1 in 4 people worldwide die of conditions caused by thrombosis.  13 October is marked yearly as World Thrombosis Day. Thrombosis, the medical term for a blood clot, leads to diseases including heart attack, stroke and venous thromboembolism (VTE). These diseases are classified under cardiovascular diseases (CVD), which have been an increasing burden in the Asia Pacific region over the years. In the region, 8.2 million cases of mortality from CVD were reported in 2015, showing a marked increase of 21% from 6.8 million in 2005. In 2012, the World Health Organisation (WHO) showed that 46% of CVD-related deaths were due to stroke. 
Thrombosis is more specifically termed as venous and arterial thromboembolism (VAT). VAT encompasses venous thromboembolism (VTE) and arterial thromboembolism. VTE leads to pulmonary embolism (PE) and deep vein thrombosis (DVT). Arterial thromboembolism leads to stroke and heart attack.
VTE is the third most common CVD worldwide, and the most common avoidable cause of hospital death. [3, 4] This implies that VTE is a serious and possibly fatal disease, but yet, there is little awareness of VTE. This is unlike the infamous conditions like stroke and heart attack, which stem from thrombosis as well. VTE occurs when a blood clot forms in a vein. If the blockage is in a deep vein, most commonly found in the leg, DVT occurs. If the blood clot breaks off and travels to the lungs, PE occurs and it can be potentially fatal. With an ageing population and an increasingly sedentary lifestyle, these risk factors cause the incidence of DVT and PE in the Asia Pacific region to be predicted to increase by about 50% from 2015 to 2025. 
The more well-known disease, stroke, accounts for the second most common cause of death worldwide, causing 6.7 million deaths in 2012. A strong factor leading to stroke is atrial fibrillation (AF). AF happens because the atria of the heart fail to contract regularly, so the atria do not empty completely. The improper blood flow may then lead to formation of blood clots. Patients with AF are 5 times more likely to get a stroke. By 2050, Asia is projected to have 72 million AF patients, and 2.9 million of these patients are likely to suffer from an AF-associated stroke. 
So what is being done about this growing medical issue of stroke and thrombosis incidence in Asia Pacific? Bayer is one such company who is striving to focus its R&D efforts in meeting unmet medical needs such as these. Bayer is one of the fastest growing multinational companies in the Asia Pacific region, ranking amongst the Top 20. In 2015, Bayer raised its investment in R&D by 21% to approximately EUR 4.3 billion.
With the mission of "Science for A Better Life", Bayer is committed to deliver a diverse portfolio of innovative products to the market. "The strong uptake of our innovative medicines shows our close alignment with the region's growing healthcare needs. It demonstrates our commitment to leverage on science to develop treatments that help people live better lives," said Claus Zieler, Senior Vice President & Head of Commercial Operations at Bayer Pharmaceuticals Division Asia Pacific. "Our robust performance in Asia today supports the positive outlook for our Pharma business. Our solid pharmaceutical portfolio will continue to serve vital, yet unmet medical needs of patients in the region over the coming years."
One of the actions Bayer’s Pharmaceuticals division has taken was to organise a media briefing and panel dialogue on the burden of stroke and thrombosis in Asia Pacific. Present were Claus Zieler and Dr. Chuan Kit Foo, Head of Medical Affairs at Bayer Pharmaceuticals Asia Pacific, who emphasised Bayer's responsibility towards the use of its innovative medicine worldwide. A panel of experts including Dr. Tan Ru San, a cardiologist at National Heart Centre Singapore, and Amit Backliwal, Vice President of Technology and Services at IMS Health, were invited to discuss the issue of rising stroke and thrombosis in the region.
Anticoagulants have traditionally been used to treat blood clots through blood thinning. In the 1930s, heparin was the prescribed medicine. It was effective but injection is required for administration. Vitamin K antagonists (VKA) (e.g. warfarin) were used in the 1940s. They were effective as well, but limitations such as a narrow therapeutic range and many food-drug interactions made the drug difficult to use in practice.  Heparin and warfarin were considered the gold standards in drugs for treating thrombosis. In the 2000s, novel non-vitamin K antagonist oral anticoagulants (NOACs) were invented. It matched the efficacy of warfarin, also with the advantages of being orally administered, having a rapid onset action, not needing routine monitoring of anti-coagulation and no or little significant drug-drug or drug-food interactions.  Examples of NOACs in the market are Rivaroxaban, Apixaban, Edoxaban and Dabigatran.
The most prescribed NOAC, Rivaroxaban, is developed by Bayer. Rivaroxaban has already been prescribed worldwide to more than 18 million patients. This drug has been well-studied in both clinical trials and Real World Evidence (RWE). The study programme of Rivaroxaban is expected to include more than 275,000 patients in clinical trials and real world studies. XANTUS is a prospective, international, observational RWE that evaluated the safety and effectiveness of Rivaroxaban in 6784 patients with AF from 311 clinical practices across Europe, Israel and Canada. Results found Rivaroxaban to be safe, with 96.1% of patients not experiencing any major bleeding. Persistence of the usage of the anti-clotting drug was high as well, with 80% continuing their treatment during the 1 year study period, and 75% who indicated they were 'Satisfied' or 'Very Satisfied' with Rivaroxaban.
However, the existence of these NOACs cannot be maximised to their full potential of decreasing the incidence of thrombosis and its related diseases, if people stick to the mainstay drugs of heparins and warfarins. There are several challenges faced. One is the higher costs of the newer NOAC drugs, that may deter people from choosing NOACs for treatment. "The average combined patient and insurer cost associated with starting a NOAC is $900 greater than the costs of starting warfarin", according to lead investigator Niteesh K. Choudhry, who led a study on the adoption of novel NOACs into clinical practice in America.  However, a recent study on the Singapore healthcare system, concluded rivaroxaban was a cost-effective therapy compared with warfarin for the prevention of stroke in patients with AF. Probability sensitivity analysis showed that the probability of rivaroxaban being the optimal choice was 97.8% and 99.5% at a willingness-to-pay threshold of SG$65,000 and SG$130,000 respectively .
Another is the lack of awareness amongst patients of the advantages that NOACs have over traditional VKAs, so they may be unwilling to try out a new drug unfamiliar to them. Another drug, aspirin, is also a hindrance factor in the uptake of NOACs. Aspirin has been the commonly preferred and prescribed drug for stroke prevention in the Asia Pacific region for years, due to a misconception that aspirin is safer than warfarin. In 2008, a report from the National Health Insurance Research database of Taiwan stated that, "only 15.4% of patients received warfarin, while 50.6% of them received aspirin". Recent data has shown that aspirin is not effective in AF-induced stroke. A 2006 trial conducted in Japan proved that aspirin actually increased the risk of bleeding. And in 2014, in Hong Kong, the use of aspirin was shown again to be ineffective. 
Although VKAs like warfarin are effective in treating AF-associated stroke, there are many disadvantages that make VKAs a drug that should be phased out slowly in favour of NOACs. For Asia/Pacific, some obstacles of using VKAs include: Poor control of diet restrictions, use of herbal medicine that will interact with the drug and lack of structured anti-coagulation clinics for regular monitoring in many Asian countries. Furthermore, Asians are found to have a higher chance of bleeding with VKA treatment. The annual risk of haemorrhagic stroke among Asian patients using warfarin ranged from 0.75-1.33%, compared to 0.32-0.41% among non-Asians.  Thus, there is a great need for NOACs in the Asia Pacific region for treating of thrombosis-related diseases. NOACs have much benefits over VKAs: (a) Easy to administer orally; (b) Significantly reduces the risk of life-threatening bleeding, especially intracranial bleeding; (c) Rapid onset of action; (d) Predictive anticoagulation, no dose or monitoring adjustment needed; (e) Low risk of drug-drug or drug-food interactions; (f) Wide therapeutic range. The lack of monitoring and dose adjustments needed, are indeed significant improvements of NOACs over VKAs, coupled with little drug or food interactions.
Besides meeting the needs of more effective treatment options, preventive measures need to be taken to inform the public on ways to reduce or prevent thrombosis-related diseases, especially VTE. For instance, people have to be educated on the risk factors associated with thrombosis-related diseases: being overweight, lack of exercise, heavy drinking, high blood pressure, drug use, smoking, high cholesterol, cardiovascular disease, sleep apnoea and diabetes.  With diabetes being another major concern in the Asia Pacific region, the educating of people on these possible risk factors is crucial. The Asian Diabetes Prevention Initiative states that "60% of diabetics worldwide live in Asia" and "For the same BMI, Asians have 3-5% higher body fat compared to people of European ancestry".  This makes Asians more prone to diabetes, and thus possibly leading to thrombosis. The channeling of the thrombosis message can be done through healthcare stakeholders (pharmaceutical companies, healthcare workers, clinicians, etc.), social media campaigns, or even by roping in of celebrities for greater exposure. Currently, World Thrombosis Day 2016 is running a Twitter hashtag campaign with photo contests.  Bayer Pharmaceuticals supports the Global Anticoagulant Registry in the Field (GARFIELD), a RWE by the Thrombosis Research Institute in London. GARFIELD determines the real-life practice of AF management in patients. Bayer is also committed to raising awareness through holding media dialogue sessions. Additional investments and joint collaborations with other research institutions can be done as well to advance the field of treating thrombosis.
Raising awareness on thrombosis prevention and availability of novel improved drugs for thrombosis treatment have to go hand in hand, in curbing the increasing fatalities from thrombosis-related diseases. It is a pity when a disease could have been easily prevented or treated, but lack of information and awareness lead the patient down the path of medical bills or complications. Patients have to be receptive and willing to accept changes as well, to complement the innovations that healthcare stakeholders roll out.
- Asia – Differentiated Products Needed to Leverage the Cardiovascular Disease Segment. BMI research report, February 12, 2016
- Decision Resources 2015, Deep Vein Thrombosis and Pulmonary Thromboembolism
Written by APBN Writer, Cheryl Lee Zhi Qin