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Biomedical subjects

Alan T Hirsch

Publications and source records attributed to Alan T Hirsch.

13 recordsLinked to original sources
PubMed2003

Treatment of intermittent claudication with beraprost sodium, an orally active prostaglandin I2 analogue: a double-blinded, randomized, controlled trial.

OBJECTIVES: In the current study, we hypothesized that beraprost would: 1) improve treadmill exercise performance and quality of life; and 2) decrease rates of ischemic events in patients with intermittent claudication. BACKGROUND: Previous trials with beraprost sodium, an orally active prostaglandin I(2) analogue, in the treatment of claudication in patients with peripheral arterial disease (PAD) have been inconsistent. METHODS: Patients with intermittent claudication (n = 897) were randomized to receive either 40 microg three times a day of beraprost with meals (n = 385) or placebo (n = 377) in a double-blinded manner for one year. The primary efficacy parameter was treadmill-measured maximum walking distance, as assessed at three and six months after randomization. Secondary efficacy parameters included treadmill-measured pain-free walking distance and change in quality of life. RESULTS: There was no significant improvement in maximum walking distance in the beraprost group (16.7%) as compared with the placebo group (14.6%, p = NS). Administration of beraprost did not improve the pain-free walking distance (p = NS between treatment groups), and there was no improvement in the quality-of-life measures between the treatment groups. The incidence of critical cardiovascular events was 7.3% in the beraprost group and 11.4% in the placebo group (p = NS). There was a significant reduction in the combination of cardiovascular death and myocardial infarction in the beraprost group (p = 0.01). CONCLUSIONS: Despite previous investigations suggesting efficacy, these results indicate that beraprost is not an effective treatment to improve symptoms of intermittent claudication in patients with PAD. The potential benefit of beraprost on critical cardiovascular events would require confirmation in a larger prospective investigation.

Administration, Oral↗
PubMed2003

Regional Angiogenesis with Vascular Endothelial Growth Factor (VEGF) in peripheral arterial disease: Design of the RAVE trial.

BACKGROUND: Patients with intermittent claudication caused by infrainguinal atherosclerosis have limited pharmacologic options "Therapeutic angiogenesis" is a novel treatment approach that seeks to improve perfusion of ischemic limbs by the induction of collateral vessel formation. This trial is a phase 2 randomized double-blind placebo-controlled proof of concept trial that will use an intramuscular adenoviral gene transfer approach of vascular endothelial growth factor, 121 isoform (Ad(GV)VEGF(121.10)) to patients with severe IC caused by infrainguinal disease. METHODS: This is a phase 2, double-blind, randomized, placebo-controlled, dose-finding, multicenter study. Patients with severe intermittent claudication caused by infrainguinal atherosclerosis predominantly involving the superficial femoral artery confirmed with imaging studies that meet inclusion criteria will be stratified on the basis of the presence or absence of diabetes mellitus and randomized in a 1:1:1 fashion to low dose (4 x 10(9) particle units), high dose (4 x 10(10) particle units), or placebo arms (35-36 patients per group). Subjects are required to have exercise-limiting IC in the index extremity during 2 qualifying exercise treadmill tests, with peak walking times between 1 and 10 minutes. A single dose of Ad(GV)VEGF(121.10) will be administered as 20 intramuscular injections throughout the area of the lower limb requiring collateralization. RESULTS: The primary efficacy parameter for the Regional Angiogenesis With Vascular Endothelial Growth Factor (RAVE) trial is the change in peak walking time at 12 weeks compared with baseline. The sample size is expected to provide an 80% power to detect a difference of 1.5 minutes between any of the 2 treatment groups and the placebo group. Secondary efficacy parameters include claudication onset time, hemodynamic effects of therapy assessed with ankle-brachial index, assessment of physical impairment, and health-related quality of life as measured with the Walking Impairment Questionnaire and SF-36 Health Survey. All randomized patients will also be evaluated for safety.

Adenoviridae↗
PubMed2003

Developing pharmaceutical treatments for peripheral artery disease.

Peripheral artery disease (PAD) is a debilitating atherosclerotic disease of the lower limbs and is associated with an increased risk of cardiovascular morbidity and mortality. Treatment goals should be aimed at providing symptom relief (claudication) and reducing the risk of systemic cardiovascular morbidity and mortality. In the development of pharmaceutical treatment for PAD, aggressive non-pharmacological intervention and pharmacological treatment of the risk factors associated with PAD should be given. Antiplatelet therapy, aspirin, should be given to every PAD patient if there are no contraindications. Should symptoms worsen or intolerance to aspirin develop, ticlopidine or clopidogrel would be the alternative. Several pharmacological agents have been developed to improve the functional state of the claudicant and to relieve the symptoms. Many studied drugs have shown either no, small or potential benefit. With future development of new drugs for PAD, there is an absolute need for very strict, well-designed protocols in order to evaluate the claudication distance and progression of the disease, as well as the reduction in cardiovascular morbidity and mortality.

Animals↗
PubMed2002

Atherosclerotic risk factor reduction in peripheral arterial diseasea: results of a national physician survey.

OBJECTIVE: Individuals with peripheral arterial disease (PAD) have a 3- to 6-fold increased risk of coronary heart disease and stroke compared to those without PAD. We documented physician-reported practice behavior, knowledge, and attitudes regarding atherosclerotic risk factor reduction in patients with PAD. DESIGN: National physician survey. PATIENTS/PARTICIPANTS: General internists (N = 406), family practitioners (N = 435), cardiologists (N = 473), and vascular surgeons (N = 264) randomly identified using the American Medical Association's physician database. MEASUREMENTS AND MAIN RESULTS: Physicians were randomized to 1 of 3 questionnaires describing a) a 55- to 65-year-old patient with PAD; b) a 55- to 65-year-old patient with coronary artery disease (CAD), or c) a 55- to 65-year-old patient without clinically evident atherosclerosis (no disease). A mailed questionnaire was used to compare physician behavior, knowledge, and attitude regarding risk factor reduction for each patient. Rates of prescribed antiplatelet therapy were significantly lower for the patient with PAD than for the patient with CAD. Average low-density lipoprotein levels at which physicians "almost always" initiated lipid-lowering drugs were 121.6 +/- 23.5 mg/dL, 136.3 +/- 28.9 mg/dL, and 149.7 +/- 24.4 mg/dL for the CAD, PAD, and no-disease patients, respectively (P <.001). Physicians stated that antiplatelet therapy (P <.001) and cholesterol-lowering therapy (P <.001) were extremely important significantly more often for the CAD than for the PAD patient. Perceived importance of risk factor interventions was highly correlated with practice behavior. Compared to other specialties, cardiologists had lowest thresholds, whereas vascular surgeons had the highest thresholds for initiating cholesterol-lowering interventions for the patient with PAD. Cardiologists were significantly more likely to report "almost always" prescribing antiplatelet therapy for the patient with PAD than were all other physicians. CONCLUSIONS: Deficiencies in physician knowledge and attitudes contribute to lower rates of atherosclerotic risk factor reduction for patients with PAD. Reversing these deficiencies may reduce the high rates of cardiovascular morbidity and mortality associated with PAD.

Adult↗
PubMed2002

Peripheral arterial disease: medical care and prevention of complications.

Peripheral arterial disease (PAD) is a common but under-recognized problem affecting older patients. Intermittent claudication is the most frequent symptom of PAD, although the diagnosis of PAD is often overlooked until the patient presents with limb-threatening ischemia. Importantly, PAD is a marker for generalized atherosclerosis and is closely associated with coronary and cerebrovascular disease. The severity of PAD has been correlated with an increased risk of myocardial infarction, stroke, and cardiovascular death. The recognition and diagnosis of PAD, combined with its appropriate medical management, may well reduce the overall risk of cardiovascular morbidity. When diagnosed early, both exercise and pharmacotherapy can ameliorate symptoms of claudication, augment functional performance, and improve quality of life.

Aged↗
PubMed2002

A patient-derived perspective of health-related quality of life with peripheral arterial disease.

PURPOSE: To evaluate the effects of peripheral artery disease (PAD) on health-related quality of life (HRQoL) from the patient's perspective to establish a foundation for systematic PAD-specific HRQoL assessment in this population. DESIGN: Grounded theory methodology. METHODS: Open-ended, tape-recorded interviews were conducted with 38 patients (24 men, 14 women) 44 to 83 years old (mean 65) from two US medical centers to report patient experience of PAD and its perceived effects on HRQoL. Tapes were transcribed and analyzed to identify themes and conceptual domains pertinent to the experience of PAD in this population. RESULTS: Seven major themes were identified: (a) delay in diagnosis and frustration with management of disease; (b) pain; (c) limitation in physical functioning; (d) limitation in social and role functioning; (e) compromise of self; (f) uncertainty and fear; and (g) adaptation to the effects of the disease and demonstration of resiliency. CONCLUSIONS: These findings indicate important psychosocial and emotional consequences of PAD that existing HRQoL questionnaires do not indicate. More complete data might lead to greater understanding of the effects of PAD, serving as the foundation for a more sensitive instrument to assess HRQoL as a basis for more effective interventions.

Adult↗
PubMed2002

Undertreatment of dyslipidemia in peripheral arterial disease and other high-risk populations: an opportunity for cardiovascular disease reduction.

Atherosclerosis is a form of arterial disease that manifests in the coronary circulation as coronary artery disease (CAD), in the carotid arteries as cerebrovascular disease, and in the aorta and lower extremity arteries as peripheral arterial disease (PAD). The systemic nature of the disease is reflected in the fact that individuals with PAD or carotid artery disease are more likely to have CAD than those without. Since individuals with PAD are at markedly increased risk of cardiovascular ischemic events, early identification of this population and more aggressive medical interventions could substantially improve both morbidity and survival. The incidence of PAD in the general population is high, and currently affects 8-10 million Americans. The risk of developing PAD is predicted by both age and common atherosclerosis risk factors (e.g., smoking and diabetes). Efficient office-based PAD detection depends on the application of objective techniques to establish this diagnosis. Objective noninvasive tests, such as measurement of the ankle-brachial index (ABI), are known to be more sensitive than traditional clinical assessments. Since the major threat to patients with PAD is from secondary cardiovascular ischemic events, a primary therapeutic goal is to modify atherosclerotic risk factors. While national recommendations mandate aggressive lowering of serum low-density lipoprotein cholesterol (LDL-C) levels as a primary treatment goal in all patients with overt atherosclerosis, as 'coronary heart disease risk equivalent' syndromes, individuals with PAD are less intensively treated than those with CAD. Statins are the most effective of current treatments in lowering LDL-C, and have proven efficacy in secondary prevention among patients with established CAD. The use of statin medications in high-risk groups such as PAD patients could prove particularly beneficial in reducing cardiovascular morbidity and mortality and therefore merits prospective clinical investigation.

Clinical Trials as Topic↗