This is a Prospective, Open-label Phase 2 Pilot Study With Independent Evaluation of All Outcomes and a Historical Control Group to Determine if Rivaroxaban (Xarelto) is Feasible and Safe for Prevention of Major Complications in Patients Undergoing a Mechanical Aortic Heart Valve Replacement.

Background

Although the overall incidence of complications associated with prosthetic cardiac valve implantation has decreased considerably since its introduction more than 3 decades ago, valvular thrombosis and systemic thromboembolism remain a major concern for cardiothoracic surgeons, cardiologists, and other practicing clinicians because of the well-known potential to cause devastating events including ischemic stroke and death.

Factors that contribute to the thrombogenicity of prosthetic heart valves include: altered blood flow and haemostatic activation caused by vessel-wall disruption during surgery or exposure of artificial surfaces to the circulating blood. Short-term parenteral anticoagulation with unfractionated heparin or low-molecular-weight heparin is often used until therapeutic concentrations of an oral vitamin K antagonist are reached. Vitamin K antagonists, alone or in combination with aspirin, are used for long-term management of these patients. However, Vitamin K antagonists are cumbersome to use, because of their multiple interactions with food and drugs, and they require frequent laboratory monitoring. Therefore, they are often not used, and when they are, rates of discontinuation are high. Many patients receiving Phenprocoumon still have inadequate anticoagulation. Thus, there is a need for new anticoagulant agents.

Patients who self-monitor therapy with vitamin K antagonists at home rather than in a laboratory are more often in the therapeutic range and have a lower incidence of complications and hospital admissions than those who do not. Meta-analyses of randomized trials have recently found that patient self-monitoring was associated with a 33% reduction of risk of death, a 55% reduction of risk of thromboembolism, and a slight decrease in major haemorrhage. Self-monitoring was also associated with improved quality of life and satisfaction. However, the number of INR values within the target range in self-monitored patients is still very poor, which is no more than 70% !, even taking in account a wide range of INR 2.5-4.5. Another main obstacle to widespread use of patient self-monitoring is cost. In the UK National Health Service, the estimated cost of patient self-monitoring is £122 000 per quality-adjusted life year (QALY) over 5 years and £63 000 over 10 years. This is not cost-effective considering the commonly accepted threshold of £30 000 per QALY. Costs are related to the portable INR-monitoring device, test strips, and patient education programs.

The oral direct thrombin inhibitor - dabigatran etexilate - and two oral direct factor Xa inhibitors - rivaroxaban and apixaban - are in advanced stages of clinical development and are expected to replace oral vitamin K antagonists for many indications.