Literature DB >> 15765890

Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial--Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial.

Peter S Sever1, Björn Dahlöf, Neil R Poulter, Hans Wedel, Gareth Beevers, Mark Caulfield, Rory Collins, Sverre E Kjeldsen, Arni Kristinsson, Gordon T McInnes, Jesper Mehlsen, Markku Nieminen, Eoin O'Brien, Jan Ostergren.   

Abstract

BACKGROUND: The lowering of cholesterol concentrations in individuals at high risk of cardiovascular disease improves outcome. No study, however, has assessed benefits of cholesterol lowering in the primary prevention of coronary heart disease (CHD) in hypertensive patients who are not conventionally deemed dyslipidaemic.
METHODS: Of 19 342 hypertensive patients (aged 40-79 years with at least three other cardiovascular risk factors) randomised to one of two antihypertensive regimens in the Anglo-Scandinavian Cardiac Outcomes Trial, 10,305 with nonfasting total cholesterol concentrations 6.5 mmol/L or less were randomly assigned additional atorvastatin 10 mg or placebo. These patients formed the lipid-lowering arm of the study. We planned follow-up for an average of 5 years, the primary endpoint being non-fatal myocardial infarction and fatal CHD. Data were analysed by intention to treat.
FINDINGS: Treatment was stopped after a median follow-up of 3.3 years. By that time, 100 primary events had occurred in the atorvastatin group compared with 154 events in the placebo group (hazard ratio 0.64 [95% CI 0.50-0.83], p = 0.0005). This benefit emerged in the first year of follow-up. There was no significant heterogeneity among prespecified subgroups. Fatal and non-fatal stroke (89 atorvastatin vs 121 placebo, 0.73 [0.56-0.96], p = 0.024), total cardiovascular events (389 vs 486, 0.79 [0.69-0.90], p = 0.0005), and total coronary events (178 vs 247, 0.71 [0.59-0.86], p = 0.0005) were also significantly lowered. There were 185 deaths in the atorvastatin group and 212 in the placebo group (0.87 [0.71-1.06], p = 0.16). Atorvastatin lowered total serum cholesterol by about 1.3 mmol/L compared with placebo at 12 months, and by 1.1 mmol/L after 3 years of follow-up.
INTERPRETATION: The reductions in major cardiovascular events with atorvastatin are large, given the short follow-up time. These findings may have implications for future lipid-lowering guidelines.

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Year:  2004        PMID: 15765890     DOI: 10.2165/00003495-200464002-00005

Source DB:  PubMed          Journal:  Drugs        ISSN: 0012-6667            Impact factor:   9.546


  28 in total

1.  Targeting lipid-lowering drug therapy for primary prevention of coronary disease: an updated Sheffield table.

Authors:  L E Ramsay; I U Haq; P R Jackson; W W Yeo; D M Pickin; J N Payne
Journal:  Lancet       Date:  1996-08-10       Impact factor: 79.321

2.  Rationale, design, methods and baseline demography of participants of the Anglo-Scandinavian Cardiac Outcomes Trial. ASCOT investigators.

Authors:  P S Sever; B Dahlöf; N R Poulter; H Wedel; G Beevers; M Caulfield; R Collins; S E Kjeldsen; G T McInnes; J Mehlsen; M Nieminen; E O'Brien; J Ostergren
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10.  Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. West of Scotland Coronary Prevention Study Group.

Authors:  J Shepherd; S M Cobbe; I Ford; C G Isles; A R Lorimer; P W MacFarlane; J H McKillop; C J Packard
Journal:  N Engl J Med       Date:  1995-11-16       Impact factor: 91.245

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9.  Interaction between a commercially available St. John's wort product (Movina) and atorvastatin in patients with hypercholesterolemia.

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Review 10.  Clinical Update: Cardiovascular Disease in Diabetes Mellitus: Atherosclerotic Cardiovascular Disease and Heart Failure in Type 2 Diabetes Mellitus - Mechanisms, Management, and Clinical Considerations.

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