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Biomedical subjects

C D Furberg

Publications and source records attributed to C D Furberg.

At least 91 records · Page 5Linked to original sources
PubMed1996

Risk of gastrointestinal haemorrhage with calcium antagonists in hypertensive persons over 67 years old.

BACKGROUND: Calcium antagonists are used frequently in management of hypertension. In addition to their cardiovascular effects, these drugs inhibit platelet aggregation. Therefore we examined whether the use of calcium antagonists was associated with an increased risk of gastrointestinal haemorrhage (GIH). METHODS: A prospective cohort study was conducted from 1985 through 1992 on 1636 hypertensive persons aged > or = 68 years living in three communities. The participants were taking beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, or calcium antagonists; those taking combinations of these drugs were excluded. The incidence of GIH was assessed by surveying hospital discharge diagnoses and deaths. Age, gender, disability, arterial pressure, other drugs, and comorbid conditions were examined as confounders. FINDINGS: Compared with beta-blockers (4819 person-years, 65 events), after adjustment for confounders the relative risk for GIH associated with ACE inhibitor (772 person-years, 13 events) was 1.23 (95% CI 0.66-2.28) and with calcium antagonists (1510 person-years, 42 events) it was 1.86 (1.22-2.82). The risks for verapamil, diltiazem, and nifedipine did not differ significantly. The results were unchanged when the analyses were restricted to severe events (GIH in conjunction with blood transfusion or death). INTERPRETATION: Calcium antagonists were associated with an increased risk of GIH in this population. Therefore caution is needed in prescription of these agents to old patients who have other risk factors for gastrointestinal bleeding.

Adrenergic beta-Antagonists↗
PubMed1996

[Reduction of cardiovascular events with pravastatin. A pooled analysis of clinical events within the scope of the Pravastatin Atherosclerosis Intervention Program].

BACKGROUND: It has been documented that the HMG coenzyme A reductase inhibitors, or statins, can decrease cardiovascular events and mortality in patients with clinical coronary disease and moderately to severely elevated lipid levels. Additional data are required to demonstrate a reduction of vascular events in coronary patients with less than severely elevated lipid levels and in subgroups of this population. METHODS AND RESULTS: Clinical data from four atherosclerosis regression trials that evaluated pravastatin were pooled for a predetermined analysis of the effect of that agent on the risk of coronary events. All trials were double-masked, placebo-controlled designs that used pravastatin as monotherapy for 2 to 3 years. The 1891 participants in the trials had evidence of atherosclerosis and mildly to moderately elevated lipid levels. For fatal or nonfatal myocardial infarction, there was a 62% reduction in events attributable to pravastatin (p = .001). This effect was evident in younger and older patients, men and women, and patients with and without histories of hypertension and prior infarction. There was a 46% reduction in all-cause mortality (p = 17), which, although not statistically significant, is consistent with the results of other statin trials. There also was a 62% reduction in the risk of fatal or nonfatal stroke (p = .054). CONCLUSIONS: These pooled results provide strong evidence that pravastatin reduces the risk of cardiovascular events in patients with atherosclerotic disease and mildly to moderately elevated lipid levels. The benefit for reducing myocardial infarction is evident in older and younger patients, men and women, and patients with and without histories of hypertension and prior infarction.

Adult↗
PubMed1996

Should calcium antagonists be first-line agents in the treatment of cardiovascular disease? The public health perspective.

The calcium antagonist (CA) controversy has been fueled in part by disagreements among scientists and clinicians over the scientific documentation required for drugs used to treat lifelong conditions. From a public health perspective, there are three unanswered questions: (1) Does long-term use of CAs convey health benefits to patients with cardiovascular disease (CVD)? (2) Is the long-term use of CAs safe? (3) Is the use of CAs cost effective? The answers to these questions determine the pertinence of three secondary questions: (4) Do the effects of CAs reflect a class action or are there important differences in health outcomes among subclasses of CAs? (5) Are the short-acting, immediate-release (IR) formulations different from the long-acting or the slow-release (SR) formulations? (6) What is prudent use of CAs? The purpose of this report is to summarize the answers to these questions from a public health perspective. (1) To date, use of CAs has not been documented to reduce the risks of cardiovascular complications of hypertension-stroke, myocardial infarction, congestive heart failure, or renal dysfunction. (2) The clinical trial database is inadequate to determine the long-term safety of CAs. The available data suggest that some formulations of CAs may be associated with an increased risk of cardiovascular and noncardiovascular events. (3) Even if slow-release CAs conveyed a benefit, their cost-effectiveness ratios are unlikely to be acceptable. (4) The non-dihydropyridines may offer an advantage over the dihydropyridines. (5) Whether the slow-release formulations differ from the immediate-release formulations in terms of their health effects remains to be seen. (6) It may be prudent clinically to restrict the use of CAs until proper documentation of long-term safety and efficacy and cost effectiveness is available.

Calcium Channel Blockers↗
PubMed1996

Assessment of temporal bias in longitudinal measurements of carotid intimal-medial thickness in the Asymptomatic Carotid Artery Progression Study (ACAPS). ACAPS Research Group.

A randomly selected subset of 100 pairs of baseline and 36-month follow-up carotid B-mode ultrasound examinations from the 919 patients participating in the Asymptomatic Carotid Artery Progression Study (ACAPS) were subjected to a blinded rereading at the conclusion of the trial to assess temporal bias in the measurement of carotid artery intimal-medial thickness (IMT). The original measurements of the primary outcome variable and five secondary outcome variables at baseline and 36 months, respectively, and the 3-year change in each of these variables, were compared with those obtained from the rereadings. For the primary outcome variable, the mean value of 12 IMT measurements obtained from predefined carotid segments, the mean difference (original-rereading) and the 95% confidence interval which resulted from the rereadings were -0.005 (-0.033, 0.023) mm at baseline and -0.009 (-0.031, 0.013) mm at 36 months. The difference in the 3-year change was -0.004 (-0.038, 0.028) mm. The 95% confidence interval for the mean difference between the rereadings and the original readings for the baseline and the 36-month follow-up examinations included zero for all of the six outcome variables as was also the case for the 3-year change in each variable. The magnitude of the mean differences for these 18 variables ranged from 0.004 to 0.034 mm. Intraclass correlation coefficients between the original readings and rereadings ranged from 0.56 to 0.87 with the 3-year changes in outcome variables tending to have lower correlations and the 36-month examinations higher correlations. The carotid IMT measurement process, when combined with uniform reader training, certification and monitoring of reading performance throughout the course of the study, can avoid the temporal bias observed in other studies.

Anticholesteremic Agents↗
PubMed1996

Hypertension and outcomes research. From clinical trials to clinical epidemiology.

Outcomes research seeks to identify effective evidence-based methods of providing the best medical care. While randomized clinical trials (RCT) usually provide the clearest answers, they are often not done or not practicable. More than a decade after the introduction of calcium channel blockers and angiotensin converting enzyme (ACE) inhibitors, clinical trial data about their effect on major disease endpoints in patients with hypertension are still not available. The primary alternatives are the use of randomized trials that include surrogate endpoints, such as level of blood pressure or extent of carotid atherosclerosis, and the use of observational studies that include major disease endpoints. Both approaches, their strengths and limitations, are discussed in detail. The possibility of residual confounding limits the strength of inferences that can be drawn from observational studies. Similarly, the possibility of important drug effects, other than those involving the surrogate endpoint, limits the inferences that can be drawn from randomized trials that rely solely on surrogate outcomes as guides to therapy. In the absence of evidence from large clinical trials that include major disease endpoints, treatment decisions and guidelines need to synthesize the best available information from a variety of sources. Consistency of findings across various study designs, outcomes, and populations is critical to the practice of evidence-based medicine and the effort to maximize the health benefits of antihypertensive therapies.

Clinical Trials as Topic↗
PubMed1996

Rationale and design for the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). ALLHAT Research Group.

Are newer types of antihypertensive agents, which are currently more costly to purchase on average, as good or better than diuretics in reducing coronary heart disease incidence and progression? Will lowering LDL cholesterol in moderately hypercholesterolemic older individuals reduce the incidence of cardiovascular disease and total mortality? These important medical practice and public health questions are to be addressed by the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), a randomized, double-blind trial in 40,000 high-risk hypertensive patients. ALLHAT is designed to determine whether the combined incidence of fatal coronary heart disease (CHD) and nonfatal myocardial infarction differs between persons randomized to diuretic (chlorthalidone) treatment and each of three alternative treatments--a calcium antagonist (amlodipine), an angiotensin converting enzyme inhibitor (lisinopril), and an alpha-adrenergic blocker (doxazosin). ALLHAT also contains a randomized, open-label, lipid-lowering trial designed to determine whether lowering LDL cholesterol in 20,000 moderately hypercholesterolemic patients (a subset of the 40,000) with a 3-hydroxymethylglutaryl coenzyme A (HMG CoA) reductase inhibitor, pravastatin, will reduce all-cause mortality compared to a control group receiving "usual care." ALLHAT's main eligibility criteria are: 1) age 55 or older; 2) systolic or diastolic hypertension; and 3) one or more additional risk factors for heart attack (eg, evidence of atherosclerotic disease or type II diabetes). For the lipid-lowering trial, participants must have an LDL cholesterol of 120 to 189 mg/dL (100 to 129 mg/dL for those with known CHD) and a triglyceride level below 350 mg/dL. The mean duration of treatment and follow-up is planned to be 6 years. Further features of the rationale, design, objectives, treatment program, and study organization of ALLHAT are described in this article.

Antihypertensive Agents↗
PubMed1996

Utility of new electrocardiographic models for left ventricular mass in older adults. The Cardiovascular Health Study Collaborative Research Group.

Several multivariate statistical models have recently been introduced for estimation of left ventricular mass from standard 12-lead electrocardiographic measurements. The validity of these algorithms has not been adequately evaluated. The objective of this investigation was to compare the associations between echocardiographic and electrocardiographic left ventricular mass values with clinical and subclinical indexes of coronary heart disease. The evaluation was performed with participants of the Cardiovascular Health Study, a population-based sample of 5201 men and women aged 65 years and older. Echocardiographic M-mode measurements of left ventricular mass were performed from videotape recordings with the use of a strictly standardized protocol. Electrocardiographic algorithms of the Novacode program and new algorithms derived from the Cardiovascular Health Study population were used for left ventricular mass prediction. Echocardiographic and electrocardiographic determinations of left ventricular mass were technically successful in 3410 (65.6%) and 5013 (96.4%) participants, respectively. The Novacode model overestimated echocardiographic left ventricular mass. Compared with the Novacode model, the new Cardiovascular Health Study electrocardiographic model, which includes adjustment for body weight, eliminated left ventricular mass prediction bias and improved the correlation between echocardiographic and electrocardiographic left ventricular mass from .33 to .54 in women and from .46 to .51 in men. Echocardiographic and electrocardiographic models both demonstrated similar and about equally strong associations with overt and subclinical disease and with risk factors for left ventricular hypertrophy. These observations demonstrate the potential utility of electrocardiographic models for left ventricular mass estimation.

Age Factors↗
PubMed1996

Thickening of the carotid wall. A marker for atherosclerosis in the elderly? Cardiovascular Health Study Collaborative Research Group.

BACKGROUND AND PURPOSE: We investigated the relationships between prevalent coronary heart disease (CHD), clinically manifest atherosclerotic disease (ASD), and major established risk factors for atherosclerosis and intima-media thickness (IMT) in the common carotid arteries (CCA) and internal carotid arteries (ICA) separately and in combination in older adults. We wished to determine whether a noninvasive measurement can serve as an indicator of clinically manifest atherosclerotic disease and to determine which of the two variables, CCA IMT or ICA IMT, is a better correlate. METHODS: IMT of the CCA and ICA was measured with duplex ultrasound in 5117 of 5201 individuals enrolled in the Cardiovascular Health Study, a study of the risk factors and the natural history of cardiovascular disease in adults aged 65 years or more. Histories of CHD, peripheral arterial disease, and cerebrovascular disease were obtained during baseline examination. Risk factors included cholesterol levels, cigarette smoking, elevated blood pressure, diabetes, age, and sex. Relationships between risk factors and IMT were studied by multiple regression analysis and canonical variate analysis. Prediction of prevalent CHD and ASD by IMT measurements in CCAs and ICAs were made by logistic regression, adjusting for age and sex. RESULTS: IMT measurements of the CCAs and ICAs were greater in persons with CHD and ASD than those without, even after controlling for sex (P < .001). IMT measurements in the ICA were greater than those in the CCA. Risk factors for ASD accounted for 17% and 18% of the variability in IMT in the CCA and ICA, respectively. These same risk factors accounted for 25% of the variability of a composite measurement consisting of the sum of the ICA IMT and CCA IMT. The ability to predict CHD and ASD was greater for ICA IMT (odds ratio [confidence interval]: 1.36 [1.31 to 1.41] and 1.35 [1.25 to 1.44], respectively) than for CCA IMT (1.09 [1.05 to 1.13] and 1.17 [1.09 to 1.25]). CONCLUSIONS: Whereas CCA IMT is associated with major risk factors for atherosclerosis and existing CHD and ASD in older adults, this association is not as strong as that for ICA IMT. The combination of these measures relates more strongly to existing CHD and ASD and cerebrovascular disease risk factors than either taken alone.

Adult↗
PubMed1996

Reliability of longitudinal ultrasonographic measurements of carotid intimal-medial thicknesses. Asymptomatic Carotid Artery Progression Study Research Group.

BACKGROUND AND PURPOSE: Serial ultrasonic B-mode measurements of intimal-medial thickness (IMT) of the carotid artery are commonly used as surrogates for describing atherosclerosis progression. This report describes the longitudinal reliability of IMT measurement during a multicenter clinical trial, quantifies the error attributable to differences among readers, and discusses how studies can be efficiently designed. METHODS: Serial B-mode measurements of carotid IMT from the 3-year Asymptomatic Carotid Artery Progression Study (ACAPS; formerly Asymptomatic Carotid Artery Plaque Study) were used to estimate the contributions to longitudinal measurement error of systematic reader effects, nonvisualization, and nonsystematic error and to describe the distribution of "true" progression rates that underlie the observed data. Variance components were estimated from random-effects models fitted to outcome measures formed by averaging IMTs from different sets of carotid artery walls. These were used to contrast the relative efficiency of study designs. RESULTS: Of the total variance of measured IMT, 11% was attributable to systematic differences among readers. Nonvisualization contributed less than 7%. Thus, the predominant source of error was unaccounted for (ie, random error or "noise," which in our analyses included any drift, nonlinearity, and sonographer differences). For studies with measurement protocols similar to ACAPS, follow-up times of 2 years or more are desirable for describing the mean progression rates of cohorts, and of 6 years or more for categorizing progression within individuals. In 3-year studies, sample sizes as low as 237 provide 90% statistical power for detecting risk factors that have correlations with IMT progression of .50 or greater. CONCLUSIONS: The ACAPS measurement protocol provided highly reliable serial IMT data. Moderate-sized multicenter studies using B-mode outcomes are feasible.

Adult↗
PubMed1996

Nimodipine neuroprotection in cardiac valve replacement: report of an early terminated trial.

BACKGROUND: We conducted a double-blind, randomized clinical trial in patients undergoing cardiac valve replacement to determine whether nimodipine, a dihydropyridine calcium antagonist, reduced the risk of new neurological, neuro-ophthalmologic, or neuropsychological deficits-common complications associated with cardiac surgery-1 week after surgery. METHODS AND RESULTS: Enrollment for a total of 400 patients started in May 1992 and was stopped in September 1994, with 150 patients randomized to the study. Nimodipine was given to the patients during the perioperative period. Patients underwent examinations before surgery and at approximately 1 week, 1 month, and 6 months after surgery. Major adverse events, including deaths and strokes, were monitored monthly. The trial was terminated early because of both an unexpected disparity in death rates between groups and a lack of evidence of a beneficial effect of nimodipine. New deficits were observed in 72% of the placebo group versus 77% of the nimodipine group (p=.55). In the 6-month follow-up period, 8 deaths (10.7%) occurred in the nimodipine group (n=75) compared with 1 death (1.3) in the placebo group (n=74) (p=.02). Major bleeding occurred in 10 patients in the nimodipine group versus 3 in the placebo group (13.3% versus 4.1%; P=.04). Six (46.2%) of the 13 patients with major bleeding died compared with 3 deaths (2.2%) among the 136 patients without major bleeding. CONCLUSIONS: Our findings add to the growing evidence that calcium antagonists have a prohemorrhagic effect in some patients and suggest that nimodipine use should be restricted perioperatively in patients scheduled for cardiac valve replacement.

Adult↗
PubMed1995

Estrogen replacement therapy and progression of intimal-medial thickness in the carotid arteries of postmenopausal women. ACAPS Investigators. Asymptomatic Carotid Atherosclerosis Progression Study.

The effect of estrogen replacement therapy (ERT) on 3-year changes in carotid intimal-medial thickness (IMT) was explored using serial B-mode ultrasound measurements collected during 1989-1993 as part of the Asymptomatic Carotid Atherosclerotic Progression Study (ACAPS). Eligibility included increased IMT and elevated low density lipoprotein cholesterol. Of the 186 postmenopausal ACAPS women randomly assigned to receive either placebo or lovastatin, 34% reported use of ERT. Users tended to be younger than nonusers by an average of 3 years, to have more favorable high and low density lipoprotein cholesterol levels, and to be more likely to have had hysterectomies. Baseline blood pressure, body mass index, and cross-sectional IMT were similar among ERT users and nonusers. In the placebo group, IMT tended to progress among ERT nonusers but to regress among ERT users: Mean covariate-adjusted progression rates were 0.015 +/- 0.007 mm/year versus -0.012 +/- 0.012 mm/year, respectively (p = 0.05). This difference appeared to be independent of lipoprotein concentrations. Lovastatin was associated with an approximately 25% lowering of low density lipoprotein cholesterol among both ERT users and nonusers and had a marked impact on IMT progression (p = 0.004) in these women. ERT appeared to have little additional effect on IMT in women assigned to lovastatin. ERT may reduce or halt the progression of early atherosclerosis in women not receiving active lipid-lowering medication.

Adult↗
PubMed1995

Reduction in cardiovascular events during pravastatin therapy. Pooled analysis of clinical events of the Pravastatin Atherosclerosis Intervention Program.

BACKGROUND: It has been documented that the HMG coenzyme A reductase inhibitors, or statins, can decrease cardiovascular events and mortality in patients with clinical coronary disease and moderately to severely elevated lipid levels. Additional data are required to demonstrate a reduction of vascular events in coronary patients with less than severely elevated lipid levels and in subgroups of this population. METHODS AND RESULTS: Clinical data from four atherosclerosis regression trials that evaluated pravastatin were pooled for a predetermined analysis of the effect of that agent on the risk of coronary events. All trials were double-masked, placebo-controlled designs that used pravastatin as monotherapy for 2 to 3 years. The 1981 participants in the trials had evidence of atherosclerosis and mildly to moderately elevated lipid levels. For fatal or nonfatal myocardial infarction, there was a 62% reduction in events attributable to pravastatin (P = .001). This effect was evident in younger and older patients, men and women, and patients with and without histories of hypertension and prior infarction. There was a 46% reduction in all-cause mortality (P = .17), which, although not statistically significant, is consistent with the results of other statin trials. There also was a 62% reduction in the risk of fatal or nonfatal stroke (P = .054). CONCLUSIONS: These pooled results provide strong evidence that pravastatin reduces the risk of cardiovascular events in patients with atherosclerotic disease and mildly to moderately elevated lipid levels. The benefit for reducing myocardial infarction is evident in older and younger patients, men and women, and patients with and without histories of hypertension and prior infarction.

Age Factors↗