In South Africa, dabigatran is indicated to reduce the risk of stroke and systemic embolism (SE) in patients living with atrial fibrillation (AFib), as well as for the treatment of acute for the prevention of venous thromboembolism (VTE) in adult patients who have undergone hip and knee replacement surgery, and prevention of recurrent deep vein thrombosis (DVT) and/or pulmonary embolism (PE).¹ 

AFib and the risk of stroke/systemic embolism 

AFib is the most common cardiac arrythmia seen in clinical practice. AFib affects between one in three to five individuals >45-years. Patients living with AFib have a high risk of stroke/SE, which can occur in isolation or concurrently with various pathologies such as mitral stenosis.^3,4 

In the Randomized Evaluation of Long-Term Anticoagulant Therapy (RE-LY) With Dabigatran Etexilate study, Connolly et al randomly assigned 18 113 patients living with AFib and at risk of stroke to receive either fixed-doses of dabigatran (110mg or 150mg twice daily) or adjusted-dose warfarin. The median follow-up period was two years. The primary outcome was the occurrence of stroke/SE.⁵ 

The annual rates of the primary outcome were 1.69% in the warfarin group, 1.53% in the 110mg dabigatran group (relative risk [RR] with dabigatran 0.91), and 1.11% in the 150mg dabigatran group (RR 0.66). The rate of major bleeding was 3.36% per year in the warfarin group, compared to 2.71% per year in the 110mg dabigatran group and 3.11% per year in the 150mg dabigatran group.⁵  

The incidence of haemorrhagic stroke was 0.38% per year in the warfarin group, compared to 0.12% per year in the 110mg dabigatran group and 0.10% per year in the 150mg dabigatran group. The mortality rate was 4.13% per year in the warfarin group, compared to 3.75% per year in the 110mg dabigatran group and 3.64% per year in the 150mg dabigatran group.⁵ 

The authors concluded that in patients living with AFib, 110mg dabigatran resulted in stroke/SE rates similar to those with warfarin, but with lower rates of major haemorrhage. The 150mg dabigatran dose was associated with lower rates of stroke/SE compared to warfarin, while maintaining similar rates of major haemorrhage.⁵ 

Risk reduction and treatment of VTE 

VTE is the third most common cause of cardiovascular disease (CVD) globally. It is associated with a high risk of mortality and morbidity, substantial healthcare costs, and a high rate of recurrence. Surgery contributes significantly to its occurrence (25%).^6,7  

Non-vitamin K antagonist oral anticoagulants (NOACs) like dabigatran have emerged as effective options for VTE prevention and treatment. Dabigatran, rivaroxaban, and apixaban have demonstrated efficacy and safety, with dabigatran being the first NOAC approved by the American Food and Drug Administration.^8-11 

Numerous studies support the efficacy of dabigatran etexilate in preventing thromboembolic events post-surgery, treating acute VTE, and thromboprophylaxis following primary total hip arthroplasty.^12-20 

Dabigatran is currently licensed for long-term, and extended VTE treatment. 

Anticoagulants are used in the acute (first seven days), long-term (seven days to three months), and extended (>3 months to indefinite) treatment phases of VTE. Anticoagulation is recommended for at least three months in most patients with DVT and/or PE.^21,22,23 

The goals of anticoagulant therapy are to avoid fatal PE, to prevent recurrence and to reduce the risk of long-term complications such as post-thrombotic syndrome, long-standing exertional dyspnoea, and chronic thromboembolic pulmonary hypertension. Traditionally, VTE provoked by a major transient risk factor, such as surgery or trauma, only required a three-month course of anticoagulation, whereas unprovoked VTE or VTE associated with a major persistent risk factor, such as cancer, required extended therapy beyond three months.^21,22,23 

The Efficacy and Safety of Dabigatran Compared to Warfarin for 6 Month Treatment of Acute Symptomatic Venous Thromboembolism (RE-COVER) trials confirmed dabigatran's non-inferiority to conventional therapy in preventing recurrent VTE, with a favourable safety profile regarding major bleeding incidents.¹⁷ 

For extended treatment, dabigatran was compared with placebo in the Twice-Daily Oral Direct Thrombin Inhibitor Dabigatran Etexilate in the Long Term Prevention of Recurrent Symptomatic VTE (RE-SONATE) trial and with warfarin in the A Phase III, Randomised, Multi-Center, Double-blind, Parallel-group, Active Controlled Study To Evaluate The Efficacy And Safety Of Oral Dabigatran Etexilate Compared To Warfarin (INR 2.0-3.0) For The Secondary Prevention Of Venous Thromboembolism (RE-MEDY) trial. The RE-MEDY trial demonstrated that dabigatran was non-inferior to warfarin in preventing recurrent VTE, offering a safer profile with significantly fewer major bleeding events.^18,19 

Conclusion 

Given the high incidence of VTE globally and its association with significant morbidity, mortality, and healthcare costs, the availability of effective anticoagulant therapy like dabigatran etexilate is crucial. Moreover, the diverse range of risk factors contributing to VTE underscores the importance of preventive measures and tailored treatment approaches. 

Clinical trials have demonstrated the efficacy and safety of dabigatran etexilate in various settings, including post-operative care and extended treatment phases. Its non-inferiority to conventional therapies and favourable safety profile makes it a compelling option for both acute and extended VTE management. 

The introduction of generic alternatives like dabigatran etexilate represents a significant step forward in improving patient outcomes and reducing the burden of this life-threatening condition. 

References 

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