Effects of beta-blockers and calcium channel blockers in acute myocardial infarction.

beta-blockers and calcium channel blockers have been evaluated extensively during the acute phase and following myocardial infarction. beta-blockers, when administered early and intravenously, reduce early mortality, reinfarction and cardiac arrests by about 16%. The reduction in mortality is likely to be due to multiple mechanisms including reductions in cardiac rupture, reinfarction and ventricular fibrillation. Recent data also suggest a reduction in intracranial haemorrhage when administered in conjunction with thrombolytic therapy. Prolonged use of beta-blockers for a year or two after myocardial infarction leads to significant reductions in total mortality, sudden deaths and reinfarction. The benefits of beta-blockers are probably mediated through a number of mechanisms, including reduction in heart rate and prevention of plaque rupture, in addition to the mechanisms stated above. Calcium channel blockers do not reduce mortality. It appears that some agents that increase heart rate (e.g. dihydropyridines) may increase the risk of death and reinfarction. On the other hand, agents that reduce heart rate (verapamil and diltiazem) appear to have a neutral effect on mortality but may reduce reinfarction rates. The benefits of beta-blockers appear to be consistent in most subgroups of patients examined, whereas the adverse effects of calcium channel blockers are most marked in those with large infarcts or heart failure. In conclusion, beta-blockers are preferable to calcium channel blockers in the acute phase and long-term after myocardial infarction.

Effects of intravenous magnesium in suspected acute myocardial infarction: overview of randomised trials.

OBJECTIVE: To investigate the effect of intravenous magnesium on mortality in suspected acute myocardial infarction. DESIGN: Systematic overview of all available randomised trials in which patients were allocated to receive either intravenous magnesium or otherwise similar treatment without magnesium. SETTING: Coronary care units of several hospitals. PATIENTS: 1301 patients in seven randomised trials. MAIN OUTCOME MEASURE: Short term mortality. RESULTS: Considering the seven trials collectively there were 25 (3.8%) deaths among 657 patients allocated to receive magnesium and 53 (8.2%) deaths among 644 patients allocated control, generally during hospital follow up. This represents a 55% reduction in the odds of death (p less than 0.001) with 95% confidence intervals ranging from about one third to about two thirds. 70 of 648 patients allocated magnesium compared with 109 of 641 controls had serious ventricular arrhythmias, suggesting that magnesium reduces the incidence, though the definition varied among trials. Other adverse effects were rare in the limited number of patients for whom this data were available. CONCLUSION: Despite the limited number of patients randomised this overview suggests that intravenous magnesium therapy may reduce mortality in patients with acute myocardial infarction. Further large scale trials to confirm (or refute) these findings are desirable.

Effects of tissue-type plasminogen activator and anisoylated plasminogen streptokinase activator complex on mortality in acute myocardial infarction.

An overview of eight randomized controlled trials of tissue-type plasminogen activator (Alteplase or Duteplase) and 10 of anisoylated plasminogen streptokinase activator complex (Anistreplase) showed that the odds of early death were reduced by 29% by tissue-type plasminogen activator and 46% by anisoylated plasminogen streptokinase activator complex, with overlapping 95% confidence intervals. Although the beneficial effects of both agents are consistent and are strengthened when all the trials are considered together, the available data do not permit comparisons of the relative efficacy of these two agents with each other or with streptokinase.

Calcium channel blockers in acute myocardial infarction and unstable angina: an overview.

OBJECTIVE: To assess the effects of calcium channel blockers on development of infarcts, reinfarction, and mortality. DESIGN: A systematic overview of all randomised trials of calcium channel blockers in myocardial infarction and unstable angina. PATIENTS: 19,000 Patients in 28 randomised trials. RESULTS: In the trials of myocardial infarction 873 deaths occurred among 8870 patients randomised to active treatment compared with 825 deaths among 8889 control patients (odds ratio of 1.06, 95% confidence interval of 0.96 to 1.18). There was no evidence of a beneficial effect on development and size of infarcts or rate of reinfarction. The results were similar in short term trials in which treatment was confined to the acute phase and those in which treatment was started some weeks later and continued for a year or two. There was no evidence of heterogeneity among different calcium channel blockers in their effects on any end point. The results were similar in the unstable angina trials (110 out of 561 patients treated with calcium channel blocker compared with 104 out of 548 controls developed a myocardial infarction; 14 out of 591 treated compared with nine out of 578 controls died). CONCLUSIONS: Calcium channel blockers do not reduce the risk of initial or recurrent infarction or death when given routinely to patients with acute myocardial infarction or unstable angina.

Central haemodynamic effects of metoprolol early in acute myocardial infarction. A placebo controlled randomized study of patients with low heart rate.

The central haemodynamic effects of metoprolol in patients with acute myocardial infarction and with heart rate less than or equal to 65 beats min-1 have been investigated in a randomized double-blind trial. The aim was to study the tolerance in this selected patient group and to assess possible differences in haemodynamic response amongst patients with initially higher heart rates. Exclusion criteria were: treatment with beta blockers; heart rate greater than 65 beats min-1; systolic blood pressure less than 110 mmHg; and physical signs of serious heart failure. Following pulmonary artery catheterization, 22 patients were randomized to metoprolol 15 mg i.v. + 50 mg q.i.d. orally (N = 12) or placebo (N = 10). Central pressures and cardiac output were recorded before and during the 24 hours after drug administration. There was a significant fall in heart rate, cardiac index, rate pressure product and stroke work index of 10-20% in the metoprolol, compared with the placebo group. The differences were most pronounced immediately after the metoprolol injection. The pulmonary artery capillary wedge pressure was not significantly changed. The overall haemodynamic response to metoprolol was similar to that reported in patients with acute myocardial infarction and heart rate above 65 beats min-1. Tolerance was good.

Central haemodynamics in acute myocardial infarction in relation to mortality and peak enzyme activity.

The relation of central haemodynamic changes to subsequent mortality and peak enzyme activity was investigated in 190 patients with acute myocardial infarction. The mean delay time from onset of symptoms to the haemodynamic study was 7.2 hours. Major exclusion criteria were heart rate less than 65 beats min-1, systolic blood pressure less than 105 mmHg and lung rales to a distance of greater than 10 cm above the lung bases. Nine patients (4.7%) died within 15 days and 16 patients (8.4%) within 90 days after the infarction. Compared to survivors, non-survivors were characterized by baseline depression of cardiac index, stroke volume index and left ventricular stroke work index, while pulmonary capillary wedge pressure and peripheral resistance were increased. However, a wide overlap between survivors and non-survivors makes the predictive value low in the individual patient. Peak serum aspartate aminotransferase (S-ASAT) activity was weakly related to baseline pulmonary capillary wedge pressure (r = 0.28; P less than 0.001) and stroke volume index (r = -0.22; P less than 0.01). The correlation to pulmonary capillary wedge pressure was only found in anterior (r = 0.34) infarcts. Peak serum lactate dehydrogenase (LD1) was not correlated with baseline haemodynamics.

Natural evolution of left ventricular haemodynamics following uncomplicated acute myocardial infarction.

In an attempt to investigate the changes in left ventricular haemodynamics following uncomplicated myocardial infarction 95 patients with definite electrocardiographic signs of infarction, without clinical signs of cardiac failure, were monitored with a Swan Ganz catheter for the first 24 hours after admission to hospital. The median delay from onset of symptoms was 6.8 hours. Mean heart rate increased (83-86 beats/min; P less than 0.05) while stroke volume index fell (38.4-36.6 ml/m2; P less than 0.05); cardiac index therefore remained unchanged during the observation period. As a result of a fall in arterial pressure both systemic vascular resistance and left ventricular stroke work index fell significantly (P less than 0.01). Pulmonary wedge pressure also fell (13.6-10.5 mm Hg; P less than 0.001), but this fall was confined to patients whose initial reading was above the median of 13 mm Hg. Pulmonary wedge pressure fell both among the 41 patients who required some medical therapy (15.6-10.8 mm Hg; P less than 0.001) and the 54 who received no medication throughout the 24 hours (12.0-9.8 mm Hg; P less than 0.05). The 39 patients with anterior wall infarction had higher baseline pulmonary wedge pressure and systemic vascular resistance than the 42 with inferior wall infarction. Later the stroke volume and stroke work index were persistently lower reflecting the greater degree of impairment of left ventricular function in anterior wall infarction. In conclusion, following an uncomplicated myocardial infarction, cardiac index was maintained, despite a fall in stroke volume, by an increase in heart rate. Pulmonary wedge pressure showed both a spontaneous fall and a fall in those patients given additional medical therapy during the study period.

Metoprolol in acute myocardial infarction. A pharmacokinetic and pharmacodynamic study.

A combined i.v. and oral dosage regimen of metoprolol early in acute myocardial infarction has been evaluated. Metoprolol 15 mg i.v. in three divided doses followed by 200 mg orally in divided doses was administered to 20 patients. The median delay from onset of pain to start of treatment was 7.5 h. Following the i.v. dose absorption of the first oral dose was prolonged in several patients, but the plasma metoprolol concentration rapidly stabilized at a mean of about 200 nmol/l. A significant correlation was found between the change in resting heart rate and the plasma concentration of metoprolol 15 min after the start of treatment. Blood pressure was not correlated with metoprolol concentration. Nine patients were restudied after 16-19 days of chronic therapy. The time to maximal plasma concentration of metoprolol on chronic treatment was reduced compared to that observed after the first oral dose. The median minimum plasma concentration during steady state averaged around 200 nmol/l and was comparable to the mean trough levels 24 and 48 h after the start of therapy. In the majority of patients, the dosage regimen rapidly produced and maintained plasma levels of metoprolol which should induce a significant degree of beta-blockade.

Hemodynamic effects of metoprolol in acute myocardial infarction. A randomized, placebo-controlled multicenter study.

The central hemodynamic effects of metoprolol in acute myocardial infarction have been studied in a multicenter, double-blind, randomized trial. One hundred and ninety patients with acute myocardial infarction not previously on beta blockers with heart rate greater than 65 beats/min and blood pressure greater than 105 mm Hg and without clinical signs of serious heart failure were included. After insertion of a pulmonary artery catheter, patients were randomized to metoprolol, 15 mg intravenously, and 50 mg 4 times a day orally (n = 95) or placebo (n = 95) with a mean delay of 7.2 hours. Hemodynamic measurements were made at baseline and repeatedly during 24 hours. Heart rate, systolic blood pressure and cardiac index were all immediately reduced by 10 to 20% in the metoprolol group and the difference compared with placebo was maintained throughout the 24 hours (p less than 0.001). Pulmonary capillary wedge pressure (PCWP) in the metoprolol group increased from 13.7 +/- 6.7 to a peak of 15.5 +/- 5.5 mm Hg 30 minutes after injection. The difference compared with placebo was maintained for 8 hours (p less than 0.01). This increase was seen only in the patient group with initial PCWP below the median of 13 mm Hg. In patients with initial PCWP above the median a continuous decrease was observed in both the placebo and metoprolol groups. Thus high initial PCWP was not associated with intolerance to metoprolol. Based on hemodynamic measurements tolerance to metoprolol was good.