Premature Ticagrelor Discontinuation in Secondary Prevention of Atherosclerotic CVD: JACC Review Topic of the Week

Ticagrelor is a cornerstone of modern antithrombotic therapy alongside aspirin in patients with acute coronary syndrome and after percutaneous coronary intervention. Adverse effects such as bleeding and dyspnea have been associated with premature ticagrelor discontinuation, which may limit any potential advantage of ticagrelor over clopidogrel. The randomized trials of ticagrelor captured adverse events, offering the opportunity to more precisely quantify these effects across studies. Therefore, a meta-analysis of 4 randomized clinical trials of ticagrelor conducted between January 2007 and June 2017 was performed to quantify the incidence and causes of premature ticagrelor discontinuation. Among 66,870 patients followed for a median 18 months, premature ticagrelor discontinuation was seen in 25%; bleeding was the most common cause of discontinuation followed by dyspnea. Versus the comparators, the relative risk of dyspnea-related discontinuation during follow-up was 6.4-fold higher, the relative risk of bleeding was 3.2-fold higher, and the relative risk of discontinuation due to any adverse event was 59% higher for patients receiving ticagrelor. Understanding these potential barriers to adherence to ticagrelor is crucial for informed patient-physician decision making and can inform future efforts to improve ticagrelor adherence. This review discusses the incidence, causes, and biological mechanisms of ticagrelor-related adverse effects and offers strategies to improve adherence to ticagrelor.     

Investigation of the phenylalanine hydroxylase gene and tardive dyskinesia.

Phenylketonuria (PKU), an inborn error of phenylalanine metabolism, has been shown to be a risk factor for tardive dyskinesia (TD). In male psychiatric patients there was a significant relationship between TD and measures of plasma phenylalanine following ingestion of a standardized phenylalanine dose that was indicative of higher brain availability of phenylalanine in patients with TD. In addition, a medical food formulation consisting of branched chain amino acids, which compete with phenylalanine for transport across the blood-brain barrier, has been demonstrated to be an efficacious treatment for TD. Cumulatively these findings suggested that TD was related to phenylalanine metabolism and thus that sequence variants in the gene for phenylalanine hydroxylase (PAH), the rate-limiting enzyme in the catabolism of phenylalanine, could be associated with TD susceptibility. Genetic screening of PAH in a group of 123 psychiatric patients revealed ten sequence polymorphisms and two mutations, but none appeared to be a significant risk factor for TD.     

Introducing dental students to clinical patient care: The complete denture prosthodontics transition clinic

Using complete denture treatment as an introduction to clinical patient care for dental students, the purposes of the Complete Denture Prosthodontics Transition Clinic at the University of Colorado School of Dentistry are to reduce the time lapse between the preclinical complete denture prosthodontics course and the first denture patient experience, and to encourage development of student self-confidence and skills. In the 2002 spring semester, faculty at the University of Colorado School of Dentistry initiated the Complete Denture Prosthodontics Transition Clinic for DS-II (second-year) dental students, as an introduction to clinical patient care. Each patient was assigned to a team of two dental students. Three Division of Prosthodontics faculty members staffed each clinic session, providing a student-to-faculty ratio of approximately 6.6:1 and a patient-to-faculty ratio of approximately 3.3:1. All DS-II students in the Class of 2004 delivered their first complete dentures no later than 8 months (average, 184 days) after the last day of the preclinical complete denture prosthodontics course. The time from the diagnostic appointment through the denture placement appointment averaged 39 days for patients treated in this program, compared with an average of 98 days or more for previous classes. The program was successful in achieving the goal of reducing the time lapse between the preclinical complete denture prosthodontics course and the first denture patient experience.