The burden of treatment failure in type 2 diabetes: response to Brown et al.
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Blood Glucose↗
Biomedical subjects
Robert P Byington
Publications and source records attributed to Robert P Byington.
Additive benefits of pravastatin and aspirin to decrease risks of cardiovascular disease: randomized and observational comparisons of secondary prevention trials and their meta-analyses.
BACKGROUND: In randomized trials of secondary prevention, pravastatin sodium and aspirin reduce risks of cardiovascular disease. Pravastatin has a predominantly delayed antiatherogenic effect, and aspirin has an immediate antiplatelet effect, raising the possibility of additive clinical benefits. METHODS: In 5 randomized trials of secondary prevention with pravastatin (40 mg/d), comprising 73 900 patient-years of observation, aspirin use was also prescribed in varying frequencies, and data were available on a large number of confounding variables. We tested whether pravastatin and aspirin have additive benefits in the 2 large trials (Long-term Intervention With Pravastatin in Ischaemic Disease trial and the Cholesterol and Recurrent Events trial) that were designed to test clinical benefits. We also performed meta-analyses of these 2 trials and 3 smaller angiographic trials that collected clinical end points. In all analyses, multivariate models were used to adjust for a large number of cardiovascular disease risk factors. RESULTS: Individual trials and all meta-analyses demonstrated similar additive benefits of pravastatin and aspirin on cardiovascular disease. In meta-analysis, the relative risk reductions for fatal or nonfatal myocardial infarction were 31% for pravastatin plus aspirin vs aspirin alone and 26% for pravastatin plus aspirin vs pravastatin alone. For ischemic stroke, the corresponding relative risk reductions were 29% and 31%. For the composite end point of coronary heart disease death, nonfatal myocardial infarction, coronary artery bypass graft, percutaneous transluminal coronary angioplasty, or ischemic stroke, the relative risk reductions were 24% and 13%. All relative risk reductions were statistically significant. CONCLUSION: More widespread and appropriate combined use of statins and aspirin in secondary prevention of cardiovascular disease will avoid large numbers of premature deaths.
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Lessons learned from the prospective pravastatin pooling project.
The Prospective Pravastatin Pooling (PPP) Project was a prospectively defined collaboration of three randomized, placebo-controlled, long-term, monotherapy (40 mg/d) trials of the lipid-lowering agent pravastatin. A pooled database of 19,768 participants with a mean of 5.2 years of follow-up was created, providing the investigators with over 100,000 patient-years of experience to address questions on total and cause-specific mortality, coronary incidence, stroke, and safety. One trial (West of Scotland Coronary Prevention Study) was primary prevention and two (Cholesterol and Recurrent Events and Long-term Intervention with Pravastatin in Ischemic Disease) were secondary prevention. Pravastatin was shown to safely reduce all-cause mortality, fatal and nonfatal coronary events, and stroke events in patients with a broad range of patient characteristics.
Adult↗
Pregnancy-related death and health care services.
OBJECTIVE: To examine the association between health care services variables and pregnancy-related death using a contemporary geographically defined population and enhanced methods for case identification. METHODS: This is a population-based, case-control study from North Carolina for the 7-year period 1992-1998. Pregnancy-related deaths after a live birth (n = 118) were identified after review of pregnancy-associated deaths (n = 400) ascertained from death certificate codes and linkage of birth and death files. Controls (n = 3697) were randomly selected from all registered live births for the same 7-year period and were not matched with cases. This sample size was sufficient to ensure that the standard errors for subgroup prevalences were less than 1%. The associations between pregnancy-related death and health care services were explored with univariate and multivariable regression analysis. RESULTS: Neither maternity care coordination nor nutritional services were protective. There was no association with source of care, private versus public. The adjusted odds ratio (OR) for pregnancy-related death associated with cesarean delivery was 3.9 (95% confidence interval [CI] 2.5, 6.1). The adjusted OR for pregnancy-related death associated with the receipt of prenatal care was 0.2 (95% CI 0.1, 0.6). CONCLUSION: Removing barriers to and actively promoting use of prenatal care services and decreasing the rate of cesarean deliveries could decrease the number of pregnancy-related deaths.
Case-Control Studies↗
Effect of estrogen plus progestin on progression of carotid atherosclerosis in postmenopausal women with heart disease: HERS B-mode substudy.
OBJECTIVE: The Heart and Estrogen/Progestin Replacement Study (HERS) found no overall effect of estrogen plus progestin (compared with placebo) on coronary event rates in 2763 postmenopausal women with established coronary disease (mean 4.1 years of follow-up). In addition to the events trial, a carotid ultrasound substudy was established in 1993 to be conducted concurrently to determine whether hormone therapy affects the progression of the underlying atherosclerotic process. METHODS AND RESULTS: Within the larger HERS, a subset of 362 participants underwent carotid B-mode ultrasound examinations at baseline and the end of follow-up. Progression of carotid atherosclerosis was measured as the temporal change in intimal-medial thickness (IMT). CONCLUSIONS: IMT progressed in the hormone treatment and placebo groups, although there was no statistical difference between the rates: IMT progressed 26 microm/y (95% CI 18 to 34 microm/y) in the hormone group and 31 microm/y (95% CI 21 to 40 microm/y) in the placebo group (P=0.44). There were also no significant treatment effects when the results were examined by carotid segment or were adjusted for covariates. These data support the American Heart Association recommendation that women with established coronary disease should not initiate hormone therapy with an expectation of atherosclerotic benefit.
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Safety and tolerability of pravastatin in long-term clinical trials: prospective Pravastatin Pooling (PPP) Project.
BACKGROUND: Therapeutic decisions regarding pharmacological therapy should be based on safety and tolerability as well as efficacy data. Clinical trials designed to assess efficacy are often insufficiently powered to generate reliable safety data. METHODS AND RESULTS: The West of Scotland Coronary Prevention Study (WOSCOPS), the Cholesterol and Recurrent Events (CARE), and Long-term Intervention with Pravastatin in Ischemic Disease (LIPID) studies collectively accumulated >112 000 person-years of exposure in double-blind randomized trials comparing placebo and pravastatin (40 mg once daily). During 5 years of exposure, the incidence of fatal and nonfatal cancers was similar between pravastatin and placebo groups. No differences in noncardiovascular serious adverse events were detected. With >243 000 blood sample analyses, the percentage of patients with any abnormal liver function test after baseline sampling was similar (>3x the upper limit of normal for alanine aminotransferase: 128 [1.4%] versus 131 [1.4%] patients for pravastatin versus placebo, respectively). Study medication was withdrawn in 3 pravastatin and 7 placebo patients due to creatine phosphokinase elevations; no cases of mild or severe myopathy were reported. A Cox regression model considering treatment group, age, diabetes, smoking, whether primary or secondary prevention study, and cardiovascular serious adverse events indicates that the likelihood of discontinuing pravastatin was less than placebo. CONCLUSIONS: This prospective analysis indicates that during prolonged exposure, 40 mg of pravastatin is well tolerated, with no excess of noncardiovascular serious adverse events, including liver function abnormalities and laboratory and clinical evidence for myositis. These extensive safety and tolerability data provide important information for therapeutic decisions regarding this pharmacological agent.
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