title: The Anglo-Scandinavian Cardiac Outcomes Trial: 11-year mortality follow-up of the lipid-lowering arm in the U.K.
abstract: OBJECTIVE
  The aim of this study was to determine the outcome benefits in those originally assigned atorvastatin in the Anglo-Scandinavian Cardiac Outcomes Trial-8 years after closure of the lipid-lowering arm (LLA) of the trial (ASCOT-LLA) among the U.K. population.
  
  
  RESULTS
  ASCOT-LLA was a factorially designed double-blind placebo-controlled trial of atorvastatin in 10 305 hypertensive patients enrolled into the ASCOT-Blood Pressure Lowering Arm (BPLA) of the trial and with total cholesterol concentrations, at baseline, of <6.5 mmol/L. ASCOT-LLA was stopped prematurely after a median 3.3-year follow-up because of a 36% relative risk reduction (RRR) in non-fatal myocardial infarction and fatal coronary heart disease (CHD) (the primary outcome) in favour of atorvastatin and a non-significant reduction in CV deaths (16%) and all-cause mortality (13%). After a further 2.2 years at the end of ASCOT-BPLA, despite extensive crossovers from and to statin usage, the RRR in all endpoints remained essentially unchanged. A median 11 years after initial randomization and ∼8 years after closure of LLA, all-cause mortality (n=520 and 460 in placebo and atorvastatin, respectively) remained significantly lower in those originally assigned atorvastatin (HR 0.86, CI 0.76-0.98, P=0.02). CV deaths were fewer, but not significant (HR 0.89, CI 0.72-1.11, P=0.32) and non-CV deaths were significantly lower (HR 0.85, CI 0.73-0.99, P=0.03) in those formerly assigned atorvastatin attributed to a reduction in deaths due to infection and respiratory illness.
  
  
  CONCLUSIONS
  Legacy effects of those originally assigned atorvastatin may contribute to long-term benefits on all-cause mortality. An explanation for long-term benefits on non-CV deaths has not been established.
authors.affiliation: Clinical Pharmacology and Therapeutics, Imperial College London, International Centre for Circulatory Health, 59 North Wharf Road, London W2 1PG, UK. p.sever@imperial.ac.uk
authors.forename: Peter S
authors.initials: PS
authors.lastname: Sever
authors.forename: Choon L
authors.initials: CL
authors.lastname: Chang
authors.forename: Ajay K
authors.initials: AK
authors.lastname: Gupta
authors.forename: Andrew
authors.initials: A
authors.lastname: Whitehouse
authors.forename: Neil R
authors.initials: NR
authors.lastname: Poulter
mesh_terms: D000328:Adult; D000368:Aged; D000069059:Atorvastatin; D002423:Cause of Death; D003327:Coronary Disease / Q000401:mortality / Q000517:prevention & control; D004311:Double-Blind Method; D057239:Early Termination of Clinical Trials; D005260:Female; D005500:Follow-Up Studies; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D006937:Hypercholesterolemia / Q000401:mortality / Q000517:prevention & control; D006973:Hypertension / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011758:Pyrroles / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D000069059:Atorvastatin