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.

Erroneous computer electrocardiogram interpretation of atrial fibrillation and its clinical consequences.

BACKGROUND: The aim of this study was to determine the frequency and nature of errors made by computer electrocardiogram (ECG) analysis of atrial fibrillation (AF), and the clinical consequences. HYPOTHESIS: Computer software for interpreting ECGs has advanced. METHODS: A total of 10279 ECGs were collected, automatically interpreted by the built-in ECG software, and then reread by 2 cardiologists. AF-related ECGs were classified into 3 groups: overinterpreted AF (rhythms other than AF interpreted as AF), misinterpreted AF (AF interpreted as rhythms other than AF), and true AF (AF interpreted as AF by both computer ECG interpretation and cardiologists). RESULTS: There were 1057 AF-related ECGs from 409 patients. Among these, 840 ECGs (79.5%) were true AF. Overinterpretation occurred in 98 (9.3%) cases. Sinus rhythm and sinus tachycardia with premature atrial contraction and/or baseline artifact and sinus arrhythmia were commonly overinterpreted as AF. Heart rate ≤60 bpm and baseline artifact significantly increased the likelihood of overinterpreted AF. Misdiagnosis occurred in 119 (11.3%) cases, in which AF was usually misdiagnosed as sinus or supraventricular tachycardia. The presence of tachycardia and low-amplitude atrial activity significantly increased the likelihood of misdiagnosis of AF. Among the erroneous computer ECG interpretations, 17 cases (7.8%) were not corrected by the ordering physicians and/or repeat computer-ECG interpretation; inappropriate follow-up studies or treatments of the patients were undertaken with no serious sequelae. CONCLUSIONS: Erroneous computer ECG interpretation of AF was not rare. Attention should be concentrated on educating physicians about ECG appearance and confounding factors of AF, along with ongoing quality control of built-in software for automatic ECG interpretation.