43. Jahrgang Heft 07, Juli 2020

Mitochondrial Diseases

Mitochondial diseases are a heterogenous group of syndroms. Their common ground is a dysfunction of mitochondria. The prevalance of mitochondrial diseases (MD) is estimated at about 1 : 5000. Thus MD rank among the most common hereditary neurological diseases. Defects in mitochondrial as well as nuclear DNA can be the etiological cause of MD. Characteristic symptoms are myopathy or myalgia, external ophthalmoplegia, migraine, epilepsy, polyneuropathy, diabetes and involvement of heart or internal ear. Until recently therapeutic options were limited to symptomatic therapy and supplementation of various co-factors of the mitochondrial metabolism. At the present though there are several new promising therapeutic options (e.g. gene therapy) in development.

ACL inhibition with bempedoic acid – a new therapeutic approach for lipid lowering

Bempedoic acid is a once-daily, oral therapy that can significantly reduce LDL-C levels, when added to other lipid-lowering therapies in patients with primary hyperlipidemia. Bempedoic acid is a prodrug that is converted to its active moiety primarily in the liver. This active form inhibits adenosine triphosphate citrate lyase (ACL), an enzyme of the cholesterol biosynthesis pathway, two steps upstream from HMG-CoA reductase. The reduction of cholesterol synthesis results in LDL receptor upregulation and increased clearance of LDL cholesterol from the bloodstream. Bempedoic acid has been investigated in the large phase 3 clinical development program CLEAR, alone, as add-on to statins and in a fixed-dose combination with ezetimibe. Bempedoic acid was studied in approximately 4,000 patients with atherosclerotic cardiovascular disease (ASCVD), or who are at a high risk for ASCVD, and hypercholesterolemia, who continue to have elevated levels of LDL-C despite taking maximally-tolerated statins. In all these studies, bempedoic acid reduced the LDL-C-levels significant more effective than placebo or the lipid-lowering therapy. Bempedoic acid was well tolerated, with no severe adverse advents. In addition, a cardiovascular outcomes trial was designed to assess the effects of bempedoic acid on the occurrence of major cardiovascular events in patients with – or at high risk for – cardiovascular disease (CVD), and who are only able to tolerate less than the lowest approved daily starting dose of a statin.

Medication review for a patient with CTEPH

This case study reports on a 67-year-old patient with progressive chronic thromboembolic pulmonary hypertension (CTEPH) and various comorbid conditions (e.g. type 2 diabetes, arterial hypertension and COPD). He suffered from severe dyspnoea when initially admitted to the hospital in order to adjust his medication for CTEPH. His medication plan was examined according to the SOAP scheme. The analysis revealed several drug-related problems. With respect to the medication for CTEPH, the patient was treated according to the currently valid guideline, except for insufficient dosing of riociguat as a result of miscommunication. Furthermore, elevated blood glucose levels, (dark) discoloured spots on his legs and the patient’s poor adherence to his insulin therapy indicated the need of optimizing his medication for diabetes. The status of the antihypertensive therapy could not be fully evaluated due to an incomplete documentation of the blood pressure values and therapy alterations. As riociguat not only lowers the blood pressure in pulmonary arterioles but also in the entire body circulation, the patient’s antihypertensive medication needs to be adjusted when the dosage of riociguat is increased. In conclusion, this case report emphasizes the importance of seamless communication and thorough documentation for the transition of in- to outpatient-care. Moreover, regular pharmacist-led medication reviews can facilitate closing safety and supply gaps. Proper exchange and communication between pharmacists and other healthcare professionals can reduce the physicians' workload and improve the patients' situation by interprofessional collaboration, especially for those patients receiving polymedication.