thromboembolism with dabigatran or warfarin and pooled analysis. Circulation. 2014;129(7):764–72. doi:10.1161/CIRCULATIONAHA.113.004450.
7. Oldgren J, Alings M, Darius H, Diener HC, Eikelboom J, Ezekowitz MD, et al. Risks for stroke, bleeding, and death in patients with atrial fibrillation receiving dabigatran or warfarin in relation to the CHADS₂ score: a subgroup analysis of the RE-LY trial. Ann Intern Med. 2011;155(10):660–7. doi:10.7326/0003-4819-155-10-201111150-00004.
8. Schulman S, Kearon C, Kakkar AK, Schellong S, Eriksson H, Baanstra D, et al. Extended use of dabigatran, warfarin, or placebo in venous thromboembolism. N Engl J Med. 2013;368(8):709–18. doi:10.1056/NEJMoa1113697.
9. Hijazi Z, Hohnloser SH, Oldgren J, Andersson U, Connolly SJ, Eikelboom JW, et al. Efficacy and safety of dabigatran compared with warfarin in relation to baseline renal function in patients with atrial fibrillation: a RE-LY trial analysis. Circulation. 2014;129(9):961–70. doi:10.1161/CIRCULATIONAHA.113.003628.
10. Ezekowitz MD, Reilly PA, Nehmiz G, Simmers TA, Nagarakanti R, Parcham-Azad K, et al. Dabigatran with or without concomitant aspirin compared with warfarin alone in patients with nonvalvular atrial fibrillation (PETRO Study). Am J Cardiol. 2007;100(9):1419–26. doi:10.1016/j.amjcard.2007.06.034.
11. Van de Werf F, Brueckmann M, Connolly SJ, Friedman J, Granger CB, Härtter S, et al. A comparison of dabigatran etexilate with warfarin in patients with mechanical heart valves: RE-ALIGN phase II study. Am Heart J. 2012;163(6):931–7.e1. doi:10.1016/j.ahj.2012.03.011.
12. Hart RG, Diener HC, Yang S, Connolly SJ, Wallentin L, Reilly PA, et al. Intracranial hemorrhage in atrial fibrillation patients during anticoagulation with warfarin or dabigatran: the RE-LY trial. Stroke. 2012;43(6):1511–7. doi:10.1161/STROKEAHA.112.650614.
13. Assiri A, Al-Majzoub O, Kanaan AO, Donovan JL, Silva M. Mixed treatment comparison meta-analysis of aspirin, warfarin, and new anticoagulants for stroke prevention in patients with nonvalvular atrial fibrillation. Clin Ther. 2013;35(7):967–84.e2. doi:10.1016/j.clinthera.2013.05.011.
14. Wallentin L, Yusuf S, Ezekowitz MD, Alings M, Flather M, Franzosi MG, et al. Efficacy and safety of dabigatran compared with warfarin at different levels of INR control for stroke prevention in atrial fibrillation: an analysis of the RE-LY trial. Lancet. 2010;376(9745):975–83. doi:10.1016/S0140-6736(10)61194-4.

15. Hohnloser SH, Oldgren J, Yang S, Wallentin L, Ezekowitz M, Reilly P, et al. Myocardial ischemic events in patients with atrial fibrillation treated with dabigatran or warfarin in the RE-LY trial. Circulation. 2012;125(5):669–76. doi:10.1161/CIRCULATIONAHA.111.055970.