The Efficacy and Tolerability of Irbesartan/Amlodipine Combination Therapy in Patients With Essential Hypertension Whose Blood Pressure Were not Controlled by Irbesartan Monotherapy.

PURPOSE: This study aimed to evaluate the efficacy and tolerability of irbesartan (IRB) and amlodipine (AML) combination therapy in patients with essential hypertension whose blood pressure (BP) was not controlled by IRB monotherapy. METHODS: Two multicenter, randomized, double-blind, placebo-controlled, phase III studies were conducted in Korea (the I-DUO 301 study and the I-DUO 302 study). After a 4-week run-in period with either 150 mg IRB (I-DUO 301 study) or 300 mg IRB (I-DUO 302 study), patients with uncontrolled BP (ie, mean sitting systolic BP [MSSBP] ≥140 mmHg to <180 mmHg and mean sitting diastolic BP <110 mmHg) were randomized to the placebo, AML 5 mg, or AML 10 mg group. A total of 428 participants were enrolled in the 2 I-DUO studies. In the I-DUO 301 study, 271 participants were randomized in a 1:1:1 ratio to receive either IRB/AML 150/5 mg, IRB/AML 150/10 mg, or IRB 150 mg/placebo. In the I-DUO 302 study, 157 participants were randomized in a 1:1 ratio to receive IRB/AML 300/5 mg or IRB 300 mg/placebo. The primary endpoint was the change in MSSBP from baseline to week 8. Tolerability was assessed according to the development of treatment-emergent adverse events (TEAEs) and clinically significant changes in physical examination, laboratory tests, pulse, and 12-lead electrocardiography. FINDINGS: In I-DUO 301, the mean (SD) changes of MSSBP at week 8 from baseline were -14.78 (12.35) mmHg, -21.47 (12.78) mmHg, and -8.61 (12.19) mmHg in the IRB/AML 150/5 mg, IRB/AML 150/10 mg, and IRB 150 mg/placebo groups, respectively. In I-DUO 302, the mean (SD) changes of MSSBP at week 8 from baseline were -13.30 (12.47) mmHg and -7.19 (15.37) mmHg in the IRB/AML 300/5 mg and IRB 300 mg/placebo groups, respectively. In both studies, all combination groups showed a significantly higher reduction in MSSBP than the IRB monotherapy groups (P < 0.001 for both). TEAEs occurred in 10.00%, 10.99%, and 12.22% of participants in the IRB/AML 150/5 mg, IRB/AML 150/10 mg, and IRB 150 mg/placebo groups, respectively, in I-DUO 301 and in 6.33% and 10.67% of participants in the IRB/AML 300/5 mg and IRB 300 mg/placebo groups, respectively, in I-DUO 302, with no significant between-group differences. Overall, there was one serious adverse event throughout I-DUO study. IMPLICATIONS: The combination of IRB and AML has superior antihypertensive effects compared with IRB alone over an 8-week treatment period, with placebo-like tolerability. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05476354 (I-DUO 301), NCT05475665 (I-DUO 302).

Rosuvastatin versus atorvastatin treatment in adults with coronary artery disease: secondary analysis of the randomised LODESTAR trial.

OBJECTIVE: To compare the long term efficacy and safety of rosuvastatin with atorvastatin treatment in adults with coronary artery disease. DESIGN: Randomised, open label, multicentre trial. SETTING: 12 hospitals in South Korea, September 2016 to November 2019. PARTICIPANTS: 4400 adults (age ≥19 years) with coronary artery disease. INTERVENTIONS: Participants were assigned to receive either rosuvastatin (n=2204) or atorvastatin (n=2196) using 2×2 factorial randomisation. MAIN OUTCOME MEASURES: The primary outcome was a three year composite of all cause death, myocardial infarction, stroke, or any coronary revascularisation. Secondary outcomes were safety endpoints: new onset diabetes mellitus; hospital admissions due to heart failure; deep vein thrombosis or pulmonary thromboembolism; endovascular revascularisation for peripheral artery disease; aortic intervention or surgery; end stage kidney disease; discontinuation of study drugs owing to intolerance; cataract surgery; and a composite of laboratory detected abnormalities. RESULTS: 4341 of the 4400 participants (98.7%) completed the trial. Mean daily dose of study drugs was 17.1 mg (standard deviation (SD) 5.2 mg) in the rosuvastatin group and 36.0 (12.8) mg in the atorvastatin group at three years (P<0.001). The primary outcome occurred in 189 participants (8.7%) in the rosuvastatin group and 178 (8.2%) in the atorvastatin group (hazard ratio 1.06, 95% confidence interval 0.86 to 1.30; P=0.58). The mean low density lipoprotein (LDL) cholesterol level during treatment was 1.8 mmol/L (SD 0.5 mmol/L) in the rosuvastatin group and 1.9 (0.5) mmol/L in the atorvastatin group (P<0.001). The rosuvastatin group had a higher incidence of new onset diabetes mellitus requiring initiation of antidiabetics (7.2% v 5.3%; hazard ratio 1.39, 95% confidence interval 1.03 to 1.87; P=0.03) and cataract surgery (2.5% v 1.5%; 1.66, 1.07 to 2.58; P=0.02). Other safety endpoints did not differ between the two groups. CONCLUSIONS: In adults with coronary artery disease, rosuvastatin and atorvastatin showed comparable efficacy for the composite outcome of all cause death, myocardial infarction, stroke, or any coronary revascularisation at three years. Rosuvastatin was associated with lower LDL cholesterol levels but a higher risk of new onset diabetes mellitus requiring antidiabetics and cataract surgery compared with atorvastatin. TRIAL REGISTRATION: ClinicalTrials.gov NCT02579499.

Randomized, multicenter, parallel, open, phase 4 study to compare the efficacy and safety of rosuvastatin/amlodipine polypill versus atorvastatin/amlodipine polypill in hypertension patient with dyslipidemia.

The authors performed this study to investigate the efficacy and safety of a rosuvastatin (RSV)/amlodipine (AML) polypill compared with those of atorvastatin (ATV)/AML polypill. We included 259 patients from 21 institutions in Korea. Patients were randomly assigned to 1 of 3 treatment groups: RSV 10 mg/AML 5 mg, RSV 20 mg/AML 5 mg, or ATV 20 mg /AML 5 mg. The primary endpoint was the efficacy of the RSV 10.20 mg/AML 5 mg via percentage changes in LDL-C after 8 weeks of treatment, compared with the ATV 20 mg /AML 5 mg. There was a significant difference in the mean percentage change of LDL-C at 8 weeks between the RSV 10 mg/AML 5 mg and the ATV 20 mg/AML 5 mg (full analysis set [FAS]: -7.08%, 95% CI: -11.79 to -2.38, p = .0034, per-protocol analysis set [PPS]: -6.97%, 95% CI: -11.76 to -2.19, p = .0046). Also, there was a significant difference in the mean percentage change of LDL-C at 8 weeks between the RSV 20 mg/AML 5 mg and the ATV 20 mg/AML 5 mg (FAS: -10.13%, 95% CI: -15.41 to -4.84, p = .0002, PPS: -10.96%, 95% CI: -15.98 to -5.93, p < .0001). There was no significant difference in the adverse events rates between RSV 10 mg/AML 5 mg, RSV 20 mg/AML 5 mg, and ATV 20 mg/AML 5 mg. In conclusion, while maintaining safety, RSV 10 mg/AML 5 mg and the RSV 20 mg/AML 5 mg more effectively reduced LDL-C compared with the ATV 20 mg /AML 5 mg (Clinical trial: NCT03951207).

Impact of Cardiovascular Risk Factors and Cardiovascular Diseases on Outcomes in Patients Hospitalized with COVID-19 in Daegu Metropolitan City.

BACKGROUND: Data regarding the association between preexisting cardiovascular risk factors (CVRFs) and cardiovascular diseases (CVDs) and the outcomes of patients requiring hospitalization for coronavirus disease 2019 (COVID-19) are limited. Therefore, the aim of this study was to investigate the impact of preexisting CVRFs or CVDs on the outcomes of patients with COVID-19 hospitalized in a Korean healthcare system. METHODS: Patients with COVID-19 admitted to 10 hospitals in Daegu Metropolitan City, Korea, were examined. All sequentially hospitalized patients between February 15, 2020, and April 24, 2020, were enrolled in this study. All patients were confirmed to have COVID-19 based on the positive results on the polymerase chain reaction testing of nasopharyngeal samples. Clinical outcomes during hospitalization, such as requiring intensive care and invasive mechanical ventilation (MV) and death, were evaluated. Moreover, data on baseline comorbidities such as a history of diabetes, hypertension, dyslipidemia, current smoking, heart failure, coronary artery disease, cerebrovascular accidents, and other chronic cardiac diseases were obtained. RESULTS: Of all the patients enrolled, 954 (42.0%) had preexisting CVRFs or CVDs. Among the CVRFs, the most common were hypertension (28.8%) and diabetes mellitus (17.0%). The prevalence rates of preexisting CVRFs or CVDs increased with age (P < 0.001). The number of patients requiring intensive care (P < 0.001) and invasive MV (P < 0.001) increased with age. The in-hospital death rate increased with age (P < 0.001). Patients requiring intensive care (5.3% vs. 1.6%; P < 0.001) and invasive MV (4.3% vs. 1.7%; P < 0.001) were significantly greater in patients with preexisting CVRFs or CVDs. In-hospital mortality (12.9% vs. 3.1%; P < 0.001) was significantly higher in patients with preexisting CVRFs or CVDs. Among the CVRFs, diabetes mellitus and hypertension were associated with increased requirement of intensive care and invasive MV and in-hospital death. Among the known CVDs, coronary artery disease and congestive heart failure were associated with invasive MV and in-hospital death. In multivariate analysis, preexisting CVRFs or CVDs (odds ratio [OR], 1.79; 95% confidence interval [CI], 1.07-3.01; P = 0.027) were independent predictors of in-hospital death after adjusting for confounding variables. Among individual preexisting CVRF or CVD components, diabetes mellitus (OR, 2.43; 95% CI, 1.51-3.90; P < 0.001) and congestive heart failure (OR, 2.43; 95% CI, 1.06-5.87; P = 0.049) were independent predictors of in-hospital death. CONCLUSION: Based on the findings of this study, the patients with confirmed COVID-19 with preexisting CVRFs or CVDs had worse clinical outcomes. Caution is required in dealing with these patients at triage.

Heterotopic Ossification of the Xiphoid Process after Abdominal Surgery for Traumatic Hemoperitoneum.

Heterotopic ossification of the xiphoid process is extremely rare, with only three cases previously reported. However, the surgical pathology for postoperative elongation of the xiphoid process after abdominal surgery has not yet been reported. We report a case of the postoperative elongation of the xiphoid process, 8 years after abdominal surgery for traumatic hemoperitoneum in a 53-year-old man. The patient underwent surgical excision of the elongated mass of the xiphoid process. Histopathology revealed multiple exostoses. Heterotopic ossification can occur after surgical trauma to soft or bone tissue. Surgical excision with primary closure is the treatment of choice for symptomatic heterotopic ossification.

Treatment patterns and their outcomes of acute aortic intramural hematoma in real world: multicenter registry for aortic intramural hematoma.

BACKGROUND: Intramural hematoma of the aorta (IMH), a variant of classic aortic dissection, shows very dynamic process in the early phase. The aim of this study is to evaluate clinical outcomes of patients with acute aortic IMH from real world registry data. METHODS: We analyzed 165 consecutive patients with acute IMH from five medical centers in Korea. All patients were divided into two groups; type A (n = 61, 37.0%) and type B (n = 104, 63.0%) according to the Stanford classification. Clinical outcomes and morphological evolution by CT were analyzed for 2 years. RESULTS: Most of the patients (77.0% of type A and 99.0% of type B, P < 0.001) were treated medically during their initial hospitalization. There were no significant differences in in-hospital mortality (4.9% vs. 2.9%, P = 0.671) and 2-year mortality (13.1% vs. 11.5%, P = 0.765) between two groups. During the 2-year follow up period, progression to aortic dissection (18.0% vs. 6.7%, P = 0.037) and surgical treatment (29.5% vs. 2.9%, P < 0.001) were higher in type A. For the type A patients, there were no significant difference in in-hospital mortality (7.1% of surgery vs. 4.3% of medical, P = 0.428) and 2-year mortality (7.1% of surgery vs. 14.9% of medical, P = 0.450) in terms of initial treatment strategy. CONCLUSION: For real world practice in Korea, most of IMH patients were treated medically at presentation and showed favorable outcomes. Thus, even in type A acute IMH, early medical treatment with alternative surgical conversion for selected, complicated cases would be a favorable treatment option.

Histopathologic validation of the intravascular ultrasound diagnosis of calcified coronary artery nodules.

A calcified nodule is a type of potentially vulnerable plaque accounting for approximately 2% to 7% of coronary events. Because its intravascular ultrasound (IVUS) features have never been validated, the aim of this study was to assess the IVUS characteristics of calcified nodules in comparison to histopathology. IVUS was performed in 856 pathologic slices in 29 coronary arteries (11 left anterior descending, 5 left circumflex, and 13 right coronary arteries) in 18 autopsy hearts. Pathologic sections were analyzed every 2 mm; qualitative and quantitative findings of matched IVUS were analyzed. IVUS detected calcification in 285 frames; 17 (6.0%) were calcified nodules, and 268 (94.0%) were non-nodular calcium by histopathology. Two calcified nodules (11.8%) were solitary, and 15 (88.2%) were adjacent to non-nodular calcium. IVUS characteristics of calcified nodules were (1) a convex shape of the luminal surface (94.1% in calcified nodules vs 9.7% in non-nodular calcium, p <0.001), (2) a convex shape of the luminal side of calcium (100% vs 16.0%, p <0.001), (3) an irregular luminal surface (64.7% vs 11.6%, p <0.001), and (4) an irregular leading edge of calcium (88.2% vs 19.0%, p <0.001). Luminal area at the calcified nodule site was larger (6.2 ± 2.4 vs 4.3 ± 1.6 mm(2), p <0.001) and plaque burden less (57 ± 6% vs 68 ± 5%, p <0.001) than at the minimum luminal area site. In conclusion, calcified nodules have distinct IVUS features (irregular and convex luminal surface) permitting their prospective identification in vivo.

Reversible pulmonary hypertension in adolescent with left atrial myxoma.

We report a patient of left atrial huge myxoma presenting with severe pulmonary hypertension in adolescents. A patient was a 14-year-old boy presented with sudden onset dyspnea. Transthoracic echocardiographic study revealed the presence of a nodular, 4.34 × 8.11 cm sized, mobile, hyperechoic mass in the left atrium and severe pulmonary hypertension with tricuspid insufficiency. After surgical therapy, tricuspid regurgitation and pulmonary hypertension was decreased and the patient was stabilized and had an uneventful clinical course.

The culprit lesion score on multi-detector computed tomography can detect vulnerable coronary artery plaque.

Vulnerable plaques are characterized by large lipid cores, positive remodeling and small coronary calcium deposits. Multi-detector computed tomography (MDCT) has recently been shown to be able to characterize coronary artery plaques. The aim of this study was to evaluate culprit coronary lesions for differentiating acute coronary syndrome (ACS) from stable angina pectoris (SAP) using MDCT. 64-slice MDCT was conducted on 71 patients (ACS: 35, SAP: 36). The culprit coronary lesions were assessed according to the type and plaque attenuation (PA) of the plaque and the remodeling index (RI) as the ratio of the lesion and the reference area. The culprit lesion score (CLS) was defined as the sum of every score as 1.2 for a PA ≤ 60 Hounsfield units (HU), 1.1 for a RI ≥ 1.05 and 1.2 for a non-calcified or spotty calcification. More spotty calcification (95.0% vs. 23.1%, P < 0.001), a lower PA (40.17 ± 20.08 HU vs. 96.96 ± 58.19 HU, respectively, P < 0.001) and a higher RI (1.44 ± 0.43 vs. 0.90 ± 0.44, respectively, P < 0.001) were observed in the ACS patients. Also, the CLS of the ACS patients was significantly higher than that of the SAP patients (3.07 ± 0.63 vs. 1.18 ± 1.12, respectively, P < 0.001). A CLS more than 2.0 helped us to differentiate ACS from SAP with a sensitivity of 97.1% and a specificity of 67.6%. The CLS might be a useful tool for differentiating ACS from SAP.