Anticoagulation http://www.cheapjordans.us/air-jordan-retro-1101/air-jordan-retro-23 for three versus six months in patients with deep vein thrombosis or pulmonary embolism cheap jordans retro 3AbstractObjective To determine the optimum duration of oral anticoagulant therapy after an episode of deep vein thrombosis or pulmonary embolism, or both.Interventions Three (n=369) or six months (n=380) of anticoagulation with heparin for five days accompanied and followed by warfarin, with a target international normalised ratio of 2.0 3.5.Main outcome measures Death from deep vein thrombosis or pulmonary embolism; failure to resolve, extension, recurrence of during treatment; recurrence after treatment; and major haemorrhage during treatment.Results In the patients allocated to three months' treatment two died from deep vein thrombosis or pulmonary embolism during or after treatment, compared with three in the six month group. During treatment deep vein thrombosis or pulmonary embolism failed to resolve, extended, or recurred in six patients in the three month group without fatal consequences, compared with 10 in the six month group. After treatment there were 23 non fatal recurrences in the three month group and 16 in the six month group. Fatal and non fatal deep vein thrombosis or pulmonary embolism during treatment, and after treatment thus occurred in 31(8%) of those who had received three months' anticoagulation compared with 29 (8%) of those who had received six months' (P=0.80, 95% confidence interval for difference 3.1% to 4.7%). There were no fatal haemorrhages during treatment but there were eight major haemorrhages in those treated for http://www.cheapjordans.us/air-jordan-retro-1101/air-jordan-retro-34 six months and none in those treated for three months (P=0.008, 3.5% to 0.7%). Thus 31 (8%) of the patients receiving three months' anticoagulation experienced cheap retro air jordan 2 adverse outcomes as a result of deep vein thrombosis or pulmonary embolism or its treatment compared with 35 (9%) of those receiving six months' (P=0.79, 4.9% to 3.2%).Conclusion For patients in the UK with deep vein thrombosis or pulmonary embolism and no known risk factors for recurrence, there seems to be little, if any, advantage in increasing the duration of anticoagulation from three to six months. Any possible advantage would be small and would need to be judged against the increased risk of haemorrhage associated with the longer duration of treatment with warfarin.Trial registration Clinical Trials IntroductionIn 1960 Barritt and Jordan established that anticoagulation reduced the risk of death and of recurrent embolism in patients with pulmonary embolism,1 a conclusion subsequently supported by retrospective studies from Oxford2 and the United States.3 Treatment regimens now consist of heparin for four to five days,4 5 6 with anticoagulation maintained thereafter by warfarin.For those centres not already routinely using low molecular weight heparin, an expanded design was used to compare low molecular weight heparin with unfractionated heparin in terms of outcome during treatment outcome after the end of anticoagulation, and duration of inpatient stay. Too few patients (n=22) were entered into this randomisation for meaningful comparions of these outcomes and so we used their results solely in the comparisons of three months versus six months of anticoagulation.MethodsPatientsEligible patients were those aged 18 with suspected or proved deep vein thrombosis or pulmonary embolism, or both, whom the clinician intended to treat with anticoagulant. We encouraged confirmation of diagnosis with ultrasound, radioisotope, venographic, angiographic, or other objective tests but patients managed without the aid of such tests were accepted for the trial. Categories of definite, probable (high or moderate probability), low probability, or negative were taken from the reports of the results.Several factors or conditions excluded patients from entry. These were deep vein thrombosis or pulmonary embolism deemed so severe by the clinician as to require thrombolysis or pulmonary embolectomy; neoplasia diagnosed or requiring treatment, or both, within the previous three years; pregnancy; deep vein thrombosis or pulmonary embolism in the preceding three years; known polycythaemia, thrombocythaemia, antithrombin III deficiency, lupus anticoagulant, homozygous factor V Leiden, protein C or protein S deficiency, or other similar predisposing haematological disorders; any condition that would result in prolonged or continuous immobility or confinement to bed, such as advanced multiple sclerosis or orthopaedic problems of the lower limbs; previous allergy to heparin or warfarin; requirement for long term anticoagulant therapy; and inability to give informed consent.DesignPatients were randomised to three or six months of warfarin, the clinicians being asked to start warfarin on day one of the scheduled five days of heparin. Participating physicians used international normalised ratios to monitor anticoagulation with warfarin according to a standardised protocol.17 The aim was to achieve ratios between 2.0 and 3.5.Within each centre randomisation was by permuted blocks of eight through a series of numbered envelopes kept at a central point in each hospital or unit. Each envelope also contained an entry card to be posted to the coordinator as notification of entry. On receipt of that card the coordinator sent a form to the clinician, confirming the allocated treatment and requesting further details of the patient. This form also contained a section for the clinician to notify the coordinator of alteration of diagnosis or discontinuation of anticoagulation, or both: if a patient was found to fulfil any of the criteria for exclusion, that patient was removed from the analysis before we had any knowledge of the outcome of the study.The individual clinicians were responsible for decisions about inpatient or outpatient management. For purposes of the trial, physicians were asked to arrange follow up appointments at three, six, and 12 months from the date of entry. Brief review forms were sent to the clinician a fortnight or so before each follow up date for completion and return to the coordinator. The forms requested information on failure of resolution (swelling of the leg(s) or pain or tenderness that did not settle down during treatment), extension or recurrence of deep vein thrombosis or pulmonary embolism, results of international normalised ratios, dates of start and completion of therapy with heparin and with warfarin, and adverse events. Clinicians were asked to confirm suspected failure of resolution, extension, or recurrence by radiological or ultrasonic imaging, or both.Predetermined primary adverse outcomes were death from deep vein thrombosis or pulmonary embolism, failure during treatment (failure to resolve, extension, recurrence during treatment), recurrence after the end of treatment, and major haemorrhage during treatment. Patients experiencing any of the above were grouped together under the heading of "adverse outcome," and we reported this as a further point of comparison between the groups.We graded anticoagulation as good if the international normalised ratios were between 2.0 and 3.5 on at least two thirds of occasions, moderate if within that range on a third but less than two thirds of occasions, or poor if within that range for less than a third of occasions, as used previously.11 For patients in the six month group we applied these gradings separately for the first three months and for the second three months.Haemorrhage was defined as major if the treating clinician deemed transfusion necessary, if the haemoglobin concentration fell by 20 g/l, if bleeding was intracranial or retroperitoneal, or if it was sufficiently serious for the clinician to discontinue anticoagulation.Each participant gave written informed consent before entry into the trial, and clinicians used standardised letters to inform the patients' general practitioners.Statistical analysisWe calculated that we would need 2400 patients to have 80% power to detect a difference, significant at the 5% level, between recurrence rates of 6% and 9%. The coordinator and the coordinating physician checked all entry forms on receipt to ensure the patients' eligibility. After exclusion of ineligible patients we analysed the results by standard statistical methods according to the randomisation to define a full analysis population.18Type of anticoagulantWe offered centres a supply of a low molecular weight heparin (dalteparin) to use in the trial. In centres already using another low molecular weight heparin we asked participating clinicians to change to dalteparin, but inability or unwillingness to do so did not exclude their patients from the trial. The standard oral anticoagulant was warfarin, but clinicians could use an alternative coumarin if necessary.ResultsFrom mid September 1999 to the end of December 2002, 137 consultants from 46 hospitals (37 in England, four in Scotland, four in Wales, and one in Northern Ireland) entered 810 patients. Sixty one patients were excluded from analysis because they did not satisfy the entry criteria (27 in the three month group, 34 in the six month group), leaving 369 patients randomised to three months of treatment and 380 to treatment for six months (fig 1). These two groups were comparable over a broad range of characteristics, though a slightly higher proportion of men and of patients with pulmonary embolism were allocated to six months' treatment (table 1). Diagnosis was confirmed as definite in 91% of those receiving three months' anticoagulation and 92% of those receiving six months' and as probable in 6% and 6%, respectively, an overall frequency of definite or probable of 97%.View larger version:In a new windowDownload as PowerPoint SlideFig 1 Flow of patients through trial (DVT=deep vein thrombosis; PE=pulmonary embolism)Table 1 Characteristics of treatment groups at entry to trial. Figures are numbers (percentages) unless stated otherwiseAmong those for whom we had the data, heparin was given for three to seven days in 74% of patients in the three month group and 77% of those in the six month group (table 2). The minority of patients who received heparin for less than five days did so because the target international normalised ratio had been achieved early. Among those who received more than five days' heparin the usual reason was that the target ratio had not been achieved, though in a few patients an intervening weekend seemed to be the only reason. If we allowed three weeks either side of three months and six weeks either side of six months and considered those in whom durations were known (322 of three month group and 348 of six month group), 259 (80%) of those allocated to three months' treatment and 307 (88%) of those allocated six months received treatment with warfarin as per protocol. In those with shorter or longer durations, variations were because of errors by physicians or general practitioners, misunderstanding in patients, and rescheduling of follow up clinics.
eparin was given for three to
Anticoagulation http://www.cheapjordans.us/air-jordan-retro-1101/air-jordan-retro-23 for three versus six months in patients with deep vein thrombosis or pulmonary embolism cheap jordans retro 3AbstractObjective To determine the optimum duration of oral anticoagulant therapy after an episode of deep vein thrombosis or pulmonary embolism, or both.Interventions Three (n=369) or six months (n=380) of anticoagulation with heparin for five days accompanied and followed by warfarin, with a target international normalised ratio of 2.0 3.5.Main outcome measures Death from deep vein thrombosis or pulmonary embolism; failure to resolve, extension, recurrence of during treatment; recurrence after treatment; and major haemorrhage during treatment.Results In the patients allocated to three months' treatment two died from deep vein thrombosis or pulmonary embolism during or after treatment, compared with three in the six month group. During treatment deep vein thrombosis or pulmonary embolism failed to resolve, extended, or recurred in six patients in the three month group without fatal consequences, compared with 10 in the six month group. After treatment there were 23 non fatal recurrences in the three month group and 16 in the six month group. Fatal and non fatal deep vein thrombosis or pulmonary embolism during treatment, and after treatment thus occurred in 31(8%) of those who had received three months' anticoagulation compared with 29 (8%) of those who had received six months' (P=0.80, 95% confidence interval for difference 3.1% to 4.7%). There were no fatal haemorrhages during treatment but there were eight major haemorrhages in those treated for http://www.cheapjordans.us/air-jordan-retro-1101/air-jordan-retro-34 six months and none in those treated for three months (P=0.008, 3.5% to 0.7%). Thus 31 (8%) of the patients receiving three months' anticoagulation experienced cheap retro air jordan 2 adverse outcomes as a result of deep vein thrombosis or pulmonary embolism or its treatment compared with 35 (9%) of those receiving six months' (P=0.79, 4.9% to 3.2%).Conclusion For patients in the UK with deep vein thrombosis or pulmonary embolism and no known risk factors for recurrence, there seems to be little, if any, advantage in increasing the duration of anticoagulation from three to six months. Any possible advantage would be small and would need to be judged against the increased risk of haemorrhage associated with the longer duration of treatment with warfarin.Trial registration Clinical Trials IntroductionIn 1960 Barritt and Jordan established that anticoagulation reduced the risk of death and of recurrent embolism in patients with pulmonary embolism,1 a conclusion subsequently supported by retrospective studies from Oxford2 and the United States.3 Treatment regimens now consist of heparin for four to five days,4 5 6 with anticoagulation maintained thereafter by warfarin.For those centres not already routinely using low molecular weight heparin, an expanded design was used to compare low molecular weight heparin with unfractionated heparin in terms of outcome during treatment outcome after the end of anticoagulation, and duration of inpatient stay. Too few patients (n=22) were entered into this randomisation for meaningful comparions of these outcomes and so we used their results solely in the comparisons of three months versus six months of anticoagulation.MethodsPatientsEligible patients were those aged 18 with suspected or proved deep vein thrombosis or pulmonary embolism, or both, whom the clinician intended to treat with anticoagulant. We encouraged confirmation of diagnosis with ultrasound, radioisotope, venographic, angiographic, or other objective tests but patients managed without the aid of such tests were accepted for the trial. Categories of definite, probable (high or moderate probability), low probability, or negative were taken from the reports of the results.Several factors or conditions excluded patients from entry. These were deep vein thrombosis or pulmonary embolism deemed so severe by the clinician as to require thrombolysis or pulmonary embolectomy; neoplasia diagnosed or requiring treatment, or both, within the previous three years; pregnancy; deep vein thrombosis or pulmonary embolism in the preceding three years; known polycythaemia, thrombocythaemia, antithrombin III deficiency, lupus anticoagulant, homozygous factor V Leiden, protein C or protein S deficiency, or other similar predisposing haematological disorders; any condition that would result in prolonged or continuous immobility or confinement to bed, such as advanced multiple sclerosis or orthopaedic problems of the lower limbs; previous allergy to heparin or warfarin; requirement for long term anticoagulant therapy; and inability to give informed consent.DesignPatients were randomised to three or six months of warfarin, the clinicians being asked to start warfarin on day one of the scheduled five days of heparin. Participating physicians used international normalised ratios to monitor anticoagulation with warfarin according to a standardised protocol.17 The aim was to achieve ratios between 2.0 and 3.5.Within each centre randomisation was by permuted blocks of eight through a series of numbered envelopes kept at a central point in each hospital or unit. Each envelope also contained an entry card to be posted to the coordinator as notification of entry. On receipt of that card the coordinator sent a form to the clinician, confirming the allocated treatment and requesting further details of the patient. This form also contained a section for the clinician to notify the coordinator of alteration of diagnosis or discontinuation of anticoagulation, or both: if a patient was found to fulfil any of the criteria for exclusion, that patient was removed from the analysis before we had any knowledge of the outcome of the study.The individual clinicians were responsible for decisions about inpatient or outpatient management. For purposes of the trial, physicians were asked to arrange follow up appointments at three, six, and 12 months from the date of entry. Brief review forms were sent to the clinician a fortnight or so before each follow up date for completion and return to the coordinator. The forms requested information on failure of resolution (swelling of the leg(s) or pain or tenderness that did not settle down during treatment), extension or recurrence of deep vein thrombosis or pulmonary embolism, results of international normalised ratios, dates of start and completion of therapy with heparin and with warfarin, and adverse events. Clinicians were asked to confirm suspected failure of resolution, extension, or recurrence by radiological or ultrasonic imaging, or both.Predetermined primary adverse outcomes were death from deep vein thrombosis or pulmonary embolism, failure during treatment (failure to resolve, extension, recurrence during treatment), recurrence after the end of treatment, and major haemorrhage during treatment. Patients experiencing any of the above were grouped together under the heading of "adverse outcome," and we reported this as a further point of comparison between the groups.We graded anticoagulation as good if the international normalised ratios were between 2.0 and 3.5 on at least two thirds of occasions, moderate if within that range on a third but less than two thirds of occasions, or poor if within that range for less than a third of occasions, as used previously.11 For patients in the six month group we applied these gradings separately for the first three months and for the second three months.Haemorrhage was defined as major if the treating clinician deemed transfusion necessary, if the haemoglobin concentration fell by 20 g/l, if bleeding was intracranial or retroperitoneal, or if it was sufficiently serious for the clinician to discontinue anticoagulation.Each participant gave written informed consent before entry into the trial, and clinicians used standardised letters to inform the patients' general practitioners.Statistical analysisWe calculated that we would need 2400 patients to have 80% power to detect a difference, significant at the 5% level, between recurrence rates of 6% and 9%. The coordinator and the coordinating physician checked all entry forms on receipt to ensure the patients' eligibility. After exclusion of ineligible patients we analysed the results by standard statistical methods according to the randomisation to define a full analysis population.18Type of anticoagulantWe offered centres a supply of a low molecular weight heparin (dalteparin) to use in the trial. In centres already using another low molecular weight heparin we asked participating clinicians to change to dalteparin, but inability or unwillingness to do so did not exclude their patients from the trial. The standard oral anticoagulant was warfarin, but clinicians could use an alternative coumarin if necessary.ResultsFrom mid September 1999 to the end of December 2002, 137 consultants from 46 hospitals (37 in England, four in Scotland, four in Wales, and one in Northern Ireland) entered 810 patients. Sixty one patients were excluded from analysis because they did not satisfy the entry criteria (27 in the three month group, 34 in the six month group), leaving 369 patients randomised to three months of treatment and 380 to treatment for six months (fig 1). These two groups were comparable over a broad range of characteristics, though a slightly higher proportion of men and of patients with pulmonary embolism were allocated to six months' treatment (table 1). Diagnosis was confirmed as definite in 91% of those receiving three months' anticoagulation and 92% of those receiving six months' and as probable in 6% and 6%, respectively, an overall frequency of definite or probable of 97%.View larger version:In a new windowDownload as PowerPoint SlideFig 1 Flow of patients through trial (DVT=deep vein thrombosis; PE=pulmonary embolism)Table 1 Characteristics of treatment groups at entry to trial. Figures are numbers (percentages) unless stated otherwiseAmong those for whom we had the data, heparin was given for three to seven days in 74% of patients in the three month group and 77% of those in the six month group (table 2). The minority of patients who received heparin for less than five days did so because the target international normalised ratio had been achieved early. Among those who received more than five days' heparin the usual reason was that the target ratio had not been achieved, though in a few patients an intervening weekend seemed to be the only reason. If we allowed three weeks either side of three months and six weeks either side of six months and considered those in whom durations were known (322 of three month group and 348 of six month group), 259 (80%) of those allocated to three months' treatment and 307 (88%) of those allocated six months received treatment with warfarin as per protocol. In those with shorter or longer durations, variations were because of errors by physicians or general practitioners, misunderstanding in patients, and rescheduling of follow up clinics.