Unused potential of lipid-lowering therapy in very high-risk patients with atherosclerotic cardiovascular disease. A retrospective data analysis.

BACKGROUND: Atherosclerotic cardiovascular disease (ASCVD) is the most common cause of death in Europe. Although the 2019 European Society of Cardiology/European Atherosclerosis Society Guidelines for the management of dyslipidaemias claim a target low-density lipoprotein cholesterol (LDL-C) value of <55 mg/dL for very high-risk patients by use of lipid-lowering therapy (LLT) and lifestyle adaptations, the target level achievement is not satisfactory. We examined LLT use in ASCVD patients exceeding LDL-C target levels at admission and its adaptations at discharge. METHODS AND RESULTS: Between January 2017 and February 2020, 1091 patients with LDL-C >100 mg/dL and ASCVD defined as diagnosis of angina pectoris (AP, n = 179), acute myocardial infarction (AMI, n = 317), chronic ischemic heart disease (CHD, n = 195), or peripheral artery disease (PAD, n = 400) were extracted from hospital records. LLT use on admission and discharge as well as recommendations on lifestyle and nutrition were analysed. On admission, 51% of the patients were not taking LLT. At discharge, 91% were prescribed statins and 87% were advised on lifestyle adaptation and/or pharmacological treatment. High-intensity statin use at discharge was present in 63% of the AP-group, 92% of the AMI-group, 62% of the CHD-group and 71% of the PAD-group. Ezetimibe was present in 16% and proprotein convertase subtilisin/kexin 9 inhibitors (PCSK9i) in 1%. However, of those on high-intensity statin, 25% remained on insufficient statin dosage. CONCLUSION: Switch to high-intensity statins and use of ezetimibe and PCSK9i was low in chronic ASCVD patients. Even though statin intake was high in high-risk patients, target levels were still not reached.

In-patient characteristics of peripheral artery disease in Germany.

Background: Peripheral artery disease (PAD) frequently leads to hospital admission. Sex related differences in in-patient care are a current matter of debate. Patients and methods: Data were provided from the German national in-patient sample provided by the Federal Bureau of Statistics (DESTATIS). Trends on risk profiles, therapeutic procedures, and outcomes were evaluated from 2014 until 2019 stratified by sex and PAD severity. Results: Two-thirds of an annual >191,000 PAD in-patient cases applied to male sex. Chronic limb-threatening ischemia (CLTI) was recorded in 49.6% of male and 55.2% of female cases (2019). CLTI was as a major risk factor of in-hospital amputation (OR 229) and death (OR 10.5), whereas endovascular revascularisation (EVR) with drug-coated devices were associated with decreased risk of in-hospital amputation (OR 0.52; all p<0.001). EVR applied in 47% of CLTI cases compared to 71% in intermittent claudication (IC) irrespective of sex. In-hospital mortality was 4.3% in male vs. 4.8% in female CLTI cases, minor amputations 18.4% vs. 10.9%, and major amputation 7.5% vs. 6.0%, respectively (data 2019; all p<0.001). After adjustment, female sex was associated with lower risk of amputation (OR 0.63) and death (OR 0.96) during in-patient stay. Conclusions: Male PAD patients were twice as likely to be admitted for in-patient treatment despite equal PAD prevalence in the general population. Among in-patient cases, supply with invasive therapy did not relevantly differ by sex, however is strongly reduced in CLTI. CLTI is a major risk factor of adverse short-term outcomes, whereas female sex was associated with lower risk of in-patient amputation and/or death.

Contemporary secondary prevention in survivors of ST-elevation myocardial infarction with and without chronic kidney disease: a retrospective analysis.

Background: Survivors of myocardial infarction have an elevated risk of long-term mortality. We sought to evaluate guideline-directed medical treatment and its impact on long-term mortality in survivors of ST-elevation myocardial infarction (STEMI) according to their chronic kidney disease (CKD) stage. Methods: Using German health insurance claims data, 157 663 hospitalized survivors of STEMI were identified. Regarding different CKD stages, we retrospectively analysed the filled prescriptions of platelet inhibitors (PAI)/oral anticoagulation, statins, beta-blocker and angiotensin-converting enzyme inhibitors/angiotensin II type 1 receptor antagonists (ACE-I/AT1-A) and their association with long-term mortality. Results: Prescription rates for all four guideline-directed drugs were highest in patients without or with mild CKD and lowest in patients on dialysis. They dropped from 73.4% to 39.2% in patients without CKD and from 47.1% to 29% in patients on dialysis within the 5-year follow-up period. Mortality rates were dramatically increased in patients with CKD compared with patients without CKD (5-year mortality: no CKD, 16.7%; CKD stage 3, 47.1%; CKD stage 5d, 69.7%). Filled prescriptions of at least one drug class [one drug: hazard ratio (HR) 0.70, 95% confidence interval (95% CI) 0.66-0.74; four drugs: HR 0.28, 95% CI 0.27-0.30; P < .001 for both] as well as the distinct drug classes (statins: HR 0.55, 95% CI 0.54-0.56; ACE-I/AT1-A: HR 0.68, 95% CI 0.67-0.70; beta-blocker: HR 0.87, 95% CI 0.85-0.90; PAI/oral anticoagulation: HR 0.97, 95% CI 0.95-1.00; all P < .05) improved long-term mortality. Conclusions: An improved long-term guideline-recommended drug therapy after STEMI regardless of renal impairment might lead to beneficial effects on long-term mortality.

Analysis of endovascular therapy for peripheral arterial disease in all German hospitals.

Background: The quality of vascular care has significantly improved in part by the expansion of endovascular techniques for the treatment of symptomatic peripheral artery disease (PAD) in recent years. In Germany these are primarily provided by the three disciplines of vascular surgery, angiology, and interventional radiology (IR). However, the relative contribute of angiologists to the total number of cases performed is unknown. Patients and methods: In the present study, we analysed the respective contribution of vascular surgery, angiology, and IR to the delivery of endovascular revascularisations in symptomatic PAD in Germany based on the legally mandatory quality reports representative for the reporting year 2018. Results: Vascular surgery is the most common speciality reporting procedures in German hospitals (n=579; 25.1%), followed by IR (n=264; 11.5%), angiology (n=189; 8.2%) and cardiology (n=17; 0.7%). The combination of vascular surgery and IR was reported in 202 (8.8%), vascular surgery and angiology in 167 (7.2%) and angiology and IR in 65 (2.8%) hospitals, and 63 (2.7%) hospitals reported the combination of all three disciplines. Not every department performed catheter interventions. The analysis of procedures per centre revealed that angiology centres provided the highest numbers for both basic procedures and more complex techniques such as atherectomy, rotational thrombectomy, lithoplasty, selective thrombolysis or the use of re-entry devices. In total, angiology centres provided 24.4% of the total procedures or 23.9% of the so-called basic procedures as a surrogate for patient numbers. Conclusions: While each of the disciplines contribute significantly to the endovascular procedures, angiology centres perform more procedures per centre and more complex procedures than the other disciplines highlighting the important quantitative and qualitative contribution of angiology specialists to the care of vascular patients. The inpatient catheter interventional care of patients with PAD is still too rarely carried out in a multi-disciplinary manner in Germany.

Survival of Patients with Acute Coronary Syndrome and Hematologic Malignancies-A Real-World Analysis.

BACKGROUND: The impact of the encounter between coronary heart disease (CHD) and cancer, and in particular hematologic malignancies (HM), remains poorly understood. OBJECTIVE: The aim of this analysis was to clarify how HM affects the prognosis of acute coronary syndrome (ACS). We analyzed German health insurance data from 11 regional Ortskrankenkassen (AOK) of patients hospitalized for ACS between January 2010 and December 2018, matched by age, sex and all comorbidities for short- and long-term survival and major adverse cardiac events (MACE). RESULTS: Of 439,716 patients with ACS, 2104 (0.5%) also had an HM. Myelodysplastic/myeloproliferative disorders (27.7%), lymphocytic leukemias (24.8%), and multiple myeloma (22.4%) predominated. These patients were about 6 years older (78 vs. 72 years *). They had an ST-segment elevation myocardial infarction (STEMI, 18.2 vs. 34.9% *) less often and more often had a non-STEMI (NSTEMI, 81.8 vs. 65.1% *). With the exception of dyslipidemia, these patients had more concomitant and previous cardiovascular disease and a worse NYHA stage. They were less likely to undergo coronary angiography (65.3 vs. 71.6% *) and percutaneous coronary intervention (PCI, 44.3 vs. 52.0% *), although the number of bleeding events was not relevantly increased (p = 0.22). After adjustment for the patients' risk profile, the HM was associated with reduced long-term survival. However, this was not true for short-term survival. Here, there was no difference in the STEMI patients, * p < 0.001. CONCLUSION: Survival in ACS and HM is significantly lower, possibly due to the avoidance of PCI because of a perceived increased risk of bleeding.

Contemporary Treatment and Outcome of Patients with Ischaemic Lower Limb Amputation: A Focus on Sex Differences.

OBJECTIVE: Chronic limb threatening ischaemia (CLTI) has a devastating prognosis with high rates of lower limb amputation (LLA) and deaths. This is an illustration of contemporary management and the long term fate of patients after ischaemic LLA, particularly with respect to sex, using real world data. METHODS: This was a multisectoral cross sectional and longitudinal analysis of health claims data from the largest German health insurance database (AOK). Data of 39 796 propensity score matched patients hospitalised for ischaemic LLA between 2010 and 2018 were analysed for cardiovascular comorbidities, treatment, and for subsequent cardiovascular and limb events, with a distinct focus on sex. Matching was performed, to ensure that the rate of major amputations and the age distribution were equal in both groups (in both sexes). An observation period of two years before index and a follow up (FU) period until 2019 were included. RESULTS: Before index amputation, 68% of patients had received any kind of peripheral revascularisation. The use of statins (37.0% vs. 42.6%) and antithrombotic substances (54.9% vs. 61.8%) was lower in women than in men (p < .001). During two year FU, cardiovascular and limb events occurred among women and men as follows: limb re-amputation (26.7% vs. 31.2%), myocardial infarction (10.9% vs. 14.5%), stroke (20.8% vs. 20.7%), and death from any cause (51.0% vs. 53.3%, p < .001 except for stroke). After adjustment for cardiovascular comorbidities and vascular procedures, female sex was associated with a higher probability of death (HR 1.04, 95% CI 1.04 - 1.04). CONCLUSION: Patients undergoing ischaemic LLA still have a poor prognosis marked by high rates of recurrent cardiovascular and limb events resulting in a > 50% mortality rate within two years. The continuous lack of guideline recommended therapies, particularly in women, may be associated with the persisting poor outcome, necessitating urgent further investigation.

Sex disparities in guideline-recommended therapies and outcomes after ST-elevation myocardial infarction in a contemporary nationwide cohort of patients over an eight-year period.

BACKGROUND AND AIMS: Acute myocardial infarction (AMI) is the leading cause of death worldwide. Outcome has improved during the last decades due to secondary prevention and widespread coronary interventions, but recent studies still show sex differences and insufficient drug adherence. We aimed to determine differences in the treatment strategies and outcomes between women and men with ST-elevation myocardial infarction (STEMI) in Germany. METHODS: From the Federal Association of the Local Health Insurance Funds (Allgemeine Ortskrankenkasse), 175,187 patients were identified who were hospitalized due to STEMI in Germany between January 1, 2010 and December 31, 2017. RESULTS: Compared to men, women were older (median 76 vs. 64 years) and had more often diabetes, hypertension, chronic heart failure, and chronic kidney disease (all p <0.001). Women suffered from higher rates of in-hospital complications such as bleeding (9.3 vs. 6.6%), longer hospitalizations (12.2 vs. 11.7 days) and were less likely to undergo percutaneous coronary intervention (75.5 vs. 85.2%). After adjustment for patient's risk profile, female sex was associated with decreased overall survival (HR 1.02, 95% confidence interval (CI) 1.00-1.04; p=0.036). Notably, more men received all four guideline-recommended drugs after STEMI (women 65.7% vs. men 69.8% after 90 days; p <0.001). With increasing number of prescribed drugs, patients benefit even more. This concerned both sexes, but was more pronounced in men (with 4 prescribed drugs: women HR 0.52, 95%CI 0.50-0.55; men HR 0.48, 95% CI 0.47-0.50, pint = 0.014). CONCLUSIONS: In a contemporary nationwide analysis, women with STEMI were older, had more comorbidities, underwent revascularization less often and had an increased risk for major complications as well as overall survival. Guideline-recommended drug therapy was applied less frequently in women although associated with an improved overall-survival.

Contemporary in-hospital and long-term prognosis of patients with acute ST-elevation myocardial infarction depending on renal function: a retrospective analysis.

BACKGROUND: Cardiovascular disease is often associated with chronic kidney disease (CKD), resulting in an increased risk for poor outcome. We sought to determine short-term mortality and overall survival in ST-elevation myocardial infarction (STEMI) patients with different stages of CKD. METHODS: In our retrospective cohort study with health insurance claims data of the Allgemeine Ortskrankenkasse (AOK), anonymized data of all STEMI patients hospitalized between 2010 and 2017 were analyzed regarding presence and severity of concomitant CKD. RESULTS: A total of 175,187 patients had an index-hospitalisation for STEMI (without CKD: 78.6% patients, CKD stage 1: 0.8%, CKD stage 2: 4.8%, CKD stage 3: 11.7%, CKD stage 4: 2.8%, CKD stage 5: 0.7%, CKD stage 5d: 0.6%). Patients with CKD were older and had more co-morbidities than patients without CKD. With increasing CKD severity, patients received less revascularization therapies (91.2%, 85.9%, 87.0%, 81.8%, 71.7%, 76.9% and 78.6% respectively, p < 0.001). After 1 year, guideline-recommended medications were prescribed less frequently in advanced CKD (83.4%, 79.3%, 81.5%, 74.7%, 65.0%, 59.4% and 53.7%, respectively, p < 0.001). CKD stages 4, 5 and 5d as well as chronic limb threatening ischemia (CLTI) were associated with decreased overall survival [CKD stage 4: hazard ratio (HR) 1.72; 95% CI 1.66-1.78; CKD stage 5: HR 2.55; 95% CI 2.37-2.73; CKD stage 5d: 5.64; 95% CI 5.42-5.86; CLTI: 2.06; 95% CI 1.98-2.13; all p < 0.001]. CONCLUSIONS: CKD is a frequent co-morbidity in patients with STEMI and is associated with a worse prognosis especially in advanced stages. Guideline-recommended therapies in patients with STEMI and CKD are still underused.

A Randomized Controlled Trial Comparing Apixaban With the Vitamin K Antagonist Phenprocoumon in Patients on Chronic Hemodialysis: The AXADIA-AFNET 8 Study.

BACKGROUND: Non-vitamin K oral anticoagulants have become the standard therapy for preventing stroke and ischemic thromboembolism in most patients with atrial fibrillation (AF). The effectiveness and safety of non-vitamin K oral anticoagulants in patients on hemodialysis is not well known. METHODS: From June 2017 through May 2022, AXADIA-AFNET 8 (Compare Apixaban and Vitamin K Antagonists in Patients With Atrial Fibrillation and End-Stage Kidney Disease), an investigator-initiated PROBE (prospective randomized open blinded end point) outcome assessment trial, randomized patients with AF on chronic hemodialysis to either apixaban (2.5 mg BID) or the vitamin K antagonist (VKA) phenprocoumon (international normalized ratio, 2.0 to 3.0). The composite primary safety outcome was defined by a first event of major bleeding, clinically relevant nonmajor bleeding, or all-cause death. The primary efficacy outcome was a composite of ischemic stroke, all-cause death, myocardial infarction, and deep vein thrombosis or pulmonary embolism. Our hypothesis was that apixaban is noninferior to VKA. RESULTS: Thirty-nine sites randomized 97 patients (30% women; mean age 75 years; mean CHA2DS2-VASc [congestive heart failure, hypertension, age ≥75 years, diabetes, stroke or transient ischemic attack, vascular disease, age 65 to 74 years, female sex] score, 4.5; baseline characteristics balanced between groups): 48 to apixaban and 49 to VKA. The median follow-up time was 429 days (range, 37 to 1370) versus 506 days (range, 101 to 1379), respectively. Adherence to apixaban was >80% in 44 of 48 patients; the median time in therapeutic range on VKA was 50.7%. Composite primary safety outcome events occurred in 22 patients (45.8%) on apixaban and in 25 patients (51.0%) on VKA (hazard ratio, 0.93 [95% CI, 0.53-1.65]; Pnoninferiority=0.157). Composite primary efficacy outcome events occurred in 10 patients (20.8%) on apixaban and in 15 patients (30.6%) on VKA (P=0.51; log rank). There were no significant differences regarding individual outcomes (all-cause mortality, 18.8% versus 24.5%; major bleeding, 10.4% versus 12.2%; and myocardial infarction, 4.2% versus 6.1%, respectively). CONCLUSIONS: In this randomized trial comparing apixaban and VKA in patients with AF on hemodialysis with long follow-up, no differences were observed in safety or efficacy outcomes. Even on oral anticoagulation, patients with AF on hemodialysis remain at high risk of cardiovascular events. Larger randomized trials are needed to determine the optimal anticoagulation regimen for patients with AF on hemodialysis. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02933697.

[Sex Disparities in Treatment and Outcome of Patients with Lower Extremity Arterial Disease: A Secondary Data Analysis]. / Geschlechtsspezifische Unterschiede in der Versorgung und dem Outcome von pAVK Patienten ­ Eine Sekundärdatenanalyse.

AIM OF THE STUDY: The aim of our study was to analyse sex-specific differences in diagnosis and treatment of patients with lower extremity artery disease (LEAD) at Rutherford stage (RF) 1-3, based on secondary data. Furthermore, we focussed on the influence of the biological sex on short- and long-term outcome. METHODS: The GenderVasc project is carried out in cooperation with the AOK Research Institute (WIdO). As data basis, anonymized routine data from all insured patients of the AOK were used. All patients hospitalized due to a main diagnosis of LEAD at RF 1-3 were included and in addition to the multisectoral cross-sectional analysis, longitudinal analysis (follow-up of up to 10 years) of the health claims data was performed and evaluated. RESULTS: Our secondary data analysis of 42,197 patients with intermittent claudication (IC, LEAD at RF 1-3) showed that male patients were more often hospitalized due to LEAD, while women were older at time-point of index hospitalisation (female: 72.6 vs. male: 66.4 years). Fewer vascular procedures (diagnostic angiography and revascularisation) were carried out in females. Moreover, the prescription of guideline-recommended medications (statins and antithrombotic therapy) was lower in women compared to men. Multivariable Cox regression showed, after adjusting for age, cardiovascular risk profile and performed vascular procedure, that female sex was protective with respect to overall survival and progression of LEAD (progress to chronic limb-threatening ischemia or ischemic amputation). CONCLUSION: In Germany, female LEAD patients were older and less likely to receive guideline-recommended therapy, while female sex is protective in terms of overall survival and progression of LEAD. The extent to which increased age or the presence of other comorbidities influence the decision for or against a vascular procedure can only be assumed from a secondary data analysis. Furthermore, the prescription of drugs in multimorbid patients is challenging and the compliance of the patients with prescribed medication intake is not part of our analysis. Nevertheless, targeted analysis, as in the GenderVasc project, are urgently needed to identify and describe differences in the medical care between the sexes.

Secondary Prevention in Lower Extremity Artery Disease Patients: Lipid-Lowering Therapy and Long-Term Guideline Adherence.

Lower extremity artery disease (LEAD) affects millions of elderly patients and is associated with elevated cardiovascular morbidity and mortality. Risk factor modification, including the therapy of dyslipidaemia, is mandatory to reduce cardiovascular event rates and to improve survival rates. However, only a minority achieve the recommended low-density lipoprotein cholesterol (LDL-C) target level < 55 mg/dL, according to the current ESC/EAS guidelines on the treatment of dyslipidaemia. This study elucidated the implementation of the lipid-lowering guideline recommendations of 400 LEAD patients with LDL-C > 100 mg/dL and their adherence to treatment adjustment during follow-up. Despite a sustained statin prescription in 93% of the patients, including 77% with high-intensity statins at follow-up, only 18% achieved the target level. Ezetimibe appeared in 21% and LDL-C goals were reached significantly more often with combination therapy. Recurrent revascularization appeared more often (28%) than coronary artery or cerebrovascular disease progression (14%) and 7% died. Despite the frequent use of high-intensity statins and expandable rates of ezetimibe, the progression of cardiovascular events remained inevitable. Only 18% of the patients had received recommendations on lifestyle modification, including dietary adaptations, which is key for a holistic approach to risk factor control. Thus, efforts for both pharmacological and behavioral strategies are needed to improve clinical outcomes and survival rates.

Outcome in octogenarian patients with lower extremity artery disease after endovascular revascularisation: a retrospective single-centre cohort study using in-patient data.

OBJECTIVES: To investigate the clinical benefit of endovascular revascularisation (EVR) in octogenarian (aged ≥80 years) patients with lower extremity artery disease (LEAD). DESIGN: Retrospective single-centre study. SETTING: University hospital with a specialised centre for vascular medicine. PARTICIPANTS: 681 LEAD patients undergoing EVR between 2010 and 2016 were stratified by age. MAIN OUTCOME MEASURE: Technical success, complications and mortality. RESULTS: The cohort comprised 172 (25.3%) octogenarian and 509 (74.7%) non-octogenarian patients. Despite higher LEAD stages and complexity of EVR in octogenarians, primary technical success rate (79% octogenarians vs 86% non-octogenarians, p=0.006) and 1-year survival (87% vs 96%, p<0.001) were overall on high levels. Especially for the octogenarians, 1-year survival depends on the presence of chronic limb-threatening ischaemia (CLTI) (octogenarians: non-CLTI 98%; CLTI 79% p<0.001 vs non-octogenarians: non-CLTI 99%; CLTI 91%, p<0.001). In octogenarians, female sex (HR 0.45; 95% CI (0.24 to 0.86); p=0.015), the intake of statins (HR 0.34; 95% CI 0.19 to 0.65; p=0.001) and platelet aggregation inhibitors (HR 0.10; 95% CI 0.02 to 0.45; p=0.003) were independently associated with improved survival after EVR. CONCLUSION: EVR can be performed safely and with sustained clinical benefit also in octogenarian patients with LEAD. After-care including medical adherence is of particular importance to improve long-term survival.

ST-Elevation Myocardial Infarction as a First Event.

BACKGROUND: Survival after ST-elevation myocardial infarction (STEMI) as a first event in Germany was analyzed. METHODS: Adults with a first-event STEMI were included for analysis on the basis of insurance data from a German health insurance provider (AOK; approximately 26 million members; median follow-up 48.5 months). The primary endpoints were 30-day mortality, reinfarction or death, major adverse cardiovascular and cerebro - vascular events (MACCE), long-term survival for more than 90 days, and overall survival (OS). RESULTS: STEMI occurred in 17 444 patients (32.8% women). The women were older than the men (median age 74 versus 60 years) and suffered more frequently from cardiovascular comorbidities such as diabetes mellitus, chronic renal disease, and arterial hypertension. Women underwent endovascular or surgical treatment less frequently, but sustained complications (cardiogenic shock, resuscitation) more frequently. After adjustment of the data, women were at higher risk of 30-day mortality (odds ratio [OR] 1.17, 95% confidence interval [95% CI] [1.07; 1.28]), reinfarction or death (hazard ratio [HR] 1.09, 95% CI [1.04; 1.16]), MACCE (HR 1.09, 95% CI [1.04; 1.15]), and poorer OS (HR 1.10, 95% CI [1.04; 1.17]). This effect was especially pronounced in women aged ≤ 60 years. No differences between the sexes were seen among patients who survived for 90 days after the infarction. CONCLUSION: In Germany, women ≤ 60 years display a higher 30-day mortality after first-event STEMI, which affects their overall survival. Younger women should receive intensified medical attention after STEMI, especially in the early phase.

Sex-related differences in treatment and outcome of chronic limb-threatening ischaemia: a real-world cohort.

AIMS: The prevalence of chronic limb-threatening ischaemia (CLTI) is increasing and available data often derive from cohorts with various selection criteria. In the present study, we included CLTI patients and studied sex-related differences in their risk profile, vascular procedures, and long-term outcome. METHODS AND RESULTS: We analysed 199 953 unselected patients of the largest public health insurance in Germany (AOK: Local healthcare funds), hospitalized between 2010 and 2017 for a main diagnosis of CLTI. A baseline period of 2 years before index hospitalization to assess comorbidities and previous procedures, and a follow-up period until 2018 were included. Female CLTI patients were older (median 81.4 vs. 73.8 years in males; P < 0.001) and more often diagnosed with hypertension, atrial fibrillation, chronic heart failure, and chronic kidney disease. Male patients suffered more frequently from diabetes mellitus, dyslipidaemia, smoking, cerebrovascular disease, and chronic coronary syndrome (all P < 0.001). Within hospitalized CLTI patients, females represent the minority (43% vs. 57%; P < 0.001) and during index hospitalization, women underwent less frequently diagnostic angiographies (67 vs. 70%) and revascularization procedures (61 vs. 65%; both P < 0.001). Moreover, women received less frequently guideline-recommended drugs like statins (35 vs. 43%) and antithrombotic therapy (48 vs. 53%; both P < 0.001) at baseline. Interestingly, after including age and comorbidities in a Cox regression analysis, female sex was associated with increased overall-survival (OS) [hazard ratio (HR) 0.95; 95% confidence interval (CI) 0.94-0.96] and amputation-free survival (AFS) (HR 0.84; 95% CI 0.83-0.85; both P < 0.001). CONCLUSION: Female patients with CLTI were older, underwent less often vascular procedures, and received less frequently guideline-recommended medication. Nevertheless, female sex was independently associated with better OS and AFS during follow-up.

Sex-related differences in outcome after endovascular revascularization for lower extremity artery disease.

Background: Sex-related differences may influence the outcome of endovascular revascularization (EVR) in patients with lower extremity arterial disease (LEAD) even under optimized healthcare supply. Patients and methods: LEAD patients who underwent EVR at the Department of Cardiology I - Coronary and Peripheral Vascular Disease, Heart Failure, University Hospital Muenster, Germany between 2014 and 2016 were included into the retrospective study. Detailed information on risk factors and co-morbidities, medication, LEAD related measures, and interventional parameters were assessed. Outcome defined as technical success rate, complications, and mortality was analyzed up to 12 months follow-up. Results: In total, 165 female and 437 male LEAD patients were included. Women and men presented with comparable severity of LEAD in terms of critical limb threatening ischemia (46.2%), wound status (34.9%), and amputation rate (9.6%, all n.s.) at index. Intake of platelet inhibitors (65.8% female vs. 70.0% male), oral anticoagulants (21.3% vs. 25.4%), and statins (65.6% vs. 76.0%) was observed less frequently in female patients. Against the background of high technical success (85%), in-hospital death (0.8%), severe adverse cardiac (MCE; 1.7%), and limb events (MALE; 6.1%) occurred at low rates in either sex. Adjusted long-term mortality was not affected by patients' sex (female HR 0.755; p=0.312). Conclusions: Despite critical LEAD stages in every second patient, EVR was performed safe with high technical success rates in female and male patients. Long-term outcomes were observed at comparatively low rates in both sexes at the specialized vascular center. During aftercare, supply with statin therapy turned out improvable particularly in female LEAD patients.

Acute and Long-Term Outcomes of ST-Elevation Myocardial Infarction in Cancer Patients, a 'Real World' Analysis with 175,000 Patients.

BACKGROUND: Acute myocardial infarction (AMI) and cancer are common and serious diseases. As the prognosis and treatment of both diseases has improved, more cancer patients will suffer an AMI. Unfortunately, data on these "double hit" patients is scarce. METHODS: From the largest public German health insurance, anonymized data of all patients with pre-existing cancer who were hospitalized due to ST-elevation MI (STEMI) between 2010 and 2017 were analyzed and followed-up until 2018. RESULTS: Of 175,262 STEMI patients, 27,213 had pre-existing cancer (15.5%). Most frequent were skin (24.9%), prostate (17.0%), colon (11.0%), breast (10.9%), urinary tract (10.6%), and lung cancer (5.2%). STEMI patients with malignancies were older and presented more often with coronary three-vessel disease, atrial arrhythmias, chronic kidney disease, chronic heart failure, cerebrovascular and peripheral artery disease (PAD, each p < 0.001). They showed more often previous AMI, percutaneous coronary interventions (PCI), cardiac surgery, and stroke (all p < 0.001). Acute PCIs were applied between 2 and 6% less frequently compared to those without cancer. In-hospital adverse events occurred more frequently in cancer. Eight-year survival was 57.3% (95% CI 57.0-57.7%) without cancer and ranged between 41.2% and 19.2% in distinct cancer types. Multivariable Cox regression for all-cause mortality found, e.g., lung cancer (HR 2.04), PAD stage 4-6 (HR 1.78), metastasis (HR 1.72), and previous stroke (HR 1.44) to have the strongest impact (all p < 0.001). CONCLUSION: In this large "real world" data, prognosis after STEMI in cancer patients was markedly reduced but differed widely between cancer types. Of note, no withholding of interventional treatments in cancer patients could be observed.

Access Site Related Vascular Complications following Percutaneous Cardiovascular Procedures.

Vascular access site complications (ASC) are among the most frequent complications of percutaneous cardiovascular procedures (PCP) and are associated with adverse outcome and high resources utilization. In this prospective study, we investigated patients with postprocedural clinical suspicion of ASC evaluated by duplex ultrasound (DUS) for the presence of ASC. We assessed the incidence, in-hospital outcome, treatment of complications and predictors for ASC. Overall, 12,901 patients underwent PCP during a 40 months period. Of those, 2890 (22.4%) patients had postprocedural clinical symptoms of ASC and were evaluated using DUS. An ASC was found in 206 of the DUS examined patients (corresponding to 7.1% of the 2890 DUS examined patients). In 6.7% of all valvular/TAVI procedures, an ASC was documented, while coronary, electrophysiological and peripheral PCP had a comparable and low rate of complications (1.2-1.5%). Pseudoaneurysm (PSA) was the most frequent ASC (67.5%), followed by arteriovenous fistula (13.1%), hematoma (7.8%) and others (11.7%). Of all PSA, 84 (60.4%) were treated surgically, 44 (31.6%) by manual compression and 11 (7.9%) conservatively. Three (0.02%) patients died due to hemorrhagic shock. In conclusion, femoral ASC are rare in the current era of PCP with PSA being the leading type of ASC. Nonetheless, patients with predisposing risk factors and postprocedural suspicious clinical findings should undergo a DUS to early detect and mitigate ASC-associated outcome.

Sex-specific differences and long-term outcome of patients with coronary artery disease and chronic kidney disease: the Coronary Artery Disease and Renal Failure (CAD-REF) Registry.

BACKGROUND: Cardiovascular morbidity and mortality are closely linked to chronic kidney disease (CKD). Sex-specific long-term outcome data of patients with coronary artery disease (CAD) and CKD are scarce. METHODS: In the prospective observational multicenter Coronary Artery Disease and REnal Failure (CAD-REF) Registry, 773 (23.1%) women and 2,579 (76.9%) men with angiographically documented CAD and different stages of CKD were consecutively enrolled and followed for up to 8 years. Long-term outcome was evaluated using survival analysis and multivariable Cox-regression models. RESULTS: At enrollment, women were significantly older than men, and suffered from more comorbidities like CKD, hypertension, diabetes mellitus, and multivessel coronary disease. Regarding long-term mortality, no sex-specific differences were observed (Kaplan-Meier survival estimates: 69% in women vs. 69% in men, plog-rank = 0.7). Survival rates decreased from 89% for patients without CKD at enrollment to 72% for patients with CKD stages 1-2 at enrollment and 49% for patients with CKD stages 3-5 at enrollment (plog-rank < 0.001). Cox-regression analysis revealed that sex or multivessel coronary disease were no independent predictors of long-term mortality, while age, CKD stages 3-5, albumin/creatinine ratio, diabetes, valvular heart disease, peripheral artery disease, and left-ventricular ejection fraction were predictors of long-term mortality. CONCLUSIONS: Sex differences in CAD patients mainly exist in the cardiovascular risk profile and the extent of CAD. Long-term mortality was not depended on sex or multivessel disease. More attention should be given to treatment of comorbidities such as CKD and peripheral artery disease being independent predictors of death. Clinical Trail Registration ClinicalTrials.gov Identifier: NCT00679419.

Feasibility and impact of carbon dioxide angiography on acute kidney injury following endovascular interventions in patients with peripheral artery disease and renal impairment.

BACKGROUND: Post-contrast acute kidney injury (AKI) is a dreaded complication of endovascular revascularization using iodinated contrast medium in patients with peripheral artery disease and concomitant chronic kidney disease (CKD). This study sought to evaluate the incidence of AKI in patients with peripheral artery disease and CKD undergoing endovascular revascularization and using carbon dioxide (CO2) as contrast medium. METHODS AND RESULTS: From 04/2015 to 07/2018, all consecutive peripheral artery disease patients with CKD stage ≥ 3 referred for endovascular revascularization of symptomatic peripheral artery disease were prospectively included. During endovascular revascularization, CO2 as contrast medium was manually injected and iodinated contrast medium was additionally used when needed. The reference group consisted of 211 cardiovascular risk factor-matched patients undergoing endovascular revascularization with iodinated contrast medium only. CO2-guided endovascular revascularization was performed in 102 patients, thereof 16 (15.7%) patients exclusively with CO2. Baseline CKD stage ≥ 4 and iodinated contrast medium volume > 50 ml were disproportionally associated with post-procedural post-contrast AKI. At CKD stage 4 the odds ratio for post-contrast AKI was 13.2 (95% CI 1.489-117.004; p = 0.02) for iodinated contrast medium volume 51-100 ml and 37.7 (95% CI 3.927-362.234; p = 0.002) for iodinated contrast medium volume > 100 ml. The corresponding values at CKD stage 5 were 23.7 (95% CI 2.666-210.583; p = 0.005) and 28.3 (95% CI 3.289-243.252; p = 0.002), respectively. Radiation (dose area product) was significantly higher in the CO2-endovascular revascularization group (6.025 ± 6.926 cGy*cm2 vs. 4.281 ± 4.722 cGy*cm2, p = 0.009). CONCLUSION: CO2 is an applicable and safe alternative to iodinated contrast medium for endovascular revascularization in peripheral artery disease patients with concomitant CKD. Patients with CKD stage 4 or 5, being at highest risk for post-contrast AKI, should primarily be treated by CO2-guided endovascular revascularization.

[Medication-based secondary prevention in patients with peripheral arterial occlusive disease : An analysis based on secondary data]. / Medikamentöse Sekundärprävention bei Patienten mit peripherer arterieller Verschlusskrankheit : Eine sekundärdatenbasierte Analyse.

BACKGROUND: Peripheral arterial occlusive disease (PAOD) is an atherosclerotic vascular disease with high morbidity and mortality. A consistent medication-based secondary prevention is part of the essential and evidence-based treatment of PAOD. The aim of this study was to ascertain the status quo of medicinal secondary prevention based on submitted prescriptions. METHODS: In the time period from 2014 to 2017 patients with a confirmed PAOD coding (I70.2-/I73.9-) were identified based on secondary data of the Association of Statutory Health Insurance Physicians Westphalia-Lippe (KVWL). The prescriptions submitted with respect to platelet inhibitors, oral anticoagulants, lipid lowering therapy (LLT) and angiotensin-converting enzyme (ACE) inhibitors in the fourth quarter year after diagnosis coding were collated. RESULTS: In the diagnosis period 2014/2015 a total of 238,397 patients had PAOD in the catchment area of the KVWL. The proportion of submitted prescriptions in the fourth quarter year after diagnosis was 25.9% for LLT, 13.6% for acetylsalicylic acid, 4.5% for clopidogrel, 5.5% for vitamin K antagonists (VKA), 3.5% for non-vitamin K­dependent oral anticoagulants (NOAC) and 26.8% for ACE inhibitors. Over the course of the 3 years (n = 241,375 patients with PAOD 2016/2017) the proportion of submitted prescriptions for all substances except VKA increased (p < 0.001), whereby the largest relative increase was noted for NOAC (relative increase of 81.7%). CONCLUSION: The guideline-conform medicinal secondary prevention in patients with PAOD in Germany is still in need of improvement. A consistent implementation of evidence-based medicinal secondary prevention harbors a great potential for improvement of the overall prognosis in patients with PAOD.