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.
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.


RESULTS
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.


CONCLUSIONS
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.
Sever
Peter S
PS
Imperial College, London, UK.
Dahlöf
Björn
B
Poulter
Neil R
NR
Wedel
Hans
H
Beevers
Gareth
G
Caulfield
Mark
M
Collins
Rory
R
Kjeldsen
Sverre E
SE
Kristinsson
Arni
A
McInnes
Gordon T
GT
Mehlsen
Jesper
J
Nieminen
Markku
M
O'Brien
Eoin
E
Ostergren
Jan
J
D000328:Adult; D000368:Aged; D000069059:Atorvastatin; D002784:Cholesterol / Q000097:blood*; D003327:Coronary Disease / Q000401:mortality / Q000517:prevention & control*; D023381:Endpoint Determination; D005260:Female; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D006973:Hypertension / Q000150:complications*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology / Q000517:prevention & control; D016016:Proportional Hazards Models; D011758:Pyrroles / Q000627:therapeutic use*; D012537:Scandinavian and Nordic Countries; D020521:Stroke / Q000401:mortality / Q000517:prevention & control*; D016896:Treatment Outcome; D006113:United Kingdom
D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D002784:Cholesterol; D000069059:Atorvastatin