Venous Thromboembolism
Original Investigation Research
Invited Commentary
Venous Thromboembolism Prophylaxis for Medical Patients Who Needs It? Michael B. Rothberg, MD, MPH
In medicine, the quality and safety movement attempts to improve processes of care through careful measurement and application of industrial quality improvement techniques. When outcomes are publicly reported or tied to reimRelated article page 1577 bursement, hospitals’ ability to improve their performance has been impressive. On the other hand, choosing what to measure has been more challenging, and several measures that were formerly tied to reimbursement have been revised or rescinded. Moreover, quality measures have rarely allowed for personalization, such as adjusting hemoglobin A1C targets for age or mammography rates for patient preference. In this issue of JAMA Internal Medicine, Flanders et al1 report on one such measure that should be entirely personalized—venous thromboembolism (VTE) prophylaxis. The study, produced by a quality improvement consortium in Michigan, represents an impressive data collection effort, including more than 20 000 patients at 35 hospitals. Ascertainment of outcomes at 90 days was accomplished through universal medical record review, and 58% of patients also had telephone follow-up. As a quality improvement initiative, the consortium was certainly successful. The rates of VTE prophylaxis attained were much higher than have been previously reported, with the top one-third of hospitals achieving pharmacologic prophylaxis rates in excess of 85%. Even low-performance hospitals provided prophylaxis to more than half their patients. The disappointing finding was that low-performance hospitals had rates of VTE that were identical to those of high-performance hospitals, despite having similar patients. How should these results be interpreted? One way would be to conclude that VTE prophylaxis is not effective in medical patients and that the Joint Commission core measure2 (the number of patients who received VTE prophylaxis or have documentation on why no VTE prophylaxis was given) should be abandoned. This interpretation flies in the face of randomized clinical trial evidence, which has found conclusively for high-risk medical patients that VTE prophylaxis can prevent one-third to half of symptomatic VTE events, in particular pulmonary emboli. Given the low rate of events in the study by Flanders et al1 (approximately 1% at 90 days) and the small differences in prophylaxis rates among the hospitals (approximately 30% between top and bottom performers), it was underpowered to detect even a 50% relative risk reduction due to pharmacologic prophylaxis. Another interpretation would be that giving prophylaxis to large numbers of low-risk patients is an inefficient way to reduce VTE and that hospitals might achieve similar outcomes with far fewer painful injections and less expense. jamainternalmedicine.com
The 2012 American College of Chest Physicians antithrombotic therapy guidelines estimate that the number needed to treat to prevent 1 inpatient VTE is at least 500.3 Whether a few days of inpatient prophylaxis can prevent VTE in the following 90 days is an important but unanswered question. The extremely low rate of VTE in this study (just 0.16% during hospitalization) underscores the need to perform careful risk assessment—exactly what the Joint Commission standard originally measured. However, in the latest version of this measure, once prophylaxis is given there is no need to demonstrate that risk assessment was performed. There is only a requirement to document low risk for patients who do not receive prophylaxis, and there is no penalty for prescribing prophylaxis unnecessarily or even when it is contraindicated. Flanders et al1 did not report on rates of inappropriate prophylaxis or bleeding, but at least one study4 found that a quality improvement initiative with a standard admission order set failed to increase appropriate prescribing but led to an increase in inappropriate prophylaxis and major bleeding. Unfortunately, validated tools for performing risk assessment are lacking. Citing venous thromboembolism as the most common cause of preventable hospital death and frustrated by years of low rates of VTE prophylaxis worldwide, proponents of VTE prophylaxis have generally erred on the side of overuse, arguing that less than 5% of medical patients were at low risk for VTE. Flanders et al1 used a Caprini score cutoff of 2 or greater to identify high-risk patients, but a perusal of the Caprini scoring sheet reveals how exaggerated this approach is: a 41-year-old with a body mass index of 26 already has a score of 2, as does anyone older than 60 years.5 It is no wonder, then, that despite having a mean Caprini score of 5.8 (reported predicted risk of 40%-80%),5 the rate of VTE in this population was low. Although the risk factors for VTE are well known, the appropriate weights to assign the factors in determining VTE risk are not. The fact that each hospital in this consortium used their own method of risk assessment attests to the lack of guidance in the Joint Commission measures. Several models are readily available for inpatient use. The Caprini model, which was developed more than 20 ago, was recently validated using American College of Surgeons National Surgical Quality Improvement Program data; surgical patients with scores between 5 and 6 (similar to the Flanders’ cohort) had a 1.33% risk of VTE.6 The model does not appear to have been validated in medical patients, which is concerning because few of its 35 risk factors were independently associated with VTE. The most recent version of the American College of Chest Physicians antithrombotic guidelines recommends using the Padua Prediction Score, which was prospectively validated on 1180 patients JAMA Internal Medicine October 2014 Volume 174, Number 10
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://archinte.jamanetwork.com/ by a Ndsu Library Periodicals User on 05/21/2015
1585
Research Original Investigation
Venous Thromboembolism
in Padua, Italy.7 The model is simple, comprising 11 risk factors, each assigned a point value. Using a cutoff of 4, the prediction tool neatly separated patients into a high-risk group (approximately 40% of patients) in which 11% developed VTE and a low-risk group in which 0.4% developed VTE. Several aspects of the Padua study raise doubts about its applicability to US patients, including an overall risk of VTE that was 3 times that seen in the study by Flanders et al and a mean length of stay longer than 9 days. A predictive model based on the International Medical Prevention Registry on Venous Thromboembolism registry includes only 4 Padua factors but with different weights.8 Patients with more than 4 points also had an 11% risk of VTE, but only 0.4% of patients had scores this high; 56% of patients had a risk of 1.0%, and 33% of patients had a risk of 0.5%. It is time to balance our goal of ensuring that every highrisk patient receives prophylaxis with ensuring that low-risk patients do not. After more than 20 years of research on VTE ARTICLE INFORMATION Author Affiliation: Center for Value-Based Care Research, Medicine Institute, Cleveland Clinic, Cleveland, Ohio. Corresponding Author: Michael B. Rothberg, MD, MPH, Center for Value-Based Care Research, Medicine Institute, Cleveland Clinic, 9500 Euclid Ave, Cleveland, OH 44195 ([email protected]). Published Online: August 18, 2014. doi:10.1001/jamainternmed.2014.3357. Conflict of Interest Disclosures: Dr Rothberg reports receiving research support from the Agency for Healthcare Research and Quality. REFERENCES 1. Flanders SA, Greene MT, Grant P, et al. Hospital performance for pharmacologic venous thromboembolism prophylaxis and rate of venous
1586
prophylaxis, 2 critical gaps in our knowledge remain. First, how do we reliably predict risk? There is a need for a validated prediction model that incorporates the known VTE risk factors. It need not be perfect, but it should achieve separation between low- and high-risk patients. Simply validating the Padua Prediction Score in a US population might be sufficient. The study by Flanders et al1 appears to have the data necessary to do so and would be a good place to start. Second, what is meant by low risk? There is need for a decision analytic model to determine a threshold for treatment. Given that most patients have risks ranging from 0.5% to 1.0%, understanding this threshold is crucial. Surprisingly, there are no published models to determine at what probability of VTE the benefits of prophylaxis would outweigh the harms. Ideally, these questions would have been answered before VTE prophylaxis was implemented as a hospital quality measure. But it is not too late. Adding the “who” to the “what” would be a welcome enhancement to the next generation of VTE measures.
thromboembolism: a cohort study [published online August 18, 2014]. JAMA Intern Med. doi:10 .1001/jamainternmed.2014.3384.
5. Caprini JA. Thrombosis risk assessment as a guide to quality patient care. Dis Mon. 2005; 51(2-3):70-78.
2. The Joint Commission. Venous Thromboembolism (VTE) Core Measure Set. 2014. http://www.jointcommission.org/core_measure _sets.aspx. Accessed June 20, 2014.
6. Bahl V, Hu HM, Henke PK, Wakefield TW, Campbell DA Jr, Caprini JA. A validation study of a retrospective venous thromboembolism risk scoring method. Ann Surg. 2010;251(2):344-350.
3. Kahn SR, Lim W, Dunn AS, et al. Prevention of VTE in nonsurgical patients: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012;141(2 suppl):e195Se226S.
7. Barbar S, Noventa F, Rossetto V, et al. A risk assessment model for the identification of hospitalized medical patients at risk for venous thromboembolism: the Padua Prediction Score. J Thromb Haemost. 2010;8(11):2450-2457.
4. Khanna R, Vittinghoff E, Maselli J, Auerbach A. Unintended consequences of a standard admission order set on venous thromboembolism prophylaxis and patient outcomes. J Gen Intern Med. 2012;27 (3):318-324.
8. Spyropoulos AC, Anderson FA Jr, Fitzgerald G, et al; IMPROVE Investigators. Predictive and associative models to identify hospitalized medical patients at risk for VTE. Chest. 2011;140(3):706-714.
JAMA Internal Medicine October 2014 Volume 174, Number 10
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://archinte.jamanetwork.com/ by a Ndsu Library Periodicals User on 05/21/2015
jamainternalmedicine.com
Original Investigation Research
Invited Commentary
Venous Thromboembolism Prophylaxis for Medical Patients Who Needs It? Michael B. Rothberg, MD, MPH
In medicine, the quality and safety movement attempts to improve processes of care through careful measurement and application of industrial quality improvement techniques. When outcomes are publicly reported or tied to reimRelated article page 1577 bursement, hospitals’ ability to improve their performance has been impressive. On the other hand, choosing what to measure has been more challenging, and several measures that were formerly tied to reimbursement have been revised or rescinded. Moreover, quality measures have rarely allowed for personalization, such as adjusting hemoglobin A1C targets for age or mammography rates for patient preference. In this issue of JAMA Internal Medicine, Flanders et al1 report on one such measure that should be entirely personalized—venous thromboembolism (VTE) prophylaxis. The study, produced by a quality improvement consortium in Michigan, represents an impressive data collection effort, including more than 20 000 patients at 35 hospitals. Ascertainment of outcomes at 90 days was accomplished through universal medical record review, and 58% of patients also had telephone follow-up. As a quality improvement initiative, the consortium was certainly successful. The rates of VTE prophylaxis attained were much higher than have been previously reported, with the top one-third of hospitals achieving pharmacologic prophylaxis rates in excess of 85%. Even low-performance hospitals provided prophylaxis to more than half their patients. The disappointing finding was that low-performance hospitals had rates of VTE that were identical to those of high-performance hospitals, despite having similar patients. How should these results be interpreted? One way would be to conclude that VTE prophylaxis is not effective in medical patients and that the Joint Commission core measure2 (the number of patients who received VTE prophylaxis or have documentation on why no VTE prophylaxis was given) should be abandoned. This interpretation flies in the face of randomized clinical trial evidence, which has found conclusively for high-risk medical patients that VTE prophylaxis can prevent one-third to half of symptomatic VTE events, in particular pulmonary emboli. Given the low rate of events in the study by Flanders et al1 (approximately 1% at 90 days) and the small differences in prophylaxis rates among the hospitals (approximately 30% between top and bottom performers), it was underpowered to detect even a 50% relative risk reduction due to pharmacologic prophylaxis. Another interpretation would be that giving prophylaxis to large numbers of low-risk patients is an inefficient way to reduce VTE and that hospitals might achieve similar outcomes with far fewer painful injections and less expense. jamainternalmedicine.com
The 2012 American College of Chest Physicians antithrombotic therapy guidelines estimate that the number needed to treat to prevent 1 inpatient VTE is at least 500.3 Whether a few days of inpatient prophylaxis can prevent VTE in the following 90 days is an important but unanswered question. The extremely low rate of VTE in this study (just 0.16% during hospitalization) underscores the need to perform careful risk assessment—exactly what the Joint Commission standard originally measured. However, in the latest version of this measure, once prophylaxis is given there is no need to demonstrate that risk assessment was performed. There is only a requirement to document low risk for patients who do not receive prophylaxis, and there is no penalty for prescribing prophylaxis unnecessarily or even when it is contraindicated. Flanders et al1 did not report on rates of inappropriate prophylaxis or bleeding, but at least one study4 found that a quality improvement initiative with a standard admission order set failed to increase appropriate prescribing but led to an increase in inappropriate prophylaxis and major bleeding. Unfortunately, validated tools for performing risk assessment are lacking. Citing venous thromboembolism as the most common cause of preventable hospital death and frustrated by years of low rates of VTE prophylaxis worldwide, proponents of VTE prophylaxis have generally erred on the side of overuse, arguing that less than 5% of medical patients were at low risk for VTE. Flanders et al1 used a Caprini score cutoff of 2 or greater to identify high-risk patients, but a perusal of the Caprini scoring sheet reveals how exaggerated this approach is: a 41-year-old with a body mass index of 26 already has a score of 2, as does anyone older than 60 years.5 It is no wonder, then, that despite having a mean Caprini score of 5.8 (reported predicted risk of 40%-80%),5 the rate of VTE in this population was low. Although the risk factors for VTE are well known, the appropriate weights to assign the factors in determining VTE risk are not. The fact that each hospital in this consortium used their own method of risk assessment attests to the lack of guidance in the Joint Commission measures. Several models are readily available for inpatient use. The Caprini model, which was developed more than 20 ago, was recently validated using American College of Surgeons National Surgical Quality Improvement Program data; surgical patients with scores between 5 and 6 (similar to the Flanders’ cohort) had a 1.33% risk of VTE.6 The model does not appear to have been validated in medical patients, which is concerning because few of its 35 risk factors were independently associated with VTE. The most recent version of the American College of Chest Physicians antithrombotic guidelines recommends using the Padua Prediction Score, which was prospectively validated on 1180 patients JAMA Internal Medicine October 2014 Volume 174, Number 10
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://archinte.jamanetwork.com/ by a Ndsu Library Periodicals User on 05/21/2015
1585
Research Original Investigation
Venous Thromboembolism
in Padua, Italy.7 The model is simple, comprising 11 risk factors, each assigned a point value. Using a cutoff of 4, the prediction tool neatly separated patients into a high-risk group (approximately 40% of patients) in which 11% developed VTE and a low-risk group in which 0.4% developed VTE. Several aspects of the Padua study raise doubts about its applicability to US patients, including an overall risk of VTE that was 3 times that seen in the study by Flanders et al and a mean length of stay longer than 9 days. A predictive model based on the International Medical Prevention Registry on Venous Thromboembolism registry includes only 4 Padua factors but with different weights.8 Patients with more than 4 points also had an 11% risk of VTE, but only 0.4% of patients had scores this high; 56% of patients had a risk of 1.0%, and 33% of patients had a risk of 0.5%. It is time to balance our goal of ensuring that every highrisk patient receives prophylaxis with ensuring that low-risk patients do not. After more than 20 years of research on VTE ARTICLE INFORMATION Author Affiliation: Center for Value-Based Care Research, Medicine Institute, Cleveland Clinic, Cleveland, Ohio. Corresponding Author: Michael B. Rothberg, MD, MPH, Center for Value-Based Care Research, Medicine Institute, Cleveland Clinic, 9500 Euclid Ave, Cleveland, OH 44195 ([email protected]). Published Online: August 18, 2014. doi:10.1001/jamainternmed.2014.3357. Conflict of Interest Disclosures: Dr Rothberg reports receiving research support from the Agency for Healthcare Research and Quality. REFERENCES 1. Flanders SA, Greene MT, Grant P, et al. Hospital performance for pharmacologic venous thromboembolism prophylaxis and rate of venous
1586
prophylaxis, 2 critical gaps in our knowledge remain. First, how do we reliably predict risk? There is a need for a validated prediction model that incorporates the known VTE risk factors. It need not be perfect, but it should achieve separation between low- and high-risk patients. Simply validating the Padua Prediction Score in a US population might be sufficient. The study by Flanders et al1 appears to have the data necessary to do so and would be a good place to start. Second, what is meant by low risk? There is need for a decision analytic model to determine a threshold for treatment. Given that most patients have risks ranging from 0.5% to 1.0%, understanding this threshold is crucial. Surprisingly, there are no published models to determine at what probability of VTE the benefits of prophylaxis would outweigh the harms. Ideally, these questions would have been answered before VTE prophylaxis was implemented as a hospital quality measure. But it is not too late. Adding the “who” to the “what” would be a welcome enhancement to the next generation of VTE measures.
thromboembolism: a cohort study [published online August 18, 2014]. JAMA Intern Med. doi:10 .1001/jamainternmed.2014.3384.
5. Caprini JA. Thrombosis risk assessment as a guide to quality patient care. Dis Mon. 2005; 51(2-3):70-78.
2. The Joint Commission. Venous Thromboembolism (VTE) Core Measure Set. 2014. http://www.jointcommission.org/core_measure _sets.aspx. Accessed June 20, 2014.
6. Bahl V, Hu HM, Henke PK, Wakefield TW, Campbell DA Jr, Caprini JA. A validation study of a retrospective venous thromboembolism risk scoring method. Ann Surg. 2010;251(2):344-350.
3. Kahn SR, Lim W, Dunn AS, et al. Prevention of VTE in nonsurgical patients: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012;141(2 suppl):e195Se226S.
7. Barbar S, Noventa F, Rossetto V, et al. A risk assessment model for the identification of hospitalized medical patients at risk for venous thromboembolism: the Padua Prediction Score. J Thromb Haemost. 2010;8(11):2450-2457.
4. Khanna R, Vittinghoff E, Maselli J, Auerbach A. Unintended consequences of a standard admission order set on venous thromboembolism prophylaxis and patient outcomes. J Gen Intern Med. 2012;27 (3):318-324.
8. Spyropoulos AC, Anderson FA Jr, Fitzgerald G, et al; IMPROVE Investigators. Predictive and associative models to identify hospitalized medical patients at risk for VTE. Chest. 2011;140(3):706-714.
JAMA Internal Medicine October 2014 Volume 174, Number 10
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://archinte.jamanetwork.com/ by a Ndsu Library Periodicals User on 05/21/2015
jamainternalmedicine.com
