Inclisiran: A First-in-Class siRNA Therapy for Lowering Low-Density Lipoprotein Cholesterol.

OBJECTIVE: To review the current pharmacology, pharmacokinetics/pharmacodynamics, safety, and efficacy of inclisiran in lowering lipid levels. DATA SOURCES: A PubMed (from December 1, 2014 to April 15, 2022) and ClinicalTrials.gov search was conducted using ALN-PCSsc, ALN-60212, PCSK9si KJX-839, and inclisiran. Additional articles were identified by hand from references. STUDY SELECTION AND DATA EXTRACTION: We included English-language articles evaluating inclisiran pharmacology, efficacy, or safety in humans for lowering low-density lipoprotein cholesterol (LDL-C). DATA SYNTHESIS: Inclisiran is a novel small interfering RNA-based therapy administered as a twice-yearly subcutaneous injection. By binding to the messenger RNA (mRNA) precursor of proprotein convertase subtilisin/kexin type 9 (PCSK9), inclisiran inhibits expression of the PCSK9 gene, resulting in increased recycling and expression of LDL receptors and decreased levels of LDL-C. Like PCSK9 inhibitors, inclisiran was associated with a comparable extent of LDL-C reduction in several phase II/III trials. Compared with placebo, inclisiran was found to have similar adverse events except for injection-site reaction. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Currently, inclisiran lacks data on clinical outcome improvement or long-term safety. However, it may play a role in patients with atherosclerotic cardiovascular disease (ASCVD) or ASCVD risk equivalent if optimal LDL-C cannot be achieved by statins and PCSK9 inhibitors cannot be tolerated. The drug may be used for heterozygous familial hypercholesterolemia. CONCLUSION: Inclisiran is an effective and safe medication for lowering LDL-C levels. Additional data regarding efficacy on cardiovascular outcomes and long-term safety profile with inclisiran are needed.

Implementation of general medicine topics for acute care inpatient advanced pharmacy practice experiences.

INTRODUCTION: The purpose of this study was to describe the development of a general medicine student workbook to standardize acute care inpatient fourth-year pharmacy rotations among faculty with varied pharmacy practice sites. METHODS: Four faculty designed an advanced pharmacy practice experience (APPE) student workbook on general medicine topics consisting of short answer and multiple-choice questions to ensure standardization by exposing all students to the same topics. A pre- and posttest was administered on the first and last day of the five-week rotation block to evaluate the effects of the APPE workbook on student understanding of general medicine topics. A paired t-test was used to evaluate the significance of the difference in test scores. RESULTS: The average of the posttest exam was found to be significantly higher after the completion of the student workbook. The average grade on the pre-rotation 30-item exam was 22.8 (76.73%) and the post-rotation 30-item exam was 25.7 (86.26%), with a difference of 9.53% (P < .001, 95% CI = 7.11 to 11.96). CONCLUSIONS: Creating a standardized student workbook for an inpatient acute care rotation was a valuable addition. All students assigned to the faculty involved were exposed to the same topics despite variability in preceptors and practice sites. Overall the verbal feedback from the students was positive about the student workbook and discussions, especially since the information was applicable to their patients on rotation. Faculty will continue to use this workbook as a tool to teach various inpatient general medicine topics during the acute care APPE.

Bempedoic Acid: A First-in-Class Agent for Lowering Cholesterol Levels.

Despite statin therapy being the cornerstone for the treatment of hypercholesterolemia, a significant number of patients do not tolerate statin therapy because of muscle-related adverse effects or cannot achieve their individual low-density lipoproteincholesterol (LDL-C) goals with statin therapy alone. Several nonstatin agents have been evaluated for the management of LDL-C levels and reduction of cardiovascular (CV) risk in these patients, but there are some limitations with their use. Bempedoic acid is a novel nonstatin agent for the management of lipid disorders, via the inhibition of adenosine triphosphate citrate lyase (ACL). It was recently approved by the US Food and Drug Administration based on several phase III trials which showed promising results regarding safety and efficacy. Though CV outcome data are not available yet, bempedoic acid may be a useful adjunct therapy for select patients. The purpose of this review is to evaluate the major findings in these clinical trials and discuss the potential role of bempedoic acid in clinical practice and its use in older people.

Quinolone Allergy.

Quinolones are the second most common antibiotic class associated with drug-induced allergic reactions, but data on quinolone allergy are scarce. This review article discusses the available evidence on quinolone allergy, including prevalence, risk factors, diagnosis, clinical manifestations, cross-reactivity, and management of allergic reactions. Although the incidence of quinolone allergy is still lower than beta-lactams, it has been increasingly reported in recent decades, most likely from its expanded use and the introduction of moxifloxacin. Thorough patient history remains essential in the evaluation of quinolone allergy. Many diagnostic tools have been investigated, but skin tests can yield false-positive results and in vitro tests have not been validated. The drug provocation test is considered the test of choice to confirm a quinolone allergy but is not without risk. Evidence regarding cross-reactivity among the quinolones is limited and conflicting. Quinolone allergy can be manifested either as an immediate or delayed reaction, but is not uniform across the class, with moxifloxacin posing the highest risk of anaphylaxis. Quinolone should be discontinued when an allergic reaction occurs and avoided in future scenarios, but desensitization may be warranted if no alternatives are available.