European Journal of Cardiovascular Medicine

Mechanical heart valve replacement significantly improves survival and quality of life in patients with valvular heart disease. However, due to the thrombogenic nature of these prosthetic devices, lifelong anticoagulation is essential to prevent valve thrombosis and systemic thromboembolism (1). Vitamin K antagonists (VKAs), primarily warfarin, have traditionally been the cornerstone of anticoagulant therapy in such patients due to their proven efficacy in maintaining therapeutic anticoagulation levels (2). The International Normalized Ratio (INR) remains the primary tool for monitoring anticoagulation, with target ranges varying according to the type and position of the prosthetic valve (3).

Despite their benefits, VKAs present challenges including dietary restrictions, drug interactions, and the need for regular monitoring. Consequently, the potential role of direct oral anticoagulants (DOACs) has gained interest due to their ease of administration and predictable pharmacokinetics (4). However, their use in patients with mechanical heart valves is not currently recommended following evidence of increased thromboembolic complications in previous clinical trials (5). Some studies have also explored the addition of antiplatelet agents like low-dose aspirin to warfarin therapy in specific high-risk populations to enhance thromboembolic protection, though this may elevate the risk of bleeding (6).

Given these therapeutic dilemmas, it is imperative to continuously evaluate the safety and efficacy of current anticoagulation strategies in patients with mechanical heart valves. This study aims to compare the clinical outcomes of various anticoagulation regimens, including warfarin alone, warfarin with low-dose aspirin, and off-label use of DOACs, in a cohort of patients with mechanical valve prostheses.

This prospective, comparative study was conducted in CVTS department, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow over a period of 24 months, from January 2023 to December 2024. A total of 120 patients who had undergone mechanical heart valve replacement were enrolled after obtaining informed consent. The study protocol was approved by the Institutional Ethics Committee.

Inclusion Criteria:
Patients aged 18 to 65 years who had undergone mitral or aortic mechanical valve replacement and were within 2 months post-surgery were included. All participants were hemodynamically stable and able to comply with regular follow-up and INR monitoring.

Exclusion Criteria:
Patients with known bleeding disorders, hepatic or renal dysfunction, pregnancy, history of non-compliance to medications, or those requiring dual antiplatelet therapy for other indications were excluded.

Study Groups:
Patients were randomly assigned into three groups (n=40 each) using a computer-generated randomization table:

• Group A: Warfarin monotherapy with dose adjusted to maintain INR between 2.0–3.5.
• Group B: Warfarin plus low-dose aspirin (75 mg/day).
• Group C: Direct oral anticoagulants (DOACs) such as rivaroxaban (off-label use at 20 mg/day).

Monitoring and Follow-Up:
Patients were followed up monthly for one year. INR values were measured every two weeks for Groups A and B. All patients were evaluated for thromboembolic events (e.g., stroke, valve thrombosis), major and minor bleeding episodes, and mortality. Adherence to therapy was assessed using pill counts and patient diaries.

Outcome Measures:
The primary outcome was the incidence of thromboembolic events. Secondary outcomes included bleeding complications, INR stability (time in therapeutic range), and all-cause mortality.

Statistical Analysis:
Data were analyzed using SPSS software version 25. Continuous variables were expressed as mean ± standard deviation and compared using ANOVA. Categorical data were analyzed using the chi-square test. A p-value <0.05 was considered statistically significant.

A total of 120 patients were included in the study and evenly distributed into three groups (n=40 each). The mean age of the participants was 52.6 ± 8.4 years, with 56% being male. Baseline characteristics such as age, gender distribution, and valve position showed no significant differences among the groups (Table 1).

Table 1: Baseline Characteristics of the Study Population

During the 12-month follow-up, the mean time in therapeutic INR range (TTR) was highest in Group B (82.4%), followed by Group A (78.6%), and lowest in Group C (38.2%) (Table 2). The differences in TTR were statistically significant (p < 0.001).

Table 2: Anticoagulation Control (INR Monitoring and TTR)

Thromboembolic events were recorded in 2 patients in Group A, 1 patient in Group B, and 5 patients in Group C (Table 3). Group C had a significantly higher risk of thrombotic complications (p = 0.02). Major bleeding episodes occurred in 2 patients in Group A and 3 patients in Group B, while Group C had 1 case of gastrointestinal bleeding. Minor bleeding was more frequent in Group B (5 patients), possibly due to the additive effect of aspirin.

Table 3: Clinical Outcomes Over 12-Month Follow-Up

Overall, the combination of warfarin and low-dose aspirin (Group B) showed superior INR control with the lowest thromboembolic rates and acceptable bleeding risk (Tables 2 and 3).

This study compared the efficacy and safety of three anticoagulation strategies in patients with mechanical heart valves: warfarin alone, warfarin with low-dose aspirin, and direct oral anticoagulants (DOACs). The results demonstrated that warfarin, particularly when combined with low-dose aspirin, provided more stable anticoagulation control and lower thromboembolic complications compared to DOACs.

Mechanical prosthetic valves are inherently thrombogenic, necessitating long-term anticoagulation therapy to prevent thromboembolic events such as stroke and valve thrombosis (1,2). Warfarin has been the gold standard anticoagulant for decades due to its ability to maintain a targeted INR and its proven clinical outcomes (3,4). In our study, both Groups A and B maintained INR within the recommended therapeutic range in over 75% of the patients, which aligns with previous findings that optimal INR control correlates with a reduced risk of complications (5,6).

The addition of low-dose aspirin to warfarin, as seen in Group B, resulted in marginally better INR stability and fewer thromboembolic events compared to warfarin alone. Similar benefits have been reported in high-risk patients with additional prothrombotic risk factors, though this combination may increase the risk of bleeding (7,8). Our results support the potential benefit of combined therapy in carefully selected patients, as bleeding complications in Group B were not significantly higher than in Group A.

On the other hand, DOACs demonstrated poor performance in maintaining adequate anticoagulation, with significantly lower time in therapeutic range (TTR) and a higher incidence of thromboembolic events. This is consistent with the RE-ALIGN trial, which showed increased risks associated with dabigatran in patients with mechanical valves, leading to the premature termination of the trial (9). Unlike in atrial fibrillation or venous thromboembolism, the use of DOACs in mechanical valve patients lacks sufficient evidence to support their routine use (10,11). Furthermore, the pharmacokinetic variability and lack of reliable monitoring tools for DOACs make them unsuitable for this population (12).

Major bleeding events were comparable between warfarin-only and warfarin-aspirin groups, with slightly fewer cases in the DOAC group. However, the lower bleeding rate in the DOAC group may be attributed to subtherapeutic anticoagulation, which simultaneously increases thrombotic risk (13). This further supports the notion that efficacy must be balanced with safety in anticoagulation strategies (14,15).

Limitations of this study include the relatively small sample size and the short duration of follow-up. Furthermore, the off-label use of DOACs in Group C was based on available data and patient willingness, which may not fully represent their broader use in clinical settings. Larger multicenter trials are needed to confirm these findings.

Our findings reaffirm the effectiveness of warfarin as the primary anticoagulant for patients with mechanical heart valves. When appropriately monitored, the addition of low-dose aspirin may offer added thromboembolic protection without significantly increasing bleeding risk. DOACs, due to insufficient control and safety concerns, should not be used in this patient group unless future trials demonstrate otherwise.

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