David Spirk

Ultrasound-Assisted Versus Conventional Catheter-Directed Thrombolysis for Acute Iliofemoral Deep Vein Thrombosis

Background—For patients with acute iliofemoral deep vein thrombosis, it remains unclear whether the addition of intravascular high-frequency, low-power ultrasound energy facilitates the resolution of thrombosis during catheter-directed thrombolysis. Methods and Results—In a controlled clinical trial, 48 patients (mean age 50±21 years, 52% women) with acute iliofemoral deep vein thrombosis were randomized to receive ultrasound-assisted catheter-directed thrombolysis (N=24) or conventional catheter-directed thrombolysis (N=24). Thrombolysis regimen (20 mg r-tPA over 15 hours) was identical in all patients. The primary efficacy end point was the percentage of thrombus load reduction from baseline to 15 hours according to the length-adjusted thrombus score, obtained from standardized venograms and evaluated by a core laboratory blinded to group assignment. The percentage of thrombus load reduction was 55%±27% in the ultrasound-assisted catheter-directed thrombolysis group and 54%±27% in the conventional catheter-directed thrombolysis group (P=0.91). Adjunctive angioplasty and stenting was performed in 19 (80%) patients and in 20 (83%) patients, respectively (P>0.99). Treatment-related complications occurred in 3 (12%) and 2 (8%) patients, respectively (P>0.99). At 3-month follow-up, primary venous patency was 100% in the ultrasound-assisted catheter-directed thrombolysis group and 96% in the conventional catheter-directed thrombolysis group (P=0.33), and there was no difference in the severity of the post-thrombotic syndrome (mean Villalta score: 3.0±3.9 [range 0–15] versus 1.9±1.9 [range 0–7]; P=0.21), respectively. Conclusions—In this randomized controlled clinical trial of patients with acute iliofemoral deep vein thrombosis treated with a fixed-dose catheter thrombolysis regimen, the addition of intravascular ultrasound did not facilitate thrombus resolution. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT01482273.

Clinical predictors of prophylaxis use prior to the onset of acute venous thromboembolism in hospitalized patients SWIss Venous ThromboEmbolism Registry (SWIVTER)

Summary.  Background: We investigated clinical predictors of appropriate prophylaxis prior to the onset of venous thromboembolism (VTE). Methods: In 14 Swiss hospitals, 567 consecutive patients (306 medical, 261 surgical) with acute VTE and hospitalization < 30 days prior to the VTE event were enrolled. Results: Prophylaxis was used in 329 (58%) patients within 30 days prior to the VTE event. Among the medical patients, 146 (48%) received prophylaxis, and among the surgical patients, 183 (70%) received prophylaxis (P < 0.001). The indication for prophylaxis was present in 262 (86%) medical patients and in 217 (83%) surgical patients. Among the patients with an indication for prophylaxis, 135 (52%) of the medical patients and 165 (76%) of the surgical patients received prophylaxis (P < 0.001). Admission to the intensive care unit [odds ratio (OR) 3.28, 95% confidence interval (CI) 1.94–5.57], recent surgery (OR 2.28, 95% CI 1.51–3.44), bed rest > 3 days (OR 2.12, 95% CI 1.45–3.09), obesity (OR 2.01, 95% CI 1.03–3.90), prior deep vein thrombosis (OR 1.71, 95% CI 1.31–2.24) and prior pulmonary embolism (OR 1.54, 95% CI 1.05–2.26) were independent predictors of prophylaxis. In contrast, cancer (OR 1.06, 95% CI 0.89–1.25), age (OR 0.99, 95% CI 0.98–1.01), acute heart failure (OR 1.13, 95% CI 0.79–1.63) and acute respiratory failure (OR 1.19, 95% CI 0.89–1.59) were not predictive of prophylaxis. Conclusions: Although an indication for prophylaxis was present in most patients who suffered acute VTE, almost half did not receive any form of prophylaxis. Future efforts should focus on the improvement of prophylaxis for hospitalized patients, particularly in patients with cancer, acute heart or respiratory failure, and in the elderly.

Identifying acutely ill medical patients requiring thromboprophylaxis

*Service Quality of Care, Geneva University Hospitals and Faculty of Medicine, Geneva; Sanofi-Synthelabo (Switzerland), Meyrin; and Divisionof Angiology and Hemostasis, Geneva University Hospitals and Faculty of Medicine, Geneva, SwitzerlandTo cite this article: Chopard P, Spirk D, Bounameaux H. Identifying acutely ill medical patients requiring thromboprophylaxis. J Thromb Haemost2006; 4: 915–6.

Long-term anticoagulation treatment for acute venous thromboembolism in patients with and without cancer The SWIss Venous ThromboEmbolism Registry (SWIVTER) II

In patients with acute cancer-associated thrombosis, current consensus guidelines recommend anticoagulation therapy for an indefinite duration or until the cancer is resolved. Among 1,247 patients with acute venous thromboembolism (VTE) enrolled in the prospective Swiss Venous Thromboembolism Registry (SWIVTER) II from 18 hospitals, 315 (25%) had cancer of whom 179 (57%) had metastatic disease, 159 (50%) ongoing or recent chemotherapy, 83 (26%) prior cancer surgery, and 63 (20%) recurrent VTE. Long-term anticoagulation treatment for >12 months was more often planned in patients with versus without cancer (47% vs. 19%; p<0.001), with recurrent cancer-associated versus first cancer-associated VTE (70% vs. 41%; p<0.001), and with metastatic versus non-metastatic cancer (59% vs. 31%; p<0.001). In patients with cancer, recurrent VTE (OR 3.46; 95%CI 1.83-6.53), metastatic disease (OR 3.04; 95%CI 1.86-4.97), and the absence of an acute infection (OR 3.55; 95%CI 1.65-7.65) were independently associated with the intention to maintain anticoagulation for >12 months. In conclusion, long-term anticoagulation treatment for more than 12 months was planned in less than half of the cancer patients with acute VTE. The low rates of long-term anticoagulation in cancer patients with a first episode of VTE and in patients with non-metastatic cancer require particular attention.

Lack of prophylaxis before the onset of acute venous thromboembolism among hospitalized cancer patients: the SWIss Venous ThromboEmbolism Registry (SWIVTER)

BACKGROUND Venous thromboembolism (VTE) prophylaxis remains underutilized, particularly in cancer patients. We explored clinical predictors of prophylaxis in hospitalized cancer patients before the onset of acute VTE. METHODS In the SWiss Venous ThromboEmbolism Registry, 257 cancer patients (61 +/- 15 years) with acute VTE and prior hospitalization for acute medical illness or surgery within 30 days (91% were at high risk with Geneva VTE risk score > or =3) were enrolled. RESULTS Overall, 153 (60%) patients received prophylaxis (49% pharmacological and 21% mechanical) before the onset of acute VTE. Outpatient status at the time of VTE diagnosis [odds ratio (OR) 0.31, 95% confidence interval (CI) 0.18-0.53], ongoing chemotherapy (OR 0.51, 95% CI 0.31-0.85), and recent chemotherapy (OR 0.53, 95% CI 0.32-0.88) were univariately associated with the absence of VTE prophylaxis. In multivariate analysis, intensive care unit admission within 30 days (OR 7.02, 95% CI 2.38-20.64), prior deep vein thrombosis (OR 3.48, 95% CI 2.14-5.64), surgery within 30 days (OR 2.43, 95% CI 1.19-4.99), bed rest >3 days (OR 2.02, 95% CI 1.08-3.78), and outpatient status (OR 0.38, 95% CI 0.19-0.76) remained the only independent predictors of thromboprophylaxis. CONCLUSIONS Although most hospitalized cancer patients were at high risk, 40% did not receive any prophylaxis before the onset of acute VTE. There is a need to improve thromboprophylaxis in cancer patients, particularly in the presence of recent or ongoing chemotherapy.

Multicentre validation of the Geneva Risk Score for hospitalised medical patients at risk of venous thromboembolism. Explicit ASsessment of Thromboembolic RIsk and Prophylaxis for Medical PATients in SwitzErland (ESTIMATE).

There is a need to validate risk assessment tools for hospitalised medical patients at risk of venous thromboembolism (VTE). We investigated whether a predefined cut-off of the Geneva Risk Score, as compared to the Padua Prediction Score, accurately distinguishes low-risk from high-risk patients regardless of the use of thromboprophylaxis. In the multicentre, prospective Explicit ASsessment of Thromboembolic RIsk and Prophylaxis for Medical PATients in SwitzErland (ESTIMATE) cohort study, 1,478 hospitalised medical patients were enrolled of whom 637 (43%) did not receive thromboprophylaxis. The primary endpoint was symptomatic VTE or VTE-related death at 90 days. The study is registered at ClinicalTrials.gov, number NCT01277536. According to the Geneva Risk Score, the cumulative rate of the primary endpoint was 3.2% (95% confidence interval [CI] 2.2-4.6%) in 962 high-risk vs 0.6% (95% CI 0.2-1.9%) in 516 low-risk patients (p=0.002); among patients without prophylaxis, this rate was 3.5% vs 0.8% (p=0.029), respectively. In comparison, the Padua Prediction Score yielded a cumulative rate of the primary endpoint of 3.5% (95% CI 2.3-5.3%) in 714 high-risk vs 1.1% (95% CI 0.6-2.3%) in 764 low-risk patients (p=0.002); among patients without prophylaxis, this rate was 3.2% vs 1.5% (p=0.130), respectively. Negative likelihood ratio was 0.28 (95% CI 0.10-0.83) for the Geneva Risk Score and 0.51 (95% CI 0.28-0.93) for the Padua Prediction Score. In conclusion, among hospitalised medical patients, the Geneva Risk Score predicted VTE and VTE-related mortality and compared favourably with the Padua Prediction Score, particularly for its accuracy to identify low-risk patients who do not require thromboprophylaxis.

Fixed low-dose ultrasound-assisted catheter-directed thrombolysis followed by routine stenting of residual stenosis for acute ilio-femoral deep-vein thrombosis

Patients with ilio-femoral deep-vein thrombosis (DVT) are at high risk of developing the post-thrombotic syndrome (PTS). In comparison to anticoagulation therapy alone, extended venography-guided catheter-directed thrombolysis without routine stenting of venous stenosis in patients with ilio-femoral DVT is associated with an increased risk of bleeding and a moderate reduction of PTS. We performed a prospective single-centre study to investigate safety, patency and incidence of PTS in patients with acute ilio-femoral DVT treated with fixed-dose ultrasound-assisted catheter-directed thrombolysis (USAT; 20 mg rt-PA during 15 hours) followed by routing stenting of venous stenosis, defined as residual luminal narrowing >50%, absent antegrade flow, or presence of collateral flow at the site of suspected stenosis. A total of 87 patients (age 46 ± 21 years, 60% women) were included. At 15 hours, thrombolysis success ≥50% was achieved in 67 (77%) patients. Venous stenting (mean 1.9 ± 1.3 stents) was performed in 70 (80%) patients, with the common iliac vein as the most frequent stenting site (83%). One major (1%; 95% CI, 0-6%) and 6 minor bleedings (7%; 95%CI, 3-14%) occurred. Primary and secondary patency rates at 1 year were 87% (95% CI, 74-94%) and 96% (95% CI, 88-99%), respectively. At three months, 88% (95% CI, 78-94%) of patients were free from PTS according to the Villalta scale, with a similar rate at one year (94%, 95% CI, 81-99%). In conclusion, a fixed-dose USAT regimen followed by routine stenting of underlying venous stenosis in patients with ilio-femoral DVT was associated with a low bleeding rate, high patency rates, and a low incidence of PTS.

Cardiac troponin testing and the simplified Pulmonary Embolism Severity Index : The SWIss Venous ThromboEmbolism Registry (SWIVTER)

A low simplified Pulmonary Embolism Severity Index (sPESI), defined as age ≤80 years and absence of systemic hypotension, tachycardia, hypoxia, cancer, heart failure, and lung disease, identifies low-risk patients with acute pulmonary embolism (PE). It is unknown whether cardiac troponin testing improves the prediction of clinical outcomes if the sPESI is not low. In the prospective Swiss Venous Thromboembolism Registry, 369 patients with acute PE and a troponin test (conventional troponin T or I, highly sensitive troponin T) were enrolled from 18 hospitals. A positive test result was defined as a troponin level above the manufacturers assay threshold. Among the 106 (29%) patients with low sPESI, the rate of mortality or PE recurrence at 30 days was 1.0%. Among the 263 (71%) patients with high sPESI, 177 (67%) were troponin-negative and 86 (33%) troponin-positive; the rate of mortality or PE recurrence at 30 days was 4.6% vs. 12.8% (p=0.015), respectively. Overall, risk assessment with a troponin test (hazard ratio [HR] 3.39, 95% confidence interval [CI] 1.38-8.37; p=0.008) maintained its prognostic value for mortality or PE recurrence when adjusted for sPESI (HR 5.80, 95%CI 0.76-44.10; p=0.09). The combination of sPESI with a troponin test resulted in a greater area under the receiver-operating characteristic curve (HR 0.72, 95% CI 0.63-0.81) than sPESI alone (HR 0.63, 95% CI 0.57-0.68) (p=0.023). In conclusion, although cardiac troponin testing may not be required in patients with a low sPESI, it adds prognostic value for early death and recurrence for patients with a high sPESI.

Predictors of in-hospital mortality in elderly patients with acute venous thrombo-embolism: the SWIss Venous ThromboEmbolism Registry (SWIVTER)

AIMS Although acute venous thrombo-embolism (VTE) often afflicts patients with advanced age, the predictors of in-hospital mortality for elderly VTE patients are unknown. METHODS AND RESULTS Among 1247 consecutive patients with acute VTE from the prospective SWIss Venous ThromboEmbolism Registry (SWIVTER), 644 (52%) were elderly (≥65 years of age). In comparison to younger patients, the elderly more often had pulmonary embolism (PE) (60 vs. 42%; P< 0.001), cancer (30 vs. 20%; P< 0.001), chronic lung disease (14 vs. 8%; P= 0.001), and congestive heart failure (12 vs. 2%; P< 0.001). Elderly VTE patients were more often hospitalized (75 vs. 52%; P< 0.001), and there was no difference in the use of thrombolysis, catheter intervention, or surgical embolectomy between the elderly and younger PE patients (5 vs. 6%; P= 0.54), despite a trend towards a higher rate of massive PE in the elderly (8 vs. 4%; P= 0.07). The overall in-hospital mortality rate was 6.6% in the elderly vs. 3.2% in the younger VTE patients (P= 0.033). Cancer was associated with in-hospital death both in the elderly [hazard ratio (HR) 4.91, 95% confidence interval (CI) 2.32-10.38; P< 0.001] and in the younger patients (HR 4.90, 95% CI 1.37-17.59; P= 0.015); massive PE was a predictor of in-hospital death in the elderly only (HR 3.77, 95% CI 1.63-8.74; P= 0.002). CONCLUSION Elderly patients had more serious VTE than younger patients, and massive PE was particularly life-threatening in the elderly.

Lack of extended venous thromboembolism prophylaxis in high-risk patients undergoing major orthopaedic or major cancer surgery: Electronic Assessment of VTE Prophylaxis in High-Risk Surgical Patients at Discharge from Swiss Hospitals (ESSENTIAL)

Extended pharmacological venous thromboembolism (VTE) prophylaxis beyond discharge is recommended for patients undergoing high-risk surgery. We prospectively investigated prophylaxis in 1,046 consecutive patients undergoing major orthopaedic (70%) or major cancer surgery (30%) in 14 Swiss hospitals. Appropriate in-hospital prophylaxis was used in 1,003 (96%) patients. At discharge, 638 (61%) patients received prescription for extended pharmacological prophylaxis: 564 (77%) after orthopaedic surgery, and 74 (23%) after cancer surgery (p < 0.001). Patients with knee replacement (94%), hip replacement (81%), major trauma (80%), and curative arthroscopy (73%) had the highest prescription rates for extended VTE prophylaxis; the lowest rates were found in patients undergoing major surgery for thoracic (7%), gastrointestinal (19%), and hepatobiliary (33%) cancer. The median duration of prescribed extended prophylaxis was longer in patients with orthopaedic surgery (32 days, interquartile range 14-40 days) than in patients with cancer surgery (23 days, interquartile range 11-30 days; p<0.001). Among the 278 patients with an extended prophylaxis order after hip replacement, knee replacement, or hip fracture surgery, 120 (43%) received a prescription for at least 35 days, and among the 74 patients with an extended prophylaxis order after major cancer surgery, 20 (27%) received a prescription for at least 28 days. In conclusion, approximately one quarter of the patients with major orthopaedic surgery and more than three quarters of the patients with major cancer surgery did not receive prescription for extended VTE prophylaxis. Future effort should focus on the improvement of extended VTE prophylaxis, particularly in patients undergoing major cancer surgery.