Effect of Eicosapentaenoic Acid/Docosahexaenoic Acid on Coronary High-Intensity Plaques Detected Using Noncontrast T1-weighted Imaging: The AQUAMARINE EPA/DHA Randomized Study.

AIM: Omega-3 fatty acids have emerged as a new option for controlling the residual risk for coronary artery disease (CAD) in the statin era. Eicosapentaenoic acid (EPA) is associated with reduced CAD risk in the Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention trial, whereas the Statin Residual Risk with Epanova in High Cardiovascular Risk Patients with Hypertriglyceridemia trial that used the combination EPA/docosahexaenoic acid (DHA) has failed to derive any clinical benefit. These contradictory results raise important questions about whether investigating the antiatherosclerotic effect of omega-3 fatty acids could help to understand their significance for CAD-risk reduction. METHODS: The Attempts at Plaque Vulnerability Quantification with Magnetic Resonance Imaging Using Noncontrast T1-weighted Technic EPA/DHA study is a single-center, triple-arm, randomized, controlled, open-label trial used to investigate the effect of EPA/DHA on high-risk coronary plaques after 12 months of treatment, detected using cardiac magnetic resonance (CMR) in patients with CAD receiving statin therapy. Eligible patients were randomly assigned to no-treatment, 2-g/day, and 4-g/day EPA/DHA groups. The primary endpoint was the change in the plaque-to-myocardium signal intensity ratio (PMR) of coronary high-intensity plaques detected by CMR. Coronary plaque assessment using computed tomography angiography (CTA) was also investigated. RESULTS: Overall, 84 patients (mean age: 68.2 years, male: 85%) who achieved low-density lipoprotein cholesterol levels of ＜100 mg/dL were enrolled. The PMR was reduced in each group over 12 months. There were no significant differences in PMR changes among the three groups in the primary analysis or analysis including total lesions. The changes in CTA parameters, including indexes for detecting high-risk features, also did not differ. CONCLUSION: The EPA/DHA therapy of 2 or 4 g/day did not significantly improve the high-risk features of coronary atherosclerotic plaques evaluated using CMR under statin therapy.

Phase I studies of nogitecan hydrochloride for Japanese.

BACKGROUND: SmithKline Beecham synthesized camptothecin analogs and identified nogitecan hydrochloride (topotecan) with a broad spectrum of antitumor activity and less toxicity than camptothecin. Because preclinical and overseas clinical data indicated the antitumor effect of nogitecan hydrochloride with a 5-day repeat-dose schedule, we carried out phase I studies in Japan to determine the maximum tolerated dose (MTD), pharmacokinetics, and antitumor effect of nogitecan hydrochloride. METHODS: Phase I studies of nogitecan hydrochloride given by single and 5-day repeat dosing were carried out in patients with various solid tumors at 15 medical institutions in Japan. Pharmacokinetic evaluations were performed for both single and 5-day repeated dosing. RESULTS: The dose-limiting factor (DLF) was reversible leucopenia, and the maximum tolerated dose (MTD) was higher than 22.5 mg/m2 in the single-dose study. In the 5-day repeat-dose study, the DLF was also reversible leucopenia, and the MTD was estimated to be 1.5 mg/m2 per day. The plasma concentration of nogitecan hydrochloride increased with increasing dose, and the half-life after single dosing ranged from 3 to 5h. There was no evidence of accumulation or delayed excretion during 5-day repeat dosing. CONCLUSION: Based on these results and the finding that there were responders among patients treated at 1.5 mg/m2 per day by 5-day repeat dosing in overseas studies, 5-day repeat dosing of 1.2mg/m2 per day, one dose level lower than the MTD, was selected for phase II studies in Japan.