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Drugs

, Volume 64, Supplement 2, pp 43–60 | Cite as

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 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
  • ASCOT investigators
Article

Summary

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.

Keywords

Statin Atorvastatin Pravastatin Coronary Heart Disease Event Total Cholesterol Concentration 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

We thank all trial participants, physicians, nurses, and practices in the participating countries for their important contribution to the study. The study was supported by the principal funding source, Pfizer, New York, NY, USA. Funding was also provided by Servier Research Group, Paris, France, and Leo Laboratories, Copenhagen, Denmark. We thank Yvonne Green and Sandra Johnson for their help in typing and collating the report.

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Copyright information

© Adis Data Information BV 2004

Authors and Affiliations

  • Peter S Sever
    • 1
  • Björn Dahlöf
    • 2
  • Neil R Poulter
    • 1
  • Hans Wedel
    • 12
  • Gareth Beevers
    • 3
  • Mark Caulfield
    • 4
  • Rory Collins
    • 5
  • Sverre E Kjeldsen
    • 6
  • Arni Kristinsson
    • 7
  • Gordon T McInnes
    • 8
  • Jesper Mehlsen
    • 9
  • Markku Nieminen
    • 10
  • Eoin O’Brien
    • 11
  • Jan Östergren
    • 12
  • ASCOT investigators
  1. 1.Cardiovascular Studies Unit, Department of Clinical Pharmacology, Imperial College LondonNHLI, Faculty of MedicineLondonUK
  2. 2.Sahlgrenska University Hospital/ÖstraGothenburgSweden
  3. 3.City HospitalBirminghamUK
  4. 4.Barts and the London, Queen Mary’s School of MedicineLondonUK
  5. 5.Radcliffe InfirmaryOxfordUK
  6. 6.Ullevål SykehusOsloNorway
  7. 7.University HospitalReykjavikIceland
  8. 8.University of GlasgowGlasgowUK
  9. 9.H S Frederiksberg HospitalFrederiksbergDenmark
  10. 10.University Central HospitalHelsinkiFinland
  11. 11.Beaumont HospitalDublinIreland
  12. 12.Karolinska HospitalStockholmSweden

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