The Role of Antisense Therapies Targeting Lipoprotein(a).

ABSTRACT: Atherosclerotic cardiovascular disease (ASCVD) continues to be the leading cause of preventable death in the United States. Elevated low-density lipoprotein cholesterol (LDL-C) is well known to result in cardiovascular disease. Mainstay therapy for reducing LDL-C and ASCVD risk is statin therapy. Despite achieving desired LDL-C levels with lipid-lowering therapy, cardiovascular residual risk often persists. Elevated lipoprotein(a) [Lp(a)] levels have been highlighted as an inherent independent predictor of ASCVD, and decreasing Lp(a) levels may result in a significant reduction in the residual risk in high-risk patients. To date, there are no approved medications to lower Lp(a) levels. Nicotinic acid, proprotein convertase subtilisin/kexin 9 inhibitors, and antisense oligonucleotide have demonstrated modest to potent Lp(a) reduction. Spotlight has been placed on antisense oligonucleotides and their role in Lp(a) lowering. APO(a)LRx is in the frontline for selectively decreasing Lp(a) concentrations and ongoing research may prove that this medication may lower Lp(a)-mediated residual risk, translating into cardiovascular benefit.

Pharmacists' Utilization of Non-HDL-C Levels in Managing Patients With Lipid Disorders.

Background: Since 2013 there have been cholesterol guideline changes impacting pharmacists' clinical practice in managing lipid disorders. For more than a decade, cholesterol management was based on the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol Adult Treatment Panel III guideline, highlighting non-high-density lipoprotein cholesterol (non-HDL-C) as a secondary target in persons with triglycerides ≥200 mg/dL, after low-density lipoprotein cholesterol goal attainment. The 2013 American College of Cardiology and American Heart Association (ACC/AHA) guideline differed from the traditional management of dyslipidemia, in part no longer emphasizing the utilization of non-HDL-C levels. Objective: To measure pharmacists' attitudes and behavior regarding utilization of non-HDL-C level calculation before and after the inception of the 2013 ACC/AHA cholesterol guideline. Methods: Pharmacists in the American College of Clinical Pharmacy ambulatory care listserv participated in an electronic survey in November 2013, before the inception of the 2013 ACC/AHA guideline, and again in October 2018. Results: We collected 391 usable responses from participants; 212 responses in 2013 and 179 responses in 2018. The before and after comparison revealed that respondents in 2013 reported significantly higher frequency of calculating non-HDL-C levels (mean = 1.88, SD = 0.80) than respondents in 2018 (mean = 1.66, SD = 0.79) (P ≤ .001). Also, the frequency that non-HDL-C level calculation alters decisions regarding course of treatment was lower in the 2018 (mean = 3.50, SD = 1.06) in comparison with 2013 (mean = 3.77, SD = 0.88) (P ≤ .05). Furthermore, pharmacists were more favorable toward the inclusion of non-HDL-C level calculation in 2018 (mean = 3.77, SD = 1.05) than in 2013 (mean = 3.13, SD = 1.33) (P ≤ .001). Conclusion and Relevance: Clinical pharmacists' utilization of non-HDL-C levels in the clinical management of patients with hypercholesterolemia has decreased, highlighting the need for further education on the importance of evaluating non-HDL-C levels in the very high-risk atherosclerotic cardiovascular disease population.

Impact of Pharmacy Student-Driven Postdischarge Telephone Calls on Heart Failure Hospital Readmission Rates: A Pilot Program.

Background: Heart failure (HF) hospitalization rates have remained high in the past 10 years. Numerous studies have shown significant improvement in HF readmission rates when pharmacists or pharmacy residents conduct postdischarge telephone calls. Objective: The purpose of this retrospective review of a pilot program was to evaluate the impact of pharmacy student-driven postdischarge phone calls on 30- and 90-day hospital readmission rates in patients recently discharged with HF. Methods: A retrospective manual chart review was conducted for all patients who received a telephone call from the pharmacy students. The primary endpoint compared historical readmissions, 30 and 90 days prior to hospital discharge, with 30 and 90 days post discharge readmissions. For the secondary endpoints, historical and postdischarge 30-day and 90-day readmission rates were compared for patients with a primary diagnosis of HF and for patients with a secondary diagnosis of HF. Descriptive statistics were calculated in the form of means and standard deviations for continuous variables and frequencies and percentages for categorical variables. Results: Statistically significant decrease was observed for both the 30-day (P = .006) and 90-day (P = .007) readmission periods. Prior to the pharmacy students' phone calls, the overall group of 131 patients had historical readmission rates of 24.43% within 30 days and 38.17% within 90 days after hospital discharge. After the postdischarge phone calls, the readmission rates decreased to 11.45%, for 30 days, and 22.90%, for 90 days. Conclusion: Postdischarge phone calls, specifically made by pharmacy students, demonstrated a positive impact on reducing HF-associated hospital readmissions, adding to the growing body of evidence of different methods of pharmacy interventions and highlighting the clinical impact pharmacy students may have in transition of care services.

Women Versus Men: Is There Equal Benefit and Safety from Statins?

Coronary heart disease (CHD) is the leading cause of death in the United States. CHD risk differs between genders, with coronary events lagging behind ten years for women in comparison to men. Low-density lipoprotein cholesterol lowering with statin therapy is a major target for cardiovascular risk reduction. The benefit of statin therapy has been well established in men, for both primary and secondary prevention. However, the same has not been shown for women. While studies have demonstrated benefit in women for secondary prevention, their role in primary prevention of cardiovascular disease remains controversial. Data released over the past several years regarding statin efficacy and safety in men and women has been inconsistent, given that these studies had small sample sizes with numerous study limitations. A recent large scale meta-analysis of both primary and secondary statin prevention trials with sex-specific outcomes demonstrated a similar benefit in both men and women. Statins demonstrated a decrease in cardiovascular events and all-cause mortality in both sexes. In regards to statin safety, additional trials investigating the difference in adverse events of statins in men versus women, particularly new onset of diabetes, myalgias, and liver dysfunction, are warranted. Increased awareness and monitoring of female patients for myalgias and hyperglycemia should be considered as a precaution. Overall, women need to be better represented in prospective clinical trials powered to evaluate gender-specific differences in statin safety and efficacy in the management of cardiovascular disease.

Reinitiating aspirin therapy for primary prevention of cardiovascular events in a patient post-aspirin-induced upper gastrointestinal bleed: a case report and review of literature.

OBJECTIVE: To describe a case of continued aspirin use for primary prevention of a cardiovascular event in a patient post-aspirin-induced upper gastrointestinal (GI) bleed and evaluate published evidence to determine whether reinitiating aspirin therapy for this patient was appropriate. CASE SUMMARY: A 65-year-old man had been taking chronic low-dose (81 mg/day) aspirin therapy since 2002 for primary prevention of a cardiovascular event. He developed an upper GI bleed with lowered hemoglobin (9 mg/dL) and hematocrit (26.3%) after concomitantly taking 2 doses of naproxen (220 mg each). An objective causality assessment with the Naranjo probability scale revealed a probable adverse reaction of an upper GI bleed associated with concomitant naproxen and aspirin use. No further naproxen was taken. Aspirin was discontinued and pantoprazole was started, with resolution of the bleeding. Aspirin was restarted 2.5 months after pantoprazole was initiated, and no further bleeding occurred. DISCUSSION: Upper GI bleeds associated with aspirin therapy are well described in the literature. The management of cardiovascular event prophylaxis after a GI bleed is often controversial; consensus in regard to the optimal method of management does not exist. We evaluated GI protection strategies for patients with a history of aspirin-induced GI bleeding requiring cardiovascular prophylaxis. We found that the benefit of aspirin for the primary prevention of cardiovascular events needs to be carefully balanced with the risks associated with its use. The current literature supports that the best approach to prevent recurrent aspirin-induced GI bleeding is to administer a proton pump inhibitor with aspirin therapy. CONCLUSIONS: The benefit of aspirin for primary prevention of cardiovascular events needs to be carefully balanced with the risks associated with its use. Based on the current literature, the best approach to preventing recurrent aspirin-induced GI bleeds is to administer a proton pump inhibitor concomitantly with aspirin therapy.

Pharmacist-Led Deprescribing for Patients With Polypharmacy and Chronic Disease States: A Retrospective Cohort Study.

Background: Current literature and practice have demonstrated that pharmacists have an integral role in deprescribing. However, research regarding their impact on patients with chronic diseases is limited. Objective: To assess the impact of a pharmacist-led intervention on deprescribing inappropriate medication for patients with chronic diseases within a four-month study period compared to patients receiving usual care. Methods: This study was conducted at NYU Langone Health. Patients of the intervention group were referred by a provider and met the criteria of polypharmacy, required chronic disease states management, were nonadherent to medications, had poor health literacy, or required titration for heart failure (HF) guideline directed medical therapy. Results: A total of 142 patients were reviewed over a two-year period. At the end of the study period, the median number of medications for the two respective groups was similar (11 [4 - 30] vs 11 [2 - 23]). The pharmacist-led intervention had on average one medication deprescribed (m = -1.00, sd = 2.57), whereas the control group had on average .44 additional medications (m = 0.44, sd = 3.32) prescribed. Furthermore, the intervention group presented statistically significant differences (P = 0.046) regarding their diastolic blood pressure after the pharmacists' intervention (m = 72.69, sd = 11.64). Most importantly, patients with HF presented statistically significant improvement in their ejection fractions after the intervention (m = 41.46%, sd = 19.28%). Conclusion: The pharmacist-led intervention resulted in significant discontinuation of medications for patients in the intervention group compared to those in the usual care group within four-months.

Translating Evidence-based Approaches into optimal Care for individuals at High-risk of ASCVD: Pilot testing of case-based e-learning modules and design of the TEACH-ASCVD study.

BACKGROUND: Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of death in the United States. Case-based learning using electronic delivery of the modules can educate clinicians and improve translation of evidence-based guidelines into practice for high-risk ASCVD patients. OBJECTIVE: To develop and optimize module design, content, and usability of e-learning modules to teach clinicians evidence-based management in accordance with multi-society guidelines for high-risk ASCVD patients that will be implemented and evaluated in U.S. health systems in the TEACH-ASCVD study. METHODS: Seven e-learning modules were created by a committee of lipid experts. Focus groups were conducted with lipid experts to elicit feedback on case content followed by interviews with a target audience of clinicians to assess usability of the online module platform. Responses from both groups were evaluated, and appropriate changes were made to improve the e-learning modules. Design of the TEACH-ASCVD study is presented. RESULTS: Feedback regarding case content by lipid experts included providing more detailed patient histories, clarifying various diagnostic criteria, and emphasizing clinical best practices based on evidence-based guidelines. The target audience clinician group reported an agreeable experience with the e-learning modules but noted a discordance between the evidence-based guidelines and clinical decision-making in their own practices. Participants felt the modules would help educate clinicians in managing high-risk ASCVD patients. CONCLUSION: Clinicians must be informed of best practices as the field of lipidology continues to evolve. E-learning modules provide a concise, valuable, and accessible mechanism for educating clinicians regarding changes in the field to deliver the best patient care.

Insulin Dosage Adjustments After Initiation of GLP-1 Receptor Agonists in Patients With Type 2 Diabetes.

BACKGROUND: Combination of insulin and GLP-1RAs have shown reductions in the HbA1c, body weight, and the risk of hypoglycemia. To date, there are conflicting data regarding the effect of GLP-1RAs on insulin dosage(s). OBJECTIVE: The objective of this study was to evaluate adjustments of insulin doses upon initiation of GLP-1RAs. METHODS: This was a retrospective chart review of patients on insulin therapy initiated on GLP-1RAs at NYU Langone Health. Patients were included in the study if they were at least 18 years of age, history of type 2 diabetes, and were on concurrent basal or mixed insulin therapy. 45 patients met inclusion criteria and were included in the study analysis. The primary endpoint was the median change in overall basal insulin doses. Secondary endpoints included median changes in total basal, mixed, and bolus insulin doses, oral antidiabetic medications and GLP-1RA doses, HbA1c, body weight, fasting glucose, and creatinine clearance. Safety results included any adverse reactions to insulin and/or GLP-1RA. RESULTS: In the per-protocol analysis, there was a significant reduction in overall total basal insulin doses from baseline to week 24 (50 units vs. 44 units, p < 0.05). There was a median reduction in patients receiving glargine (50 units vs. 44 units) and detemir (29 units vs. 21.5 units). CONCLUSIONS: Use of GLP-1RAs after 24 weeks resulted in a statistically significant reduction in overall total basal insulin dosages from baseline. The median HbA1C in our patient population was >8%. Consider a ≥10% reduction in the overall basal insulin dose upon initiation of GLP-1RA in patients with a HbA1C >8%.

Small interfering ribonucleic acid for cholesterol lowering - Inclisiran: Inclisiran for cholesterol lowering.

Despite the development of new therapies to lower cardiovascular disease (CVD) risk in recent decades, the trend of reductions in CVD mortality has reversed. New therapies are essential for the prevention of first and recurrent CVD. The importance of lowering low-density lipoprotein cholesterol (LDL-C) in the management and prevention of atherosclerotic CVD (ASCVD) is widely reflected in clinical treatment guidelines; however, most patients with established ASCVD do not achieve guideline-recommended LDL-C targets. Common reasons include adherence challenges, public disinformation, statin tolerability issues, access barriers, and clinical inertia. Inclisiran is a novel small interfering ribonucleic acid (RNA) that lowers circulating LDL-C by ∼50% when added to maximally tolerated statins by mimicking the body's natural pathway of RNA interference to specifically prevent proprotein convertase subtilisin/kexin type 9 synthesis. The unique dosing regimen of inclisiran (initial, at 3 months, and then every 6 months) has the advantage of allowing for healthcare provider administration during recommended routine visits for patients with established ASCVD, which can circumvent adherence issues associated with currently available LDL-C-lowering therapies. Inclisiran has demonstrated favorable tolerability and safety for up to 3 years, and evidence from longer-term use is accumulating in ongoing studies. This review discusses the novel mechanism of action of inclisiran and its potential position in the clinical armamentarium.

A heart failure themed escape room approach to enhance pharmacy student learning.

INTRODUCTION: The purpose of this study was to design, pilot, and evaluate the efficacy of an educational escape room to enhance second professional year doctor of pharmacy students' knowledge of heart failure medicinal chemistry, pharmacology, and therapeutics in an integrated Modular Organ Systems Therapeutics (MOST) course and to assess students' perceptions of the game. METHODS: Heart failure pharmacology, medicinal chemistry, and pharmacotherapeutics were taught in MOST prior to the escape room activity. Students were randomized into groups of approximately eight. At the completion of the activity, students were asked to fill out a perceptions survey. A follow up survey of their perceptions was again administered four weeks after the activity. RESULTS: One-hundred-ninety-three students participated in the escape room activity. Overall, performance indicated that the escape room satisfactorily reinforced students' learning of the course material. Students expressed satisfaction toward the escape room activity on both surveys, with response rates of 92.22% and 56.99% for the initial and follow up surveys, respectively. Findings revealed no statistically significant differences between the first and the second group of responses, confirming that positive attitudes toward the activity did not alter over time. Students' satisfaction levels were inversely related to their grade point average (r = -0.20, p = 0.05). CONCLUSIONS: Positive student perceptions reported immediately after the completion of the escape room activity and measured in the follow-up survey demonstrated that the escape room is a satisfying learning activity that can engage all students.

Acute interstitial nephritis associated with coadministration of vancomycin and ceftriaxone: case series and review of the literature.

We report what we believe to be the first two cases of acute interstitial nephritis associated with vancomycin and ceftriaxone therapy in adults. A 40-year-old man with a medical history of traumatic brain injury and tonic-clonic seizure disorder was admitted to the hospital with a seizure episode and temperature of 103 degrees F. He was administered ceftriaxone, vancomycin, and acyclovir for suspected bacterial and/or viral meningitis. On day 4, the patient was noted to have diffuse erythematous plaques on the neck, chest, arms, abdomen, and back, as well as an elevated serum creatinine level of 3.1 mg/dl (baseline 0.9 mg/dl) and an elevated eosinophil count (6%). Dermatology and renal consultations were obtained, and a diagnosis of suspected acute interstitial nephritis was made. After a 3-day course of antibiotic treatment (day 4 of hospitalization), all antibiotics were discontinued and topical triamcinolone 0.1% ointment and hydrocortisone 2.5% cream were begun for the rash. The patient was discharged 5 days later with improvement in the rash, serum creatinine level (1.0 mg/dl), and eosinophil count (0.9%). A 59-year-old woman with a medical history of diabetes mellitus was admitted to the hospital with a serum creatinine level of 3.7 mg/dl, eosinophil count of 8.4%, and fractional excretion of sodium of 2.94%. The patient had been receiving treatment with vancomycin and ceftriaxone for osteomyelitis for 28 days before this hospital admission. Her baseline serum creatinine level (before antibiotic therapy) was 1.0 mg/dl. Renal consultation was obtained, and a diagnosis of probable acute interstitial nephritis was made. Ceftriaxone and vancomycin were discontinued, and her serum creatinine level gradually decreased to 3.3 mg/dl and then further to 1.5 mg/dl over the next 3 months. Use of the Naranjo adverse drug reaction probability scale revealed that the adverse reaction was possible in the first case and probable in the second case. Health care professionals need to be cognizant that drug-induced acute interstitial nephritis can be associated with concomitant administration of ceftriaxone and vancomycin therapy. Early detection of this rare adverse reaction is paramount in order to prevent acute renal insufficiency.

Optimal low-density lipoprotein cholesterol lowering--morning versus evening statin administration.

OBJECTIVE: To determine the best time to administer statins for optimal lowering of low-density lipoprotein cholesterol (LDL-C) by reviewing the clinical evidence evaluating the chronobiologic effects of morning versus evening statin administration. DATA SOURCES: Using the MeSH terms HMG-CoA reductase inhibitors, statins, morning and evening dosing, and clinical trials, a literature review was conducted to identify articles in MEDLINE (1966-December 2006), International Pharmaceutical Abstracts (1970-December 2006), and IOWA Drug Information Systems (1985-December 2006). DATA SYNTHESIS: Seven English-language studies evaluating morning and evening statin administration were identified and evaluated. Based on the available data, simvastatin demonstrated a pronounced LDL-C percentage reduction with evening dosing. Although not statistically significant, a trend in the LDL-C percentage reduction favoring evening statin administration was noted with lovastatin, pravastatin, and rosuvastatin. Atorvastatin demonstrated similar LDL-C reduction regardless of administration time. With the exception of simvastatin, the trials comparing morning versus evening effects of statins on LDL-C have several significant methodologic shortcomings, including small sample size, lack of statistical power, and inappropriate exclusion criteria that did not include or did not mention drug-induced effects on lipids. CONCLUSIONS: There are sufficient data to support evening administration of simvastatin to achieve optimal lowering of LDL-C levels. Rigorous and robust trials are necessary to determine the best administration time to achieve optimal LDL-C lowering for lovastatin, pravastatin, rosuvastatin, atorvastatin, and fluvastatin.

Effects of morning versus evening administration of atorvastatin in patients with hyperlipidemia.

PURPOSE: The effects of morning versus evening administration of atorvastatin in hyperlipidemic patients were studied. METHODS: Patients whose care was managed by a teaching hospital run by the Department of Veterans Affairs who were prescribed atorvastatin calcium 40 mg p.o. daily by their primary care physician were interviewed by a clinical pharmacist in the ambulatory care clinic for study enrollment. Patients were excluded if they had diseases or conditions or took medication known to affect serum lipoprotein levels, as were patients who consumed more than three alcoholic drinks per day and those who could not verify the time of atorvastatin administration. Blood samples were collected after a 12-hour fasting period and serum lipoprotein levels were measured at baseline and after four weeks. RESULTS: Of the 204 hyperlipidemic patients receiving atorvastatin, 64 met the inclusion criteria and were enrolled in the study, 32 of whom took the drug in the morning (before noon) and an equal number who took the drug at night (after 6 p.m. but before midnight). All patients were male outpatients with a mean +/- S.D. age of 57.8 +/- 7.8 years and 58.5 +/- 7.8 years for the morning and evening administration groups, respectively. No statistically significant differences in lipid values measured were found between the morning and evening administration group after four weeks. CONCLUSION: Changes in the levels of total cholesterol, low-density-lipoprotein cholesterol, triglycerides, and high-density-lipoprotein cholesterol were similar among hyperlipidemic patients receiving atorvastatin calcium 40 mg, regardless of the time of day the drug was administered.

What Is the Appropriate Duration of High-Dose Atorvastatin Therapy Post-Acute Coronary Syndrome?

PURPOSE: To determine the optimal duration of high-intensity atorvastatin therapy post-acute coronary syndrome (ACS). SUMMARY: A literature review was conducted using the MEDLINE database (1966-October 2013) and employing the search terms "atorvastatin OR statins AND myocardial infarction OR acute coronary syndromes." Clinical trials in the English language with available abstracts were used to identify potential data sources. Four major trials evaluating atorvastatin 80 mg daily after an ACS were identified. The duration of follow-up ranged from 16 weeks to a median of 4.9 years. High-dose atorvastatin regimens were associated with a reduction in coronary events but also with higher rates of drug discontinuation due to adverse reactions. The benefit of high-dose atorvastatin has been sustained for at least 5 years. CONCLUSION: After an ACS, high-dose atorvastatin should be continued for at least 5 years. High-dose atorvastatin demonstrated a reduction in coronary events but dose reductions and higher discontinuation rates were also noted.

Angioedema after nonsteroidal antiinflammatory drug initiation in a patient stable on an angiotensin-converting-enzyme inhibitor.

PURPOSE: A case of angioedema associated with the initiation of a nonsteroidal antiinflammatory drug in a patient stable on an angiotensin-converting-enzyme inhibitor is reported. SUMMARY: A 68-year-old African-American man with no known drug allergies and a history of hypertension, benign prostatic hypertrophy, diverticulosis, and gout arrived at the clinic with swelling of the lips and tongue three days after he started taking naproxen 375 mg every eight hours as needed for pain associated with acute gout. He denied urticaria, difficulty breathing, fever, abdominal pain, vomiting, and diarrhea. His other medications included quinapril 10 mg daily (taken for 5 years), tamsulosin hydrochloride 0.4 mg daily, omeprazole 20 mg daily, and colchicine 0.6 mg daily. He had reported smoking approximately 2.5 packs of cigarettes per week and consuming alcohol (one to two drinks) on the weekends. He denied any illicit drug use, drug rash, or seasonal allergies. Naproxen was discontinued, and the patient was treated with prednisone (tapered regimen) and acetaminophen 650-mg tablets, and his angioedema resolved. The Naranjo et al. probability scale revealed that naproxen and quinapril coadministration was the probable cause of the patient's adverse reaction (score of 7). CONCLUSION: A 68-year-old African-American man who had been receiving quinapril for 5 years developed angioedema after initiation of naproxen.

Periorbital edema associated with separate courses of ibuprofen and naproxen.

PURPOSE: A case of periorbital edema associated with separate courses of ibuprofen and naproxen is reported. SUMMARY: An 80-year-old African- American woman with a history of osteoarthritis and hypertension came to the clinic. Her medication regimen included fosinopril sodium 40 mg daily, which she began two years prior. She had no known drug allergies and denied consuming any over-the-counter medications or herbal substances and reported a negative atopic status. She had seen her primary care provider several days prior and reported pain in the hands, fingers, and ankles, which would escalate in the morning and progressively lessen during the course of the day. Her physician prescribed naproxen 375 mg every eight hours as needed. After ingesting two doses of naproxen, she developed itching, swelling, and erythema around the left eye that became progressively worse and spread to the right eye. She contacted her primary care physician, who instructed her to discontinue the naproxen, and the reaction resolved within three days. The patient was maintained on acetaminophen for the arthritic pain with no issues. Approximately three months prior, ibuprofen 600 mg every eight hours as needed was prescribed for the same pain. She stated that after ingesting two doses of ibuprofen, she experienced a reaction similar to that recently experienced with naproxen. At that time, she was instructed to discontinue the ibuprofen, and her symptoms resolved. CONCLUSION: An elderly woman developed periorbital edema after taking ibuprofen on one occasion and naproxen on another.

Sitagliptin: a novel agent for the management of type 2 diabetes mellitus.

PURPOSE: The pharmacologic, pharmacokinetic, safety, clinical efficacy, and role of sitagliptin in the management of type 2 diabetes mellitus are reviewed. SUMMARY: Sitagliptin is a dipeptidyl-peptidase IV (DPP4) inhibitor that increases insulin release and decreases glucagon levels by preventing the activation of incretin hormones--glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide. The clinical trials reviewed provide evidence that sitagliptin, either alone or in combination with metformin or thiazolidinediones, is effective in reducing glycosylated hemoglobin (HbA(1c)), fasting plasma glucose, and two-hour postprandial glucose levels in patients with type 2 diabetes. Specifically, sitagliptin has a role in patients who have been compliant with their oral hypoglycemic agents but unable to attain target HbA(1c) values with monotherapy and lifestyle modifications. Sitagliptin is generally well tolerated, with the frequency of adverse events being similar to placebo and a low frequency of hypoglycemia. Sitagliptin does not appear to alter the pharmacokinetics of metformin, rosiglitazone, glyburide, simvastatin, warfarin, or oral contraceptives. The addition of sitagliptin to a patient's oral antidiabetic regimen would necessitate close monitoring for adverse events and possible drug interactions. The sitagliptin dosage recommended by the manufacturer is 100 mg once daily as monotherapy or in combination with metformin or a thiazolidinedione. No formal pharmacoeconomic evaluations of sitagliptin therapy have been conducted. CONCLUSION: Sitagliptin, a DPP4 inhibitor, offers a novel treatment option for patients with type 2 diabetes mellitus.

Vitamin E supplementation in Alzheimer's disease, Parkinson's disease, tardive dyskinesia, and cataract: Part 2.

OBJECTIVE: To review clinical trials evaluating the safety and efficacy of vitamin E supplementation in Alzheimer's disease, Parkinson's disease, tardive dyskinesia, and cataract. DATA SOURCES: Using the MeSH terms alpha-tocopherol, tocopherols, vitamin E, Parkinson disease, tardive dyskinesia, Alzheimer disease, cataract, and clinical trials, a literature review was conducted to identify peer-reviewed articles in MEDLINE (1966-July 2005). STUDY SELECTION AND DATA EXTRACTION: Published materials including original research, review articles, and meta-analyses were reviewed. Only English-language articles and trials that included vitamin E alone or in combination with other vitamins or minerals were reviewed. Emphasis was placed on prospective, randomized, double-blind, placebo-controlled clinical trials. DATA SYNTHESIS: The clinical studies demonstrated contradicting results regarding the benefits of vitamin E in Parkinson's disease, tardive dyskinesia, and cataract. The study reviewed for Alzheimer's disease seemed to show benefit when vitamin E was used; however, the statistical methods employed are questionable. There is enough evidence from large, well-designed studies to discourage the use of vitamin E in Parkinson's disease, cataract, and Alzheimer's disease. We recommend that vitamin E be considered a treatment option in patients with tardive dyskinesia only if they are newly diagnosed. CONCLUSIONS: We encourage patients to supplement with vitamin E-rich foods. The use of a daily multivitamin, which usually contains 30 IU of alpha-tocopherol, may be beneficial; however, we discourage individual vitamin E supplements that usually contain 400 IU of alpha-tocopherol.

Vitamin E supplementation in cardiovascular disease and cancer prevention: Part 1.

OBJECTIVE: To review clinical trials evaluating the safety and efficacy of vitamin E supplementation in cardiovascular disease and cancer prevention. DATA SOURCES: Using the MeSH search terms alpha-tocopherol, tocopherols, vitamin E, cardiovascular diseases, cancer, malignancy, and clinical trials, a literature review was conducted to identify peer-reviewed articles in MEDLINE (1966-July 2005). STUDY SELECTION AND DATA EXTRACTION: Published materials including original research, and previous meta-analyses were included. Only English-language articles and trials on vitamin E alone or in combination with other vitamins or minerals were reviewed. Emphasis was placed on prospective, randomized, double-blind, placebo-controlled clinical trials. DATA SYNTHESIS: Eight clinical studies demonstrated contradicting results regarding the benefits of vitamin E in the prevention of cardiovascular disease and cancer. There is enough evidence from large, well-designed studies to discourage the use of vitamin E in the primary prevention of cardiovascular disease. Secondary prevention requires more adequate clinical trials with selected populations to examine protective effects of vitamin E in cardiovascular disease. The findings of the studies reviewed do not provide evidence that vitamin E may reduce the risk of cancer; thus, at the present time, we do not recommend daily vitamin E intake for cancer prevention is not recommended. CONCLUSIONS: Available data do not support the supplementation of vitamin E in cardiovascular disease and cancer prevention.