Venous thromboembolism (VTE), which includes deep vein thrombosis (DVT; clots in the leg veins) and pulmonary embolism (PE: clot that travels to the heart and lung circulation), is a major cardiovascular disease that affects adults of all ages and ethnicities, yet has received far less attention than heart attack and stroke. Diagnosed in 1-2 per 1000 persons per year, VTE is the 3rd most common cardiovascular disorder after acute coronary syndrome and stroke. PE, the most serious form of VTE, is the 3rd leading cause of cardiovascular death overall and sudden death in hospitalized patients. Acutely, 10% of patients with PE die rapidly prior to diagnosis, emphasizing the importance of preventing VTE. Moreover, PE has remained one of the most commonly missed diagnoses in clinical medicine as signs and symptoms can sometimes be relatively mild or wrongly attributed (both by patients and by doctors) to other pulmonary diseases. In addition to this acute disease burden, VTE also imposes life-long burden to many patients because of its frequent chronic sequelae, including recurrent episodes of VTE (average recurrence rate off anticoagulants is 5-20% per year), the post-thrombotic syndrome (PTS) (occurs in 20-40% of DVT patients) and chronic thromboembolic pulmonary hypertension (occurs in 3-4% of PE patients).
As the risk of VTE increases steeply with age, our population’s aging demographic portends a rising incidence of VTE. Not surprisingly, the health care burden of VTE is substantial: the cost to treat an individual case of acute VTE is more than 4.000 euros, and the estimated and the estimated total cost of VTE and its complications in the Netherlands is at least 100 million euros per year. Important indirect costs such as loss of productivity that affects patients, families, and society at large are also considerable.
Anticoagulants (warfarin), the mainstay of VTE treatment, are very effective at preventing VTE extension and VTE recurrence, with relative risk reductions greater than 80%. Anticoagulants are also the leading drug class linked to drug-related adverse events (e.g. life-threatening bleeding) and impose patient burden from the need for injections, frequent laboratory monitoring, and lifestyle or dietary modifications. Thus, VTE treatment needs to be individualised to optimally balance efficacy and safety. Individualisation increases treatment complexity, which poses knowledge translation (KT) challenges that can be met by developing and validating clinical decision rules to guide clinicians and patients. A number of new or direct oral anticoagulants to prevent and treat VTE have been approved in the last few years, and others are in the development or testing phases. The long-term efficacy, safety, cost-effectiveness, and comparative effectiveness of these drugs are yet unknown, and many hospital and community physicians still have limited experience with their use. Also, only selected patients were included in the trials that led to regulatory approval of these drugs, leaving key knowledge gaps about the role of new therapies in many important subgroups (obese patients, those with renal dysfunction, pregnant or lactating women, frail elderly, and cancer patients) for the research community to address. Other important knowledge gaps include inadequately understood causal factors for first and recurrent VTE, inconsistent use of proven measures to prevent VTE, limited community expertise in diagnosing and managing VTE and its complications particularly also when it comes to missing a diagnosis, and limited knowledge of VTE among the general public. Taken together, it is evident that VTE is a significant cause of death, short-term sickness, long-term disability and economic burden to the Dutch population, and that further clinical research, from early phase studies to KT, is needed to address important knowledge gaps and improve patient outcomes.
With the rising incidence of VTE and, for the first time in 60 years, the availability of numerous new oral drug options besides warfarin to treat VTE, it is an opportune time to take action to address this important public health issue in a focused, highly organized and patient centred manner. We therefore propose the creation of the Dutch Thrombosis Network (DTN), a national, patient-oriented program centered on thrombosis related research, health care innovation, patient empowerment, training for physicians and students, and knowledge transfer.