ISIS-4: a randomised factorial trial assessing early oral captopril, oral mononitrate, and intravenous magnesium sulphate in 58,050 patients with suspected acute myocardial infarction. ISIS-4 (Fourth International Study of Infarct Survival) Collaborative Group. Benefits of magnesium in acute myocardial infarction: timing is crucial. Intravenous infusion of magnesium sulphate after acute myocardial infarction: effects on arrhythmias and mortality. Magnesium substitution in acute ischaemic heart syndromes. Decreases by magnesium of QT dispersion and ventricular arrhythmias in patients with acute myocardial infarction. Protective effect of intravenous magnesium in acute myocardial infarction following thrombolytic therapy. Correlations between ventricular arrhythmias and electrolyte disturbances after acute myocardial infarction. Cardioprotective effects of magnesium sulfate in patients undergoing primary coronary angioplasty for acute myocardial infarction. A randomized study of intravenous magnesium in acute myocardial infarction treated with direct coronary angioplasty. Threatening arrhythmias in acute myocardial infarction are prevented by intravenous magnesium sulfate. Magnesium in the prevention of lethal arrhythmias in acute myocardial infarction. Adjunctive magnesium infusion therapy in acute myocardial infarction. [Intravenous magnesium in acute myocardial infarct]. Early administration of intravenous magnesium to high-risk patients with acute myocardial infarction in the Magnesium in Coronaries (MAGIC) Trial: a randomised controlled trial. Beneficial effect of magnesium sulfate in acute myocardial infarction. Effects of intravenous magnesium sulphate in suspected acute myocardial infarction on acute arrhythmias and long-term outcome. Magnesium therapy in acute myocardial infarction--a double-blind study. Magnesium therapy in acute myocardial infarction when patients are not candidates for thrombolytic therapy. Investigation of the effects of intravenous magnesium sulphate on cardiac rhythm in acute myocardial infarction. Comparison between nicorandil and magnesium as an adjunct cardioprotective agent to percutaneous coronary intervention in acute anterior myocardial infarction.
58,050 patients entering 1086 hospitals up to 24 h (median 8 h) after the onset of suspected acute myocardial infarction (MI) with no clear contraindications to the study treatments (in particular, no cardiogenic shock or persistent severe hypotension) were randomised in a "2 x 2 x 2 factorial" study. The treatment comparisons were: (i) 1 month of oral captopril (6.25 mg initial dose titrated up to 50 mg twice daily) versus matching placebo; (ii) 1 month of oral controlled-release mononitrate (30 mg initial dose titrated up to 60 mg once daily) versus matching placebo; and (iii) 24 h of intravenous magnesium sulphate (8 mmol initial bolus followed by 72 mmol) versus open control. There were no significant "interactions" between the effects of these three treatments, and the results for each are based on the randomised comparison of about 29,000 active versus 29,000 control allocated patients. Captopril There was a significant 7% (SD 3) proportional reduction in 5-week mortality (2088 [7.19%] captopril-allocated deaths vs 2231 [7.69%] placebo; 2p = 0.02), which corresponds to an absolute difference of 4.9 SD 2.2 fewer deaths per 1000 patients treated for 1 month. The absolute benefits appeared to be larger (perhaps about 10 fewer deaths per 1000) in certain higher-risk groups, such as those presenting with a history of previous MI or with heart failure. The survival advantage appeared to be maintained in the longer term (5.4 [SD 2.8] fewer deaths per 1000 at 12 months). Captopril was associated with an increase of 52 (SD 2) patients per 1000 in hypotension considered severe enough to require termination of study treatment, of 5 (SD 2) per 1000 in reported cardiogenic shock, and of 5 (SD 1) per 1000 in some degree of renal dysfunction. It produced no excess of deaths on days 0-1, even among patients with low blood pressure at entry. Mononitrate There was no significant reduction in 5-week mortality, either overall (2129 [7.34%] mononitrate-allocated deaths vs 2190 [7.54%] placebo) or in any subgroup examined (including those receiving short-term non-study intravenous or oral nitrates at entry). Further follow-up did not indicate any later survival advantage. The only significant side-effect of the mononitrate regimen studied was an increase of 15 (SD 2) per 1000 in hypotension. Those allocated active treatment had somewhat fewer deaths on days 0-1, which is reassuring a bout the safety of using nitrates early in acute MI.(ABSTRACT TRUNCATED AT 400 WORDS) To evaluate magnesium deficiency during and after acute myocardial infarction (AMI) and the role of intravenous magnesium therapy given in the early postinfarction period.
                One hundred patients with AMI were randomly assigned to 2 equal groups and monitored over a 4-week period. The placebo group received intravenous dextrose solution and the trial group was given 15 g intravenous magnesium (62 mmol) over a 48-hour period. Serum magnesium levels were measured on days 1, 2, 4, and 6 after admission by calorimetry with methyl thymol blue.
                The groups were comparable in prevalence of risk factors for coronary artery disease and other acute parameters of AMI. The serum magnesium levels of a group of 50 controls were higher (1.61 +/- 0. 21 vs 1.23 +/- 0.27mEq/L) than in patients with AMI (P <.001). There was an increase in serum magnesium levels in the trial group on day 2 (1.73 +/- 0.27 vs 1.29 +/- 0.28 mEq/L; P <.001) as well as on day 4 (1.62 +/- 0.25 vs 1.38 +/- 0.36 mEq/L; P <.001). The trial group also showed significantly lower incidence of arrhythmias (8% vs 34%) and death (4% vs 20%). The mortality rate from pump failure was reduced in the trial group (4% vs 14%).
                The serum magnesium levels in patients with AMI were lower compared with controls. The administration of intravenous magnesium to patients in the immediate postinfarction period is cardioprotective and decreases the incidence of arrhythmia, pump dysfunction, and death. Thus intravenous magnesium is a safe, effective, and inexpensive modality of treatment in AMI. Two hundred patients with acute myocardial infarction were entered into a randomised double-blind trial where they received either intravenous magnesium sulphate or saline for 24 hours after admission to hospital. The incidence of ventricular arrhythmias necessitating treatment was reduced by more than half in the group receiving magnesium sulphate. There were two deaths in the group receiving magnesium sulphate and seven receiving saline placebo. Total cardiac events were significantly reduced in the magnesium treated group. These reductions cannot be attributed to differences in risk factors or therapy between the two groups, either before or during the period of study. These results suggest that magnesium administration reduces the incidence of serious tachyarrhythmias and death after acute myocardial infarction and that this simple regime warrants further study. It has recently been suggested that intravenous infusion of magnesium may reduce mortality and the incidence of serious arrhythmias in patients with ischaemic heart disease and acute myocardial infarction. In the present double-blind, placebo-controlled study, 298 patients with suspected acute myocardial infarction were randomized to receive either intravenous magnesium chloride (80 mmol.24 h-1) or placebo. Infusions were started immediately after admission to the coronary care unit. One hundred and fifty patients received magnesium and 148 the placebo. Ischaemic heart disease was diagnosed in 244 patients. Acute myocardial infarction was observed among 83 patients in the magnesium group and 79 in the placebo group. Both treatment groups were comparable regarding sex, age, clinical status, previous cardiac disease and medication. Serum magnesium was significantly raised during magnesium infusion compared to placebo (P less than 0.01). Fatal events were only observed among patients with myocardial infarction, but neither the in-hospital mortality (magnesium: 12.1%; placebo 10.1%) nor the mortality after a follow-up period of 245 days (median observation time) was affected by magnesium substitution. Magnesium infusion was accompanied by a significantly increased incidence of atrioventricular conduction disturbances. The results suggest that patients suffering from acute ischaemic heart syndromes do not benefit from intravenous magnesium supplementation. Magnesium treatment suppresses ventricular arrhythmias in acute myocardial infarction and possibly mortality after infarction, but the underlying mechanisms are inadequately understood. We tested whether the effect of magnesium could be attributed to an influence on the autonomic control of the heart, changes in disturbed repolarization, relief of ischaemia or limitation of myocardial injury.
                Fifty-nine consecutive patients with acute myocardial infarction were randomized to receive 70 mmol of magnesium (n = 31) infused over 24 h or placebo (n = 26). Occurrence of ventricular arrhythmias and heart rate variability (SD of 5-min mean sinus beat intervals over a 24 h period, SDANN; low frequency/high frequency amplitude ratio, LF/HF ratio), and the number of ischaemic episodes on vectorcardiography were measured from the first day of treatment. QT dispersion corrected for heart rate was measured from the 12-lead ECG. Magnesium decreased the number of hourly ventricular premature beats (P < 0.001) and the number of ventricular tachycardias (P < 0.05). QT dispersion corrected for heart rate was decreased in both measurements at 24 h and 1 week (P < 0.001). SDANN and LF/HF ratio were unchanged. The number of ischaemic episodes on vectorcardiography were equal, and peak creatine kinase MB release did not differ between the groups. In testing the pathophysiological mechanisms, serum magnesium levels after infusion correlated with hourly ventricular premature beats (rs = -0.47; P < 0.01), ventricular tachycardias (rs = -0.26; P < 0.05), and QT dispersion corrected for heart rate (rs = -0.75; P < 0.001), but not with SDANN, LF/HF ratio or peak creatine kinase MB. QT dispersion corrected for heart rate correlated with hourly ventricular premature beats (rs = 0.48; P < 0.001) and ventricular tachycardias (rs = 0.27; P < 0.05).
                Magnesium suppresses early ventricular arrhythmias in acute myocardial infarction. The decreased arrhythmicity is related to enhancement of homogeneity in repolarization, but not to attenuation of prevailing ischaemia, improvement of autonomic nervous derangements or myocardial salvage. The role of intravenous magnesium therapy in patients with acute myocardial infarction (AMI) who received thrombolytic therapy is controversial. The results from previous clinical trials were not in consonance. We therefore conducted a prospective, randomized, double-blind, placebo controlled study in 350 patients with confirmed AMI during the period January 1994 to December 1996. The role of intravenous magnesium sulphate therapy (2 g over 5 min followed by 16 g over 24 h) was evaluated in patients with AMI who received thrombolytic therapy. Study group consisted of 169 patients who were administered magnesium sulphate. Control group comprised of 181 patients who were given isotonic saline. Among those in the magnesium group, 70% received magnesium within 6 h after the onset of symptoms. All patients received magnesium immediately after the completion of thrombolytic therapy. Patients were followed up for 30 days after AMI. The number of deaths in the study group was 6 (3.5%) compared with control arm in which 18 patients (9.9%) died (P value <0.01 95% Confidence intervals [CI] 1.2 to 11.6). Ventricular arrhythmias were also less in the magnesium arm; 27 patients (13%) compared with 83 patients (48.6%) in the control arm (P value 0.00001 95% Cl 26.7 to 44.5). In the magnesium group 15 patients (8.8%) had re-infarction compared with 23 patients (12.7%) in the placebo arm (P value not significant). Post myocardial infarction angina was observed in 47 patients (27.8%) in the magnesium arm compared with 60 patients (33.1%) in the placebo arm (P value not significant). The main side effect of intravenous magnesium was transient flushing observed in 152 (90%) patients. Intravenous magnesium sulphate in patients with AMI is a safe and useful adjunct to thrombolytic therapy in reducing the short-term mortality and ventricular arrhythmias after AMI. Seven 24-hour ECG recordings and blood samples were taken within 3 weeks in 42 patients who had suffered an acute myocardial infarction (AMI). Ca, K and Mg concentrations in serum, and K and Mg in the erythrocytes, were determined by atomic absorption spectroscopy. One half of the patients were infused with 81 mval/day MgSO4 for 3 days. In patients who exhibited intense electrolyte alterations 10-20 days after AMI, there was a significantly higher rate in the frequency of couplets and/or tachycardia in the 2- to 20-day period after AMI. In patients infused with MgSO4, the fluctuation in serum electrolytes and the rate of arrhythmias were significantly reduced. Experimental evidence indicates that magnesium sulfate may have potential cardioprotective properties as an adjunct to coronary reperfusion. The present study was designed to examine the hypothesis that magnesium might have beneficial effects on left ventricular (LV) function and coronary microvascular function in patients with acute myocardial infarction (AMI).
                The study population of 180 consecutive patients with a first AMI (anterior or inferior) underwent successful primary coronary intervention. Patients were randomized to treatment with either intravenous magnesium (magnesium group, n=89) or normal saline (control group, n=91). Pre-discharge left ventriculograms were used to assess LV ejection fraction (LVEF), regional wall motion (RWM) within the infarct-zone and LV end-diastolic volume index. The Doppler guidewire was used to assess coronary flow velocity reserve (CFVR) as an index of coronary microvascular function. Magnesium group subjects showed significantly better LV systolic function (LVEF 63+/-9% vs 55+/-13%, p<0.001; RWM: -1.01+/-1.29 SD/chord vs -1.65+/-1.11 SD/chord, p=0.004), significantly smaller LV end-diastolic volume index (63+/-17 ml/m(2) vs 76+/-20 ml/m(2), p<0.001), and significantly higher CFVR (2.95+/-0.76 vs 2.50+/-0.99, p=0.023) than controls.
                Magnesium sulfate as an adjunct to primary coronary intervention shows favorable functional outcomes in patients with AMI. Notwithstanding the negative result of the International Study of Infarct Survival-4 (ISIS-4), the controversy about the role of magnesium in acute myocardial infarction is still open because, according to experimental data, magnesium could decrease myocardial damage and mortality only if infusion is started before reperfusion. This randomized placebo-controlled trial was designed to evaluate the effect of intravenous magnesium, delivered before, during, and after direct coronary angioplasty, in patients with acute myocardial infarction.
                One-hundred fifty patients were randomized to intravenous magnesium sulfate or placebo. The primary end point was an infarct zone wall motion score index at 30 days, as a measure of infarct size. The secondary end points included creatine kinase peak, ventricular fibrillation/tachycardia within the first 24 hours, death and congestive heart failure within the 30-day follow-up, and 30-day left ventricular ejection fraction. Analysis was by intention to treat.
                There were no significant differences between the magnesium and placebo groups in the 30-day infarct zone wall motion score index (1.93 +/- 0.61 vs 1.85 +/- 0.51, P =.39), ventricular arrhythmias (24% vs 15%, P =.15), death (0 vs 1%, P =.32), heart failure (8% vs 7%, P =.75), and 30-day left ventricular ejection fraction (49% +/- 11% vs 50% +/- 9%, P = 0.55). There was a trend toward a higher creatine kinase peak in the magnesium group (3059 +/- 2359 vs 2404 +/- 1673,P =.052).
                Intravenous magnesium delivered before, during, and after reperfusion did not decrease myocardial damage and did not improve the short-term clinical outcome in patients with acute myocardial infarction treated with direct angioplasty. nan Seven of 48 patients (14.6%) with acute myocardial infarction who were given 2.4 g of magnesium sulfate as a single intravenous dose had potentially lethal arrhythmias during the first 24 hours after admission, whereas 16 (34.8%) of 46 patients receiving placebo had similar arrhythmias. In addition, 14 of these 16 patients in the placebo group had their first arrhythmia (in the intensive coronary-care unit) within two hours after the start of the study, whereas in the magnesium-treated group, there were no such arrhythmias until some four hours later. The higher the lymphocyte potassium concentration, the greater the reduction in the incidence of arrhythmias. Serum magnesium levels increased by 16.5% and lymphocyte magnesium concentrations by 72% in the magnesium treated group. Intravenous magnesium reduces the incidence of serious arrhythmias after acute myocardial infarction. Intravenous magnesium therapy in acute myocardial infarction (MI) has been shown to be beneficial in many studies. However, these effects are not consistent from one trial to another, and their clinical significance is often questionable. A total of 78 consecutive patients were included in a prospective placebo controlled, randomized study of the effects of intravenous magnesium sulfate infusion in acute MI. Of these, 52 (66%) received intravenous streptokinase and the rest belonged to a non-thrombolysed group. These patients were randomized to receive magnesium sulfate infusion (8 mmol over 5 min followed by 65 mmol over 24 h) or placebo. The end points were serious arrhythmias, left ventricular ejection fraction (LVEF) and death during hospital stay and at the end of 28 days. LVEF measured by radionuclide ventriculography at discharge (9 +/- 5 days) was similar in two groups (41 +/- 11 vs. 39 +/- 10; magnesium vs. placebo respectively, P = 0.40). However, the LVEF of the placebo-treated thrombolysed group was higher than the non-thrombolysed group (42 +/- 10 vs. 37 +/- 0, P = 0.02). Incidence of nonsustained ventricular tachycardia (NSVT) was higher with placebo than with magnesium (50% vs. 23% respectively, P < 0.02, odds ratio = 0.29; 95% confidence intervals (CI) 0.1-0.85). Mortality during hospital stay and at the end of 28 days was also similar in both the groups. Thus, the administration of magnesium infusion as an adjunct to thrombolytic therapy remains to be of questionable benefit. The effects of magnesium (Mg) on the incidence of arrhythmias and on mortality were evaluated in 61 patients with documented acute myocardial infarction (AMI), in a randomized, double blind placebo controlled study. During the first 24 hours 31 patients received infusion of 1000 ml isotonic saline with 17 g MgSO4 and 30 ones received only equal volumes of saline as placebo. The baseline characteristics of the population including serum Mg and potassium were similar in the two groups. Severe arrhythmias were not as frequent in the Mg group (22%) as in the placebo one (36%), but the difference was not statistically significant (p = 0.05). There is no significant difference between the groups neither in mortality (3.2%; 0%) nor in conduction disturbances (3.2%; 3%). The adverse effects of Mg therapy were transient and therapy interruption was not required.
                Although the trial is not an extensive one, and the results are nonsignificant, we consider intravenous Mg therapy to be simple and cheap with its place in the treatment of AMI in properly selected patients. According to available data it should be administered as soon as possible after the onset of AMI symptoms, before thrombolytic therapy, in 24-hrs. dose not exceeding 50-65 mmol probably through several days, but the optimal duration of therapy should be further investigated. The benefits of supplemental administration of intravenous magnesium in patients with ST-elevation myocardial infarction (STEMI) are controversial. Despite promising results from work in animals and the ready availability of this simple, inexpensive treatment, conflicting results have been reported in clinical trials. Our aim was to compare short-term mortality in patients with STEMI who received either intravenous magnesium sulphate or placebo.
                We did a randomised, double-blind trial in 6213 patients with acute STEMI who were assigned a 2 g intravenous bolus of magnesium sulphate administered over 15 min, followed by a 17 g infusion of magnesium sulphate over 24 h (n=3113), or matching placebo (n=3100). Our primary endpoint was 30-day all-cause mortality. At randomisation, patients were stratified by their eligibility for reperfusion therapy. The first stratum included patients who were aged 65 years or older and eligible for reperfusion therapy, and the second stratum included patients of any age who were not eligible for reperfusion therapy. Analysis was by intention-to-treat.
                At 30 days, 475 (15.3%) patients in the magnesium group and 472 (15.2%) in the placebo group had died (odds ratio 1.0, 95% CI 0.9-1.2, p=0.96). No benefit or harm of magnesium was observed in eight prespecified subgroup analyses of patients and in 15 additional exploratory subgroup analyses. After adjustment for factors shown to effect mortality risk in a multivariate regression model, no benefit of magnesium was observed (1.0, 0.8-1.1, p=0.53).
                Early administration of magnesium in high-risk patients with STEMI has no effect on 30-day mortality. In view of the totality of the available evidence, in current coronary care practice there is no indication for the routine administration of intravenous magnesium in patients with STEMI. The effects of magnesium on the incidence of arrhythmias and on mortality were evaluated in 103 patients with documented acute myocardial infarction (AMI) in a randomized, double-blind, placebo-controlled study. Fifty patients received a magnesium infusion for 48 hours and 53 received only the vehicle (isotonic glucose) as placebo. The baseline characteristics of the population were similar in the 2 groups. Tachyarrhythmias requiring drug therapy were recorded in 32% of the patients in the magnesium group and in 45% of the placebo group. Conduction disturbances were found in 23% of the placebo group as compared to 14% in the magnesium group. The intrahospital mortality was 2% (1 patient) in the magnesium group, compared to 17% (9 patients) in the placebo group (p less than 0.01). No adverse effects were observed during and after the magnesium infusion. These data support a possible protective role of magnesium in patients with AMI. A total of 252 patients with suspected acute myocardial infarction were included in a double blind study and randomised to 50 mmol magnesium sulfate infusion under 20 h or corresponding placebo. Acute myocardial infarction was verified in 117 patients and 59% of these had concomitant treatment with thrombolysis. One-hundred ninety-four patients had Holter registrations during the first day in the coronary care unit. Intention-to-treat analysis showed an increase in long RR-intervals (> 3 s) in the magnesium treated group (P = 0.006) and a tendency toward a reduction in episodes of ventricular premature complexes in triplets (P = 0.09). During hospital stay and a mean of 22 months follow-up, 23 fatal events occurred in the magnesium allocated group and 31 fatal events among the placebo allocated group (P = 0.1). Mortality rate from cardiac disease was reduced by 54% (95% C.I. 30-99%, P < 0.05). Subgroup analysis on acute myocardial infarction patients showed a 48% mortality risk reduction in the magnesium treated acute myocardial infarction group compared to the placebo treated acute myocardial infarction group (95% C.I. 23-104%, P = 0.06). There was no significant interaction between the effects of magnesium and thrombolytic treatment on total mortality or cardiac events. This study supports the results of other small double blind placebo controlled studies regarding effects of magnesium therapy on mortality in acute myocardial infarction, but are in discordance to the conclusion from the ISIS-4 study. The reasons for these discrepancies cannot be elucidated by our data. Various methods have been proposed and tried to limit the extent of myocardial damage at the time of infarction. We chose to assess the usefulness of intravenous magnesium in this regard because of its important role in myocardial metabolism and function and the suggestion of its deficiency in ischemic hearts. A double-blind randomized trial was carried out and results analyzed in 76 patients. At the end of the infusion period the mean serum Mg++ level for the treated group was 3.6 versus 1.9 mg/dl for the control group. The estimated size of infarction (as measured by MB-CK release) was not significantly smaller overall in the treated group (37.4 +/- 4.3 vs. 45.6 +/- 4.6 MB-CK g/Eq), but was significantly smaller in the treated subgroup without heart failure (31.6 +/- 5.8 vs. 44.7 +/- 4.8 MB-CK g/Eq). A trend toward less ventricular ectopy was seen in the group treated with magnesium. There was significantly less lidocaine used for the treatment of ventricular dysrhythmias in this group. Magnesium supplementation in patients undergoing acute coronary events is promising and deserves further study. Thrombolytic therapy reduces in-hospital mortality. However, 70% to 80% of patients do not receive thrombolysis and their in-hospital mortality is high. During the last decade some clinical trials demonstrated that magnesium sulfate reduced in-hospital mortality. The aim of this study was to evaluate the effects of magnesium sulfate in patients with acute myocardial infarction (AMI) who were considered unsuitable for thrombolytic therapy. Intravenous magnesium sulfate was evaluated in 194 patients with AMI ineligible for thrombolytic therapy in a randomized, double-blind, placebo-controlled study. Group I consisted of 96 patients who received 48-hour intravenous magnesium. Group II consisted of 98 patients who received isotonic glucose as a placebo. Magnesium reduced the incidence of arrhythmias, congestive heart failure, and conduction disturbances compared with placebo (27% vs 40%, p = 0.04; 18% vs 23%, p = 0.27; 10% vs 15%, p = 0.21, respectively). Left ventricular ejection fraction 72 hours and 1 to 2 months after admission was higher in patients who received magnesium sulfate than in those taking placebo (49% vs 43% and 52% vs 45%; p = 0.01, respectively). In-hospital mortality was significantly reduced in patients receiving magnesium sulfate than in those receiving placebo (4% vs 17%; p < 0.01), and also in the subgroup of elderly patients (> 70 years) (9% vs 23%; p = 0.09). In conclusion, magnesium sulfate should be considered as an alternative therapy to thrombolysis in patients with AMI. To examine the effect of doubling serum magnesium concentration on the incidence of arrhythmias in patients with suspected acute myocardial infarction.
                Randomised double blind clinical trial.
                Coronary care unit of a teaching hospital.
                Clinical data were collected on 2316 randomised patients with suspected acute myocardial infarction. Holter monitoring was performed in a subgroup of 70 patients and analysed in 48 patients in whom acute myocardial infarction was confirmed.
                By random allocation, patients received either an intravenous loading dose of 8 mmol magnesium sulphate over five minutes plus 65 mmol over the next 24 hours, or equal volumes of saline.
                (a) Clinically documented arrhythmias; (b) use of antiarrhythmic treatments, cardioversion, and insertion of a pacemaker; (c) incidence of all abnormal rhythms during Holter monitoring.
                In the main trial the incidence of rhythm disturbance while in the coronary care unit (expressed as the odds ratio (OR) for magnesium: placebo and its 95% confidence interval) was not significantly different between treatment groups for ventricular fibrillation (OR 0.74; 0.46 to 1.20), ventricular tachycardia (OR 0.87; 0.63 to 1.20), supraventricular tachycardia (OR 0.69; 0.38 to 1.26), atrial fibrillation (OR 0.92; 0.69 to 1.23), or heart block of any degree (OR 1.17; 0.83 to 1.65). Sinus bradycardia was significantly more common in the magnesium group (OR 1.38; 1.03 to 1.85; p = 0.02). These findings were corroborated by the use of treatments for rhythm disturbance and the data from Holter monitoring.
                The regimen of intravenous magnesium sulphate used here had no significant effect on arrhythmia in acute myocardial infarction. The reduction in mortality that has been shown with this form of treatment is not attributable to suppression of life threatening rhythm disturbances. It has been reported that both nicorandil and magnesium have a cardioprotective effect in experimental ischemia - reperfusion models. In the present study, the cardioprotective effects of nicorandil and magnesium as an adjunct to reperfusion therapy in patients with acute myocardial infarction (AMI) were compared.
                Forty consecutive patients with AMI caused by occlusion of anterior descending coronary artery were randomized into 3 groups: (1) Group N: nicorandil was given as 4 mg iv and 4 mg ic before reperfusion, followed by continuous infusion at 4 mg/h for 24 h; (2) Group M: magnesium was administered at 10 mmol iv before reperfusion, followed by continuous infusion at 0.4 mmol/h for 24 h; and (3) Group C: neither nicorandil nor magnesium was given. Left ventriculography was performed immediately after reperfusion and 3 months later. There was no significant change in regional wall motion (RWM) in either Group C or M, whereas that of group N improved significantly. The change in RWM in Group N was significantly greater than in Group C (Group N: 0.92+/-0.92, Group M: 0.44+/-0.80, Group C: -0.01+/-0.65, p<0.05).
                The early administration of nicorandil as an adjunct to reperfusion is useful for cardioprotection in AMI, but magnesium is not.
Owing to the likelihood of publication bias and marked heterogeneity of treatment effects, it is essential that the findings are interpreted cautiously. From the evidence reviewed here, we consider that: (1) it is unlikely that magnesium is beneficial in reducing mortality both in patients treated early and in patients treated late, and in patients already receiving thrombolytic therapy; (2) it is unlikely that magnesium will reduce mortality when used at high dose (>=75 mmol); (3) magnesium treatment may reduce the incidence of ventricular fibrillation, ventricular tachycardia, severe arrhythmia needing treatment or Lown 2-5, but it may increase the incidence of profound hypotension, bradycardia and flushing; and (4) the areas of uncertainty regarding the effect of magnesium on mortality remain the effect of low dose treatment (< 75 mmol) and in patients not treated with thrombolysis.