Dose-dependent statin-related myotoxicity (SRM) is a rare adverse effect of statin treatment.Differences in the pharmacokinetics and interactions with environmental and genetic factors constitute important risk factors for the development of SRM.We present the case of an 82-year-old female patient with severe simvastatin-related myotoxicity and several risk factors of SRM, namely a pharmacokinetic interaction with verapamil, a pharmacogenetic interaction with a SL-CO1B1*1/*5 variant, high age, female gender and impaired renal function.A comprehensive evaluation of distinct pharmacokinetic and pharmacogenetic properties of different statins and a pharmacogenetic panel test guided the diagnosis and options for further clinical management.Inspired by this and other similar cases, we developed a pocket card as practical companion for statin prescribing in clinical practice and provide it as an addition to this report.

Aim: Implementation of CYP2C19 point-of-care (POC) pharmacogenetic (PGx) testing with personalized treatment recommendations. Methods: POC CYP2C19 genotyping plus expert evaluation of risk factors for ischemic and bleeding events. Results: 167 patients underwent PGx testing, 54 (32.3%) were CYP2C19 loss of function carriers, and POC versus standard PGx analysis results for *2 and *3 variants matched in 100%. Antiplatelet therapy was adjusted in 44 patients (26.3%), but always required consideration of patient-specific factors. Conclusion: CYP2C19 POC-PGx is reliable and offers clinically relevant advantages for immediate evidence-based adaptations of antiplatelet therapy, whereas in less acute cases conventional PGx testing can also have advantages. Antiplatelet therapy has become more complex, and implementation of PGx-based personalized antiplatelet therapy requires complementary expert knowledge.

Purpose: Endovascular therapy of erection-related arteries was shown to be a promising treatment option for patients with severe erectile dysfunction. Purpose of this study was to assess the longer-term safety and clinical success rate of endovascular revascularization of erection-related arteries with the Angiolite BTK stent in patients with arteriogenic erectile dysfunction. Materials and Methods: A total of 147 consecutive men (63.5±9.3 years) with erectile dysfunction due to 345 atherosclerotic lesions underwent endovascular revascularization. Patients received an International Index of Erectile Function (IIEF)-15 questionnaire at 30.3±7.2 months (follow-up [FU] period no less than 18 months) after stenting. An improvement by 4 points in the erectile function domain consisting of 6 questions (IIEF-6) was defined as minimal clinically important difference (MCID). Results: Technical success was achieved in 99% of lesions. One major adverse event occurred after endovascular revascularization. Sixty-eight (46%) patients completed their latest FU at least 18 months following the last intervention. Minimal clinically important difference was achieved in 54% (37/68) of patients. Conclusions: In patients with arteriogenic erectile dysfunction not responding to phosphodiesterase-5-inhibitors (PDE-5-Is), endovascular therapy with a novel thin-strut sirolimus-eluting stent is a safe and effective treatment option during short- and longer-term FU. Clinical Impact Patients with severe erectile dysfunction profit greatly from endovascular therapy of erection-related arteries. Stable clinical outcomes are seen beyond a 1-year timeframe. It is proven that, the drug-eluting stent therapy for atherosclerotic ED in patients who have not responded to PDE-5-I therapy is safe and effective during longer-term follow-up.

Potential medication errors and related adverse drug events (ADE) pose major challenges in clinical medicine. Clinical decision support systems (CDSSs) help identify preventable prescription errors leading to ADEs but are typically characterized by high sensitivity and low specificity, resulting in poor acceptance and alert-overriding. With this cross-sectional study we aimed to analyze CDSS performance, and to identify factors that may increase CDSS specificity. Clinical pharmacology services evaluated current pharmacotherapy of 314 patients during hospitalization across three units of two Swiss tertiary care hospitals. We used two CDSSs (pharmaVISTA and MediQ), primarily for the evaluation of drug-drug interactions (DDI). Additionally, we evaluated potential drug-disease, drug-age, drug-food, and drug-gene interactions. Recommendations for change of therapy were forwarded without delay to treating physicians. Among 314 patients, automated analyses by both CDSSs produced an average of 15.5 alerts per patient. In contrast, additional expert evaluation resulted in only 0.8 recommendations per patient to change pharmacotherapy. For clinical pharmacology experts, co-factors such as comorbidities and laboratory results were decisive for the classification of CDSS alerts as clinically relevant in individual patients in about 70% of all decisions. Such co-factors should therefore be used for the development of multidimensional CDSS alert algorithms with improved specificity. In combination with local expert services, this poses a promising approach to improve drug safety in clinical practice.

Background: Arteriogenic erectile dysfunction is a common disease oftentimes not satisfactory treatable with medical therapy. Aim: To assess the safety and clinical success rate of endovascular revascularization of erection-related arteries with the angiolite BTK stent in patients with arteriogenic erectile dysfunction. Methods: A total of 100 consecutive men (61.8 +/- 10 years) with atherosclerotic lesions in erection-related arteries agreed to participate and were included into a single-center all-comers registry. Endovascular therapy with angiolite BTK drug-eluting stents was performed on a total of 211 lesions. Patients received a baseline International Index of Erectile Function (IIEF)-15 questionnaire at first presentation and 3 and 12 months after stenting. An improvement by 4 points in the erectile function domain consisting of 6 questions (IIEF-6) was defined as minimal clinically important difference. A total of 24 patients with 52 stented arterial lesions underwent angiographic follow-up of the initially treated arterial side during secondary revascularization of the contralateral side (angiographic sub-study). Outcome: Clinical improvement of erections in 100 patients undergoing endovascular revascularization of erection-related arteries. Results: No major adverse events occurred during endovascular revascularization or within 30 days thereafter. Technical success was achieved in all lesions and procedural success in all patients. At 1 year, 55 of 97 patients (56.7%) improved by at least 4 points in IIEF-6 score and thus achieved a clinically relevant improvement of erectile function.In the angiographic sub-study, arterial patency and binary restenosis were observed in 46 of 52 (88.5%) and in 8 of 52 (15.4%), respectively, after a mean follow-up of 9.6 +/- 5.8 months. Clinical Implications: In patients with arteriogenic erectile dysfunction, endovascular therapy with a novel thin strut sirolimus eluting stent is a safe and feasible treatment option. Strengths & Limitations: This real-world arterial revascularization registry included patients with a multitude of risk factors for ED, thereby representing the heterogeneity in patients in the clinical practice, which is one of its strengths but also one of its weaknesses. Another strength was the focus being laid on analyzing outcomes of patients with arteriogenic ED using only a single endovascular device. Further studies are warranted to better define subgroups of patients with impaired clinical outcomes. Conclusion: Within the present all-comers registry, endovascular therapy of erectile dysfunction with the angiolite BTK stent was shown to be a safe and feasible treatment option resulting in clinical improvement rates comparable to earlier clinical trials although also showing that further research is warranted to define patient subgroups with particular benefits of endovascular therapy. Copyright (C) 2020, International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

Purpose The antiplatelet prodrug clopidogrel is bioactivated by the polymorphic enzyme CYP2C19. Prospective clinical studies demonstrated an association between CYP2C19 loss of function (LoF) variants and an increased risk of thrombotic events under clopidogrel, but pharmacogenetic (PGx) testing is not frequently implemented in clinical practice. We report our experience with PGx-guided clopidogrel therapy with particular regard to clinically relevant patient management changes. Methods We conducted an observational study analyzing patients that underwent PGx testing for clopidogrel therapy at two Swiss hospitals. Primary outcome was the proportion of patients with clinically relevant PGx-based management recommendations and their implementation. The association of recurrent ischemic events under clopidogrel with CYP2C19 LoF variants and other factors was explored in a multivariate case-control analysis. Results Among 56 patients undergoing PGx testing, 18 (32.1%) were classified as CYP2C19 intermediate or poor metabolizers. This resulted in 17 recommendations for a change of antiplatelet therapy, which were implemented in 12 patients (70.1%). In the remaining five patients, specific reasons for non-implementation could be identified. Recurrent ischemic events under clopidogrel were associated with LoF variants (OR 2.2, 95% CI 0.3-14.4) and several cardiovascular risk factors. Associations were not statistically significant in our small study, but plausible and in line with estimates from large prospective studies. Conclusion PGx-guided clopidogrel therapy can identify patients with an elevated risk of ischemic events and offer evidence-based alternative treatments. Successful implementation in clinical practice requires a personalized interdisciplinary service that evaluates indications and additional risk factors, provides specific recommendations, and proactively follows their implementation.

Background and Purpose: There is an increasing number of evidence-based indications for pharmacogenetic (PGx) tests and a growing demand for PGx screening. We aimed to evaluate clinical relevance of a 16-gene panel test for PGx-guided pharmacotherapy. Experimental Approach: Observational cohort study of subjects tested with a PGx panel for variants of ABCB1, COMT, CYP1A2, CYP2B6, CYP3A4, CYP3A5, CYP2C9, CYP2C19, CYP2D6, CYP4F2, DPYD, OPRM1, POR, SLCO1B1, TPMT and VKORC1. Specialized clinical pharmacology consultations with PGx-guided pharmacotherapy management were supported by the PGx expert system SONOGEN XP. Study outcomes were PGx-based changes and recommendations regarding current and potential future medication. Key Results: PGx-testing was triggered by specific drug-gene pairs in 102 subjects, whereas screening was performed in 33. Based on PHARMGKB expert guidelines the 16-gene panel identified at least one “actionable” variant relevant for current or potential future medication in all 135 (100%) tested patients. Drugs that triggered PGx-testing were clopidogrel in 60, tamoxifen in 15, polypsychopharmacotherapy in 9, opioids in 7, and other in 11 patients. Among those, PGx variants resulted in clinical recommendations to change PGx-triggering drugs in 33 (32.4 %), and other current pharmacotherapy in 23 (22.5%). Conclusion and Implications: The 16-gene PGx panel detected clinically relevant variants in a high proportion of tested patients, and SONOGEN XP supported their interpretation based on latest evidence. Additional costs of panel vs. single gene tests are moderate, and the efficiency of PGx panel testing challenges traditional cost-benefit calculations for single drug-gene pairs. However, PGx-guided pharmacotherapy requires specialized consultations with interdisciplinary collaborations.

AIM To analyse the incidental findings during computed tomographic angiography (CTA) diagnostic work-up in patients with arteriogenic erectile dysfunction (ED). PATIENTS AND METHODS The medical records of all patients with suspected arteriogenic ED were entered into a database. Risk factors and underlying comorbidities were also collected. Pathological CTA findings were extracted from the CT readings and entered into the database. Incidental findings on CTA were classified as those requiring immediate medical treatment, requiring deferred medical treatment or of no clinical importance. RESULTS A total of 200 patients underwent CTA for suspected arteriogenic ED. Mean patient age was 59.6 ± 11.7 years. Of these, 181 patients (90.5%) had obstructions of erection-related arteries. In 168 patients (84.0%), CTA showed multiple incidental pathological findings. Eighty-five of 200 patients (42.5%) exhibited incidental findings requiring immediate further medical workup and/or treatment: coronary artery calcification was diagnosed in 75/200 (37.5%), aorto-iliac aneurysms in 8/200 (4%) of patients and incidentally detected embolism in 1/200 patient. Pancreatic and liver tumours were less frequent (incidence 1.5% and 1%, respectively). Incidental findings requiring deferred medical workup and/or treatment were detected in 175/200 patients (87.5%). The findings with the highest prevalence were liver steatosis followed by colon diverticulosis and prostate hyperplasia. Findings of little to no clinical importance were reported in 117 (58.5%) patients. These included uncomplicated renal cysts, spinal degeneration and renal vascular anomalies. Almost every second patient presenting with ED had an incidental finding which required immediate treatment. CONCLUSIONS Incidental findings not directly related to ED were common among patients undergoing CTA scans for suspected arterial obstructions. Coronary artery calcification was the leading finding requiring further medical workup and/or treatment. Thus, the benefit of CTA investigations extends beyond the anatomic description of arterial obstructions of erection-related arteries.