Vincenzo Bucca

Does captopril treatment before thrombolysis in acute myocardial infarction attenuate reperfusion damage ? Short-term and long-term effects

Several experimental studies carried out on animals and on isolated heart preparations show that captopril can reduce post-ischemic reperfusion injury. Our study was aimed at investigating the effects of captopril before thrombolysis in acute myocardial infarction (AMI) and included 259 patients, hospitalized within 4 h of the onset of symptoms. Patients were randomly subdivided into two groups: the first group (131 patients, Group A, pretreatment) received 6.25 mg captopril orally about 15 min before i.v. administration of urokinase (2 million), the second group (128 patients, Group B, late-treatment), received captopril about 3 days after thrombolytic treatment. Captopril doses were later increased in both groups according to blood pressure. All patients were subdivided according to the localization of infarction. Anterior AMI was shown by 166 patients (84 from Group A and 82 from Group B); 93 patients showed inferior AMI (47 from Group A and 46 from Group B). Ventricular hyperkinetic arrhythmias (VHAs) due to reperfusion were evaluated during the first 2 h. VHAs occurred in 11.9% of patients with anterior AMI in Group A vs. 37.8% in Group B (P < 0.001). CK peak normalization time in the group with anterior AMI was achieved after 58 +/- 2 h in Group A vs. 71 +/- 2 h in Group B (P < 0.001). CK peak was 1719 +/- 152 in Group A vs. 2184 +/- 164 U/l in Group B, (P < 0.039). Late arrhythmias, higher than Lowns Class 2 were found to occur in 15.4% of patients with anterior AMI of Group A vs. 31.7% in Group B (P < 0.022), at predischarge Holter test.(ABSTRACT TRUNCATED AT 250 WORDS)

Does the addition of losartan improve the beneficial effects of ACE inhibitors in patients with anterior myocardial infarction? A pilot study

OBJECTIVE To verify the efficacy of the combination of captopril (75 mg day) and losartan (25 mg/day) in early postinfarction phases of reperfused anterior acute myocardial infarction. DESIGN AND PATIENTS 99 patients, hospitalised for suspected anterior acute myocardial infarction within four hours from the onset of symptoms, were randomised into two groups: group A included 50 patients who received captopril 75 mg/day and placebo; group B included 49 patients who received captopril 75 mg/day within three days of admission plus losartan 12.5 mg, as a first dose, and 25 mg/day successively. An additional 23 patients with anterior acute myocardial infarction received losartan 25 mg alone and acted as controls (group C) to check the effects of losartan on plasma angiotensin II (AII) concentrations. Noradrenaline (norepinephrine) (NA) and AII plasma concentrations were measured on the third and 10th day after admission in 93 patients (35 from group A, 35 from group B, and 23 from group C). 90 days after admission patients underwent echocardiography to determine end systolic volume (ESV) and ejection fraction (EF). RESULTS Patients in groups A and B were similar with regard to age, sex, creatine kinase peak, EF, ESV, and risk factors. Group B (captopril plus losartan) patients showed a significant reduction in mean (SD) systolic blood pressure within the group (basal 128 (10) mm Hg; 10 days after admission 105 (9) mm Hg, p < 0.001), and in comparison with group A (captopril) patients (basal 127 (11) mm Hg; 10 days after admission 116 (10) mm Hg, p < 0.001). Diastolic blood pressure was also lower in group B patients versus group A (66 (11)v 77 (11) mm Hg). Group C (losartan) patients also showed a significant reduction in systolic blood pressure (131 (13) mm Hg down to 121 (12) mm Hg, p < 0.001). Neither NA nor AII plasma concentrations in groups A and B differed significantly in basal samples (NA 673 (138) v 675 (141) pg/ml; AII 12.77 (4.79) v 12.65 (4.71) pg/ml) or 10 days after admission (NA 283 (93)v 277 (98) pg/ml; AII 5.31 (2.25)v 6.09 (3.31) pg/ml). However, patients in group C had higher plasma concentrations of AII (14.79 (5.7) pg/ml on the third day and 7.98 (4.92) pg/ml on the 10th day) than patients in either group A or B (p = 0.006). After 90 days following treatment, group B (captopril plus losartan) patients had a smaller ESV than patients in group A (captopril) and group C (losartan). CONCLUSION The data suggest that the combination of captopril plus losartan is feasible in the early treatment of acute myocardial infarction patients, and it appears that this combination has more effect on ESV than captopril alone in the short term.

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 UI/1 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.

Safety, Tolerability, and Neurohormonal Changes of the Combination Captopril Plus Losartan in the Early Postinfarction Period: A Pilot Study

Suppression of formation of angiotensin II (A-II) is thought to be a major contributor to the hemodynamic response to angiotensin-converting enzyme inhibition (ACE-in) therapy. However, angiotensin II (A-II) plasma levels may rebound during ACE-in treatment. The study sought to verify the feasibility, safety, and tolerability of the combination of captopril (75 mg/d) plus losartan (25 mg/d). We also wished to establish whether the combination was able to avoid the increase of angiotensin II resulting from losartan treatment in early postinfarction phases of reperfused anterior acute myocardial infarction (AMI). Forty-four patients, hospitalized for suspected anterior AMI within 4 hours from the onset of symptoms, suitable for thrombolysis (first episode), Killip class I-II and reperfused, receiving 75 mg/d of captopril within 3 days from admission, and with systolic blood pressure (BP) >120 mmHg were randomized (single-blind) into two groups: Group A included 22 patients (6 women and 16 men) and received captopril 75 mg/d and placebo. Group B included 22 patients (5 women and 17 men) and received captopril 75 mg/d within 3 days from admission plus losartan 12.5 mg, as the first dose, and 25 mg/d (BP >110 mmHg) successively. Norepinephrine (NE) and A-II levels were measured on the 3rd and 10th days after admission. The two groups were similar with regard to age, sex, creatinine kinase peak, ejection fraction, end-systolic volume, and risk factors. Group B (captopril plus losartan) showed a significant reduction of BP, from 124 ± 8.5 mmHg to 108 ± 6.4 mmHg, P < 0.001, at 10 days after admission. In group A, BP was 122 ± 9 mmHg, and 10 days after admission BP was 118 ± 11 mmHg. NE and A-II values did not show significant differences in basal samples. At 10 days after admission values were NE 298 + 90 versus 272 ± 86 pg/mL and A-II 6.07 ± 2.97 versus 5.29 ± 2.05 pg/mL for the two groups. Our data suggest, for the first time, that the combination of captopril plus losartan is feasible and does not produce serious side effects. When losartan was added to ACE-in treatment, there was no significant increase in A-II.

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.

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)

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.

Thrombolysis plus heparin versus heparin alone in the acute phases of unstable angina: preliminary findings

Abstract Several studies have shown conflicting effects of thrombolysis in patients with unstable angina. In these trials the time between presentation with chest pain and randomization was long (12 hours to 3 days). This study compared thrombolysis and heparin with heparin-alone treatment in patients in the acute phase of unstable angina. One hundred fifty-three consecutive patients hospitalized with chest pain at rest (first episode) lasting >5 minutes but P = 0.013). Data suggest that thrombolysis plus heparin produces faster clinical stabilization than heparin alone in patients treated during the acute phase of unstable angina.

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 (Lowns 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)

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.