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Biomedical subjects

C D Furberg

Publications and source records attributed to C D Furberg.

At least 163 records · Page 9Linked to original sources
PubMed1989

Controlled clinical trials of drug treatment for hypertension. A review.

We reviewed the designs and major results of 17 large-scale, controlled, clinical trials that reported the effects of drug treatment for hypertension on morbidity or mortality. Seven trials conducted in study populations with more-severe hypertension (diastolic blood pressures 100-120 mm Hg or higher), including the more-severe stratum of the Veterans Administration Trial, showed large reductions in stroke, other "hypertensive" events, and, in one trial, total mortality. Of 11 trials in populations with less-severe hypertension (diastolic blood pressures predominantly below 105 mm Hg), including the less-severe stratum of the Veterans Administration Trial, nine met the criteria for pooling of results. Among the aggregate 43,000 patients in the nine trials who were followed up for an average of 5.6 years, mean diastolic blood pressure reduction was 5.8 mm Hg, and a significant 11% reduction in total mortality was observed. This benefit was largely attributable to a 38% reduction in fatal strokes; nonfatal strokes were similarly reduced. Coronary heart disease mortality was 8% lower in drug treatment than in control groups, but this difference was not significant. A similar result was observed for combined coronary mortality and nonfatal myocardial infarction. A possible explanation for the inconclusive result regarding coronary end points was an adverse trend, observed in several trials, in a subgroup with baseline resting electrocardiographic abnormalities. Because all the trials except the propranolol arm of the Medical Research Council trial used drug regimens based on thiazide-like diuretic agents, and because there are now several new drug classes proposed as initial therapy, additional large-scale clinical trials may need to be considered.

Antihypertensive Agents↗
PubMed1989

Diuretic agents versus beta-blockers. Comparison of effects on mortality, stroke, and coronary events.

Three recently concluded large randomized clinical trials have compared the preventive effects of diuretic agents and beta-blockers in the treatment of approximately 22,000 subjects with hypertension. In the Medical Research Council trial, bendrofluazide (10 mg daily) was compared with a dose of propranolol (as much as 240 mg daily), a nonselective beta-blocker without intrinsic sympathomimetic activity. Two selective beta-blockers, atenolol (100 mg daily) and metoprolol (200 mg daily), were compared with bendrofluazide (5-10 mg daily) and hydrochlorothiazide (50-100 mg daily) in the Heart Attack Primary Prevention in Hypertension trial. In the International Prospective Primary Prevention Study in Hypertension, 160 mg of slow-release oxprenolol, a beta-blocker with intrinsic sympathomimetic activity, was compared with a diuretic-based regimen not containing beta-blockers. In each trial, similar reductions in mean diastolic blood pressure were achieved with diuretic and beta-blocker treatment that lasted for several years. All-cause mortality and fatal and nonfatal stroke and coronary event rates were also similar in the treatment groups. Thus, it appears that beta-blockers are as effective as diuretic agents in improving survival and in preventing major morbid events. Regarding cigarette smoking and stroke incidence, observations based on post hoc subgroup analyses of the Medical Research Council trial were not supported by subgroup findings in the Heart Attack Primary Prevention in Hypertension and the International Prospective Primary Prevention Study in Hypertension trials, and these observations should not form the basis for any treatment recommendations.

Adrenergic beta-Antagonists↗
PubMed1989

Morbidity and mortality in the Systolic Hypertension in the Elderly Program (SHEP) pilot study.

The pilot study of the Systolic Hypertension in the Elderly Program was a randomized, double-blind, placebo-controlled trial of drug therapy for isolated systolic hypertension. It followed 551 elderly participants with untreated blood pressures of greater than 160/less than 90 mm Hg for an average of 34 months. Mean age of the participants was 72 years; 63% were women, and 82% were white. Pretreatment blood pressures averaged 172/75 mm Hg. Participants were randomly assigned to treatment with chlorthalidone or placebo as Step I medication. Blood pressures at annual visits averaged 141/68 and 157/73 mm Hg for the drug-treated and placebo-treated groups, respectively, with 60% and 33% of the survivors on blinded medication having systolic blood pressures of less than 160 mm Hg at their last annual visit. All-cause mortality rates for the drug-treated and placebo-treated groups were 25.4 and 22.7 deaths per 1,000 participant-years of risk, and rates for definite "first stroke" were 8.3 and 12.8 per 1,000 years of risk. Differences between groups were significant for systolic and diastolic blood pressure but not for death or stroke rates. A full-scale study has begun to determine the effects of drug therapy for isolated systolic hypertension on stroke and mortality rates.

Antihypertensive Agents↗
PubMed1989

The Systolic Hypertension in the Elderly Program (SHEP): an intervention trial on isolated systolic hypertension. SHEP Cooperative Research Group.

The Systolic Hypertension in the Elderly Program (SHEP) is a randomized double-blind placebo-controlled trial to determine if antihypertensive treatment of isolated systolic hypertension (ISH) [systolic blood pressure (SBP) greater than or equal to 160 mmHg, diastolic blood pressure (DBP) less than 90 mmHg] reduces the 5 year incidence of fatal and nonfatal stroke. Between March 1, 1985 and January 15, 1988, 4736 persons (target 4800) with ISH, age 60 years and over, were enrolled. Potential participants met blood pressure (BP) and age criteria. Those on antihypertensive medication prior to enrollment without documented diastolic hypertension had their medication tapered and discontinued, and then met BP criteria (33% of cohort). Stepped-care therapy with chlorthalidone and atenolol (alternative, reserpine) or matching placebos was initiated as first and second steps. At baseline the trial population was 43.1% male, 56.9% female; 13.9% black, 86.1% non-black. Also, the mean age was 71.6 years; the mean SBP was 170.3 mmHg and the mean DBP was 76.6 mmHg; 59.8% had codeable resting electrocardiographic abnormalities. The trial is now in follow-up phase with scheduled termination in 1991.

Aged↗
PubMed1989

Beta-adrenergic blockers in patients with acute myocardial infarction.

Beta-blockers given within the first 24 hours of an acute MI, first as an intravenous bolus followed by oral therapy, have been shown to reduce in-hospital mortality following a myocardial infarction. For the long-term, beta-blockers represent the only documented effective prophylactic treatment for MI patients. The reduction in all-cause mortality is due primarily to a reduction in atherosclerotic cardiovascular deaths, particularly sudden cardiac deaths. This finding is consistent with the experimental observation that beta-blockers raise the threshold for ventricular fibrillation. Indeed, MI patients with complex ventricular arrhythmias respond very favorably to beta-blockers. However, reductions in nonsudden deaths and nonfatal reinfarctions have also been observed, suggesting that the beneficial effects of beta-blockers are not limited to antiarrhythmic effects alone and that these drugs may also have anti-ischemic effects. The prime candidates for beta-blocker therapy are the high-risk MI patients with transient electrical and/or pump complications during the acute phase. If therapy is initiated within hours of an acute infarction, it seems reasonable to continue it after hospital discharge. Evidence from the large, long-term trials suggest that, in the absence of any troublesome adverse reaction and given that most post-MI patients experience ventricular arrhythmias and angina, it seems reasonable not to limit the duration of treatment.

Adrenergic beta-Antagonists↗
PubMed1988

Effect of drug therapy on survival in chronic congestive heart failure.

A review of the current evidence on the effects of various agents on survival among patients with congestive heart failure (CHF) suggests that angiotensin-converting enzyme inhibitors probably offer the greatest potential for benefit. Trials undertaken before the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS) revealed favorable trends among patients in New York Heart Association functional classes II to IV who received angiotensin-converting enzyme inhibitors. Data from CONSENSUS clearly demonstrate that enalapril reduces mortality rates among patients in New York Heart Association class IV, but conclusions regarding effects in patients with mild or moderate CHF must await the results of future studies. In contrast, the large data base on alpha-adrenergic blockers suggests that these drugs are not likely to improve survival. Information on inotropic agents is sparse, but it is possible that these drugs may not improve survival and, in fact, may have a harmful effect. Mortality data on CHF patients treated with beta blockers and calcium channel blockers are likewise limited; conclusions concerning effects on survival must be postponed until further studies are conducted. Many of the investigations undertaken thus far to examine survival in patients with CHF have been small and of short duration, so any comparisons of the effects of various drugs must be interpreted with caution.

Adrenergic beta-Antagonists↗
PubMed1988

The secondary prevention trials. Lessons learned, questions raised.

In clinical trials to date, only two types of treatment have been shown to have a positive effect on survival in patients after acute myocardial infarction: beta blockers in acute-phase as well as long-term therapy and thrombolytic agents administered within three to four hours of the onset of symptoms. The favorable trial results from these interventions have raised new questions of scientific and clinical significance. What is the mechanism of the favorable action? Do all patients stand to benefit from treatment? What is the optimal time for initiation of treatment? How long is the treatment beneficial? What are the risks and costs? What is the public health impact of widespread use of these interventions?

Acute Disease↗
PubMed1988

The systolic hypertension in the elderly pilot program: methodological issues.

The Systolic Hypertension in the Elderly Program (SHEP) Pilot Study was conducted to determine the feasibility of conducting a long-term placebo-controlled randomized clinical trial in elderly subjects. Enrolled in the study were 551 men and women between the ages of 60 and 90 years with isolated systolic hypertension (SBP greater than or equal to 160 mmHg and DBP less than 90 mmHg). The study showed that it is possible to recruit old and very old subjects into a clinical trial; the elderly are good compliers (drugs and follow-up visits), with some decline after the age of 80; control of blood pressure was accomplished in the large majority of patients; evaluation of side effects represents a potential problem as varied complaints increase with age thus creating difficulties in distinguishing those attributed to the study drug; and finally, cause-specific mortality is probably preferable to all-cause mortality as an end-point in prevention trials of antihypertensive regimens.

Age Factors↗
PubMed1988

Secondary prevention trials after myocardial infarction.

Secondary prevention trials after myocardial infarction have been compared and reviewed. The data suggest that beta-blockers particularly those without intrinsic sympathomimetic activity (ISA) improve long-term survival after myocardial infarction. Platelet-active drugs reduce the rate of reinfarctions and may have a beneficial effect on survival. In contrast lipid-lowering regimens, anticoagulants, calcium channel blockers, and antiarrhythmics have not shown convincing beneficial effects on survival thus far. Difficulties with subgroup analysis and statistical evaluation of treatment effects are discussed.

Humans↗
PubMed1988

Relation between blood lipids, lipoproteins, and cerebrovascular atherosclerosis. A review.

Although blood lipids and lipoproteins are strongly related to coronary atherosclerosis, their association with cerebrovascular atherosclerosis is less clear. A review of more than 20 publications in which a relation was sought between plasma lipid and lipoprotein concentrations and cerebrovascular atherosclerosis leads to the general conclusion that such a relation exists and that it is stronger in older than in younger individuals. A relation was found between blood lipids and/or lipoproteins and the extent and/or severity of cerebrovascular atherosclerosis in all but three of 26 reviewed studies. However, the specific nature of the relation is obscure because the various studies cannot easily be compared with one another. Interstudy variations in lipoprotein fraction analyzed, methodology for the analysis of lipids and lipoproteins, arterial segment examined, population sampled, control selection in case-control studies, statistical analytic approach taken, and methodology for the assessment of arterial disease preclude pooled analyses. There is a clear need for further evaluation of this relation using standardized and up-to-date methodologies both for analyses of lipids and lipoproteins and for assessment of cerebrovascular disease in symptom-free volunteers as well as in symptomatic patients.

Arteriosclerosis↗
PubMed1987

Secondary prevention trials after acute myocardial infarction.

Of those patients who reach the hospital after an acute myocardial infarction, 18% die during their stay and 85% to 90% of the remainder will eventually die of coronary artery disease. Several secondary preventive approaches have been made to prolong life in these patients. Long-term controlled trials involving nonsurgical measures and at least 100 patients will be reviewed. Lipid-lowering regimens have shown no demonstrable effect on survival over a 4- to 6-year period but show some benefit with respect to nonfatal infarction. Survival was not improved essentially by anticoagulants, antiarrhythmic agents or calcium channel blockers, although new trials are underway that might clarify their role. Platelet-active drugs achieved little reduction in mortality but showed benefit in nonfatal infarction (30% reduction with aspirin). Pooled data on physical exercise programs demonstrated a 15% benefit on mortality but larger trials are required to confirm this. The data on beta blockers (particularly those without intrinsic sympathomimetic activity) show that these drugs improve long-term survival after myocardial infarction, reducing all-cause mortality by as much as 25% to 30%. Larger trials are necessary to detect statistically significant reductions in mortality both overall and in selected subgroups of patients.

Adrenergic beta-Antagonists↗
PubMed1987

Survival analysis of adverse effects data in the Beta-Blocker Heart Attack Trial.

Monitoring for adverse effects in an integral part of controlled clinical trials. Traditionally the results of monitoring are reported as either cumulative percentages at the end of the study or cross-sectional percentages at a given time in the study. These results are likely to underestimate the true number of complaints because participants may be withdrawn (e.g., deaths, losses to follow-up, and refusals) before they ever complain of an adverse effect. However, survival analysis methods can be used to compare the distributions of "time to first complaint" in the active and placebo treatment groups, taking into account withdrawals. Participants in the Beta-Blocker Heart Attack Trial were monitored for possible adverse effects. On each follow-up visit they were asked whether they had had any of four conditions (blacking out, fatigue, depression, and bronchospasm) since their previous visit about 3 months earlier. The patients were followed for up to 30 months. For fatigue and bronchospasm, the complaint-free time was significantly longer in the placebo vs. active (propranolol) treatment group (P less than 0.005).

Adult↗