Gregory A. Maynard, MD, MS, MHM

Venous thromboembolism (VTE), comprised of pulmonary embolism (PE) and deep vein thrombosis (DVT), impacts hundreds of thousands of Americans annually.[1] The complications of VTE can be severe, including the post‐thrombotic syndrome, pulmonary hypertension, and complications of anticoagulation. VTE is often a complication of hospitalization, and PE is a common preventable cause of hospital mortality.[2, 3] Pharmacologic VTE prophylaxis (VTEP) in at‐risk patients is effective and endorsed by prominent guidelines.[4, 5, 6] However, VTEP is underutilized, with only 30% to 50% of eligible patients receiving the right drug, dose, and duration.[7, 8]

Public reporting and reimbursement policies reflect the magnitude of VTE as a public health concern. The Centers for Medicare and Medicaid Services (CMS) withholds incremental payment for VTE complications.[9] The rate of hospital‐associated VTE (HA‐VTE) is used by benchmarking organizations as a quality indicator.[10, 11]

The University of California (UC) has 5 major academic medical centers, located in Irvine (UCI), Los Angeles (UCLA), Sacramento (UC Davis [UCD]), San Diego (UCSD), and San Francisco (UCSF). In both 2010 and 2011, almost 700 UC patients suffered from HA‐VTE annually. Barriers to optimal VTEP included the absence of standardized VTE risk assessment, lack of consensus on appropriate VTEP options for various inpatient populations, and a lack of collaborative infrastructure. Other barriers included poor adherence to mechanical prophylaxis and suboptimal measurement of prophylaxis and HA‐VTE outcomes.

In late 2011, leaders from the 5 medical centers, supported by an internal competitive grant from the UC Office of the President and the Center for Health Quality and Innovation, formed a collaborative to address barriers, optimize VTEP in inpatients, and reduce HA‐VTE across the system. Prior efforts at UCSD illustrated single‐center improvement, with an increase in adequate VTEP from 50% to over 95%, and a nearly 40% reduction in the incidence of HA‐VTE.[12] We set out to scale this success across all 5 sites as a coordinated collaborative.

METHODS

This was a prospective, unblinded, open‐intervention study with historical controls that assessed prespecified outcomes before, during, and after institution of multiple VTEP strategies in 5 independent, but cooperating, academic hospitals. All adult medical and surgical inpatients were included; psychiatric, obstetricsgynecology, rehabilitation, observation status, and pediatric populations were excluded. The study period was July 1, 2012 through June 30, 2015. Calendar year (CY) 2011 was the baseline year for comparison; interventions were initiated in CY 2012 to CY 2014, and CY 2014 was considered the mature postintervention period.

RESULTS

Robust sampling (421 to 728 patients at each site) revealed attainment of high rates of adequate VTE prophylaxis (82% to 96% at all sites, collectively 89%) by early 2014. Common measures for adequate VTEP were not finalized and collected by all sites until early 2013, so we did not capture baseline VTEP rates, and could not compare baseline to mature prophylaxis rates. Reliable administration of mechanical and anticoagulant prophylaxis was monitored and targeted by each institution, albeit not in an identical fashion at each site. Adherence to mechanical prophylaxis was reported as improved at the sites, but these data were not collated and analyzed centrally.

Hospital‐Associated VTE

There were 2431 HA‐VTE events observed in 306,906 adult inpatients across CY 2011 to 2014 (Table 1). The baseline incidence of HA‐VTE was 0.90% (667 events in 73,941 hospitalizations in 2011). The incidence of HA‐VTE in the postintervention period was 0.69% (546 HA‐VTE events in 79,565 hospitalizations in 2014, P < 0.001), an overall reduction of 24%. The absolute risk for PE decreased from 0.49% to 0.39% (RR: 0.79, 95% CI: 0.68‐0.92), a reduction of 21%, and the absolute risk of leg DVT fell from 0.41% to 0.30% (RR: 0.73, 95% CI: 0.61‐0.86), a reduction of 27%. Both proximal and distal DVT were reduced significantly. Proximal DVT was much more commonly diagnosed than distal DVT. Proximal DVT incidence decreased from 0.32% to 0.25% (RR: 0.77, 95% CI: 0.64‐0.93), whereas distal DVT incidence decreased from 0.09% to 0.05% (RR: 0.58, 95% CI: 0.39‐0.86). The lower overall VTE rate in the postimplementation period compared with the baseline period corresponds to an estimated 170 fewer cases of VTE per year (89 DVT, 81 PE).

Table 1.Pulmonary and Deep Vein Thrombosis Rates Calendar Years 2011 to 2014

	2011 (Baseline), No./%	2012, No./%	2013, No./%	2014 (Mature), No./%	2014 Versus 2011 Relative Risk (95% CI)	2014 Versus 2011 Estimated Averted Events (95% CI)
NOTE: All adult Inpatients (with and without cancer diagnosis), discharged from all University of California Hospitals are included. The impact of improvement efforts was highest in the surgical population. See text for additional detail on proximal versus distal DVT. Abbreviations: CI, confidence interval; DVT, deep vein thrombosis; PE, pulmonary embolism.
Total discharges (medical and surgical)	73,941	76,100	77,300	79,565
Total PE + leg DVT	667/0.90%	650/0.85%	568/0.73%	546/0.69%	0.761 (0.680‐0.852)	170 (103‐247)
Total PE	363/0.49%	359/0.47%	340/0.44%	309/0.39%	0.791 (0.680‐0.920)	81 (32‐135)
Total leg DVT	304/0.41%	291/0.38%	228/0.29%	237/0.3%	0.725 (0.612‐0.858)	89(40‐135)
Medical discharges	31,219	32,597	33,805	34,875
Total PE + leg DVT	178/0.57%	168/0.52%	164/0.49%	179/0.51%	0.900 (0.732‐1.1071)
PE	110/0.35%	94/0.29%	106/0.31%	104/0.30%	0.846 (0.648‐1.106)
Leg DVT	68/0.22%	74/0.23%	58/0.17%	75/0.22%	0.987 (0.711‐1.371)
Surgical discharges	42,722	43,503	43,495	44,690
Total PE + leg DVT	489/1.14%	482/1.11%	404/0.93%	367/0.82%	0.718 (0.627‐0.821)
PE	253/0.59%	265/0.61%	234/0.54%	205/0.46%	0.775 (0.645‐0.931)
Leg DVT	236/0.55%	217/0.50%	180/0.41%	162/0.36%	0.656 (0.538‐0.801)

The baseline rate of HA‐VTE and degree of improvement varied between institutions (Figure 1). UCI and UCD began the study with significantly higher VTE rates, and enjoyed the largest improvements. UCLA's VTE rate decreased to a lesser extent, whereas UCSD and UCSF rates remained relatively flat or were marginally higher. In contrast to the highly variable 2011 baseline rate of HA‐VTE (0.60%1.36%), all 5 sites had HA‐VTE rates within a very narrow range (0.65%0.73%) at maturity in 2014.

jhm2658-fig-0001-m.png

Cancer Versus Noncancer Patients

The incidence of HA‐VTE was higher in cancer patients than in noncancer patients. In 2011, 227 of 18,487 (1.23%) cancer patients developed VTE, versus 440 of 55,454 (0.79%) noncancer patients (Figure 2). After implementation of the VTE prevention initiative, the incidence of VTE in cancer patients fell by 0.21% (210 events in 20,544 patients in 2014, 1.02%), and the incidence of VTE in noncancer patients fell by 0.22% (336 events in 59,021 patients, 0.57%). The relative risk of HA‐VTE after the VTE interventions was reduced by 17% (RR: 0.83, 95% CI: 0.69‐1.00) in cancer patients and 28% (RR: 0.72, 95% CI: 0.62‐0.83) in noncancer patients.

jhm2658-fig-0002-m.png

DISCUSSION

Our initiative, comprised of a collaborative infrastructure, a proven quality‐improvement framework, and a bundle of interventions, was associated with a 24% reduction in the risk of HA‐VTE across our 5 academic medical centers. This represents avoidance of significant clinical morbidity (an estimated 81 PEs and 89 DVTs per year) and significant cost. Assuming costs of $9250 per DVT and $13,050 per PE,[17] the estimated short‐term cost savings are almost $1.9 million per year (minus expenditures on VTEP). Further savings might be expected over a longer time horizon because of the avoidance of recurrent VTE, post‐thrombotic syndrome, and the costs and complications of long‐term anticoagulation.

We believe the highly variable degree of improvement seen across our 5 sites was due to the relatively mature VTEP efforts at the onset of this collaborative improvement effort at UCSD and UCSF. As we noted earlier, the interventional bundle and methods were derived from earlier work at UCSD that had already demonstrated published marked improvement in prophylaxis and a 40% decrease in HA‐VTE.[14] The narrow range of low HA‐VTE rates in 2014 (the mature intervention time period) suggests there may be some HA‐VTE rate beyond which further prevention efforts are less productive.

Our study has several limitations. As a longitudinal collaborative improvement effort introducing a bundle of interventions, we cannot ascribe improved outcomes to individual components in the bundle; for example, we did not record the number of measure‐vention calls or resulting prophylaxis changes. We also did not measure adverse events due to VTEP, believing benefits to be greater than risks, but some adverse events likely did occur and attenuated benefits and cost savings. Although we had rigorous measures to assess the prevalence of appropriate prophylaxis, we failed to capture the baseline rate of VTEP, which means we cannot show that improved HA‐VTE rates corresponded to improvements in VTEP rates. The bundle of interventions was not implemented uniformly. Some metrics, like adherence to mechanical prophylaxis, were monitored in a decentralized fashion, without collation or collective analysis.

Were improved VTE rates due to decreases in HA‐VTE detection? We could not detect postdischarge HA‐VTE that presented to other hospitals, but we have no reason to think the proportion of missed HA‐VTE changed over the study. We discouraged the practice of routinely extending duplex ultrasound testing below the knee, and also discouraged surveillance of asymptomatic patients with Doppler ultrasound. This raises the question of ascertainment bias. Did we have fewer HA‐VTE in 2014 because our interventions worked, or did we reduce how aggressively we looked for HA‐VTE? Higher frequencies of ultrasound testing are correlated with higher rates of DVT because of surveillance bias.[18] Although some reduction in DVT was due to changes in ultrasound practices, several factors suggest the majority of improvement resulted from our interventions. First, only 1 of our 5 sites (UCD) routinely extended ultrasound testing below the knee in the baseline period. Second, we distinguished distal DVT from proximal/unspecified DVT, and the rates of both showed significant improvement. Screening asymptomatic patients with ultrasounds for DVT was limited to a few services in special circumstances (for example, the trauma service at UCSD screened patients at highest risk who could not be prophylaxed with anticoagulation). We did not have the capability to formally track which patients were being diagnosed with screening exams versus for symptoms, but screen‐detected patients were a small minority. We did not successfully dissuade these few services from stopping this approach, but we did head off some services that were considering this strategy, and think it likely that at best, we kept screening from spreading. Third, PE was reduced by over 20%, in addition to reductions in DVT, even though several of our sites acquired computed tomography scanners more sensitive for small thrombi/emncidental PE. Finally, the aggressiveness of ultrasound testing often goes up with aggressive prevention efforts, which would have led to surveillance bias with increasedrather than decreasedrates of HA‐VTE.

Our study has a number of strengths. Our effort encompassed a large and inclusive adult inpatient population over a long period of observation, with a relatively large reduction in HA‐VTE. These reductions occurred even though the proportion of patients with cancer (our most powerful predictor of VTE risk) was 34.8% in 2014 versus 33.3% in 2011. Our metrics captured patients readmitted to the hospital within 30 days of a prior VTE‐free admission as well as patients suffering VTE during the hospital stay, with the limitation that we captured only patients readmitted back to our own institutions. Our metrics for VTEP scrutinized prophylaxis rates at different points during hospitalizations, and risk‐appropriate prophylaxis was assessed, in contrast to some common regulatory measures that monitor only whether any prophylaxis is in place on the first day of admission or transfer.[11]

Our study should be instructive in terms of focusing improvement efforts. The rate of HA‐VTE was much higher in cancer and surgical patients than in medical patients, and we only achieved a nonsignificant 10% reduction in risk among medical patients (RR: 0.90, 95% CI: 0.73‐1.11). This is consistent with literature demonstrating a more limited benefit of prophylaxis in medical inpatients.[19] Although we continue to recommend prophylaxis in high‐risk medical inpatients, efforts targeting cancer and surgical populations are likely to yield greater results.

Our collaborative used methods that are portable, sustainable, and provide an excellent platform for spread of improvement across a system. The portability of these strategies is underlined by the variable baseline performance and the different stages of electronic health record development at our unique sites. Toolkits that describe the interventions (such as order sets, educational tools, measures, measure‐vention) are freely available, and reflect established guidelines.[1] Our collaborative model is consistent with successful models published in the literature.[1, 14, 20] In these models, clinical experts distill the evidence down into key best practices, and design processes that need to occur with the lowest barriers to use. Metrics, expert advice, and toolkits are assembled centrally, while each hospital identifies local barriers to implementation, educates and engages staff, executes implementation, and continually evaluates performance, modifying interventions accordingly. Embedding clinical decision and risk‐assessment into VTE prevention modules within commonly used order sets and documentation tools helps to hard‐wire the interventions, tightly linking risk assessment to appropriate prophylaxis options. The approach to standardization allows for flexibility for special populations and special needs of unique patients, while minimizing needless variation based on the ordering providers. Program management tools and regular webinars keeps sites on track, coordinate interventions, sustain enthusiasm, and provide a venue for sharing tools and lessons learned. Multiple active interventions are utilized rather than relying on passive educational techniques or order sets alone. Active surveillance (i.e., measure‐vention) deserves special attention. Measure‐vention has demonstrated utility in inpatient glycemic control and a variety of hospital‐associated infections in addition to VTE prevention, and some systems now uses measure‐ventionists as the lynchpin for a whole host of successful improvement programs.[12, 14, 21, 22] We believe high‐quality metrics, standardized protocol‐driven order sets, and measure‐vention are the crucial elements for success.

CONCLUSIONS

Hospital systems can reduce HA‐VTE by implementing a bundle of active interventions including standardized VTEP orders with embedded risk assessment and measure‐vention. Good measurement of HA‐VTE, appropriate VTEP that exceeds minimum regulatory standards, and a robust collaborative infrastructure inform and accelerate improvement. Surgical and cancer populations are at higher risk for HA‐VTE and should be a prime focus of improvement efforts.

Venous thromboembolism (VTE), comprised of pulmonary embolism (PE) and deep vein thrombosis (DVT), impacts hundreds of thousands of Americans annually.[1] The complications of VTE can be severe, including the post‐thrombotic syndrome, pulmonary hypertension, and complications of anticoagulation. VTE is often a complication of hospitalization, and PE is a common preventable cause of hospital mortality.[2, 3] Pharmacologic VTE prophylaxis (VTEP) in at‐risk patients is effective and endorsed by prominent guidelines.[4, 5, 6] However, VTEP is underutilized, with only 30% to 50% of eligible patients receiving the right drug, dose, and duration.[7, 8]

Public reporting and reimbursement policies reflect the magnitude of VTE as a public health concern. The Centers for Medicare and Medicaid Services (CMS) withholds incremental payment for VTE complications.[9] The rate of hospital‐associated VTE (HA‐VTE) is used by benchmarking organizations as a quality indicator.[10, 11]

The University of California (UC) has 5 major academic medical centers, located in Irvine (UCI), Los Angeles (UCLA), Sacramento (UC Davis [UCD]), San Diego (UCSD), and San Francisco (UCSF). In both 2010 and 2011, almost 700 UC patients suffered from HA‐VTE annually. Barriers to optimal VTEP included the absence of standardized VTE risk assessment, lack of consensus on appropriate VTEP options for various inpatient populations, and a lack of collaborative infrastructure. Other barriers included poor adherence to mechanical prophylaxis and suboptimal measurement of prophylaxis and HA‐VTE outcomes.

In late 2011, leaders from the 5 medical centers, supported by an internal competitive grant from the UC Office of the President and the Center for Health Quality and Innovation, formed a collaborative to address barriers, optimize VTEP in inpatients, and reduce HA‐VTE across the system. Prior efforts at UCSD illustrated single‐center improvement, with an increase in adequate VTEP from 50% to over 95%, and a nearly 40% reduction in the incidence of HA‐VTE.[12] We set out to scale this success across all 5 sites as a coordinated collaborative.

METHODS

This was a prospective, unblinded, open‐intervention study with historical controls that assessed prespecified outcomes before, during, and after institution of multiple VTEP strategies in 5 independent, but cooperating, academic hospitals. All adult medical and surgical inpatients were included; psychiatric, obstetricsgynecology, rehabilitation, observation status, and pediatric populations were excluded. The study period was July 1, 2012 through June 30, 2015. Calendar year (CY) 2011 was the baseline year for comparison; interventions were initiated in CY 2012 to CY 2014, and CY 2014 was considered the mature postintervention period.

RESULTS

Robust sampling (421 to 728 patients at each site) revealed attainment of high rates of adequate VTE prophylaxis (82% to 96% at all sites, collectively 89%) by early 2014. Common measures for adequate VTEP were not finalized and collected by all sites until early 2013, so we did not capture baseline VTEP rates, and could not compare baseline to mature prophylaxis rates. Reliable administration of mechanical and anticoagulant prophylaxis was monitored and targeted by each institution, albeit not in an identical fashion at each site. Adherence to mechanical prophylaxis was reported as improved at the sites, but these data were not collated and analyzed centrally.

Hospital‐Associated VTE

There were 2431 HA‐VTE events observed in 306,906 adult inpatients across CY 2011 to 2014 (Table 1). The baseline incidence of HA‐VTE was 0.90% (667 events in 73,941 hospitalizations in 2011). The incidence of HA‐VTE in the postintervention period was 0.69% (546 HA‐VTE events in 79,565 hospitalizations in 2014, P < 0.001), an overall reduction of 24%. The absolute risk for PE decreased from 0.49% to 0.39% (RR: 0.79, 95% CI: 0.68‐0.92), a reduction of 21%, and the absolute risk of leg DVT fell from 0.41% to 0.30% (RR: 0.73, 95% CI: 0.61‐0.86), a reduction of 27%. Both proximal and distal DVT were reduced significantly. Proximal DVT was much more commonly diagnosed than distal DVT. Proximal DVT incidence decreased from 0.32% to 0.25% (RR: 0.77, 95% CI: 0.64‐0.93), whereas distal DVT incidence decreased from 0.09% to 0.05% (RR: 0.58, 95% CI: 0.39‐0.86). The lower overall VTE rate in the postimplementation period compared with the baseline period corresponds to an estimated 170 fewer cases of VTE per year (89 DVT, 81 PE).

Table 1.Pulmonary and Deep Vein Thrombosis Rates Calendar Years 2011 to 2014

	2011 (Baseline), No./%	2012, No./%	2013, No./%	2014 (Mature), No./%	2014 Versus 2011 Relative Risk (95% CI)	2014 Versus 2011 Estimated Averted Events (95% CI)
NOTE: All adult Inpatients (with and without cancer diagnosis), discharged from all University of California Hospitals are included. The impact of improvement efforts was highest in the surgical population. See text for additional detail on proximal versus distal DVT. Abbreviations: CI, confidence interval; DVT, deep vein thrombosis; PE, pulmonary embolism.
Total discharges (medical and surgical)	73,941	76,100	77,300	79,565
Total PE + leg DVT	667/0.90%	650/0.85%	568/0.73%	546/0.69%	0.761 (0.680‐0.852)	170 (103‐247)
Total PE	363/0.49%	359/0.47%	340/0.44%	309/0.39%	0.791 (0.680‐0.920)	81 (32‐135)
Total leg DVT	304/0.41%	291/0.38%	228/0.29%	237/0.3%	0.725 (0.612‐0.858)	89(40‐135)
Medical discharges	31,219	32,597	33,805	34,875
Total PE + leg DVT	178/0.57%	168/0.52%	164/0.49%	179/0.51%	0.900 (0.732‐1.1071)
PE	110/0.35%	94/0.29%	106/0.31%	104/0.30%	0.846 (0.648‐1.106)
Leg DVT	68/0.22%	74/0.23%	58/0.17%	75/0.22%	0.987 (0.711‐1.371)
Surgical discharges	42,722	43,503	43,495	44,690
Total PE + leg DVT	489/1.14%	482/1.11%	404/0.93%	367/0.82%	0.718 (0.627‐0.821)
PE	253/0.59%	265/0.61%	234/0.54%	205/0.46%	0.775 (0.645‐0.931)
Leg DVT	236/0.55%	217/0.50%	180/0.41%	162/0.36%	0.656 (0.538‐0.801)

The baseline rate of HA‐VTE and degree of improvement varied between institutions (Figure 1). UCI and UCD began the study with significantly higher VTE rates, and enjoyed the largest improvements. UCLA's VTE rate decreased to a lesser extent, whereas UCSD and UCSF rates remained relatively flat or were marginally higher. In contrast to the highly variable 2011 baseline rate of HA‐VTE (0.60%1.36%), all 5 sites had HA‐VTE rates within a very narrow range (0.65%0.73%) at maturity in 2014.

jhm2658-fig-0001-m.png

Cancer Versus Noncancer Patients

The incidence of HA‐VTE was higher in cancer patients than in noncancer patients. In 2011, 227 of 18,487 (1.23%) cancer patients developed VTE, versus 440 of 55,454 (0.79%) noncancer patients (Figure 2). After implementation of the VTE prevention initiative, the incidence of VTE in cancer patients fell by 0.21% (210 events in 20,544 patients in 2014, 1.02%), and the incidence of VTE in noncancer patients fell by 0.22% (336 events in 59,021 patients, 0.57%). The relative risk of HA‐VTE after the VTE interventions was reduced by 17% (RR: 0.83, 95% CI: 0.69‐1.00) in cancer patients and 28% (RR: 0.72, 95% CI: 0.62‐0.83) in noncancer patients.

jhm2658-fig-0002-m.png

DISCUSSION

Our initiative, comprised of a collaborative infrastructure, a proven quality‐improvement framework, and a bundle of interventions, was associated with a 24% reduction in the risk of HA‐VTE across our 5 academic medical centers. This represents avoidance of significant clinical morbidity (an estimated 81 PEs and 89 DVTs per year) and significant cost. Assuming costs of $9250 per DVT and $13,050 per PE,[17] the estimated short‐term cost savings are almost $1.9 million per year (minus expenditures on VTEP). Further savings might be expected over a longer time horizon because of the avoidance of recurrent VTE, post‐thrombotic syndrome, and the costs and complications of long‐term anticoagulation.

We believe the highly variable degree of improvement seen across our 5 sites was due to the relatively mature VTEP efforts at the onset of this collaborative improvement effort at UCSD and UCSF. As we noted earlier, the interventional bundle and methods were derived from earlier work at UCSD that had already demonstrated published marked improvement in prophylaxis and a 40% decrease in HA‐VTE.[14] The narrow range of low HA‐VTE rates in 2014 (the mature intervention time period) suggests there may be some HA‐VTE rate beyond which further prevention efforts are less productive.

Our study has several limitations. As a longitudinal collaborative improvement effort introducing a bundle of interventions, we cannot ascribe improved outcomes to individual components in the bundle; for example, we did not record the number of measure‐vention calls or resulting prophylaxis changes. We also did not measure adverse events due to VTEP, believing benefits to be greater than risks, but some adverse events likely did occur and attenuated benefits and cost savings. Although we had rigorous measures to assess the prevalence of appropriate prophylaxis, we failed to capture the baseline rate of VTEP, which means we cannot show that improved HA‐VTE rates corresponded to improvements in VTEP rates. The bundle of interventions was not implemented uniformly. Some metrics, like adherence to mechanical prophylaxis, were monitored in a decentralized fashion, without collation or collective analysis.

Were improved VTE rates due to decreases in HA‐VTE detection? We could not detect postdischarge HA‐VTE that presented to other hospitals, but we have no reason to think the proportion of missed HA‐VTE changed over the study. We discouraged the practice of routinely extending duplex ultrasound testing below the knee, and also discouraged surveillance of asymptomatic patients with Doppler ultrasound. This raises the question of ascertainment bias. Did we have fewer HA‐VTE in 2014 because our interventions worked, or did we reduce how aggressively we looked for HA‐VTE? Higher frequencies of ultrasound testing are correlated with higher rates of DVT because of surveillance bias.[18] Although some reduction in DVT was due to changes in ultrasound practices, several factors suggest the majority of improvement resulted from our interventions. First, only 1 of our 5 sites (UCD) routinely extended ultrasound testing below the knee in the baseline period. Second, we distinguished distal DVT from proximal/unspecified DVT, and the rates of both showed significant improvement. Screening asymptomatic patients with ultrasounds for DVT was limited to a few services in special circumstances (for example, the trauma service at UCSD screened patients at highest risk who could not be prophylaxed with anticoagulation). We did not have the capability to formally track which patients were being diagnosed with screening exams versus for symptoms, but screen‐detected patients were a small minority. We did not successfully dissuade these few services from stopping this approach, but we did head off some services that were considering this strategy, and think it likely that at best, we kept screening from spreading. Third, PE was reduced by over 20%, in addition to reductions in DVT, even though several of our sites acquired computed tomography scanners more sensitive for small thrombi/emncidental PE. Finally, the aggressiveness of ultrasound testing often goes up with aggressive prevention efforts, which would have led to surveillance bias with increasedrather than decreasedrates of HA‐VTE.

Our study has a number of strengths. Our effort encompassed a large and inclusive adult inpatient population over a long period of observation, with a relatively large reduction in HA‐VTE. These reductions occurred even though the proportion of patients with cancer (our most powerful predictor of VTE risk) was 34.8% in 2014 versus 33.3% in 2011. Our metrics captured patients readmitted to the hospital within 30 days of a prior VTE‐free admission as well as patients suffering VTE during the hospital stay, with the limitation that we captured only patients readmitted back to our own institutions. Our metrics for VTEP scrutinized prophylaxis rates at different points during hospitalizations, and risk‐appropriate prophylaxis was assessed, in contrast to some common regulatory measures that monitor only whether any prophylaxis is in place on the first day of admission or transfer.[11]

Our study should be instructive in terms of focusing improvement efforts. The rate of HA‐VTE was much higher in cancer and surgical patients than in medical patients, and we only achieved a nonsignificant 10% reduction in risk among medical patients (RR: 0.90, 95% CI: 0.73‐1.11). This is consistent with literature demonstrating a more limited benefit of prophylaxis in medical inpatients.[19] Although we continue to recommend prophylaxis in high‐risk medical inpatients, efforts targeting cancer and surgical populations are likely to yield greater results.

Our collaborative used methods that are portable, sustainable, and provide an excellent platform for spread of improvement across a system. The portability of these strategies is underlined by the variable baseline performance and the different stages of electronic health record development at our unique sites. Toolkits that describe the interventions (such as order sets, educational tools, measures, measure‐vention) are freely available, and reflect established guidelines.[1] Our collaborative model is consistent with successful models published in the literature.[1, 14, 20] In these models, clinical experts distill the evidence down into key best practices, and design processes that need to occur with the lowest barriers to use. Metrics, expert advice, and toolkits are assembled centrally, while each hospital identifies local barriers to implementation, educates and engages staff, executes implementation, and continually evaluates performance, modifying interventions accordingly. Embedding clinical decision and risk‐assessment into VTE prevention modules within commonly used order sets and documentation tools helps to hard‐wire the interventions, tightly linking risk assessment to appropriate prophylaxis options. The approach to standardization allows for flexibility for special populations and special needs of unique patients, while minimizing needless variation based on the ordering providers. Program management tools and regular webinars keeps sites on track, coordinate interventions, sustain enthusiasm, and provide a venue for sharing tools and lessons learned. Multiple active interventions are utilized rather than relying on passive educational techniques or order sets alone. Active surveillance (i.e., measure‐vention) deserves special attention. Measure‐vention has demonstrated utility in inpatient glycemic control and a variety of hospital‐associated infections in addition to VTE prevention, and some systems now uses measure‐ventionists as the lynchpin for a whole host of successful improvement programs.[12, 14, 21, 22] We believe high‐quality metrics, standardized protocol‐driven order sets, and measure‐vention are the crucial elements for success.

CONCLUSIONS

Hospital systems can reduce HA‐VTE by implementing a bundle of active interventions including standardized VTEP orders with embedded risk assessment and measure‐vention. Good measurement of HA‐VTE, appropriate VTEP that exceeds minimum regulatory standards, and a robust collaborative infrastructure inform and accelerate improvement. Surgical and cancer populations are at higher risk for HA‐VTE and should be a prime focus of improvement efforts.

Venous thromboembolism (VTE), comprised of pulmonary embolism (PE) and deep vein thrombosis (DVT), impacts hundreds of thousands of Americans annually.[1] The complications of VTE can be severe, including the post‐thrombotic syndrome, pulmonary hypertension, and complications of anticoagulation. VTE is often a complication of hospitalization, and PE is a common preventable cause of hospital mortality.[2, 3] Pharmacologic VTE prophylaxis (VTEP) in at‐risk patients is effective and endorsed by prominent guidelines.[4, 5, 6] However, VTEP is underutilized, with only 30% to 50% of eligible patients receiving the right drug, dose, and duration.[7, 8]

Public reporting and reimbursement policies reflect the magnitude of VTE as a public health concern. The Centers for Medicare and Medicaid Services (CMS) withholds incremental payment for VTE complications.[9] The rate of hospital‐associated VTE (HA‐VTE) is used by benchmarking organizations as a quality indicator.[10, 11]

The University of California (UC) has 5 major academic medical centers, located in Irvine (UCI), Los Angeles (UCLA), Sacramento (UC Davis [UCD]), San Diego (UCSD), and San Francisco (UCSF). In both 2010 and 2011, almost 700 UC patients suffered from HA‐VTE annually. Barriers to optimal VTEP included the absence of standardized VTE risk assessment, lack of consensus on appropriate VTEP options for various inpatient populations, and a lack of collaborative infrastructure. Other barriers included poor adherence to mechanical prophylaxis and suboptimal measurement of prophylaxis and HA‐VTE outcomes.

In late 2011, leaders from the 5 medical centers, supported by an internal competitive grant from the UC Office of the President and the Center for Health Quality and Innovation, formed a collaborative to address barriers, optimize VTEP in inpatients, and reduce HA‐VTE across the system. Prior efforts at UCSD illustrated single‐center improvement, with an increase in adequate VTEP from 50% to over 95%, and a nearly 40% reduction in the incidence of HA‐VTE.[12] We set out to scale this success across all 5 sites as a coordinated collaborative.

METHODS

This was a prospective, unblinded, open‐intervention study with historical controls that assessed prespecified outcomes before, during, and after institution of multiple VTEP strategies in 5 independent, but cooperating, academic hospitals. All adult medical and surgical inpatients were included; psychiatric, obstetricsgynecology, rehabilitation, observation status, and pediatric populations were excluded. The study period was July 1, 2012 through June 30, 2015. Calendar year (CY) 2011 was the baseline year for comparison; interventions were initiated in CY 2012 to CY 2014, and CY 2014 was considered the mature postintervention period.

RESULTS

Robust sampling (421 to 728 patients at each site) revealed attainment of high rates of adequate VTE prophylaxis (82% to 96% at all sites, collectively 89%) by early 2014. Common measures for adequate VTEP were not finalized and collected by all sites until early 2013, so we did not capture baseline VTEP rates, and could not compare baseline to mature prophylaxis rates. Reliable administration of mechanical and anticoagulant prophylaxis was monitored and targeted by each institution, albeit not in an identical fashion at each site. Adherence to mechanical prophylaxis was reported as improved at the sites, but these data were not collated and analyzed centrally.

Hospital‐Associated VTE

There were 2431 HA‐VTE events observed in 306,906 adult inpatients across CY 2011 to 2014 (Table 1). The baseline incidence of HA‐VTE was 0.90% (667 events in 73,941 hospitalizations in 2011). The incidence of HA‐VTE in the postintervention period was 0.69% (546 HA‐VTE events in 79,565 hospitalizations in 2014, P < 0.001), an overall reduction of 24%. The absolute risk for PE decreased from 0.49% to 0.39% (RR: 0.79, 95% CI: 0.68‐0.92), a reduction of 21%, and the absolute risk of leg DVT fell from 0.41% to 0.30% (RR: 0.73, 95% CI: 0.61‐0.86), a reduction of 27%. Both proximal and distal DVT were reduced significantly. Proximal DVT was much more commonly diagnosed than distal DVT. Proximal DVT incidence decreased from 0.32% to 0.25% (RR: 0.77, 95% CI: 0.64‐0.93), whereas distal DVT incidence decreased from 0.09% to 0.05% (RR: 0.58, 95% CI: 0.39‐0.86). The lower overall VTE rate in the postimplementation period compared with the baseline period corresponds to an estimated 170 fewer cases of VTE per year (89 DVT, 81 PE).

Table 1.Pulmonary and Deep Vein Thrombosis Rates Calendar Years 2011 to 2014

	2011 (Baseline), No./%	2012, No./%	2013, No./%	2014 (Mature), No./%	2014 Versus 2011 Relative Risk (95% CI)	2014 Versus 2011 Estimated Averted Events (95% CI)
NOTE: All adult Inpatients (with and without cancer diagnosis), discharged from all University of California Hospitals are included. The impact of improvement efforts was highest in the surgical population. See text for additional detail on proximal versus distal DVT. Abbreviations: CI, confidence interval; DVT, deep vein thrombosis; PE, pulmonary embolism.
Total discharges (medical and surgical)	73,941	76,100	77,300	79,565
Total PE + leg DVT	667/0.90%	650/0.85%	568/0.73%	546/0.69%	0.761 (0.680‐0.852)	170 (103‐247)
Total PE	363/0.49%	359/0.47%	340/0.44%	309/0.39%	0.791 (0.680‐0.920)	81 (32‐135)
Total leg DVT	304/0.41%	291/0.38%	228/0.29%	237/0.3%	0.725 (0.612‐0.858)	89(40‐135)
Medical discharges	31,219	32,597	33,805	34,875
Total PE + leg DVT	178/0.57%	168/0.52%	164/0.49%	179/0.51%	0.900 (0.732‐1.1071)
PE	110/0.35%	94/0.29%	106/0.31%	104/0.30%	0.846 (0.648‐1.106)
Leg DVT	68/0.22%	74/0.23%	58/0.17%	75/0.22%	0.987 (0.711‐1.371)
Surgical discharges	42,722	43,503	43,495	44,690
Total PE + leg DVT	489/1.14%	482/1.11%	404/0.93%	367/0.82%	0.718 (0.627‐0.821)
PE	253/0.59%	265/0.61%	234/0.54%	205/0.46%	0.775 (0.645‐0.931)
Leg DVT	236/0.55%	217/0.50%	180/0.41%	162/0.36%	0.656 (0.538‐0.801)

The baseline rate of HA‐VTE and degree of improvement varied between institutions (Figure 1). UCI and UCD began the study with significantly higher VTE rates, and enjoyed the largest improvements. UCLA's VTE rate decreased to a lesser extent, whereas UCSD and UCSF rates remained relatively flat or were marginally higher. In contrast to the highly variable 2011 baseline rate of HA‐VTE (0.60%1.36%), all 5 sites had HA‐VTE rates within a very narrow range (0.65%0.73%) at maturity in 2014.

jhm2658-fig-0001-m.png

Cancer Versus Noncancer Patients

The incidence of HA‐VTE was higher in cancer patients than in noncancer patients. In 2011, 227 of 18,487 (1.23%) cancer patients developed VTE, versus 440 of 55,454 (0.79%) noncancer patients (Figure 2). After implementation of the VTE prevention initiative, the incidence of VTE in cancer patients fell by 0.21% (210 events in 20,544 patients in 2014, 1.02%), and the incidence of VTE in noncancer patients fell by 0.22% (336 events in 59,021 patients, 0.57%). The relative risk of HA‐VTE after the VTE interventions was reduced by 17% (RR: 0.83, 95% CI: 0.69‐1.00) in cancer patients and 28% (RR: 0.72, 95% CI: 0.62‐0.83) in noncancer patients.

jhm2658-fig-0002-m.png

DISCUSSION

Our initiative, comprised of a collaborative infrastructure, a proven quality‐improvement framework, and a bundle of interventions, was associated with a 24% reduction in the risk of HA‐VTE across our 5 academic medical centers. This represents avoidance of significant clinical morbidity (an estimated 81 PEs and 89 DVTs per year) and significant cost. Assuming costs of $9250 per DVT and $13,050 per PE,[17] the estimated short‐term cost savings are almost $1.9 million per year (minus expenditures on VTEP). Further savings might be expected over a longer time horizon because of the avoidance of recurrent VTE, post‐thrombotic syndrome, and the costs and complications of long‐term anticoagulation.

We believe the highly variable degree of improvement seen across our 5 sites was due to the relatively mature VTEP efforts at the onset of this collaborative improvement effort at UCSD and UCSF. As we noted earlier, the interventional bundle and methods were derived from earlier work at UCSD that had already demonstrated published marked improvement in prophylaxis and a 40% decrease in HA‐VTE.[14] The narrow range of low HA‐VTE rates in 2014 (the mature intervention time period) suggests there may be some HA‐VTE rate beyond which further prevention efforts are less productive.

Our study has several limitations. As a longitudinal collaborative improvement effort introducing a bundle of interventions, we cannot ascribe improved outcomes to individual components in the bundle; for example, we did not record the number of measure‐vention calls or resulting prophylaxis changes. We also did not measure adverse events due to VTEP, believing benefits to be greater than risks, but some adverse events likely did occur and attenuated benefits and cost savings. Although we had rigorous measures to assess the prevalence of appropriate prophylaxis, we failed to capture the baseline rate of VTEP, which means we cannot show that improved HA‐VTE rates corresponded to improvements in VTEP rates. The bundle of interventions was not implemented uniformly. Some metrics, like adherence to mechanical prophylaxis, were monitored in a decentralized fashion, without collation or collective analysis.

Were improved VTE rates due to decreases in HA‐VTE detection? We could not detect postdischarge HA‐VTE that presented to other hospitals, but we have no reason to think the proportion of missed HA‐VTE changed over the study. We discouraged the practice of routinely extending duplex ultrasound testing below the knee, and also discouraged surveillance of asymptomatic patients with Doppler ultrasound. This raises the question of ascertainment bias. Did we have fewer HA‐VTE in 2014 because our interventions worked, or did we reduce how aggressively we looked for HA‐VTE? Higher frequencies of ultrasound testing are correlated with higher rates of DVT because of surveillance bias.[18] Although some reduction in DVT was due to changes in ultrasound practices, several factors suggest the majority of improvement resulted from our interventions. First, only 1 of our 5 sites (UCD) routinely extended ultrasound testing below the knee in the baseline period. Second, we distinguished distal DVT from proximal/unspecified DVT, and the rates of both showed significant improvement. Screening asymptomatic patients with ultrasounds for DVT was limited to a few services in special circumstances (for example, the trauma service at UCSD screened patients at highest risk who could not be prophylaxed with anticoagulation). We did not have the capability to formally track which patients were being diagnosed with screening exams versus for symptoms, but screen‐detected patients were a small minority. We did not successfully dissuade these few services from stopping this approach, but we did head off some services that were considering this strategy, and think it likely that at best, we kept screening from spreading. Third, PE was reduced by over 20%, in addition to reductions in DVT, even though several of our sites acquired computed tomography scanners more sensitive for small thrombi/emncidental PE. Finally, the aggressiveness of ultrasound testing often goes up with aggressive prevention efforts, which would have led to surveillance bias with increasedrather than decreasedrates of HA‐VTE.

Our study has a number of strengths. Our effort encompassed a large and inclusive adult inpatient population over a long period of observation, with a relatively large reduction in HA‐VTE. These reductions occurred even though the proportion of patients with cancer (our most powerful predictor of VTE risk) was 34.8% in 2014 versus 33.3% in 2011. Our metrics captured patients readmitted to the hospital within 30 days of a prior VTE‐free admission as well as patients suffering VTE during the hospital stay, with the limitation that we captured only patients readmitted back to our own institutions. Our metrics for VTEP scrutinized prophylaxis rates at different points during hospitalizations, and risk‐appropriate prophylaxis was assessed, in contrast to some common regulatory measures that monitor only whether any prophylaxis is in place on the first day of admission or transfer.[11]

Our study should be instructive in terms of focusing improvement efforts. The rate of HA‐VTE was much higher in cancer and surgical patients than in medical patients, and we only achieved a nonsignificant 10% reduction in risk among medical patients (RR: 0.90, 95% CI: 0.73‐1.11). This is consistent with literature demonstrating a more limited benefit of prophylaxis in medical inpatients.[19] Although we continue to recommend prophylaxis in high‐risk medical inpatients, efforts targeting cancer and surgical populations are likely to yield greater results.

Our collaborative used methods that are portable, sustainable, and provide an excellent platform for spread of improvement across a system. The portability of these strategies is underlined by the variable baseline performance and the different stages of electronic health record development at our unique sites. Toolkits that describe the interventions (such as order sets, educational tools, measures, measure‐vention) are freely available, and reflect established guidelines.[1] Our collaborative model is consistent with successful models published in the literature.[1, 14, 20] In these models, clinical experts distill the evidence down into key best practices, and design processes that need to occur with the lowest barriers to use. Metrics, expert advice, and toolkits are assembled centrally, while each hospital identifies local barriers to implementation, educates and engages staff, executes implementation, and continually evaluates performance, modifying interventions accordingly. Embedding clinical decision and risk‐assessment into VTE prevention modules within commonly used order sets and documentation tools helps to hard‐wire the interventions, tightly linking risk assessment to appropriate prophylaxis options. The approach to standardization allows for flexibility for special populations and special needs of unique patients, while minimizing needless variation based on the ordering providers. Program management tools and regular webinars keeps sites on track, coordinate interventions, sustain enthusiasm, and provide a venue for sharing tools and lessons learned. Multiple active interventions are utilized rather than relying on passive educational techniques or order sets alone. Active surveillance (i.e., measure‐vention) deserves special attention. Measure‐vention has demonstrated utility in inpatient glycemic control and a variety of hospital‐associated infections in addition to VTE prevention, and some systems now uses measure‐ventionists as the lynchpin for a whole host of successful improvement programs.[12, 14, 21, 22] We believe high‐quality metrics, standardized protocol‐driven order sets, and measure‐vention are the crucial elements for success.

CONCLUSIONS

Hospital systems can reduce HA‐VTE by implementing a bundle of active interventions including standardized VTEP orders with embedded risk assessment and measure‐vention. Good measurement of HA‐VTE, appropriate VTEP that exceeds minimum regulatory standards, and a robust collaborative infrastructure inform and accelerate improvement. Surgical and cancer populations are at higher risk for HA‐VTE and should be a prime focus of improvement efforts.