Reliable measurement of glycated hemoglobin in frozen blood samples: implications for epidemiologic studies.
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Biomedical subjects
Publications and source records attributed to Rory Collins.
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BACKGROUND: Statin therapy reduces the rates of heart attack, stroke, and revascularisation among a wide range of individuals. Reliable assessment of its cost-effectiveness in different circumstances is needed. METHODS: 20,536 adults (aged 40-80 years) with vascular disease or diabetes were randomly allocated 40 mg simvastatin daily (10,269) or placebo (10,267) for an average of 5 years. Comparisons were made of hospitalisation and statin costs (2001 UK prices) during the scheduled treatment period between all simvastatin-allocated versus all placebo-allocated participants. Cost-effectiveness was estimated among different categories of participant. FINDINGS: Allocation to simvastatin was associated with a highly significant 22% (95% CI 16-27; p<0.0001) proportional reduction in hospitalisation costs for all vascular events, with similar proportional reductions in every subcategory of participant studied. During an average of 5 years, estimated absolute reductions in vascular event costs per person allocated 40 mg simvastatin daily ranged from UK 847 pounds sterling (SE 137) in the highest risk quintile studied to 264 pounds sterling (48) in the lowest. Mean excess cost of statin therapy among participants allocated simvastatin was 1497 pounds sterling (8), with similar absolute increases in every subcategory. Costs of preventing a major vascular event with 40 mg simvastatin daily ranged from 4500 pounds sterling (95% CI 2300-7400) among participants with a 42% 5-year major vascular event rate to 31,100 pounds sterling (22,900-42,500) among those with a 12% rate (corresponding to 5-year major coronary event rates of 22% and 4%, respectively). INTERPRETATION: Statin therapy is cost effective for a wider range of individuals with vascular disease or diabetes than previously recognised (particularly with lower-priced generics). It would be appropriate to consider reducing the estimated level of vascular event risk at which statin therapy is recommended.
BACKGROUND: The apparent shortfall in prevention of coronary heart disease (CHD) noted in early hypertension trials has been attributed to disadvantages of the diuretics and beta blockers used. For a given reduction in blood pressure, some suggested that newer agents would confer advantages over diuretics and beta blockers. Our aim, therefore, was to compare the effect on non-fatal myocardial infarction and fatal CHD of combinations of atenolol with a thiazide versus amlodipine with perindopril. METHODS: We did a multicentre, prospective, randomised controlled trial in 19 257 patients with hypertension who were aged 40-79 years and had at least three other cardiovascular risk factors. Patients were assigned either amlodipine 5-10 mg adding perindopril 4-8 mg as required (amlodipine-based regimen; n=9639) or atenolol 50-100 mg adding bendroflumethiazide 1.25-2.5 mg and potassium as required (atenolol-based regimen; n=9618). Our primary endpoint was non-fatal myocardial infarction (including silent myocardial infarction) and fatal CHD. Analysis was by intention to treat. FINDINGS: The study was stopped prematurely after 5.5 years' median follow-up and accumulated in total 106 153 patient-years of observation. Though not significant, compared with the atenolol-based regimen, fewer individuals on the amlodipine-based regimen had a primary endpoint (429 vs 474; unadjusted HR 0.90, 95% CI 0.79-1.02, p=0.1052), fatal and non-fatal stroke (327 vs 422; 0.77, 0.66-0.89, p=0.0003), total cardiovascular events and procedures (1362 vs 1602; 0.84, 0.78-0.90, p<0.0001), and all-cause mortality (738 vs 820; 0.89, 0.81-0.99, p=0.025). The incidence of developing diabetes was less on the amlodipine-based regimen (567 vs 799; 0.70, 0.63-0.78, p<0.0001). INTERPRETATION: The amlodipine-based regimen prevented more major cardiovascular events and induced less diabetes than the atenolol-based regimen. On the basis of previous trial evidence, these effects might not be entirely explained by better control of blood pressure, and this issue is addressed in the accompanying article. Nevertheless, the results have implications with respect to optimum combinations of antihypertensive agents.
The Heart Protection Study (HPS), with over 20,500 subjects, is the largest trial of statin therapy ever conducted. It provides important and definitive new information on women, the elderly, diabetics, and people with low baseline cholesterol pre-treatment and those with prior occlusive non-coronary vascular disease. It is a prospective double blind randomised controlled trial with a 2 x 2 factorial design investigating prolonged use (>5 years) of simvastatin 40 mg and a cocktail of antioxidant vitamins (650 mg vitamin E, 250 mg vitamin C and 20 mg beta-carotene). The HPS specifically included patients with high risk for coronary heart disease (CHD) but characteristics that excluded them from participation in previous statin trials. Simvastatin 40 mg treatment showed benefit across all patient groups regardless of age, gender or baseline cholesterol value and proved safe and well tolerated. Results show a 12% reduction in total mortality, a 17% reduction in vascular mortality, a 24% reduction in CHD events, a 27% reduction in all strokes and a 16% reduction in non-coronary revascularisations. Among high-risk patients in this western population (with a minimum total cholesterol [TC] > or = 3.5 mmol/l at entry) there appears to be no threshold cholesterol value below which statin therapy is not associated with benefit; even among those with pre-treatment cholesterol levels below current national recommended targets. Over the 5.5 year study period patients and their doctors were encouraged to add an active non-study statin to the study regimen if they wished to do so. Thus the trial eventually had only two-thirds complying with the original intention-to-treat design. Nevertheless, results were highly significant for the study statin--simvastatin 40 mg once daily. Preliminary results of the HPS are negative for the antioxidant vitamin cocktail but provide reassurance that vitamins do no harm.