Introduction: The ACC/AHA hypertension guidelines recommended chlorthalidone (CTD) over hydrochlorothiazide (HCTZ) due to its longer half-life and proven reduction in major adverse cardiovascular events. The mechanism of the potential benefit of CTD compared to HCTZ has not been established. Unlike other thiazide diuretics, studies suggest that CTD may affect platelet aggregation, gene transcription, angiogenesis, and vascular permeability. We aimed to compare the antiplatelet effects of CTD versus HCTZ. Methods: We conducted a prospective, double-blind, randomized, three-way crossover study comparing the antiplatelet effects of CTD, HCTZ, and aspirin (ASA) in healthy volunteers ≥ 19 years of age. ASA was included in the study as a known control for inhibition of platelet aggregation. Whole blood aggregometry was used to assess the impact of treatments on platelet activation and aggregation. Results: Of the 40 subjects, 34 (85%) completed the 3-way crossover comparison. Six subjects were excluded due to non-compliance and adverse effects. Compared to ASA, both CTD and HCTZ had no antiplatelet effects (Table 1). There was no statistically significant difference between CTD and HCTZ in terms of platelet function. Conclusions: Although recent studies showed increased cardiovascular benefit with CTD compared to HCTZ, CTD and HCTZ do not have antiplatelet effects. Larger studies are needed to confirm our findings.

Chlorthalidone (CTD) may be superior to hydrochlorothiazide (HCTZ) in the reduction of adverse cardiovascular events in hypertensive patients. The mechanism of the potential benefit of CTD could be related to antiplatelet effects. The objective of this study was to determine if CTD or HCTZ have antiplatelet effects. This study was a prospective, double-blind, randomized, three-way crossover comparison evaluating the antiplatelet effects of CTD, HCTZ, and aspirin (ASA) in healthy volunteers. The effects of these treatments on platelet activation and aggregation were assessed using a well-established method with five standard platelet agonists. Thirty-four patients completed the three-way crossover comparing pre- and post-treatment changes in platelet activation and aggregation studies. There were statistically significant antiplatelet effects with ASA but not with CTD or HCTZ. Hypokalemia occurred in 0 (0%), 10 (30%), and 6 (18%) of the ASA, CTD, and HCTZ patients, respectively. The results of our study suggest that the benefits of CTD and HCTZ in reducing adverse cardiovascular events in patients with hypertension is not a result of an antiplatelet effect. In our study, hypokalemia with CTD was more prevalent than that reported in a large outcome trial in patients with hypertension. The clinical relevance of this finding is uncertain.

SESSION TITLE: Cardiovascular Disease SESSION TYPE: Original Investigation Poster PRESENTED ON: Wednesday, October 26, 2016 at 01:30 PM - 02:30 PM PURPOSE: Rates of readmission remain high following admission for acute decompensated heart failure (ADHF) and inadequate decongestion is one of the major contributors. While laboratory markers such as brain natriuretic peptide(BNP) have previously been identified, there is a need to identify additional clinical markers of adequate decongestion prior to discharge to improve outcomes. The purpose of this studywas to prospectively assess the utility of change (Δ) in QRS voltage (predischarge - baseline) and the 6-minute walk test (6-MWT) for predicting 1 year outcomes in patients admitted with ADHF. METHODS: This was a prospective observational study of patients admitted to the Creighton University Medical Center with ADHF (acute coronary syndrome excluded). An electrocardiogram (ECG) was obtained within 24 hours of admission and at discharge. The 6-MWT was administered on the day of discharge if the patient had no contraindications such as elevated fall risk. Follow up data were obtained by phone interview every 3 months for up to 12 months or until an occurrence of a primary outcome event (hospital and death records were reviewed where applicable). The primary outcome was a composite of all-cause mortality or readmission for heart failure (HF).ECG voltages were determined by 2 investigators blinded to the clincal and outcome data.6-MWT was administered by a trained nurse. RESULTS: Of the 46 patients enrolled, 1 withdrew consent leaving 45 for analysis. During 1 year of follow up, 25 (55%) had a primary outcome event. Nine (20%) died and 22 (49%) were readmitted for HF. Twenty eight (68%) had a decreased ejection fraction, 53% were male, Twenty eight (68%) had a decreased ejection fraction and 53% were male, 40% had diabetes, 89% had Hypertension 49% had coronary artery disease. There was no significant difference in Δ QRS voltage among those with and without the composite outcome. Patients with primary outcome event had a mean predischarge 6-MWT distance of 134±86 meters compared to 214±119 meters in those without. Advanced age, high creatinine level, non-use of angiotensin antagonists, and 6-MWT distance were predictors of primary outcome. A cut off of ≥100 meters on 6-MWT had a 73% sensitivity and 67% specificity for identifying freedom from the composite outcome at 1 year (area under the curve 0.78; p=0.01). CONCLUSIONS: In patients admitted with ADHF, pre-discharge 6-MWT distance was a predictor of the composite end point of all-cause mortality or re-hospitalization for HF, while ECG voltage changes were not. The independent utility of 6-MWT over and above existing predictors will need to be tested in future large prospective studies. CLINICAL IMPLICATIONS: In patients admitted for ADHF, predischarge 6-MWT can be a useful predictor of adeuqcy of decongestion and risk of readmission for HF. If the utility of this relatively inexpinsive and easily administered test is confirmed in larger studies, it can help identify patients who need further hospitalization and decongestion or close clinical follow up after discharge. DISCLOSURE: The following authors have nothing to disclose: Venkata Alla, Vimalkumar Veerappan Kandasamy, Janardhana Janardhana Gorthi, Manu Kaushik, Ajay Kaja, Zulie Zulkosky, Joshu teBensel, Tammy Burns, Mark Williams, Claire Hunter, Aryan Mooss, Dennis Esterbrooks No Product/Research Disclosure Information

Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays an essential role in the degradation of low-density lipoprotein C (LDL-C) receptors, and PCSK9 inhibitors have recently emerged as a potential treatment option to reduce LDL-C. Our paper reviewed the current available Phase II clinical trials of PCSK9 inhibitors for the treatment of dyslipidemia. A second objective of this review was to evaluate the potential clinical role of PCSK9 inhibitors in the management of dyslipidemia. Studies evaluating the efficacy and safety of any PCSK9 inhibitors in patients with dyslipidemia were included. The monoclonal antibodies REGN727/SAR236553 and AMG145 have the most published clinical data. Seven phase II trials were retrieved that evaluated the efficacy and safety of REGN727/SAR236553 or AMG145 in patients with either hypercholesterolemia or heterozygous familial hypercholesterolemia (HeFH). These two agents significantly decreased LDL-C levels either as monotherapy or in combination with other lipid-lowering agents. REGN727/SAR236553 and AMG145 have been well tolerated. The ongoing phase III trials of these two agents are summarized. REGN727/SAR236553 and AMG145 have demonstrated the potential to further decrease LDL-C levels when added to conventional lipid-lowering therapy. Morbidity and mortality data are required to define their roles in clinical practice.

Background: There are little published data on outcomes of blood conservation (BC) patients after noncardiac surgery. The objective of this study was to compare the surgical outcomes of patients enrolled in our BC program with that of the general population of surgical patients.Methods: BC patients at our institution undergoing various surgical procedures were identified from the 2007-2009 National Surgical Quality Improvement Program database and compared with a cohort of conventional care (CC) patients matched by age, gender, and surgical procedure. Univariate and multiple logistic regression analyses were performed to evaluate 30-d postoperative outcomes.Results: One hundred twenty BC patients were compared with 238 CC patients. The two groups were similar for all preoperative variables except smoking, which was lower in the BC group. On univariate analysis, BC patients had similar mean operating time (148 versus 155 min; P = 0.5), length of stay (5.9 versus 5.5 d; P = 0.7), and rate of return to the operating room (7.5% versus 5.5%; P = 0.4) compared with CC patients. BC and CC patients had similar 30-d morbidity (18% versus 14%; P = 0.3) and mortality rates (1.6% versus 1.3%; P = 1.0), respectively. On multivariable analysis, enrollment in the BC program had no impact on postoperative 30-d morbidity (odds ratio, 1.78; 95% confidence interval, 0.71-4.47) or 30-d mortality (unadjusted odds ratio, 1.33; 95% confidence interval, 0.22-8.05).Conclusions: Short-term postoperative outcomes in BC patients are similar to the general population, and these patients should not be denied surgical treatment based on their unwillingness to receive blood products. (C) 2014 Elsevier Inc. All rights reserved.

Introduction:Effective interventions for smoking cessation are critically needed. Yoga has only begun to be evaluated for smoking cessation.Aims:The primary aim was to assess participant satisfaction and perceived benefit of Hatha yoga. Secondary aims were to test evaluation tools, recruitment and retention techniques, and to generate preliminary effect size for a randomized trial.Methods:This was a non-randomized, single-group, pilot study. Thirty-one participants entered the study and received group behavioural therapy followed by 30 minutes of Hatha yoga instruction. Participant satisfaction was assessed at the conclusion of eight sessions. Point prevalence smoking abstinence was assessed at the end of the intervention period.Results:Participants were 36% male with an average age of 47 years (range 22–72) and a mean of 12.7 ± 5.6 cigarettes per day. Mean duration of smoking was 26.1 ± 15 years. Participant satisfaction was very high (88% very satisfied). Smoking abstinence at the end of the intervention was 29%.Conclusions:Hatha yoga is acceptable and feasible to aid in smoking cessation. A regimen that includes breathing, postures, and meditation has been developed for testing in a randomized trial.

ObjectivesTo evaluate the efficacy and long‐term safety of transulnar approach in complex coronary interventions.BackgroundThe success rate of transulnar approach in complex coronary interventions and its long‐term safety remains to be proven.MethodsWe conducted a retrospective chart review of patients undergoing transulnar coronary angiography and interventions at our institution from January 2004 through July 2009. Primary endpoint of the study was the success rate of the procedure. Secondary endpoints were major bleeding, local vascular and neurological complications, cerebrovascular accident (CVA)/transient ischemic attack (TIA), myocardial infarction (MI), all‐cause mortality, and major adverse cardiovascular events (MACE) rate that was a composite of MI, CVA/TIA, and all‐cause mortality.ResultsOf 81 patients undergoing transulnar approach, 41 (50.6%) patients underwent intervention on 65 lesions. Twelve percent of the interventions were performed on coronary bypass grafts and 9.2% on the left main coronary artery. Success rates for transulnar access, coronary angiography, and coronary/bypass graft interventions were 93.8%, 100%, and 92.6%, respectively. Follow‐up data was available on 71 patients at short term (30 days) and 58 patients at long term (1 year). At 30‐day follow‐up, vascular complication rate was 2.8 %. At 1‐year follow‐up, there were no residual deficits from vascular or neurological complications associated with the index procedure and the overall MACE rate was 3.4%.ConclusionIn this first study evaluating long‐term safety and feasibility of transulnar coronary angiography and complex coronary interventions, we conclude that transulnar approach appears to be safe and effective. © 2013 Wiley Periodicals, Inc.

SESSION TITLE: Cardiovascular Posters

Background Ranolazine is a novel antianginal medication approved for the treatment of chronic angina. There are only limited data concerning the efficacy of ranolazine in reducing healthcare resource utilization in patients with refractory angina pectoris. Objective The primary objective of this analysis was to evaluate the efficacy and safety of ranolazine in refractory angina pectoris. In addition, the impact of ranolazine on healthcare resource utilization was assessed. Methods Consecutive patients with refractory angina pectoris treated with ranolazine at two cardiology practices in the state of Nebraska were included in this analysis. The Canadian Cardiovascular Society (CCS) angina class and frequency and type of healthcare resource consumption were determined during the 12 months prior to and the 12 months after initiation of ranolazine. Results A total of 150 pts (64 % men) with a mean age of 66 ± 12 years were included in this analysis. All patients had previously undergone coronary revascularization. Nitrates, β-adrenoceptor antagonists (β-blockers), and calcium antagonists (calcium channel blockers) were being used in 83, 97, and 75 % of patients, respectively. During ranolazine treatment, a significant improvement in CCS angina class was observed, with 23 patients improving by one class and no patient experiencing a deterioration in functional class ( p = 0.025). A total of 53 side effects occurred in 28 (19 %) patients receiving ranolazine. Of those patients with side effects, four required dose reduction and seven required drug discontinuation. The frequency of clinic visits and emergency room visits was lower during ranolazine treatment, but the differences in frequency were not significant. The number of patients hospitalized and the number of hospitalizations were significantly lower during ranolazine therapy than in the pre-ranolazine study period ( p = 0.002). Conclusion Ranolazine improved the CCS angina class and reduced hospitalizations over a 12-month follow-up period in a group of patients with difficult-to-treat refractory angina pectoris.

Reduction of tobacco use around the world is a high priority. This review will provide the current status of tobacco control with particular focus on progress and initiatives in the United States. Primary literature was retrieved through PubMed and review article reference lists. Reports from government and global oversight organizations including the World Health Organization, Centers for Disease Control and Prevention, and the U.S. Department of Health and Human Services are the primary sources for data and statistics. Information about the Tobacco Master Settlement Agreement, Framework Convention on Tobacco Control, clean air laws, and tobacco excise taxes in the United States was also included. Continued progress in tobacco control is critical to reducing the tremendous global morbidity and mortality related to tobacco. Strong policies at all levels are critical to making strides toward eliminating the public health burden of tobacco use. Coordinated global efforts to restrict tobacco are necessary to the successful eradication of tobacco use. The United States has recently made sweeping changes in tobacco control policy and the momentum must be maintained through advocacy and action.

The prevalence of obesity has increased dramatically in the past 20 years. As a public health concern, obesity is associated with a health care resource burden that is quickly approaching that associated with tobacco use. Although lifestyle intervention (diet and exercise) remains the mainstay of treatment of obesity, its effectiveness is limited by poor long-term adherence. Drug therapy has historically been unsuccessful in producing sustained weight loss. Many older weight loss drugs have adverse benefit-to-risk profiles. This review provides an overview of nonpharmacologic interventions for weight loss. The safety and efficacy of older weight loss drugs, as well as current data related to lorcaserin, phentermine/topiramate, and naltrexone-bupropion, are evaluated. Although associated with modest weight loss and some improvement in adverse obesity-related metabolic effects, none of these drugs has been demonstrated to reduce mortality. In addition, the long-term safety of these drugs remains largely unknown. Bariatric surgery is an option for patients with morbid obesity who have failed conventional treatment.

BACKGROUND:To assess the efficacy of aliskiren in patients failing to reach blood pressure (BP) goals with angiotensin converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB).METHODS:A total of 107 patients who failed to reach BP goals on ACEI or ARB were switched to aliskiren. Changes in BP were determined during maximal ACEI, ARB, or aliskiren therapy.RESULTS:Mean reduction in sBP and dBP with ACEI was 8.5 ± 6.3 mmHg and 6.0 ± 4.7 mmHg, respectively. Mean reduction in sBP and dBP with ARB was 8.3 ± 6.7 mmHg and 5.0 ± 5.2 mmHg, respectively. Mean reduction in sBP and dBP with aliskiren 150 mg/d was 6.7 ± 5.4 mmHg and 5.4 ± 4.8 mmHg, respectively. Mean reduction in sBP and dBP with aliskiren 300 mg/d was 8.6 ± 6.3 mmHg and 6.0 ± 4.9 mmHg, respectively. BP reductions between ACEI, ARB, and aliskiren were not significantly different.CONCLUSIONS:Aliskiren is ineffective in patients failing ACEI or ARB therapy. Given the label changes restricting the use of aliskiren in combination with ACEI and ARB, excess cost compared to ACEI and ARB, and a paucity of outcome data, there is a limited role for aliskiren in practice.

OBJECTIVE:Acknowledging evidence of possible detrimental effects of tightly controlled blood glucose levels, the American Association of Clinical Endocrinologists and the American Diabetes Association published a consensus statement recommending less strict control for most diabetic patients. As a result of these recommendations, our academic center at Creighton University Medical Center revised its adult insulin infusion protocol to target blood glucose levels ranging from 120 to 180 mg/dL for regular (standard) glycemic control and 80 to 120 mg/dL for tight control; previous targets had ranged from 80 to 180 mg/dL and 70 to 110 mg/dL, respectively. The primary objective was to evaluate the time that blood glucose values were within the target range for patients receiving the new protocol, compared with patients receiving the previous protocol.METHODS:Our study was designed to evaluate the effectiveness and safety of the revised protocol. Using a retrospective chart review, we collected data for 4 months from patients on the old insulin protocol (May to August 2009) and for 4 months from patients on the new protocol (September to December 2009). Secondary endpoints included the number of hypoglycemic episodes (blood glucose below 70 mg/dL) and severe hypoglycemic episodes (blood glucose 40 mg/dL or lower) experienced by patients receiving the new insulin protocol compared with those receiving the former protocol.RESULTS:Patient characteristics were similar at baseline. Blood glucose values stayed within the target range for a significantly shorter time with the new protocol than with the former protocol (44.6% vs. 56.8%, respectively; P < 0.001), probably because of the narrower target range in the revised protocol. No statistically significant differences in hypoglycemia were observed after the protocol was changed. Hypoglycemia occurred in 31% of the former-protocol patients compared with 18% of the revised-protocol patients. Severe hypoglycemia was experienced by 2.1% of patients on the old protocol and by 3.1% of patients on the new protocol. Rates of severe hypoglycemia were low (2.6%) with the original protocol.CONCLUSION:Patients' blood glucose levels were within the target range for a shorter time with the new protocol. Fewer episodes of hypoglycemia were recorded with the new protocol, but rates of severe hypoglycemia were similar with both protocols.

Abstract Purpose: This article reviews the current status of lipid–lowering drugs and their impact on cardiovascular morbidity and mortality. Because there is compelling evidence to suggest that substantial residual risk persists despite the use of current lipid–lowering treatments, novel strategies for managing dyslipidemia are discussed. Summary: Statins remain the drugs of choice for the treatment of dyslipidemia in patients with coronary heart disease or substantial risk factors for coronary heart disease. The evidence supporting the use of non–statin monotherapy for reductions in cardiovascular morbidity and mortality is examined. Furthermore, the evidence supporting the use of combinations of lipid–lowering drugs, primarily a statin plus another agent, for reductions in cardiovascular morbidity and mortality is discussed. Available clinical data for novel dyslipidemia drugs that can potentially expand on the current known benefits of statin therapy are reviewed. The cholesteryl ester transfer protein inhibitors, which predominantly increase high–density lipoprotein cholesterol levels and can also substantially lower low–density lipoprotein cholesterol levels, have the most robust clinical trial data, including some phase 3 study results. The proprotein convertase subtilisin/kexin type 9 inhibitors, which predominantly impact low–density lipoprotein cholesterol, are also being tested in phase 3 studies, but their widespread application may be limited by their need to be administered by injection. Peroxisome proliferator–activated receptor (PPAR) agonists with dual agonism of PPAR–α and PPAR–γ to optimize glycemic and lipid profiles may benefit patients with both diabetes and cardiovascular disease. The other novel lipid–lowering drugs are in earlier–phase human testing. Conclusion: Novel agents have the potential to be valuable additions to current treatment of dyslipidemia to reduce cardiovascular morbidity and mortality. These new drugs will not only have to be able to demonstrate an improvement in patients' lipid profiles, but will also have to be able to demonstrate that they reduce cardiovascular morbidity and mortality, typically in combination with statin therapy.

BACKGROUND:Erythropoietin stimulating agents (ESAs) are high-cost medications that have a significant impact on many pharmacy budgets. Recently, ESAs have received stronger safety warnings and reimbursement has been curtailed by third-party payers including the Centers for Medicare and Medicaid Services. For these reasons, many hospitals are developing strategies to optimize their use. A required order form with acceptable indications and dosing was implemented at an academic medical center in an attempt to improve dosing and appropriate utilization of ESAs.OBJECTIVE:To determine whether implementation of a required order form increased appropriate use and/or decreased total utilization of recombinant human erythropoietin (rHuEPO).METHODS:This was a retrospective cohort study of rHuEPO utilization for 4 months pre- and 6 months post-implementation (April 2008-January 2009).RESULTS:Implementation of a required order form for rHuEPO resulted in significantly fewer patients receiving inappropriate doses of rHuEPO (51.3% vs 19.2%, p < 0.001). The number of patients treated, adjusted to hospital census, was also reduced after implementation of the order form (0.003 vs 0.004 pts./average pt. days, p = 0.03). Annual spending for rHuEPO was reduced by 47% during 2008 despite an increased acquisition cost.CONCLUSIONS:Implementation of a required order form with evidence-based dosing recommendations can be an effective strategy to improve appropriate utilization of rHuEPO.