Krystal L. Edwards

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.

Insulin Glargine and Cancer Risk: An Opinion Statement of the Endocrine and Metabolism Practice and Research Network of the American College of Clinical Pharmacy

Diabetes mellitus has reached epidemic proportions worldwide, eliciting extensive research on both the disease process and its treatment. Regardless of diabetes type, the progressive nature of the disease makes insulin the long‐term mainstay of diabetes management. Recently, the insulin analog glargine was reported in several epidemiologic studies to be associated with an increased risk of cancer. Inconsistent study results and media attention have caused much angst and concern to health care professionals and the general population. A clear understanding of the current evidence is needed to adequately develop a patient‐oriented risk:benefit assessment. Members of the Endocrine and Metabolism Practice and Research Network of the American College of Clinical Pharmacy evaluated available evidence to provide guidance and discussion on the risk of cancer with insulin glargine use. We believe the current link between insulin glargine and cancer is tenuous but merits further evaluation. An independent analysis of all available glargine clinical trial data should be performed, and a vigorous postmarketing safety study of glargine should be conducted. Until more substantial data are available, however, neither the choice of initial insulin therapy nor insulin maintenance regimens should be influenced by the current information linking insulin glargine to cancer.

An Update in Incretin-Based Therapy: A Focus on Dipeptidyl Peptidase - 4 Inhibitors

Dipeptidyl peptidase -4 inhibitors represent a novel way to augment the incretin system and one of the newest class of medications in the treatment of type 2 diabetes mellitus. Their mechanism of action is to decrease the inactivation of glucagon-like peptide 1 and glucose-dependent insulinotropic polypeptide, both of which are involved in maintaining euglycemia subsequent to carbohydrate intake. Currently investigated agents include sitagliptin, vildagliptin, saxagliptin, linagliptin, and alogliptin. Each agent has been shown to provide significant improvements in glycemic control compared to placebo. They are effective when added to other oral diabetes agents and in the cases of sitagliptin, vildagliptin, and alogliptin in addition to insulin. These agents may not provide as significant improvement in glucose concentrations as some other medications including metformin, thiazolidinediones, or glucagon-like peptide 1 agonists. The lack of head to head clinical data comparing the various dipeptidyl peptidase 4 inhibitors does not allow for specific recommendations if one agent is more effective or safer than another within the class. Their side effect profile suggests they are very well tolerated and have few drug interactions. For patients with mildly elevated glucose concentrations, they are therapeutic options in both drug-naive patients as well as those not optimally controlled on other diabetes medications.

Evaluation of thiazide diuretic use as preferred therapy in uncomplicated essential hypertension patients

Thiazide diuretics are effective antihypertensive medications shown to reduce the risk of cardiovascular events and stroke. Despite being the preferred choice for uncomplicated essential hypertension, thiazide diuretics continue to be underutilized. Methods Uncomplicated essential hypertension patients taking a single antihypertensive medication were evaluated upon enrollment, diagnosis after enrollment or initiation of therapy in treatment naïve patients. Clinician prescribing habits were determined for both pre-existing and newly diagnosed hypertensive patients. For the cost savings analysis, hydrochlorothiazide (HCTZ) 25mg daily was selected as the preferred conversion medication. Results Four hundred seventy-eight patients were included. ACE inhibitors were the most prescribed at 35.4% (n=169), followed by dihydropyridine calcium channel blockers (DHP CCB) and thiazide diuretics, both at 20.3% (n=97). Only 12.9% (n=33) of patients with hypertension that were taking an antihypertensive medication upon enrollment were either continued or started on thiazide diuretic therapy. Newly diagnosed or treatment naïve patients were prescribed a thiazide diuretic 28.8% (n=64) of the time. DHP CCB accounted for 58.8% of the total medication cost per month with thiazide diuretics responsible for 0.8% of the cost. If all patients had been prescribed HCTZ 25mg daily, 95.8% of the total medication cost per month could have been saved. Conclusions Thiazide diuretics were underutilized as preferred therapy in patients with pre-existing or newly diagnosed uncomplicated essential hypertension. While cost of therapy should not be the sole reason for medication selection, thiazide diuretics are an attractive option and should be considered as a preferred therapy in this patient population.

Race as a Factor for Intensification of Diabetes Medications

Purpose The purpose of this study was to investigate if patients of nonwhite race are less likely to receive insulin therapy for treatment of poorly controlled diabetes than patients of white race. Methods A retrospective review was performed of patients with an A1C >10%. The primary objective was to determine any difference in the initiation of insulin between white and nonwhite patients. Secondary outcomes measured the impact of clinic type and provider specialty on the initiation of insulin therapy. Exclusion criteria included those patients with type 1 diabetes mellitus, those who were previously receiving insulin, and those without an outpatient clinic visit within 14 days of an A1C >10%. Results A total of 277 patients were included. Of these patients, 132 (47.7%) were white, followed by 95 (34.2%) black non-Hispanic patients and 30 (10.8%) Hispanic/Latino patients. No difference was found in receipt of insulin therapy for nonwhite patients as compared to white patients (12.5 vs 21.4, P = .117). Neither clinic type nor provider specialty impacted initiation of insulin therapy. No changes to medication regimen were made at 35% of clinic visits. Conclusions Failure to intensify diabetic medications was common in this outpatient setting. There were no disparities in the receipt of insulin therapy between white and nonwhite patients.

Provider Decisions and Patient Outcomes After Premature Metformin Discontinuation

The purpose of this study was to evaluate the effects of alternative antihyperglycemic therapy after discontinuation of metformin due to documented declining renal function. This retrospective, single-site study evaluated patients who had metformin discontinued between 1 January 1999 and 30 September 2013. Medical records were evaluated for documented adverse events, subsequent glycemic control, and costs associated with the alternative therapy. Patients served as their own controls. A total of 179 patients met study entry criteria, and their peak A1C was significantly higher within the year after metformin discontinuation (P <0.001). After the provider added new medications to control patients’ blood glucose, their A1C by the end of the first year after discontinuing metformin was similar to their A1C while taking metformin. Significant weight gain accompanied the use of the medications added to replace metformin, with an average increase of 3.81 kg (P <0.001). Additionally, after discontinuing metformin, more patients experienced hypoglycemia with the addition of other medications to control their blood glucose (P <0.001). As expected, the cost of therapy was significantly higher (P <0.0001) after metformin was discontinued because metformin was generically available, whereas the replacement medications frequently were not. Providers should consider the expanded recommendations for the use of metformin in patients with mild to moderate stable renal dysfunction to help such patients avoid weight gain, hypoglycemia, loss of blood glucose control, and increased costs.

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.

An Evidence-Based Review of Statin Use in Patients With Nonalcoholic Fatty Liver Disease

Background: Nonalcoholic fatty liver disease (NAFLD) is a common complication in patients with metabolic syndrome. The role of statin therapy specifically for the treatment of NAFLD remains unknown. The aim of this review is to discuss outcomes of recent articles analyzing statin therapy in patients with NAFLD. Findings: A total of 12 trials met the inclusion criteria. Statins were not found to increase the prevalence of NAFLD once confounding variables were considered. Statins were also found to be beneficial in treating dyslipidemia and improving liver function. Histological liver outcomes in patients with NAFLD were controversial. One trial found a reduction in the incidence of hepatocellular carcinoma associated with the use of statins. Conclusions: Overall, therapy with statins appears to be safe for use in patients with NAFLD. Several trials have validated the use of statins for the treatment of dyslipidemia; however, it remains unknown as to whether statins should be used to specifically treat NAFLD.

Sodium-glucose co-transporter 2 inhibitors: evidence and place in therapy

Type 2 diabetes effects millions of people yet remains difficult to treat with oral pharmacotherapy. Metformin is the first line recommended therapy, and current guidelines suggest individualized therapy for second line selection. Sodium-glucose co-transporter 2 (SGLT-2) inhibitors are the newest class of agents in treating type 2 diabetes via an insulin independent mechanism to lower blood glucose. Currently marketed agents, including canagliflozin, dapagliflozin, empagliflozin, and luseogliflozin, reduce hemoglobin A1c (HbA1c) ~0.8–1%, reduce fasting and post prandial glucose, and have little hypoglycemia associated with them when added to therapies including metformin, a sulfonylurea, pioglitazone, or insulin. Patients receiving SGLT-2 inhibitors have reduced weight and blood pressure, but are more susceptible to urinary tract infections and genital mycotic infections. This review summarizes current literature regarding the SGLT-2 inhibitors.