Nina Rehnqvist

Long-term treatment with metoprolol after myocardial infarction: Effect on 3 year mortality and morbidity

The effects of metoprolol treatment in patients surviving acute myocardial infarction have been investigated in a double-blind randomized study. The patients were stratified according to age, infarct size and type of ventricular arrhythmias before administration of metoprolol, 100 mg twice daily (n = 154), or placebo (n = 147). All patients were followed up for 36 months. There were 31 (29 cardiac) and 25 (20 cardiac) deaths in the placebo and metoprolol groups, respectively. Subgroup analyses showed a significant reduction of cardiac death in patients with a large infarct (32.1% with placebo versus 12.5% with metoprolol, p less than 0.05) as a result of active treatment. Sudden death rates were 14.7% in the placebo versus 5.8% in the metoprolol group (p less than 0.05). The incidence of nonfatal reinfarction was 21.1% in the placebo versus 11.7% in the metoprolol group (p less than 0.05). The reduction in nonfatal reinfarction was similar in all pretreatment risk strata. The difference between the two groups in cumulative number of cardiac deaths and patients experiencing nonfatal reinfarction increased throughout the study. Furthermore, cerebrovascular events (p less than 0.05) and coronary bypass surgery (p = 0.058) were more frequent in the placebo group. In conclusion, after 36 months of metoprolol treatment after myocardial infarction, there was a significant reduction of nonfatal reinfarction and sudden death in all patients and a reduction of cardiac death in those with a large infarct.

Coenzyme Q10 as an adjunctive in the treatment of chronic congestive heart failure

Seventy-nine patients with stable chronic congestive heart failure were randomized into a double-blind, crossover placebo controlled study with 3-month treatment periods, where either 100 mg coenzyme Q10 (CoQ10) or placebo was added to conventional therapy. Mean patient age was 61 +/- 10 years, ejection fraction at rest was 22% +/- 10%, and maximal exercise tolerance was 91 +/- 30 W. The follow-up examinations included ejection fraction (primary objective), exercise test, and quality of life questions. Ejection fraction at rest, during a slight volume load, and during a submaximal supine exercise increased slightly compared with placebo: 24% +/- 12% versus 23% +/- 12% (NS), 25% +/- 13% versus 23% +/- 12% (P < .05), and 23% +/- 11% versus 22% +/- 11% (NS). Maximal exercise capacity increased from 94 +/- 31 W during the placebo period to 100 +/- 34 W during the CoQ10 period (P < .05). Total score for the quality of life assessment increased significantly from 107 +/- 23 during the placebo period to 113 +/- 22 during the CoQ10 period (P < .05). The results indicate that oral long-term treatment with 100 mg CoQ10 in patients with congestive heart failure only slightly improves maximal exercise capacity and the quality of life and that the clinical importance of this needs to be further evaluated.

Combination therapy with metoprolol and nifedipine versus monotherapy in patients with stable angina pectoris. Results of the International Multicenter Angina Exercise (IMAGE) Study.

OBJECTIVES This study was designed to investigate whether combination therapy with metoprolol and nifedipine provides a greater anti-ischemic effect than does monotherapy in individual patients with stable angina pectoris. BACKGROUND Combination therapy with a beta-adrenergic blocking agent (which reduces myocardial oxygen consumption) and a dihydropyridine calcium antagonist (which increases coronary blood flow) is a logical approach to the treatment of stable angina pectoris. However, it is not clear whether, in individual patients, this combined therapy is more effective than monotherapy. METHODS Two hundred eighty patients with stable angina pectoris were enrolled in a double-blind trial in 25 European centers. Patients were randomized (week 0) to metoprolol (controlled release, 200 mg once daily) or nifedipine (Retard, 20 mg twice daily) for 6 weeks; placebo or the alternative drug was then added for a further 4 weeks. Exercise tests were performed at weeks 0, 6 and 10. RESULTS At week 6, both metoprolol and nifedipine increased the mean exercise time to 1-mm ST segment depression in comparison with week 0 (both p < 0.01); metoprolol was more effective than nifedipine (p < 0.05). At week 10, the groups randomized to combination therapy had a further increase in time to 1-mm ST segment depression (p < 0.05 vs. placebo). Analysis of the results in individual patients revealed that 7 (11%) of 63 patients adding nifedipine to metoprolol and 17 (29%) of 59 patients (p < 0.0001) adding metoprolol to nifedipine showed an increase in exercise tolerance that was greater than the 90th percentile of the distribution of the changes observed in the corresponding monotherapy + placebo groups. However, among these patients, an additive effect was observed only in 1 (14%) of the 7 patients treated with metoprolol + nifedipine and in 4 (24%) of the 17 treated with nifedipine + metoprolol. CONCLUSIONS The mean additive anti-ischemic effect shown by combination therapy with metoprolol and nifedipine in patients with stable angina pectoris is not the result of an additive effect in individual patients. Rather, it may be attributed to the recruitment by the second drug of patients not responding to monotherapy.

Emotional distress before coronary bypass grafting limits the benefits of surgery

BACKGROUND The inclusion of large, heterogeneous groups of patients for coronary bypass grafting (CABG) surgery has resulted in a more mixed treatment outcome. Thus it becomes important to identify patients who are less likely to benefit from surgery or who may require additional support to improve treatment outcome. The aim of the present study was to examine whether psychological status measured before CABG can contribute to prediction of short- and long-term outcomes of the surgery. METHODS AND RESULTS One hundred seventy-one consecutive patients from two large university hospitals in Stockholm completed a psychosocial questionnaire before being scheduled for surgery. One year after CABG, patients again completed the questionnaire. Follow-up of medical charts was conducted during the first 3 years after surgery. All major cardiac events (cardiac death, definite myocardial infarction, revascularization, and unstable angina verified by angiography or myocardial scintigraphy) were recorded. Although the overall effect of surgery was excellent in the majority of cases, the patients exhibiting a high degree of distress (anxiety, depression, and tiredness) before surgery assessed their status as being much worse both before the operation and at the 1-year follow-up. Equally important was the fact that patients considered distressed before surgery had significantly higher rates of cardiac events (16%) in the 3-year follow-up period compared with nondistressed patients (5%) (chi-square=5.11, degrees of freedom=1, p < 0.02). CONCLUSIONS Systematic evaluation and treatment of emotional distress in the candidates for coronary revascularization may be expected to result in more optimal subjective results and a reduction in the number of serious cardiac events after surgery.

Diagnostic value of programmed ventricular stimulation in patients with bifascicular block: A prospective study of patients with and without syncope

OBJECTIVES The aim of this study was to examine the inducibility of ventricular arrhythmias in patients with bifascicular block both with and without a history of syncope and to relate the findings to clinical events during follow-up. BACKGROUND Patients with bifascicular block have an increased risk of sudden death that is not reduced by pacemaker treatment. This risk could be related to a high incidence of ventricular arrhythmias. METHOD Programmed ventricular stimulation was performed in 101 patients with bifascicular block: 41 had a history of unexplained syncope, and 60 were asymptomatic. RESULTS Programmed ventricular stimulation resulted in a sustained ventricular arrhythmia in 18 patients (18%), 8 in the syncope group and 10 in the nonsyncope group (p = NS). Three patients in each group had an inducible sustained monomorphic ventricular tachycardia. During a mean follow-up of 21 months, 10 patients experienced a clinical event defined as sudden death (n = 4), syncope (n = 5) or appropriate discharges from an implantable cardioverter-defibrillator (n = 1). Only one of these patients had an inducible ventricular arrhythmia at baseline. CONCLUSIONS The inducibility of ventricular arrhythmias is high in patients with bifascicular block and of the same magnitude in patients with and without a history of syncope. Clinical events during follow-up were not predicted by programmed ventricular stimulation in either of the two groups. The finding of inducible ventricular arrhythmia in patients with bifascicular block should therefore be interpreted with caution.

Quality of life after myocardial infarction: effect of long term metoprolol on mortality and morbidity.

A double blind randomised study of 154 patients with myocardial infarction assigned to metoprolol (100 mg twice daily) and 147 assigned to placebo compared the effects of treatment in relation to health state over three years. Health state was evaluated by a new method based on the average number of days spent in each of seven mutually exclusive categories of health. The scale took into account death, history of serious complications, functional state, and side effects of treatment. Of the maximum attainable 1095 days alive during the three years patients given metoprolol attained 992 days and those given placebo 964 days. During the period alive the metoprolol treated group spent an average of 278 days in an optimal functional state as compared with 176 days for the placebo treated group. This included 221 and 156 days respectively in a completely asymptomatic state (that is, without either cardiac symptoms or side effects of treatment). The time spent with a serious non-fatal complication was shortened by 56 days in the metoprolol group. The overall differences between the groups were statistically significant (p = 0.03). Aside from bringing an improved quality of life after myocardial infarction, metoprolol may add up to one month to life expectancy for three years of treatment.

Prognostic implications of autonomic function assessed by analyses of catecholamines and heart rate variability in stable angina pectoris

Objective: To assess the prognostic impact of autonomic activity, as reflected by catecholamines and heart rate variability (HRV), in patients with stable angina pectoris. Design: Double blind, randomised treatment with metoprolol or verapamil. 24 hour ambulatory ECG, used for frequency domain analyses of HRV, and symptom limited exercise tests at baseline and after one month of treatment. Catecholamine concentrations were measured in plasma (rest and exercise) and urine. Setting: Single centre at a university hospital. Patients: 641 patients (449 men) with stable angina pectoris. Main outcome measures: Cardiovascular (CV) death, non-fatal myocardial infarction (MI). Results: During follow up (median 40 months) there were 27 CV deaths and 26 MIs. Patients who died of CV causes had lower total power and high (HF), low (LF), and very low (VLF) frequency components of HRV. HRV was not altered in patients who suffered non-fatal MI. Catecholamines did not differ between patients with and those without events. Metoprolol increased HRV. Verapamil decreased noradrenaline (norepinephrine) excretion. Multivariate Cox analyses showed that total power, HF, LF, and VLF independently predicted CV death (also non-sudden death) but not MI. LF:HF ratios and catecholamines were not related to prognosis. Treatment effects on HRV did not influence prognosis. Conclusions: Low HRV predicted CV death but not non-fatal MI. Neither the LF:HF ratio nor catecholamines carried any prognostic information. Metoprolol and verapamil influenced LF, HF, and catecholamines differently but treatment effects were not related to prognosis.

QTc intervals in acute myocardial infarction: first-year prognostic implications.

Corrected QT (QTc) intervals were measured retrospectively in 160 consecutive survivors of acute myocardial infarction under 66 years of age. Calculations were made the first 2 d in the coronary care unit (CCU), the first post‐CCU day, at discharge, and at 1–3, 6, and 12 months after discharge. All patients were in sinus rhythm and without bundle branch block at discharge from the hospital. Sixteen patients died during the first follow‐up year. Twenty patients suffered a reinfarction, five of whom died.

Platelet aggregability in vivo is attenuated byverapamil but not bymetoprolol in patients with stable angina pectoris

The effects of 1 month of treatment with either verapamil or metoprolol on several aspects of platelet function were studied at rest and during physical exercise or mental stress in patients with stable angina pectoris participating in the Angina Prognosis Study in Stockholm. Platelet aggregability was measured by filtragometry ex vivo, which reflects platelet aggregability in vivo and by Born aggregometry in vitro. Platelet secretion in vivo was assessed by measurements of beta-thromboglobulin in plasma. Verapamil reduced plasma norepinephrine levels (from 2.6 +/- 1.0 to 2.2 +/- 1.0 nmol/L; p < 0.01) and attenuated platelet aggregability at rest (filtragometry readings were prolonged from 219 to 295 seconds; p < 0.05, n = 46). Aggregability in platelet-rich plasma was not influenced. Metoprolol did not significantly affect filtragometry readings (n = 58) or aggregability in vitro (there was a tendency toward enhanced adenosine diphosphate sensitivity; p = 0.08). beta-thromboglobulin levels were low (approximately 25 ng/ml) and not influenced by either treatment. Physical exercise (bicycle ergometry) increased platelet aggregability in vivo both before and after drug treatment. Verapamil also attenuated platelet aggregability after exercise, whereas metoprolol had no such effect. Platelet function was not seriously altered by mental stress (Stroops color word test) despite significant effects on hemodynamics and plasma catecholamines either before or after treatment with either drug. Thus, verapamil attenuates platelet aggregability in patients with stable angina pectoris, whereas metoprolol has no such effect.

Inflammatory and hemostatic markers in relation to cardiovascular prognosis in patients with stable angina pectoris Results from the APSIS study

Increased inflammatory activity and platelet activation have been associated with an increased risk of cardiovascular (CV) events in epidemiological studies, but their prognostic importance in patients with stable angina pectoris is less well established. The Angina Prognosis Study in Stockholm (APSIS), comprised 809 patients (2766 patient years) with stable angina pectoris on double-blind treatment with verapamil or metoprolol. Plasma levels of fibrinogen and orosomucoid (an acute phase reactant), white blood cell counts (WBC), platelet counts and the urinary excretion of beta-thromboglobulin (reflecting platelet secretion), were related to the risk of CV death (n=36), non-fatal myocardial infarction (MI) (n=30) or revascularization (n=99) in a subgroup of 782 patients. Verapamil and metoprolol had only minor effects on the inflammatory variables. In multivariate Cox regression analyses (adjusted for previous MI, hypertension, diabetes mellitus and smoking), fibrinogen and WBC were independent predictors of CV death or non-fatal MI, as well as the risk of revascularization. Orosomucoid did not carry any independent information. Platelet counts and urinary beta-thromboglobulin were not significantly related to CV prognosis. The treatment given did not significantly influence the prognostic impact of either fibrinogen or WBC. Fibrinogen and WBC were independent predictors of CV death or non-fatal MI as well as disease progression leading to revascularization in patients with stable angina pectoris. As fibrinogen is also an acute-phase reactant, the present findings indicate that inflammatory activity is involved in disease progression in stable angina pectoris.