This study evaluates the use of a lower INR target (1.5 to 2.5) in patients with a mechanical bileaflet heart valve in the aortic position. This study will inform physicians about whether a lower INR target will decrease the risk of bleeding or increase the risk of blood clot formation and stroke. These results have the potential to reduce the burden of bleeding in patients with a mechanical heart valve who require lifelong warfarin (Coumadin) treatment.
Warfarin (Coumadin) is a blood thinner used to prevent blood clot formation in patients with mechanical heart valves. Blood clots can block blood flow to the brain, heart, or other parts of the body. Mechanical heart valves increases the risk of clot so patients with a mechanical heart valve must take warfarin to reduce their risk of stroke and other blood clot-related problems. The degree to which warfarin 'works' varies from person to person, and so dosage is determined by measuring each person's response to the drug as an 'international normalized ratio' or INR. A patient with an INR over 1.0 has blood that takes longer to clot than average, and increasing INR values represent increasing time required for blood to clot. While an INR over 1.0 decreases clotting risk, it also increases bleeding risk. It is important to carefully balance these risks. Specific INR targets have been recommended for patients with a mechanical heart valve, but these recommendations differ between scientific groups and are based on low quality evidence. Recent studies suggest that a lower INR target range than is currently recommended can be used safely. A laboratory study showed that warfarin effectively prevents blood clot formation on mechanical heart valves as long as the INR is 1.5 or above. Two moderately-sized clinical studies showed that an INR target range of 1.5-2.5 resulted in less bleeding than the usual higher target range without increasing blood clot formation or stroke in patients with a newer valve model. Whether we could use a lower INR target range for patients with a mechanical aortic valve remains controversial. This study evaluates the use of a lower INR target (1.5 to 2.5) in patients with a mechanical bileaflet heart valve in the aortic position. This study will inform physicians about whether a lower INR target will decrease the risk of bleeding or increase the risk of blood clot formation and stroke. These results have the potential to reduce the burden of bleeding in patients with a mechanical heart valve who require lifelong warfarin (Coumadin) treatment.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
2,625
Participants in both arms will be on warfarin therapy post-mechanical valve replacement as is standard, but will have different INR target ranges.
Ziekenhuis Oost-Limburg
Genk, Limburg, Belgium
RECRUITINGAZ Oostende
Ostend, West-Vlaanderen, Belgium
RECRUITINGImelda Hospital
Keerbergen, Belgium
RECRUITINGUniversitair Ziekenhuis Leuven
Leuven, Belgium
Thrombosis/thromboembolism
Number of patients who have at least one of the following: ischemic stroke, systemic thromboembolism, and valve thrombosis
Time frame: Through study completion, an expected mean of 2-3 years
Major bleeding
Number of patients that have bleeding that results in the following: 1. Death and/or, 2. Symptomatic bleeding in critical area or organ (e.g. intracranial, intraspinal, intraocular, retroperitoneal, intraarticular, pericardial, in a non-operated joint, or intramuscular with compartment syndrome) and/or, 3. Bleeding that causes drop of hemoglobin level by 20 g/L or more, or that requires the transfusion of 2 or more units of packed red blood cells or whole blood
Time frame: Through study completion, an expected mean of 2-3 years
All cause mortality
Selected rather than cardiovascular mortality, as cause-specific mortality is often difficult to ascertain or define in complex cardiovascular patients in whom multi-end-organ dysfunction may accompany cardiovascular decline.
Time frame: Through study completion, an expected mean of 2-3 years
All clinically important bleeding
Number of patients that experience all clinically important bleeding (major and minor)
Time frame: Through study completion, an expected mean of 2-3 years
Minor bleeding
Number of patients that experience a bleed that does not meet major bleeding criteria
Time frame: Through study completion, an expected mean of 2-3 years
All stroke
Number of patients that experience a strokes, including ischemic stroke, ischemic with secondary transformation, stroke of uncertain classification and hemorrhagic stroke
Time frame: Through study completion, an expected mean of 2-3 years
Ischemic stroke
Number of patients that experience an ischemic stroke, defined as focal brain infarction caused by an arterial (or rarely venous) obstruction and as documented by CT/MRI that is normal or shows an infarct in the clinicall expected area
Time frame: Through study completion, an expected mean of 2-3 years
Hemorrhagic stroke
Number of patients that experience a hemorrhagic stroke, defined as requiring neuroimaging or autopsy confirmation, and includes two subcategories: primary intracerebral hemorrhage and primary subarachnoid hemorrhage
Time frame: Through study completion, an expected mean of 2-3 years
Type 1, 2 or 3 myocardial infarction
Number of patients who experience a type 1, 2 or 3 myocardial infarction
Time frame: Through study completion, an expected mean of 2-3 years
Systemic thromboembolism
Number of patients who experience a systemic thromboembolism
Time frame: Through study completion, an expected mean of 2-3 years
Valve thrombosis
Number of patients who experience a valve thrombosis
Time frame: Through study completion, an expected mean of 2-3 years
Pulmonary embolism
Number of patients who experience a pulmonary embolism
Time frame: Through study completion, an expected mean of 2-3 years
Deep vein thrombosis
Number of patients who experience a deep vein thrombosis
Time frame: Through study completion, an expected mean of 2-3 years
New renal replacement therapy
Number of patients requiring new renal replacement therapy
Time frame: Through study completion, an expected mean of 2-3 years
Time in therapeutic range
The percentage of time the patient's INR was within the target range
Time frame: Through study completion, an expected mean of 2-3 years
Proportion of patients with extreme INR values (>4)
The proportion of patients with at least one reported INR value above 4
Time frame: Through study completion, an expected mean of 2-3 years
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University of Botswana, at Princess Marina Hospital
Gaborone, Botswana
RECRUITINGSociedade Hospitalar Angelina Caron
Campina Grande do Sul, Paraná, Brazil
RECRUITINGHEW Cardiologia LTDA
Joinville, Santa Catarina, Brazil
RECRUITINGInCor-HCFMUSP
Cerqueira César, São Paulo, Brazil
RECRUITINGFundação Universitária de Cardiologia mantededora do Instituto de Cardiologia e Transplantes do Distrito Federal
Brasília, Brazil
RECRUITINGHospital de Messejana
Fortaleza, Brazil
RECRUITING...and 35 more locations