The Relationship Between Hospital Procedure Volume and Outcomes After Endovascular or Open Surgical Revascularisation for Peripheral Arterial Disease: An Analysis of Health Insurance Claims Data.

OBJECTIVE: There is a paucity of data on the relationship between hospital procedure volume and outcomes after inpatient treatment of symptomatic peripheral arterial disease (PAD). This study aimed to generate meaningful hypotheses to support the ongoing discussion. METHODS: Data derived from BARMER, Germany's second largest insurance provider, were linked with nationwide hospital procedure volumes from mandatory hospital quality reports. All endovascular (EVR) and open surgical revascularisations (OSR) provided to patients (≥ 40 years) with symptomatic PAD between 1 January 2013 and 31 December 2018 were included. Hospital volume was defined as the number of procedures performed by a hospital in the previous calendar year (in quartiles). Freedom from re-intervention, amputation, and overall mortality rate within 12 months after discharge were analysed using multivariable Cox proportional hazards models. In hospital mortality was determined by generalised estimating equations logistic regression models. RESULTS: There were 88 187 revascularisations (72.4% EVR; EVR: 72.7 years and 45.2% females; OSR: 71.9 years and 41.9% females) registered by 668 hospitals. No statistically significant association was found between 12 month freedom from re-intervention and hospital volume (EVR: 4; quartile HR 1.05; 95% CI 0.94 - 1.16. OSR: 4; quartile HR 1.05; 95% CI 0.92 - 1.21). Patients with OSR had a decreased hazard of 12 month mortality in a high volume hospital compared with a low volume hospital (HR 0.85; 95% CI 0.73 - 0.98), but not with EVR (HR 1.03; 95% CI 0.91 - 1.16). Patients who were treated in hospitals with highest volumes showed decreased hazards of 12 month freedom from amputation when compared with low volume hospitals (EVR: HR 0.72; 95% CI 0.52 - 0.99. OSR: HR 0.61; 95% CI 0.44 - 0.85). CONCLUSION: This large retrospective analysis of insurance claims suggests that higher procedure volume is associated with lower major amputation rates, although there is a need for standardisation of the definition of volume stratification. Future studies should address the impact of subsequent outpatient care and surveillance to further examine the complex interaction between treatment and outcomes.

Antithrombotic Treatment Patterns of Patients with Symptomatic Peripheral Arterial Occlusive Disease in Germany: Evidence from Health Insurance Claims Data.

OBJECTIVES: Patients with peripheral arterial occlusive disease (PAOD) are at risk of worsening limb symptoms, major adverse cardiovascular events and exhibit an impaired life expectancy. There is a lack of evidence on the extent of pharmacological secondary prevention in PAOD patients. This study assesses treatment patterns of antithrombotic agents in symptomatic PAOD patients. METHODS: This is a retrospective cohort study using data from the second largest insurance fund in Germany, BARMER. We included symptomatic PAOD patients undergoing in-hospital treatment with an index admission between 1 January 2010 and 31 December 2017. Outcomes were proportions of single antiplatelets (SAPT), dual antiplatelets (DAPT), vitamin-K antagonists (VKA), or direct oral anticoagulants (DOAC) in the 12 months prior and 6 months after the index hospitalization. Non-parametric cumulative incidence for competing risks was estimated to account for censoring and death after discharge from hospital stay. Patient flows were visualised by alluvial diagrams. All analyses were stratified by intermittent claudication (IC) and chronic limb-threatening ischaemia (CLTI). The protocol was registered to ClinicalTrials.gov (NCT03909022). RESULTS: A total of 80,426 unique patient encounters were identified. Mean age was 72.7 (46.3% female). Amongst all patients, 25.6% were on SAPT, 4.1% on DAPT, 9.1% on VKA, 3.9% on DOAC, 3.9% on both antiplatelets and oral anticoagulation, and 53.3% without any antithrombotic therapy during the 12 months before index stay. The estimated cumulative incidence was 37.9% SAPT, 14.8% DAPT, 7.5% VKA, 4.3% DOAC, 7.4% both, and 28.1% without any antithrombotic therapy during the 6 months after index stay. The considerable increases in antiplatelet therapy were mainly driven by the group of patients without antithrombotics before index stay. As compared with IC, patients who suffered from CLTI received less often antiplatelets but more often anticoagulants both before and after index stay. CONCLUSIONS: Utilisation rates of antithrombotic therapy increased considerably after in-hospital treatment for PAOD. Yet, remarkably high rates of symptomatic patients without any blood-thinning therapy constitute a major concern with respect to adequate secondary prevention of PAOD patients.

How Does Female Sex Affect Complex Endovascular Aortic Repair? A Single Centre Cohort Study.

OBJECTIVE: There is growing evidence of a female patient disadvantage in complex endovascular aortic repair using fenestrated and branched endografts (FB-EVAR) primarily related to peri-procedural events including ischaemic and access vessel complications. This study aimed to determine the impact of sex differences on treatment patterns, and in hospital outcomes in a single centre cohort. METHODS: This was a retrospective cross sectional single centre cohort study of all consecutive FB-EVAR procedures provided to patients with asymptomatic pararenal and thoraco-abdominal aortic aneurysm (TAAA) between 1 January 2010 and 28 February 2021. Adjusted multivariable logistic regression models were developed using backward (Wald) elimination of variables to determine the independent impact of female sex on short term outcomes. RESULTS: In total, 445 patients (24.3% females, median age 73.0 years, IQR 66, 78) were included. Female patients had a smaller aneurysm diameter, less frequent coronary artery disease (29.6% vs. 44.8%, p = .007) and history of myocardial infarction (2.8% vs. 15.4%, p < .001) when compared with males. Females were more frequently treated for TAAA than males (49.1% vs. 25.2%, p < .001). The median length of post-procedural hospital stay was 10 days in females and 9 in males. In adjusted analyses, female sex was independently associated with higher mortality (odds ratio [OR] 10.135, 95% CI 2.264 - 45.369), post-procedural complications (OR 2.500, 95% CI 1.329 - 4.702), spinal cord ischaemia (OR 4.488, 95% CI 1.610 - 12.509), sepsis (OR 4.940, 95% CI 1.379 - 17.702), and acute respiratory insufficiency (OR 3.283, 95% CI 1.015 - 10.622) after pararenal aortic aneurysm repair during the hospital stay. CONCLUSION: In this analysis of consecutively treated patients, female sex was associated with increased in hospital mortality, peri-procedural complications, and spinal cord ischaemia after elective complex endovascular repair of pararenal aortic aneurysm, while no differences were revealed in the TAAA subgroup. These results suggest that sex related patient selection and peri-procedural management should be studied in future research.

Sex Disparities in Long-Term Mortality after Paclitaxel Exposure in Patients with Peripheral Artery Disease: A Nationwide Claims-Based Cohort Study.

BACKGROUND: Randomized controlled trials have reported excess mortality in patients treated with paclitaxel-coated devices versus uncoated devices, while observational studies have reported the opposite. This study aims to determine the underlying factors and cohort differences that may explain these opposite results, with specific focus on sex differences in treatment and outcomes. METHODS: Multicenter health insurance claims data from a large insurance fund, BARMER, were studied. A homogeneous sample of patients with an index of endovascular revascularization for symptomatic peripheral arterial occlusive disease between 2013 and 2017 was included. Adjusted logistic regression and Cox regression models were used to determine the factors predicting allocation to paclitaxel-coated devices and sex-specific 5-year all-cause mortality, respectively. RESULTS: In total, 13,204 patients (54% females, mean age 74 ± 11 years) were followed for a median of 3.5 years. Females were older (77 vs. 71 years), and had less frequent coronary artery disease (23% vs. 33%), dyslipidemia (44% vs. 50%), and diabetes (29% vs. 41%), as well as being less likely to have a history of smoking (10% vs. 15%) compared with males. Mortality differences were mostly attributable to the female subgroup who were revascularized above the knee (hazard ratio, HR 0.78, 95% CI: 0.64-0.95), while no statistically significant differences were observed in males. CONCLUSIONS: This study found that females treated above the knee benefited from paclitaxel-coated devices, while no differences were found in males. Ongoing and future registries and trials should take sex disparities into account.

A health insurance claims analysis on the effect of female sex on long-term outcomes after peripheral endovascular interventions for symptomatic peripheral arterial occlusive disease.

OBJECTIVE: Several reports have addressed sex disparities in peripheral arterial occlusive disease (PAOD) treatment with inconclusive or even conflicting results. However, most previous studies have neither been sufficiently stratified nor used matching or weighting methods to address severe confounding. In the present study, we aimed to determine the disparities between sexes after percutaneous endovascular revascularization (ER) for symptomatic PAOD. METHODS: Health insurance claims data from the second-largest insurance fund in Germany, BARMER, were used. A large cohort of patients who had undergone index percutaneous ER of symptomatic PAOD from January 1, 2010 to December 31, 2018 were included in the present study. The study cohort was stratified by the presence of intermittent claudication, ischemic rest pain, and wound healing disorders. Propensity score matching was used to adjust for confounding through differences in age, treated vessel region, comorbidities, and pharmacologic treatment. Sex-related differences regarding cardiovascular event-free survival, amputation-free survival, and overall survival within 5 years of surgery were determined using Kaplan-Meier time-to-event curves, log-rank test, and Cox regression analysis. RESULTS: In the present study, 50,051 patients (47.2% women) were identified and used to compose a matched cohort of 35,232 patients. Among all strata, female patients exhibited lower mortality (hazard ratio [HR], 0.69-0.90), fewer amputations or death (HR, 0.70-0.89), and fewer cardiovascular events or death (HR, 0.78-0.91). The association between female sex and improved long-term outcomes was most pronounced for the patients with intermittent claudication. CONCLUSIONS: In the present propensity score-matched analysis of health insurance claims, we observed superior cardiovascular event-free survival, amputation-free survival, and overall survival during 5 years of follow-up after percutaneous ER in women with symptomatic PAOD. Future studies should address sex disparities in the open surgical treatment of PAOD to illuminate whether the conflicting data from previous reports might have resulted from insufficient stratification of the studies.

Female Sex and Outcomes after Endovascular Aneurysm Repair for Abdominal Aortic Aneurysm: A Propensity Score Matched Cohort Analysis.

OBJECTIVE: Previous studies have showed a potential disadvantage of female patients who underwent abdominal aortic aneurysm (AAA) repair. The current study aims to determine sex-specific perioperative and long-term outcomes using propensity score matched unselected nationwide health insurance claims data. METHODS: Insurance claims from a large German fund were used, covering around 8% of the insured German population. Patients who underwent endovascular aortic repair (EVAR) for intact AAA from 1 January 2011 to 30 April 2017 were included in the cohort. A 1:2 female to male propensity score matching was applied to adjust for confounding variables. Perioperative and long-term outcomes after 5 years were determined using matching and regression methods. RESULTS: Among a total of 3736 patients (19.3% females, mean 75 years) undergoing EVAR for intact AAA, we identified 1863 matched patients. Before matching, females were more likely to be previously diagnosed with hypothyroidism, electrolyte disorders, rheumatoid disorders, and depression, while males were more often diabetics. In the matched sample, 23.4% of the females and 25.8% of the males died during a median follow-up of 776 and 792 days, respectively. Perioperatively, females were more likely to exhibit acute limb ischemia (5.3% vs. 3.2%, p = 0.031) and major bleeding (22.0% vs. 15.9%, p = 0.001) before they were discharged to rehabilitation (5.5% vs. 1.5%, p < 0.001) when compared to males. No statistically significant difference in perioperative (odds ratio 1.12, 95% CI 0.54-2.16) or long-term mortality (hazard ratio 0.91, 95% CI 0.76-1.08) was observed between sexes. This was also true regarding aortic reintervention rates after 1 year (2.0% vs. 2.9%) and 5 years (10.9% vs. 8.1%). CONCLUSION: The current retrospective matched analysis of insurance claims revealed high early access-related morbidity in females when compared to their male counterparts. Short-term or long-term survival and reintervention outcomes were similar between sexes.

Editor's Choice - The GermanVasc Score: A Pragmatic Risk Score Predicts Five Year Amputation Free Survival in Patients with Peripheral Arterial Occlusive Disease.

OBJECTIVE: Patients with peripheral arterial occlusive disease (PAOD) face an increased risk of both lower limb amputation and death. To date, it has been challenging to predict the long term outcomes for PAOD. The aim was to develop a risk score to predict worse five year amputation free survival (AFS). METHODS: In this retrospective analysis of claims data, symptomatic PAOD patients were split into training and validation sets. Variables in the model were patient age and sex, Elixhauser comorbidities, and the 190 most common secondary diagnoses. Penalised Cox regression (least absolute shrinkage and selection operator [LASSO]) with tenfold cross validation for variable selection was performed and patients were categorised into five risk groups using the ten most important variables. All analyses were stratified by intermittent claudication (IC) and chronic limb threatening ischaemia (CLTI). RESULTS: In total, 87 293 patients with PAOD (female 45.3%, mean age 71.4 ± 11.1 years) were included in the analysis. The most important variable predicting worse five year AFS was patient age >80 years. The GermanVasc score exhibited good predictive accuracy both for IC (c statistic = 0.70, 95% confidence interval [CI] 0.69-0.71) and CLTI (c statistic = 0.69, 95% CI 0.68-0.70) with adequate calibration due largely to alignment of observed and expected risk. Depending on the cumulative point score, the five year risk of amputation or death ranged from 9% (low risk) to 48% (high risk) for IC, and from 25% to 88% for CLTI. CONCLUSION: The GermanVasc score predicts worse five year AFS stratified for inpatients suffering from IC and CLTI, with good predictive accuracy. By separating low from high risk patients, the GermanVasc score may support patient centred consent.

Sex Disparities in Long Term Outcomes After Open Surgery for Chronic Limb Threatening Ischaemia: A Propensity Score Matched Analysis of Health Insurance Claims.

OBJECTIVE: Several studies suggest a disadvantage for women in peri-operative morbidity and mortality after open surgery in peripheral arterial occlusive disease. In addition to their heterogeneity regarding design and analysed cohorts, long term data are mostly missing. This study aimed to determine sex disparities in outcomes after open revascularisation in chronic limb threatening ischaemia (CLTI). METHODS: Using health insurance claims data of the second largest insurance fund in Germany, BARMER, a large cohort of patients was sampled consecutively for analysis including index open surgical revascularisations of CLTI performed between 1 January 2010, and 31 December 2018. Propensity score matching was used to adjust for confounding. Sex related differences regarding overall survival, amputation free survival (AFS), and cardiovascular event free survival (CVEFS) during the five years after surgery were determined using Kaplan-Meier time to event curves, log rank test, logistic, and Cox regression. RESULTS: Among 9 526 patients (49.5% women) in the entire cohort, 6 502 patients were matched. Before matching, women were older at presentation (78.0 vs. 71.8 years, p < .001) and suffered more often from multiple comorbidities (van Walraven score > 9, 55.5% vs. 50.6%, p < .001). During the hospital stay, there were 692 (7.3%) deaths, while 4 631 deaths (48.6%) occurred during the follow up. In the matched cohort, the median follow up was 746 days for women and 871 days for men. In the matched analyses, female sex was significantly associated with better overall survival (hazard ratio, HR, 0.80, log rank p < .001), AFS (HR 0.81, log rank p < .0001), and CVEFS (HR 0.84, log rank p < .001) five years after the index treatment. CONCLUSION: In this largest propensity score matched analysis of health insurance claims to date from Germany, evidence was found for better long term outcomes in women after open surgical revascularisations for chronic limb threatening ischaemia. Future guidelines and studies should address the impact of sex on patient selection practice and outcomes to determine the underlying reasons for existing disparities.

Long-Term Effectiveness and Safety of Initiating Statin Therapy After Index Revascularization In Patients With Peripheral Arterial Occlusive Disease.

Background An increasing number of patients with a peripheral arterial occlusive disease were put on statins during the past years. This study assessed whether statin therapy was effective and safe for these new users. Methods and Results Using health insurance claims data from Germany's second-largest insurance fund, BARMER, we identified patients with peripheral arterial occlusive disease who had index revascularization between 2008 and 2018 without prior statin therapy. We compared patients with and without statin therapy in addition to antithrombotics during the first quarter after discharge (new users versus nonusers). Outcomes were all-cause mortality, cardiovascular events, and incident major amputation for effectiveness and incident diabetes mellitus and incident myopathy for safety. Propensity score matching was used to balance the study groups. All analyses were stratified into patients with chronic limb-threatening ischemia and intermittent claudication. A total of 22 208 patients (mean age 71.1 years and 50.3% women) were included in the study. In 10 922 matched patients, statin initiation was associated with lower all-cause mortality (chronic limb-threatening ischemia: hazard ratio [HR], 0.75 [95% CI, 0.68-0.84]; intermittent claudication: HR, 0.80 [95% CI, 0.70-0.92]), lower risk of major amputation in patients with chronic limb-threatening ischemia (HR, 0.73; 95% CI, 0.58-0.93) and lower risk of cardiovascular events (hazard ratio, 0.80; 95% CI, 0.70-0.92) in patients with intermittent claudication during 5 years of follow-up. Safety outcomes did not differ among the study groups. Conclusions Initiating statin therapy in patients with peripheral arterial occlusive disease after index revascularization is efficient and safe with an effect size comparable to earlier studies. Awareness campaigns for evidence-based optimal pharmacological treatment among patients are recommended.

Editor's Choice - International Variations and Sex Disparities in the Treatment of Peripheral Arterial Occlusive Disease: A Report from VASCUNET and the International Consortium of Vascular Registries.

OBJECTIVE: The aim of this study was to determine sex specific differences in the invasive treatment of symptomatic peripheral arterial occlusive disease (PAOD) between member states participating in the VASCUNET and International Consortium of Vascular Registries. METHODS: Data on open surgical revascularisation and peripheral vascular intervention (PVI) of symptomatic PAOD from 2010 to 2017 were collected from population based administrative and registry data from 11 countries. Differences in age, sex, indication, and invasive treatment modality were analysed. RESULTS: Data from 11 countries covering 671 million inhabitants and 1 164 497 hospitalisations (40% women, mean age 72 years, 49% with intermittent claudication, 54% treated with PVI) in Europe (including Russia), North America, Australia, and New Zealand were included. Patient selection and treatment modality varied widely for the proportion of female patients (23% in Portugal and 46% in Sweden), the proportion of patients with claudication (6% in Italy and 69% in Russia), patients' mean age (70 years in the USA and 76 years in Italy), the proportion of octogenarians (8% in Russia and 33% in Sweden), and the proportion of PVI (24% in Russia and 88% in Italy). Numerous differences between females and males were observed in regard to patient age (72 vs. 70 years), the proportion of octogenarians (28% vs. 15%), proportion of patients with claudication (45% vs. 51%), proportion of PVI (57% vs. 51%), and length of hospital stay (7 days vs. 6 days). CONCLUSION: Remarkable differences regarding the proportion of peripheral vascular interventions, patients with claudication, and octogenarians were seen across countries and sexes. Future studies should address the underlying reasons for this, including the impact of national societal guidelines, reimbursement, and differences in health maintenance.

Long Term Outcomes After Revascularisations Below the Knee with Paclitaxel Coated Devices: A Propensity Score Matched Cohort Analysis.

OBJECTIVE: Endovascular revascularisation has become a standard approach for below knee lesions and paclitaxel coated devices have been widely used in patients with chronic limb threatening ischaemia. A recent meta-analysis reported higher mortality in paclitaxel coated devices compared with uncoated devices in femoropopliteal lesions. This study aimed to determine long term outcomes in below the knee interventions using paclitaxel coated devices in routine vascular care using a large and contemporary cohort. METHODS: A large cohort was created using all inclusive health insurance claims data of patients covered by the second largest insurance fund in Germany. The cohort included patients with index revascularisation of arteries below the knee performed from 1 January 2010, to 31 December 2018. Only patients with first paclitaxel coated device exposure were included. The study cohort was stratified into balloon vs. stent treatment and patients with paclitaxel coated devices were matched with uncoated devices using propensity score. Outcomes were evaluated using the Kaplan-Meier method and Cox regression. RESULTS: There were 14 738 patients (mean age 77.6 years, 43.6% female) and 6 568 matched patients included in the study. Increasing use of paclitaxel coated devices was observed during the study period (6% in 2010 vs. 31% in 2018, p < .001), and a total of 2 611 (39.8%) deaths occurred within five years of follow up. In the propensity score matched Cox model, a paclitaxel related reduction of five year mortality (hazards ratio, HR 0.84, 95% confidence interval, CI 0.78-0.91), amputation or death (HR 0.87, 95% CI 0.81-0.94), and cardiovascular event or death (HR 0.86, 95% CI 0.80-0.92) were observed. CONCLUSION: In this propensity score matched cohort, reduced long term all cause mortality, reduced rates of amputation or death and cardiovascular event or death were observed at five years after the use of paclitaxel coated devices when compared with uncoated devices for the treatment of chronic limb threatening ischaemia.

Incidence, predictors, and outcomes of spinal cord ischemia in elective complex endovascular aortic repair: An analysis of health insurance claims.

OBJECTIVE: This study aimed to determine predictors and outcomes associated with spinal cord ischemia (SCI) after elective fenestrated or branched endovascular aneurysm repair (F/BEVAR) of thoracoabdominal aortic aneurysm (TAAA), abdominal aortic aneurysm (AAA), or aortic dissection. METHODS: Health insurance claims data of Germany's third largest insurance provider, DAK-Gesundheit, were used to investigate SCI in elective F/BEVAR performed between 2008 and 2017. The International Classification of Diseases and German Operation and Procedure Classification System were used. We stratified the results into F/BEVAR with one or two (AAA) vs three or more (TAAA) fenestrations or branches. RESULTS: A total of 877 patients (18.9% female; 5.8% with SCI) matching the inclusion criteria were identified during the study period. SCI occurred more often after F/BEVAR of TAAA vs AAA (10.7% vs 3.0%; P < .001). SCI was associated with female sex in the AAA group (odds ratio, 3.87; 95% confidence interval [CI], 1.25-11.15; P = .014) and with cardiac arrhythmias in the TAAA group (odds ratio, 2.98; 95% CI, 1.24-7.06; P = .013). Compared with patients without SCI, SCI patients were more likely to suffer from drug use disorders (eg, opioids, cannabinoids, sedatives) in the TAAA group (17.6% vs 2.1%; P < .05). After F/BEVAR of TAAA, the occurrence of SCI was associated with higher 90-day mortality (14.7% vs 1.1%; P < .05), longer postoperative hospital stay (22 vs 9 days; P < .05), and severe adverse events, such as acute respiratory insufficiency (44.1% vs 12.7%), acute renal failure (35.3% vs 11.3%), and pneumonia (29.4% vs 4.9%; all P < .05). In adjusted analyses, SCI was associated with worse long-term survival after F/BEVAR for TAAA (hazard ratio, 2.54; 95% CI, 1.37-4.73; P < .003). CONCLUSIONS: Female AAA patients and TAAA patients with cardiac arrhythmias are at highest risk for development of SCI after F/BEVAR. The occurrence of this event was strongly associated with higher major complication rates and worse short-term and long-term survival. This emphasizes a need to further illuminate the value of spinal cord protection protocols in F/BEVAR.

A retrospective cohort study on the provision and outcomes of pharmacological therapy after revascularisation for peripheral arterial occlusive disease: a study protocol.

BACKGROUND: Symptomatic peripheral arterial occlusive disease (PAOD) involves highly complex and costly revascularisations for preventing adverse limb events and impaired survival. Contrary to recommendations from valid guidelines, a large group of patients do not receive adequate pharmacological therapy after such interventions. Based on health insurance claims data, our study aims to assess (1) the extent of provision of pharmacological therapy after revascularisation and (2) related long-term outcomes for all patients and subgroups, that is, gender and disease severity. METHODS: A retrospective observational population-based cohort study will be based on data from the second largest statutory health insurance fund in Germany (BARMER) covering about 13% of the insured population (~10 million patients). Study entry is the index revascularisation for symptomatic PAOD. Study variables will be analysed and compared among subgroups using parametric and non-parametric tests, generalised linear regression analysis and survival models. DISCUSSION: This study will provide a comprehensive insight in the extent and time trends of adequate provision of pharmacological therapy and long-term outcomes for patients with symptomatic PAOD. This may help to identify those patients benefiting most from improved pharmacological therapy for increasing the success of revascularisations in general. TRIAL REGISTRATION: NCT03909022.