title: Potential synergy between lipid-lowering and blood-pressure-lowering in the Anglo-Scandinavian Cardiac Outcomes Trial.
abstract: OBJECTIVE
  A prespecified objective of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) was to assess whether any synergistic effects were apparent between the lipid-lowering and blood-pressure-lowering regimens in preventing cardiovascular events.
  
  
  RESULTS
  A total of 19 257 hypertensive subjects were randomized to an amlodipine-based regimen or an atenolol-based regimen. Of these, 10 305 subjects with total cholesterol < or =6.5 mmol/L were further randomized to atorvastatin 10 mg daily or placebo. In this analysis, the effects of atorvastatin were compared with placebo on coronary heart disease (CHD), cardiovascular and stroke events in those assigned amlodipine-based and atenolol-based regimens. In the ASCOT lipid-lowering arm (LLA), overall, atorvastatin reduced the relative risk of the primary endpoint of non-fatal myocardial infarction and fatal CHD events by 36% (HR 0.64, CI 0.50-0.83, P=0.0005), total cardiovascular events by 21% (HR 0.79, CI 0.69-0.90, P=0.0005), and stroke by 27% (HR 0.73, CI 0.56-0.96, P=0.024). However, atorvastatin reduced the relative risk of CHD events by 53% (HR 0.47, CI 0.32-0.69, P<0.0001) among those allocated the amlodipine-based regimen, and by 16% (HR 0.84, CI 0.60-1.17, p: n.s.) among those allocated the atenolol-based regimen (P=0.025 for heterogeneity). There were no significant differences between the effects of atorvastatin on total cardiovascular events or strokes among those assigned amlodipine (HR 0.73, CI 0.60-0.88, P<0.005 and HR 0.69, CI 0.45-1.06, P: n.s., respectively) or atenolol (HR 0.85, CI 0.71-1.02, P: n.s and HR 0.76, CI 0.53-1.08, P: n.s, respectively). Differences in blood pressure and lipid parameters (placebo corrected) between the two antihypertensive treatment limbs could not account for the differences observed in CHD outcome.
  
  
  CONCLUSIONS
  These findings of an apparent interaction between atorvastatin and an amlodipine-based regimen in the prevention of CHD events are of borderline significance, and hence generate an hypothesis that merits independent evaluation in other trials.
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
authors.initials: P
authors.lastname: Sever
authors.forename: Björn
authors.initials: B
authors.lastname: Dahlöf
authors.forename: Neil
authors.initials: N
authors.lastname: Poulter
authors.forename: Hans
authors.initials: H
authors.lastname: Wedel
authors.forename: Gareth
authors.initials: G
authors.lastname: Beevers
authors.forename: Mark
authors.initials: M
authors.lastname: Caulfield
authors.forename: Rory
authors.initials: R
authors.lastname: Collins
authors.forename: Sverre
authors.initials: S
authors.lastname: Kjeldsen
authors.forename: Arni
authors.initials: A
authors.lastname: Kristinsson
authors.forename: Gordon
authors.initials: G
authors.lastname: McInnes
authors.forename: Jesper
authors.initials: J
authors.lastname: Mehlsen
authors.forename: Markku
authors.initials: M
authors.lastname: Nieminem
authors.forename: Eoin
authors.initials: E
authors.lastname: O'Brien
authors.forename: Jan
authors.initials: J
authors.lastname: Ostergren
mesh_terms: D000328:Adult; D000368:Aged; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D004338:Drug Combinations; D004357:Drug Synergism; D005260:Female; D006801:Humans; D006949:Hyperlipidemias / Q000188:drug therapy*; D006973:Hypertension / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged
chemical_list: D000924:Anticholesteremic Agents; D000959:Antihypertensive Agents; D004338:Drug Combinations