Ezetimibe and Rosuvastatin Combination Treatment Can Reduce the Dose of Rosuvastatin Without Compromising Its Lipid-lowering Efficacy.

PURPOSE: The goal of this study was to compare the lipid-lowering efficacy of the combination of ezetimibe and low- or intermediate-intensity statin therapy versus that of high-intensity statin monotherapy. METHODS: This study is a post hoc analysis of an 8-week, randomized, double-blind, Phase III trial. Patients who had hypercholesterolemia and required lipid-lowering treatment were randomly assigned to 1 of 6 treatment groups: rosuvastatin 5 mg (R5, n = 68), rosuvastatin 10 mg (R10, n = 67), rosuvastatin 20 mg (R20, n = 69), and ezetimibe 10 mg combined with rosuvastatin 5 mg (R5 + E10, n = 67), rosuvastatin 10 mg (R10 + E10, n = 68), and rosuvastatin 20 mg (R20 + E10, n = 68) daily. The effects of coadministration of ezetimibe and a low dose of rosuvastatin on lipid parameters and the target achievement rate were compared between the R5 + E10 and R10 treatment groups, the R5 + E10 and R20 treatment groups, and the R10 + E10 and R20 treatment groups. FINDINGS: Reductions in total cholesterol, LDL-C, apolipoprotein B, the apolipoprotein B/A1 ratio, and non-HDL-C were not different between the R5 + E10 and R10 treatment groups (all, P > 0.017), the R5 + E10 and R20 treatment groups (all, P > 0.017), and the R10 + E10 and R20 treatment groups (all, P > 0.017). R5 + E10 treatment showed efficacy comparable to that of R10 or R20 in affording LDL levels <50% of the baseline level (R5 + E10 vs R10, 73.13% vs 62.69% [P = 0.1952]; R5 + E10 vs R20, 73.13% vs 73.91% [P = 0.9180]), LDL-C levels <70 mg/dL (R5 + E10 vs R10, 64.18% vs 55.22% [P = 0.2906]; R5 + E10 vs R20, 64.18% vs 62.32% [P = 0.8220]), and LDL-C levels <50% of the baseline level or <70 mg/dL (R5 + E10 vs R10, 77.61% vs 70.15% [P = 0.3255]; R5 + E10 vs R20, 77.61% vs 78.26% [P = 0.9273]). The R10 + E10 treatment group was better than the R20 treatment group in achieving the target LDL-C level <70 mg/dL (83.82% vs 62.32%; P = 0.0046), even among participants with a baseline LDL-C level >135 mg/dL (77.5% vs 48.8%, respectively; P = 0.0074). IMPLICATIONS: Ezetimibe combined with low- or intermediate-intensity statin therapy has lipid-lowering efficacy comparable to or better than that of high-intensity rosuvastatin monotherapy. The results of the present study indicate that the combination treatment with ezetimibe is advantageous in that it permits dose reduction of rosuvastatin without compromising the lipid-lowering efficacy of rosuvastatin. ClinicalTrials.gov identifier: NCT02205606.

Long-Term Comparison of Platinum Chromium Everolimus-Eluting Stent vs. Cobalt Chromium Zotarolimus-Eluting Stent　- 3-Year Outcomes From the HOST-ASSURE Randomized Clinical Trial.

BACKGROUND: There are limited data on the long-term outcome of platinum chromium-based everolimus-eluting stents (PtCr-EES) vs. cobalt chromium-based zotarolimus-eluting stents (CoCr-ZES).Methods and Results:A total of 3,755 patients undergoing percutaneous coronary intervention (PCI) were randomized 2:1 to PtCr-EES or CoCr-ZES, and 96.0% of patients completed the 3-year clinical follow-up. The primary outcome was target lesion failure (TLF), defined as a composite of cardiac death, target vessel-related myocardial infarction (MI), and clinically-driven target lesion revascularization (TLR). At 3 years, TLF occurred in 5.3% and in 5.4% of the PtCr-EES and CoCr-ZES groups, respectively (hazard ratio 0.978; 95% confidence interval 0.730-1.310, P=0.919). There were no significant differences in the individual components of TLF. Routine angiographic follow-up was performed in 38.9% of the total patients. In a landmark analysis of the subgroup that had follow-up angiography, the clinically-driven TLR rate of CoCr-ZES was significantly higher than PtCr-EES group during the angiography follow-up period (P=0.009). Overall definite and probable stent thrombosis rates were very low in both groups (0.5% vs. 0.6%, P=0.677). CONCLUSIONS: PtCr-EES and CoCr-ZES had similar and excellent long-term outcomes in both efficacy and safety after PCI in an all-comer population.

Cardioprotective Effects of a Phlorotannin Extract Against Doxorubicin-Induced Cardiotoxicity in a Rat Model.

Long-term therapy with doxorubicin (DOX) is associated with high incidence of cumulative and irreversible dilated cardiomyopathy. The goal of this study was to evaluate the cardioprotective effects and safety of a phlorotannin extract from a brown algae Ecklonia cava (Seapolynol™, SPN) against DOX-induced cardiotoxicity in a rat model. A total of 42 rats were divided into six groups: control, low-dose SPN (LDS), high-dose SPN (HDS), DOX, DOX with low-dose SPN (DOX+LDS), and DOX with high-dose SPN (DOX+HDS). Echocardiography was performed at baseline and after 6 weeks. In left ventricular (LV) ejection fraction, DOX and DOX+LDS groups showed significant decreases (P < .001), while LDS, HDS, and DOX+HDS groups showed no significant change compared with control group. In LV mass index, DOX and DOX+LDS groups showed significant increases (P < .001 and P = .013), while LDS, HDS, and DOX+HDS groups showed no significant change compared with control group. In electron microscopy of the LV wall tissue, DOX+HDS group showed markedly less impaired myofibrils and mitochondria compared with both DOX and DOX+LDS groups. On the findings in echocardiography and electron microscopy, 6-week oral administration of SPN was safe and cardioprotective in a DOX-induced rat cardiotoxicity model in a dose-dependent manner.

Efficacy and Tolerability of Combination Therapy Versus Monotherapy with Candesartan and/or Amlodipine for Dose Finding in Essential Hypertension: A Phase II Multicenter, Randomized, Double-blind Clinical Trial.

PURPOSE: Intensive blood pressure (BP) lowering is important for the treatment of hypertension; however, it has been a challenge to achieve target BP in many patients. The purpose of this study was to explore the optimal dosage of a fixed-dose combination of candesartan cilexetil (CAN) and amlodipine besylate (AML), by examining the tolerability and efficacy of CAN/AML combination therapy compared with those of monotherapy with either drug in patients with essential hypertension. METHODS: This Phase II multicenter, randomized, double-blind clinical trial enrolled patients aged 19 years or older with essential hypertension, defined as a mean sitting diastolic BP (msDBP) between 95 and 115 mm Hg, and a mean sitting systolic BP (msSBP) of <200 mm Hg after a 2-week placebo run-in period. A total of 635 patients were screened, of whom 439 were randomized to receive treatment; 425 patients were included in the full analysis set (combination therapy, 212; monotherapy, 213). Participants were randomly assigned to receive 1 of 8 treatments: CAN (8 or 16 mg), AML (5 or 10 mg), CAN/AML (8 mg/5 mg, 8 mg/10 mg, 16 mg/5 mg, or 16 mg/10 mg), once daily for 8 weeks. FINDINGS: After 8 weeks of treatment, changes in msDBP were significantly greater in the groups receiving CAN/AML combination therapies compared with monotherapies at matched doses, with the exception of CAN 8 mg/AML 10 mg versus AML 10 mg. The response to treatment and the achievement of target BP (both msSBP and msDBP) at week 8 were significantly greater overall in the groups that received combination therapy versus monotherapy. All medications were relatively well tolerated in each group. IMPLICATIONS: Eight-week administration of CAN/AML (8 mg/5 mg, 16 mg/5 mg, and 16 mg/10 mg) resulted in a significantly greater BP reduction than that with CAN or AML monotherapy, and was determined to be well tolerated. ClinicalTrials.gov identifier: NCT02944734.

Effects of metabolic syndrome on aortic pulse wave velocity.

BACKGROUND: The purpose of this study was to compare the value and evaluate the validity of non-invasive methods for the detection of vascular stiffness in never-treated individuals with metabolic syndrome (MetS). METHODS: A total of 59 subjects (mean age, 60 ± 12 years; male:female = 35:24) were enrolled in the study and were categorized into the positive MetS (MetS[+]: N = 32) and negative group (MetS[-]: N = 27), according to the parameters set by the National Cholesterol Education Program's Adult Treatment Panel III. Pulse wave velocity (PWV) of the aorta, arm, and leg, Framingham risk score (FRS), ankle-brachial index (ABI), and carotid intima-media thickness (IMT) for vascular aging were measured for the two groups. RESULTS: Aortic PWV (PWVaor) was significantly higher in MetS(+) than MetS(-) group (7.0 ± 1.4 m/s vs. 8.4 ± 1.6 m/s, p < 0.01), while ABI was significantly lower in MetS(+) than MetS(-) group (1.2 ± 0.1 vs. 1.1 ± 0.2, p = 0.03), respectively. FRS was significantly higher in MetS(+) than MetS(-) group (11 ± 5 vs. 14 ± 4, p = 0.05). The both mean IMT was higher in MetS(+) than MetS(-) group (right: 0.94 ± 0.20 mm vs. 0.81 ± 0.20 mm, p = 0.03; left: 0.93 ± 0.20 mm vs. 0.79 ± 0.20 mm, p = 0.03, respectively). For predicting the probability of the presence of MetS, PWVaor was an independent tool (p = 0.04; odds ratio, 1.88; 95% confidence interval, 1.03 to 3.42) and a cut-off value of PWVaor of 7.4 m/s showed a sensitivity of 66.7% and a specificity of 47.6%. CONCLUSIONS: We suggest that PWVaor, combined with traditional tools, can play an important role as a complementary or alternative tool for the detection of vascular stiffness in never-treated individuals with MetS.

Efficacy and safety of two fixed-dose combinations of S-amlodipine and telmisartan (CKD-828) versus S-amlodipine monotherapy in patients with hypertension inadequately controlled using S-amlodipine monotherapy: an 8-week, multicenter, randomized, double-blind, Phase III clinical study.

PURPOSE: To evaluate the blood pressure (BP) lowering efficacy and safety of CKD-828, a fixed-dose combination of S-amlodipine (the more active isomer of amlodipine besylate, which is calcium channel blocker) and telmisartan (long acting angiotensin receptor blocker), in patients with hypertension inadequately controlled with S-amlodipine monotherapy. PATIENTS AND METHODS: Eligible patients (N=187) who failed to respond after 4-week S-amlodipine 2.5 mg monotherapy (sitting diastolic blood pressure [sitDBP] ≥90 mmHg) to receive CKD-828 2.5/40 mg (n=63), CKD-828 2.5/80 mg (n=63), or S-amlodipine 2.5 mg (n=61) for 8 weeks. The primary efficacy endpoint, mean sitDBP change from baseline to Week 8, was compared between the combination (CKD-828 2.5/40 mg and CKD-828 2.5/80 mg) and S-amlodipine monotherapy groups. The safety was assessed based on adverse events, vital signs, and physical examination findings. RESULTS: After the 8-week treatment, changes in sitDBP/systolic BP (SBP) were -9.67±6.50/-12.89±11.78, -10.72±6.19/-13.79±9.41, and -4.93±7.26/-4.55±11.27 mmHg in the CKD-828 2.5/40 mg (P<0.0001/P<0.0001), CKD-828 2.5/80 mg (P<0.0001/P<0.0001), and S-amlodipine 2.5 mg (P<0.0001/P=0.0027) groups, respectively, which were all significant BP reductions. At Week 8, the CKD-828 2.5/40 mg (sitDBP/SBP: P=0.0002/P<0.0001) and CKD-828 2.5/80 mg (sitDBP/SBP: P=0.0001/P<0.0001) showed superior BP-lowering effects to S-amlodipine 2.5 mg (P<0.001). At Week 4, all groups showed significant antihypertensive effects but both CKD-828 combinations (CKD-828 2.5/40 mg and CKD-828 2.5/80 mg) exhibited superior BP-lowering effects to that of S-amlodipine 2.5 mg (sitDBP/SBP: P=0.0028/P=0.0001 and P<0.0001/P=0.0012, respectively). The adverse event incidence was significantly lower in the CKD-828 2.5/40 mg (9.52%, P=0.0086) than in the S-amlodipine 2.5 mg group (27.87%) and increasing the telmisartan dose induced no unexpected adverse events, suggesting the safety of CKD-828. CONCLUSION: CKD-828 is an effective and safe option for patients with inadequate responses to S-amlodipine monotherapy.

Effect of fixed-dose combinations of ezetimibe plus rosuvastatin in patients with primary hypercholesterolemia: MRS-ROZE (Multicenter Randomized Study of ROsuvastatin and eZEtimibe).

AIM: We aimed to compare the effects of fixed-dose combinations of ezetimibe plus rosuvastatin to rosuvastatin alone in patients with primary hypercholesterolemia, including a subgroup analysis of patients with diabetes mellitus (DM) or metabolic syndrome (MetS). METHOD: This multicenter eight-week randomized double-blind phase III study evaluated the safety and efficacy of fixed-dose combinations of ezetimibe 10 mg plus rosuvastatin, compared with rosuvastatin alone in patients with primary hypercholesterolemia. Four hundred and seven patients with primary hypercholesterolemia who required lipid-lowering treatment according to the ATP III guideline were randomized to one of the following six treatments for 8 weeks: fixed-dose combinations with ezetimibe 10 mg daily plus rosuvastatin (5, 10, or 20 mg daily) or rosuvastatin alone (5, 10, or 20 mg daily). RESULTS: Fixed-dose combination of ezetimibe plus rosuvastatin significantly reduced LDL cholesterol, total cholesterol, and triglyceride levels compared with rosuvastatin alone. Depending on the rosuvastatin dose, these fixed-dose combinations of ezetimibe plus rosuvastatin provided LDL cholesterol, total cholesterol, and triglyceride reductions of 56%-63%, 37%-43%, and 19%-24%, respectively. Moreover, the effect of combination treatment on cholesterol levels was more pronounced in patients with DM or MetS than in non-DM or non-MetS patients, respectively, whereas the effect of rosuvastatin alone did not differ between DM vs non-DM or MetS vs non-MetS patients. CONCLUSION: Fixed-dose combinations of ezetimibe and rosuvastatin provided significantly superior efficacy to rosuvastatin alone in lowering LDL cholesterol, total cholesterol, and triglyceride levels. Moreover, the reduction rate was greater in patients with DM or MetS.

Beneficial Effect on Surrogate Markers of Heart Failure with Bisoprolol Up-Titration to Recommended Targets in Korean Patients with Heart Failure and Left Ventricular Systolic Dysfunction.

INTRODUCTION: The objective of this study was to establish the benefit of bisoprolol up-titration toward recommended dosage targets, versus lower-dose maintenance, in heart failure (HF) patients with systolic dysfunction. METHODS: Korean HF patients received bisoprolol 1.25 mg/day, incrementally up-titrated toward 10 mg/day in the absence of contraindications. After 26 weeks' treatment, patients were grouped as low-dose (<3.75 mg/day) or high-dose (≥3.75 mg/day). Primary endpoint was change in serum N-terminal probrain natriuretic peptide (NT-proBNP). Other markers of HF were also evaluated. RESULTS: 159 of 180 enrolled patients were evaluable. After 16 weeks' follow-up, there were 52 and 107 patients in the low- and high-dose groups respectively. Mean bisoprolol dosage was 5.4 mg/day; 24% of patients achieved target (10 mg/day). Mean logNT-proBNP significantly decreased in both groups, with no significant difference in the magnitude of change between groups. Mean heart rate (HR) and blood pressure decreased significantly in both groups, but only HR showed a significantly greater change in high-dose versus low-dose patients. In both groups, mean left ventricular (LV) end-systolic and end-diastolic dimensions were significantly decreased and mean LV ejection fraction was significantly improved. Mean 6-min walk test distances improved in both groups (significant in low-dose patients only). Functional class improvement was observed in both low- and high-dose patients. No patients were rehospitalized due to aggravated HF. CONCLUSIONS: In HF patients with systolic dysfunction, any bisoprolol dose is beneficial, but an attempt to up-titrate toward guideline-recommended dosages offers additional benefit in terms of restoration of LV systolic function and remodeling.

Impact of the ß-1 adrenergic receptor polymorphism on tolerability and efficacy of bisoprolol therapy in Korean heart failure patients: association between ß adrenergic receptor polymorphism and bisoprolol therapy in heart failure (ABBA) study.

BACKGROUND/AIMS: We evaluated the association between coding region variants of adrenergic receptor genes and therapeutic effect in patients with congestive heart failure (CHF). METHODS: One hundred patients with stable CHF (left ventricular ejection fraction [LVEF] < 45%) were enrolled. Enrolled patients started 1.25 mg bisoprolol treatment once daily, then up-titrated to the maximally tolerable dose, at which they were treated for 1 year. RESULTS: Genotypic analysis was carried out, but the results were blinded to the investigators throughout the study period. At position 389 of the ß-1 adrenergic receptor gene (ADRB1), the observed minor Gly allele frequency (Gly389Arg + Gly389Gly) was 0.21, and no deviation from Hardy-Weinberg equilibrium was observed in the genotypic distribution of Arg389Gly (p = 0.75). Heart rate was reduced from 80.8 ± 14.3 to 70.0 ± 15.0 beats per minute (p < 0.0001). There was no significant difference in final heart rate across genotypes. However, the Arg389Arg genotype group required significantly more bisoprolol compared to the Gly389X (Gly389Arg + Gly389Gly) group (5.26 ± 2.62 mg vs. 3.96 ± 2.05 mg, p = 0.022). There were no significant differences in LVEF changes or remodeling between two groups. Also, changes in exercise capacity and brain natriuretic peptide level were not significant. However, interestingly, there was a two-fold higher rate of readmission (21.2% vs. 10.0%, p = 0.162) and one CHF-related death in the Arg389Arg group. CONCLUSIONS: The ADRB1 Gly389X genotype showed greater response to bisoprolol than the Arg389Arg genotype, suggesting the potential of individually tailoring ß-blocker therapy according to genotype.

Evaluation of the Efficacy and Safety of the Lercanidipine/Valsartan Combination in Korean Patients With Essential Hypertension Not Adequately Controlled With Lercanidipine Monotherapy: A Randomized, Multicenter, Parallel Design, Phase III Clinical Trial.

PURPOSE: The objective of this study was to evaluate the efficacy and safety of the lercanidipine/valsartan combination compared with lercanidipine monotherapy in patients with hypertension. METHODS: Part 1 of this study was the randomized, multicenter, double-blind, parallel group, Phase III, 8-week clinical trial to compare superiority of lercanidipine 10 mg/valsartan 80 mg (L10/V80) and lercanidipine 10 mg/valsartan 160 mg (L10/V160) combinations with lercanidipine 10 mg (L10) monotherapy. At screening, hypertensive patients, whose diastolic blood pressure (DBP) was >90 mm Hg after 4 weeks with L10, were randomized to 3 groups of L10, L10/V80, and L10/V160. The primary end point was the change in the mean sitting DBP from baseline (week 0) after 8 weeks of therapy. Patients who were randomly assigned to L10/V160 and whose mean DBP was still ≥ 90 mm Hg in part 1 were enrolled to the up-titration extension study with lercanidipine 20 mg/valsartan 160 mg (L20/V160) (part 2). FINDINGS: Of 772 patients screened, 497 were randomized to 3 groups (166 in the L10 group, 168 in the L10/V80 group, and 163 in the L10/V160 group). Mean (SD) age was 55 (9.9) years, and male patients comprised 69%. The mean (SD) baseline systolic blood pressure (SBP)/DBP were 148.4 (15.1)/94.3 (9.5) mm Hg. No significant differences were found between groups in baseline characteristics except the percentages of previous history of antihypertensive medication. The primary end points, the changes of mean (SD) DBP at week 8 from the baseline were -2.0 (8.8) mm Hg in the L10 group, -6.7 (8.5) mm Hg in L10/V80 group, and -8.1 (8.4) mm Hg in L10/V160 group. The adjusted mean difference between the combination groups and the L10 monotherapy group was -4.6 mm Hg (95% CI, -6.5 to -2.6; P < 0.001) in the L10/V80 group and -5.9 mm Hg (95% CI, -7.9 to -4.0, P < 0.001) in the L10/V160 group, which had significantly greater efficacy in BP lowering. A total of 74 patients were enrolled in the part 2 extension study. Changes of mean (SD) DBP and SBP from week 8 to week 12 and week 16 were -5.6 (7.9)/-8.0 (12.0) mm Hg and -5.5 (7.0)/-8.5 (11.3) mm Hg, respectively. For evaluation of the safety profile, the frequencies of adverse events between groups were also not significantly different. The most frequently reported adverse events were headache (6 cases, 20.7%) in the L10 group, dizziness (8 cases, 16.3%) in L10/V80 group, and nasopharyngitis (3 cases, 9.4%) in L10/V160 group, and the incidences of adverse events were not different between groups. IMPLICATIONS: Treatment of L10/V80 or L10/V160 combination therapy resulted in significantly greater BP lowering compared with L10 monotherapy. Moreover, the L20/V160 high dose combination had additional BP lowering effect compared with nonresponders with the L10/V160 combination. ClinicalTrials.gov: NCT01928628.

Usefulness of the parameters of quantitative myocardial perfusion contrast echocardiography in patients with chronic total occlusion and collateral flow.

BACKGROUND: Microvascular obstruction becomes more severe with longer duration of ischemia, such as chronic total occlusion (CTO) which used to have collateral flow. In this study, we explored the correlation between parameters measured using quantitative myocardial perfusion contrast echocardiography (MCE) and the angiographic collateral flow grades in patients with CTO. Furthermore, we investigated the usefulness of the parameters of quantitative MCE for the measurement of microvasculature changes after revascularization of CTO lesions. METHODS: Between January 2011 and January 2013, 44 patients who had undergone coronary angiography (CAG) due to chest pain and had confirmed CTO lesions were enrolled in this prospective observational study. All patients had baseline MCE within 24 hours after diagnostic CAG. Patients were then assigned to one of two groups: a medical therapy group (Group I, n = 20) or a reperfusion group with percutaneous coronary intervention (PCI) (Group II, n = 24). All patients had follow-up MCE 3 months later. RESULTS: Consistent with the CAG results in both groups, on baseline MCE, the myocardial blood flow (AI × ß) values were higher in Grade III collateral flow than in Grade I or II collateral flow (AI of collateral flow Grade I vs. Grade II vs. Grade III: 2.34 ± 2.65 vs. 2.52 ± 2.67 vs. 3.87 ± 4.57, P = 0.038). The plateau acoustic intensity (AI) and wall-motion score index (WMSI) were significantly improved at the 3-month follow-up after successful reperfusion with PCI (5.75 ± 3.52 before vs. 8.11 ± 6.02 after, P = 0.004) and (1.76 ± 0.83 before vs. 1.43 ± 0.64 after, P ≤ 0.001), respectively. However, the AI and WMSI values were not improved in the medical treatment group, (6.04 ± 4.64 before vs. 6.01 ± 5.52 after, P = 0.966) and (1.61 ± 0.82 before vs. 1.66 ± 0.67 after, P = 0.616), respectively. CONCLUSIONS: MCE is a useful tool for estimating microvascularity in patients with CTO lesions and correlates well with angiographic collateral flow.

Three-year patient-related and stent-related outcomes of second-generation everolimus-eluting Xience V stents versus zotarolimus-eluting resolute stents in real-world practice (from the Multicenter Prospective EXCELLENT and RESOLUTE-Korea Registries).

Long-term outcomes are imperative to confirm safety of drug-eluting stents. There have been 2 randomized controlled trials comparing everolimus-eluting stents (EESs) and Resolute zotarolimus-eluting stents (ZES-Rs). To date, long-term clinical outcomes of these stents were limited to only 1 report, which has recently reported 4-year comparisons of these stents. Therefore, more evidence is needed regarding long-term clinical outcomes of the second-generation stents. This study compared the long-term clinical outcomes of EES with ZES-R in "all-comer" cohorts up to 3-year follow-up. The EXCELLENT and RESOLUTE-Korea registries prospectively enrolled 3,056 patients treated with EES and 1,998 with ZES-R, respectively, without exclusions. Stent-related composite outcomes (target lesion failure) and patient-related composite events up to 3-year follow-up were compared in crude and propensity score-matched analyses. Of 5,054 patients, 3,830 patients (75.8%) had off-label indication (2,217 treated with EES and 1,613 treated with ZES-R). The stent-related outcome (189 [6.2%] vs 127 [6.4%], p = 0.812) and the patient-related outcome (420 [13.7%] vs 250 [12.5%], p = 0.581) did not differ between EES and ZES-R, respectively, at 3 years, which was corroborated by similar results from the propensity score-matched cohort (hazard ratio [HR] 0.92, 95% confidence interval [CI] 0.70 to 1.20, p = 0.523 and 0.85, 95% CI 0.70 to 1.02, p = 0.081, for stent- and patient-related outcomes, respectively). The rate of definite or probable stent thrombosis up to 3 years (22 [0.7%] vs 10 [0.5%], p = 0.370) was also similar. The rate of very late definite or probable stent thrombosis was very low and comparable between the 2 stents (3 [0.1%] vs 1 [0.1%], p = 0.657). In multivariate analysis, chronic renal failure (adjusted HR 3.615, 95% CI 2.440 to 5.354, p <0.001) and off-label indication (adjusted HR 1.782, 95% CI 1.169 to 2.718, p = 0.007) were the strongest predictors of target lesion failure at 3 years. In conclusion, both stents showed comparable safety and efficacy at 3-year follow-up in this robust real-world registry with unrestricted use of EES and ZES-R. Overall incidences of target lesion failure and definite stent thrombosis, including very late stent thrombosis, were low, even in the patients with off-label indications, suggesting excellent long-term safety and sustained efficacy of both types of second-generation drug-eluting stents.

Doppler-derived left ventricular negative dP/dt as a predictor of atrial fibrillation or ischemic stroke in patients with degenerative mitral regurgitation and normal ejection fraction.

INTRODUCTION: The aim of this study was to investigate the role of Doppler-derived left ventricular (LV) -dP/dt in predicting atrial fibrillation (AF) or ischemic stroke in patients with moderate to severe degenerative mitral regurgitation (MR). METHODS: Doppler-derived LV -dP/dt was determined from the continuous-wave Doppler spectrum of the MR jet (-dP/dt = 32/time between 3 and 1 m/sec) in 80 patients (mean age 59 ± 16 years, 41% men) with moderate to severe degenerative MR, normal LV ejection fraction (LVEF ≥ 60%), and sinus rhythm at diagnosis. Events were defined as new AF or ischemic stroke. RESULTS: During a mean follow-up of 18 ± 13 months, there were 9 events (6 new AF, 3 ischemic strokes). Univariate analysis showed that older age, decreased LV -dP/dt, increased LV mass index, and left atrial volume index (LAVI), shortened deceleration time (DT), reduced A' velocity, and elevated E/E' ratio, prolongation of pulmonary venous (PV) atrial reversal (AR) flow duration relative to mitral inflow A-wave duration (AR-Adur) were associated with events. In multivariate Cox regression analysis, Doppler-derived LV -dP/dt (for each 100 mmHg/sec increase, hazard ratio: 0.165, 95% confidence interval: 0.036-0.761, P = 0.021) and E/E' (hazard ratio: 0.820, 95% confidence interval: 0.682-0.987, P = 0.036) were significant independent predictors of AF or ischemic stroke. CONCLUSIONS: Doppler-derived LV -dP/dt is independently associated with the occurrence of AF or ischemic stroke in patients with moderate to severe degenerative MR and provides additional prognostic information.

Benidipine has effects similar to losartan on the central blood pressure and arterial stiffness in mild to moderate essential hypertension.

BACKGROUND: Central blood pressure (BP) is pathophysiologically more important than peripheral BP for the pathogenesis of cardiovascular disease. Arterial stiffness is also a good predictor of cardiovascular morbidity and mortality. The effects of benidipine, a unique dual L-/T-type calcium channel blocker, on central BP have not been reported. This study aimed to compare the effect of benidipine and losartan on the central BP and arterial stiffness in mild to moderate essential hypertensives. METHODS: This 24 weeks, multi-center, open label, randomized, active drug comparative, parallel group study was designed as a non-inferiority study. The eligible patients (n = 200) were randomly assigned to receive benidipine (n = 101) or losartan (n = 99). Radial artery applanation tonometry and pulse wave analysis were used to measure the central BP, pulse wave velocity (PWV) and augmentation index (AIx). We also measured the metabolic and inflammatory markers. RESULTS: After 24 weeks, the central BP decreased significantly from baseline by (16.8 ± 14.0/10.5 ± 9.2) mmHg (1 mmHg = 0.133 kPa) (systolic/diastolic BP; P < 0.001) in benidipine group and (18.9 ± 14.7/12.1 ± 10.2) mmHg (P < 0.001) in losartan group respectively. Both benidipine and losartan groups significantly lowered peripheral BP (P < 0.001) and AIx (P < 0.05), but there were no significant differences between the two groups. The mean aortic, brachial and femoral PWV did not change in both groups after 24-week treatment. There were no significant changes of the blood metabolic and inflammatory biomarkers in each group. CONCLUSION: Benidipine is as effective as losartan in lowering the central and peripheral BP, and improving arterial stiffness.

C-type natriuretic Peptide as a surrogate marker in variant angina pectoris.

BACKGROUND AND OBJECTIVES: The purpose of this study was to assess the value of C-type natriuretic peptide (CNP) as a surrogate marker for detection of coronary artery spasm in variant angina pectoris (VAP). SUBJECTS AND METHODS: Sixty-six patients (mean age: 51±11 years, M : F=40 : 26) who underwent coronary angiography on suspicion of angina and who were diagnosed with VAP by the acetylcholine-induced spasm provocation test (SPT) were enrolled and divided into a SPT (-) group (n=23) and a SPT (+) group (n=43). Concentrations of CNP and other markers were determined by immunoassay in both groups. RESULTS: Plasma CNP and creatine kinase myoglobin band (CK-MB) concentrations were significantly increased in the SPT (+) group relative to the SPT (-) group (CNP, 5.268±1.800 pg/mL vs. 3.342±1.150 pg/mL, p=0.002; CK-MB, 2.54±1.03 ng/dL vs. 1.86±0.96 ng/dL, p=0.019, respectively) while plasma high sensitivity C-reactive protein (hs-CRP) and N-terminal pro-brain natriuretic peptide (NT pro-BNP) concentrations were not significantly different between the SPT (-) group and SPT (+) group (hs-CRP, 2.76±4.99 mg/L vs. 3.13±4.88 mg/L, p=0.789; NT pro-BNP, 49±47 pg/mL vs. 57±63 pg/mL, p=0.818, respectively). Plasma CNP concentration was independently associated with the VAP via SPT {odds ratio: 2.014 (95% confidence interval: 1.016-3.992), p=0.045}. A CNP cut-off value of 4.096 pg/mL was found to have a sensitivity of 68.2% and a specificity of 40.0% for predicting the probability of VAP via SPT. CONCLUSION: Increased plasma CNP concentration in patients with VAP may have an impact on the regulation of endothelial function in accordance with the progression of atherosclerosis. Further analysis is warranted to develop clinical applications of this finding.

Randomized trial comparing the efficacy between different types of paclitaxel-eluting stents: the comparison of efficacy between COroflex PLEASe ANd Taxus stent (ECO-PLEASANT) randomized controlled trial.

AIMS: Paclitaxel-eluting stents (PESs) have been shown to inhibit neointimal hyperplasia after percutaneous coronary intervention. Coroflex Please (B Braun, Melsungen, Germany) is a newly developed PES. We compared the clinical and angiographic efficacy of Coroflex Please with Taxus Liberte (Boston Scientific, Natick, MA) in a real-world practice. METHODS AND RESULTS: We performed a prospective, open-label, randomized, controlled study that enrolled 945 patients undergoing percutaneous coronary interventions in 18 centers in Korea. The primary end point was clinically driven target vessel revascularization at 9 months. The baseline characteristics were mostly similar and comparable between 2 groups. At 9 months, the incidence of clinically driven target vessel revascularization was 14.6% for Coroflex and 6.4% for Taxus, which was significantly different (hazard ratio 2.43, 95% CI 1.50-3.94, noninferiority P value = 1.000). This is well corroborated by the difference of in-stent late loss between 2 stents (0.71 ± 0.64 mm vs 0.52 ± 0.50 mm, P < .001) by 9-month follow-up angiography (n = 415 vs 215). Among secondary clinical end points, stent thrombosis (definite and probable) for 1 year was 2.2% in Coroflex and 1.3% in Taxus (P = .317). Also, myocardial infarction for 9 months was higher in Coroflex group than that in Taxus (4.9% vs 1.6%, P = .012), which was partly contributed by the higher incidence of periprocedural myocardial infarction in Coroflex arm (2.2% vs 0.3%, P = .028). CONCLUSIONS: Coroflex Please was inferior to Taxus Liberte with regard to clinical and angiographic efficacy.

Left atrial eccentricity in chronic mitral regurgitation: relation to left atrial function.

AIMS: The aim of this study was to assess the changes in the left atrial (LA) shape and to identify the determinants of these changes in chronic mitral regurgitation (MR). METHODS AND RESULTS: We enrolled 125 consecutive patients (56 ± 16 years, 51% men) with chronic MR caused by myxomatous mitral valve disease in sinus rhythm and 45 control patients (54 ± 15 years, 55% men) undergoing transthoracic Doppler echocardiography. The LA eccentricity index (LAEi) and the LA volume index (LAVi) were used to estimate the LA shape and size, respectively. There were significant decreases in LAEi (r= -0.723, P< 0.001) and increases in LAVi (r= 0.642, P< 0.001) with increasing severity of MR. In multivariate stepwise linear regression analysis, regurgitant fraction (RF) was an independent determinant of the LAE, whereas RF, left ventricular (LV) mass index and LV diastolic dysfunction grade were independent determinants of the LA volume. The LAEi was positively related to the velocity of A' in the entire population (r = 0.238, P = 0.002). On the receiver operating characteristic (ROC) curve analysis, LAEi ≤1.30 was the best cut-off value to reflect the LA systolic dysfunction (A' velocity <7 cm/s; area under the curve was 0.78, P < 0.001). CONCLUSION: LA becomes more spherical with increasing severity of MR, suggesting a decrease in LAE, which is mainly determined by the volume overload. LAE might be closely related to the LA systolic function in chronic MR.

Porcelain heart: rapid progression of cardiac calcification in a patient with hemodialysis.

Cardiac calcification usually occurs in patients with end-stage renal disease. However, rapid progression of cardiac calcification is rarely associated with secondary hyperparathyroidism of end-stage renal disease. We report a patient with end-stage renal disease who showed moderate left ventricular hypertrophy at the first echocardiography, and showed severe myocardial calcification and severe mitral valve stenosis 4 years later. We suspected a rapid progression 'porcelain heart' cardiomyopathy secondary to hyperparathyroidism of end-stage renal disease. The patient underwent parathyroidectomy, and considered mitral valve replacement.

Six-month versus 12-month dual antiplatelet therapy after implantation of drug-eluting stents: the Efficacy of Xience/Promus Versus Cypher to Reduce Late Loss After Stenting (EXCELLENT) randomized, multicenter study.

BACKGROUND: The optimal duration of dual antiplatelet therapy (DAPT) after implantation of drug-eluting coronary stents remains undetermined. We aimed to test whether 6-month DAPT would be noninferior to 12-month DAPT after implantation of drug-eluting stents. METHODS AND RESULTS: We randomly assigned 1443 patients undergoing implantation of drug-eluting stents to receive 6- or 12-month DAPT (in a 1:1 ratio). The primary end point was a target vessel failure, defined as the composite of cardiac death, myocardial infarction, or ischemia-driven target vessel revascularization at 12 months. Rates of target vessel failure at 12 months were 4.8% in the 6-month DAPT group and 4.3% in the 12-month DAPT group (the upper limit of 1-sided 95% confidence interval, 2.4%; P=0.001 for noninferiority with a predefined noninferiority margin of 4.0%). Although stent thrombosis tended to occur more frequently in the 6-month DAPT group than in the 12-month group (0.9% versus 0.1%; hazard ratio, 6.02; 95% confidence interval, 0.72-49.96; P=0.10), the risk of death or myocardial infarction did not differ in the 2 groups (2.4% versus 1.9%; hazard ratio, 1.21; 95% confidence interval, 0.60-2.47; P=0.58). In the prespecified subgroup analysis, target vessel failure occurred more frequently in the 6-month DAPT group than in the 12-month group (hazard ratio, 3.16; 95% confidence interval, 1.42-7.03; P=0.005) among diabetic patients. CONCLUSIONS: Six-month DAPT did not increase the risk of target vessel failure at 12 months after implantation of drug-eluting stents compared with 12-month DAPT. However, the noninferiority margin was wide, and the study was underpowered for death or myocardial infarction. Our results need to be confirmed in larger trials. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00698607.

Complete Atrioventricular Block due to Infective Endocarditis of Bicuspid Aortic Valve.

A 38-year-old man visited our emergency department presenting with a 6-day persistent fever. The man had undergone an orthodontic procedure 7 days prior to the visit. He had a fever with a temperature of 38.2℃ and a diastolic murmur (grade III) was detected at the left sternal border. Reddish-brown lines beneath the nails were present, and raised lesions which were red and painful were detected on the soles of the patient's feet. Laboratory findings showed an elevated inflammatory marker. Transthoracic and transesophageal echocardiograms, showed a bicuspid aortic valve, and moderate aortic regurgitation and vegetation were noted. Treatment with antibiotics was given, but 4 days later, a 12 lead electrocardiogram revealed complete atrioventricular (AV) block. Immediately, a temporary pacemaker was inserted, and the following day an aortic valve replacement was performed. Intraoperative findings revealed a fistula around the AV node. He has suffered no subsequent cardiac events during the follow-up.