SLCO1B1 gene-based clinical decision support reduces statin-associated muscle symptoms risk with simvastatin.

Background: SLCO1B1 variants are known to be a strong predictor of statin-associated muscle symptoms (SAMS) risk with simvastatin. Methods: The authors conducted a retrospective chart review on 20,341 patients who had SLCO1B1 genotyping to quantify the uptake of clinical decision support (CDS) for genetic variants known to impact SAMS risk. Results: A total of 182 patients had 417 CDS alerts generated, and 150 of these patients (82.4%) received pharmacotherapy that did not increase risks for SAMS. Providers were more likely to cancel simvastatin orders in response to CDS alerts if genotyping had been done prior to the first simvastatin prescription than after (94.1% vs 28.5%, respectively; p < 0.001). Conclusion: CDS significantly reduces simvastatin prescribing at doses associated with SAMS.

The Clinical Pharmacogenetics Implementation Consortium Guideline for SLCO1B1, ABCG2, and CYP2C9 genotypes and Statin-Associated Musculoskeletal Symptoms.

Statins reduce cholesterol, prevent cardiovascular disease, and are among the most commonly prescribed medications in the world. Statin-associated musculoskeletal symptoms (SAMS) impact statin adherence and ultimately can impede the long-term effectiveness of statin therapy. There are several identified pharmacogenetic variants that impact statin disposition and adverse events during statin therapy. SLCO1B1 encodes a transporter (SLCO1B1; alternative names include OATP1B1 or OATP-C) that facilitates the hepatic uptake of all statins. ABCG2 encodes an efflux transporter (BCRP) that modulates the absorption and disposition of rosuvastatin. CYP2C9 encodes a phase I drug metabolizing enzyme responsible for the oxidation of some statins. Genetic variation in each of these genes alters systemic exposure to statins (i.e., simvastatin, rosuvastatin, pravastatin, pitavastatin, atorvastatin, fluvastatin, lovastatin), which can increase the risk for SAMS. We summarize the literature supporting these associations and provide therapeutic recommendations for statins based on SLCO1B1, ABCG2, and CYP2C9 genotype with the goal of improving the overall safety, adherence, and effectiveness of statin therapy. This document replaces the 2012 and 2014 Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for SLCO1B1 and simvastatin-induced myopathy.

SLCO1B1*5 Allele Is Associated With Atorvastatin Discontinuation and Adverse Muscle Symptoms in the Context of Routine Care.

The SLCO1B1 genotype is known to influence patient adherence to statin therapy, in part by increasing the risk for statin-associated musculoskeletal symptoms (SAMSs). The SLCO1B1*5 allele has previously been associated with simvastatin discontinuation and SAMSs. Prior analyses of the relationship between SLCO1B1*5 and atorvastatin muscle side effects have been inconclusive due to insufficient power. We now quantify the impact of SLCO1B1*5 on atorvastatin discontinuation and SAMSs in a large observational cohort using electronic medical record data from a single health care system. In our study cohort (n = 1,627 patients exposed to atorvastatin during the course of routine clinical care), 56% (n = 912 of 1,627 patients) discontinued atorvastatin and 18% (n = 303 of 1,627 patients) developed SAMSs. A univariate model revealed that SLCO1B1*5 increased the likelihood that patients would stop atorvastatin during routine care (odds ratio 1.2; 95% confidence interval (CI), 1.1-1.5; P = 0.04). A multivariate Cox proportional hazards model further demonstrated that this same variant was associated with time to atorvastatin discontinuation (hazard ratio 1.2; 95% CI, 1.1-1.4; P = 0.004). Additional time-to-event analyses also revealed that SCLO1B1*5 was associated with SAMSs (hazard ratio 1.4; 95% CI, 1.1-1.7; P = 0.02). Atorvastatin discontinuation was associated with SAMSs (odds ratio 1.67; P = 0.0001) in our cohort.

A Rare Case of Pulmonary Lymphomatoid Granulomatosis.

In this report, we discuss an unusual case of pulmonary lymphomatoid granulomatosis (LYG), a rare form of angiocentric and angiodestructive lymphoproliferative disorder. This disease is thought to be caused by Epstein-Barr virus-induced lymphoproliferation. A 39-year-old male with no signi ficant past medical history presented with flu-like symptoms. Upon further evaluation, laboratory studies noted pancytopenia, and a chest X-ray showed bilateral nodular densities. A computerized tomography (CT) scan demonstrated bilateral pulmonary nodules and splenomegaly. A biopsy of the pulmonary nodules revealed polymorphous, CD3-positive, lymphohistiocytic, inflammatory in filtrate within the walls of the arterioles and venules with associated necrosis. This histopathology is consistent with LYG. The patient was started on a regimen of rituximab, and he signi ficantly improved within a few weeks after the initiation of therapy, including resolution of the pancytopenia. A repeat CT scan showed the decreased size of the lung nodules. This case was histopathologically consistent with LYG but negative for Epstein-Barr virus ribonucleic acid. This demonstrates the potential for diagnostic difficulty in a case presentation of multiple pulmonary nodules. Extensive work-up for neoplastic, infectious, inflammatory, and autoimmune etiologies needs to be done in such cases. A prompt diagnosis of LYG is necessary for optimal management and improved patient outcomes.