| 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. |
- Dellborg, M, et al.
(författare)
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Changes in the use of medication after acute myocardial infarction : Possible impact on post-myocardial infarction mortality and long-term outcome
- 2001
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Ingår i: Coronary Artery Disease. - : Lippincott Williams & Wilkins. - 0954-6928 .- 1473-5830. ; 12:1, s. 61-67
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To describe the change in the use of medication after acute myocardial infarction (AMI) and discuss its possible impact on risk and risk indicators for death. Patients: All patients discharged alive after hospitalization for AMI at Sahlgrenska Hospital (covering half the community of Goteborg, i.e. 250 000 of 500 000 inhabitants) during 1986-1987 (period I) and at Sahlgrenska Hospital and Ostra Hospital (covering the whole community of Goteborg, 500 000 inhabitants) during 1990-1991 (period II). Methods: Overall mortality was retrospectively evaluated during 5 years of follow-up. Results: In all, 740 patients were included in the study during period I and 1448 during period II. The 5-year mortalities were 44.1% for period I patients and 39.3% for period II patients (P = 0.036). The relative risk of death for period II patients was 0.78 [95% confidence interval (CI) 0.67-0.89, P = 0.0005] after adjustment for differences at baseline. There was a significant interaction with a history of congestive heart failure; improvement in duration of survival was found only for patients without such a history. During period I, only 3% of patients were administered fibrinolytic agents, compared with 33% of patients during period II (P < 0.0001). During period I, aspirin was prescribed for 13% of patients discharged from hospital compared with 79% during period II. Other changes in treatment on going from period I to period II included increases in prescription of [beta]-blockers and angiotensin converting enzyme inhibitors. After adjustment for various risk indicators for death, relative risk of death for those administered fibrinolytic agents was 0.60 (95% CI 0.18-2.02) for patients in the period-I cohort and 0.68% (95% CI 0.51-0.91) for those in the period-II cohort. Adjusted relative risk of death for those prescribed aspirin upon discharge from hospital was 0.81 (95% CI 0.52-1.25) for period-I patients and 0.71 (95% CI 0.56-0.91) for period-II patients. The adjusted relative risk of death for those administered [beta]-blockers was 0.72 (95% CI 0.55-0.96) for period-I patients and 0.70 (95% CI 0.55-0.90) for period-II patients. Conclusion: Increased use of fibrinolytic agents and aspirin for AMI as well as a moderate increase in use of [beta]-blockers and angiotensin converting enzyme inhibitors was associated with a parallel reduction in age-adjusted mortality during the 5 years after discharge from hospital. However, this improvement was seen only for patients without histories of congestive heart failure.
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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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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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| 5. |
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| 6. |
- 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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| 7. |
- Herlitz, Johan, et al.
(författare)
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Göteborg Metoprolol Trial : design, patient characteristics and conduct
- 1984
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Ingår i: American Journal of Cardiology. - : Excerpta Medica, Inc.. - 0002-9149 .- 1879-1913. ; 53:13, s. 3D-8D
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Tidskriftsartikel (refereegranskat)abstract
- The Göteborg Metoprolol Trial was a double-blind, placebo-controlled, stratified trial aimed at evaluating the effect of the beta 1-selective blocker, metoprolol, in suspected acute myocardial infarction and during 2 years of follow-up. The primary end-point was 3-month mortality (blind treatment period). Secondary end-points were 2-year mortality, indirect signs of infarct size, chest pain, arrhythmias and tolerability. The entry criteria were fulfilled in 2,802 patients, 1,395 of whom were included in the trial. Treatment started as soon as possible after arrival in hospital with intravenous administration followed by oral treatment for 3 months. All patients were randomized 48 hours or less after estimated onset of infarction and 69% were randomized at 12 hours or less. The blind treatment had to be withdrawn in 19% of all randomized patients before the end of the 3-month follow-up.
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| 8. |
- Herlitz, Johan, et al.
(författare)
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Long term mortality after acute myocardial infarction in relation to prescribed dosages of a beta-blocker at hospital discharge
- 2001
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Ingår i: Cardiovascular Drugs and Therapy. - : Springer New York LLC. - 0920-3206 .- 1573-7241. ; 14:6, s. 589-595
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Tidskriftsartikel (refereegranskat)abstract
- his 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="">le100 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.
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| 9. |
- Herlitz, Johan, et al.
(författare)
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Similar risk reduction of death of extended-release metoprolol once daily and immediate release metoprolol twice daily during 5 years after myocardial infarction
- 1999
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Ingår i: Cardiovascular Drugs and Therapy. - : Springer New York LLC. - 0920-3206 .- 1573-7241. ; 13:2, s. 127-135
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Tidskriftsartikel (refereegranskat)abstract
- The pooled results from five placebo-controlled postinfarction studies with metoprolol have shown a significant reduction in total mortality. All five studies used immediate-release metoprolol twice daily. An extended-release formulation of metoprolol for once-daily use has since been developed. The aim of the present study was to compare the two different forms of metoprolol with regard to the risk reduction of death for 5 years postinfarction and to analyze whether treatment with the beta-blocker metoprolol is associated with a reduced mortality after the introduction of modern therapies such as thrombolysis, aspirin, and ACE inhibitors. All patients discharged after an acute myocardial infarction (AMI) from Sahlgrenska University Hospital (SU) during 1986-1987 (n = 740, Period I) and during 1990-1991 (n = 1446, Period II) from both SU and Ostra Hospital, Göteborg, Sweden, were included in the study. During Period I, 56% were prescribed immediate-release metoprolol compared with 61% prescribed extended-release metoprolol during Period II. Immediate-release metoprolol was not available for outpatient use during Period II. In a multivariate analysis, all variables significantly associated with either increased or decreased postinfarction mortality during Periods I and II (univariate analysis of patient characteristics, medical history, complications during the AMI medication at discharge) studied were with Cox's proportional hazards model. Treatment with immediate-release metoprolol was significantly associated with reduced mortality over 5 years during Period I (relative risk reduction for total mortality, -34%, P = 0.003; 95% CI for RR, 0.51-0.87), and treatment with extended-release metoprolol was significantly associated with reduced mortality during Period II (-34%, P < 0.0001; 95% CI for RR, 0.53-0.82). Thrombolysis and the use of aspirin and ACE inhibitors were more frequently used during Period II. The results showed that postinfarction treatment with extended-release metoprolol given once daily was associated with a similar risk reduction of death over 5 years as immediate-release metoprolol given twice daily. The data, furthermore, indicate that the beta-blocker metoprolol is associated with a reduced risk of death after the introduction of modern therapy such as thrombolysis, aspirin, and ACE inhibitors.
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| 10. |
- Herlitz, Johan, et al.
(författare)
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Tolerans för betablockad hos äldre
- 1982
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Ingår i: Hypertoni hos äldre. - : Almqvist & Wiksell. ; , s. 101-105
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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