Hospital Performance for Pharmacologic Venous Thromboembolism Prophylaxis and Rate of Venous Thromboembolism : A Cohort Study | Clinical Pharmacy and Pharmacology | JAMA Internal Medicine | JAMA Network
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    2 Comments for this article
    'Rebound Hypercoagulation' from Prophylactic Anticoagulants May Increase Fatal Pulmonary Emboli
    David K. Cundiff | LA County + USC Medical Center (Retired)
    'Rebound Hypercoagulation' from Prophylactic Anticoagulants May Increase Fatal Pulmonary EmboliFlanders and colleagues reported on an observational study regarding prophylactic anticoagulants for patients at high risk for venous thromboembolism (VTE).1 Table 3 shows a nonsignificant trend toward prophylactic anticoagulants increasing the odds of a VTE (Hazard ratio: 1.09, 95% CI 0.80 – 1.48). Since the reason we prescribe prophylactic anticoagulants for high VTE risk patients is to prevent fatal pulmonary emboli (FPE), the all important missing data in this report involve the prophylactic anticoagulant statuses of patients who subsequently developed FPE. The authors indicated that VTE events leading to death were captured.In a previous wide ranging literature review involving VTE, my colleagues and I reported on two studies in which prophylactic anticoagulants were associated with much higher odds of FPE.2 As far as I know, these are the only hospital acquired FPE data, involving tens of thousands of hospitalizations, categorized by prophylactic anticoagulation status in the literature. Goldhaber and colleagues tracked the incidence of developing VTE during or up to 30 days after hospital discharge in about 80,000 patients admitted to Boston's Brigham and Women's Hospital.3 Out of 384 patients with hospital-acquired VTE, 170 (53%) had received prophylactic anticoagulants. Of 13 patients diagnosed with FPE, 12 (92%) were in patients that had received anticoagulants. An autopsy study by Lindblad and colleagues4 from Malmo, Sweden corroborated the high rate of FPE with anticoagulant prophylaxis. From a population of 31,238 post-operative patients from the 1980s, they reported that 27/30 patients (90%) with autopsy-proven FPE had received post-op prophylactic anticoagulants. Neither Goldhaber nor Lindblad reported the proportion of high VTE risk patients in their studies or the proportion of high risk patients that received anticoagulant prophylaxis. However, with any reasonable assumptions about numbers of high VTE risk patients and proportions of such patients anticoagulated, we will have highly statistically significant associations of anticoagulants with FPE in both studies. Taking rough estimates of prophylactic anticoagulant rates in both studies, I estimated an excess of FPE in prophylactically anticoagulated patients in the range of about 1/800 patients.2If the patients in Flanders’ study had a similar rate of FPE relative to the hospital acquired VTE incidence as in the Goldhaber study (i.e., 13 FPE /384 VTE = 3.4%), then we would expect somewhere around 4-12 cases of FPE (226 hospital acquired VTE patients x 0.034= 7.7). I suggest that Flanders and colleagues go back to their data and report the prophylactic anticoagulation status of patients developing FPE. If there is no reduction in FPE with prophylactic anticoagulants, there is no efficacy and only potential harm from this intervention. In addition to concerns about increased FPE, placebo versus prophylactic anticoagulants RCTs in hospitalized patients show an increase of 4 of major bleeding events per 1000 patients (CI, 1 to 7 events).5 Unless FPE is significantly reduced with prophylactic anticoagulants this time, we should stop prescribing prophylactic anticoagulants to high VTE risk hospitalized patients.David K. Cundiff, MD References1. Flanders SA, Greene M, Grant P, et al. Hospital performance for pharmacologic venous thromboembolism prophylaxis and rate of venous thromboembolism : A cohort study. JAMA Internal Medicine. 2014. Available at: Cundiff D, Agutter P, Malone P, Pezzullo J. Diet as prophylaxis and treatment for venous thromboembolism? Theoretical Biology and Medical Modelling. 2010; 7(1). Available at: Goldhaber S, Dunn K, MacDougall R. New onset of venous thromboembolism among hospitalized patients at Brigham and Women’s Hospital is caused more often by prophylaxis failure than by withholding treatment. Chest. 2000; 118:1680-1684. Available at: Lindblad B, Eriksson A, Bergqvist D. Autopsy-verified pulmonary embolism in a surgical department: analysis of the period from 1951 to 1988. Br J Surg. 1991; 78(7):849-8525. Lederle FA, Zylla D, MacDonald R, Wilt TJ. Venous Thromboembolism Prophylaxis in Hospitalized Medical Patients and Those With Stroke: A Background Review for an American College of Physicians Clinical Practice Guideline. Annals of Internal Medicine. 2011; 155(9):602-615. Available at:
    Is Prophylactic Anticoagulation to Prevent VTE Just One More Clinical Myth?
    George D Lundberg | Chief Medical Officer, CollabRx, San Francisco, CA
    Oh My.Might a large part of the current mass movement to anti coagulate so many medical and surgical patients of so many types be yet another example of too much therapy without good scientific reason? Waste and the introduction of new hazards follow the \"law of unintended consequences\".Be not so afraid of the malpractice lawyers and the hospital risk managers. Seek and follow the best evidence. Less is more.
    Original Investigation
    October 2014

    Hospital Performance for Pharmacologic Venous Thromboembolism Prophylaxis and Rate of Venous Thromboembolism : A Cohort Study

    Author Affiliations
    • 1Michigan Hospital Medicine Safety Consortium
    • 2Department of Internal Medicine, University of Michigan Medical School, Ann Arbor
    • 3Hurley Medical Center, Flint, Michigan
    • 4Henry Ford Health System, Detroit, Michigan
    • 5Oakwood Health System, Dearborn Heights, Michigan
    • 6Spectrum Health, Grand Rapids, Michigan
    • 7VA Ann Arbor Health Care System, Ann Arbor, Michigan
    • 8Blue Cross Blue Shield of Michigan, Detroit
    JAMA Intern Med. 2014;174(10):1577-1584. doi:10.1001/jamainternmed.2014.3384

    Importance  Hospitalization for acute medical illness is associated with increased risk of venous thromboembolism (VTE). Although efforts designed to increase use of pharmacologic VTE prophylaxis are intended to reduce hospital-associated VTE, whether higher rates of prophylaxis reduce VTE in medical patients is unknown.

    Objective  To examine the association between pharmacologic VTE prophylaxis rates and hospital-associated VTE.

    Design, Setting, and Participants  Retrospective, multicenter cohort study conducted at 35 Michigan hospitals participating in a statewide quality collaborative from January 1, 2011, through September 13, 2012. Trained medical record abstractors at each hospital collected data from 31 260 general medical patients. Use of VTE prophylaxis on admission, VTE risk factors, and VTE events 90 days after hospital admission were recorded using a combination of medical record review and telephone follow-up. Hospitals were grouped into tertiles of performance based on rate of pharmacologic prophylaxis use on admission for at-risk patients.

    Main Outcomes and Measures  Association between hospital performance and time to development of VTE within 90 days of hospital admission.

    Results  A total of 14 563 of 20 794 patients (70.0%) eligible for pharmacologic prophylaxis received prophylaxis on admission. The rates of pharmacologic prophylaxis use at hospitals in the high-, moderate-, and low-performance tertiles were 85.8%, 72.6%, and 55.5%, respectively. A total of 226 VTE events occurred during 1 765 449 days of patient follow-up. Compared with patients at hospitals in the highest-performance tertile, the hazard of VTE in patients at hospitals in moderate-performance (hazard ratio, 1.10; 95% CI, 0.74-1.62) and low-performance (hazard ratio, 0.96, 95% CI, 0.63-1.45) tertiles did not differ after adjusting for potential confounders. Results remained robust when examining mechanical prophylaxis, prophylaxis use throughout the hospitalization, and subsequent inpatient stays after discharge from the index hospitalization.

    Conclusions and Relevance  The occurrence of 90-day VTE in medical patients after hospitalization is low. Patients who receive care at hospitals that have lower rates of pharmacologic prophylaxis do not have higher adjusted hazards of VTE, even after accounting for individual receipt of pharmacologic prophylaxis. Efforts to increase rates of pharmacologic VTE prophylaxis in hospitalized medical patients may not substantively reduce this adverse outcome.