The combination ace-inhibitors plus canreonate in patients with anterior myocardial infarction: safety and tolerability study.

BACKGROUND: There is recent evidence that aldosterone (ALDO) exerts pro-fibrotic effects, acting via the mineral-corticoid receptors in cardiovascular tissues and partial aldosterone escape during ACE-inhibition treatment occurs. METHODS: A double blind randomised study was performed to evaluate the feasibility, and tolerability of the administration of the 25 mg/day of canreonate plus captopril versus captopril alone in patients with anterior AMI unsuitable for thrombolysis and/or not receiving thrombolytic treatment, and unreperfused after thrombolysis. Fifty five patients hospitalised for anterior AMI,with a serum creatinine concentration <2.0 mg/dl and a serum K concentration <5.0 mmol per liter were randomised in 2 groups: Group A included 27 patients who received captopril and 25 mg i.v. of canreonate (1 mg/h for the 1st 72 h and then orally 25 mg/day. Group B (28 patients) received captopril and placebo. Ten days after admission they underwent echocardiography to determine end systolic volume (ESV), ejection fraction (EF), End diastolic diameter EDD, E/A ratio, E deceleration time (dec. time) and isovolumetric relaxation time (IVRT), E and A peak velocities. RESULTS: All patients did not show patency of the infarct related artery (7-10 days after AMI) and the 2 groups were similar in regard to age, sex, diabetes, smoking habits, hypertension, CK enzymatic peak, adjuvant therapy, EF, ESV, and incidence of CABG/PTCA. One patient only showed increase of serum K>5.5 mmol/dl and creatinine >2.0 mg per liter after 10 days of treatment (group A). The mitral E/A ratio was higher in group A than group B (0.85+/-0.18 and 0.75+/-0.14) respectively, P=0.024. Creatinine, blood urea and serum K did not show significant differences between groups. No side effects were observed during the study period. The incidence of vessel diseases was similar in both groups. CONCLUSIONS: Our data suggest that the combination of captopril plus canreonate in feasible in early treatment of AMI patients.

Effects of trimetazidine administration before thrombolysis in patients with anterior myocardial infarction: short-term and long-term results.

Reperfusion may prevent or reduce the development and extent of necrosis, but may also lead to an increase in reperfusion damage. Experimental studies performed in various animal models of myocardial ischemia have demonstrated the anti-ischemic properties of trimetazidine (TMZ) and have suggested that TMZ has antioxidant properties, without any direct hemodynamic effects. Our study was aimed at investigating the effects of TMZ before thrombolysis in acute anterior myocardial infarction and included 81 patients, hospitalized within 4 hours of the onset of symptoms. Patients were randomly (double-blind) subdivided in two groups The first group (40 patients, Group A, TMZ-pretreatment), received 40 mg TMZ orally about 15 minute before thrombolysis and, subsequently, 20 mg every 8 hours. The second group (41 patients, Group B) received placebo before thrombolysis. Ventricular arrhythmias (VA) due to reperfusion were evaluated in the first 2 hours. VA occurred in 15 of patients in group A, versus 29 in group B, p<0.05. Creatine kinase (CK) normalization time was achieved after 55.7+/-12.5 hours in group A, versus 61.2+/-12.1 hour in group B, p = 0.048. CK peak was 1772+/-890 in group A vs. 2285+/-910 Ul/l in group B, (p = 0.012). In the follow-up (range 6-22 months), there were 4 deaths, two patients in each group. After 180 days from treatment, the TMZ group showed a smaller end systolic volume than the placebo group (echocardiographic data), 46.2+/-12 and 52.8+/-13 ml/m2, respectively, p = 0.037. Our data suggest that TMZ probably reduces reperfusion damage and/or infarct size in patients with anterior AMI subjected to thrombolysis and affects the post-AMI remodeling. Our data must be interpreted with caution because of the selection of patients. These findings require further extensive trials.

Early captopril treatment reduces plasma endothelin concentrations in the acute and subacute phases of myocardial infarction: a pilot study.

It has been reported that endothelin-1 (ET-1) increases in acute myocardial infarction (AMI). Experimental studies showed that captopril administration reduces ET-1 secretion. In addition, it was reported that the increased ET-1 levels are a negative prognostic index. The study sought to verify whether captopril can reduce plasma ET levels in the acute and subacute phases of reperfused anterior AMI. Forty-five patients, hospitalized for suspected anterior AMI within 4 h from the onset of symptoms, suitable for thrombolysis (first episode), Killip class I-2, were randomized (double blind) into two groups: group A (23; seven women/16 men) received captopril (as first dose) 2-4 h after starting thrombolysis (the dose was then increased up to 25 mg every 8 h). Group B (22; five women/17 men) received placebo after thrombolysis. All the patients met the reperfusion criteria. The two groups were similar with regard to age, sex, CK peak, ejection fraction, end-systolic volume and risk factors. Plasma ET levels were measured at entry, and 2, 12, 24, 48, and 72 h after starting thrombolysis. Mean concentrations of ET +/- SD: Group A basal, 1.50 +/- 0.67; at 2h, 2.31 +/- 1.24; 12 h, 1.84 +/- 1.45; 24 h, 1.30 +/- 0.72; 48 h, o.95 +/- 0.50; 72 h, 0.60 +/- 0.15 fmol/ml; p < 0.001. Group B basal, 1.58 +/- 0.83; at 2 h, 2.38 +/- 1.35; 12 h, 2.33 +/- 1.71; 24 h, 1.80 +/- 1.41; 48h, 1.46 +/- 0.88; 72 h, 0.93 +/- 0.44 fmol/ml; p < 0.001. Difference between the two groups was significant at the beginning of the test (between 2 and 12 h, p[=]0.002). After that, the values of the plasma endothelin decreased in parallel, p < 0.001. Our data suggest that captopril affects plasma ET levels in the acute and subacute phases of AMI. Moreover, these results provide additional evidence for a beneficial effect of early captopril treatment.

Captopril plus losartan in early post-infarction. Neurohormonal effects: a pilot study.

BACKGROUND: Suppression of the formation of angiotensin II (A II) is thought to be a major contributor to the hemodynamic response to angiotensin-converting enzyme inhibition (ACE-inhibitor) therapy. However, during ACE-inhibitor treatment, A II plasma levels may also recover through tissue chymase. This study has attempted to verify the feasibility, safety and tolerability of a combined treatment using captopril (75 mg/day) and losartan (25 mg/day), and to ascertain its ability to reduce the formation and action of A II in the early post-infarction phase of reperfused anterior myocardial infarction (AMI). METHOD: Forty-four patients hospitalized for suspected AMI within 4 hours of the onset of symptoms, who were suitable for thrombolysis (first episode), in Killip class I-II, reperfused, treated with 75 mg/day of captopril within 3 days of admission and with a blood pressure level of more than 120 mmHg, were randomized (single-blind) into two groups that were similar with regard to age, sex, blood pressure, CK peak, ejection fraction, end-systolic volume and risk factors. Group A (22 subjects: 6 women/16 men) received captopril (75 mg/day) and placebo, while group B (22 subjects: 5 women/17 men) was given captopril (75 mg/day) plus losartan, initially at 12.5 mg and then at 25 mg/day thereafter (BP > 110 mmHg). Norepinephrine (NE) and A II plasma levels were measured on the third and tenth day after admission. RESULTS: Ten days after admission, group B (captopril plus losartan) showed a significant decrease in blood pressure (BP) on an intragroup level (p < 0.001) as well as in comparison with group A (p < 0.001), with values of 108 + 6.4 and 118 + 11 mmHg respectively. At the same time interval, NE and A II values did not show significant differences within or between groups. CONCLUSIONS. For the first time, our data suggest that a combined captopril-losartan treatment is feasible and that it has no particular side effects. In addition, it shows no significant increase of A II that would be produced by losartan alone.

Captopril does not affect plasma endothelin-1 during thrombolysis and reperfusion.

Studies showed that endothelin-1 (ET-1) was increased in the acute myocardial infarction (AMI). Experimental studies reported that captopril was able to reduce ET-1 secretion, and that ET-1 was increased during reperfusion. This study was aimed to verify if captopril was able to reduce plasma ET-1 during thrombolysis in AMI. Seventy-three patients, hospitalized for suspected AMI within 4 h from the onset of symptoms suitable for thrombolysis (1st episode), Killip class 1-2, were randomized (double blind) into two groups: group 1 (37 pts), 8 F/29 M, received captopril, 6.25 mg, orally 15 min before thrombolysis. Group 2: (36 pts) 8 F/28 M, received placebo before thrombolysis. All patients met the reperfusion criteria. Plasma ET-1 were checked on admission, at 1 h and at 2 h, after starting thrombolysis. Group 1 contained ten unstable angina, 17 anterior and ten inferior AMIs. Group 2 contained ten unstable angina, 16 anterior and ten inferior AMIs. Mean concentrations of ET-1: Unstable angina: group 1, basal--4.56, at 1 h--4.47, 2 h--5.89 pg/ml; group 2: basal--4.17, at 1 h--4.59, 2 h--5.24 pg/ml. Inferior AMI: group 1: basal--6.87, 1 h--7.75, 2 h--8.47; group 2: basal--6.34, 1 h--6.68, 2 h--7.98 pg/ml. Anterior AMI: group 1: basal--7.17, 1 h--7.93, 2 h--10.76 pg/ml (between basal and 2-h samples P < 0.05); group 2: basal--7.46, 1 h--7.51, 2 h--10.74 pg/ml. Differences between the two groups were not significant. Our data suggest that captopril does not affect plasma ET-1 during thrombolysis.

Advantages of immediate two-dimensional echocardiography in patients with acute cardiac ischemic events.

UNLABELLED: We hypothesized that the assessment of kinetic alterations on two dimensional echocardiogram (2DE) would provide greater diagnostic information than clinical symptoms and ECG changes only. The study was aimed to determine sensitivity of 2DE in patients with cardiac ischemic events and to improve the indications to thrombolysis. Three-hundred ninety-one patients (87 F; 304 M) hospitalized for suspected acute myocardial infarction (AMI), first episode, within 4 h from the onset of symptoms, suitable for thrombolysis Killip class I-II and with unstable angina (UA), were admitted in the study. Patients had to show ECG changes and alterations of segmentary motion on 2DE performed at entry, or 2DE alterations without ECG changes. The 2DE variables analyzed included right ventricular function and left ventricular systolic function. Thrombolysis was performed when 2DE and ECG changes were evidenced at the same time and when 2DE alterations without ECG changes were observed. Patients with UA treated with heparin alone were also studied. The presence of segmentary motion alterations was mandatory. RESULTS: Inferior AMIs, 87 patients (60 +/- 13 years), anterior AMI, 169 patients (61 +/- 11 years); UA group subjected to thrombolysis, 87 patients (62 +/- 12 years); UA group treated with heparin, 48 patients (62 +/- 12 years). We noted only one patient false negative, and five patients false positive. Alterations of right ventricular function were observed in 24, 14 and nine patients with inferior, anterior AMI and UA, respectively. Normal ECG at entry was observed in seven, two and seven patients with inferior, anterior AMI and UA, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of the administration of captopril, metoprolol and of the captopril-metoprolol combination as adjuvant therapy during thrombolysis in acute myocardial infarction.

UNLABELLED: The aim of the study was to verify, during thrombolysis in patients with anterior acute myocardial infarction, the safety and effects of beta-blockers or ACE-inhibitors and their combination in the short and long term. One-hundred sixty-six patients hospitalized within 4 h from the onset of the symptoms (first episode), eligible for thrombolysis, Killip class I-II, were randomized (single blind) into four groups. Group A (42 patients) received 6.25 mg captopril (orally) 15 min before thrombolysis and metoprolol (i.v.) not later than 1 h, and orally afterwards. Group B (42 patients) received 6.25 mg captopril 15 min before thrombolysis. Group C (37 patients) received metoprolol not later than 1 h. Group D (45 patients) received thrombolysis only. Later (day 3), groups C and D also received captopril. We checked ventricular arrhythmias (first 2h) from thrombolysis, creatine kinase peak, creatine kinase peak normalization time, late ventricular arrhythmias at Holter test pre-discharge (Lown's class > 2). At follow-up (mean 30.5 +/- 2 months), mortality was evaluated for reinfarction and ventricular failure. Age and sex were similar. RESULTS: Early ventricular arrhythmias: Group A, five cases; Group B, five cases; Group C, 15 cases; Group D, 16 cases. Creatine kinase peak: Group A, 1875 +/- 220 U/l; Group B, 1566 +/- 168 U/l; Group C, 2274 +/- 212 U/l; Group D 2103 +/- 232 U/l. Creatine kinase peak normalization time: Group A, 57.7 +/- 3 h; Group B, 58.1 +/- 3 h; Group C, 72.7 +/- 3 h; Group D, 69.5 +/- 2 h (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)