Authors: Peter S. Sever¹; Björn Dahlöf²; Neil R. Poulter¹; Hans Wedel³; Gareth Beevers⁴; Mark Caulfield⁵; Rory Collins⁶; Sverre E. Kjeldsen⁷; Arni Kristinsson⁸; Gordon T. McInnes⁹; Jesper Mehlsen¹⁰; Markku Nieminen¹¹; Eoin O'Brien¹²; Jan Östergren¹³

Source: Drugs, Volume 64, Supplement 2, 2004 , pp. 43-60(18)

Publisher: Adis International

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.

Lancet 2003; 361: 1149--58. Published online April 2, 2003 <affiliation><affid="affiliation15">http://image.thelancet.com/extras/03art3046web.pdf</affiliation> see Commentary Page 1144

Document Type: Research article

Affiliations: 1: Imperial College, London, UK 10: H S Frederiksberg Hospital, Frederiksberg, Denmark 11: University Central Hospital, Helsinki, Finland 12: Beaumont Hospital, Dublin, Ireland 13: Karolinska Hospital, Stockholm, Sweden 2: Sahlgrenska University Hospital/Östra, Gothenburg, Sweden 3: Nordic School of Public Health, Gothenburg, Sweden 4: City Hospital, Birmingham, UK 5: Barts and the London, Queen Mary's School of Medicine, London, UK 6: Radcliffe Infirmary, Oxford, UK 7: Ullevål Sykehus, Oslo, Norway 8: University Hospital, Reykjavik, Iceland 9: University of Glasgow, Glasgow, UK

Publication date: 2004-01-01

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• In this Subject: Pharmacology ,  Therapeutics & Alternative Medicine
• By this author: Peter S. Sever ;  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 Östergren

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