Increased reperfusion by glycoprotein IIb/IIIa receptor antagonist administration in case of unsuccessful and failed thrombolysis in patients with acute myocardial infarction: a pilot study.

BACKGROUND: The aim of this study was to evaluate the effectiveness of glycoprotein (GP) IIb/IIIa receptor inhibitors in acute myocardial infarction (AMI) patients in case of unsuccessful and failed thrombolysis. METHODS: Eighty-four patients hospitalized within 4 hours of symptom onset were randomized (single blind) into two groups. Regardless of the group, placebo or GP IIb/IIIa inhibitors were administered to patients who did not present with reperfusion signs (failed thrombolysis) 30 min after starting thrombolysis and 30-60 min after the end of full thrombolysis in patients with pain recurrence and ST-segment elevation (unsuccessful thrombolysis). Reperfusion was assessed by the creatine kinase peak occurring within 12 hours, by the observation of rapid ST-segment reduction (50-70% within 1 hour) in the 12-lead ECG continuous tracing, by the rapid regression of pain and by the development of early ventricular arrhythmias. Group 1 patients (n = 42) received, during failed thrombolysis or after 30-60 min of effective thrombolysis but with pain recurrence and ST-segment elevation (unsuccessful thrombolysis), treatment with i.v. GP IIb/IIIa inhibitors, heparin according to the TIMI 14 trial, and aspirin. Group 2 patients (n = 42) received a full dose of recombinant tissue-type plasminogen activator (rt-PA 100 mg) and placebo either during failed thrombolysis or, after 30 min of effective thrombolysis but with pain recurrence and ST-segment elevation, and standard heparin treatment and aspirin. RESULTS: In group 1, 39 patients showed rapid reperfusion (4 +/- 3 min); 22 patients received rt-PA 65 mg and 20 patients received rt-PA 100 mg and subsequent GP IIb/IIIa inhibitor treatment. Coronary angiography, performed after 12-72 hours showed patency of the infarct-related artery in 39 patients whose clinical picture was suggestive of rapid reperfusion during administration of a bolus of GP IIb/IIIa inhibitors. In group 2, no patients showed reperfusion and they were submitted to rescue coronary angioplasty (p < 0.05). Side effects occurred in 3 cases in group 1 and in 2 cases in group 2. Patients receiving GP IIb/IIIa inhibitors showed a reduced incidence of stent treatment (p = NS) and a significant reduction in the occurrence of events (angina) within 30 days of treatment (p = NS). CONCLUSIONS: Our data suggest that in patients with AMI and failed thrombolysis, treatment with GP IIb/IIIa receptor inhibitors is feasible. The increase in the risk of bleeding was acceptable. The most important result was that this combination is safe.

Additional beneficial effects of canrenoate in patients with anterior myocardial infarction on ACE-inhibitor treatment. A pilot study.

BACKGROUND: Recent evidence suggests that, via the mineralocorticoid receptors present in cardiovascular tissues, aldosterone exerts profibrotic effects, and that partial aldosterone escape occurs during ACE-inhibitor treatment. METHODS: A double-blind, randomized study was performed in order to evaluate the feasibility, tolerability, and the effects of the administration of 25 mg/day of canrenoate plus captopril versus captopril alone to patients with anterior acute myocardial infarction (AMI) unsuitable for or not receiving thrombolytic treatment and to patients in whom such treatment resulted or did not result in reperfusion. One hundred eighty-seven patients with anterior AMI were included in the present study. In all cases serum creatinine concentrations and serum K concentrations were < 2.0 mg/dl and < 5.5 mmol/l respectively. The patients were randomized in two groups: the canrenoate group included 94 patients who received captopril and 25 mg i.v. of canrenoate (1 mg/hour for the first 72 hours and then orally 25 mg/day) whereas the placebo group (93 patients) received captopril and placebo. On admission and on days 10, 90 and 180 all patients underwent echocardiography in order to determine the end-systolic volume (ESV), the ejection fraction (EF), the end-diastolic diameter, the E/A ratio, the E deceleration time as well as the isovolumetric relaxation time (IVRT) and the E and A peak velocities. RESULTS: Unreperfused patients did not show patency of the infarct-related artery whereas in reperfused patients this vessel was patent (7-10 days after AMI). The two groups were similar in age, sex, incidence of diabetes, smoking habits, hypertension, creatine kinase enzymatic peak, adjuvant therapy, baseline EF, ESV, and incidence of coronary artery bypass grafting/coronary angioplasty. Following 10 days of treatment (canrenoate group), only 9 patients presented with serum K and creatinine concentrations respectively > 5.5 mmol/l and > 2.0 mg/dl. Among those patients receiving canrenoate, the mitral E/A ratio was higher compared to the placebo group (p = 0.001) whereas the ESV was significantly reduced (p < 0.05). The deceleration time for reperfused patients receiving canrenoate was higher than that observed for reperfused patients in the placebo group. The intragroup EF was significantly increased (p = 0.042). Compared to the placebo group, the IVRT was significantly higher for unreperfused patients receiving canrenoate than in the placebo group (p = 0.001). Serum creatinine, blood urea and K levels as well as the incidence and extent of vessel disease were similar for both groups. No side effects were observed during the study period. CONCLUSIONS: Our data suggest that the combination of captopril plus canrenoate is feasible for the initial treatment of patients presenting with AMI. Besides, compared to captopril alone it is more efficacious in improving the E/A ratio, the ESV, the EF, and the IVRT.

Comparison of the effects of felodipine and cilazapril on exercise performance in patients with mild to moderate hypertension. A crossover study.

This double-blind crossover study was designed to compare the effects of felodipine and cilazapril on exercise performance in hypertensive patients. After a 2-week placebo run-in period, 40 patients with mild to moderate hypertension were randomized into two parallel groups to receive either felodipine (10 mg) or cilazapril (5 mg) for 4 weeks. After another 2-week washout period, treatments were then crossed over for a further 4-week study period. All patients were given an extensive rest and exercise evaluation at the end of the placebo period. Extensive rest and exercise evaluations were repeated after a 4-week treatment period and again after the second washout period and after the second 4-week treatment period. Before each exercise test, epinephrine, norepinephrine and dopamine plasma levels and plasma renin activity were measured. Two groups were similar at baseline for systolic and diastolic blood pressure and heart rate as well as for laboratory and hormonal variables and duration of exercise test. At the end of treatment diastolic blood pressure was significantly reduced in the felodipine group (p = 0.019). Duration of exercise test was longer than at baseline (p = 0.031) in the felodipine group. Plasma dopamine levels were significantly increased in the cilazapril group. Plasma renin activity significantly increased in the felodipine group. In conclusion, our data show that the two drugs have the same effectiveness in resting conditions but that felodipine is more effective in lowering maximum exercise diastolic blood pressure and in improving exercise time with an double product increase (not significant); it has no statistically significant effect on maximal exercise systolic blood pressure.