The Anglo-Scandinavian Cardiac Outcomes Trial lipid lowering arm: extended observations 2 years after trial closure.
OBJECTIVE
To determine the cardiovascular benefits in those originally assigned atorvastatin in the Anglo-Scandinavian Cardiac Outcomes Trial-2.2 years after closure of the lipid-lowering arm of the trial (ASCOT-LLA).


RESULTS
The Blood Pressure Lowering Arm of the ASCOT trial (ASCOT-BPLA) compared two different antihypertensive treatment strategies on cardiovascular outcomes. ASCOT-LLA was a double-blind placebo-controlled trial of atorvastatin in those enrolled into ASCOT-BPLA with total cholesterol concentrations at baseline of < or =6.5 mmol/L. A total of 19 342 hypertensive patients were enrolled in ASCOT-BPLA and 10 305 were further assigned either atorvastatin, 10 mg, or placebo. ASCOT-LLA was stopped prematurely after a median 3.3 years follow-up because of substantial cardiovascular benefits in those assigned atorvastatin. Trial physicians were invited to offer atorvastatin to all ASCOT-LLA patients until the end of ASCOT-BPLA. The primary outcome of ASCOT-LLA was combined fatal coronary heart disease (CHD) or non-fatal myocardial infarction. Secondary outcomes included all coronary events, all cardiovascular events and procedures, fatal and non-fatal stroke, cardiovascular mortality, all cause mortality, development of chronic stable angina, heart failure, and peripheral arterial disease. By the end of ASCOT-LLA, there was a 36% relative risk reduction in primary events (n = 254) in favour of atorvastatin [hazard ratio (HR) 0.64, 95% CI: 0.50-0.83, P = 0.0005]. At the end of ASCOT-BPLA, 2.2 years later, despite extensive crossovers from and to statin usage, the relative risk reduction in primary events (n = 412) among those originally assigned atorvastatin remained at 36% (HR 0.64, 95% CI: 0.53-0.78, P = 0.0001). For almost all other endpoints, risk reductions also remained essentially unchanged and in the case of all cause mortality, the risk reduction of 15% now achieved borderline statistical significance (P = 0.02).


CONCLUSIONS
Carry-over benefits from those originally assigned atorvastatin but no longer taking the drug may account for unchanged relative risk reductions in most cardiovascular endpoints observed 2 years after ASCOT-LLA closed.
Sever
Peter S
PS
International Centre for Circulatory Health, Imperial College London, 59 North Wharf Road, London W2 1PG, UK. p.sever@imperial.ac.uk
Poulter
Neil R
NR
Dahlof
Bjorn
B
Wedel
Hans
H
Beevers
Gareth
G
Caulfield
Mark
M
Collins
Rory
R
Kjeldsen
Sverre E
SE
Kristinsson
Arni
A
McInnes
Gordon
G
Mehlsen
Jesper
J
Nieminen
Markku S
MS
O'Brien
Eoin T
ET
Ostergren
Jan
J
D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use; D000069059:Atorvastatin; D003327:Coronary Disease / Q000401:mortality / Q000517:prevention & control*; D004812:Epidemiologic Methods; D005260:Female; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D006937:Hypercholesterolemia / Q000517:prevention & control*; D006973:Hypertension / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000401:mortality / Q000517:prevention & control*; D011758:Pyrroles / Q000627:therapeutic use*; D020521:Stroke / Q000401:mortality / Q000517:prevention & control
D000924:Anticholesteremic Agents; D000959:Antihypertensive Agents; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D000069059:Atorvastatin