The goal of this study was to assess the safety and tolerability of omecamtiv mecarbil treatment during symptom-limited exercise in patients with ischemic cardiomyopathy and angina. These patients may have increased vulnerability to prolongation of the systolic ejection time.
Omecamtiv mecarbil is a selective cardiac myosin activator that augments cardiac contractility in patients with systolic heart failure through a dose-dependent increase in systolic ejection time.
In this double-blind, placebo-controlled study, patients with chronic heart failure were randomized 2:1 to receive omecamtiv mecarbil or placebo in 2 sequential cohorts of escalating doses designed to achieve plasma concentrations previously shown to increase systolic function. Patients underwent 2 symptom-limited exercise treadmill tests (ETTs) at baseline (ETT1 and ETT2) and again before the end of a 20-h infusion of omecamtiv mecarbil (ETT3).
The primary pre-defined safety endpoint (i.e., the proportion of patients who stopped ETT3 because of angina at a stage earlier than baseline) was observed in 1 patient receiving placebo and none receiving omecamtiv mecarbil. No dose-dependent differences emerged in the proportion of patients stopping ETT3 for any reason or in the pattern of adverse events.
Doses of omecamtiv mecarbil producing plasma concentrations previously shown to increase systolic function were well tolerated during exercise in these study patients with ischemic cardiomyopathy and angina. There was no indication that treatment increased the likelihood of myocardial ischemia in this high-risk population. (Pharmacokinetics [PK] and Tolerability of Intravenous [IV] and Oral CK-1827452 in Patients With Ischemic Cardiomyopathy and Angina; NCT00682565).
Tooth-whitening using carbamide peroxide delivered in a custom-fitted tray (nightguard bleaching) is a relatively new procedure, yet it is currently one of the most commonly used types of esthetic dental treatment in private practice. This study determined the extent that nightguard bleaching (NGB) has been included in dental school curricula. All sixty-five dental schools in North America were surveyed about curriculum content and treatment protocol for the use of nightguard and other bleaching procedures, generating an 82 percent response. The survey covered eighteen subject areas related to NGB ranging from clinical requirements and indications to products and recall intervals used. The most commonly taught tooth-whitening procedure was NGB, which was most often taught by operative and restorative faculty. Although no schools had clinical requirements for NGB, 92 percent taught it. The most common indications for NGB were esthetic shade change and pre-restorative lightening of teeth. Unrestored caries, defective restorations, and pre-existing sensitivity were common contraindications. Most schools do not use a specific NGB consent form, but most use written patient instructions. Most schools use at least two different NGB products, bleach for two to four weeks, and use reservoired and scalloped trays. An average of 25 percent of NGB patients were estimated to develop sensitivity, for which treatment recommendations include fluoride, desensitizing toothpaste, and reduced exposure time. Curriculum time and safety concerns were reasons for not teaching NGB (8 percent schools). Most schools indicated that the relative importance of NGB in the curriculum was increasing.