Entresto

The two groups of patients were evaluated after enrollment and received general treatments such as oxygen inhalation and rest. Conventional antiheart failure drugs were treated for more than two weeks. The control group received basic pharmacological treatments including Diovan, β-blockers, CCB, nitrate drugs, antiplatelet drugs, etc. In the treatment group, 50 mg sacubitril and valsartan sodium tablets were added to β-blockers, CCB, nitrate drugs, and antiplatelet drugs (Entresto: 50 mg/tablet, manufacturer: Novartis Pharma Stein AG) orally, twice a day. All patients were evaluated after ten weeks of treatment. These are two drugs with different mechanisms of action and the efficacy after the combination is superior to either alone and does not occur.

Patients were allowed a light breakfast at the day of each infusion. [¹⁷⁷Lu]Lu-PP-F11N was produced as previously described [3 (link)]. Each patient received two short infusions (4 min) of 1.08 ± 0.05 GBq (70.3 ± 7.3 µg) [¹⁷⁷Lu]Lu-PP-F11N (mean ± SD) in an interval of 28.9 ± 2.5 days with and without Entresto^® (Novartis Pharma Schweiz AG, Rotkreuz, Switzerland) premedication in a randomized cross-over order. Entresto^® was given at an oral dose of 100 mg, containing 48.6 mg sacubitril and 51.4 mg valsartan 2 h before the start of one of the two infusions. Vital signs were recorded, and a 12-lead electrocardiogram was obtained before and after each injection. Adverse events were recorded and graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.

To determine the optimal dose of SV to be used in MMVD dogs, we studied SV pharmacodynamics through blood pressure (BP), heart rate (HR), and myocardial oxygen consumption (MVO₂) inferred from the rate pressure product (RPP). Beagle dogs with MMVD stage B1 (n = 2) and stage B2 (n = 2) were randomized to receive a single oral dose of either placebo (lactose powder packed in a capsule) or SV (5, 10, or 20 mg/kg; Entresto, Novartis Pharmaceuticals, Basel, Switzerland) with a Latin square design. The SV doses were based on the drug composition of SV in the tablets and the dose of valsartan used in dogs (16 (link)). On the experimental day, dogs were allowed to become acclimatized to the clinical environment for at least 15 min. Dogs were gently restrained in right lateral recumbency. At baseline and after dosing, the arterial BP and HR were recorded using an oscillometric device (petMAP, CardioCommand, Inc., Tampa, FL, U.S.A.) placed at the left forelimb upon the median artery between the elbow and the carpal pad. All parameters were obtained hourly at baseline (before dosing), 1–6, 12, and 24 h after dosing. Five consecutive measurements of BP and HR were obtained at each timepoint and the mean of three consistent BP and HR was used as an average of those parameters (17 (link)). Due to its short elimination half-life, the washout period between each treatment was 7 d.