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.

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.

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.

Cardiovascular prognosis in relation to apolipoproteins and other lipid parameters in patients with stable angina pectoris treated with verapamil or metoprolol: results from the Angina Prognosis Study in Stockholm (APSIS).

Relationships between apolipoproteins and other lipid parameters and cardiovascular (CV) prognosis were evaluated in the Angina Prognosis Study In Stockholm (APSIS). Out of 809 patients with stable angina pectoris, lipid variables were obtained in 786 patients at baseline, and after one month's double-blind treatment with metoprolol or verapamil, to evaluate treatment effects on these lipid variables. During a median follow-up time of 3.3 years (2663 patient years), 37 patients suffered a CV death, 30 suffered a non-fatal myocardial infarction (MI) and 100 underwent a revascularization. Apolipoprotein (apo) A-I, high-density lipoprotein cholesterol and triglycerides were predictors of CV death or non-fatal MI in univariate analyses, but only apo A-I remained as an independent predictor in multivariate analyses. All lipid variables except low density lipoprotein cholesterol were related to the risk of revascularization in univariate analyses, but only apo A-I and apo B were independent predictors of such events. Triglycerides were weakly, but not independently, associated with prognosis. Verapamil and metoprolol had differential short-term effects on lipids, with a shift towards a more atherogenic profile in metoprolol treated patients. However, there was no significant impact of the treatment given, or of these treatment effects on the risk of CV events. Results of the present study suggest that apolipoprotein levels were better predictors of CV events than other lipid parameters in patients with stable angina pectoris.

Inflammatory and hemostatic markers in relation to cardiovascular prognosis in patients with stable angina pectoris. Results from the APSIS study. The Angina Prognosis Study in Stockholm.

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.

Arrhythmias and their treatment in patients with heart failure.

Heart failure is almost without exception associated with arrhythmias, which may be either supraventricular or ventricular. Supraventricular arrhythmias include frequent supraventricular extrasystoles, and episodic or chronic atrial fibrillation. The absence of atrial contraction may further reduce cardiac output, as may impaired control of QRS frequency. Therefore, supraventricular arrhythmias may be markers of the degree of heart failure and these arrhythmias will respond to heart failure therapy including diuretics, nitrates and, possibly, angiotensin-converting enzyme (ACE) inhibitors. Ventricular rate will be controlled by cardiac glycosides and further rate reduction obtained by verapamil or diltiazem. The rationale for this therapy is to optimize heart rate without compromising contractility. Severe heart failure is generally accompanied by severe ventricular arrhythmias including repetitive forms. Improving left ventricular function by ACE inhibition is accompanied by a reduction in the number of ventricular premature complexes and also a reduction in the rate of ventricular tachycardia. ACE inhibition reduces mortality but does not seem to influence sudden death rate, and sudden death patients may have different neurohormonal responses compared with patients destined to die of progressive heart failure. Uncontrolled trials with class IA or class III antiarrhythmic drugs have suggested that prognosis may be improved, but other studies have pointed out the increased risk of proarrhythmic responses in patients with low ejection fraction.

Treatment of ventricular arrhythmias in the coronary patient: what sort of patient? For which rhythm disorder? With which procedure?

In the patient with coronary artery disease, complex ventricular arrhythmias and frequent ventricular arrhythmias appear to be independent risk factors for subsequent death, particularly in patients who have had myocardial infarction. In patients with symptomatic arrhythmias, treatment must be instituted and tested during rigorous supervision of the patient. Using both the noninvasive Holter monitoring/exercise test procedure and invasive electrophysiologic testing, a beneficial antiarrhythmic response after institution of antiarrhythmic agents indicates improved prognosis. However, a negative treatment response during programmed stimulation does not necessarily indicate bad prognosis. This is particularly true for testing during amiodarone treatment. For unselected patients, routine antiarrhythmic treatment cannot currently be recommended. Continuing studies will show whether screening for electrical instability of the myocardium, and institution of antiarrhythmic therapy thereafter, will improve overall survival. If patients tolerate beta-blocking treatment, this should probably be instituted because reductions in mortality have been found, particularly in high-risk patients.

Influence of long-term metoprolol treatment on early and late exercise test performance after acute myocardial infarction.

The effect of therapy on exercise performance during a 3-year follow-up after acute myocardial infarction (AMI) was evaluated in a double-blind randomized comparison between 154 patients given metoprolol (100 mg twice daily) and 147 patients given placebo. Exercise tests were performed 1.5, 6, 12, 24 and 36 months after AMI. Maximal accomplished workloads were similar in the 2 groups throughout follow-up. Maximal heart rate was significantly higher in the placebo-treated group throughout the study (p less than 0.001). At the 6-week test more patients in the placebo group terminated exercise due to angina pectoris (40 vs 25%, p less than 0.05) and showed exercise-induced ST-depressions (38 vs 27%, p = 0.05) compared with the metoprolol group. Exercise-induced ventricular arrhythmias were significantly more common in the placebo group during the initial 6 months. Death, another AMI or both were significantly reduced by metoprolol treatment in patients with exercise-induced ST depression greater than or equal to 1 mm at the 6-week test. In a multiple logistic regression analysis maximal accomplished workload at 6 weeks (p less than 0.026), male sex (relative risk [rr] = 3.57, p = 0.016), previous AMI (rr = 3.07, p = 0.001), therapy with placebo (rr = 2.14, p = 0.007) and left ventricular failure (rr = 2.04, p = 0.023) were shown to carry independent prognostic information as well as exercise-induced ST-depression (greater than or equal to 1 mm) in placebo-treated patients (rr = 2.70, p = 0.01).

Prognosis of patients with stable angina pectoris on antianginal drug therapy.

Antianginal drug treatment reduces symptoms and ischemia but may also influence the prognosis of patients with stable angina pectoris. The Atenolol Silent Ischemia Study (ASIST) compared atenolol and placebo treatment (about 140 patient-years on each) in patients with mainly silent ischemia and found less aggravation of angina and a tendency toward fewer cardiac complications with atenolol treatment. The Total Ischaemic Burden European Trial (TIBET) compared slow release nifedipine, atenolol, or the combination (about 450 patient-years on each) and found no significant differences with regard to cardiac complications, a nonsignificant trend toward better prognosis on combined treatment, and more side effects on nifedipine alone compared with the other treatments. The Angina Prognosis Study in Stockholm (APSIS) compared metoprolol and verapamil (about 1,400 patient-years on each) and found similar effects on cardiovascular endpoints, tolerability, and psychosocial variables with the 2 treatments. Hypothesis-generating subgroup analyses in APSIS suggest that treatment effects may differ in hypertensive and diabetic subgroups. Beneficial effects in primary and secondary prevention, together with data from ASIST, suggest that beta 1 blockade influences prognosis favorably. The safety of short-acting nifedipine in ischemic heart disease is questioned, but TIBET data suggest that slow release nifedipine may be safe. Verapamil has beneficial effects after myocardial infarction (Danish Verapamil Infarction Trial II) and shows similar efficacy as metoprolol in the APSIS study. The paucity of placebo data (antianginal treatment cannot be withheld during long periods of time in symptomatic patients) precludes firm conclusions regarding effects of drug treatment on prognosis. It is argued that patients with stable angina pectoris do well on medical treatment, and that beta 1 blockers, verapamil, and, possibly, slow-release nifedipine may influence their prognosis favorably.

Prognostic information from on-line vectorcardiography in acute myocardial infarction.

The present study assesses the prognostic information from continuous on-line vectorcardiography in patients with acute myocardial infarction (AMI). A series of 203 patients with AMI were studied. Vectorcardiographic (VCG) recordings were obtained continuously for 24 hours. Analysis was performed on-line with the commercial system MIDA CoroNet. QRS vector difference (QRS-VD), ST change vector magnitude (STC-VM), and ST vector magnitude (ST-VM) were monitored. Patients were followed for 538 +/- 220 days. During follow-up, 36 patients died from cardiac causes and 38 patients had reinfarction. A significantly higher occurrence of transient VCG changes (QRS-VD, STC-VM, and ST-VM; p < 0.001) was seen in patients who died from cardiac causes or experienced either cardiac death or reinfarction at follow-up. The end value for QRS-VD was higher in patients who died from cardiac causes and correlated with the maximal value for creatine kinase when all patients were considered (r = 0.66; p < 0.001). Significantly lower mortality was seen in patients with VCG trend curves suggestive of coronary reperfusion (p < 0.01). In multivariate analysis, occurrence of transient changes in STC-VM, high QRS-VD end value, and VCG trend curves not suggestive of reperfusion gave additional prognostic information beyond that of age, gender, maximal creatine kinase value, heart size on chest x-ray, occurrence of ventricular fibrillation during hospitalization, and the inability to perform exercise tests. VCG monitoring during the first 24 hours of hospitalization for an AMI is a promising method for early detection of patients with increased risk for subsequent cardiac death or reinfarction.

Platelet aggregability in vivo is attenuated by verapamil but not by metoprolol 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 (Stroop's 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.

Prognostic implications of ambulatory myocardial ischemia and arrhythmias and relations to ischemia on exercise in chronic stable angina pectoris (the Angina Prognosis Study in Stockholm [APSIS]).

The prognostic significance of ambulatory ischemia, alone and in relation to ischemia during exercise was assessed in 686 patients (475 men) with chronic stable angina pectoris taking part in the Angina Prognosis Study In Stockholm (APSIS), who had 24-hour ambulatory electrocardiographic registrations and exercise tests at baseline (n = 678) and after 1 month (n = 607) of double-blind treatment with metoprolol or verapamil. Ambulatory electrocardiograms were analyzed for ventricular premature complexes and ST-segment depression. During a median follow-up of 40 months, 29 patients died of cardiovascular (CV) causes, 27 had a nonfatal myocardial infarction, and 89 underwent revascularization. Patients with CV death had more episodes (median 5 vs. 1; p<0.01) and longer median duration (24 vs. 3 minutes; p<0.01) of ST-segment depression than patients without events. For those who had undergone revascularization, the duration was also longer (12 vs. 3 minutes; p<0.05). In a multivariate Cox model including sex, history of previous myocardial infarction, hypertension, and diabetes, the duration of ST-segment depression independently predicted CV death. When exercise testing was included, ambulatory ischemia carried additional prognostic information only among patients with ST-segment depression > or =2 mm during exercise. When the treatment given and treatment effects on ambulatory ischemia were added to the Cox model, no significant impact on prognosis was found. Ventricular premature complexes carried no prognostic information. Thus, in patients with stable angina pectoris, ischemia during ambulatory monitoring showed independent prognostic importance regarding CV death. Ambulatory electrocardiographic monitoring and exercise testing provide complementary information, but only among patients with marked ischemia during exercise. Treatment reduced ambulatory ischemia, but the short-term treatment effects did not significantly influence prognosis.

Pharmacokinetics of felodipine and effect on digoxin plasma levels in patients with heart failure.

Some calcium antagonist drugs used in hypertension and cardiac diseases have been shown to increase plasma digoxin levels mainly as a result of reduced renal clearance. Felodipine is a new dihydropyridine calcium antagonist drug with cardiovascular effects, whose pharmacokinetics and effects on plasma digoxin levels have been studied in patients with left ventricular failure. 12 patients (11 men) on long term digoxin therapy were given 2.5 or 5 mg felodipine bid for 7 days followed by 1 week on 10mg bid. Plasma levels of digoxin and felodipine were measured before dosage and 30, 60 and 90 minutes and 2, 3, 4, 6, 8, 10 and 24 hours after the first dose and after 1 week of therapy (steady state). The area under plasma concentration versus time curve was calculated after the first dose and in steady state both for digoxin and felodipine. The absorption characteristics Cmax and Tmax were calculated both for felodipine and digoxin on the different felodipine doses. There was a linear relationship between dose and plasma level of felodipine. Plasma half-life in the 4- to 10-hour period of felodipine was 5.5 hours after a 10mg single dose, and 12 hours after 10mg bid. Felodipine 2.5mg, 5mg and 10mg all transiently increased peak plasma digoxin concentrations (by about 40%) at 1 hour after intake. Urinary excretion of digoxin during the day was unchanged, but impaired renal clearance may account for the transient increase in digoxin plasma level after felodipine.

Mononitrates as monotherapy in the prophylactic treatment of angina pectoris.

This article reviews the results of double-blind comparative studies on the therapeutic use of isosorbide 5-mononitrate as monotherapy in the prophylaxis of angina pectoris. Isosorbide 5-mononitrate appears at least as effective as the same dosage of isosorbide dinitrate and is probably superior to the calcium antagonists. Recent data have shown that isosorbide 5-mononitrate in a controlled-release formulation given once daily has a significantly better antianginal effect than placebo without inducing the development of tolerance.

Abrupt withdrawal of isosorbide 5-mononitrate (Imdur) after long term treatment in stable angina pectoris. A preliminary report.

32 patients with stable angina pectoris who had been receiving a controlled-release formulation Durules of isosorbide 5-mononitrate (Imdur) 60 to 120 mg daily with concomitant beta-blocker therapy for at least 1 year were entered into a study to evaluate possible rebound phenomena from the abrupt withdrawal of isosorbide 5-mononitrate and to determine whether nitrate tolerance had developed. Isosorbide 5-mononitrate was abruptly withdrawn and substituted with placebo for 2 weeks, after which the active drug was reintroduced. No deterioration of exercise performance could be detected during withdrawal of therapy, but an increase was seen after reinstitution. No tolerance was found for systolic blood pressure and ST segment changes or for the number of anginal attacks and short-acting glyceryl trinitrate tablets consumed. Three patients had to be hospitalised because of a sudden deterioration of symptoms on withdrawal of isosorbide 5-mononitrate. It was concluded that isosorbide 5-mononitrate in Durules has a beneficial effect and that tolerance does not appear to be clinically relevant.

Clinical experience with three different defibrillators for resuscitation of out of hospital cardiac arrest.

Three defibrillators, one manual and two different semiautomatic, were prospectively compared during a one year period for out-of-hospital use by ordinary ambulance personnel with short additional training. Eighty-three cardiac arrest patients were treated with one of two different semiautomatic defibrillators and 26 by an ordinary manual defibrillator. Twenty-nine were found in ventricular fibrillation. Five of these patients were successfully resuscitated and admitted for further hospital care, two survived to be discharged home. The semiautomatic defibrillators were found to be accurate in ECG interpretation, sensitivity and specificity was 100%, respectively, and both were equally effective in defibrillation. There were no differences in conversion rate or in the clinical outcome between the three defibrillators tested. Both semiautomatic defibrillators tested seemed to be safe, reliable and cost-effective. The low survival rate found is most certainly due to a long ambulance delay.

Metoprolol in acute myocardial infarction reduces ventricular arrhythmias both in the early stage and after the acute event.

Fifty three of the 5778 patients included in the MIAMI (Metoprolol in Acute Myocardial Infarction) trial were investigated with long-term ECG recordings in order to evaluate the effect of acute beta-blockade on premature ventricular complexes in and after acute myocardial infarction. Twenty five patients were given placebo and 28 metoprolol in a double-blind randomized fashion for 15 days. After this period the patients were put on open beta-blockade without breaking individual study codes. The mean number of premature ventricular complexes during the inclusion day (day 0) was the same in the two groups. The median numbers were also similar in the two groups: 190 and 154 in the placebo and metoprolol groups, respectively. Metoprolol significantly reduced the median number of premature ventricular complexes in the randomized period. The median numbers on days 1, 2 and 15 were 146, 101, 84 in the placebo group and 73, 59 and 10 in the metoprolol group, respectively (P less than 0.05). Also during the further follow-up, when investigated 1, 3 and 6 months after the infarction, the median number of premature ventricular complexes was lower in the metoprolol group (74, 257, 142 in the placebo group and 7, 5 and 11 in the metoprolol group, P less than 0.05). This indicates that metoprolol treatment in the acute phase of myocardial infarction reduces ventricular arrhythmias both in the early stage and also after the acute event.

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. The highest QTc values were registered in the CCU and the lowest at the 1-year control. Patients with subendocardial infarcts had longer QTc intervals than those with transmural infarcts, especially during the acute phase. Patients with inferior infarcts had shorter QTc intervals during the CCU period. Those who reinfarcted or died a cardiac death (particularly when sudden) during the follow-up year had longer QTc intervals during the post-CCU phase. A multivariate analysis of risk factors revealed that the QTc interval at discharge was of significant independent value for predicting major cardiac events after discharge from the hospital. It is concluded that repeated measurements of QTc may be of value when assessing prognosis after acute myocardial infarction.

The Swedish National Donor Register.

The large number of individuals who have registered with the National donor register indicates that the general public feels there is a need for such a register. It also indicates that the register is accepted by the general public. Considering that the Swedish transplant act is an opting out law, it was to be expected that those objecting to donation would be overrepresented as compared to their representation in the general public. This was confirmed when the opinions of the first 300,000 persons to register were compared to a survey of attitudes made at the same time. According to the guidelines for the medical profession issued by the Board, the Register always has to be consulted in the case of a potential donor. The Register is frequently consulted and found useful by the licensed procurement coordinators. The rulings of the Swedish Data inspection board are to be followed and any divergence will be noted and acted upon by the Board. The new legislation was proposed at a time when the number of cadaver donors was declining. The number of cadaver organ donors remains unchanged. It is concluded that it is for governments to decide on donor registers and for government agencies and professionals to design safe registries and continuously supervise how they are used. The Swedish National Donor Register is safe and operational.

Information on new transplant legislation: how it was received by the general public and the action that ensued.

The information campaign was successful. The leaflet was observed by many and discussed by two-thirds of those who had seen it, most often with relatives. All who have registered with the donor register have taken a stand on the donation of organs and tissues for transplantation or other medical purposes. Many more have probably signed donor cards or told the next of kin. It is suggested that the population has been properly informed. The number of cadaver donors, which has decreased the last number of years, seems to be unaffected.