Estimated GFR Variability and Risk of Cardiovascular Events and Mortality in SPRINT (Systolic Blood Pressure Intervention Trial).

RATIONALE AND OBJECTIVE: Although low estimated glomerular filtration rate (eGFR) is associated with cardiovascular disease (CVD) events and mortality, the clinical significance of variability in eGFR over time is uncertain. This study aimed to evaluate the associations between variability in eGFR and the risk of CVD events and all-cause mortality. STUDY DESIGN: Longitudinal analysis of clinical trial participants. SETTINGS AND PARTICIPANTS: 7,520 Systolic Blood Pressure Intervention Trial (SPRINT) participants ≥50 year of age with 1 or more CVD risk factors. PREDICTORS: eGFR variability, estimated by the coefficient of variation of eGFR assessments at the 6th, 12th, and 18-month study visits. OUTCOMES: The SPRINT primary CVD composite outcome (myocardial infarction, acute coronary syndrome, stroke, heart failure, or CVD death) and all-cause mortality from month 18 to the end of follow-up. ANALYTICAL APPROACH: Cox models were used to evaluate associations between eGFR variability and CVD outcomes and all-cause mortality. Models were adjusted for demographics, randomization arm, CVD risk factors, albuminuria, and eGFR at month 18. RESULTS: Mean age was 68 ± 9 years; 65% were men; and 58% were White. The mean eGFR was 73 ± 21 (SD) mL/min/1.73 m2 at 6 months. There were 370 CVD events and 154 deaths during a median follow-up of 2.4 years. Greater eGFR variability was associated with higher risk for all-cause mortality (hazard ratio [HR] per 1 SD greater variability, 1.29; 95% CI, 1.14-1.45) but not CVD events (HR, 1.05; 95% CI, 0.95-1.16) after adjusting for albuminuria, eGFR, and other CVD risk factors. Associations were similar when stratified by treatment arm and by baseline CKD status, when accounting for concurrent systolic blood pressure changes, use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and diuretic medications during follow up. LIMITATIONS: Persons with diabetes and proteinuria > 1 g/d were excluded. CONCLUSIONS: In trial participants at high risk for CVD, greater eGFR variability was independently associated with all-cause mortality but not CVD events.

Osteopontin and LDLR Are Upregulated in Hearts of Sudden Cardiac Death Victims With Heart Failure With Preserved Ejection Fraction and Diabetes Mellitus.

Background: Diabetes mellitus (DM) is associated with increased risk of sudden cardiac death (SCD), particularly in patients with heart failure with preserved ejection fraction (HFpEF). However, there are no known biomarkers in the population with DM and HFpEF to predict SCD risk. Objectives: This study was designed to test the hypothesis that osteopontin (OPN) and some proteins previously correlated with OPN, low-density lipoprotein receptor (LDLR), dynamin 2 (DNM2), fibronectin-1 (FN1), and 2-oxoglutarate dehydrogenase-like (OGDHL), are potential risk markers for SCD, and may reflect modifiable molecular pathways in patients with DM and HFpEF. Methods: Heart tissues were obtained at autopsy from 9 SCD victims with DM and HFpEF and 10 age and gender-matched accidental death control subjects from a Finnish SCD registry and analyzed for the expression of OPN and correlated proteins, including LDLR, DNM2, FN1, and OGDHL by immunohistochemistry. Results: We observed a significant upregulation in the expression of OPN, LDLR, and FN1, and a marked downregulation of DNM2 in heart tissues of SCD victims with DM and HFpEF as compared to control subjects (p < 0.01). Conclusions: The dysregulated protein expression of OPN, LDLR, FN1, and DNM2 in patients with DM and HFpEF who experienced SCD provides novel potential modifiable molecular pathways that may be implicated in the pathogenesis of SCD in these patients. Since secreted OPN and soluble LDLR can be measured in plasma, these results support the value of further prospective studies to assess the predictive value of these plasma biomarkers and to determine whether tuning expression levels of OPN and LDLR alters SCD risk in patients with DM and HFpEF.

Comparison of Cardiovascular Outcomes by Dialysis Modality: A Systematic Review and Meta-Analysis.

Debates exist regarding the merit of starting one dialysis modality over the other for improved cardiovascular outcomes. Five previously published prospective and retrospective cohort studies have reported inconsistent conclusions on this topic. The aim of this systematic review and meta-analysis is to evaluate the influence initiation of hemodialysis (HD) vs peritoneal dialysis (PD) may have on the relative risk (RR) of subsequent development of adverse cardiovascular events (ACVE) in patients with end-stage renal disease (ESRD). Of the 518 records identified, 5 cohort studies, assessing a total of 47,062 patients were included in the meta-analysis. With regard to the subsequent development of ACVE following initiation on the different dialysis modalities, the pooled RR was found to be non-significant. Peritoneal dialysis is a suitable and cost-effective alternative to HD for ESRD patients at risk of cardiovascular disease.

Incidence and Outcome of Pericardial Effusion in Pediatric Patients After Hematopoietic Stem Cell Transplant: A Single-institution Experience.

BACKGROUND: Pericardial effusion (PE) is a known complication after hematopoietic stem cell transplant (HSCT). Limited data is currently available regarding the incidence and outcomes of PE in pediatric HSCT. METHODS: We conducted a retrospective study on a cohort of patients who underwent HSCT between 2004 and 2015. Risk factors associated with development of PE were evaluated. RESULTS: In 111 HSCT, stem cell source was bone marrow in 37 (33.3%), peripheral blood-42 (37.8%) and cord blood-32 (28.8%). Incidence of PE after HSCT was 37.8%. Insignificant effusion (trivial or small) was noted in 30 (27.0%) transplants, and significant (moderate or large) PE in 12 (10.8%). There were no associations between incidence of effusion and stem cell source, graft versus host disease or CMV infection. Risk factors associated with development of PE included systemic hypertension (P<0.05), total body irradiation (P<0.05), and sinusoidal obstruction syndrome formerly known as venoocclusive disease (P=0.03). Overall mortality was 22.5% after HSCT, but 38.1% among those with effusion (P<0.05). None of these deaths were attributed to primary cardiac etiologies. CONCLUSIONS: The incidence of PE in this cohort of pediatric HSCT recipients is high and associated with higher morbidity and mortality.

Can We Identify Minority Patients at Risk of Nonadherence to Antiplatelet Medication at the Time of Coronary Stent Placement?

BACKGROUND: Lack of medication adherence is associated with significant morbidity and mortality, particularly among minorities. We aim to identify predictors of nonadherence to antiplatelet medications at the time of percutaneous coronary intervention (PCI) with stent among African American and Hispanic patients. METHODS: We used data collected for a randomized clinical trial that recruited 452 minority patients from a large US health insurance organization in 2010 post-PCI to compare telephone-based motivational interviewing by trained nurses with an educational video. The primary outcome was 12-month adherence to antiplatelet medications measured by the claims-based medication possession ratio (MPR). Adequate adherence was defined as an MPR of 0.80 or higher. RESULTS: More than half of the sample (age, 69.52 ± 8.8 years) was male (57%) and Hispanic (57%). Most (78%) had a median income below $30 000 and 22% completed high school or higher. Univariate analyses revealed that symptoms of depression (<.01) and not having a spouse (P = .03) were associated with inadequate adherence. In multivariate analysis, baseline self-reported adherence (1.4; 95% confidence interval [CI], 1.05-1.89), depressive symptoms (0.49; 95% CI, 0.7-0.90), comorbidity (0.89; 95% CI, 0.80-0.98), and telephone-based motivational interviewing by trained nurses (3.5; 95% CI, 1.9-2.70) were associated with adherence. CONCLUSIONS: Having multiple comorbidities, depression, suboptimal adherence to medications, and low English proficiency at the time of PCI increase the risk of poor 12-month adherence to antiplatelets among minorities. Identifying these risk factors can guide PCI therapy and the use of evidence-based strategies to improve long-term adherence.

A meta-analysis of randomized clinical trials assessing hemodialysis access thrombosis based on access flow monitoring: where do we stand?

The National Kidney Foundation Kidney Disease Outcomes Quality Initiative recommends the routine use of hemodialysis arteriovenous (AV) access surveillance to detect hemodynamically significant stenoses and appropriately correct them to reduce the incidence of thrombosis and to improve accesses patency rates. Access blood flow monitoring is considered as one of the preferred surveillance method for both AV fistulas (AVF) and AV grafts (AVG); however, published studies have reported conflicting results of its utility that led healthcare professionals to doubt the benefits of this surveillance method. We performed a meta-analysis of the published randomized controlled trials (RCTs) of AV access surveillance using access blood flow monitoring. Our hypothesis was that access blood flow monitoring lowers the risk of AV access thrombosis and that the outcome differs between AVF and AVG. The estimated overall pooled risk ratio (RR) of thrombosis was 0.87 (95% confidence interval [CI], 0.67-1.13) favoring access blood flow monitoring. The pooled RR of thrombosis were 0.64 (95% CI, 0.41-1.01) and 1.06 (95% CI, 0.77-1.46) in the subgroups of only AVF and only AVG, respectively. Our results added to the uncertainty of access blood flow monitoring as a surveillance method of hemodialysis accesses.

Can phone-based motivational interviewing improve medication adherence to antiplatelet medications after a coronary stent among racial minorities? A randomized trial.

BACKGROUND: Minorities have lower adherence to cardiovascular medications and have worst cardiovascular outcomes post coronary stent placement OBJECTIVE: The aim of this study is to compare the efficacy of phone-delivered Motivational Interviewing (MINT) to an educational video at improving adherence to antiplatelet medications among insured minorities. DESIGN: This was a randomized study. PARTICIPANTS: We identified minorities with a recently placed coronary stent from an administrative data set by using a previously validated algorithm. INTERVENTIONS: MINT subjects received quarterly phone calls and the DVD group received a one-time mailed video. MAIN MEASURES: Outcome variables were collected at baseline and at 12-month post-stent, using surveys and administrative data. The primary outcome was antiplatelet (clopidogrel and prasugrel) adherence measured by Medication Possession Ratio (MPR) and self- reported adherence (Morisky score). We also measured appropriate adherence defined as an MPR ≥ 0.80. KEY RESULTS: We recruited 452 minority subjects with a new coronary stent (44 % Hispanics and 56 % Black). The patients had a mean age of 69.5 ± 8.8, 58 % were males, 78 % had an income lower than $30,000 per year and only 22 % had achieved high school education or higher. The MPR for antiplatelet medications was 0.77 for the MINT group compared to 0.70 for the DVD group (p < 0.05). The percentage of subjects with adequate adherence to their antiplatelet medication was 64 % in the MINT group and 50 % in the DVD group (p < 0.01). Self-reported adherence at 12 months was higher in the MINT group compared to the DVD group (p < 0.01). Results were similar among drug-eluting stent (DES) recipients. CONCLUSIONS: Among racial minorities, a phone-based motivational interview is effective at improving adherence to antiplatelet medications post coronary stent placement. Phone-based MINT seems to be a promising and cost-effective strategy to modify risk behaviors among minority populations at high cardiovascular risk.

Can claims-based data be used to recruit black and Hispanic subjects into clinical trials?

OBJECTIVE: Evaluate the accuracy of an algorithm at identifying ethnic minorities from administrative claims for enrollment into a clinical trial. DATA SOURCES/STUDY SETTING: Claims data from a health benefits company. STUDY DESIGN: We compared results of a three-step algorithm to self-reported race/ethnicity. DATA COLLECTION/EXTRACTION METHODS: Using the algorithm, we identified subjects with high probability of being minority and ascertained self-reported race/ethnicity. PRINCIPAL FINDINGS: We identified 164 subjects as likely minority based on our algorithm. Of these, 94 completed the survey and 87 identified themselves as black or Hispanic. The positive predictive value of the algorithm was 93 percent (CI: 85-97). CONCLUSIONS: Claims data can be used to efficiently identify minorities for participation in clinical trials.

Blood viscosity and hematocrit as risk factors for type 2 diabetes mellitus: the atherosclerosis risk in communities (ARIC) study.

Several lines of evidence support the notion that elevated blood viscosity may predispose to insulin resistance and type 2 diabetes mellitus by limiting delivery of glucose, insulin, and oxygen to metabolically active tissues. To test this hypothesis, the authors analyzed longitudinal data on 12,881 initially nondiabetic adults, aged 45-64 years, who were participants in the Atherosclerosis Risk in Communities (ARIC) Study (1987-1998). Whole blood viscosity was estimated by using a validated formula based on hematocrit and total plasma proteins at baseline. At baseline, estimated blood viscosity was independently associated with several features of the metabolic syndrome. In models adjusted simultaneously for known predictors of diabetes, estimated whole blood viscosity and hematocrit predicted incident type 2 diabetes mellitus in a graded fashion (P(trend (linear)) < 0.001): Compared with their counterparts in the lowest quartiles, adults in the highest quartile of blood viscosity (hazard ratio = 1.68, 95% confidence interval: 1.53, 1.84) and hematocrit (hazard ratio = 1.63, 95% confidence interval: 1.49, 1.79) were over 60% more likely to develop diabetes. Therefore, elevated blood viscosity and hematocrit deserve attention as emerging risk factors for insulin resistance and type 2 diabetes mellitus.

The perception of gastroenterology fellows towards the relationship between hand size and endoscopic training.

Some endoscopic trainees find it difficult to manipulate an endoscope's controls, possibly due to small hand size. To assess this, a survey was mailed to all gastroenterology fellows in the US. Two hundred twenty-seven of 1,295 (17.5%) fellows responded. Median surgical glove size was 7.5. Ninety-three respondents (41.0%) considered their hand too small for a standard endoscope's handle; 176 (78.2%) felt that hand size affects the ability to learn endoscopy. Seventy-seven (34.2%) would use smaller handled endoscopes if available. Of the 38 respondents with glove sizes < or =6.5, 37 (97.4%) were female. These respondents were more likely to consider their hand too small (P < 0.001), want to use smaller handled endoscopes (P < 0.001), and feel that training programs should offer them (P = 0.009). These results suggest that a significant number of trainees, especially women, perceive that their hands are too small for standard endoscopes and believe that hand size plays a role in learning and performing endoscopy.

Review of the evidence on diagnosis of deep venous thrombosis and pulmonary embolism.

PURPOSE: This review summarizes the evidence regarding the efficacy of techniques for diagnosis of deep venous thrombosis (DVT) and pulmonary embolism. METHODS: We searched for studies using MEDLINE, MICROMEDEX, the Cochrane Controlled Trials Register, and the Cochrane Database of Systematic Reviews through June 2006. We reviewed randomized controlled trials, systematic reviews of trials, and observational studies if no trials were available. Paired reviewers assessed the quality of each included article and abstracted the data into summary tables. Heterogeneity in study designs precluded mathematical combination of the results of the primary literature. RESULTS: Our review found 22 relevant systematic reviews and 36 primary studies. The evidence strongly supports the use of clinical prediction rules, particularly the Wells model, for establishing the pretest probability of DVT or pulmonary embolism in a patient before ordering more definitive testing. Fifteen studies support that when a D-dimer assay is negative and a clinical prediction rule suggests a low probability of DVT or pulmonary embolism, the negative predictive value is high enough to justify foregoing imaging studies in many patients. The evidence in 5 systematic reviews regarding the use of D-dimer, in isolation, is strong and demonstrates sensitivities of the enzyme-linked immunosorbent assay (ELISA) and quantitative rapid ELISA, pooled across studies, of approximately 95%. Eight systematic reviews found that the sensitivity and specificity of ultrasonography for diagnosis of DVT vary by vein; ultrasonography performs best for diagnosis of symptomatic, proximal vein thrombosis, with pooled sensitivities of 89% to 96%. The sensitivity of single-detector helical computed tomography for diagnosis of pulmonary embolism varied widely across studies and was below 90% in 4 of 9 studies; more studies are needed to determine the sensitivity of multidetector scanners. CONCLUSIONS: While the strength of the evidence varies across questions, it is generally strong.

Duration of vitamin K antagonist therapy for venous thromboembolism: a systematic review of the literature.

PURPOSE: The aim of this study was to evaluate the evidence on the optimal duration of vitamin K antagonist (VKA) therapy for venous thromboembolism (VTE). METHODS: Randomized controlled trials of VKA for VTE were identified by a computerized database search. Summary event rates for relevant outcomes were calculated using a random effects model with 95% confidence intervals (95% CI). RESULTS: Ten studies met inclusion criteria. The incidence of recurrent VTE (3 months, 7.9 VTE per 100 patient-years [95% CI, 5.2 to 10] versus 4-12 months, 4.9 VTE per 100 patient-years [95% CI, 3.6 to 6.2] versus continuous therapy, 0.7 VTE per 100 patient-years [95% CI, 0.3 to 1.1]) and total adverse events (3 months, 11.2 events per 100 patient-years [95%CI, 7.1 to 15.4] versus 4-12 months, 7.4 events per 100 patient-years [95%CI, 6.2 to 8.5] versus continuous therapy 3.1 events per 100 patient-years [95%CI, 2.2 to 4.0] declined as VKA therapy duration increased. Continuous reduced intensity therapy (INR 1.5-2) was associated with more recurrent VTE (2.3 VTE per 100 patient-years [95%CI, 1.5 to 3.0]). Continuous VKA therapy (INR 2-3) was beneficial for patients with a second VTE and antiphospholipid antibodies. The incidence of recurrent VTE was similar with 6 or 12 weeks of therapy for isolated calf DVT. CONCLUSION: Randomized controlled trials indicate that continuous VKA therapy (INR 2-3) for VTE is associated with better clinical outcomes than shorter durations. Patients with a second VTE or antiphospholipid antibodies also benefit from continuous anticoagulation. Patients with calf DVT should be treated for at least 6 weeks.

Accuracy of CT in the diagnosis of pulmonary embolism: a systematic literature review.

OBJECTIVE: We sought to summarize systematically the published evidence describing the accuracy of contrast-enhanced helical CT for diagnosing pulmonary embolism. MATERIALS AND METHODS: We selected all systematic reviews published before December 2003 that evaluated the accuracy of CT angiography for the diagnosis of pulmonary embolism. We also selected all prospective studies from the same time period in the primary literature in which all subjects underwent both CT and conventional angiography, the latter being considered the reference standard. Articles were identified through a computerized MEDLINE search and by other means. The quality and content of each article were evaluated independently by pairs of researchers. RESULTS: Six systematic reviews and eight primary studies were selected. The combined sensitivities of CT for detecting pulmonary embolism ranged from 66% to 93% across the systematic reviews and the combined specificities ranged from 89% to 97%. Only one of the reviews reported a combined sensitivity of greater than 90%. Among the eight primary studies, the sensitivities ranged from 45% to 100% and specificities ranged from 78% to 100%. Only three of the eight primary studies reported a sensitivity greater than 90%. None of the primary studies used scanners with four or more detectors. CONCLUSION: A systematic literature review revealed a wide range of reported sensitivities, only a minority of which exceeded 90%. Pooled estimates of sensitivity and specificity reported by systematic literature reviews should be interpreted with caution because of potential selection bias and heterogeneity in the reviewed studies. Accuracy studies of recent generations of MDCT scanners are not yet available despite the current dissemination of this technology.

Usefulness of clinical prediction rules for the diagnosis of venous thromboembolism: a systematic review.

PURPOSE: To summarize the evidence on the predictive value of clinical prediction rules for the diagnosis of venous thromboembolism. METHODS: We selected all studies in the English literature in which a clinical prediction rule was prospectively validated against a reference standard, and calculated likelihood ratios, predictive values, and the area under the receiver operating characteristic (ROC) curve for each prediction rule. RESULTS: Twenty-three studies met our eligibility criteria: 17 evaluated prediction rules for the diagnosis of deep venous thrombosis and six evaluated rules for pulmonary embolism. The most frequently evaluated prediction rule for deep vein thrombosis was the Wells rule, which had median positive likelihood ratios of 6.62 for patients with a high pretest probability, 1 for moderate pretest probability, and 0.22 for low pretest probability. The median area under the ROC curve was 0.82. Addition of the D-dimer test to the prediction rule increased the median area under the curve to 0.90. The Wells prediction rule was the most commonly studied for pulmonary embolus and had median positive likelihood ratios of 6.75 for those with high pretest probability, 1.82 for moderate pretest probability, and 0.13 for low pretest probability. The median area under the ROC curve was 0.82. CONCLUSION: The Wells prediction rule is useful in identifying patients at low risk of being diagnosed with venous thromboembolism. The addition of a rapid latex D-dimer assay improved the overall performance of the prediction rule.

Large vessel involvement in ANCA-associated vasculitides: report of a case and review of the literature.

Vasculitides are currently classified according to the size of the vessels involved and characteristic clinical and histopathologic findings. Antineutrophil cytoplasmic antibodies (ANCA) and other serologic tests have been used to further characterize small vessel vasculitides. Large vessel involvement in ANCA-associated small vessel vasculitides has been overlooked in the medical literature. Here, we report a case of fatal aortitis and aortic dissection in a patient with microscopic polyangiitis and review reported cases of large vessel involvement in ANCA-associated vasculitides since 1990. We have attempted to characterize this subgroup of patients. Large vessel disease in ANCA-associated vasculitis may present as stenosing large vessel arteritis, aneurysmal disease, aortic dissection, aortic rupture, aortic regurgitation, and death. Prominent perivascular inflammation may present as mediastinal, cervical or abdominal soft tissue masses. ANCA-associated large vessel disease should be considered in the differential diagnosis of these disorders. The epidemiologic, clinical and pathologic characteristics of these patients differ from those of the well-defined large vessel vasculitides such as giant cell (temporal) arteritis or Takayasu's arteritis. We suggest that large vessel involvement is part of the spectrum of ANCA-associated vasculitis rather than an overlap with other large vessel vasculitides. It occurs in both myeloperoxidase- and proteinase 3-positive patients with either Wegener's granulomatosis or microscopic polyangiitis, but has not been reported in Churg-Strauss syndrome. Large vessel vasculitis can precede small vessel vasculitis or occur in the absence of small vessel involvement. We hope this report will contribute to the ongoing development of classification systems for the vasculitic syndromes.

Pharmacological rate control of atrial fibrillation.

To control ventricular rate in patients with AF, physicians should seek to control heart rate at rest and with exertion. The goal has to be achieved while minimizing costs and adverse effects. For emergency use, i.v. diltiazem or esmolol are drugs useful because of their rapid onset of action. They have to be used with caution in patients with concomitant left ventricular failure symptoms, however. For most patients with AF, chronic control of the ventricular rate can be achieved with one drug. For the chronic control of ventricular rate in patients with AF and normal ventricular function, diltiazem, atenolol, are metoprolol are probably the drugs of choice. For patients with AF and structurally abnormal hearts, atenolol, metoprolol, or carvedilol are appropriate choices. Adequate ventricular rate control by pharmacological agents should be evaluated by either 24-hour Holter monitoring or a submaximal stress test to determine the resting and exercise ventricular rate. If the mean ventricular rate is not close to 80 beats per minute, or the heart rate on moderate exertion is not between 90 to 115 beats per minute, a second agent to control the rate should be added. Excessive reductions in ventricular rates that could limit exercise tolerance should be avoided.

Management of atrial fibrillation: review of the evidence for the role of pharmacologic therapy, electrical cardioversion, and echocardiography.

PURPOSE: This review summarizes the available evidence regarding the efficacy of medications used for ventricular rate control, stroke prevention, acute conversion, and maintenance of sinus rhythm, as well as the efficacy of electrical cardioversion and the use of echocardiography in patients with atrial fibrillation. DATA SOURCES: The Cochrane Collaboration's database of controlled clinical trials and MEDLINE. STUDY SELECTION: Primarily randomized, controlled trials of medications. DATA EXTRACTION: Paired reviewers obtained data on efficacy and safety. Strength of evidence was assessed. DATA SYNTHESIS: Recent clinical trial results showed that most patients with atrial fibrillation have similar outcomes with strategies for controlling ventricular rate compared with strategies for restoring sinus rhythm. For efficacy of primary stroke prevention, compared with placebo, evidence was strong for warfarin and suggestive for aspirin. The evidence for an increased risk for major bleeding was suggestive for warfarin and inconclusive for aspirin. For ventricular rate control, verapamil, diltiazem, atenolol, and metoprolol were qualitatively superior to digoxin and placebo, particularly during exercise. For efficacy of acute conversion, compared with placebo, evidence was strong for ibutilide, flecainide, dofetilide, propafenone, amiodarone, and quinidine. For efficacy of maintenance of sinus rhythm after conversion from atrial fibrillation, evidence was strong for amiodarone, propafenone, disopyramide, and sotalol. Echocardiography was found to be useful in estimating risk for thromboembolism and potentially useful in estimating likelihood of successful cardioversion and maintenance. CONCLUSIONS: For several key questions in the pharmacologic management of atrial fibrillation, strong evidence exists to support 1 or more treatment options.

Outpatient therapy with low molecular weight heparin for the treatment of venous thromboembolism: a review of efficacy, safety, and costs.

PURPOSE: To summarize the evidence comparing the efficacy, safety, and costs of outpatient and inpatient treatment of venous thromboembolism. METHODS: We searched the literature through March 2002 for studies comparing outpatient and inpatient treatment of venous thromboembolism with low molecular weight heparin or unfractionated heparin, and for studies addressing the costs of low molecular weight heparin use in any setting. We included studies with comparison groups or decision analyses. RESULTS: Eight studies (three randomized trials and five cohort studies) compared outpatient use of low molecular weight heparin with inpatient use of unfractionated heparin in 3762 patients. The incidence of recurrent deep venous thrombosis was similar in the two groups (median, 4% [range, 0% to 7%] vs. 6% [range, 0% to 9%]), as was major bleeding (median, 0.5% [range, 0% to 2%] vs. 1% [range, 0% to 2%]). Use of low molecular weight heparin was associated with shorter hospitalization (median, 2.7 days [range, 0.03 to 5.1 days] vs. 6.5 days [range, 4 to 9.6 days]) and lower costs (median difference, 1600 dollars). Comparisons of outpatient and in-hospital use of low molecular weight heparin reported no difference in outcomes, but there were savings in hospitalization costs. Low molecular weight heparin was also found to be more cost saving and cost-effective than unfractionated heparin, with savings of 0% to 64% (median, 57%). CONCLUSION: The evidence indicates that outpatient treatment of deep venous thrombosis with low molecular weight heparin is likely to be efficacious, safe, and cost-effective.