Comparative effects of three beta blockers (atenolol, metoprolol, and propranolol) on survival after acute myocardial infarction

The beneficial impact of beta blockade after an acute myocardial infarction (AMI) is clear, but beta-adrenergic blockers differ in multiple characteristics, including lipophilicity and selectivity. The impact of these factors on the effects of beta blockade is unknown. We therefore compared the effects of different beta blockers on mortality after AMI. Charts of 201,752 patients with AMI were abstracted by the Cooperative Cardiovascular Project, a quality assurance program sponsored by the Health Care Financing Administration. Of the 69,338 patients prescribed beta blockers, we compared mortality of patients receiving different beta-adrenergic blockers using the Cox proportional-hazards model accounting for multiple factors that might influence survival. The mortality rates of the 2 selective agents, metoprolol and atenolol, were virtually identical (13.5% and 13.4% 2-year mortality, respectively). Compared with metoprolol, patients discharged on propranolol had a slightly increased mortality (15.9% 2-year mortality), which may be related to undetected differences at baseline. Survival with all of the drugs was superior to the 23.9% 2-year mortality seen in patients not receiving beta blockers. Beta blockade overall was associated with a 40% improvement in survival. Although the use of beta blockade after AMI has major prognostic importance, the present study suggests that the specific beta blocker chosen will have little influence on mortality.     

One-year prognosis in patients hospitalized with a history of unstable angina pectoris

The prognosis during 1 year of follow-up in 715 patients admitted to one single hospital due to suspected acute myocardial infarction (AMI) with a history of unstable angina pectoris immediately preceding hospitalization is described. AMI developed in 192 patients (27%) during the first three days and in 255 patients (38%) during the first year. The mortality during hospitalization was 7% (50 patients) and during 1 year 19% (130 patients). Of the nonsurvivors, 54% died of AMI, 28% of congestive heart failure, and 20% of cardiogenic shock. Based on simple clinical parameters on admission to the emergency room, risk indicators for death during the following year could be identified as follows, in the order of significance: high age (p < 0.001), ST-segment depression on admission (p < 0.001), and a history of diabetes mellitus (p < 0.05). At admission to the emergency room, risk indicators for development of AMI during the following year were as follows: initial degree of suspicion of AMI (p < 0.001), electrocardiographic signs of acute ischemia on admission (p < 0.001), ST-segment elevation on admission (p < 0.01), age (p < 0.05), and lack of a previous history of chronic stable angina pectoris (p < 0.05). We conclude that, among patients admitted to hospital due to suspected AMI with a history of unstable angina pectoris immediately preceding hospitalization, 38% developed a confirmed infarction and 19% died during the following year.     

Occurrence of angina pectoris prior to acute myocardial infarction and its relation to prognosis

In 917 patients with acute myocardial infarction (AMI) we evaluatedthe impact of previous angina pectoris on the prognosis. Thirty-fourpercent of the patients had chronic angina prior to AMI, and22% had angina pectoris of short duration. Patients with chronicangina pectoris differed from the remaining patients havinga more frequent previous history of AMI, diabetes mellitus,hypertension, and congestive heart failure. They less frequentlydeveloped a Q-wave AMI, and had smaller infarcts according tomaximum serum-enzyme activity as compared with the remainingpatients. They had a higher one-year mortality rate (36%) ascompared with those having angina pectoris of short duration(22%), and those with no angina pectoris (26%). Their reinfarctionrate was also higher (26%) as compared with that in the othertwo groups (15% and 9% respectively). In a multivariate analysisconsidering age, sex, clinical history, initial symptoms, initialelectrocardiogram and estimated infarct size, previous chronicangina pectoris was not an independent risk factor for death,but was independently associated with the risk of reinfarction(P<0.001) Among patients with a history of angina pectoristhe outcome was related to medication prior to onset of AMIand at discharge from hospital. Patients in whom beta-blockerswere prescribed at discharge had a one-year mortality of 13%as compared with 30% in the remaining patients (P<0.001).     

Five-year mortality after acute myocardial infarction in relation to previous history, level of initial care, complications in hospital, and medication at discharge

Summary The purpose of this study was to describe the prognosis during 5 years of follow-up in a consecutive population of patients discharged from hospital after acute myocardial infarction (AMI) in relation to clinical history, level of initial care, complications during hospitalization, and medication at discharge. All patients admitted to a single hospital from February 15, 1986 to November 9, 1987 due to AMI, regardless of age and whether or not they were treated in the coronary care unit, and who were discharged alive from hospital were included in the study. There were 862 patients with AMI, 740 of whom were discharged alive. Information on medication at discharge was available in 713 patients (96%). In a multivariate analysis taking into account age, sex, history of cardiovascular diseases, whether patients were admitted to coronary care unit or not, complications during hospitalization, and medication at discharge, the following factors appeared to be independent predictors of mortality: age (p<0.001), history of AMI (p<0.001), congestive heart failure in hospital (p<0.001), whether beta-blockers had been prescribed at discharge (p<0.01), and a history of diabetes (p<0.01). This study indicates that in consecutive patients surviving the hospital phase of AMI, the development of complications while in hospital and the manner in which medication was prescribed at discharge independently influenced their longterm prognosis, but age was the most important factor in long-term prognosis.     

Factors leading to shorter survival after acute myocardial infarction in patients ages 65 to 75 years compared with younger patients

Although the number of elderly patients with acute myocardial infarction (AMI) has steadily increased and these patients are known to have a higher early subsequent mortality than younger patients, the reasons for this adverse prognosis are poorly understood. We compared the clinical courses of 217 patients, ages 65 to 75 years, with 631 patients younger than 65 years of age enrolled in the Multicenter Investigation of the Limitation of Infarct Size (MILIS). The older group had a higher prevalence of adverse baseline risk factors, including history of congestive heart failure (14 vs 7%, p less than 0.001), previous AMI (28 vs 22%, p less than 0.05), angina pectoris (42 vs 34%, p less than 0.05), systemic hypertension (64 vs 52%, p less than 0.01), diabetes mellitus (24 vs 17%, p less than 0.05) and female gender (37 vs 24%, p less than 0.001). Despite having a smaller infarct size index than younger patients (15 +/- 1 vs 18 +/- 1 CK-MB g-Eq/m2, p less than 0.002), the elderly patients had a lower admission left ventricular ejection fraction (43 +/- 1 vs 47 +/- 1%, p less than 0.01) and a higher frequency of clinical congestive heart failure (44 vs 28%, p less than 0.001) and in-hospital death (14 vs 7%, p less than 0.01). The 1-year mortality for elderly hospital survivors was also markedly greater (19 vs 5%, p less than 0.001) as was the 4-year mortality (35 vs 13%, p less than 0.001). Adjustment for 7 adverse baseline characteristics in the elderly could account for their increased in-hospital mortality. However, these and 12 additional in-hospital characteristics did not account for the increased 1- and 4-year mortalities of the elderly hospital survivors, which are presumably affected by variables not included in the present age-associated study.     

Influence of gender on survival,mode of death,reinfarction, use of medication,and aspects of well being during a period of five years after onset of acute myocardial infarction

Background and hypothesis: This study was undertaken to describe prognosis during a period of 5 years after an acute myocardial infarction (AMI) in relation to gender. Methods: All patients studied were hospitalized in a single hospital during a period of 21 months due to AMI, regardless of age and whether they were admitted to the coronary care unit or another ward. A total of 862 AMI patients [581 (67%) men and 281 (33%) women] were prospectively evaluated. Males were younger and less frequently had a history of congestive heart failure and hypertension. Results: The overall 5-year mortality rate was 48% among men compared with 61 % among women (p < 0.001). However, in a multivariate analysis considering age, gender, and a previous history of cardiovascular diseases, female gender was not independently associated with death. Revascularization in terms of coronary artery bypass grafting and percutaneous transluminal angioplasty did not differ significantly between men and women. The rate of reinfarction was 34% among men and 38% among women (p > 0.2). Conclusion: During 5 years of follow-up in a consecutive series of 862 AMI patients, women had a worse prognosis than men, with a mortality of 61 % compared with 48% (p < 0.001). However, after controlling for a number of potentially confounding prognostic factors, female gender was not independently associated with mortality.     

Prognosis in acute myocardial infarction in relation to development of Q waves.

In a totally nonselected group of patients with acute myocardial infarction (AMI) (n = 921) admitted from the emergency department to the coronary care unit or other hospital ward, the occurrence of non-Q-wave AMI and the prognosis in these patients was determined and compared with those in whom Q waves were developed. Fifty-two percent had AMI without new Q waves. Patients with a non-Q-wave AMI differed from patients with Q-wave AMI, more frequently having a previous history of AMI (p less than 0.001), angina pectoris (p less than 0.01), diabetes mellitus (p less than 0.05), congestive heart failure (p less than 0.001), and a higher mean age (p less than 0.001), whereas smoking was more common in Q-wave AMI. Patients with non-Q-wave AMI had a 1-year mortality of 31% compared with 26% in Q-wave AMI (p greater than 0.2) and a reinfarction rate of 20% compared with 12% for Q-wave AMI (p less than 0.01). Among patients aged less than 75 years without a previous history of AMI, congestive heart failure, and diabetes mellitus, the 1-year mortality rate was 16% for patients with Q waves versus 15% for those without Q waves (NS). Appearance of Q waves was not independently associated with death. We conclude that in a nonselected group of patients with AMI the occurrence of a non-Q-wave AMI is much higher than previously reported. The prognosis in AMI during one year of follow-up is not associated with development of Q waves.     

Long-term Mortality after Acute Myocardial Infarction in Relation to Prescribed Dosages of a Beta-Blocker at Hospital Discharge

This study was designed to describe the 5-year mortality rate in relation to the dose of metoprolol prescribed at hospital discharge after hospitalisation for acute myocardial infarction (AMI). All patients discharged alive after being hospitalized for AMI at Sahlgrenska Hospital (covering half of the community of Göteborg, with 500,000 inhabitants) during 1986–1987 (period I) and all patients discharged alive after hospitalization for AMI at Sahlgrenska Hospital and östra Hospital (covering the whole area of the community of Göteborg) in 1990–1991 (period II) were included. Overall mortality was retrospectively evaluated over 5 years of follow-up. In all there were 2161 patients who were discharged after AMI. Seventy-three percent of these patients were prescribed a beta-blocker and 59% were prescribed metoprolol. Of the patients prescribed metoprolol, 34% were on 200 mg, 46% on 100 mg, and 20% on 50 mg or less. Information on 5-year mortality was available for 2142 of the 2161 patients (99.1%). The 5-year mortality was 24% among patients prescribed 200 mg, 33% among patients prescribed 100 mg, and 43% among patients prescribed 50 mg (P < 0.0001). Patients prescribed another beta-blocker had a 5-year mortality of 39%, and patients prescribed no beta-blocker at all had a 5-year mortality of 61%. When correcting for dissimilarities at baseline, patients who were prescribed 100 mg had an adjusted risk ratio for death of 0.79 (95% confidence limit 0.64–0.96; P = 0.021) as compared with patients not prescribed a beta blocker. The corresponding figure for patients prescribed >100 mg was 0.63 (95% confidence limit 0.48–0.84; P = 0.001). Both patients prescribed high and low doses of metoprolol after AMI appeared to benefit from treatment. There was a trend indicating more benefit when larger doses were prescribed.     

Hospital and long-term survival of patients with acute pulmonary edema associated with coronary artery disease

Cardiogenic acute pulmonary edema (APE) associated with coronary artery disease was diagnosed in 44 patients admitted over a 1-year period to a general university hospital. The patients' clinical characteristics at presentation were variable. Acute myocardial infarction (AMI) was present in 26 patients (59%). The hospital mortality rate was 46% (12 of 26 patients) in the presence of AMI and 6% (1 of 18) in its absence (p = 0.006). Long-term follow-up of all hospital survivors revealed that 8 of 30 (27%) had died at 1 year and that 21 of 30 patients (70%) had died at 6 years. However, there was no significant difference in subsequent survival between the AMI and non-AMI groups. A history of congestive heart failure was selected as the most important predictor of increased mortality risk by univariate analysis of the clinical characteristics of the hospital survivors (p = 0.02). The mortality rate at 6 years of follow-up was 85% (17 of 20 patients) in the presence of a history of congestive heart failure and 40% (6 of 10) in its absence.     

Long-term prognosis after acute myocardial infarction in patients with left ventricular hypertrophy on the electrocardiogram. SPRINT Study Group.

Among 4,720 consecutive hospital survivors from acute myocardial infarction (AMI) treated in 13 coronary care units between July 1981 and August 1983, the estimated prevalence of electrocardiographic left ventricular (LV) hypertrophy was 6.1%. The prevalence of electrocardiographic LV hypertrophy increased with age and was higher in patients with previous myocardial infarction, angina and systemic hypertension. Mean age of patients with electrocardiographic LV hypertrophy was 67.2 vs 61.4 years in counterparts free of electrocardiographic LV hypertrophy. Patients with electrocardiographic LV hypertrophy had a higher rate of congestive heart failure on admission, or developing during their stay in coronary care units. The 1- and 5-year mortality rates were 19.7 and 46.6% among patients with electrocardiographic LV hypertrophy versus 8.7 and 26.2%, respectively (p less than 0.001) in patients without this finding. The covariate-adjusted odds ratio of 1-year mortality was 1.88 for the presence of electrocardiographic LV hypertrophy when age alone was adjusted for, and 1.51 (90% confidence interval, 1.09 to 2.10) when multiple covariate adjustment was undertaken. After multiple covariate adjustment for 5-year mortality after discharge, the relative risk associated with electrocardiographic LV hypertrophy was 1.51 (90% confidence interval, 1.26 to 1.80). The results of the present study showed that the presence of electrocardiographic LV hypertrophy on the discharge electrocardiogram of survivors from AMI is associated with a 1.5-fold increase of short- and long-term mortality. Patients with electrocardiographic LV hypertrophy, potentially at an increased post-discharge risk, may be candidates for early noninvasive testing and more intensive follow-up after recovering from AMI.     

One-year outcome of patients after acute coronary syndromes (from the Canadian Acute Coronary Syndromes Registry)

The objective of this study was to determine the management and outcome of fewer selected patients with an acute coronary syndrome during hospitalization and up to 1 year after discharge. The Canadian Acute Coronary Syndromes Registry was a prospective observational study of patients admitted with suspected acute coronary syndromes. Data on demographic and clinical characteristics, in-hospital treatment, and outcomes were recorded. At 1 year, vital status, medication use, recurrent cardiac events, and procedures were determined by telephone contact. Of the 5,312 patients enrolled, 4,627 had a final diagnosis of acute coronary syndrome, with Q-wave myocardial infarction in 27.7%, non-Q-wave myocardial infarction in 33.2%, and unstable angina pectoris in 39.1%. During hospitalization, coronary angiography and revascularization were performed in 39.6% and 20.3% of patients, respectively. The in-hospital mortality rate was 2.4% overall. At discharge, 87.8%, 76.4%, 56.0%, and 54.8% of patients were prescribed aspirin, β blockers, angiotensin-converting enzyme inhibitors, and lipid-lowering agents, respectively. Unadjusted 1-year mortality rates for hospital survivors were 6.5%, 10%, and 5.4% for those with Q-wave myocardial infarction, non-Q-wave myocardial infarction, and unstable angina pectoris groups, respectively (p <0.0001). This difference in mortality rate remained significant after adjusting for other prognosticators, whereas the use of coronary angiography and revascularization after discharge was similar across patients. At 1 year, fewer patients were maintained on aspirin and β blockers, whereas the use of lipid-lowering therapy increased (all p <0.0001). Despite similar rates of coronary angiography and revascularization after discharge, patients with non-Q-wave myocardial infarction had worse outcomes at 1 year. Moreover, there was a significant opportunity to enhance the discharge and long-term use of evidence-based secondary prevention therapies.     

Effect of beta blockers, particularly carvedilol, on reducing the risk of events after acute myocardial infarction

The morbidity and mortality rates of patients who have had acute myocardial infarctions (AMIs) are high. Clinical guidelines recommend that most survivors of AMIs without contraindications should receive long-term treatment with beta blockade. Beta blockers have been shown to reduce mortality and reinfarction after AMI, but the pharmacologic differences among beta blockers may affect their ability to reduce these adverse events. The beta blocker carvedilol has adjunctive pharmacologic properties, including alpha1-blocking, antioxidant, anti-inflammatory, and antiarrhythmic activities that appear to underlie the outcomes demonstrated in experimental models and clinical trials. In conclusion, this review explores the experimental and clinical evidence supporting the preferential use of carvedilol in post-AMI patients with left ventricular dysfunction.     

Characteristics and prognosis of patients with acute myocardial infarction in relation to whether they were treated in the coronary care unit or in another ward.

The characteristics and the prognosis in 921 consecutive patients with acute myocardial infarction (AMI) admitted to one single hospital are described and related to whether they were treated in the coronary care unit or not. Patients treated in the coronary care unit (n = 779) had a 1-year mortality rate of 26% as compared with 41% for patients treated in general wards (n = 115; p < 0.001) and 74% for patients treated in the intensive care unit (n = 27; p < 0.001). Patients treated outside the coronary care unit had a different risk factor pattern including a higher age and a higher prevalence of a previous cardiovascular disease. Independent clinical risk indicators for death among patients in the coronary care unit were in order of significance, high age (p < 0.001), arrhythmia on admission (p < 0.01), acute congestive heart failure on admission (p < 0.01) and a history of diabetes mellitus (p < 0.05). In patients treated in general wards, the only risk indicator for death was a history of congestive heart failure.     

Mortality in the Jerusalem 70-year-olds longitudinal study: Does nifedipine have a role?

Background: Short-acting nifedipine was found to be associated with increased mortality in elderly patients in some studies. Methods: We examined effects of long-acting nifedipine in a longitudinal study of Jerusalem 70 year olds (448 participants). Results: After follow-up of 6.5 years (1990--1996) 70 subjects died. We examined the effects of baseline variables on total mortality. Hypertensives had higher mortality than normotensives, 21.2% versus 13.8%, p = 0.01. Diuretic-treated patients (n = 72), mostly hypertensive (n = 71), had significantly higher mortality than non-diuretic-treated patients (n = 375), 45.5% versus 14.1%; p < 0.001. Although nifedipine-treated patients had a higher prevalence of coronary heart disease diagnosis than diuretic-treated patients (52% versus 35%), their relative risk of mortality was 0.8 (CI 0.4--1.4) of that of diuretic-treated patients. A multiple logistic regression model, including gender, systolic blood pressure, creatinine, cholesterol, diagnosis of congestive heart failure, cardiovascular arrest, diabetes, previous myocardial infarction, physical activity, nifedipine, other calcium channel and beta blockers and diuretics, found only serum creatinine and diuretic therapy associated with total mortality, p = 0.004 and p < 0.02, respectively. When interaction terms were added to account for drug combinations, diuretic therapy lost significance, but the combination of diuretics and beta blockers (probably representing a more severe form of hypertension) became significant, p = 0.03. Conclusion: Long acting nifedipine is not associated with increased mortality in elderly hypertensives.     

Comparison of mortality from acute myocardial infarction between 1979 and 1992 in a geographically defined stable population

This study documents mortality from acute myocardial infarction (AMI), in hospital and at 1 year, for each of 3 selected 1-year periods in a stable community over a 13-year period beginning in 1979 and continuing into the thrombolytic era, to detect any changes occurring in conjunction with the introduction of new therapies. Every patient with AMI occurring in a geographically defined stable community (Hamilton, Ontario, Canada) in 31 — year periods (1979 to 1980 [n = 816], 1986 to 1987 [n = 816], and 1991 to 1992 [n = 831]) was identified and clinically characterized by standardized criteria. Subsequent in-hospital and 1 -year survival were ascertained prospectively. The 3 cohorts were similar in prognostic factors. Mean age was progressively greater over the study period from 63 years in 1979 to 1980, to 67 years in 1991 to 1992 (p = 0.02). There was no change in in-hospital mortality rates from 1979 to 1980 (17%) and 1986 to 1987 (16%). However, from 1986 to 1987 and 1991 to 1992, in-hospital mortality decreased from 16% to 9% (p < 0.001) and 1-year mortality decreased from 26% to 19% (p < 0.001). For patients who survived the hospital phase of AMI, 1-year mortality did not change and was between 11% and 12% in each of the 3 study periods. From 1986 to 1987 and 1991 to 1992, there was an increase in the use of thrombolytic therapy from 5% to 44% of patients. The acute use of aspirin increased from 30% to 88% and the acute use of β blockers increased from 19% to 48% of patients. The observed increase in use of these agents could account for half of the actual mortality reduction observed. This prospective population-based survey demonstrates improved in-hospital survival after AMI associated with increased use of established effective therapies between 1987 and 1992. The 1-year mortality of hospital survivors of AMI was unchanged throughout the period of study, remaining at 11% to 12%.