D. Wayne Taylor

The North American Symptomatic Carotid Endarterectomy Trial: Surgical Results in 1415 Patients

BACKGROUND AND PURPOSE This study reports the surgical results in those patients who underwent carotid endarterectomy in the North American Symptomatic Carotid Endarterectomy Trial (NASCET). METHODS The rates of perioperative stroke and death at 30 days and the final assessment of stroke severity at 90 days were calculated. Regression modeling was used to identify variables that increased or decreased perioperative risk. Nonoutcome surgical complications were summarized. The durability of carotid endarterectomy was examined. RESULTS In 1415 patients there were 92 perioperative outcome events, for an overall rate of 6.5%. At 30 days the results were as follows: death, 1.1%; disabling stroke, 1.8%; and nondisabling stroke, 3.7%. At 90 days, because of improvement in the neurological status of patients judged to have been disabled at 30 days, the results were as follows: death, 1.1%; disabling stroke, 0.9%; and nondisabling stroke, 4.5%. Thirty events occurred intraoperatively; 62 were delayed. Most strokes resulted from thromboembolism. Five baseline variables were predictive of increased surgical risk: hemispheric versus retinal transient ischemic attack as the qualifying event, left-sided procedure, contralateral carotid occlusion, ipsilateral ischemic lesion on CT scan, and irregular or ulcerated ipsilateral plaque. History of coronary artery disease with prior cardiac procedure was associated with reduced risk. The risk of perioperative wound complications was 9.3%, and that of cranial nerve injuries was 8.6%; most were of mild severity. At 8 years, the risk of disabling ipsilateral stroke was 5.7%, and that of any ipsilateral stroke was 17.1%. CONCLUSIONS The overall rate of perioperative stroke and death was 6.5%, but the rate of permanently disabling stroke and death was only 2.0%. Other surgical complications were rarely clinically important. Carotid endarterectomy is a durable procedure.

Low-dose and high-dose acetylsalicylic acid for patients undergoing carotid endarterectomy: a randomised controlled trial *

BACKGROUND Endarterectomy benefits certain patients with carotid stenosis, but benefits are lessened by perioperative surgical risk. Acetylsalicylic acid lowers the risk of stroke in patients who have experienced transient ischaemic attack and stroke. We investigated appropriate doses and the role of acetylsalicylic acid in patients undergoing carotid endarterectomy. METHODS In a randomised, double-blind, controlled trial, 2849 patients scheduled for endarterectomy were randomly assigned 81 mg (n=709), 325 mg (n=708), 650 mg (n=715), or 1300 mg (n=717) acetylsalicylic acid daily, started before surgery and continued for 3 months. We recorded occurrences of stroke, myocardial infarction, and death. We compared patients on the two higher doses of acetylsalicylic acid with patients on the two lower doses. FINDINGS Surgery was cancelled in 45 patients, none were lost to follow-up by 30 days, and two were lost by 3 months. The combined rate of stroke, myocardial infarction, and death was lower in the low-dose groups than in the high-dose groups at 30 days (5.4 vs 7.0%, p=0.07) and at 3 months (6.2 vs 8.4%, p=0.03). In an efficacy analysis, which excluded patients taking 650 mg or more acetylsalicylic acid before randomisation, and patients randomised within 1 day of surgery, combined rates were 3.7% and 8.2%, respectively, at 30 days (p=0.002) and 4.2% and 10.0% at 3 months (p=0.0002). INTERPRETATION The risk of stroke, myocardial infarction, and death within 30 days and 3 months of endarterectomy is lower for patients taking 81 mg or 325 mg acetylsalicylic acid daily than for those taking 650 mg or 1300 mg.

IMPROVEMENT OF MEDICATION COMPLIANCE IN UNCONTROLLED HYPERTENSION

38 hypertensive Canadian steelworkers who were neither compliant with medications nor at goal diastolic blood-pressure six months after starting treatment were allocated either to a control group or to an experimental group who were taught how to measure their own blood-pressures, asked to chart their home blood-pressures and pill taking, and taught how to tailor pill taking to their daily habits and rituals; these men were also seen fortnightly by a highschool graduate with no formal health professional training who reinforced the experimental manoeuvres and rewarded improvements in compliance and blood-pressure. Six months later, average compliance had fallen by 1.5% in the control group but rose 21.3% in the experimental group. Blood-pressures fell in 17 of 20 experimental patients (to goal in 6) and in 10 of 18 control patients (to goal in 2).

Increased Absenteeism from Work after Detection and Labeling of Hypertensive Patients

A study of hypertension in an industrial setting allowed us to confirm and explore an earlier retrospective finding that the labeling of patients as hypertensive resulted in increased absenteeism from work. After screening and referral, we found that absenteeism rose (mean +/- 1 S.E.) 5.2 +/- 2.3 days per year (P less than 0.025); this 80 per cent increase greatly exceeded the 9 per cent rise in absenteeism in the general employee population during this period. The main factors associated with increased absenteeism were becoming aware of the condition (P less than 0.01) and low compliance with treatment (P less than 0.001). Subsequent absenteeism among patients unaware of their hypertension before screening was not related to the degree of hypertension, whether the worker was started on therapy, the degree of blood-pressure control achieved or exposure to attempts to promote compliance. These results have major implications for hypertension screening programs, especially since absenteeism rose among those previously unaware of their condition, regardless of whether antihypertensive therapy was begun.

Randomised clinical trial of strategies for improving medication compliance in primary hypertension.

230 Canadian steelworkers with hypertension took part in a randomised trial to see if compliance with antihypertensive drug regimens could be improved. For care and follow-up these men were randomly allocated to see either their own family doctors outside working-hours or industrial physicians during work shifts; the same men were randomly allocated to receive or not receive an educational programme aimed at instructing them about hypertension and its treatment. Surprisingly, the convenience of follow-up at work had no effect upon these mens compliance with antihypertensive drug regimens. Similarly, although men receiving health education learned a lot about hypertension, they were not more likely to take their medicine.

Further Evidence Relating Mitral-Valve Prolapse to Cerebral Ischemic Events

Echocardiography demonstrates prolapse of the mitral valve in at least 5 per cent of the population. Since some observations have linked this condition to stroke, we studied its incidence in two groups of patients with cerebral ischemia. The older group contained 141 patients over 45 years of age (mean, 64.7 years) who had transient ischemia or partial stroke. Prolapse was found in eight (5.7 per cent) of these patients and in 10 (7.1 per cent) of 141 age-matched controls. The second group contained 60 patients who had transient ischemia or partial stroke and were under 45 years old (mean 33.9 years). Prolapse was detected in 24 patients (40 per cent) but in only five (6.8 per cent) of 60 age-matched controls (mean age, 33.7 years). The odds ratio, 9.33, was highly significant (P less than 0.001). In six of the 24 patients there were other potential causes for cerebral ischemia leaving 18 whom the only recognizable potential cause was a prolapsing mitral valve (odds ratio, 7.00; P less than 0.001). This study suggests that this entity has a role in cerebral ischemia, at least in younger patients. (N Engl J Med 302:139-144, 1980).

A controlled trial of digoxin in congestive heart failure

Because of conflicting results from studies examining the usefulness of digoxin in congestive heart failure (CHF) patients in sinus rhythm, a cross-over trial was conducted in which 20 patients received 7 weeks of digoxin titrated to a level of 1.54 to 2.56 nmol/liter and 7 weeks of matched placebo. The order of treatments was determined by random allocation and patients, clinicians and research staff were blind to allocation. In patients with deteriorating condition, the treatment period was terminated and outcome measures were obtained. If deterioration occurred during the first period, the patient was crossed over without the code being broken. Seven patients required premature termination of study periods because of increasing symptoms of CHF. All 7 were taking placebo at the time (p = 0.016). Small differences in dyspnea (p = 0.044), walking test score (p = 0.055), clinical assessment of CHF (p = 0.036) and ejection fraction (p = 0.004) favored the digoxin treatment group. Patients with more severe CHF were more likely to benefit from digoxin administration. It was concluded that oral digoxin, in doses titrated to produce a serum level of 1.54 to 2.56 nmol/liter, improved quality of life and functional exercise capacity in some patients with CHF in sinus rhythm.

Should study subjects see their previous responses

To test the relative merits of administering questionnaires with previous responses available (the informed condition) or unavailable (the blind condition), we administered blind and informed versions of a quality of life questionnaire to two groups of patients. One, a group of 43 stable subjects with chronic cardiorespiratory disease, were seen three times at fortnightly intervals; a separate series of 13 patients with chronic lung disease were evaluated before and after optimization of therapy. In the stable patients the informed strategy resulted in substantial decrease in the variance in the measurement of dyspnea, fatigue, and of emotional function. Large improvements in dyspnea, fatigue, and emotional function seen in patients undergoing treatment optimization were comparable using blind and informed methods. These results suggest that by letting patients see their previous responses we can decrease the sample size needed to detect changes in quality of life in clinical trials.

Effects of labelling on income, work and social function among hypertensive employees☆

Two hundred and thirty hypertensive Canadian steelworkers were followed for 5 years after screening and referral. Data on income, absenteeism and measures of work and social function were collected on these men and on a matched group of 230 normotensive employees. In the fifth year after screening, hypertensive employees earned an average of Can.

Patient compliance with antihypertensive regimens

1093 less than normotensive employees despite similar incomes in the year before screening. This adverse effect on income was observed regardless of awareness of hypertension at the time of screening or compliance with treatment. Illness-related absenteeism among hypertensives rose in the year following screening and remained elevated for 4 years after screening. Normotensive and hypertensive employees reported similar levels of physical ability and psychological well-being. These findings need verification in other settings before inclusion in cost-effectiveness analyses of the management of hypertension.