Comparison of the effects of long-acting nifedipine CR and diltiazem R in patients with vasospastic angina: Aomori coronary spastic angina study.

OBJECTIVES: We compared the efficacy of once-daily administration of nifedipine CR 40 mg (N) with that of twice-daily diltiazem R 100mg (D) in patients with vasospastic angina (VSA) registered in 8 cardiovascular institutes in Aomori Prefecture. METHODS AND RESULTS: VSA was diagnosed by the ischemic ST segment changes during chest pain attacks at rest and/or acetylcholine induction test done during coronary angiography. Thirty-seven patients were randomly allocated to either the N (n=20) or D group (n=17). The number of symptomatic attacks and amount of short-acting nitrate use were examined based on data in diaries written by the patients. There were no significant differences in the baseline characteristics between the two groups. The mean number (median number) of attacks per week was significantly decreased in the N group from 2.56 (2.0) at baseline to 0.41 (0.0) after 4 weeks of treatment, to 0.24 (0.0) after 8 weeks, and to 0.36 (0.0) after 12 weeks (all p<0.05 vs. baseline). It was also decreased in D group from 2.71 (2.0) at baseline to 0.55 (0.0) after 4 weeks, to 0.32 (0.0) after 8 weeks, and to 0.27 (0.0) after 12 weeks (all p<0.05 vs. baseline). The numbers of attacks before and after treatment were comparable between N and D groups. In one patient in each of the N and D groups, the allocated drug was crossed over to the other due to recurrence of the attacks. One patient in each group experienced adverse effects and the drug was changed to the other. CONCLUSION: Once-daily administration of nifedipine CR was as effective as twice-daily diltiazem R in the prevention of VSA attacks.

Circulating level of gelatinase activity predicts ventricular remodeling in patients with acute myocardial infarction.

BACKGROUND: Matrix metalloproteinase (MMP) plays an important role in the development of ventricular remodeling in an animal model of acute myocardial infarction (AMI). We examined whether circulating MMP activity can predict left ventricular (LV) remodeling after AMI in humans. METHODS: We measured the circulating level of MMP-2 and MMP-9 activities (gelatinase activity) at 14 days after the onset of AMI by gelatin zymography in 52 consecutive patients (age 62+/-2). All patients underwent direct PTCA and stenting at an acute stage, and were treated subsequently with losartan or enalapril. Biplane left ventriculography was performed at admission, and 2 weeks and 6 months after the onset of AMI. RESULTS: We expressed gelatinolysis activity as the ratio to MMP-2 standard. Mean gelatinase activity was 0.721+/-0.013. We divided patients into two groups, groups with gelatinolysis activity <0.72 (low group, n=27) and >0.72 (high group, n=25). Either change in LV end-diastolic volume index (LVEDVI, ml/m(2)) or end-systolic volume index (LVESVI, ml/m(2)) from admission to 2 weeks was not different between the two groups. Changes in both LVEDVI and LVESVI from 2 weeks to 6 months were greater in high gelatinolysis activity group than those in low activity group. Moreover, circulating level of gelatinolysis activity was positively correlated with changes in LVEDVI and LVESVI from 2 weeks to 6 months. CONCLUSION: These results demonstrate that circulating level of gelatinase activity can predict LV remodeling after AMI. Inhibition of gelatinase activity at the acute phase may be a therapeutic strategy for the prevention of remodeling after AMI.

Nicorandil improves cardiac function and clinical outcome in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention: role of inhibitory effect on reactive oxygen species formation.

BACKGROUND: Early reperfusion therapy improves the clinical outcomes of patients with acute myocardial infarction (AMI), but benefits are limited by reperfusion injury in some patients. We examined the effect of nicorandil, a hybrid of K(ATP) channel opener and nicotinamide nitrate, on reactive oxygen species (ROS) formation and clinical outcomes after primary percutaneous coronary intervention (PCI) for AMI. METHODS: Fifty-eight patients with AMI were randomized into control (n = 25) and nicorandil pretreatment groups (n = 33). In the nicorandil group, nicorandil (4 mg as a bolus injection followed by constant infusion at 8 mg/hour for 24 hours) was administered just after admission. ROS formation was assessed by measuring urinary excretion of 8-epi-prostaglandin F2alpha (PGF2alpha) and compared between the 2 groups. Cardiac function and the incidence of reperfusion injury and cardiac events were also compared. RESULTS: Urinary 8-epi-PGF2alpha excretion was increased 2-fold at 60 to 90 minutes after PCI in the control group, whereas it was unchanged after PCI in the nicorandil group (P <.0001 between the 2 groups). The incidence of no-reflow phenomenon was lower in the nicorandil group than in the control group. Left ventricular ejection fraction and cardiac index at 6 months were greater in the nicorandil group than in controls. Plasma brain natriuretic peptide level at 6 months was lower in the nicorandil group. Incidences of inhospital cardiac events and rehospitalization were lower in the nicorandil group than in controls. CONCLUSIONS: Nicorandil improves cardiac function and clinical outcomes in patients with AMI. Suppression of ROS formation may be involved in the mechanism.

Effect of allopurinol pretreatment on free radical generation after primary coronary angioplasty for acute myocardial infarction.

Allopurinol, an inhibitor of xanthine oxidase, was shown to improve the regional ventricular function after coronary artery occlusion and reperfusion in animal models. The effects of oral administration of allopurinol on a transient increase in free radical generation after primary percutaneous transluminal coronary angioplasty (PTCA) in patients with acute myocardial infarction (AMI) and on their clinical outcomes were examined. Thirty-eight AMI patients undergoing primary PTCA were randomly assigned to control (group 1, n = 20) and allopurinol treatment groups (group 2, n = 18). Allopurinol (400 mg) was administered orally just after the admission (approximately 60 min before reperfusion). Free radical production was assessed by successive measurement of urinary excretion of 8-epi-prostaglandin F(2alpha) (PGF(2alpha)) after PTCA. Urinary 8-epi-PGF(2alpha) excretion was increased by twofold at 60-90 min after PTCA compared with the baseline value in group 1. This increase was completely inhibited in group 2. Plasma allopurinol concentration was 1,146 +/- 55 ng/ml in group 2 when reperfusion was achieved. Slow flow in the recanalized coronary artery after PTCA occurred less frequently in group 2 than in group 1. Cardiac index determined just after reperfusion and left ventricular ejection fraction at 6 months after PTCA were both significantly greater in group 2 than in group 1 although pulmonary capillary wedge pressure was similar in the two groups. In conclusion, allopurinol pretreatment is effective in inhibiting generation of oxygen-derived radicals during reperfusion therapy and the recovery of left ventricular function in humans.