Comparison between febuxostat and allopurinol uric acid-lowering therapy in patients with chronic heart failure and hyperuricemia: a multicenter randomized controlled trial.

OBJECTIVE: Heart failure (HF) is a common and highly morbid cardiovascular disorder. Oxidative stress worsens HF, and uric acid (UA) is a useful oxidative stress marker. The novel anti-hyperuricemic drug febuxostat is a potent non-purine selective xanthine oxidase inhibitor. The present study examined the UA-lowering and prognostic effects of febuxostat in patients with HF compared with conventional allopurinol. METHODS: This multicenter, randomized trial included 263 patients with chronic HF who were randomly assigned to two groups and received allopurinol or febuxostat (UA >7.0 mg/dL). All patients were followed up for 3 years after enrollment. RESULTS: There were no significant differences in baseline clinical characteristics between the two groups. The UA level was significantly decreased after 3 years of drug administration compared with the baseline in both groups. Urine levels of the oxidative stress marker 8-hydroxy-2'-deoxyguanosine were lower in the febuxostat group than in the allopurinol group (11.0 ± 9.6 vs. 22.9 ± 15.9 ng/mL), and the rate of patients free from hospitalization due to worsening HF tended to be higher in the febuxostat group than in the allopurinol group (89.0% vs. 83.0%). CONCLUSIONS: Febuxostat is potentially more effective than allopurinol for treating patients with chronic HF and hyperuricemia.This study was registered in the University Hospital Medical Information Network Clinical Trials Registry (https://www.umin.ac.jp/ctr/; ID: 000009817).

Acute myocardial infarction in Fukushima area of Japan.

Although acute myocardial infarction (AMI) is the most serious coronary disease, the background of its onset and the mortality are not fully understood, especially in Japan. From June 1999 to May 2005, we mailed an annual questionnaire to eighteen hospitals in which emergency cardiac catheterization and percutaneous coronary intervention (PCI) were available in the Fukushima area of Japan. A total of 1,590 patients were included. The onset time of AMI had two peaks, i.e., from 9:00 AM to 10:00 AM and 9:00 PM to 10:00 PM. As for reperfusion therapy, four groups were analyzed, the non-reperfusion therapy group (Group N, n = 233), thrombolysis alone group (Group T, n = 80), PCI without thrombolysis group (Group P, n = 1106), and PCI with thrombolysis group (Group TP, n = 151). The in-hospital mortality rate was significantly reduced in Group P (8.4%) compared with that in Group N (33.0%, p < 0.01) and Group T (18.8%, p < 0.01). However, the in-hospital mortality in Group P did not differ from that in Group TP (9.9%). The in-hospital mortality was analyzed by the logistic regression analysis among age, arrival time after onset, peak creatine kinase (CK) values, coronary risk factors, reperfusion therapy, PCI, and thrombolysis. There were significant differences in age (P < 0.01), peak CK values (p < 0.01), hypertension (p < 0.05), and diabetes mellitus (p < 0.01). These results suggest that the onset of AMI may be partly related to human biorhythms, and that PCI would be effective in reducing the in-hospital mortality.

Effects of angiotensin-converting enzyme inhibitors or an angiotensin receptor blocker in combination with aspirin and cilostazol on in-stent restenosis.

It remains to be determined whether adding an angiotensin-converting enzyme inhibitor (ACEI) or an angiotensin II receptor blocker (ARB) to antiplatelet therapy has a therapeutic benefit on in-stent restenosis. After successful coronary stenting, 165 patients (167 lesions) were randomly assigned to a basal (aspirin 162 mg + cilostazol 200 mg/day), ACEI (basal treatment + quinapril 10 mg or perindopril 4 mg/day), or ARB (basal treatment + losartan 50 mg/day) treatment group. Quantitative coronary angiography was performed before, immediately following, and 6 months after stenting. Follow-up coronary angiography was completed in 126 patients (128 lesions). Restenosis rates tended to be higher (12, 26, and 12% for the basal, ACEI, and ARB groups, respectively), and target lesion revascularization rates were higher in the ACEI group than in the other groups (9, 23,* and 5%, respectively, *P < 0.05 versus basal group). Moreover, late lumen loss was higher in the ACEI group than in the basal group (0.60 +/- 0.55, 0.98 +/- 0.61* and 0.73 +/- 0.64 mm in the basal, ACEI, and ARB groups, respectively). The combinations of an ACEI or ARB with aspirin and cilostazol are ineffective for the prevention of in-stent restenosis, and an ACEI may even promote intimal proliferation after stent implantation.