Acute effects of intravenous nicorandil on hemodynamics in patients hospitalized with acute decompensated heart failure.

BACKGROUND: Nicorandil injection, a potent vasodilator with K(ATP) channel opening action and nitrate-like action, has been used for treatment of unstable angina. In the present investigation, we examined the effect of intravenous nicorandil on hemodynamics in patients with acute decompensated heart failure (ADHF). METHODS: ADHF patients admitted to hospital with pulmonary artery wedge pressure (PAWP)≥18 mm Hg were enrolled. Patients received nicorandil by an intravenous bolus injection of 0.2mg/kg/5 min followed by continuous infusion at a rate of 0.05, 0.10, or 0.20mg/kg/h for 6h. RESULTS: Nicorandil administration caused a significant decrease in PAWP and increase in the cardiac index (CI) that began immediately after the injection and were maintained during the continuous infusion. After 6h, nicorandil administration at 0.2mg/kg/5 min followed by 0.20mg/kg/h resulted in a decrease in PAWP (26.5%, p<0.01), an increase in CI (15.8%, p<0.05), and a decrease in total peripheral resistance (13.8%, p<0.01) in a dose-dependent manner. Nicorandil decreased blood pressure significantly, without an excessive decrease or negative impact even in patients with lower systolic blood pressure. CONCLUSION: Intravenous administration of nicorandil, by bolus injection followed by continuous infusion, improves PAWP and CI in ADHF patients immediately and continuously as a potent vasodilator with combined preload and afterload reduction. These results demonstrate that nicorandil is a safe and effective new medication for the treatment of ADHF.

[Diagnosis of coronary artery disease by thallium-201 myocardial scintigraphy with intravenous infusion of SUNY4001 (adenosine) in effort angina pectoris--the clinical trial report at multi-center: phase II].

Forty-four patients with effort angina pectoris were evaluated with SUNY4001 (adenosine) thallium-201 (201Tl) myocardial scintigraphy to detect coronary artery disease. These patients had single-vessel disease (> or = AHA 90% stenosis) in either RCA or LAD. Adenosine was infused at the rate of 120 or 140 microg/kg/min for six minutes. 111 MBq of 201Tl was injected after three minutes of the start of the infusion. The early and delayed images were obtained by SPECT imaging. The sensitivity was 94.7% at 120 microg/kg/min and 84.2% at 140 microg/kg/min. Adenosine 201Tl myocardial scintigraphy showed high accuracy for detecting significant coronary artery disease. Adverse reactions occurred in 77.3% of the patients. Regarding the rates of the adverse reactions, there was no significant difference between 120 and 140 microg/kg/min. Major adverse reactions were Chest pain/discomfort (52.3%) and Flushing/Feeling of warmth (27.3%). No serious complication was observed at any infusion rate. Most of adverse reactions disappeared sortly. Only two patients required treatment for moderate chest pain, which, however, disappeared in several minutes. One of the treatments was merely the termination of adenosine infusion, and the other was sublingual spray of nitroglycerin. Adenosine infusion caused slight decrease in blood pressure and increase in heart rate. The hemodynamic changes resolved within several minutes after the adenosine infusion. Decrease in systolic blood pressure of more than 20 mmHg from the base level occurred in 26.1% and 52.4% at 120 and 140 microg/kg/min infusion rate respectively. Therefore, the adenosine infusion at 120 microg/kg/min should be considered safe and useful for the diagnosis of coronary artery disease by pharmacologic stress imaging.

[The diagnostic value for ischemic heart disease of thallium-201 myocardial scintigraphy by intravenous infusion of SUNY4001 (adenosine)--the report of clinical trial at multi-center: phase III].

With two hundred and seven patients unable to exercise adequately, the diagnostic accuracy and adverse reaction of 201Tl myocardial scintigraphy with the pharmacologic stress by SUNY4001 (adenosine) infusion were studied. Adenosine was infused for six minutes at the rate of 120 microg/kg/min, and then 201Tl was injected after three minutes from the start of infusion. The early and delayed images were obtained by SPECT imaging. According to angiography, > or = AHA 90% stenosis was defined as significant. The sensitivity of detecting coronary artery disease was 87.1% and the specificity was 46.0%. Adverse reactions occurred in 66.7% of the patients, most of which disappeared shortly with no need for treatment. Major adverse reactions were chest pain/discomfort (30.4%), flushing/feeling of warmth (22.4%) and blood pressure decrease (17.4%). Adenosine infusion caused slight decrease in blood pressure and increase in heart rate. These hemodynamic changes were resolved within several minutes from the termination of adenosine infusion. We concluded that adenosine-201Tl imaging is safe and useful to detect coronary artery disease in patients unable to exercise adequately.

[Comparison of myocardial perfusion imaging by thallium-201 single-photon emission computed tomography with SUNY4001 (adenosine) and exercise--crossover clinical trial at multi-center].

We compared the ischemic diagnosis ability and adverse events of 201Tl myocardial perfusion imaging with SUNY4001 (adenosine) stress to that with exercise (ergometer) stress both on random crossover trial. Thirty one known or suspected chronic stable angina patients who are able to exercise and 10 healthy volunteers were enrolled for the trial. The early and delayed images were obtained by SPECT imaging. The concordance of diagnoses [ischemia vs. no ischemia] between the two types of stresses was 97.3% (36/37) [Kappa: 0.9068]. The sensitivity and specificity based on the exercise test were 100% (6/6) and 96.8% (30/31) respectively. The incidence of adverse events caused by SUNY4001 and the exercise were 44.7% (17/38) and 52.6% (20/38), respectively. Major adverse events caused by SUNY4001 were BP decrease, flushing and headache. And those by exercise were ST decrease, dyspnea and chest pain. None of the adverse events required the intervention or caused life-threatening complication in the trial. The trial showed that the ischemic diagnosis ability and safety of 201Tl scintigraphy with SUNY4001 stress are almost equal to those of the exercise stress that is considered as the standard stress method. We concluded that 201Tl imaging with SUNY4001 is safe and useful for detecting ischemic heart disease, especially for patients unable to exercise adequately.

Is angiotensin-converting enzyme inhibitor useful in a Japanese population for secondary prevention after acute myocardial infarction? A final report of the Japanese Acute Myocardial Infarction Prospective (JAMP) study.

BACKGROUND: Although angiotensin-converting enzyme (ACE) inhibitors have appeared to be useful for secondary prevention after acute myocardial infarction (AMI) in Western countries, that has not been confirmed in non-western countries. We investigated whether ACE inhibitors improve survival rates in patients who have survived an AMI in Japan. METHODS: A randomized controlled trial, the first non-pharmaceutical company-supported multicenter trial of a medication in Japan, was carried out in 48 institutions from 1993 to 2000. A total of 888 of 1163 patients with AMI were eligible for the full analysis set (FAS). The mean patient age was 62 years, and 78% of patients were men. Subjects were randomized to 2 groups; 422 received ACE inhibitors and 466 did not receive ACE inhibitors. The primary end point was combined cardiac events, which was defined as cardiac or non-cardiac death, recurrent non-fatal myocardial infarction, coronary revascularization, and hospitalization because of worsening angina or congestive heart failure. The mean follow-up period was 5.8 years. RESULTS: There were no significant differences in the 2 groups in baseline data. During the follow-up period, 3 patients were lost to follow-up. With Kaplan-Meier analysis, the annual rate of total cardiac events was 32% in both groups. After adjustment for clinical baseline data, ACE inhibitor administration was not revealed with Cox regression analysis to have a significant prognostic effect in our study. CONCLUSION: We did not show a significant improvement in outcome with ACE inhibitor administration in subjects who survived after AMI in a Japanese study population. Further evaluations with a larger population or in subjects who are at a higher risk for AMI are necessary to confirm our findings.

Anti-anginal effect of fasudil, a Rho-kinase inhibitor, in patients with stable effort angina: a multicenter study.

Rho-kinase plays an important role in calcium sensitization for vascular smooth muscle (VSMC) contraction and may be involved in the inappropriate coronary vasoconstriction during exercise-induced myocardial ischemia. In this multicenter phase II study, the anti-anginal effect of fasudil, which is metabolized to a specific Rho-kinase inhibitor hydroxyfasudil after oral administration, was examined in patients with stable effort angina. In the phase IIa trial, after a 2-week washout period of anti-anginal drugs, 45 patients received increasing doses of fasudil (5, 10, and 20 mg TID for every 2 weeks). The fasudil treatment significantly prolonged the maximum exercise time and the time to the onset of 1-mm ST segment depression on treadmill exercise test (both p < 0.01), whereas blood pressure and heart rate during exercise were unchanged before and after the treatment. Higher doses of fasudil (20 and 40 mg TID) were subsequently tested in 22 patients in the same manner with similar positive results. In the phase IIb trial, after a 2-week washout period of anti-anginal drugs, 125 patients were assigned, in a double-blind manner, to a 4-week oral treatment with a different dose of fasudil (5, 10, 20, or 40 mg TID) and treadmill exercise test was performed before and after the treatment. Again, both maximum exercise time and time to the onset of 1-mm ST segment depression were prolonged in all groups. A significant dose-response relation was noted across the treatment groups for the exercise tolerance index that was determined by the combined effect of exercise time and ST segment depression (p = 0.006). Fasudil was well tolerated in both trials without any serious adverse reactions. These results suggest the efficacy and adequate safety profile of fasudil, the first drug in a novel class of vasodilators, for the treatment of stable effort angina.