| 1. |
- Hjamarson, A, et al.
(författare)
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Effects of controlled-release metoprolol on total mortality, hospitalizations, and well-being in patients with heart failure. The Metoprolol CR/XL randomized intervention trial in congestive heart failure
- 2000
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Ingår i: Journal of the American Medical Association. - : JAMA. - 0221-7678. ; 283:10, s. 1295-1302
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Tidskriftsartikel (refereegranskat)abstract
- Results from recent studies on the effects of beta1-blockade in patients with heart failure demonstrated a 34% reduction in total mortality. However, the effect of beta1-blockade on the frequency of hospitalizations, symptoms, and quality of life in patients with heart failure has not been fully explored. OBJECTIVE: To examine the effects of the beta1-blocker controlled-release/extended-release metoprolol succinate (metoprolol CR/XL) on mortality, hospitalization, symptoms, and quality of life in patients with heart failure. DESIGN: Randomized, double-blind controlled trial, preceded by a 2-week single-blind placebo run-in period, conducted from February 14, 1997, to October 31, 1998, with a mean follow-up of 1 year. SETTING: Three hundred thirteen sites in 14 countries. PARTICIPANTS: Patients (n = 3991) with chronic heart failure, New York Heart Association (NYHA) functional class II to IV, and ejection fraction of 0.40 or less who were stabilized with optimum standard therapy. INTERVENTIONS: Patients were randomized to metoprolol CR/XL, 25 mg once per day (NYHA class II), or 12.5 mg once per day (NYHA class III or IV), titrated for 6 to 8 weeks up to a target dosage of 200 mg once per day (n = 1990); or matching placebo (n = 2001). MAIN OUTCOME MEASURES: Total mortality or any hospitalization (time to first event), number of hospitalizations for worsening heart failure, and change in NYHA class, by intervention group; quality of life was assessed in a substudy of 741 patients. RESULTS: The incidence of all predefined end points was lower in the metoprolol CR/XL group than in the placebo group, including total mortality or all-cause hospitalizations (the prespecified second primary end point; 641 vs 767 events; risk reduction, 19%; 95% confidence interval [CI], 10%-27%; P<.001); total mortality or hospitalizations due to worsening heart failure (311 vs 439 events; risk reduction, 31%; 95% CI, 20%-40%; P<.001), number of hospitalizations due to worsening heart failure (317 vs 451; P<.001); and number of days in hospital due to worsening heart failure (3401 vs 5303 days; P<.001). NYHA functional class, assessed by physicians, and McMaster Overall Treatment Evaluation score, assessed by patients, both improved in the metoprolol CR/XL group compared with the placebo group (P = .003 and P = .009, respectively). CONCLUSIONS: In this study of patients with symptomatic heartfailure, metoprolol CR/XL improved survival, reduced the need for hospitalizations due to worsening heart failure, improved NYHA functional class, and had beneficial effects on patient well-being.
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| 2. |
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| 3. |
- Herlitz, Johan, et al.
(författare)
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Clinical observations after treatment with metoprolol in suspected acute myocardial infarction in relation to age
- 1985
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Ingår i: Acta Medica Scandinavica. - : Wiley-Blackwell Publishing Ltd.. - 0001-6101. ; 217:3, s. 293-298
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Tidskriftsartikel (refereegranskat)abstract
- A double-blind trial with the beta 1-selective blocker metoprolol in suspected acute myocardial infarction and during 3 months' follow-up included 1395 patients, aged 40-74 years, 698 on metoprolol and 697 on placebo. In order to further evaluate the tolerability to beta-blockade in the elderly, the total series was divided into 2 groups according to median age (61 years) and into quartiles, the lowest quartile (40-57 years) being compared with the highest (67-74 years). The decrease in heart rate and systolic blood pressure after intravenous metoprolol in the acute phase was similar in the elderly and the younger patients. Hypotension was observed more often in the metoprolol-treated than in the placebo-treated younger patients, while no difference was observed in the elderly. Bradycardia was observed more often in the metoprolol group in both age groups, while there was no difference regarding the incidence of congestive heart failure in either the younger or in the elderly patients. The effect on mortality, serious ventricular arrhythmias and chest pain seemed to be similar in different age groups. From the present series we conclude that hemodynamic reactions and tolerability to beta-blockade can be expected to be similar in elderly and younger patients.
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| 4. |
- Herlitz, Johan, et al.
(författare)
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Correlation between enzymatic estimation of infarct size and early mortality rate.
- 1983
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Ingår i: British Heart Journal. - : BMJ Group. - 0007-0769. ; 50:6, s. 520-524
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Tidskriftsartikel (refereegranskat)abstract
- In 585 patients with a first acute myocardial infarction the maximum activity of heat stable lactate dehydrogenase (EC 1.1.1.27) was correlated with mortality at three months. The patients participated in a double blind trial with metoprolol in acute myocardial infarction. In all patients not taking a beta blocker a highly significant correlation was found, but this was not evident in those who were. When patients with anterior or inferior infarctions treated with a placebo were analysed separately the correlation remained, as it did when the patients who were alive on the fourth day after the onset of pain were analysed separately. No correlation was observed between enzyme activity and three month mortality in these subgroups if only patients treated with metoprolol were included. In a subsample of only 171 patients it was found that the maximum activity of creatine kinase (EC 2.7.3.2) and creatine kinase subunit B did not correlate with three month mortality regardless of treatment. Thus it is concluded that when a sufficiently large number of patients are investigated there is a highly significant correlation between the enzymatic estimation of infarct size and early mortality in acute myocardial infarction. This relation did not persist when patients treated with beta blockade were analysed.
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| 5. |
- Herlitz, Johan, et al.
(författare)
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Effect of metoprolol on indirect signs of the size and severity of acute myocardial infarction
- 1983
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Ingår i: American Journal of Cardiology. - : Elsevier Excerpta Medica, Inc.. - 0002-9149 .- 1879-1913. ; 51:8, s. 1282-1288
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Tidskriftsartikel (refereegranskat)abstract
- In a double-blind randomized trial, 1,395 patients with suspected acute myocardial infarction (MI) were investigated to evaluate the possibility of limiting indirect signs of the size and severity of acute MI with the beta1-selective adrenoceptor antagonist metoprolol. Metoprolol (15 mg) was given intravenously and followed by oral administration for 3 months (200 mg daily). Placebo was given in the same way. The size of the MI was estimated by heat-stable lactate dehydrogenase (LD[EC 1.1.1.27]) analyses and precordial electrocardiographic mapping. Lower maximal enzyme activities compared with placebo were seen in the metoprolol group (11.1 ± 0.5 μkat · liter−1)when the patient was treated within 12 hours of the onset of pain (13.3 ± 0.6 μkat · liter−1; n = 936; p = 0.009). When treatment was started later than 12 hours, no difference was found between the 2 groups. Enzyme analyses were performed in all but 20 patients (n = 1,375). Precordial mapping with 24 chest electrodes was performed in patients with anterior wall MI. The final total R-wave amplitude was higher and the final total Q-wave amplitude lower in the metoprolol group than in the placebo group. Patients treated with metoprolol ≤12 hours also showed a decreased need for furosemide, a shortened hospital stay, and a significantly reduced 1-year mortality compared with the placebo group, whereas no difference was observed among patients treated later on. After 3 months, however, there was a similar reduction in mortality among patients in whom therapy was started 12 hours and >12 hours after the onset of pain. The results support the hypothesis that intravenous metoprolol followed by oral treatment early in the course of suspected myocardial infarction can limit infarct size and improve longterm prognosis.
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| 6. |
- Herlitz, Johan, et al.
(författare)
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Effect of metoprolol on the prognosis among patients with suspected acute myocardial infarction and indirect signs of congestive heart failure. (A subgroup analysis of the Göteborg Metoprolol Trial)
- 1997
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Ingår i: American Journal of Cardiology. - : Excerpta Medica, Inc.. - 0002-9149 .- 1879-1913. ; 80:9B, s. 40J-44J
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study is to describe the impact of early treatment with metoprolol on prognosis during 1 year of follow-up in patients with suspected acute myocardial infarction (AMI) and indirect signs of congestive heart failure (CHF). Patients aged 40-74 years who presented within 48 hours of onset of symptoms raising suspicion of AMI were assessed for inclusion. All patients participated in the Göteborg Metoprolol Trial and had indirect indices of CHF according to various clinical criteria. As soon as possible after hospital admission, patients received either placebo or metoprolol (15 mg) divided into 3 intravenous injections, then oral treatment, 200 mg daily for 3 months. Thereafter, most patients in both treatment groups received metoprolol in an open manner. Among the 1,395 randomized patients, 262 (19%) had signs of mild-to-moderate CHF before randomization. Of these, 131 were randomized to metoprolol and 131 to placebo. During the first 3 months, mortality was 10% among patients randomized to metoprolol versus 19% among patients randomized to placebo (p = 0.036). The corresponding figures for the first year were 14% and 27%, respectively (p = 0.0099). Patients randomized to placebo who showed signs of CHF had a 1-year mortality rate of 28% compared with 10% among patients without such signs (p <0.001). The results suggest that early treatment with metoprolol markedly reduces mortality in patients having suspected AMI and signs of CHF.
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| 7. |
- Herlitz, Johan, et al.
(författare)
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Effects of work and acute beta-receptor blockade on myocardial noradrenaline release in congestive cardiomyopathy
- 1979
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Ingår i: Clinical Cardiology. - : John Wiley & Sons, Inc. - 0160-9289 .- 1932-8737. ; 2:6, s. 424-430
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Tidskriftsartikel (refereegranskat)abstract
- Systemic hemodynamic changes and noradrenaline concentrations in coronary sinus blood were studied at rest and during work before and after acute beta-receptor blockade. Patients with congestive cardiomyopathy were compared to patients with primary valvular diseases and to healthy subjects. Noradrenaline concentrations were higher in coronary sinus blood than in arterial blood and increased after beta blockade and during work. Noradrenaline concentrations were more increased in patients with more pronounced myocardial failure and did not seem to separate patients with congestive cardiomyopathy from those with valvular disease. Patients with congestive cardiomyopathy showed a good hemodynamic tolerance toward acute beta blockade.
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| 8. |
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| 9. |
- Herlitz, Johan, et al.
(författare)
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Enzymatically and electrocardiographically estimated infarct size in relation to pain in acute myocardial infarction
- 1984
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Ingår i: Cardiology. - : S. Karger AG. - 0008-6312 .- 1421-9751. ; 71:5, s. 239-246
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Tidskriftsartikel (refereegranskat)abstract
- In 563 patients with acute myocardial infarction and no previous myocardial infarction, the estimated infarct size was related to the estimated duration of pain and the amount of analgesics given. The size of infarction estimated from analyses of heat-stable lactate dehydrogenase (EC 1.1.1.27) at 12-hour intervals for 48-108 h and from Q- and R-wave changes in the ECG correlated positively, although weakly with duration of the pain and the amount of analgesics given. These data support the hypothesis that larger infarcts, as a group, evolve over a longer time period than smaller infarcts and that the duration of pain in many patients might be an indicator of the infarct size. In the individual patient, however, one cannot predict the size of the infarction from the severity of pain.
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| 10. |
- Herlitz, Johan, et al.
(författare)
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Göteborg Metoprolol Trial : mortality and causes of death
- 1984
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Ingår i: American Journal of Cardiology. - : Excerpta Medica, Inc.. - 0002-9149 .- 1879-1913. ; 53:13, s. 9-14
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Tidskriftsartikel (refereegranskat)abstract
- During the 3-month blind treatment period there were 40 deaths in the metoprolol group compared with 62 deaths in the placebo group (p = 0.024). During the first year (after 3 months the 2 groups were treated similarly) there were 64 deaths in the metoprolol group vs 93 in the placebo group (p = 0.017) and during 2 years 92 patients died in the metoprolol group vs 120 in the placebo group (p = 0.043). The relative incidence of different causes of death did not differ significantly between the 2 treatment groups, indicating that metoprolol reduced all causes of death to the same extent as its effect on overall mortality.
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