FDA approved for 2 pediatric indications:
1) Venous thromboembolism in children - after at least 5 days of parenteral anticoagulant treatment.
2) Thromboprophylaxis in pediatric patients < 2 yrs of age after Fontan operation.
Showing posts with label Anticoagulation. Show all posts
Showing posts with label Anticoagulation. Show all posts
Monday, May 9, 2022
Saturday, March 17, 2012
CLARINET trial
Wessel, D. et al.
(Presented at AHA 2010)
Background: Infants with cyanotic congenital heart disease (CCHD) palliated with a systemic-to-pulmonary artery (PA) shunt are at increased risk for shunt thrombosis and mortality.
Methods: We conducted a multi-center, randomized, double-blind, placebo-controlled trial to determine whether the addition of clopidogrel, 0.2mg/kg/day, to conventional therapy reduces all-cause mortality and shunt-related morbidity in infants with CCHD palliated with a PA shunt. The clopidogrel dose was selected to inhibit ADP-induced platelet aggregation by 30-50%, similar to the 75 mg adult dose. The primary efficacy outcome event was the first occurrence of any component of the composite endpoint of death, shunt thrombosis or a cardiac procedure before 120 days of age following an event considered of thrombotic nature. This event-driven trial conducted in 32 countries had 80% power to detect a 30% relative reduction in the primary event rate with 172 events and .05 overall type I error rate.
Results: 906 infants <3 months of age who had undergone a PA shunt were randomly assigned to receive clopidogrel (467, 51.5%) or placebo (439, 48.5%) in addition to conventional therapy. Median duration of treatment was 162 days. Concomitant aspirin was administered in 88% of subjects.
The primary composite outcome rate did not differ significantly between the clopidogrel vs. placebo groups: 19.1% vs. 20.5%, respectively, with relative risk reduction = 11.1% (95%CI: –19.2, 33.6; p=.43).
Components of the composite primary outcome, analyzed separately, also did not differ significantly between clopidogrel and placebo groups: mortality rate was 11.8% vs 13.9%; shunt thrombosis was 5.8% vs. 4.8%, and cardiac-related interventions occurred in 4.5% vs. 3.2%, respectively.
Clopidogrel treatment was not significantly beneficial within any subgroups, specific cardiac defect groups or shunt types. The percentage of subjects in the clopidogrel vs. placebo groups with any bleeding event (18.8% vs. 20.2%) and with severe bleeding events (4.1% vs. 3.4%) was similar.
Conclusion: Clopidogrel treatment of infants < 3 months of age with CCHD palliated with a PA shunt and predominantly receiving concomitant aspirin therapy does not reduce all-cause mortality or shunt-related morbidity.
(Presented at AHA 2010)
Background: Infants with cyanotic congenital heart disease (CCHD) palliated with a systemic-to-pulmonary artery (PA) shunt are at increased risk for shunt thrombosis and mortality.
Methods: We conducted a multi-center, randomized, double-blind, placebo-controlled trial to determine whether the addition of clopidogrel, 0.2mg/kg/day, to conventional therapy reduces all-cause mortality and shunt-related morbidity in infants with CCHD palliated with a PA shunt. The clopidogrel dose was selected to inhibit ADP-induced platelet aggregation by 30-50%, similar to the 75 mg adult dose. The primary efficacy outcome event was the first occurrence of any component of the composite endpoint of death, shunt thrombosis or a cardiac procedure before 120 days of age following an event considered of thrombotic nature. This event-driven trial conducted in 32 countries had 80% power to detect a 30% relative reduction in the primary event rate with 172 events and .05 overall type I error rate.
Results: 906 infants <3 months of age who had undergone a PA shunt were randomly assigned to receive clopidogrel (467, 51.5%) or placebo (439, 48.5%) in addition to conventional therapy. Median duration of treatment was 162 days. Concomitant aspirin was administered in 88% of subjects.
The primary composite outcome rate did not differ significantly between the clopidogrel vs. placebo groups: 19.1% vs. 20.5%, respectively, with relative risk reduction = 11.1% (95%CI: –19.2, 33.6; p=.43).
Components of the composite primary outcome, analyzed separately, also did not differ significantly between clopidogrel and placebo groups: mortality rate was 11.8% vs 13.9%; shunt thrombosis was 5.8% vs. 4.8%, and cardiac-related interventions occurred in 4.5% vs. 3.2%, respectively.
Clopidogrel treatment was not significantly beneficial within any subgroups, specific cardiac defect groups or shunt types. The percentage of subjects in the clopidogrel vs. placebo groups with any bleeding event (18.8% vs. 20.2%) and with severe bleeding events (4.1% vs. 3.4%) was similar.
Conclusion: Clopidogrel treatment of infants < 3 months of age with CCHD palliated with a PA shunt and predominantly receiving concomitant aspirin therapy does not reduce all-cause mortality or shunt-related morbidity.
PICOLO trial results
Dosing of Clopidogrel for Platelet Inhibition in Infants and Young Children
Primary Results of the Platelet Inhibition in Children On cLOpidogrel (PICOLO) Trial
Jennifer S, Li et al. for the PICOLO Investigators
Primary Results of the Platelet Inhibition in Children On cLOpidogrel (PICOLO) Trial
Jennifer S, Li et al. for the PICOLO Investigators
Circulation 2008;117:553-9
Background— Infants and young children with certain types of heart disease are at increased risk for thromboses. Clopidogrel 75 mg/d is used in adults to prevent thrombotic events. The dose to achieve similar platelet inhibition in children is unknown. The objectives of the present study were (1) to determine the dose of clopidogrel needed in infants and young children to achieve a mean 30% to 50% inhibition of 5-μmol/L ADP–induced platelet aggregation (ie, inhibition similar to that observed with 75 mg in adults) and (2) to assess the safety and tolerability of clopidogrel in infants and young children.
Methods and Results— We performed a prospective, multicenter, randomized, placebo-controlled trial evaluating the pharmacodynamics of clopidogrel in children (0 to 24 months) with a cardiac condition at risk for arterial thrombosis. Patients were randomized to clopidogrel versus placebo in a 3:1 ratio in 4 sequential groups (0.01, 0.10, 0.20, and 0.15 mg/kg) for 7 abd 28 days. Platelet aggregation was assessed at baseline and steady state by light-transmission aggregometry. Of 116 patients enrolled, 92 (50% neonates, 50% infants/toddlers) were randomized, and 73 completed the study. A total of 79% of the randomized and treated patients were taking aspirin.
Compared with placebo, clopidogrel 0.20 mg · kg−1 · d−1 resulted in a mean 49.3% (95% confidence interval 25.7% to 72.8%) inhibition of the maximum extent of platelet aggregation and a mean 43.9% (95% confidence interval 18.6% to 69.2%) inhibition of the rate of platelet aggregation. There was marked interpatient variability in the degree of platelet aggregation inhibition within each treatment-dose group and age group. No serious bleeding events occurred.
Conclusions— Clopidogrel 0.20 mg/kg/day in children 0 to 24 months of age achieves a platelet inhibition level similar to that in adults taking 75 mg/d. Clopidogrel is well tolerated in infants and young children at this dose.
Background— Infants and young children with certain types of heart disease are at increased risk for thromboses. Clopidogrel 75 mg/d is used in adults to prevent thrombotic events. The dose to achieve similar platelet inhibition in children is unknown. The objectives of the present study were (1) to determine the dose of clopidogrel needed in infants and young children to achieve a mean 30% to 50% inhibition of 5-μmol/L ADP–induced platelet aggregation (ie, inhibition similar to that observed with 75 mg in adults) and (2) to assess the safety and tolerability of clopidogrel in infants and young children.
Methods and Results— We performed a prospective, multicenter, randomized, placebo-controlled trial evaluating the pharmacodynamics of clopidogrel in children (0 to 24 months) with a cardiac condition at risk for arterial thrombosis. Patients were randomized to clopidogrel versus placebo in a 3:1 ratio in 4 sequential groups (0.01, 0.10, 0.20, and 0.15 mg/kg) for 7 abd 28 days. Platelet aggregation was assessed at baseline and steady state by light-transmission aggregometry. Of 116 patients enrolled, 92 (50% neonates, 50% infants/toddlers) were randomized, and 73 completed the study. A total of 79% of the randomized and treated patients were taking aspirin.
Compared with placebo, clopidogrel 0.20 mg · kg−1 · d−1 resulted in a mean 49.3% (95% confidence interval 25.7% to 72.8%) inhibition of the maximum extent of platelet aggregation and a mean 43.9% (95% confidence interval 18.6% to 69.2%) inhibition of the rate of platelet aggregation. There was marked interpatient variability in the degree of platelet aggregation inhibition within each treatment-dose group and age group. No serious bleeding events occurred.
Conclusions— Clopidogrel 0.20 mg/kg/day in children 0 to 24 months of age achieves a platelet inhibition level similar to that in adults taking 75 mg/d. Clopidogrel is well tolerated in infants and young children at this dose.
Wednesday, April 20, 2011
Interruprtions of Warfarin for procedures
Circulation: Cardiovascular Quality and Outcomes
2011;4(2):206-210
Guideline-Discordant Periprocedural Interruptions in Warfarin Therapy
Skolarus, Lesli E. MD, MS; Morgenstern, Lewis B. MD; Froehlich, James B. MD, MPH; Lisabeth, Lynda D. PhD; Brown, Devin L. MD, MS
Abstract
Background—: Periprocedural interruptions in warfarin therapy increase thromboembolic risks to patients and are not indicated for all procedures. We sought to determine the frequency and guideline concordance of periprocedural warfarin interruptions to inform a future educational intervention.
Methods and Results—: In October and November of 2009, an anonymous postal survey was sent to all patients followed for more than 1 year by the University of Michigan Anticoagulation service. Patients were asked how many times in the prior year they were requested to interrupt warfarin therapy for a medical or dental procedure or test and the specific indication for the requested interruption in warfarin therapy. A total of 1686 of 2133 (79%) subjects responded. The mean age of respondents was 69 years (SD=14 years). The majority were men (56%) and white (93%). Atrial fibrillation was the most common indication for warfarin therapy (n=966, 57%). At least 1 request to interrupt warfarin therapy in the prior year was given by 819 of 1648 (50%) respondents, including 481 of the 947 (51%) respondents taking warfarin for atrial fibrillation. Forty-eight percent of requests to interrupt warfarin among all respondents and 50% of requests to interrupt warfarin among those taking warfarin, specifically for atrial fibrillation, were for indications not supported by guideline statements.
Conclusions—: Periprocedural requests to interrupt warfarin therapy are common and are often discordant with current guidelines. Educational interventions may decrease risk of periprocedural thromboembolic complications.
2011;4(2):206-210
Guideline-Discordant Periprocedural Interruptions in Warfarin Therapy
Skolarus, Lesli E. MD, MS; Morgenstern, Lewis B. MD; Froehlich, James B. MD, MPH; Lisabeth, Lynda D. PhD; Brown, Devin L. MD, MS
Abstract
Background—: Periprocedural interruptions in warfarin therapy increase thromboembolic risks to patients and are not indicated for all procedures. We sought to determine the frequency and guideline concordance of periprocedural warfarin interruptions to inform a future educational intervention.
Methods and Results—: In October and November of 2009, an anonymous postal survey was sent to all patients followed for more than 1 year by the University of Michigan Anticoagulation service. Patients were asked how many times in the prior year they were requested to interrupt warfarin therapy for a medical or dental procedure or test and the specific indication for the requested interruption in warfarin therapy. A total of 1686 of 2133 (79%) subjects responded. The mean age of respondents was 69 years (SD=14 years). The majority were men (56%) and white (93%). Atrial fibrillation was the most common indication for warfarin therapy (n=966, 57%). At least 1 request to interrupt warfarin therapy in the prior year was given by 819 of 1648 (50%) respondents, including 481 of the 947 (51%) respondents taking warfarin for atrial fibrillation. Forty-eight percent of requests to interrupt warfarin among all respondents and 50% of requests to interrupt warfarin among those taking warfarin, specifically for atrial fibrillation, were for indications not supported by guideline statements.
Conclusions—: Periprocedural requests to interrupt warfarin therapy are common and are often discordant with current guidelines. Educational interventions may decrease risk of periprocedural thromboembolic complications.
Thursday, April 14, 2011
ACC 2011: On-X valve & INR
From Heartwire:
PROACT: Early results show high-risk patients do well with low warfarin and carbon valveApril 13, 2011 Reed Miller New Orleans - Preliminary results from the high-risk arm of PROACT presented at the American College of Cardiology (ACC) 2011 Scientific Sessions show the all-carbon On-X valve (On-X Life Technologies, Austin, TX) is safe with lower levels of anticoagulant therapy than normally prescribed to patients with mechanical aortic valves [1]. Primary investigator Dr John Puskas (Emory University, Atlanta, GA) presented early results from the high-risk aortic-valve-replacement arm of PROACT, the only arm of the trial that is fully enrolled. As hypothesized, patients with an On-X valve treated with lower-than-standard doses of aspirin and warfarin after three months on a standard regimen had the same composite rate of thromboembolism and hemorrhage as On-X patients who stayed on the standard regimen throughout the follow-up. On-X valve [Source: On-X Life Technologies] All 185 patients in the high-risk arm received an On-X valve as a replacement for a defective aortic valve and were considered to have a high potential for thrombotic or bleeding events. All patients were maintained with standard anticoagulation therapy for the first three months after surgery and then randomized into the low-anticoagulant group or the control group. The low-anticoagulant group was switched to a daily dose of either 81 or 325 mg of aspirin plus warfarin to achieve an INR target of 1.5 to 2.0. Patients randomized to the control group continued with standard anticoagulation therapy—aspirin and warfarin to achieve an INR of 2.0 to 3.5 throughout the trial, the target set in the ACC/AHA guidelines for treatment of patients with a replacement aortic valve. The average follow-up so far is about 16 months, with a total of 247 patient-years of data collected. Eventually, the investigators expect to collect 6000 patient-years of data. During the study period, five low-anticoagulant and four control patients died. The low-anticoagulant group had 2.5 bleeding events per patient-year, vs 4.4 per patient year in the control group, but the stroke rate was 1.3% per patient-year in the low-anticoagulant group vs 0.4% per patient-year in the control group. For the combined end point of stroke and thrombotic and bleeding events, the rates were 3.8% per patient-year in the low-anticoagulant group and 4.9% per patient-year in the control group. Puskas said that the goal of the study is to convince the FDA to let On-X label the valve as safe with lower doses of anticoagulation, thereby providing the durability of a mechanical valve with doses of anticoagulant drugs closer to those given tissue-valve recipients. And "one day we may be able to offer a durable mechanical heart valve with no blood thinner in selected patients," he said. The PROACT study, launched in 2006 at 40 centers, is also enrolling a lower-risk arm and a mitral-valve arm. The aortic-valve arm is comparing standard anticoagulant therapy with clopidogrel therapy in patients with the On-X aortic valve considered at relatively low risk for thrombotic or bleeding events. The mitral-valve arm is comparing anticoagulant therapy targeted to INRs of 2.0 to 2.5 vs standard anticoagulant therapy in patients with an On-X mitral valve. The company expects to complete the trial by 2014.Valve material reduces clot risk Puskas explained that patients with an On-X valve, which has been on the US market for about 10 years, may be able to get by with lower doses of anticoagulant because of the unique all-carbon material and design of the device. The On-X carbon material is a pure form of isotropic pyrolytic carbon created with a patented process that, unlike other carbon materials used for heart valves, does not require silicon alloying to ensure wear resistance. Earlier carbon valves were made out of carbon with about 8% silicon, because the technology did not exist to mill pure carbon thin enough to make a valve leaflet, Puskas explained. "When you polish pure carbon you can get an exceedingly smooth surface, to which platelets and blood don't really stick very much, but if you polish a silicon-carbon composite, the silicon over time tends to pit and leave very tiny irregularities in the surface." The valve's "trumpet-mouth end" guides blood through with a laminar—instead of turbulent—flow at a lower pressure gradient than most mechanical valves, preventing damage to the blood. The laminar flow also allows the leaflets inside the cylinder to close more quickly and to open more completely than leaflets in most valve designs, Puskas said. Because the leaflets close faster, they regurgitate less blood back through the valve, and "as a result of that lesser leak, the designers of the valve are able to be luxurious about intentionally allowing some leakage around the hinge points of the leaflets, and it's those hinge points where clotting can occur and the valve can stick," Puskas said. "So by designing leaflets that intentionally leak a little bit around the hinges, but close so quickly that the overall leakage is much less than in the predecessor valves, you can have your cake and eat it too. You have a valve that leaks very little, but leaks where you want it to leak; it washes the hinges to prevent clots from forming there." INR monitoring at home Puskas told heartwire that he expects one of the "important contributions of PROACT will be to show the superiority of home INR monitoring" vs periodic monitoring at the physician's office. On-X has provided all of the patients in the study with home INR monitoring so that they can keep continuous track of their blood's ability to clot and adjust the anticoagulant therapy accordingly. The Home INR Study (THINRS) found that weekly self-testing of INR levels did not significantly delay the time to a first stroke, major bleed, or death in patients on warfarin compared with monthly in-office testing with a higher-than-average level of clinical care, but home INR testing did help patients keep their INR within therapeutic range and improved patients' satisfaction with their anticoagulation therapy and quality of life. Puskas said that there is already evidence that patients whose INR varies widely are more prone to complications than patients who can keep their INR more stable, and he expects that the trial will be able to show that patients are better able to maintain a level INR if they can monitor it on their own without visiting their doctor. He said the trial will collect over 100 000 data points on home INR testing.
PROACT: Early results show high-risk patients do well with low warfarin and carbon valveApril 13, 2011 Reed Miller New Orleans - Preliminary results from the high-risk arm of PROACT presented at the American College of Cardiology (ACC) 2011 Scientific Sessions show the all-carbon On-X valve (On-X Life Technologies, Austin, TX) is safe with lower levels of anticoagulant therapy than normally prescribed to patients with mechanical aortic valves [1]. Primary investigator Dr John Puskas (Emory University, Atlanta, GA) presented early results from the high-risk aortic-valve-replacement arm of PROACT, the only arm of the trial that is fully enrolled. As hypothesized, patients with an On-X valve treated with lower-than-standard doses of aspirin and warfarin after three months on a standard regimen had the same composite rate of thromboembolism and hemorrhage as On-X patients who stayed on the standard regimen throughout the follow-up. On-X valve [Source: On-X Life Technologies] All 185 patients in the high-risk arm received an On-X valve as a replacement for a defective aortic valve and were considered to have a high potential for thrombotic or bleeding events. All patients were maintained with standard anticoagulation therapy for the first three months after surgery and then randomized into the low-anticoagulant group or the control group. The low-anticoagulant group was switched to a daily dose of either 81 or 325 mg of aspirin plus warfarin to achieve an INR target of 1.5 to 2.0. Patients randomized to the control group continued with standard anticoagulation therapy—aspirin and warfarin to achieve an INR of 2.0 to 3.5 throughout the trial, the target set in the ACC/AHA guidelines for treatment of patients with a replacement aortic valve. The average follow-up so far is about 16 months, with a total of 247 patient-years of data collected. Eventually, the investigators expect to collect 6000 patient-years of data. During the study period, five low-anticoagulant and four control patients died. The low-anticoagulant group had 2.5 bleeding events per patient-year, vs 4.4 per patient year in the control group, but the stroke rate was 1.3% per patient-year in the low-anticoagulant group vs 0.4% per patient-year in the control group. For the combined end point of stroke and thrombotic and bleeding events, the rates were 3.8% per patient-year in the low-anticoagulant group and 4.9% per patient-year in the control group. Puskas said that the goal of the study is to convince the FDA to let On-X label the valve as safe with lower doses of anticoagulation, thereby providing the durability of a mechanical valve with doses of anticoagulant drugs closer to those given tissue-valve recipients. And "one day we may be able to offer a durable mechanical heart valve with no blood thinner in selected patients," he said. The PROACT study, launched in 2006 at 40 centers, is also enrolling a lower-risk arm and a mitral-valve arm. The aortic-valve arm is comparing standard anticoagulant therapy with clopidogrel therapy in patients with the On-X aortic valve considered at relatively low risk for thrombotic or bleeding events. The mitral-valve arm is comparing anticoagulant therapy targeted to INRs of 2.0 to 2.5 vs standard anticoagulant therapy in patients with an On-X mitral valve. The company expects to complete the trial by 2014.Valve material reduces clot risk Puskas explained that patients with an On-X valve, which has been on the US market for about 10 years, may be able to get by with lower doses of anticoagulant because of the unique all-carbon material and design of the device. The On-X carbon material is a pure form of isotropic pyrolytic carbon created with a patented process that, unlike other carbon materials used for heart valves, does not require silicon alloying to ensure wear resistance. Earlier carbon valves were made out of carbon with about 8% silicon, because the technology did not exist to mill pure carbon thin enough to make a valve leaflet, Puskas explained. "When you polish pure carbon you can get an exceedingly smooth surface, to which platelets and blood don't really stick very much, but if you polish a silicon-carbon composite, the silicon over time tends to pit and leave very tiny irregularities in the surface." The valve's "trumpet-mouth end" guides blood through with a laminar—instead of turbulent—flow at a lower pressure gradient than most mechanical valves, preventing damage to the blood. The laminar flow also allows the leaflets inside the cylinder to close more quickly and to open more completely than leaflets in most valve designs, Puskas said. Because the leaflets close faster, they regurgitate less blood back through the valve, and "as a result of that lesser leak, the designers of the valve are able to be luxurious about intentionally allowing some leakage around the hinge points of the leaflets, and it's those hinge points where clotting can occur and the valve can stick," Puskas said. "So by designing leaflets that intentionally leak a little bit around the hinges, but close so quickly that the overall leakage is much less than in the predecessor valves, you can have your cake and eat it too. You have a valve that leaks very little, but leaks where you want it to leak; it washes the hinges to prevent clots from forming there." INR monitoring at home Puskas told heartwire that he expects one of the "important contributions of PROACT will be to show the superiority of home INR monitoring" vs periodic monitoring at the physician's office. On-X has provided all of the patients in the study with home INR monitoring so that they can keep continuous track of their blood's ability to clot and adjust the anticoagulant therapy accordingly. The Home INR Study (THINRS) found that weekly self-testing of INR levels did not significantly delay the time to a first stroke, major bleed, or death in patients on warfarin compared with monthly in-office testing with a higher-than-average level of clinical care, but home INR testing did help patients keep their INR within therapeutic range and improved patients' satisfaction with their anticoagulation therapy and quality of life. Puskas said that there is already evidence that patients whose INR varies widely are more prone to complications than patients who can keep their INR more stable, and he expects that the trial will be able to show that patients are better able to maintain a level INR if they can monitor it on their own without visiting their doctor. He said the trial will collect over 100 000 data points on home INR testing.
Saturday, December 4, 2010
Rivaroxabon - Oral factor Xa inhibitor
NEJM dt. 12/04/10:
The EINSTEIN Investigators
Rivaroxaban, an oral factor Xa inhibitor, may provide a simple, fixed-dose regimen for treating acute deep-vein thrombosis (DVT) and for continued treatment, without the need for laboratory monitoring.METHODS
We conducted an open-label, randomized, event-driven, noninferiority study that compared oral rivaroxaban alone (15 mg twice daily for 3 weeks, followed by 20 mg once daily) with subcutaneous enoxaparin followed by a vitamin K antagonist (either warfarin or acenocoumarol) for 3, 6, or 12 months in patients with acute, symptomatic DVT. In parallel, we carried out a double-blind, randomized, event-driven superiority study that compared rivaroxaban alone (20 mg once daily) with placebo for an additional 6 or 12 months in patients who had completed 6 to 12 months of treatment for venous thromboembolism. The primary efficacy outcome for both studies was recurrent venous thromboembolism. The principal safety outcome was major bleeding or clinically relevant nonmajor bleeding in the initial-treatment study and major bleeding in the continued-treatment study.
RESULTS
The study of rivaroxaban for acute DVT included 3449 patients: 1731 given rivaroxaban and 1718 given enoxaparin plus a vitamin K antagonist. Rivaroxaban had noninferior efficacy with respect to the primary outcome (36 events [2.1%], vs. 51 events with enoxaparin–vitamin K antagonist [3.0%]; hazard ratio, 0.68; 95% confidence interval [CI], 0.44 to 1.04; P<0.001). p="0.11).
CONCLUSIONS
Rivaroxaban offers a simple, single-drug approach to the short-term and continued treatment of venous thrombosis that may improve the benefit-to-risk profile of anticoagulation. (Funded by Bayer Schering Pharma and Ortho-McNeil; ClinicalTrials.gov numbers, NCT00440193and NCT00439725.)
Thursday, October 21, 2010
INR - Home testing does not improve outcome measures.
Effect of Home Testing of International Normalized Ratio on Clinical Events
David B. Matchar, M.D., Alan Jacobson, M.D., Rowena Dolor, M.D., M.H.S., Robert Edson, M.A., Lauren Uyeda, M.A., Ciaran S. Phibbs, Ph.D., Julia E. Vertrees, Pharm.D., Mei-Chiung Shih, Ph.D., Mark Holodniy, M.D., and Philip Lavori, Ph.D. for the THINRS Executive Committee and Site Investigators
N Engl J Med 2010; 363:1608-1620
October 21, 2010
Background
Warfarin anticoagulation reduces thromboembolic complications in patients with atrial fibrillation or mechanical heart valves, but effective management is complex, and the international normalized ratio (INR) is often outside the target range. As compared with venous plasma testing, point-of-care INR measuring devices allow greater testing frequency and patient involvement and may improve clinical outcomes.
Methods
We randomly assigned 2922 patients who were taking warfarin because of mechanical heart valves or atrial fibrillation and who were competent in the use of point-of-care INR devices to either weekly self-testing at home or monthly high-quality testing in a clinic. The primary end point was the time to a first major event (stroke, major bleeding episode, or death).
Results
The patients were followed for 2.0 to 4.75 years, for a total of 8730 patient-years of follow-up. The time to the first primary event was not significantly longer in the self-testing group than in the clinic-testing group (hazard ratio, 0.88; 95% confidence interval, 0.75 to 1.04; P=0.14). The two groups had similar rates of clinical outcomes except that the self-testing group reported more minor bleeding episodes. Over the entire follow-up period, the self-testing group had a small but significant improvement in the percentage of time during which the INR was within the target range (absolute difference between groups, 3.8 percentage points; P<0.001). At 2 years of follow-up, the self-testing group also had a small but significant improvement in patient satisfaction with anticoagulation therapy (P=0.002) and quality of life (P<0.001).
Conclusions
As compared with monthly high-quality clinic testing, weekly self-testing did not delay the time to a first stroke, major bleeding episode, or death to the extent suggested by prior studies. These results do not support the superiority of self-testing over clinic testing in reducing the risk of stroke, major bleeding episode, and death among patients taking warfarin therapy. (Funded by the Department of Veterans Affairs Cooperative Studies Program; ClinicalTrials.gov number, NCT00032591.)
David B. Matchar, M.D., Alan Jacobson, M.D., Rowena Dolor, M.D., M.H.S., Robert Edson, M.A., Lauren Uyeda, M.A., Ciaran S. Phibbs, Ph.D., Julia E. Vertrees, Pharm.D., Mei-Chiung Shih, Ph.D., Mark Holodniy, M.D., and Philip Lavori, Ph.D. for the THINRS Executive Committee and Site Investigators
N Engl J Med 2010; 363:1608-1620
October 21, 2010
Background
Warfarin anticoagulation reduces thromboembolic complications in patients with atrial fibrillation or mechanical heart valves, but effective management is complex, and the international normalized ratio (INR) is often outside the target range. As compared with venous plasma testing, point-of-care INR measuring devices allow greater testing frequency and patient involvement and may improve clinical outcomes.
Methods
We randomly assigned 2922 patients who were taking warfarin because of mechanical heart valves or atrial fibrillation and who were competent in the use of point-of-care INR devices to either weekly self-testing at home or monthly high-quality testing in a clinic. The primary end point was the time to a first major event (stroke, major bleeding episode, or death).
Results
The patients were followed for 2.0 to 4.75 years, for a total of 8730 patient-years of follow-up. The time to the first primary event was not significantly longer in the self-testing group than in the clinic-testing group (hazard ratio, 0.88; 95% confidence interval, 0.75 to 1.04; P=0.14). The two groups had similar rates of clinical outcomes except that the self-testing group reported more minor bleeding episodes. Over the entire follow-up period, the self-testing group had a small but significant improvement in the percentage of time during which the INR was within the target range (absolute difference between groups, 3.8 percentage points; P<0.001). At 2 years of follow-up, the self-testing group also had a small but significant improvement in patient satisfaction with anticoagulation therapy (P=0.002) and quality of life (P<0.001).
Conclusions
As compared with monthly high-quality clinic testing, weekly self-testing did not delay the time to a first stroke, major bleeding episode, or death to the extent suggested by prior studies. These results do not support the superiority of self-testing over clinic testing in reducing the risk of stroke, major bleeding episode, and death among patients taking warfarin therapy. (Funded by the Department of Veterans Affairs Cooperative Studies Program; ClinicalTrials.gov number, NCT00032591.)
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