The impact of vascular access for in-hospital major bleeding in patients with acute coronary syndrome at moderate- to very high-bleeding risk.

The aim of our study was to determine the impact of vascular access on in-hospital major bleeding (IHMB) in acute coronary syndrome (ACS). We analyzed 995 patients with non-ST elevation myocardial infarction and unstable angina at the Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA guidelines (CRUSADE) moderate- to very high-bleeding risk scores in trans-radial intervention (TRI) retrospective registry from 16 centers in Korea. A total of 402 patients received TRI and 593 patients did trans-femoral intervention (TFI). The primary end-point was IHMB as defined in the CRUSADE. There were no significant differences in in-hospital and 1-yr mortality rates between two groups. However, TRI had lower incidences of IHMB and blood transfusion than TFI (6.0% vs 9.4%, P = 0.048; 4.5% vs 9.4%, P = 0.003). The patients suffered from IHMB had higher incidences of in-hospital and 1-yr mortality than those free from IHMB (3.1% vs 15.0%, P < 0.001; 7.2% vs 30.0%, P < 0.001). TRI was an independent negative predictor of IHMB (odds ratio, 0.305; 95% confidence interval, 0.109-0.851; P = 0.003). In conclusions, IHMB is still significantly correlated with in-hospital and 1-yr mortality. Our study suggests that compared to TFI, TRI could reduce IHMB in patients with ACS at moderate- to very high-bleeding risk.

Comparison of effects of morning versus evening administration of ezetimibe/simvastatin on serum cholesterol in patients with primary hypercholesterolemia.

BACKGROUND: Ezetimibe, a first-in-its-class inhibitor of cholesterol absorption, is an effective agent for combined use with statins to achieve low-density lipoprotein cholesterol (LDL-C) goals. Ezetimibe in combination with simvastatin as a single-tablet formulation has proven to be highly effective in reducing serum LDL-C through the dual inhibition of cholesterol absorption and biosynthesis. The effect of time of administration on efficacy of this combination therapy has not been evaluated. OBJECTIVE: To compare the effects of morning versus evening administration of ezetimibe/simvastatin on serum cholesterol levels of patients with primary hypercholesterolemia. METHODS: In this multicenter, open-label, randomized, 2-sequence, 2-period crossover study, patients with primary hypercholesterolemia randomly received ezetimibe/simvastatin 10 mg/20 mg once daily, either in the morning (within 1 hour of breakfast) or in the evening (within 1 hour of dinner) for 6 weeks. RESULTS: Data on 171 patients (87 in the morning administration group and 84 in the evening administration group) were analyzed. A significant reduction (p ≤ 0.001) in the total cholesterol, triglyceride, high-density lipoprotein cholesterol, LDL-C, apo-lipoprotein B, and high-sensitivity C-reactive protein (hs-CRP) from baseline was achieved after each treatment. Noninferiority of morning administration versus evening administration was shown in the percentage reduction of the LDL-C level from baseline (difference, -1.62%; 90% CI -4.94 to 1.70). No significant difference was found between groups with respect to the percentage of changes in other lipid parameters from baseline. Furthermore, there was no significant difference in the percentage of change in hs-CRP as an antiinflammatory marker between the morning and evening administration groups. The frequency of adverse events was similar between groups. CONCLUSIONS: Morning administration of ezetimibe/simvastatin 10 mg/20 mg is noninferior to evening administration with respect to LDL-C-lowering ability.

A Randomized, Multicenter, Double-blind, Placebo-controlled, 3 × 3 Factorial Design, Phase II Study to Evaluate the Efficacy and Safety of the Combination of Fimasartan/Amlodipine in Patients With Essential Hypertension.

PURPOSE: The objective of this study was to evaluate the efficacy and safety of a fimasartan/amlodipine combination in patients with hypertension and to determine the optimal composition for a future single-pill combination formulation. METHODS: This Phase II study was conducted by using a randomized, multicenter, double-blind, placebo-controlled, 3 × 3 factorial design. After a 2-week placebo run-in period, eligible hypertensive patients (with a sitting diastolic blood pressure [SiDBP] between 90 and 114 mm Hg) were randomized to treatment. They received single or combined administration of fimasartan at 3 doses (0, 30, and 60 mg) and amlodipine at 3 doses (0, 5, and 10 mg) for 8 weeks. The primary efficacy end point was the change in SiDBP from baseline and at week 8; secondary end points included the change in SiDBP from baseline and at week 4 and the changes in sitting systolic blood pressure from baseline and at weeks 4 and 8. Treatment-emergent adverse events (AEs) were also assessed. FINDINGS: 420 Korean patients with mild to moderate hypertension were randomly allocated to the 9 groups. Mean (SD) SiDBP changes in each group after 8 weeks were as follows: placebo, -6.0 (8.5) mm Hg; amlodipine 5 mg, -10.6 (9.2) mm Hg; amlodipine 10 mg, -15.9 (7.2) mm Hg; fimasartan 30 mg, -10.1 (9.1) mm Hg; fimasartan 60 mg, -13.0 (10.0) mm Hg; fimasartan 30 mg/amlodipine 5 mg, -16.2 (8.5) mm Hg; fimasartan 30 mg/amlodipine 10 mg, -19.5 (7.5) mm Hg; fimasartan 60 mg/amlodipine 5 mg, -16.6 (6.9) mm Hg; and fimasartan 60 mg/amlodipine 10 mg, -21.5 (8.3) mm Hg. All treatment groups produced significantly greater reductions in blood pressure compared with the placebo group. In addition, all combination treatment groups had superior reductions in blood pressure compared with the monotherapy groups. In the combination treatment groups, doubling fimasartan dose in the given dose of amlodipine did not show further BP reduction, whereas doubling amlodipine dose showed significantly further BP reduction in the given dose of fimasartan. During the study period, 75 (17.9%) of 419 patients experienced 110 AEs. Ninety-five AEs were mild, 9 were moderate, and 6 were severe in intensity. Eight patients discontinued the study due to AEs. There was no significant difference in incidence of AEs among groups (P = 0.0884). The most common AE was headache (12 patients [2.9%]), followed by dizziness (11 patients [2.6%]) and elevated blood creatine phosphokinase levels (6 patients [1.4%]). IMPLICATIONS: Fimasartan combined with amlodipine produced superior blood pressure reductions and low levels of AEs compared with either monotherapy. Therefore, a single-pill combination with fimasartan 60 mg/amlodipine 10 mg will be developed. ClinicalTrials.gov: NCT01518998.

Effect of atorvastatin and clopidogrel co-administration after coronary stenting in korean patients with stable angina.

BACKGROUND AND OBJECTIVES: It was reported that atorvastatin co-administered with clopidogrel for 8 months did not affect the anti-platelet potency of clopidogrel in Korean patients with acute coronary syndrome, but not in patients with stable angina. We investigated whether co-administration of statins with clopidogrel affected the anti-platelet efficacy of clopidogrel in Korean patients with stable angina. SUBJECTS AND METHODS: This was a randomized, open-label and two-period crossover design study conducted at two centers. Two hundreds thirty three patients with stable angina scheduled for coronary stenting were randomized into two groups. In Group A, 119 patients first received atorvastatin (10 mg) followed by fluvastatin (80 mg) for 12 weeks per treatment. In Group B, 114 patients received the same treatments in reverse order. RESULTS: Baseline adenosine diphosphate (ADP, 10 µmol/L)-induced platelet aggregation was 54.4±9.1% in Group A and 53.8±9.0% in Group B (p=0.44), and significant differences were noted after each treatment period (p<0.001). Inhibition of platelet aggregation was similar between Group A and Group B at 24 hours following clopidogrel loading (29.2±11.0% vs. 30.4±12.7%; p=0.42). The two treatment least square means of 12-week ADP (10 mol/L)-induced platelet aggregation [29.50±0.79 {standard error (SE)}% on the atorvastatin treatment group vs. 28.16±0.70 (SE)% in the fluvastatin treatment group] in a 2×2 cross-over study were not significantly different (p=0.204). CONCLUSION: Statin and clopidogrel co-administration for 12 weeks is not associated with attenuated anti-platelet activity of clopidogrel in Korean patients with stable angina after coronary stenting, in support of the findings of similar studies conducted in Caucasian populations.

Beneficial Effect of Efonidipine, an L- and T-Type Dual Calcium Channel Blocker, on Heart Rate and Blood Pressure in Patients With Mild-to-Moderate Essential Hypertension.

BACKGROUND AND OBJECTIVES: Efonidipine hydrochloride, an L- and T-type dual calcium channel blocker, is suggested to have a heart rate (HR)-slowing action in addition to a blood pressure (BP)-lowering effect. The aim of this study was to determine the effect of efonidipine on HR and BP in patients with mild-to-moderate hypertension. SUBJECTS AND METHODS: In a multi-center, prospective, open-labeled, single-armed study, we enrolled 53 patients who had mild-to-moderate hypertension {sitting diastolic BP (SiDBP) 90-110 mmHg}. After a 2-week washout, eligible patients were treated with efonidipine (40 mg once daily for 12 weeks). The primary end point was the change in HR from baseline to week 12. The secondary end-point included the change in trough sitting BP and 24-hour mean BP between baseline and week 12. Laboratory and clinical adverse events were monitored at each study visit (4, 8, and 12 weeks). RESULTS: Fifty-two patients were included in the intention-to-treat analysis. After 12 weeks of treatment with efonidipine, the resting HR decreased significantly from baseline to week 12 {from 81.5±5.3 to 71.8±9.9 beats/minute (difference, -9.9±9.0 beats/minute), p<0.0001}. The trough BP {sitting systolic blood pressure (SiSBP) and SiDBP} and 24-hour mean BP also decreased significantly (SiSBP: from 144.6±8.2 to 132.9±13.5 mmHg, p<0.0001; SiDBP: from 96.9±5.4 to 88.3±8.6 mmHg, p<0.0001, 24-hour mean systolic BP: from 140.4±13.5 to 133.8±11.6 mmHg, p<0.0001; 24-hour mean diastolic BP: from 91.7±8.7 to 87.5±9.5 mmHg, p<0.0001). CONCLUSION: Efonidipine was effective in controlling both HR and BP in patients with mild-to-moderate hypertension.