Clinical and economic outcomes in thrombolytic treatment of peripheral arterial occlusive disease and deep venous thrombosis

PurposeOver the past 2 decades the use of thrombolytic therapy in the management of peripheral occlusive diseases, most notably peripheral arterial occlusion (PAO) and deep venous thrombosis (DVT), has become an accepted and potentially preferable alternative to surgery. We examined the period when urokinase was in short supply and subsequently unavailable, to explore potential differences in clinical outcome and economic effect between urokinase and recombinant tissue plasminogen activator (rt-PA).Material and methodsData were obtained from the Premier Perspective Database, a broad clinical database that contains information on inpatient medical practices and resource use. The study population included all patients hospitalized in 1999 and 2000 with a primary or secondary diagnosis of PAO or DVT. Incidence was calculated for common adverse events, including bleeding complications, intracranial hemorrhage, amputation, and death. Cost data were also abstracted from the database, and are expressed as mean ± SD.ResultsDemographic variables were similar in the urokinase and rt-PA groups. The rate of bleeding complications was similar in the urokinase and rt-PA groups. There were no intracranial hemorrhages in the urokinase group, compared with a rate of 1.5% in the rt-PA PAO group (P = .087) and 1.9% in the rt-PA DVT group (P = .175). The in-hospital mortality rate was lower in the urokinase-treated PAO subgroup (3.6% vs 8.5%; P = .026), but a similar finding in the DVT subgroup did not achieve statistical significance (4% vs 9.8%; P = .069). While pharmacy costs were greater in the urokinase-treated group ($5472 ±$5579 vs $3644 ±$6009, P < .001; PAO subgroup, $11,070 ±$15,409 vs $6150 ±$12,398, P = .003), overall hospital costs did not differ significantly between the 2 groups. This finding appears to be explained by a shorter hospital stay and reduced room and board costs in the urokinase-treated group.ConclusionThere were significant differences in outcome in patients with PAO and DVT who received treatment with urokinase and rt-PA. While pharmacy costs were significantly greater when urokinase was used, reduction in length of stay accounted for similar total hospital costs compared with rt-PA. These findings must be considered in the context of the retrospective nature of the analysis and the potential to use dosing regimens that differ from those in this study

Economic analysis of endovascular repair versus surveillance for patients with small abdominal aortic aneurysms

BackgroundThe Positive Impact of EndoVascular Options for Treating Aneurysms Early (PIVOTAL) trial enrolled individuals with small (4.0- to 5.0-cm diameter) abdominal aortic aneurysms (AAA) and reported no difference in rupture or aneurysm-related death for patients who received early endovascular repair (EVAR) vs surveillance with serial imaging studies. We evaluated resource use, medical cost, and quality of life outcomes associated with the PIVOTAL treatment strategies.MethodsThis prospective economic and quality of life study was conducted within a randomized trial, with PIVOTAL sites participating in the quality of life (n = 67) and economic (n = 63) studies. The PIVOTAL trial randomized 728 patients (366 early EVAR and 362 surveillance). We used information from 701 quality of life (351 early EVAR and 350 surveillance) and 614 economic (314 early EVAR and 300 surveillance) study participants enrolled in the PIVOTAL trial. The main outcome measures were total medical costs and the aneurysm repair rate at 48 months.ResultsAfter 6 months, the rate of aneurysm repair was 96 vs 10 per 100 patients in the early EVAR and surveillance groups, respectively (difference, 86; 95% confidence interval [CI], 82-90; P < .0001), and total medical costs were greater in the early EVAR group ($33,471 vs$5520; difference, $27,951; 95$25,156-$30,746; P < .0001). In months 7 through 48, however, the rate of aneurysm repair was 54 per 100 patients in the surveillance group, and total medical costs were higher for patients in the surveillance vs the early EVAR group ($40,592 vs $15,197; difference,$25,394; 95% CI, $15,184-$35,605; P < .0001). At 48 months' follow-up, early EVAR patients had greater cumulative use of AAA repair (97 vs 64 per 100 patients; difference, 34; 95% CI, 21-46; P < .0001), but there was no difference in total medical costs ($48,669 vs$46,112; difference, $2557; 95$8043 to $13,156; P = .64). After discounting at 3$47,765 vs $43,532; difference, 4232; 95$5561 to $14,025; P = .40). There were no treatment-related differences in quality of life at 24 months.ConclusionsA treatment strategy involving early repair of smaller AAA with EVAR is associated with no difference in total medical costs at 48 months vs surveillance with serial imaging studies. Longer follow-up is required to determine whether the late medical cost increases observed for surveillance will persist beyond 48 months

A volumetric index for the quantification of deep venous thrombosis

AbstractPurpose: The evaluation of treatment strategies for deep venous thrombosis (DVT) is assessed through the use of a reliable method of quantifying the extent of the thrombotic process. Previous indices of thrombus burden have suffered from various limitations, including lack of clinical relevance, poor correlation with actual thrombus mass, and failure to include important venous segments in the methodology. The use of a novel scheme of quantifying venous thrombus was evaluated as an alternative method that would avoid some of the drawbacks of existing indices. Methods: The volumes of 14 venous segments (infrarenal inferior vena cava, common iliac, hypogastric, external iliac, common femoral, profunda, superficial femoral, and popliteal and six tibial veins) were calculated from computed tomography (pelvic vein diameter), duplex ultrasound scan (infrainguinal vein diameter), and contrast venography (length of all segments) measurements. A venous volumetric index (VVI) was assigned with the normalization of the values to the volume of a single calf vein. The VVI was validated with the assessment of the ability to discriminate between asymptomatic and symptomatic DVT and between those DVT that were associated with pulmonary emboli and those that were not. Results: With the imaging data, the VVI ranged from 1 for a single calf vein thrombus to 26 for the infrarenal inferior vena cava. Each VVI unit represented 2.3 mL of thrombus, with a maximum possible score of 63 representing a thrombus burden of 145 mL for a single extremity, including the infrarenal inferior vena cava. In 885 patients with DVT, the VVI ranged from 1 to 56, averaging 3.9 ± 0.2 in patients who were asymptomatic and 8.7 ± 0.3 in patients who were symptomatic (P < .001). The VVI was similar in the patients with pulmonary emboli as compared with those without (9.6 ± 1.2 vs 7.7 ± 0.2, respectively). In comparison with the three existing methods of quantifying venous thrombus burden, the receiver operating characteristic curve analysis results suggested that the VVI and the Venous Registry index were better than the other two indices in the discrimination of patients with symptomatic and asymptomatic DVT (P < .001). Conclusion: A novel index of venous thrombus burden, on the basis of actual venous volume measurements, was more accurate than present indices in the differentiation between clinical categories of patients with DVT. As such, it offers an acceptable alternative to current scoring systems. (J Vasc Surg 1999;30:1060-6.

Safety of paclitaxel-coated balloon angioplasty for femoropopliteal peripheral artery disease

OBJECTIVES: The aim of this study was to assess safety outcomes of femoropopliteal drug-coated balloon (DCB) angioplasty using patient-level data from the Lutonix clinical program. BACKGROUND: A recent systematic review and meta-analysis of heterogenous trials and summary-level data identified increased long-term mortality in patients treated with paclitaxel-coated balloons and stents. METHODS: We evaluated DCB angioplasty (n = 1,093) and uncoated balloon angioplasty (percutaneous transluminal angioplasty [PTA]) (n = 250) outcomes in LEVANT 1 (The Lutonix Paclitaxel-Coated Balloon for the Prevention of Femoropopliteal Restenosis), LEVANT 2 (Moxy Drug Coated Balloon vs. Standard Balloon Angioplasty for the Treatment of Femoropopliteal Arteries), and the LEVANT Japan Clinical Trial. Hazard ratios (HRs) were calculated with Cox proportional hazards modeling. RESULTS: There were no significant differences in mortality rates between DCB angioplasty and PTA. The 5-year HR was 1.01 (95% confidence interval [CI]: 0.68 to 1.52) in the aggregated LEVANT trials. The 2-year HR after DCB angioplasty was 0.99 (95% CI: 0.25 to 3.95) in LEVANT 1, 1.40 (95% CI: 0.62 to 3.14) in LEVANT 2, and 0.32 (95% CI: 0.05 to 1.92) in the LEVANT Japan Clinical Trial. The 5-year HR was 1.60 (95% CI: 0.94 to 2.72) in LEVANT 2. Adverse events and causes of death were balanced, without clustering between DCB angioplasty and PTA. Patients who underwent paclitaxel or nonpaclitaxel reinterventions had higher survival rates than those who did not undergo reinterventions. Baseline covariates predicting mortality included, among others, age (HR: 1.03 per year; p \u3c 0.0001), prior treatment of target lesion (HR: 1.67; p = 0.022), arrhythmia (HR: 1.65; p = 0.031), and diabetes (HR: 1.18; p = 0.047), without differences between the 2 arms. No dose-response relationship was identified when adjusted for key predictors of mortality. CONCLUSIONS: Analyses of patient-level data identified no mortality differences between DCB angioplasty and PTA. Furthermore, the lack of dose-response relationships or clustering of causes of death argues against a causal relationship between paclitaxel and mortality. (LEVANT 1, The Lutonix Paclitaxel-Coated Balloon for the Prevention of Femoropopliteal Restenosis [LEVANT 1], NCT00930813; Moxy Drug Coated Balloon vs. Standard Balloon Angioplasty for the Treatment of Femoropopliteal Arteries [LEVANT 2], NCT01412541; LEVANT 2 Continued Access Registry, NCT01628159; LEVANT Japan Clinical Trial, NCT01816412)

A Semiautomated Method for Measuring the 3-Dimensional Fabric to Renal Artery Distances to Determine Endograft Position After Endovascular Aneurysm Repair

PurposeTo report a methodology for 3-dimensional (3D) assessment of the stent-graft deployment accuracy after endovascular aneurysm repair (EVAR).MethodsA methodology was developed and validated to calculate the 3D distances between the endograft fabric and the renal arteries over the curve of the aorta. The shortest distance between one of the renal arteries and the fabric (SFD) and the distance from the contralateral renal artery to the fabric (CFD) were determined on the first postoperative computed tomography (CT) scan of 81 elective EVAR patients. The SFDs were subdivided into a target position (0-3 mm distal to the renal artery), high position (partially covering the renal artery), and low position (>3 mm distal to the renal artery). Data are reported as the median (interquartile range, IQR).ResultsIntra- and interobserver agreements for automatic and manual calculation of the SFD and CFD were excellent (ICC >0.892, pConclusionThe novel methodology using 3D CT reconstructions enables accurate evaluation of endograft position and slope within the proximal aortic neck. In this series, only 44% of endografts were placed within the target position with regard to the lowermost renal artery

Propensity-matched cohort validates findings of the VALOR trial

IntroductionThe Evaluation of the Medtronic Vascular Talent Thoracic Stent Graft System for the Treatment of Thoracic Aortic Aneurysms (VALOR) trial findings noted superior 30-day and 1-year outcomes of the Talent thoracic endograft (Medtronic Vascular, Santa Rosa, Calif) compared with surgical repair of descending thoracic aneurysms (DTAs). Data from 195 prospective thoracic endovascular aneurysm repair (TEVAR) patients treated with the Talent device and 189 retrospective controls undergoing open surgical repair (OSR) from three centers of excellence were included in the trial after completion of TEVAR enrollment and compared. Such comparisons are biased by baseline differences among TEVAR vs OSR, however, propensity score (PS) analysis can reduce bias and validate such comparisons.MethodsLogistic regression was used to generate a PS (range, 0-1) to identify baseline characteristics more likely in TEVAR. The PS estimated the probability that any patient would undergo TEVAR (eg, a PS of 0.99 represents a 99% chance a patient belongs to TEVAR). PSs were then generated for all patients, and TEVAR and OSR patients were divided into tertiles based on the PS to reduce up to 80% of inherent bias. Outcomes from the middle tertile (T2), patients equally likely (midrange PS) to be in TEVAR or OSR and therefore best matched, were compared using regression analysis and were also compared with the outcomes in the overall trial group.ResultsCorrelates of membership in TEVAR were smaller aneurysm (P < .001), anticoagulants (P < .01), no previous abdominal aortic aneurysm (AAA) repair (P < .01), no peripheral vascular disease (P = .001), statin use (P = .002), aspirin use (P = .002), older age (P = .028), race (P = .007), male gender (P = .02), and heart failure (P = .035). T2 included 68 TEVAR (PS, 0.58 ± 0.2) and 67 OSR patients (PS, 0.46 ± 0.2). VALOR overall reported differences in aneurysm size (56 mm TEVAR vs 69 mm open) and prior AAA repair (19% TEVAR vs 37% open), and this adjusted to no differences in T2 patients. In the well-matched T2 cohort, TEVAR patients had similar 30-day mortality (0% vs 3% OSR; P = .2) and improved 1-year aneurysm-related mortality rates (0% TEVAR vs 8% OSR; P = .05) compared with the OSR patients. This finding was in concurrence with the VALOR trial reporting similar benefit in TEVAR patients. The all-cause 1-year mortality showed a favorable trend for TEVAR in the VALOR trial; however, in T2 patients, 1-year all-cause mortality was similar in both groups of patients (17% TEVAR vs 15% OSR; P = .8). Age (P = .01), history of cerebrovascular accident (P < .05), antiarrhythmia medication (P = .04), and renal disease (P < .03) independently predicted all-cause and aneurysm-related mortality by regression analysis.ConclusionsPS analysis is an important tool for elimination of bias inherent when retrospective controls are used. Its application to VALOR validates the long-term benefit in aneurysm-related mortality conferred by TEVAR in patients undergoing endovascular DTA repair

Safety and efficacy of limited-dose tissue plasminogen activator in acute vascular occlusion

AbstractObjective: The purposes of this study were to evaluate the safety and efficacy of limited-dose tissue plasminogen activator (t-PA) in patients with acute vascular occlusion and to compare these results with those obtained in equivalent patients receiving urokinase. Methods: We compared the results of 60 patients receiving catheter-directed urokinase from November 1997 to November 1998 (240,000 units/h × 4 h, 120,000 units/h thereafter for a maximum of 48 h) with those of 45 patients receiving catheter-directed t-PA from November 1998 to August 2000 (2 mg/h, total dose ≤100 mg) for acute arterial occlusion (AAO) and acute venous occlusion (AVO). Interventional approaches such as cross-catheter and coaxial techniques were used to reduce the dose of lytic agent needed to achieve pre–lysis-treatment goals (eg, complete lysis of all thrombus/unmasking graft stenosis or establishing outflow target). Statistical analysis was performed using Student t test and Fisher exact test. Results: The urokinase and t-PA groups were comparable with regard to age, comorbidities (coronary artery disease, hypertension, diabetes, renal insufficiency, smoking), duration of ischemic or occlusive symptoms, location of occlusive process, pretreatment with warfarin, and thrombotic versus embolic and native versus graft occlusion in patients with AAO. In patients with AAO and in those with AVO, t-PA was equivalent to or better than urokinase with regard to percent of clot lysis, incidence of major bleeding complications, limb salvage, and mortality. Achievement of pretreatment goals (arterial patients only) was 50% for urokinase patients and 76% for t-PA patients (P =.02). Analysis of success in individual pretreatment-goal achievement showed urokinase and t-PA to be equivalent in unmasking stenoses (85% and 84%, respectively; P = NS), whereas t-PA was superior to urokinase in the more critical task of establishing run-off (39% versus 81% for urokinase and t-PA, respectively; P =.001). Additional interventions, either endovascular or surgical, were required in 60% and 51% (P = NS) of patients receiving urokinase and t-PA, respectively, for AAO, and in 54% and 62% (P = NS) of patients receiving urokinase and t-PA, respectively, for AVO. Conclusions: Limited-dose t-PA is a safe and effective therapy for AAO and AVO when administered by experienced teams using innovative but well-established interventional techniques. (J Vasc Surg 2001;34:854-9.