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Biomedical subjects

C D Furberg

Publications and source records attributed to C D Furberg.

At least 181 records · Page 10Linked to original sources
PubMed1987

Overview of completed sudden death trials: US experience.

Ventricular arrhythmias are the major cause of death in patients with coronary heart disease. By suppressing the arrhythmias, antiarrhythmic agents have the theoretical potential of preventing sudden arrhythmic deaths. A large number of randomized, controlled clinical trials of these agents have been conducted during the early hospital phase after an acute myocardial infarction as well as after discharge. Included in this review are approximately 20 mortality trials of antiarrhythmic drugs, including beta blockers, which have been conducted in the United States and Australia. Results of the trials of antiarrhythmics reported to date have not demonstrated an effect on patient survival or risk of sudden death. Three possible explanations exist. First, these agents do not improve prognosis, which is contrary to massive evidence from animal, clinical, and epidemiologic studies. Second, drug treatment prolongs life, but benefit has not been observed in the trials. This explanation is plausible, since the completed trials have methodologic limitations. Third, control of ventricular arrhythmias helps some patients but harms others. Larger, properly designed trials are needed to resolve the uncertainty about the value of antiarrhythmics in the prevention of sudden death. The short- and long-term trials of beta blockers have documented an effect on survival. The benefit seems to be explained primarily through a reduction in sudden or instantaneous death. Whether this effect is mediated through a reduction in ventricular ectopies or an elevation of the fibrillation threshold is debated, as is the effect, if any, of beta-2 blockade on the incidence of ventricular fibrillation.

Adrenergic beta-Antagonists↗
PubMed1986

Prognostic value of exercise electrocardiogram in men at high risk of future coronary heart disease: Multiple Risk Factor Intervention Trial experience.

The prognostic value of the exercise electrocardiogram was examined in the 6,438 usual care men of the Multiple Risk Factor Intervention Trial in relation to fatal and nonfatal coronary heart disease events, rest electrocardiographic abnormalities and coronary heart disease risk factors. An abnormal response to exercise, defined as an ST depression integral of 16 microV-s or more, was observed in 12.2% of the men. There was a nearly fourfold increase in 7 year coronary mortality among men with an abnormal response to exercise compared with men with a normal ST segment in exercise (risk ratio 3.8, 95% confidence limits 2.5 to 5.5). The risk ratio for coronary death, adjusted for age, diastolic blood pressure, serum cholesterol and smoking status at baseline was 3.5, and the corresponding adjusted risk ratio for death from all causes was 1.6. A similar trend toward excess coronary events was seen for angina pectoris (risk ratio of 1.6). The trend was not significant for nonfatal myocardial infarction. Multivariate analyses indicated that the ST depression integral was a strong independent predictor of future coronary death (p less than 0.001). Men with an abnormal electrocardiogram at rest (mainly high amplitude R waves) and with an abnormal ST response to exercise had an over sixfold relative risk for coronary death compared with men with an abnormal electrocardiogram at rest and a normal ST response to exercise. These results suggest that exercise testing may be indicated for improved risk assessment and the assessment of the significance of minor rest electrocardiographic abnormalities in middle-aged men with elevated levels of coronary heart disease risk factors.

Adult↗
PubMed1986

Effect of propranolol in patients with myocardial infarction and ventricular arrhythmia.

The Beta-Blocker Heart Attack Trial was a placebo-controlled, randomized, double-blind clinical trial of the long-term administration of propranolol hydrochloride to patients who had had at least one myocardial infarction. Among 3,837 patients followed up for an average of 25 months, 3,290 (85.7%) had 24 hour ambulatory electrocardiograms performed at the baseline examination. Four classifications of arrhythmia were examined. One of these, the presence of complex ventricular arrhythmias (at least 10 ventricular premature beats/h, or at least one pair or run of ventricular premature beats or multiform ventricular premature beats) was the subgroup of major interest. Regardless of the classification, the presence of arrhythmia identifies a group of patients with a higher risk of total mortality, coronary heart disease mortality, sudden cardiac death and instantaneous cardiac death. The a priori subgroup hypothesis that sudden death would be preferentially reduced by propranolol in patients with complex ventricular arrhythmias was not supported. The relative benefit of propranolol in reducing sudden death for this subgroup was 28 versus 16% for the subgroup without ventricular arrhythmia (relative risk of 0.72 versus 0.84, a nonsignificant relative difference of 14%). There were similar findings for two of the three other classifications of arrhythmia and for the other response variables. Although propranolol does not appear to be of special relative benefit in patients with ventricular arrhythmia, the presence of the arrhythmia does identify a high-risk group. The mechanism by which propranolol reduces mortality is still unclear, but is probably not solely an antiarrhythmic one.

Adult↗
PubMed1986

Use of diuretics in treatment of hypertension in the elderly.

Men and women with isolated systolic hypertension who were at least 60 years of age were treated for 1 year with chlorthalidone (25-50 mg daily) or matching placebo as the step I drug. Most patients reached goal blood pressure without requiring a step II drug. The blood pressure response was similar in all age, sex and race subgroups, with an overall difference between the randomised groups of 17 mm Hg for systolic blood pressure (p less than 0.001) and 6mm Hg for diastolic blood pressure (p less than 0.001). The only common adverse effects were asymptomatic changes in the serum concentrations of potassium (0.5 mmol/L lower in the chlorthalidone group, p less than 0.001), uric acid (0.9 mg/dl higher, p less than 0.001), and creatinine (0.08 mg/dl higher, p = 0.02). Compliance was good, and more than 80% of participants were still taking the study medications at the end of the year.

Aged↗
PubMed1986

Relationship of blood pressure to coronary and stroke morbidity and mortality in clinical trials and epidemiological studies.

We compared pooled mortality and morbidity results from nine randomized trials of antihypertensive drug treatment (total n = 43,139), in which diastolic blood pressure (DBP) was reduced by a mean of 5.8 mmHg, with mortality and morbidity differences associated with the same DBP difference in two large prospective, observational studies [the follow-up study of the Multiple Risk Factor Intervention Trial (MRFIT) screenees and the Framingham Study]. These results indicate that the effect on stroke of BP reduction in the trials (-36%, 95% confidence interval +/- 10%) was about 80% of that estimated from the epidemiological studies, suggesting that the effects of long-term BP elevation on the cerebral vasculature are mostly reversible over 5-6 years of BP reduction. For coronary heart disease (CHD), the effect of BP reduction in the trials (-9 +/- 10%) was about 36% of that estimated from the epidemiological studies. This difference may reflect chronic processes involved in the pathophysiological association of BP with CHD; however, selective treatment of control patients at high risk of CHD and an adverse effect of diuretics on serum cholesterol may have influenced the effect of treatment in the trials.

Blood Pressure↗
PubMed1986

Systolic Hypertension in the Elderly Program, Pilot Study (SHEP-PS): morbidity and mortality experience.

SHEP-Pilot Study, a randomized, double-blind, placebo-controlled trial of drug therapy for isolated systolic hypertension, followed 551 participants aged 60 years or more with untreated blood pressures of greater than or equal to 160/less than 90 mmHg for an average of 34 months. Mean age was 72 years, 63% were female and 82% white. Pretreatment blood pressures averaged 172/75 mmHg. As their Step I drug, 443 participants were assigned chlorthalidone and 108 placebo. Of 512 surviving participants, 80% and 84% of the chlorthalidone and placebo groups, respectively, attended their last clinic visit; 71% and 60% were still taking blinded drug; and 60% and 33% had systolic blood pressures less than 160 mmHg. Final blood pressures averaged 140/67 and 154/72 mmHg for the chlorthalidone and placebo groups, respectively. All-cause mortality rates were 25 and 23 deaths per 1000 participant-years of risk, respectively; rates for 'definite' first strokes were 8.3 and 13 deaths. Differences between chlorthalidone and placebo groups were significant for blood pressure but not for event rates.

Aged↗
PubMed1985

Systolic Hypertension in the Elderly Program (SHEP): antihypertensive efficacy of chlorthalidone.

The Systolic Hypertension in the Elderly Program (SHEP) is a randomized, blinded test of the efficacy of antihypertensive drug treatment. In a large feasibility trial, 551 men and women who had isolated systolic hypertension and were at least 60 years old received chlorthalidone (25 to 50 mg/day) or matching placebo as the step I drug. After 1 year, 83% of the chlorthalidone group and 80% of the placebo group were still taking SHEP medications. Of those still taking chlorthalidone, 88% had reached goal blood pressure (BP) without requiring a step II drug, and most had responded to the lower dose (25 mg/day). The BP response was similar in all age, sex and race subgroups, with an overall mean difference between randomized groups of 17 mm Hg for systolic BP (p less than 0.001) and 6 mm Hg for diastolic BP (p less than 0.001). The only common adverse effects were asymptomatic changes in the serum levels of potassium (0.5 mEq/liter lower in the chlorthalidone group, p less than 0.001), uric acid (0.9 mg/dl higher, p less than 0.001) and creatinine (0.08 mg/dl higher, p = 0.02). This study indicates that chlorthalidone is effective for lowering BP in elderly patients with systolic hypertension and sets the stage for a larger trial of the effects of such treatment on the incidence of cardiovascular disease.

Aged↗
PubMed1985

Potential for altering the natural history of congestive heart failure: need for large clinical trials.

Congestive heart failure (CHF) is a major clinical and public health problem; moreover, its incidence is increasing. Once this syndrome is manifest, the mortality rate is very high. To date, none of the drugs available for its treatment has been shown to reduce mortality. It is theoretically possible that in patients with overt CHF, drug treatment may not alter prognosis. This hypothesis suggests that patients at high risk of heart failure should be treated before CHF becomes manifest. Alternatively, the trials of patients with manifest CHF may have been unpromising, simply because they were too small. These considerations indicate an urgent need for very large studies of both categories of patients--a "prevention" trial in those without overt CHF and a "treatment" trial in those with overt CHF.

Aged↗
PubMed1985

Drug treatment trials in hypertension: a review.

Thirteen controlled clinical trials (11 randomized) reporting morbidity and mortality results during 1960-1982 are summarized. Given the diverse design features, results are presented both for individual trials and for several combinations of similar studies, to provide more stable estimates of effects. Two of three trials in severe hypertension, while lacking enough events to evaluate effect on mortality, found significant reductions in "hypertensive" events, with the overall estimate being an 80% reduction. Similarly, combining six trials in less severe hypertension with untreated controls showed a 54% reduction in such events. The favorable trend in all-causes mortality from these trial results, whether viewed separately or in combination, was not significant. However, the findings from a large randomized trial with community controls, the Hypertension Detection and Follow-up Program, indicated significant reduction of all-causes mortality, the magnitude of which was consistent with the other trials. Outcomes of hypertensive participants in the Multiple Risk Factor Intervention Trial raised questions about mortality benefits in certain subgroups. These and other issues about patient benefit are further addressed with trial data and reference to the 1984 Report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. We note also 1) that evidence for reduction of coronary heart disease death or nonfatal myocardial infarction with antihypertensive drug treatment is weak, perhaps due to inadequate power to detect such a difference, and that data are limited regarding effects on quality of life. Nevertheless, the overall trial results provide strong support for drug treatment of severe hypertension, and for most individuals with less severe hypertension, when nonpharmacologic treatment will not suffice.

Adult↗
PubMed1985

Biologic determinants of propranolol disposition: results from 1308 patients in the Beta-Blocker Heart Attack Trial.

Our objective was to identify biologic determinants of propranolol serum levels in 1308 patients after myocardial infarction (MI). Patients had had their MI within the previous month. A steady-state propranolol dosage of 40 mg every 8 hours produced a mean trough concentration of 42 ng/ml with extremely great (fiftyfold) interindividual variability. Univariate and multivariate analyses suggested that this variability was the result of many biologic factors. Serum levels were higher in women, in older patients, and in patients receiving concomitant therapy with other antiarrhythmic drugs. Serum levels were also higher in patients with elevated serum creatinine and lactate dehydrogenase levels. Serum levels were lower in black patients than in white patients. Also, serum levels in smokers were lower than those in nonsmokers, but only markedly so in the outpatient setting (6 months after the MI). The influence of sex and race on drug disposition has not previously been reported for beta-blocking drugs. Although a genetic deficiency in the oxidative metabolism of propranolol has been indicated, the frequency distribution of serum propranolol levels did not demonstrate a bimodal distribution for genetically distinct populations.

Adult↗
PubMed1985

The Beta-blocker Heart Attack Trial.

The preventive effect of long-term beta-blocker therapy in patients who have survived the acute phase of myocardial infarction has been examined in several controlled clinical trials. The largest, the Beta-Blocker Heart Attack Trial, has convincingly demonstrated that propranolol in a daily dose of 180 to 240 mg given to patients without absolute or relative contraindications to the drug, prolongs life while producing moderate side effects. The predominant benefit appears to be in the first 12-18 months. The prime candidates for treatment seem to be patients at high risk, i.e. with complicated infarctions or complex arrhythmias. The likely mechanisms of action are anti-arrhythmic and anti-ischemic. Beta-2 blockade may be a contributing factor.

Adrenergic beta-Antagonists↗