Showing papers on "Randomized controlled trial published in 1985"

Ten-year results of a randomized clinical trial comparing radical mastectomy and total mastectomy with or without radiation

Abstract: In 1971 we began a randomized trial to compare alternative local and regional treatments of breast cancer, all of which employ breast removal. Life-table estimates were obtained for 1665 women enrolled in the study for a mean of 126 months. There were no significant differences among three groups of patients with clinically negative axillary nodes, with respect to disease-free survival, distant-disease--free survival, or overall survival (about 57 per cent) at 10 years. The patients were treated by radical mastectomy, total ("simple") mastectomy without axillary dissection but with regional irradiation, or total mastectomy without irradiation plus axillary dissection only if nodes were subsequently positive. Similarly, no differences were observed between patients with clinically positive nodes treated by radical mastectomy or by total mastectomy without axillary dissection but with regional irradiation. Survival at 10 years was about 38 per cent in both groups. Our findings indicate that the location of a breast tumor does not influence the prognosis and that irradiation of internal mammary nodes in patients with inner-quadrant lesions does not improve survival. The data also demonstrate that the results obtained at five years accurately predict the outcome at 10 years. We conclude that the variations of local and regional treatment used in this study are not important in determining survival of patients with breast cancer.

Expanding patient involvement in care. Effects on patient outcomes.

Abstract: An intervention was developed to increase patient involvement in care. Using a treatment algorithm as a guide, patients were helped to read their medical record and coached to ask questions and negotiate medical decisions with their physicians during a 20-minute session before their regularly scheduled visit. In a randomized controlled trial we compared this intervention with a standard educational session of equal length in a clinic for patients with ulcer disease. Six to eight weeks after the trial, patients in the experimental group reported fewer limitations in physical and role-related activities (p less than 0.05), preferred a more active role in medical decision-making, and were as satisfied with their care as the control group. Analysis of audiotapes of physician-patient interactions showed that patients in the experimental group were twice as effective as control patients in obtaining information from physicians (p less than 0.05). Results of the intervention included increased involvement in the interaction with the physician, fewer limitations imposed by the disease on patients' functional ability, and increased preference for active involvement in medical decision-making.

Efficacy of low-dose methotrexate in rheumatoid arthritis.

Abstract: Twenty-eight patients with refractory rheumatoid arthritis completed a randomized 24-week double-blind crossover trial comparing oral methotrexate (2.5 to 5 mg every 12 hours for three doses weekly) with placebo. The methotrexate group had significant reductions (P less than 0.01 as compared with the placebo group) in the number of tender or painful joints, the duration of morning stiffness, and disease activity according to physician and patient assessments at the 12-week crossover visit; reductions in the number of swollen joints (P less than 0.05) and 15-m walking time (P less than 0.03) also occurred. These variables, as well as the grip strength and erythrocyte sedimentation rate, showed significant (P less than 0.01) improvement at 24 weeks in the population crossed over to methotrexate. A significantly increased frequency (P less than 0.03) of the HLA-DR2 haplotype occurred in the eight patients with the most substantial response to methotrexate. Adverse reactions during methotrexate therapy included transaminase elevation (21 per cent), nausea (18 per cent), and diarrhea (12 per cent); one patient was withdrawn from the trial because of diarrhea. One patient died while receiving the placebo. Methotrexate did not affect measures of humoral or cellular immunity. We conclude that this trial provides evidence of the short-term efficacy of methotrexate in rheumatoid arthritis, but the mechanism of action is unknown. Longer trials will be required to determine the ultimate safety and effectiveness of this drug.

A randomized trial of coronary artery bypass surgery. Survival of patients with a low ejection fraction.

Abstract: The Coronary Artery Surgery Study (CASS) was designed to compare medical and surgical treatment of selected patients with chronic, stable coronary artery disease. This report concerns a subset of patients with reduced ventricular function. Of 780 patients randomly assigned to medical or surgical treatment, 160 had ejection fractions above 0.34 but below 0.50 at base line and have been followed for an average of seven years. Eighty-two patients were assigned to medical therapy, and 78 to surgery; the two groups were comparable at base line with regard to prognostically important variables. At seven years, 84 per cent of patients in the surgical group were alive, as compared with 70 per cent of the medical group (P = 0.01). Nearly half the patients with impaired ventricular function had triple-vessel disease at entry; at seven years, observed survival in this group was 88 and 65 per cent for those assigned to surgical and medical treatment, respectively (P = 0.009). Survival of patients with single-vessel or double-vessel disease was similar in the two treatment groups. We conclude that patients with triple-vessel disease and ejection fractions higher than 0.34 but lower than 0.50 appear to have improved seven-year survival with elective bypass surgery.

Extracorporeal circulation in neonatal respiratory failure: a prospective randomized study.

Abstract: A prospective controlled randomized study of the use of extracorporeal membrane oxygenation to treat newborns with respiratory failure was carried out using the "randomized play-the-winner" statistical method. In this method the chance of randomly assigning an infant to one treatment or the other is influenced by the outcome of treatment of each patient in the study. If one treatment is more successful, more patients are randomly assigned to that treatment. A group of 12 infants with birth weight greater than 2 kg met objective criteria for high mortality risk. One patient was randomly assigned to conventional treatment (that patient died); 11 patients were randomly chosen for extracorporeal membrane oxygenation (all survived). Intracerebral hemorrhage occurred in one of 11 surviving children. Extracorporeal membrane oxygenation allows lung rest and improves survival compared to conventional ventilator therapy in newborn infants with severe respiratory failure.

High-dose vitamin C versus placebo in the treatment of patients with advanced cancer who have had no prior chemotherapy. A randomized double-blind comparison.

Abstract: It has been claimed that high-dose vitamin C is beneficial in the treatment of patients with advanced cancer, especially patients who have had no prior chemotherapy. In a double-blind study 100 patients with advanced colorectal cancer were randomly assigned to treatment with either high-dose vitamin C (10 g daily) or placebo. Overall, these patients were in very good general condition, with minimal symptoms. None had received any previous treatment with cytotoxic drugs. Vitamin C therapy showed no advantage over placebo therapy with regard to either the interval between the beginning of treatment and disease progression or patient survival. Among patients with measurable disease, none had objective improvement. On the basis of this and our previous randomized study, it can be concluded that high-dose vitamin C therapy is not effective against advanced malignant disease regardless of whether the patient has had any prior chemotherapy.

Family management in the prevention of morbidity of schizophrenia: Clinical outcome of a two-year longitudinal study.

Abstract: • Environmental stress may contribute to the clinical morbidity of established cases of schizophrenia treated with optimal neuroleptic drugs. A family-based approach that aimed to enhance the problem-solving capacity of the index patient and his family caregivers was compared with a patientoriented approach of similar intensity over a two-year period. Thirty-six patients who returned to stressful parental households after florid episodes of schizophrenia (CATEGO andDSM-III) were stabilized with optimal neuroleptics before being randomly assigned to family or individual therapy in a comprehensive community management program. After nine months, family-managed patients had fewer exacerbations of schizophrenia, lower ratings of schizophrenic psychopathology, fewer hospital admissions, and a trend toward lower deficit symptoms and reduced neuroleptic dosage. This reduced clinical morbidity was sustained throughout the second year of less intensive follow-up. The relative efficacy of the family approach in this clinical management study did not appear to be due to prognostic factors, rater bias, stressful life events, or the effectiveness of pharmacotherapy. Definitive tests of these findings with respect to efficacy require further well-designed studies.

A perspective on the three large multicenter randomized clinical trials of coronary bypass surgery for chronic stable angina.

Abstract: Myocardial ischemia is an important determinant of survival in patients with coronary artery disease (CAD) and it may be silent. Coronary bypass surgery (CBS) is more effective than medical treatment in the relief of myocardial ischemia, anginal pain, and of events that are related to myocardial ischemia such as episodes of angina and left ventricular dysfunction caused by ischemia. Patients with chronic, stable angina assigned to CBS have an improved survival if they have left main CAD, three-vessel CAD with normal or impaired left ventricular function, proximal left anterior descending CAD that is part of two-vessel CAD, or two- or 3-vessel CAD with a positive exercise test for ischemia. In other respects, patients assigned to medical therapy fare as well as or better than those assigned to surgical therapy. Many issues that cause concern with regard to the randomized trials were considered in detail. The greatest problems are biostatistical tenets, small numbers of patients randomized in many of the subgroups, physician bias before and after randomization, crossovers, and inappropriate conclusions and unjustified extrapolations of the results. Timely, detailed, and comprehensive publication of the methods and results of these clinical trials is necessary. Meticulous, detailed, and critical reading of all of the published data is urged.

Field evaluation of vaccine efficacy.

Abstract: This paper describes the epidemiological techniques available for measuring vaccine efficacy and recommends a practical approach to their use. The efficacy of vaccines in clinical use can be determined by a variety of means including screening outbreak investigations secondary attack rates in families or clusters vaccine coverage assessment and case-control studies. They all offer a means of monitoring vaccine programs under conditions of day-to-day vaccine use. A table summarizes the different techniques for measuring efficacy. The screening technique is the most useful and rapid means of determining whether there is a problem with a vaccine. All that is required is a reliable estimate of the proportion of cases occurring in vaccinated individuals and an estimate of the vaccine coverage in the population at risk. If the estimated efficacy is within expected limits more detailed studies are not warranted. If the results suggest low efficacy more rigorous methods are necessary to assess the efficacy more accurately. Of the more accurate methods available outbreak investigation offers the simplest means of measuring vaccine efficacy and is the preferred technique if the situation permits. The biases inherent in the method can be minimized particularly if the disease incidence rate is high during the outbreak and accurate records exist. In large populations the underlying immunization status prior to the outbreak can be estimated using the same cluster sampling method used in coverage assessments. Calculation of secondary attack rates in families is also an excellent and accurate means of measuring vaccine efficacy and is an acceptable alternative to the outbreak investigation. Vaccine coverage methods in endemic areas are best suited to urban areas where the measles incidence rate is high after age 11 months and low before 12 months and maternal histories of disease are thought to be accurate. Case-control studies are best suited to areas where reliable personal immunization records may be difficult to find but other information such as clinic records may be available. No epidemiological method is perfect because it cannot exactly duplicate the experimental conditions of a prospective randomized clinical trial. The most accurate results will be obtained when biases are anticipated and corrective measures are taken whenever possible. Clinical vaccine efficacy determinations are carried out in order to assess whether the observed pattern of illness is consistent with the proper use of a highly effective vaccine. The components of a vaccine efficacy evaluation -- case definition case ascertainment and vaccination status determination -- apply to studies on all vaccines.

The western Washington randomized trial of intracoronary streptokinase in acute myocardial infarction. A 12-month follow-up report.

Abstract: After cardiac catheterization and coronary arteriography, 134 patients who had had an acute myocardial infarction were randomly assigned to treatment with intracoronary streptokinase (4000 U per minute, begun approximately 4 1/2 hours after the onset of symptoms, for a total of 286,000 +/- 77,800 U over 72 +/- 24 minutes); 116 control patients received standard care after they returned to the coronary care unit, immediately after angiography. Preliminary results of this trial have been published in the Journal (1983; 309:1477-81). During the first 30 days, 5 deaths occurred in the streptokinase group and 13 occurred in the control group (3.7 vs 11.2 per cent, P = 0.02); during the first year, the corresponding figures were 11 and 17 deaths (8.2 vs. 14.7 per cent, P = 0.10). However, when a minor imbalance in the ejection fraction and infarct location between the two groups was adjusted by logistic regression, the difference in one-year mortality became significant (P = 0.03). In the streptokinase group, 2 of the 80 patients in whom perfusion was reestablished (2.5 per cent) had died by one year, whereas 3 of the 13 with partial reperfusion (23.1 per cent) and 6 of the 41 with no reperfusion (14.6 per cent) had died (P = 0.008). Mortality among patients with partial reperfusion was not significantly different from that among those without reperfusion (P greater than 0.90). No base-line clinical, angiographic, or hemodynamic variable was predictive of successful reperfusion, according to univariate and multivariate analyses. We conclude that intracoronary streptokinase reduces one-year mortality among patients with acute myocardial infarction, but this improvement occurs only among those in whom thrombolysis results in coronary artery reperfusion.

A controlled trial of social intervention in the families of schizophrenic patients: two year follow-up.

Abstract: The two-year follow-up results are reported of a trial of social intervention in families of schizophrenic patients in high social contact with high-expressed emotion (EE) relatives. For those patients who remained on antipsychotic medication throughout the two years, the social intervention significantly reduced the relapse rate. In those experimental families where relatives' EE and/or face-to-face contact was lowered, the relapse rate was 14% compared with 78% for control patients on regular medication (P = 0.02).

Prognostic Importance of the White Blood Cell Count for Coronary, Cancer, and All-Cause Mortality

Abstract: The relationship of white blood cell count (WBC) to fatal and nonfatal coronary heart disease (CHD) incidence and all-cause and cancer mortality was assessed in a subset of participants in the Multiple Risk Factor Intervention Trial (MRFIT). For this group of 6,222 middle aged men, total WBC count was found to be strongly and significantly related to risk of CHD, independent of smoking status. Change in WBC count from baseline to the annual examination just prior to the CHD event was found to be a significant and independent predictor of CHD risk. For each decrease in WBC count of 1,000/cu mm the risk for CHD death decreased 14%, controlling for baseline WBC count and other CHD risk factors (smoking, cholesterol level, diastolic blood pressure). The WBC count was strongly related cross-sectionally to cigarette smoking and smoking status as indicated by serum thiocyanate concentration. Smokers on average had a WBC count of 7,750/cu mm compared with 6,080/cu mm for nonsmokers. The WBC count was also significantly associated with cancer death, independent of reported smoking and serum thiocyanate levels. (JAMA1985;254:1932-1937)

Effects of aerobic exercise on depression: a controlled study.

Abstract: Rejection of catheters is generally thought to be due to patients pulling out their catheters, but we found circumstantial evidence for this in only one third of cases. Some catheters with smaller balloons drop out spontaneously, perhaps owing to laxity of the pelvic floor or urethral dilatation caused by repeated catheterisation, and others are expelled forcibly, presumably owing to uninhibited contractions of the bladder. Urinary catheters may therefore drop out, be pushed out, or be pulled out. The life expectancy of catheters in this group of patients suggests the type of catheter that should be used. We recommend cheaper latex catheters and think that expensive \"long life\" silicon catheters are inappropriate in most long stay patients. Rejection of catheters is common in poorly mobile old people with cognitive impairment. It is associated with urethral trauma and may result in septicaemia. Long term catheterisation should therefore be considered only when other methods to promote continence and provide comfort have failed.3 Further work is needed to determine why some patients pull out their catheters and whether bladder stabilising drugs might reduce episodes of spontaneous rejection of catheters.

Treatment with histamine H2 antagonists in acute upper gastrointestinal hemorrhage. Implications of randomized trials.

Abstract: Histamine H2 antagonists are widely used in treating patients with hematemesis and melena, despite the lack of reliable evidence of benefit from any of the randomized trials, considered separately. Examination of the data from all 27 available randomized trials, in which over 2500 patients were entered, suggests that treatment may reduce the rates of rebleeding, surgery, and death by about 10, 20, and 30 per cent, respectively, although these results were only marginally significant for surgery and death. Any benefit appeared to be confined to patients with bleeding gastric ulcers, but since this subgroup analysis was prompted by preliminary examination of the data in some of the individual trials reviewed here, it should be treated with particular caution. The implications of this overview are that treatment with histamine H2 antagonists appears to be moderately promising, but its effects on important end points, such as death, still need to be assessed reliably. Prevention of "only" about 20 per cent of all deaths could well be worthwhile, for the condition is common, and the treatment widely practicable. To detect such a moderate effect reliably, however, might require the randomization of 10,000 patients (or more), which would be possible only in an extremely simple multicenter collaborative trial.

Dietary therapy slows the return of hypertension after stopping prolonged medication.

Abstract: This study asks whether prolonged antihypertensive therapy will "cure" a substantial percent of rigorously treated hypertensive patients and whether nutritional change will add an antihypertensive effect and reduce the relapse rate Of 584 eligible patients normotensive while receiving therapy, 496 were randomized into control and discontinued-medication groups with and without dietary intervention At 56 weeks, 50% of those who were no longer receiving medication remained normotensive by study criteria Randomization either to weight-loss group (mean loss of 45 kg [10 lb]) or to sodium-restriction group (mean reduction of 40 mEq/day) increased the likelihood of remaining without drug therapy, with an adjusted odds ratio of 217 for the sodium group and 343 for the weight group Highest success rates were in the nonoverweight mild hypertensives with sodium restriction (78%) and the overweight mild hypertensives who were reducing their weight (72%) These data demonstrate that weight loss or sodium restriction, in hypertensives controlled for five years, more than doubles success in withdrawal of drug therapy ( JAMA 1985;253:657-664)

A reevaluation of nonhormonal cytotoxic chemotherapy in the treatment of prostatic carcinoma.

Abstract: The palliative role of nonhormonal cytotoxic chemotherapy in the treatment of endocrine-resistant prostatic carcinoma has not been established. Conventional means of quantifying tumor response are most frequently not applicable in this disease because of the lack of measurable objective parameters to allow for a reliable estimation of antitumor effects. While this problem is not unique to prostatic carcinoma, this review illustrates its magnitude in this disease. Only approximately 5% of patients studied fulfill the various criteria for complete response (CR), partial response (PR), or both, while the vast majority of patients reported as responders are actually in the stable disease category. Stable disease is highly questionable as an indicator of antitumor response and should not be used as a criterion for response in conventional phase II studies unless it is convincingly demonstrated that it occurs as a result of treatment. A study design that may allow a more reliable assessment of the value of the stable disease category is described in the text. More effective means for assessing tumor responses and better instruments to measure aspects of quality of life are needed. Review of several prospective randomized clinical trials showed that no treatment program tested during the last decade resulted in a survival advantage when compared with a concurrently treated control group. Furthermore, in two such trials, four different single chemotherapeutic agents widely used in the treatment of this disease (cyclophosphamide, 5-fluorouracil, estramustine phosphate, and streptozocin) either alone or in combination, did not produce any prolongation of survival when compared to a no chemotherapy (standard treatment) control arm. Survival curves for endocrine-resistant patients fall within a relatively narrow and possibly predictable range that may be used as an additional endpoint in conjunction with response (CRs and PRs only) in phase II trials. More definitive evidence of therapeutic efficacy in this disease should derive from phase III trials using survival as one of the major endpoints. Because of the poor results observed with chemotherapy thus far, we suggest that the appropriate control arm for phase III testing in endocrine-resistant patients continues to be a no chemotherapy control arm consisting of a best symptomatic care or a uniformly applied second-line endocrine manipulation.

The significance of intensity of rehabilitation of stroke--a controlled trial.

Abstract: Of the 373 stroke patients 95 were admitted to the feasibility study of stroke rehabilitation. The patients were divided into two groups, an intensive and a normal treatment group. In this study, the functional recovery of stroke, measured by ADL and motor function was significantly better in the intensive treatment group. There was no difference in institutionalization or incidence of death between the groups. The gain of ADL and motor function was greatest during the first three months after stroke in the intensive treatment group. The conclusion is that intensified physiotherapy seems to improve the functional recovery of stroke patients.

A randomized controlled study of a home health care team.

Abstract: This report describes the findings of a randomized study of a new team approach to home care for homebound chronically or terminally ill elderly. The team includes a physician, nurse practitioner, and social worker delivering primary health care in the patient's home, including physician house calls. Weekly team conferences assure coordination of patient care. The team is available for emergency consultation through a 24-hour telephone service. The team physician attends to the patient during necessary hospitalizations. This approach was evaluated in a randomized experimental design study measuring its impact on health care utilization, functional changes in patients, and patient and caretaker satisfaction. The team patients had fewer hospitalizations, nursing home admissions, and outpatient visits than the controls. They were more often able to die at home, if this was their wish. As expected, they used more in-home services, measured in weighted cost figures; their overall cost was lower than their controls, but the difference was not statistically significant. Their functional abilities did not change differently from the controls, but they, and especially their informal caretakers in the home, expressed significantly higher satisfaction with the care received.

The evolution and summary results of the Stanford randomized clinical trials of the management of Hodgkin's disease: 1962-1984.

Abstract: This is a summary report of the Stanford randomized clinical trials of the management of Hodgkin's disease, initiated in 1962. There have been four major changes in the treatment protocols during this 22 year period. Between 1962-67, 132 patients with CS I, II and III disease were enrolled on various radiation trials. Between 1968-74, 367 patients were enrolled on studies primarily evaluating the role of adjuvant MOPP chemotherapy. Between 1974-80, variations in the chemotherapy regimen and the sequences of the combined modality programs were studied. The current studies, initiated in 1980, have enrolled 102 patients, and test a new mild adjuvant chemotherapy, VBM, (vinblastine, bleomycin and methotrexate) and utilizes ABVD in combined modality and alternating regimens. During the two decades of these studies, involving more than 800 patients, the initial remission rate and duration and the survival of all patients treated have progressively improved.

Selection, follow-up, and analysis in the Health Insurance Plan Study: a randomized trial with breast cancer screening.

Abstract: Critical decisions made 20 years ago by those who planned the randomized trial at the Health Insurance Plan (HIP) of Greater New York to determine the efficacy of periodic screening for breast cancer are detailed. These decisions affected the age group to be screened, screening modalities, frequency of screening, sample size, primary measures for testing efficacy, and period of follow-up (long term). Results of follow-up, 16 years after entry, indicate that mortality due to breast cancer continues to be lower among study women than controls. Numerically, the differential has been stable; relatively, it has decreased. It is estimated that the study group would have experienced about a 30% reduction in breast cancer mortality if screening had been maintained. Relative case survival rates over a 14-year period after diagnosis show changes in contours of trend lines that result from screening. The study group's trend is slightly concave in contrast to the usual convex curve for the controls. The contour of the curve is more decidedly concave among subjects detected through mammography alone than for other subgroups detected through screening, although the relative survival rate remains highest in the mammography only group. Uncertainty persists about effects of screening in the HIP study on breast cancer mortality among women aged 40-49 years at entry.

Prospectively randomized trial of adjuvant active-specific immunotherapy for human colorectal cancer.

Abstract: Over the last four years a guinea pig model of active-specific immunotherapy (ASI) with a syngeneic tumor celhbacillus calmette-Guerin (BCG) vaccine was translated into a prospectively randomized, controlled clinical trial in patients with colorectal cancer. Primary tumors from patients undergoing standard surgical resection were dissociated enzymatically and cryopreserved by techniques that maintain cell viability. Patients with transmural extension of tumor or nodal metastases were randomized into groups treated by resection alone (control) or resection plus ASI. With a mean follow-up of 28 months (range, 14–24), only 3 of 20 treatment patients had recurrences and none have died, whereas 9 of 20 control patients had recurrences and 4 died. These differences are statistically significant and are sufficiently encouraging to warrant expansion of these studies into other research centers. Cancer 55:1236-1243, 1985.

Some unexpected lessons from large multicenter randomized clinical trials.

Abstract: RANDOMIZATION is considered to have started' with the report of Fisher and MacKenzie in 1923 on agricultural experiments carried out by T. Eden on the effect of manure on the crops of different potato varieties.2 Feinstein states, \"The modem era of biostatistically planned randomized trials occurred in 1947, when streptomycin was evaluated in the treatment of tuberculosis.\"' Other subsequent triumphs of randomized trials for example, penicillin for prevention of recurrences of rheumatic fever and the Veterans Administration study of drug treatment of hypertension3 4

Lack of effect of oral magnesium on high blood pressure: a double blind study.

Abstract: Seventeen unselected patients with mild to moderate essential hypertension and whose average supine blood pressure after two months' observation with no treatment was 154/100 mm Hg were entered into a double blind randomised crossover study of one month's treatment with magnesium aspartate (15 mmol magnesium/day) and treatment with placebo for a further month. This preparation of magnesium was well tolerated and did not cause diarrhoea. Despite a significant increase in plasma magnesium concentration and a significant increase in urinary excretion of magnesium while taking magnesium aspartate there was no fall in blood pressure compared with either treatment with placebo or values before treatment. The results provide no evidence for a role of dietary magnesium in the regulation of high blood pressure and are contrary to recent speculations.

Multifactorial primary prevention of cardiovascular diseases in middle-aged men. Risk factor changes, incidence, and mortality.

Abstract: In a randomized five-year multifactorial primary prevention trial of vascular diseases, hyperlipidemias, hypertension, smoking, obesity, and abnormal glucose tolerance of the high-risk test group (n=612 men) were treated with dietetic-hygienic measures and hypolipidemic (mainly probucol and clofibrate) and antihypertensive (mainly diuretics and β-blockers) agents. A matched high-risk control group (n=610) and a low-risk control group (n=593) were not treated. The program markedly improved the risk factor status, yet the five-year coronary incidence tended to be higher in the intervention group than in the control group (3.1% vs 1.5%), while the stroke incidence was significantly reduced (1.3% vs 0%). The coronary events tended to be accumulated in subgroups treated with β-blocking agents or clofibrate, but there were few in those receiving probucol or diuretics. Thus, the intervention program significantly reduced development of stroke, but the occurrence of cardiac events was not prevented. Possible adverse drug effects offsetting the probable benefit of improved risk profile are not excluded. (JAMA1985;254:2097-2102)