Deok Kyu Cho

Additive beneficial effects of valsartan combined with rosuvastatin in the treatment of hypercholesterolemic hypertensive patients.

Background and Objectives We compared the efficacy and safety of valsartan and rosuvastatin combination therapy with each treatment alone in hypercholesterolemic hypertensive patients. Subjects and Methods Patients who met inclusion criteria were randomized to receive 1 of the following 2-month drug regimens: valsartan 160 mg plus rosuvastatin 20 mg, valsartan 160 mg plus placebo, or rosuvastatin 20 mg plus placebo. The primary efficacy variables were change in sitting diastolic blood pressure (sitDBP) and sitting systolic blood pressure (sitSBP), and percentage change in low-density lipoprotein-cholesterol (LDL-C) in the combination, valsartan, and rosuvastatin groups. Adverse events (AEs) during the study were analyzed. Results A total of 354 patients were screened and 123 of them were finally randomized. Changes of sitDBP by least squares mean (LSM) were -11.1, -7.2, and -3.6 mm Hg, respectively, and was greater in the combination, as compared to both valsartan (p=0.02) and rosuvastatin (p<0.001). Changes of sitSBP by LSM were -13.2, -10.8, and -4.9 mm Hg, and was greater in the combination, as compared to rosuvastatin (p=0.006) and not valsartan (p=0.42). Percentage changes of LDL-C by LSM were -52, -4, and -47% in each group, and was greater in the combination, as compared to valsartan (p<0.001), similar to rosuvastatin (p=0.16). Most AEs were mild and resolved by the end of the study. Conclusion Combination treatment with valsartan and rosuvastatin exhibited an additive blood pressure-lowering effect with acceptable tolerability, as compared to valsartan monotherapy. Its lipid lowering effect was similar to rosuvatatin monotherapy.

Comparative effect on platelet function of a fixed-dose aspirin and clopidogrel combination versus separate formulations in patients with coronary artery disease: A phase IV, multicenter, prospective, 4-week non-inferiority trial☆

BACKGROUND/OBJECTIVESnThe effect of aspirin and clopidogrel in a fixed-dose combination (FDC) on platelet function was compared with separate formulations in patients that had undergone percutaneous coronary intervention (PCI) with drug-eluting stent (DES).nnnMETHODSnThis was a phase IV, prospective, multicenter, single-arm, non-inferiority study. Patients that had taken aspirin 100 mg and clopidogrel 75 mg once daily as separate formulations for >6 months after PCI with DES were enrolled, and then switched to an aspirin/clopidogrel FDC once-daily for 4 weeks. Platelet reactivity was determined using the VerifyNow® P2Y12 assay at baseline (immediately prior to switching) and 4 weeks later.nnnRESULTSnA total of 648 patients (the full-analysis population; age, 63.6±9.0 years; male, 76.5%) finished the study, and 565 (the per-protocol population) completed without protocol violations. In the per-protocol population, the % inhibitions of P2Y12 and ARU were not significantly different between baseline and after 4 weeks of FDC treatment (29.2±20.0% to 29.0±19.9%, P=0.708; 445.1±69.2 to 446.2±63.0, P=0.799, respectively) and the difference in P2Y12 inhibition observed did not exceed the predetermined limit of non-inferiority (95% CI, -0.9 to 1.3). In the full-analysis population, the % inhibitions of P2Y12, PRU, and ARU were not significantly changed after 4 weeks of FDC treatment.nnnCONCLUSIONSnThis study demonstrates that the efficacy of platelet inhibition by an aspirin/clopidogrel FDC was not inferior to that of separate aspirin and clopidogrel formulations in patients that had undergone PCI with DES.

Efficacy and Tolerability of Telmisartan/Amlodipine + Hydrochlorothiazide Versus Telmisartan/Amlodipine Combination Therapy for Essential Hypertension Uncontrolled With Telmisartan/Amlodipine: The Phase III, Multicenter, Randomized, Double-blind TAHYTI Study

PURPOSEnThis 8-week study in Korea aimed to evaluate the efficacy and tolerability of a telmisartan/amlodipine + hydrochlorothiazide (TAH) combination versus telmisartan/amlodipine (TA) combination in patients with essential hypertension that did not respond appropriately to 4-week treatment with TA.nnnMETHODSnAll patients who met the inclusion criteria received TA (40/5 mg) during a 4-week run-in period (period 1). Patients who met the criteria for essential hypertension (mean sitting systolic blood pressure [MSSBP], ≥140 and <200 mm Hg, or ≥130 and<200 mm Hg in those with diabetes mellitus or chronic kidney disease) after period 1 were randomly assigned to receive TA 40/5 mg + hydrochlorothiazide 12.5 mg (test group) or TA only (control group). The test and control drugs were administered in each group for 2 weeks (period 2). Patients who completed period 2 underwent 6-week treatment (period 3) with a TAH and TA dose twice that in period 2. The primary end point was the change in MSSBP at week 8 of treatment. Secondary end points were the change in MSSBP at week 2 and MS diastolic BP, BP control rate, and BP response rate at weeks 2 and 8. Treatment tolerability was assessed based on adverse events (AEs), laboratory evaluations (chemistry, hematology, and urinalysis), 12-lead ECG, and physical examination including vital sign measurements.nnnFINDINGSnWe randomized 310 patients to the treatment groups. The mean (SD) ages of the TAH and TA groups were 62.0 (10.8) and 63.4 (10.4) years, respectively. The least squares mean change in MSSBP was significantly greater in the TAH group than in the TA group after 8 weeks (-18.7 vs -12.2 mm Hg; P < 0.001). Similar results were obtained on changes in MSSBP after 2 weeks and changes in sitting diastolic BP, BP control rate, and BP response rate at weeks 2 and 8 compared with the respective baseline values. The prevalences of treatment-emergent AEs (29.0% vs 16.3%; P = 0.008) and adverse drug reactions (20.0% vs 10.5%; P = 0.020) were significantly greater in the TAH group than in the TA group. Most treatment-emergent AEs were mild or moderate; none were severe. The most frequently reported AEs were dizziness and headache.nnnIMPLICATIONnTAH triple therapy was more effective than was TA double therapy in reducing BP in these patients in Korea with essential hypertension that did not adequately respond to TA. ClinicalTrials.gov identifier: NCT02738632.

Coronary Computed Tomographic Angiography Does Not Accurately Predict the Need of Coronary Revascularization in Patients with Stable Angina

Purpose To evaluate the ability of coronary computed tomographic angiography (CCTA) to predict the need of coronary revascularization in symptomatic patients with stable angina who were referred to a cardiac catheterization laboratory for coronary revascularization. Materials and Methods Pre-angiography CCTA findings were analyzed in 1846 consecutive symptomatic patients with stable angina, who were referred to a cardiac catheterization laboratory at six hospitals and were potential candidates for coronary revascularization between July 2011 and December 2013. The number of patients requiring revascularization was determined based on the severity of coronary stenosis as assessed by CCTA. This was compared to the actual number of revascularization procedures performed in the cardiac catheterization laboratory. Results Based on CCTA findings, coronary revascularization was indicated in 877 (48%) and not indicated in 969 (52%) patients. Of the 877 patients indicated for revascularization by CCTA, only 600 (68%) underwent the procedure, whereas 285 (29%) of the 969 patients not indicated for revascularization, as assessed by CCTA, underwent the procedure. When the coronary arteries were divided into 15 segments using the American Heart Association coronary tree model, the sensitivity, specificity, positive predictive value, and negative predictive value of CCTA for therapeutic decision making on a per-segment analysis were 42%, 96%, 40%, and 96%, respectively. Conclusion CCTA-based assessment of coronary stenosis severity does not sufficiently differentiate between coronary segments requiring revascularization versus those not requiring revascularization. Conventional coronary angiography should be considered to determine the need of revascularization in symptomatic patients with stable angina.

Efficacy and Safety of DP-R202 in Patients with Chronic Artery Occlusive Disease: Multicenter Randomized Double-blind Active-controlled Parallel Group Phase III Clinical Study.

PURPOSEnSarpogrelate hydrochloride, a selective 5-hydroxytryptamine 2A antagonist, is a widely used antiplatelet agent for the treatment of peripheral arterial disease (PAD). DP-R202 is a new sarpogrelate hydrochloride product with an improved dosage regimen compared with the agent in current use. The aim of this study was to compare the efficacy and safety profile of DP-R202 and Anplag(⁎) Tab in patients with PAD.nnnMETHODSnThis study was a 12-week, multicenter, randomized, double-blinded, active-controlled, parallel group comparative Phase III clinical trial. One hundred fifty-one volunteer patients with PAD were randomized to receive DP-R202 300 mg once daily or Anplag Table 100 mg TID for 12 weeks. The primary end point was a change in patient assessment of lower leg pain intensity with the use of a visual analog scale (VAS) after 12 weeks of treatment. Results after 4, 8, and 12 weeks of treatment were compared with baseline and between treatment groups, and all patients were assessed for adverse events (AEs), clinical laboratory data, and vital signs.nnnFINDINGSnTwo hundred thirty-one patients from 25 medical centers were assessed, and 151 were enrolled and randomly assigned to 1 of 2 treatment groups. Seventy-five patients received DP-R202 300 mg once daily and 76 patients received Anplag Table 100 mg TID for 12 weeks. Analysis of the change in lower leg pain intensity as determined by VAS score between baseline and week 12 (mean [SD], 20.72 [20.06] mm vs 15.55 [21.44] mm) suggested that DP-R202 was not inferior to Anplag Tab, and no significant differences were found in the secondary end points. No significant between-group differences were observed in the prevalence of drug-related clinical- or laboratory-determined AEs. For tolerability, no specific issue was found during the treatment period.nnnIMPLICATIONnThe results of this study suggest that DP-R202 was not inferior to Anplag Tab for efficacy in patients with PAD and indicated a good safety profile.

Bioresorbable vascular scaffold Korean expert panel report

Bioresorbable vascular scaffold (BRS) is an innovative device that provides structural support and drug release to prevent early recoil or restenosis, and then degrades into nontoxic compounds to avoid late complications related with metallic drug-eluting stents (DESs). BRS has several putative advantages. However, recent randomized trials and registry studies raised clinical concerns about the safety and efficacy of first generation BRS. In addition, the general guidance for the optimal practice with BRS has not been suggested due to limited long-term clinical data in Korea. To address the safety and efficacy of BRS, we reviewed the clinical evidence of BRS implantation, and suggested the appropriate criteria for patient and lesion selection, scaffold implantation technique, and management.

Impact of National Health Checkup Service on Hard Atherosclerotic Cardiovascular Disease Events and All-Cause Mortality in the General Population

Whether health checkups favorably impact the occurrence of atherosclerotic cardiovascular disease (ASCVD) and all-cause mortality in the general population remains in debate. We investigated further the impact of health checkups on hard ASCVD events and all-cause mortality. We compared the occurrence of hard ASCVD events and all-cause deaths for 4 years starting in 2010 between participants who used the National Health Checkup Service (NHCS) more than twice and nonparticipants who never used the NHCS from 2006 to 2009. From the 342,594 survivors aged 40 to 69 years old in 2006 listed in the National Health Insurance Service-National Sample Cohort, a total of 55,275 pairs were selected by propensity matching. Hard ASCVD events were defined as the composite of myocardial infarction and stroke. In the 55,275 matched pairs, we found a significant association between the use of the NHCS and the reduction in hard ASCVD events (adjusted hazard ratiou2009=u20090.84, 95% confidence interval 0.76 to 0.92, pu2009<0.001) and all-cause deaths (adjusted hazard ratiou2009=u20090.50, 95% confidence interval 0.45 to 0.55, pu2009<0.001). The participants had more medical care, including outpatient care and hospitalizations, and took more hypertension and dyslipidemia medications, whereas hospitalizations for more than 60 days were significantly more frequent in the nonparticipants. In the subgroup analysis, the reduction in hard ASCVD events for NHCS participants was significantly greater in patients without a previous history of dyslipidemia or who did not have outpatient care. In conclusion, the use of the NHCS was significantly associated with reduced hard ASCVD events and all-cause mortality in the general population.