Usefulness and safety of intracoronary administration of nicorandil for evaluating fractional flow reserve in Japanese patients.

BACKGROUND: Fractional flow reserve (FFR) is useful for determining the functional significance of epicardial coronary stenosis and may facilitate clinical decision making in patients with an equivocal coronary stenosis for coronary revascularization. Therefore, determining an efficient and safe method to achieve hyperemia is important for evaluating FFR. We investigated the usefulness and safety of intracoronary bolus administration of nicorandil compared with intravenous administration of adenosine triphosphate (ATP) for evaluating FFR in Japanese patients with suspected angina pectoris. METHODS: First, we evaluated the most appropriate hyperemic dose of nicorandil in the first 11 consecutive patients out of 101 Japanese patients. Next, we compared the FFR induced by ATP and by 2 mg of nicorandil in 130 vessels of the 101 patients. RESULTS: FFR was measured according to nicorandil dose in 14 vessels among 11 of the 101 patients; 92.9% of the patients achieved hyperemia with 2 mg of nicorandil. The FFR values obtained with ATP were significantly correlated with those obtained with 2 mg of nicorandil (regression coefficient = 0.974, R(2) = 0.933, P < 0.001). There were no hypotension cases needing a vasopressor after ATP or nicorandil administration, and there was 1 case of transient second-degree atrioventricular block after ATP administration. The time taken to achieve hyperemia after nicorandil administration (18.9 ± 9.6 seconds) was significantly shorter than that after ATP administration (197.9 ± 23.8 seconds) (P < 0.001). CONCLUSIONS: Intracoronary nicorandil administration is more useful than and as safe as intravenous administration of ATP for evaluating FFR in Japanese patients.

Candesartan decreases carotid intima-media thickness by enhancing nitric oxide and decreasing oxidative stress in patients with hypertension.

Candesartan has been reported to produce nitric oxide (NO) and to decrease oxidative stress in animal studies. We investigated candesartan's effect on the production of NO and oxidative stress as well as on carotid intima-media thickness (IMT) in hypertensive patients. One-hundred age-matched hypertensive patients were enrolled into an angiotensin II receptor blocker (ARB) group (n=50) or a non-ARB group (n=50). The ARB group was treated with candesartan 8 mg and, when needed, Ca channel blockers, angiotesin-converting enzyme (ACE) inhibitors, and/or beta-blockers. The non-ARB group was treated with drugs other than ARB. Carotid IMT was assessed by echocardiography before and 12 and 24 months after treatment. The urine levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), an indicator of oxidative stress, and the serum levels of NOx, an indicator of NO, were measured. Blood pressure decreased to below 140/90 mmHg to the same extent in both groups. Carotid IMT decreased significantly in the ARB group, but not in the non-ARB group, at 12 and 24 months after treatment. The urine levels of 8-OHdG decreased significantly at 6 and 12 months after treatment in the ARB group but did not decrease in the non-ARB group. The serum levels of NOx increased significantly at 6 and 12 months after treatment in the ARB group but not in the non-ARB group. In conclusion, candesartan decreases carotid IMT by enhancing NO production and decreasing oxidative stress in patients with hypertension.

Effects of benidipine and some other calcium channel blockers on the prognosis of patients with vasospastic angina. Cohort study with evaluation of the ergonovine coronary spasm induction test.

BACKGROUND: It has been reported that the morbidity rate of vasospastic angina is higher in Japan compared to western countries, and its prognosis has already been reported. However, the prognosis of vasospastic angina in relation to coronary angiographic findings, prognostic risk factors and treatment has not yet been fully investigated. METHODS AND RESULTS: From January 2000 to October 2005, 1047 patients with vasospastic angina diagnosed by coronary angiography at Gifu University Hospital and related hospitals were registered in a cohort study (follow-up rate: 91.4%, median follow-up duration: 3.8 years). The presence of coronary artery stenosis, diabetes mellitus, total spasm, and age of more than 65 years had a negative prognostic impact on cardiovascular events. Patients were treated with calcium channel blockers such as diltiazem (CAS 33286-22-5, CAS 42399-41-7), amlodipine (CAS 111470-99-6), nifedipine (CAS 21829-25-4), and benidipine (CAS 91599-74-5). Among these calcium channel blockers, when patient background was matched by the propensity score in patients treated with calcium channel blockers only, the cardiovascular event rate was significantly lower in the benidipine group than in the diltiazem group. CONCLUSION: The study demonstrated for the first time that total spasm is a risk factor, independent of other factors, for cardiovascular events in patients with vasospastic angina. Treatment with benidipine showed a better prognosis than that with diltiazem.