Pragmatic trial comparing routine versus no routine functional testing in high-risk patients who underwent percutaneous coronary intervention: Rationale and design of POST-PCI trial.

BACKGROUND: Although the need to detect restenosis has diminished in the contemporary practice of percutaneous coronary intervention (PCI) with drug-eluting stents (DES), the surveillance of ischemia owing to restenosis or disease progression deserves attention in high-risk PCI settings. It is unknown whether follow-up strategy of routine noninvasive functional testing potentially reduces the risk of major cardiovascular events in high-risk PCI patients. METHODS: The POST-PCI study is an investigator-initiated, multicenter, prospective randomized trial comparing the effectiveness of two follow-up strategies in patients with high-risk anatomic or clinical characteristics who underwent PCI. Study participants were randomly assigned to either (1) the routine noninvasive stress testing (exercise electrocardiography, nuclear stress imaging, or stress echocardiography) at 12 months post-PCI or (2) the standard-care without routine testing. In the routine stress testing group, depending on the testing results, all clinical decisions regarding subsequent diagnostic or therapeutic procedures were at the treating physician's discretion. The primary endpoint was a composite outcome of death from any causes, myocardial infarction, or hospitalization for unstable angina at 2 years post-PCI. RESULTS: More than 1700 high-risk PCI patients have been randomized over 2.0 years at 11 major cardiac centers in Korea. CONCLUSION: This pragmatic POST-PCI trial will provide valuable clinical evidence on the effectiveness of follow-up strategy of routine noninvasive stress testing in high-risk PCI patients.

A prospective, randomized comparison of promus everolimus-eluting and TAXUS Liberte paclitaxel-eluting stent systems in patients with coronary artery disease eligible for percutaneous coronary intervention: the PROMISE study.

We aimed comparing two-year clinical outcomes of the Everolimus-Eluting Promus and Paclitaxel-Eluting TAXUS Liberte stents used in routine clinical practice. Patients with objective evidence of ischemia and coronary artery disease eligible for PCI were prospectively randomized to everolimus-eluting stent (EES) or paclitaxel-eluting stent (PES) groups. The primary end-point was ischemia-driven target vessel revascularization (TVR) at 2 yr after intervention, and the secondary end-point was a major adverse cardiac event (MACE), such as death, myocardial infarction (MI), target lesion revascularization (TLR), TVR or stent thrombosis. A total of 850 patients with 1,039 lesions was randomized to the EES (n=425) and PES (n=425) groups. Ischemic-driven TVR at 2 yr was 3.8% in the PES and 1.2% in the EES group (P for non-inferiority=0.021). MACE rates were significantly different; 5.6% in PES and 2.5% in EES (P = 0.027). Rates of MI (0.8% in PES vs 0.2% in EES, P = 0.308), all deaths (1.5% in PES vs 1.2% in EES, P = 0.739) and stent thrombosis (0.3% in PES vs 0.7% in EES, P = 0.325) were similar. The clinical outcomes of EES are superior to PES, mainly due to a reduction in the rate of ischemia-driven TVR.

The impact of a dose of the angiotensin receptor blocker valsartan on post-myocardial infarction ventricular remodelling.

AIMS: Although clinical guidelines advocate the use of the highest tolerated dose of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers after acute myocardial infarction (MI), the optimal dosing or the risk-benefit profile of different doses have not been fully identified. METHODS AND RESULTS: In this multicentre trial, 495 Korean patients with acute ST segment elevation MI and subnormal left ventricular (LV) ejection fraction (<50%) were randomly allocated (2:1) to receive maximal tolerated dose of valsartan (titrated up to 320 mg/day, n = 333) or low-dose valsartan (80 mg/day, n = 162) treatment. The primary objective was to assess the changes in echocardiographic parameters of LV remodelling from baseline to 12 months after discharge. After treatment, end-diastolic LV volume (LVEDV) decreased significantly in the low-dose group, but the difference in LVEDV changes was insignificant between the maximal-tolerated-dose and low-dose groups. End-systolic LV volume decreased significantly in both groups, to a similar degree between groups. LV ejection fraction rose significantly in both study groups, to a similar degree. Changes in plasma levels of neurohormones were also comparable between the two groups. Drug-related adverse effects occurred more frequently in the maximal-tolerated-dose group than in the low-dose group (7.96 vs. 0.69%, P < 0.001). CONCLUSIONS: In the present study, treatment with the maximal tolerated dose of valsartan did not exhibit a superior effect on post-MI LV remodelling compared with low-dose treatment and was associated with a greater frequency of adverse effect in Korean patients. Further study with a sufficient number of cases and statistical power is warranted to verify the findings of the present study.

Successful extracorporeal life support in sudden cardiac arrest due to coronary anomaly.

Extracorporeal life support (ECLS) has recently been reported to have a survival benefit in patients with cardiac arrest. It is now used widely as a lifesaving modality. Here, we describe a case of sudden cardiac arrest (SCA) in a young athlete with an anomalous origin of the right coronary artery from the left coronary sinus. Resuscitation was successful using ECLS before curative bypass surgery. We highlight the efficacy of ECLS for a patient with SCA caused by a rare, unexpected aetiology. In conclusion, ECLS was a lifesaving modality for SCA due to an anomalous coronary artery in this young patient.

A Randomized, Double-blind, Candesartan-controlled, Parallel Group Comparison Clinical Trial to Evaluate the Antihypertensive Efficacy and Safety of Fimasartan in Patients with Mild to Moderate Essential Hypertension.

PURPOSE: A new antihypertensive drug that selectively blocks angiotensin II receptor type 1, fimasartan, has a potent and rapidly acting antihypertensive effect. We investigated the antihypertensive effects of fimasartan 60 and 120 mg and its safety in comparison to 8 mg of candesartan. METHODS: This clinical trial is a multicenter, randomized, double-blind, active comparator, and parallel group study. Three hundred sixty-two individuals were screened, and 290 patients aged 19 to 75 years with mild to moderate hypertension (diastolic blood pressure [DBP], 90-110 mm Hg) were randomly assigned to 60 to 120 mg/d of fimasartan or 8 mg/d of candesartan after a 2-week placebo run-in period. Treatments were administered for 12 weeks without dosage adjustment. The primary end point was the differences in DBP changes at week 12. FINDINGS: After 12 weeks of treatment, DBP and systolic blood pressure (SBP) decreased significantly in all 3 groups. The decrease in DBP at week 12 was larger but not statistically significant in the fimasartan 60 mg compared with the candesartan 8 mg group with a mean (SD) difference of 1.72 (8.32) mm Hg (95% CI, -0.71 to 4.15 mm Hg; P = 0.17). The lower margin of the CI (-0.71 mm Hg) exceeded the noninferiority margin (-3.5 mm Hg). The DBP-lowering effect of fimasartan 120 mg was also nonsignificantly larger than candesartan 8 mg (difference, 1.58 [8.27] mm Hg; P = 0.20). The decrease in SBP was also nonsignificantly larger in the fimasartan 60 mg group compared with the candesartan 8 mg group (difference, 3.50 [12.63] mm Hg; P = .06). The SBP-lowering effect of fimasartan 120 mg was statistically larger than candesartan 8 mg (difference, 4.98 [13.99] mm Hg; P = .02). Response rate (DBP <90 mm Hg or DBP lowering >10 mm Hg at week 12) was also nonsignificantly greater in both fimasartan groups (Fimasartan 60 mg, 81%; fimasartan 120 mg, 72%; candesartan 8 mg, 71%). The safety profile of the fimasartan 60 mg and 120 mg was similar to candesartan 8 mg, with a slightly higher, but statistically not significant, incidence of hepatic enzyme elevation in fimasartan 120 mg. IMPLICATIONS: The antihypertensive effect of fimasartan, a newly available angiotensin II receptor type 1 blocker, is comparable, although not superior, to candesartan with a good safety profile. ClinicalTrials.gov identifier: NCT01135212.

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.

Typology of ROII Patterns on Cluster Analysis in Korean Enterprises.

OBJECTIVES: Authors investigated the pattern of the rate of occupational injuries and illnesses (ROII) at the level of enterprises in order to build a network for exchange of experience and knowledge, which would contribute to workers' safety and health through safety climate of workplace. METHODS: Occupational accidents were analyzed at the manufacturing work site unit. A two step clustering process for the past patterns regarding the ROII from 2001 to 2009 was investigated. The ROII patterns were categorized based on regression analysis and the patterns were further divided according to the subtle changes with Mahalanobis distance and Ward's linkage. RESULTS: The first clustering of ROII through regression analysis showed 5 different functions; 29 work sites of the linear function, 50 sites of the quadratic function, 95 sites of the logarithm function, 62 sites of the exponential function, and 54 sites of the sine function. Fourteen clusters were created in the second clustering. There were 3 clusters in each function categorized in the first clustering except for sine function. Each cluster consisted of the work sites with similar ROII patterns, which had unique characteristics. CONCLUSION: The five different patterns of ROII suggest that tailored management activities should be applied to every work site. Based on these differences, the authors selected exemplary work sites and built a network to help the work sites to share information on safety climate and accident prevention measures. The causes of different patterns of ROII, building network and evaluation of this management model should be evaluated as future researches.

Comparison of the efficacy and safety of fixed-dose amlodipine/losartan and losartan in hypertensive patients inadequately controlled with losartan: a randomized, double-blind, multicenter study.

BACKGROUND: Fixed-dose combination drugs may enhance blood pressure (BP) goal attainment through complementary effects and reduced side effects, which leads to better compliance. OBJECTIVE: This study aimed to evaluate the efficacy and safety profiles of once-daily combination amlodipine/losartan versus losartan. METHODS: This was an 8-week, double-blind, multicenter, randomized phase III study conducted in outpatient hospital clinics. Korean patients with essential hypertension inadequately controlled on losartan 100 mg were administered amlodipine/losartan 5 mg/100 mg combination versus losartan 100 mg. The main outcome measures were changes in sitting diastolic blood pressure (DBP) and sitting systolic blood pressure (SBP) and BP response rate from baseline values, which were assessed after 4 and 8 weeks of treatment. Safety and tolerability were also assessed. RESULTS: At week 8, both groups achieved significant reductions from baseline in DBP (11.7 ± 7.0 and 3.2 ± 7.9 mmHg), which was significantly greater in the amlodipine/losartan 5 mg/100 mg combination (n = 70) group (p < 0.0001). Additionally, the amlodipine/losartan 5 mg/100 mg combination group achieved significantly greater reductions in SBP at week 8 and in SBP and DBP at week 4 compared with the losartan 100 mg (n = 72) group (all p < 0.0001). Response rates were significantly higher in the amlodipine/losartan 5 mg/100 mg group versus the losartan 100 mg group (81.4% vs 63.9% at week 4, p < 0.0192; 90.0% vs 66.7% at week 8, p < 0.001). Both treatments were generally well tolerated. CONCLUSION: Switching to a fixed-dose combination therapy of amlodipine/losartan 5 mg/100 mg was associated with significantly greater reductions in BP and superior achievement of BP goals compared with a maintenance dose of losartan 100 mg in Korean patients with essential hypertension inadequately controlled on losartan 100 mg. CLINICAL TRIAL REGISTRATION: Registered at Clinicaltrials.gov as NCT00940680.

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.