Evolocumab effectiveness in the real-world setting: Austrian data from the pan-European observational HEYMANS study.

BACKGROUND: This real-world study examined clinical characteristics and dyslipidemia management among patients initiating evolocumab across 12 European countries. Austrian data are reported. METHODS: Data of consenting adults were collected for ≤ 6 months prior to evolocumab initiation (baseline) and ≤ 30 months post-initiation. Patient characteristics, lipid lowering therapy (LLT, i.e. statin and/or ezetimibe) and lipid values were collected from medical records. RESULTS: In Austria, 363 patients were enrolled. At baseline, 52% of patients initiated evolocumab without background LLT; the median (Q1, Q3) initial low-density lipoprotein cholesterol (LDL-C) level was 142 (111, 187) mg/dL. Within 3 months of evolocumab treatment, median LDL­C decreased by 59% to 58 (37, 91) mg/dL. This reduction was maintained over time, despite consistently infrequent use of background LLT. LDL-C < 55 mg/dL was attained by 65% of patients (76% with, 55% without background LLT). Evolocumab persistence was ≥ 90% at month 12 and month 30. CONCLUSION: In Austria, patients were initiated on evolocumab at LDL­C levels almost 3­times higher than the guideline-recommended clinical goal (< 55 mg/dL). Persistence with evolocumab was very high. Evolocumab led to a rapid and sustained LDL­C reduction with 65% attaining the LDL­C goal. Patients using evolocumab in combination with statins and/or ezetimibe were more likely to attain their LDL­C goal and thus decrease cardiovascular risk.

Characteristics and outcomes of patients with psoriasis treated with apremilast in the real-world in Austria - results the APPRECIATE study.

Background: Apremilast, an oral phosphodiesterase 4 inhibitor, is approved in the European Union for the treatment of moderate-to-severe chronic plaque psoriasis in adult patients refractory or contraindicated to or intolerant of other systemic therapies. Objectives: The APPRECIATE study assessed apremilast use in real-world practice and its clinical value to physicians and patients. APPRECIATE was a multinational, observational, retrospective, cross-sectional study. Methods: Apremilast effectiveness at 6 (±1) months was assessed on the basis of psoriasis severity and health-related quality-of-life scores and treatment satisfaction using physician/patient-reported outcomes, respectively. We report the Austrian cohort of 72 patients. Results: At 6 (±1) months, three-quarters of patients remained on apremilast, while physicians and patients reported treatment benefits across all psoriasis symptoms and manifestations. Of patients, the majority were satisfied with their treatment and achieved treatment goals considered most relevant. Patients' and physicians' perceptions of treatment effectiveness were aligned, and health-related quality-of-life scores indicated an improvement in the majority of patients. Apremilast tolerability was consistent with the known safety profile. Conclusions: Among psoriasis patients receiving apremilast in Austria, improvement in clinical outcomes were observed and satisfaction with apremilast treatment among patients and physicians was high. Registration: ClinicalTrials.gov NCT02740218.

Interpreting the Benefit and Risk Data in Between-Drug Comparisons: Illustration of the Challenges Using the Example of Mefenamic Acid versus Ibuprofen.

Evidence-based pain therapy should rely on precisely defined and personalized criteria. This includes balancing the benefits and risks not only of single drugs but often requires complex between-drug comparisons. Non-steroidal anti-inflammatory drugs (NSAIDs) have been available for several decades and their use is described in an abundance of guidelines. Most of these guidelines recommend that 'the selection of a particular NSAID should be based on the benefit-risk balance for each patient'. However, head-to-head studies are often lacking or of poor quality, reflecting the lower standards for clinical research and regulatory approval at the time. The inconsistency of approved indications between countries due to national applications adds to the complexity. Finally, a fading research interest once drugs become generic points to a general deficit in the post-marketing evaluation of medicines. Far from claiming completeness, this narrative review aimed to illustrate the challenges that physicians encounter when trying to balance benefits and risks in a situation of incomplete and inconsistent data on longstanding treatment concepts. Ibuprofen and mefenamic acid, the most frequently sold NSAIDs in Austria, serve as examples. The illustrated principles are, however, not specific to these drugs and are generalizable to any comparison of older drugs in daily clinical practice.

Lipid lowering therapy in primary and secondary prevention in Austria: are LDL-C goals achieved? : Results from the DA VINCI study.

BACKGROUND: Cardiovascular disease (CVD) is the most frequent cause of death in Austria. The European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) guidelines recommend intensive lipid lowering therapy (LLT) in patients at high or very high CV risk. Lipid management and achievement of low-density lipoprotein cholesterol (LDL-C) goals in Austria have not recently been assessed. METHODS: Subgroup analysis for Austria of a European 18 country, cross-sectional, observational study. Patients received LLT for primary (PP) or secondary prevention (SP). Data including LLT in the preceding 12 months and most recent LDL­C were collected during a single visit between June 2017 and November 2018. Achievement of the risk-based 2016 and 2019 ESC/EAS LDL­C goal while receiving stabilized LLT was assessed. RESULTS: A total of 293 patients were enrolled from 8 Austrian sites, of which 200 (PP = 104, SP = 96) received stabilized LLT at the LDL­C measurement date. Overall, 58% (71% PP, 43% SP) and 38% (52% PP, 23% SP) achieved the risk-based 2016 and 2019 goals, respectively. Most patients received moderate-intensity statin monotherapy (46%), while 34% used high-intensity statin monotherapy. Combination therapy of moderate/high-intensity statin with ezetimibe (12%), or proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors with statin ± ezetimibe (1%), was used infrequently. CONCLUSION: The current Austrian routine lipid management using mainly moderate-intensity or high-intensity statin monotherapy is insufficient to attain ESC/EAS guideline goals, in particular the more stringent 2019 recommendations, a situation comparable to other participating European countries. In addition to switching to and optimizing doses of high-intensity statins, a combination with ezetimibe or PCSK9 inhibitors will be needed in many cases.

Sex-Related Differences in Drugs with Anti-Inflammatory Properties.

There is increasing evidence of sex differences in the action of anti-inflammatory drugs, with women being at significantly higher risk of adverse effects. Nevertheless, clinicians' awareness of the implications of these sex differences on dosing and adverse event monitoring in routine practice is still in need of improvement. We reviewed the literature evaluating sex differences in terms of pharmacokinetics and pharmacodynamics of anti-inflammatory drugs. The anti-thrombotic activity of selective and non-selective COX-inhibitors tends to be stronger in men than women. Side effect profiles differ with regards to gastro-intestinal, renal and hepatic complications. Glucocorticosteroids were found to be more effective in men; women were more sensitive to corticosteroids when their oestradiol levels were high, a finding important for women taking hormonal contraception. TNF-alpha inhibitors have a longer half-life in men, leading to stronger immunosuppression and this a higher incidence of infections as side effects. Although research on sex differences in the effectiveness and safety of drugs is increasing, findings are often anecdotal and controversial. There is no systematic sex-differentiated reporting from clinical trials, and women are often under-represented. As personalized medicine is gaining in importance, sex, and gender aspects need to become integral parts of future research and policy making.

[LDL-cholesterol and cardiovascular events: the lower the better?] / LDL-Cholesterin und kardiovaskuläre Ereignisse: je niedriger desto besser?

For over 30 years, intensive research efforts investigated the role of LDL cholesterol in the pathogenesis of cardiovascular disease. In various settings, large statin trials showed an association between LDL cholesterol levels and cardiovascular event rates. This association is often referred to as the 'LDL cholesterol hypothesis'. More recent trials on agents with totally different modes of action confirmed this association and indicated a causal relationship between lower LDL cholesterol levels and improved cardiovascular outcomes. It has been proposed to term this causal relationship the 'LDL cholesterol principle'. It is to be expected that currently ongoing outcomes trials will further support the assumption of a causal relationship and will finally offer an armamentarium to therapists that will enable individualized treatment of dyslipidemias and their sequelae.

Management of secondary hyperparathyroidism: practice patterns and outcomes of cinacalcet treatment with or without active vitamin D in Austria and Switzerland - the observational TRANSIT Study.

Secondary hyperparathyroidism is a complex disorder requiring an individualized multicomponent treatment approach. This study was conducted to identify treatment combinations used in clinical practice in Austria and Switzerland and the potential to control this disorder. A total of 333 adult hemodialysis and peritoneal dialysis patients were analyzed. All patients received conventional care prior to initiation of a cinacalcet-based regimen. During the study, treatment components, e.g. cinacalcet, active vitamin D analogues and phosphate binders, were adapted to individual patient requirements and treatment dynamics were documented. Overall, the mean intact parathyroid hormone (iPTH) increased from 64.2 pmol/l to 79.6 pmol/l under conventional therapy and decreased after cinacalcet initiation to 44.0 pmol/l after 12 months (mean decrease between baseline and 12 months -45%). Calcium remained within the normal range throughout the study and phosphorus ranged around the upper limit of normal. The Kidney Disease: Improving Global Outcomes (KDIGO) target achievement for iPTH increased from 44.5% of patients at baseline to 65.7% at 12 months, corrected calcium from 58.9% to 51.9% and phosphorus from 18.4% to 24.4%. On average, approximately 30% of patients adapted their regimen from one observation period to the next. The reasons for changing a given regimen were to attain or maintain any of the bone mineral markers within recommended targets and to avoid developments to extreme values. Some regional differences in practice patterns were identified. No new safety signals emerged. In conclusion, cinacalcet appears to be a necessary treatment component to achieve recommended targets. The detailed composition of the treatment mix should be adapted to patient requirements and reassessed on a regular basis.

EARLIER: an observational study to evaluate the use of cinacalcet in incident hemodialysis patients with secondary hyperparathyroidism in daily clinical practice.

The EARLIER (Evaluation of MimpARa in incident hemodiaLysis patIEnts with secondaRy hyperparathyroidism; SHPT) observational postmarketing surveillance study evaluated incident hemodialysis patients (< 1 year dialysis vintage; n = 146) receiving cinacalcet in Austrian clinical practice. Despite intervention with vitamin D sterols and phosphate binders, 24 % had already developed severe SHPT (intact parathyroid hormone (iPTH) > 800 pg/mL) at baseline. After cinacalcet was started, median iPTH decreased substantially, from 611 pg/mL to 251 pg/mL (median decrease 58 % [IQR - 36 to - 78 %] at 12 months. Overall, 36 % of patients achieved the Kidney Disease Outcomes Quality Initiative (K/DOQI) target range (150-300 pg/mL) for iPTH; this included 35 % of those with severe SHPT at baseline. Serum phosphorus (P), calcium (Ca) (corr), and Ca (corr) × P also decreased, with 43, 34, and 62 % of patients, respectively, reaching K/DOQI targets at 12 months. Thus, in this observational study, mineral metabolism in incident dialysis patients with SHPT improved after starting cinacalcet.

Denosumab for the treatment of giant cell tumor of the bone.

Giant cell tumor of bone is typically composed of neoplastic stromal cells and non-neoplastic osteoclastic giant cells. RANK-expressing osteoclastic giant cells are recruited by RANK ligand excreted by the stromal cells, and used by these neoplastic cells to create expansion space. Denosumab specifically binds to and inhibits RANK ligand, thereby eradicating osteoclastic giant cells from the tumor and thus reducing osteolytic activity. Clinical studies reported disease stabilization and clinical benefit in terms of reduced pain and analgesics use, avoided surgeries or surgeries with less morbid procedures. Adverse events observed in patients with giant cell tumor of bone were consistent with the known safety profile of denosumab with a very low incidence of hypocalcemia and osteonecrosis. Overall, denosumab was shown to suppress osteolytic activity and slow disease progression and is thus a treatment option for patients with giant cell tumor of bone.

Darbepoetin alfa once every 2 weeks effectively maintained hemoglobin in dialysis patients in an observational study: Austrian cohort of ALTERNATE.

ALTERNATE is an international observational study evaluating biweekly darbepoetin alfa (DA) in adult dialysis patients in clinical practice. Austrian ALTERNATE results are presented here (n = 505). The follow-up study ALTERNATE follow-up (AFU) followed Austrian ALTERNATE patients for an additional 12 months (n = 135). Data were collected 6 months before and 12 months after conversion to biweekly dosing and during 12 months of follow-up. The primary measures were hemoglobin concentration 12 months after conversion and at the end of AFU, respectively. Mean (95 % CI) hemoglobin (g/dL) was 11.87 (11.75-11.99) at conversion, 11.71 (11.58-11.83) at month 12, and 11.66 (11.45-11.86) at end of AFU. Geometric mean (95 % CI) weekly dose (µg/wk) was 32.97 (30.80-35.30) at conversion, 29.90 (26.71-33.46) 12 months after conversion, and 24.38 (18.40-30.35) at end of AFU. The studies show that hemoglobin and dose could be effectively maintained over an extended period of time after conversion from higher frequency erythropoiesis-stimulating agents to biweekly DA.

Awareness of chronic kidney disease in Austria: a frequently under-recognized clinical picture.

BACKGROUND: The prevalence of chronic kidney disease (CKD) is rising at an alarming rate, thus presenting a substantial burden for the patient as an individual and-because of the enormous treatment costs-for society as a whole. Early diagnosis and therapy could slow disease progression and reduce the prevalence of cost-intensive end stage renal disease. The aim of this study was to determine the accuracy of diagnosis of CKD in acute patients presenting at an internal ward. METHODS: Routine laboratory parameters of kidney function of 238 inpatients were retrospectively evaluated to determine the prevalence of CKD, defined as estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m(2). Those results were compared with the actual documentation of the ICD-10 diagnosis CKD in the discharge reports of the respective patients. RESULTS: Of 238 patients, 228 patients were included in the analysis. The overall median (range) eGFR was 60.7 (10.4-171.9) mL/min/1.73 m(2), with no gender-specific difference. Of patients, 49.6 % (n = 113) were retrospectively diagnosed with CKD stage 3 or higher. However, the review of the discharge reports found correct diagnosis of CKD in only 38.1 % (n = 43) of these patients. CONCLUSIONS: The present analysis shows that CKD remains frequently unrecognized, even in a hospital setting. This could have dramatic implications on the care, treatment and prevention of CKD and associated complications.

The MAINTAIN study--managing hemoglobin variability with darbepoetin alfa in dialysis patients experiencing a severe drop in hemoglobin.

BACKGROUND: Dialysis patients, receiving erythropoiesis stimulating agents, typically show signs of hemoglobin variability as a consequence of their dosing patterns, bleeding, infection, etc., which is commonly managed adjusting the dose regimen of the erythropoiesis stimulating agent. However, information on dosing strategies used in daily clinical practice and their outcomes in relation to hemoglobin variability is limited. OBJECTIVES: To investigate clinical practice in Austria in relation with the management of hemoglobin variability, defined as a decrease of ³ 1 g/dL within 4 weeks from ³ 11 g/dL to £ 11 g/dL during maintenance therapy with darbepoetin alfa. The nature and incidence of clinical events related to the hemoglobin drop were also assessed. RESEARCH DESIGN AND METHODS: The MAINTAIN non-interventional study was conducted in hemodialysis patients, receiving darbepoetin alfa in accordance to the label approved in the European Union at that time. Patient data were documented retrospectively for the 3 months prior to the hemoglobin drop. Data for the 6 months post hemoglobin drop were collected retrospectively or prospectively, depending on the time of patient inclusion respective to the Hb drop. RESULTS: A hundred thirty six of 154 patients fulfilled all inclusion/exclusion criteria and had prospective documentation of 6 months. The main causes for the hemoglobin drop included surgical and medical procedures (36.1 %), and infections or infestations (24.4 %). The median treatment period was 273 days. The mean hemoglobin drop was - 1.74 g/dL (95 % confidence interval (CI): - 1.60 to - 1.87). Consequently, 81 % of the patients had their dose of darbepoetin alfa increased within a median Kaplan-Meier time to dose increase of 12.5 days (95 % CI: 6-22). The geometric mean weekly darbepoetin alfa dose increased by a factor of 1.1 from 29.1 mg (95 % CI: 24.6-34.4) in the 3 months before hemoglobin drop to 32.4 (95 % CI: 27.2-38.6) in months 4-6 post hemoglobin drop. Three patients had red blood cell transfusions before hemoglobin drop and nine patients after hemoglobin drop. The mean hemoglobin increase was 0.43 g/dL (95 % CI: 0.24-0.62) from immediately prior to 2 weeks after dose increase. The median Kaplan-Meier time to achieve a hemoglobin ³ 11 g/dL after hemoglobin drop was 36 days (95 % CI: 32-45). Frequent darbepoetin alfa dose adjustments were necessary to sustain maintenance levels. No drug-related adverse events were reported. CONCLUSIONS: This observational study describes physicians' reactions to a drop in hemoglobin in clinical practice. Using darbepoetin alfa, the drop was generally compensated without leading to overcorrection.