Potential synergy between lipid-lowering and blood-pressure-lowering in the Anglo-Scandinavian Cardiac Outcomes Trial.
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.
Sever
Peter
P
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
Dahlöf
Björn
B
Poulter
Neil
N
Wedel
Hans
H
Beevers
Gareth
G
Caulfield
Mark
M
Collins
Rory
R
Kjeldsen
Sverre
S
Kristinsson
Arni
A
McInnes
Gordon
G
Mehlsen
Jesper
J
Nieminem
Markku
M
O'Brien
Eoin
E
Ostergren
Jan
J
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
D000924:Anticholesteremic Agents; D000959:Antihypertensive Agents; D004338:Drug Combinations