Currently, recommendations for treatment are directed at symptom relief and co-morbid conditions. Frequently this involves administration of diuretics to relieve complications associated with volume overload, such as leg swelling and high blood pressure.Commonly encountered conditions that must be treated for and have independent recommendations for standard of care include atrial fibrillation, coronary artery disease, hypertension, and hyperlipidemia. There are particular factors unique to HFpEF that must be accounted for with therapy. Unfortunately, currently available randomized clinical trials addressing the therapeutic adventure for these conditions in HFpEF present conflicting or limited evidence.Specific aspects of therapeutics should be avoided in HFpEF to prevent the deterioration of the condition. Considerations that are generalizable to heart failure include avoidance of a fast heart rate, elevations in blood pressure, development of ischemia, and atrial fibrillation. More specific to HFpEF include avoidance of preload reduction. As patients display normal ejection fraction but reduced cardiac output they are especially sensitive to changes in preloading and may rapidly display signs of output failure. This means administration of diuretics and vasodilators must be monitored carefully.HFrEF and HFpEF represent distinct entities in terms of development and effective therapeutic management. Specifically cardiac resynchronization, administration of beta blockers and angiotensin converting enzyme inhibitors are applied to good effect in HFrEF but are largely ineffective at reducing morbidity and mortality in HFpEF. Many of these therapies are effective in reducing the extent of cardiac dilation and increasing ejection fraction in HFrEF patients.
Vestronidase alfa, sold under brand name Mepsevii, is a drug for the treatment of Sly syndrome. It is a recombinant form of the human enzyme beta-glucuronidase. It was approved in the United States in November 2017, to treat children and adults with an inherited metabolic condition called mucopolysaccharidosis type VII (MPS VII), also known as Sly syndrome. MPS VII is an extremely rare, progressive condition that affects most tissues and organs.The most common side effects after treatment with vestronidase alfa include infusion site reactions, diarrhea, rash (urticaria) and anaphylaxis (sudden, severe allergic reaction).The U.S. Food and Drug Administration (FDA) considers it to be a first-in-class medication. It was approved for use in the European Union in August 2018. Medical uses
Mepsevii is indicated for the treatment of non-neurological manifestations of Mucopolysaccharidosis VII (MPS VII; Sly syndrome). History
The safety and efficacy of vestronidase alfa were established in a clinical trial and expanded access protocols enrolling a total of 23 participants ranging from five months to 25 years of age. Participants received treatment with vestronidase alfa at doses up to 4 mg/kg once every two weeks for up to 164 weeks. Efficacy was primarily assessed via the six-minute walk test in ten participants who could perform the test. After 24 weeks of treatment, the mean difference in distance walked relative to placebo was 18 meters. Additional follow-up for up to 120 weeks suggested continued improvement in three participants and stabilization in the others. Two participants in the vestronidase alfa development program experienced marked improvement in pulmonary function.