Stig Holmberg

EFFECT ON MORTALITY OF METOPROLOL IN ACUTE MYOCARDIAL INFARCTION: A Double-blind Randomised Trial

The effect of metoprolol on mortality was compared with that of placebo in a double blind randomised trial in patients with definite or suspected acute myocardial infarction. Treatment with metoprolol or placebo started as soon as possible after the patients arrival in hospital and was continued for 90 days. Metoprolol was given as a 15 mg intravenous dose followed by oral administration of 100 mg twice daily. 1395 patients (697 on placebo and 698 on metoprolol) were included in the trial. Definite acute myocardial infarction developed in 809 and probable infarction in 162. Patients were allocated to various risk groups and within each group patients were randomly assigned to treatment with metoprolol or placebo. There were 62 deaths in the placebo group (8.9%) and 40 deaths in the metoprolol group (5.7%), a reduction of 36% (p less than 0.03). Mortality rates are given according to the treatment group to which the patients were initially randomly allocated.

Survival and safety of exemestane versus tamoxifen after 2-3 years' tamoxifen treatment (Intergroup Exemestane Study): a randomised controlled trial

BACKGROUND Early improvements in disease-free survival have been noted when an aromatase inhibitor is given either instead of or sequentially after tamoxifen in postmenopausal women with oestrogen-receptor-positive early breast cancer. However, little information exists on the long-term effects of aromatase inhibitors after treatment, and whether these early improvements lead to real gains in survival. METHODS 4724 postmenopausal patients with unilateral invasive, oestrogen-receptor-positive or oestrogen-receptor-unknown breast cancer who were disease-free on 2-3 years of tamoxifen, were randomly assigned to switch to exemestane (n=2352) or to continue tamoxifen (n=2372) for the remainder of a 5-year endocrine treatment period. The primary endpoint was disease-free survival; overall survival was a secondary endpoint. Efficacy analyses were intention-to-treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN11883920. RESULTS After a median follow-up of 55.7 months (range 0-89.7), 809 events contributing to the analysis of disease-free survival had been reported (354 exemestane, 455 tamoxifen); unadjusted hazard ratio 0.76 (95% CI 0.66-0.88, p=0.0001) in favour of exemestane, absolute benefit 3.3% (95% CI 1.6-4.9) by end of treatment (ie, 2.5 years after randomisation). 222 deaths occurred in the exemestane group compared with 261 deaths in the tamoxifen group; unadjusted hazard ratio 0.85 (95% CI 0.71-1.02, p=0.08), 0.83 (0.69-1.00, p=0.05) when 122 patients with oestrogen-receptor-negative disease were excluded. CONCLUSIONS Our results suggest that early improvements in disease-free survival noted in patients who switch to exemestane after 2-3 years on tamoxifen persist after treatment, and translate into a modest improvement in overall survival.

Effect of bystander cardiopulmonary resuscitation in out-of-hospital cardiac arrest patients in Sweden

BACKGROUND Information from the Swedish Cardiac Arrest Registry was used to investigate: (a) The proportion of patients suffering an out-of-hospital cardiac arrest who were given bystander cardiopulmonary resuscitation (B-CPR). (b) Where and by whom B-CPR was given. (c) The effect of B-CPR on survival. METHOD a prospective, observational study of cardiac arrests reported to the Swedish Cardiac Arrest Registry. Analyses were based on standardised reports of out-of-hospital cardiac arrests from ambulance organisations in Sweden, serving 60% of the Swedish population. From 1983 to 1995 approximately 15-20% of the population had been trained in CPR. RESULTS Of 9877 patients, collected between January 1990 and May 1995, B-CPR was attempted in 36%. In 56% of these cases, the bystanders were lay persons and in 25% they were medical personnel. Most of the arrests took place at home (69%) and only 23% of these patients were given B-CPR in contrast to cardiac arrest in other places where 53% were given CPR. Survival to 1 month was significantly higher in all cases that received B-CPR (8.2 vs. 2.5%). The odds ratio for survival to 1 month with B-CPR was in a logistic regression analysis 2.5 (95% CI 1.9-3.1). CONCLUSIONS In Sweden, the willingness and ability to perform B-CPR appears to be relatively widespread. More than half of B-CPR was performed by laypersons. B-CPR resulted in a two to threefold increase in survival.

A randomized trial comparing axillary clearance versus no axillary clearance in older patients (≥ 60 years) with breast cancer: First results of International Breast Cancer Study Group Trial 10–93

505 Background: Axillary clearance is associated with undesirable side-effects. We therefore investigated if avoiding axillary surgery in older women would result in improved quality of life (QL) and similar disease-free survival (DFS) and overall survival (OS). METHODS Between 1993 and 2002, women ≥ 60 years old with clinically N0 operable breast cancer were randomized to primary surgery plus axillary clearance (Sx+Ax) followed by tamoxifen (Tam) versus Sx without Ax followed by Tam. The primary endpoint was QL reported by the patient (using linear analogue self-assessment [LASA] scales) and by physician assessment at sequential time points. RESULTS 473 patients (234 to Sx+Ax, 239 to Sx) were randomized to meet the target accrual of 472 patients. The median age was 74 years in both arms. Other characteristics were also balanced: 80% ER-positive; 45% mastectomies; 33% breast-conserving surgery with radiotherapy (RT); 22% breast-conserving surgery without RT. The table below gives the results of 2 of the LASAs and 2 of the physician-reported side-effects. In all of these assessments the largest differences were observed from baseline to post-operative, with patients randomized to Sx+Ax having worse QL and more side effects, but the differences tended to approach baseline values in 6 to 12 months. At a median follow-up of 6 years, results for Sx+Ax vs. Sx were similar for DFS (total events: 84 vs. 77; 5-year DFS: 71% vs. 70%; relative risk (RR) [Sx+Ax/Sx]: 1.12; 95% CI: 0.82-1.53; p=0.46) and OS (total deaths: 65 vs. 62; 5-year OS: 78% vs. 80%; RR [Sx+Ax/Sx]: 1.10; 95% CI: 0.77-1.55; p=0.61). CONCLUSIONS Avoiding axillary clearance for women ≥ 60 years old who have clinically N0 disease and receive Tam results in similar efficacy with improved QL. [Figure: see text] No significant financial relationships to disclose.

Distinct Clinical and Prognostic Features of Infiltrating Lobular Carcinoma of the Breast: Combined Results of 15 International Breast Cancer Study Group Clinical Trials

PURPOSE To determine how patients with infiltrating lobular carcinoma (ILC) differ from patients with the more common infiltrating ductal carcinoma (IDC) with regard to patient and tumor factors, local treatment, and patterns of recurrence. PATIENTS AND METHODS Twelve thousand two hundred six breast cancer patients entered onto 15 International Breast Cancer Study Group trials between 1978 and 2002 were categorized as having ILC, IDC, or other/mixed types. RESULTS Seven hundred sixty-seven tumors (6.2%) were classified as ILC, 8,607 (70.5%) were classified as IDC, and 2,832 (23.2%) were classified as other. The analysis is limited to the 9,374 patients categorized as either pure IDC or ILC. The median follow-up time was 13 years. Compared with IDC, ILC was associated with older age; larger, better differentiated, and estrogen receptor (ER)-positive tumors; and less vessel invasion. Mastectomy was used more frequently for ILC (P < .01). There was a significant (P < .01) early advantage in disease-free survival and overall survival for the ILC cohort followed by a significant (P < .01) late advantage for the IDC cohort after 6 and 10 years, respectively. Similar patterns were observed in cohorts defined by ER status. ILC was associated with an increased incidence of bone events but a decrease in regional and lung events (all P < .01). CONCLUSION ILC is more than a histologic variant of breast cancer. The diagnosis of ILC carries distinct prognostic and biologic implications.

Survival after cardiac arrest outside hospital in Sweden

The voluntary Swedish Cardiac Arrest Registry has collected and analyzed 14,065 standardised reports on cardiac arrests up until May 1995. The reports have been collected from approximately half of Swedens ambulance districts, which cover 60% of the population. Resuscitation was attempted in 10,966 cases. The median age was 70 years. In 70.0% the arrest was witnessed, and in 43.3% the first recorded rhythm was VT/VF. Bystander-CPR was initiated in 32.3% of the cases. Most cardiac arrests took place at home (65.8%) and 67.1% were judged to be of cardiac origin. In 1692 cases (15.4%), the patient was admitted alive in hospital and 544 patients (5.0%) were alive after 1 month. Survival to 1 month in the subgroup which presented with VT/VF was 9.5%. We found no significant difference between survival in large cities and smaller communities. The survivors were analysed in relation to time to defibrillation and we found a strong correlation between a short time and increased survival.

Incidence, duration and survival of ventricular fibrillation in out-of-hospital cardiac arrest patients in Sweden

UNLABELLED The chance of survival from ventricular fibrillation (VF) is up to ten times higher than those with other cardiac arrest rhythms. To calculate the effect of out-of-hospital resuscitation organisations on survival, it is necessary to know the percentage of cardiac arrest patients initially in VF and the relationship between delay time to defibrillation and survival. AIM To study the incidence of VF at the time of cardiac arrest and on first ECG, the duration of VF and the relation between time to defibrillation and survival. METHOD The Swedish Cardiac Arrest Registry has collected standardised reports on out-of-hospital cardiac arrests from ambulance organisations in Sweden, serving 60% of the Swedish population. RESULTS In 14065 cases of out-of-hospital cardiac arrest collected between 1990 and 1995, resuscitation was attempted in 10966 cases. INCIDENCE The first ECG showed VF in 43% of all patients. The incidence of VF at the time of cardiac arrest was estimated to be 60-70% in all patients and 80-85% in the cases with probable heart disease. DURATION The estimated disappearance rate of VF was slow. Thirty minutes after collapse approximately 40% of the patients were in VF. SURVIVAL Overall survival to 1 month was only 1.6% for patients with non-shockable rhythms and 9.5% for patients found in VF. With increasing time to defibrillation, the survival rate fell rapidly from approximately 50% with a minimal delay to 5% at 15 min. CONCLUSIONS This study suggests a high initial incidence of VF among out-of-hospital cardiac arrest patients and a slow rate of transformation into a non-shockable rhythm. The survival rate with very short delay times to defibrillation was approximately 50%, but decreased rapidly as the delay increased.

Effect of bystander initiated cardiopulmonary resuscitation on ventricular fibrillation and survival after witnessed cardiac arrest outside hospital.

OBJECTIVE--To describe the proportion of patients who were discharged from hospital after witnessed cardiac arrest outside hospital in relation to whether a bystander initiated cardiopulmonary resuscitation. PATIENTS--All patients with witnessed cardiac arrest outside hospital before arrival of the ambulance and in whom cardiopulmonary resuscitation was attempted by the emergency medical service in Gothenburg during 1980-92. RESULTS--Cardiopulmonary resuscitation was initiated by a bystander in 18% (303) of 1,660 cases. In this group 69% had ventricular fibrillation at first recording compared with 51% in the remaining patients (P < 0.001). Among patients in whom cardiopulmonary resuscitation had been initiated by a bystander 25% were discharged alive versus 8% of the remaining patients (P < 0.001). Independent predictors of survival were in order of significance: initial arrhythmia (P < 0.001), interval between collapse and arrival of first ambulance (P < 0.001), cardiopulmonary resuscitation initiated by a bystander (P < 0.001), and age (P < 0.01). Among patients who were admitted to hospital alive 30% of patients in whom cardiopulmonary resuscitation had been initiated by a bystander compared with 58% of remaining patients (P < 0.001) had brain damage and died in hospital. Corresponding figures for death in association with myocardial damage were 18% and 29% respectively (P < 0.01). CONCLUSIONS--Cardiopulmonary resuscitation initiated by a bystander maintains ventricular fibrillation and triples the chance of surviving a cardiac arrest outside hospital. Furthermore, it seems to protect against death in association with brain damage as well as with myocardial damage.

Early Start of Adjuvant Chemotherapy May Improve Treatment Outcome for Premenopausal Breast Cancer Patients With Tumors not Expressing Estrogen Receptors

PURPOSE The proper time to commence adjuvant chemotherapy after primary surgery for breast cancer is unknown. An analysis of the International (Ludwig) Breast Cancer Study Group (IBCSG) Trial V at a median follow-up of 11 years suggested that early initiation of adjuvant chemotherapy might improve outcome for premenopausal, node-positive patients whose tumors did not express any estrogen receptor (ER). PATIENTS AND METHODS We investigated the relationship between early initiation of adjuvant chemotherapy, ER status, and prognosis in 1,788 premenopausal, node-positive patients treated on IBCSG trials I, II, and VI. The disease-free survival for 599 patients (84 with ER-absent tumors) who commenced adjuvant chemotherapy within 20 days (early initiation) was compared with the disease-free survival for 1,189 patients (142 with ER-absent tumors) who started chemotherapy 21 to 86 days after surgery (conventional initiation). The median follow-up was 7.7 years. RESULTS Among patients with ER-absent tumors, the 10-year disease-free survival was 60% for the early initiation group compared with 34% for the conventional initiation group (226 patients; hazard ratio [HR], 0. 49; 95% confidence interval [CI], 0.33 to 0.72; P =.0003). This difference remained statistically significant in a Cox multiple regression analysis controlling for study group, number of positive nodes, tumor size, age, vessel invasion, and institution (HR, 0.60; 95% CI, 0.39 to 0.92; P =.019). Conversely, early initiation of chemotherapy did not significantly improve disease-free survival for patients with tumors expressing ER (1,562 patients; multiple regression HR, 0.93; 95% CI, 0.79 to 1.10; P =.40). CONCLUSION In premenopausal patients with ER-absent tumors, early initiation of systemic chemotherapy after primary surgery might improve outcome. Further confirmatory studies are required before any widespread modification of current clinical practice. In premenopausal patients with tumors expressing some ER, gains from early initiation are unlikely to be clinically significant.

Characteristics and outcome among patients suffering in-hospital cardiac arrest in monitored and non-monitored areas

AIM To describe the characteristics and outcome among patients suffering in-hospital cardiac arrest in relation to whether the arrest took place in a ward with monitoring facilities. METHODS All patients who suffered an in-hospital cardiac arrest during a 4-year period in Sahlgrenska Hospital, Göteborg, Sweden and in whom resuscitative efforts were attempted, were prospectively recorded and described in terms of characteristics and outcome. RESULTS Among 557 patients, 292 (53%) had a cardiac arrest in wards with monitoring facilities. Those in a monitored location more frequently had a confirmed or possible acute myocardial infarction (AMI) as judged to be the cause of arrest (P < 0.0001), and the arrest was witnessed more frequently (96 vs. 79%; P < 0.0001). Ventricular fibrillation/tachycardia was observed more often as initial arrhythmia in monitored wards (56 vs. 44%; P = 0.006). The median interval between collapse and first defibrillation was 1 min in monitored wards and 5 min in non-monitored wards (P < 0.0001). Among patients with arrest in monitored wards 43.2% were discharged alive compared with 31.1% of patients in non-monitored wards (P = 0.004). Cerebral performance category (CPC-score) at discharge was somewhat better among survivors in monitored wards. CONCLUSION In a Swedish University Hospital 47% of in-hospital cardiac arrests in which resuscitation was attempted took place in wards without monitoring facilities. These patients differed markedly from those having arrest in wards with monitoring facilities in terms of characteristics, interval to defibrillation and outcome. A shortening of the interval between collapse and defibrillation in these patients might increase survival even further.