Novel Oral Anticoagulants Provide More Effective, Safer, More Convenient Treatment Option for Stroke

Novel Oral Anticoagulants Provide More Effective, Safer, More Convenient Treatment Option for Stroke


Stroke caused almost half (46%) of all cardiovascular-related deaths in the Asia Pacific in 2012, according to the World Health Organization. Stroke is the second leading cause of death in the Philippines.

A stroke occurs when the blood supply to part of the brain is interrupted or severely reduced, depriving brain tissue of oxygen and nutrients. Within minutes, brain cells begin to die. Stroke may result in severely restricted movement, paralysis, loss of speech or vision, which may be permanent, or even death.

Atrial fibrillation: major cause of stroke

Atrial fibrillation (AF) is an irregular heartbeat that causes turbulent blood flow, which can lead to the blood clotting. These blood clots can travel to the brain and trigger a major and often fatal stroke. The risk factors for AF include: advancing age, especially above 50 years; male gender; hypertension; structural heart disease, especially heart failure; and obesity. Experts estimate that in year 2050 there will be 72 million AF patients in Asia, 2.9 million of who will suffer from AF-associated stroke.

AF-related stroke devastates lives and is a major healthcare burden. AF-induced strokes are more severe and have worse prognosis than those of other cause and incur considerable corresponding burdens of mortality, morbidity and healthcare expenditure. Stroke kills 20% of such patients and disables 60% of survivors. Furthermore, stroke survivors with AF are more likely than those without AF to suffer another stroke, according to a 2015 article by Chen et al published in the International Journal of Cardiology.

NOACs: more effective, safer, more convenient

Antithrombotic therapy with oral anticoagulants is the most effective means of preventing AF- induced stroke. Anticoagulants make the blood take longer to clot; they play a vital part in helping to prevent strokes specifically caused by AF. For over 50 years, warfarin has been the drug of choice in preventing AF-related strokes. However, warfarin requires regular coagulation monitoring and dose adjustment; it also has many food and drug interactions. Another older treatment option, low-molecular-weight heparin, needs to be injected and can accumulate in patients with kidney impairment.

awdsdazxcfwaAF in Asia remains undertreated. Chen et al points out that conventional oral anticoagulation with warfarin is problematic in Asia due to suboptimal control and a propensity among Asians to warfarin-induced intracranial hemorrhage (bleeding that occurs inside the skull). Partly due to concerns about intracranial hemorrhage, there are considerable gaps between AF treatment guidelines and clinical practice in Asia, particularly the overuse of antiplatelet agents and underuse of anticoagulants.

According to Chen et al, novel oral anticoagulants (NOACs) match warfarin in stroke prevention, but are easier to administer and significantly reduce the risk of life-threatening bleeding, particularly intracranial bleeding. As such, NOACs may provide an appropriate alternative to warfarin in Asian patients. According to the updated European Society of Cardiology (ESC) Guidelines, NOACs offer better efficacy, safety and convenience than vitamin K antagonists (VKAs) such as warfarin in the management of AF. The ESC Guidelines also state the NOACs are broadly preferable to VKAs in the vast majority of patients with non-valvular AF.

Figures from the Philippine Medical Data Index (PMDI) show that NOACs accounted for 45% of anticoagulant prescriptions in June 2015, with warfarin accounting for

52% and heparin 3%. September 2015 IMS data in terms of share in value sales show that NOACs account for 51%, warfarin 31% and heparin 18%.

NOACs include a new class of oral anticoagulants called Xabans, such as rivaroxaban, apixaban and edoxaban. Clinical trials have shown that Xabans hold potential as ideal substitutes for warfarin or low-molecular-weight heparin. These trials demonstrated Xabans have superior efficacy and safety vs. warfarin for stroke prevention in AF and against low-molecular-weight heparin for the treatment and secondary prevention of venous thromboembolism (VTE) or for initial treatment and prevention of VTE in patients undergoing hip or knee replacement. VTE is the formation of blood clots in the vein. When a clot forms in a deep vein, usually in the leg, it is called a deep vein thrombosis or DVT. If that clot breaks loose and travels to the lungs, it is called a pulmonary embolism or PE.

Xabans provides several advantages. They have a rapid onset and offset of action, which reduces the need for “bridging” with a parenteral (injectable) anticoagulant; they don’t require frequent monitoring or re-dosing while having few strong drug interactions and no food interactions, leading to greater convenience for patients and doctors; and they have a lower risk of intracranial bleeding.

Developed by German pharmaceutical giant Bayer, rivaroxaban is the most prescribed NOAC in the world. Its clinical investigation program—both completed and ongoing—will include more than 275,000 patients in clinical trials and real-world settings.

Rivaroxaban protects patients from blood clots across more venous and arterial thromboembolic (VAT) conditions than any other NOAC. Once-daily rivaroxaban provides highly effective stroke prevention without the need for routine coagulation monitoring. Importantly, rivaroxaban can prevent strokes without increasing the risk of heart attack and lowers the rate of the most feared intracranial and fatal bleeds, compared with warfarin. Furthermore, rivaroxaban is available in a specific dose evaluated for patients with kidney impairment.

As a once-daily dose, rivaroxaban halves the risk of treatment discontinuation compared to warfarin. Once-daily dosing is preferred by patients with AF taking lifelong medications, and was shown to result in significantly higher adherence and persistence compared to twice-daily treatment.

Areas for improvement

Chen et al believes that there are many areas for improvement in current efforts to prevent AF-induced strokes in Asia. Key priorities include early detection of AF and identification of asymptomatic patients; assessment of stroke and bleeding risk for all AF patients; evidence-based pharmacotherapy with oral anticoagulants for AF patients at risk of stroke; controlling hypertension; and awareness-raising, education and outreach among physicians and patients.

Cohen et al recommends updating management approaches in order to improve outcomes, as well as further raising awareness and bridging gaps between the latest evidence and clinical practice.