Lisa M. Chastain

A retrospective study of the lipid-lowering efficacy and safety of ezetimibe added to hydroxy methylglutaryl coenzyme A reductase therapy in HIV-infected patients with hyperlipidemia

BACKGROUND Abnormalities in lipid metabolism are a well-described consequence of human immunodeficiency virus (HIV) infection being treated with highly active antiretroviral therapies (HAART). OBJECTIVE The purpose of this study is to evaluate the lipid-lowering efficacy and safety of ezetimibe added to existing hydroxy methylglutaryl coenzyme A reductase (statin) therapy in HIV-infected patients with hyperlipidemia. METHODS This is a retrospective study utilizing a comprehensive electronic patient registry to identify all adult HIV-infected patients seen at the Dallas Veterans Affairs (VA) Medical Center during a 4-year period from October 1, 2002 through October 1, 2006. RESULTS A total of 26 HIV-infected patients initiated on ezetimibe 10 mg were identified, with 14 adult males meeting strict criteria for inclusion. Median age was 54 years (interquartile range [IQR], 45-59) with a median duration of HIV of 13 years, CD4 count of 513 cells/mm(3) (IQR, 289-736), and 9 of 14 patients had undetectable viral loads at baseline. Initiation of ezetimibe 10 mg resulted in a significant decrease in total cholesterol (TC) from baseline (-12.9%, P = 0.001); low-density lipoprotein cholesterol (LDL-C; -25.7%, P = 0.001); and non-high-density lipoprotein cholesterol (non-HDL-C; -23.9%, P = 0.001). There was also a nonsignificant decrease in triglycerides (15.8%, P = 0.43), and an increase in number of patients achieving National Cholesterol Education Program/Adult Treatment Panel III goal for LDL-C after initiation of ezetimibe (+20.9%, P = 0.125). These improvements occurred without adverse effects or changes in virologic and immunologic control. CONCLUSION Addition of ezetimibe to existing statin therapy in HIV-infected VA patients treated with HAART significantly reduces TC, LDL-C, and non-HDL-C concentrations without apparent side effects or compromising of virologic control.

Ranolazine for the treatment of refractory angina in a veterans population.

BACKGROUND Pivotal ranolazine trials did not require optimization of conventional medical therapy including coronary revascularization and antianginal drug therapy prior to ranolazine use. This case series describes the use of ranolazine for the treatment of chronic stable angina refractory to maximal medical treatment in a veterans population. RESULTS A total of 18 patients with a median age of 66 years were identified. All patients had prior percutaneous coronary intervention and/or coronary artery bypass graft surgery; 83% had three-vessel coronary artery disease, with left main disease present in 39% of patients. Prior to initiating ranolazine, antianginal use consisted of beta blockers (94%), long-acting nitrates (83%) and calcium channel blockers (61%). Median blood pressure (116.2/61.8 mmHg) and pulse (65 beats per min) were controlled. Median preranolazine angina episodes and sublingual nitroglycerin (SLNTG) doses per week were 14 and 10, respectively, with a Canadian Cardiovascular Society (CCS) angina grade of III-IV in 67% of patients. After initiation of ranolazine, median angina episodes per week and SLNTG doses used per week decreased to 0.7 and 0, respectively, with CCS grade of III-IV declining to 17%. Of the 18 subjects enrolled, 44% had complete resolution of angina episodes. CONCLUSION The addition of ranolazine to maximally tolerated conventional antianginal drug therapy post coronary revascularization was associated with decreases in angina episodes and SLNTG utilization and improvement in CCS angina grades. Ranolazine may provide an effective treatment option for revascularized patients with refractory angina.

Combination thiazolidinedione and fibrate effect on high-density lipoprotein cholesterol (HDL-C) concentration in a Veterans Affairs patient population

BACKGROUND Type 2 diabetes mellitus (T2DM) is a coronary heart disease (CHD) risk equivalent warranting aggressive management of dyslipidemia and tight glycemic control. Recent reports demonstrate a paradoxic decrease in high-density lipoprotein cholesterol (HDL-C) with thiazolidinedione (TZD) and fibrate combination therapy. OBJECTIVE Evaluate change in HDL-C from start of combination therapy to 1 year and assess the proportion, characteristics, and regimens of patients who developed a ≥20% decrease in HDL-C from baseline. METHODS Patients with T2DM treated concurrently with a combination of TZD and fibrate were identified through retrospective query from a Veterans Affairs medical center database. HDL-C was recorded for 1 year after patients started combination therapy. Logistic regression analysis was performed to determine any predictors of HDL-C change. RESULTS A total of 322 patients were included in the analysis. There was no significant differences in mean ± standard deviation HDL-C from baseline to end point (36.8 ± 8.5 to 40.3 ± 11.8 mg/dL; P = 0.097). There was a subset of patients identified (13%; n = 43) on combination therapy who experienced a ≥20% reduction in HDL-C. Of these patients, a decrease in HDL-C was more likely to occur with fenofibrate-based regimens (odds ratio 3.08, 95% confidence interval 1.22 to 7.75; P = 0.018). There was a trend toward more of these patients in this subset to have the combination of rosiglitazone and fenofibrate in their profiles (odds ratio 2.82, 95% confidence interval 0.98 to 8.0; P = 0.064). CONCLUSION Our study demonstrated that a subset of patients with T2DM experienced a paradoxic decrease in HDL-C when taking a fibrate and TZD combination.

Combination therapies in the management of type 2 diabetes: the use of insulin degludec/liraglutide.

The global burden of type 2 diabetes is estimated to currently affect over 350 million people worldwide and is anticipated to continue increasing over the next 20 years. Current treatment guidelines recommend the choice of pharmacotherapy based upon patient-specific parameters, with combination therapy for patients with a hemoglobin A1c level ≥9%. A new combination therapy of insulin degludec + liraglutide provides a long-acting basal insulin with a glucagon-like peptide agonist. In clinical trials, this combination product has reduced hemoglobin A1c and fasting plasma glucose more than the individual agents alone. Further advantages observed with this combination include weight loss and decrease in hypoglycemia compared to basal insulin alone.

Utilizing Clinical Pharmacy Specialists to Address Access to Care Barriers in the Veteran Population for the Management of Diabetes.

Objective: To show that clinical pharmacy specialists (CPSs) can be utilized in remote facilities to provide appropriate diabetes outcomes along with potential cost savings. Methods: A retrospective cohort chart review conducted at the Veterans Affairs North Texas Healthcare System (VANTHCS) evaluated outcomes in patients with type 2 diabetes mellitus referred to CPSs at Fort Worth Outpatient Clinic (FWOPC) or the endocrinologist-managed specialty clinic at the Dallas VA Medical Center (DVAMC). The primary outcome was percentage of patients reaching hemoglobin A1c (HbA1c) goal of <8%. Secondary outcomes were percentage of patients reaching HbA1c <7%, time to reach HbA1c goals of <8% and <7%, and cost savings. Results: There was no statistically significant difference in the number of patients reaching HbA1c goal <8% in the FWOPC (65.3%) compared to the DVAMC (55.8%). Secondary end points comparing FWOPC and DVAMC found no difference in patients reaching HbA1c <7% (20.8% vs 19.2%) and time to reach HbA1c goal of <8% (4.5 vs 6 months) and <7% (8.5 vs 7.5 months). Cost-saving analysis demonstrated a composite of US

Weight effects of antidiabetic agents

350 292 could be saved by the VANTHCS facility if patients continued to be referred to CPS. Conclusion: CPSs can be utilized in diabetes management to provide similar health outcomes as the endocrinologist-managed clinic and to potentially allow for facility cost savings.

Pharmacological management of obesity in patients with type 2 diabetes

ABSTRACT Introduction: Obesity and diabetes are on the rise, which remains a continuous health concern worldwide. It is important to consider weight effects of antidiabetic agents prior to initiation as different antidiabetic agents impact weight differently. Areas covered: New agents to treat diabetes, glucagon-like peptide-1 receptor agonists and sodium glucose cotransporter 2 inhibitors, have emerged over recent years that have been shown to result in weight reduction. Unfortunately, other antidiabetic medications used can cause weight gain such as with insulin, sulfonylureas, and thiazolidediones while some remain weight neutral (metformin and dipeptidyl peptidase-4 inhibitors). The weight effects of these antidiabetic medications described are from select relevant guidelines, clinical trials, reviews, and meta-analysis found through PubMed and Ovid databases up to July 2017. Expert commentary: This article summarizes the current evidence available on the weight effects of these agents in patients with diabetes. Evaluating potential risks, such as weight gain, with potential benefits, such as improvement in glycemic control, will help with designing optimal therapeutic diabetes regimens.

Imeglimin: A Potential New Multi-Target Drug for Type 2 Diabetes.

ABSTRACT Introduction: Obesity is a growing health concern worldwide. Multiple guidelines are available to clinicians to help guide treatment of obesity. Areas covered: In their 2016 update, the American Diabetes Association included recommendations for the use of pharmacological agents in the treatment of obesity in patients with concurrent diabetes. Five agents have been approved by the Food and Drug Administration and are recommended by guidelines for the long-term treatment of obesity: orlistat, lorcaserin, phentermine/topiramate ER, naltrexone/bupropion, and liraglutide. Expert commentary: This article summarizes the current evidence available on the use of these agents in patients with diabetes.