Fixed minidose warfarin and aspirin alone and in combination vs adjusted-dose warfarin for stroke prevention in atrial fibrillation: Second Copenhagen Atrial Fibrillation, Aspirin, and Anticoagulation Study.

BACKGROUND: Despite the efficacy of warfarin sodium therapy for stroke prevention in atrial fibrillation, many physicians hesitate to prescribe it to elderly patients because of the risk for bleeding complications and because of inconvenience for the patients. METHODS: The Second Copenhagen Atrial Fibrillation, Aspirin, and Anticoagulation Study was a randomized, controlled trial examining the following therapies: warfarin sodium, 1.25 mg/d; warfarin sodium, 1.25 mg/d, plus aspirin, 300 mg/d; and aspirin, 300 mg/d. These were compared with adjusted-dose warfarin therapy (international normalized ratio of prothrombin time [INR], 2.0-3.0). Stroke or a systemic thromboembolic event was the primary outcome event. Transient ischemic attack, acute myocardial infarction, and death were secondary events. Data were handled as survival data, and risk factors were identified using the Cox proportional hazards model. The trial was scheduled for 6 years from May 1, 1993, but due to scientific evidence of inefficiency of low-intensity warfarin plus aspirin therapy from another study, our trial was prematurely terminated on October 2, 1996. RESULTS: We included 677 patients (median age, 74 years). The cumulative primary event rate after 1 year was 5.8% in patients receiving minidose warfarin; 7.2%, warfarin plus aspirin; 3.6%, aspirin; and 2.8%, adjusted-dose warfarin (P = .67). After 3 years, no difference among the groups was seen. Major bleeding events were rare. CONCLUSIONS: Although the difference was insignificant, adjusted-dose warfarin seemed superior to minidose warfarin and to warfarin plus aspirin after 1 year of treatment. The results do not justify a change in the current recommendation of adjusted-dose warfarin (INR, 2.0-3.0) for stroke prevention in atrial fibrillation.

Atrial fibrillation in the Wolff-Parkinson-White syndrome.

Atrial fibrillation in patients with Wolff-Parkinson-White (WPW) syndrome may lead to syncope, ventricular fibrillation, and sudden death. In a follow-up study of 241 patients with WPW syndrome in a relatively unselected population, 26 patients had documented atrial fibrillation (11%). These patients were followed up after 1-37 years (median 11 years; mean 15 years). During this period, 2 of 26 died suddenly. These 2 patients had the shortest RR interval during spontaneous atrial fibrillation (less than or equal to 220 msec), greater than or equal to 1 episodes of syncope, and a persistent delta wave in all available electrocardiograms. In comparison, sudden or tachycardia-related death was seen in 4 of the 241 patients. This difference is not statistically significant. Thus, atrial fibrillation of 26 patients with WPW syndrome was surprisingly well tolerated in our follow-up study with only 2 sudden deaths.

Non-invasive evaluation of the haemodynamic effects of amiodarone.

Sixteen patients were examined hemodynamically with echocardiography, calibrated apexcardiography, and systolic time intervals before treatment, after 1 week treatment with amiodarone 600 mg daily and after 2-4 months treatment with 300 mg daily. During the treatment thyroid function was controlled. The echocardiogram showed a small increase in shortening fraction, while left ventricular dimensions did not change significantly. The apexcardiogram revealed minor changes, which could not be interpreted as being due to changes in contractility. The systolic time intervals showed marked decreases in preejection period index and preejection period/left ventricular ejection time. These changes could not be correlated to changes in serum thyroxine, which was the only thyroid parameter to change significantly. The hemodynamic changes during amiodarone treatment were interpreted as mainly being due to a decrease in afterload while possible changes in preload and myocardial contractility were of minor importance.

Hepatic elimination of renin in man.

1. Hepatic elimination of renin was measured in 10 well-compensated cardiac patients with normal liver function during a control period and during a period of reduced hepatic plasma flow, induced by physical exercise (seven patients) or intravenous infusion of lysine vasopressin (three patients). 2. Hepatic renin elimination rate (hepatic plasma flow x arterial-hepatic vein difference of plasma renin activity) was found to be linearly correlated with arterial plasma renin activity (r = 0.986, P less than 0.001). 3. When hepatic plasma flow fell by 45% the hepatic extraction ratio of renin (arterial-hepatic vein plasma renin activity difference/arterial plasma renin activity) increased by 75%. Hepatic renin clearance (hepatic plasma flow x extraction ratio) remained constant. 4. The results indicate that changes in the hepatic elimination rate of renin do not contribute to changes in plasma renin activity during these events.

Renin release in relation to plasma noradrenaline during supine exercise in cardiac patients.

Plasma renin activity in the brachial artery and in the renal vein together with arterial noradrenaline concentration were determined repeatedly during and after 10 min of dynamic exercise in eight cardiac patients. Arterial renin increased slightly during exercise and gradually returned to control level after exercise. Renal vein renin increased markedly during exercise and returned to the resting value immediately after exercise, similarly to the changes in plasma noradrenaline and heart rate. A close temporal relationship between the changes in the renal veno-arterial renin difference, plasma noradrenaline and heart rate strongly suggests that the sympathetic nervous system is a major determinant of renin release in man during exercise.

Placebo-controlled, randomised trial of warfarin and aspirin for prevention of thromboembolic complications in chronic atrial fibrillation. The Copenhagen AFASAK study.

From November, 1985, to June, 1988, 1007 outpatients with chronic non-rheumatic atrial fibrillation (AF) entered a randomised trial; 335 received anticoagulation with warfarin openly, and in a double-blind study 336 received aspirin 75 mg once daily and 336 placebo. Each patient was followed up for 2 years or until termination of the trial. The primary endpoint was a thromboembolic complication (stroke, transient cerebral ischaemic attack, or embolic complications to the viscera and extremities). The secondary endpoint was death. The incidence of thromboembolic complications and vascular mortality were significantly lower in the warfarin group than in the aspirin and placebo groups, which did not differ significantly. 5 patients on warfarin had thromboembolic complications compared with 20 patients on aspirin and 21 on placebo. 21 patients on warfarin were withdrawn because of non-fatal bleeding complications compared with 2 on aspirin and none on placebo. Thus, anticoagulation therapy with warfarin can be recommended to prevent thromboembolic complications in patients with chronic non-rheumatic AF.

Chronic supraventricular tachycardia in infancy and childhood.

The results of a one to 19 year follow-up study of 9 children with supraventricular tachycardia of more than one month's duration are reported. The ECG diagnosis of tachycardia was made before birth in one patient and between the ages of 8 months and 12 years in 8. Four had sustained and 4 had repetitive tachycardia, while one patient had both patterns at different times. Reciprocal rhythm was diagnosed in 3 patients and exit block in 2. Severe symptoms had occurred in 2 patients, but as a rule symptoms were mild or absent. No treatment abolished the arrhythmias but digitalis reduced the overall ventricular rate in 6 patients. After a duration of 1-7 years, 3 patients still had tachycardia at the follow-up. In the remaining 6 patients the tachycardia had subsided 7 months to 10 years after the onset.

Congenital apical aneurysm of the left ventricle: surgical removal in two infants.

The case histories are described of 2 infants, representing either type of congenital apical left ventricular aneurysm. Case 1 had a finger-like, pulsatile, actively contracting aneurysm which was associated with a split distal end of the sternum and a ventral hernia. In contrast to most of the 55--60 cases hitherto described, no other cardiovascular anomalies were detected at heart catheterization with angiocardiography. The aneurysm was resected at the age of 23 days. Postoperative angiocardiography demonstrated a normal-sized left ventricle with good contractions and no residual aneurysm. He was last seen at the age of 15 mth, doing well. Case 2 had a noncontractile aneurysm and congenital pyloric stenosis, which hitherto has not been found in association with this type of aneurysm in the about 20 reported cases. The aneurysm was resected at the age of 9 mth; the estimated reduction of the left ventricular cavity was 20%. 1 yr after operation the patient was doing well, but the chest roentgenogram was unchanged and at angiocardiography the left ventricular appearance was largely unchanged compared to the preoperative findings. He was last seen at the age of 2 yr, doing well. The long-term prognosis in the latter type of aneurysm has still to be elucidated.

DC-conversion of atrial fibrillation after mitral valve operation. An analysis of the long-term results.

In a prospective study comprising 43 patients with atrial fibrillation after mitral valve surgery, an evaluation was made of the prognostic significance of clinical, radiological, haemodynamic and operative factors for the maintenance of sinus rhythm after DC-conversion. Atrial fibrillation with a duration of less than 12 months proved to be the only single factor of significance for sustained sinus rhythm after 12 months and it is suggested as a simple clinical criterion for selection of patients for DC-conversion after mitral valve operation.