Potent anti-ischaemic effects of statins in chronic stable angina: incremental benefit beyond lipid lowering?
OBJECTIVE
The DoUble-blind Atorvastatin AmLodipine (DUAAL) trial investigated whether atorvastatin decreases ischaemia by a vascular benefit, independent of low-density lipoprotein cholesterol lowering, in patients with coronary artery disease (CAD), both alone and in combination with the traditional anti-anginal therapy, amlodipine.


RESULTS
Randomized, double-blind, parallel-group, multicountry trial (2 weeks run-in and 24 weeks active therapy) comparing three treatments: amlodipine, atorvastatin, and amlodipine + atorvastatin; in 311 patients (78% male; mean age 62 years) with stable angina (≥ 2 attacks/week), CAD history, ≥ 3 transient myocardial ischaemia (TMI) episodes, and/or ≥ 15 min ischaemia on 48 h ambulatory electrocardiographic (AECG) monitoring. Efficacy variables were change in TMI by AECG, exercise ischaemia, angina diary data, and inflammatory biomarkers at Week 26. There was a comparable, highly significant decrease in TMI with amlodipine and atorvastatin, but no additional benefit for the combination. More than 50% of patients became TMI-free in all three groups and this was accompanied by a comparable, marked reduction in angina and nitroglycerin consumption. High-sensitivity C-reactive protein fell by 40% in patients receiving atorvastatin but there was no change with amlodipine. Adverse events were comparable among groups.


CONCLUSIONS
Atorvastatin was as potent an anti-ischaemic agent as amlodipine. Future studies of combination therapies will be instructive.


BACKGROUND
National clinical trial number: NCT00159718, protocol number A0531031 listed on http://clinicaltrials.gov/.
Deanfield
John E
JE
Great Ormond Street Hospital, University College London, London, UK. j.deanfield@ich.ucl.ac.uk
Sellier
Phillipe
P
Thaulow
Erik
E
Bultas
Jan
J
Yunis
Carla
C
Shi
Harry
H
Buch
Jan
J
Beckerman
Bruce
B
D000369:Aged, 80 and over; D017311:Amlodipine / Q000627:therapeutic use; D060050:Angina, Stable / Q000188:drug therapy*; D000959:Antihypertensive Agents / Q000627:therapeutic use; D000069059:Atorvastatin; D002908:Chronic Disease; D004311:Double-Blind Method; D004338:Drug Combinations; D015716:Electrocardiography, Ambulatory; D005080:Exercise Test; D005260:Female; D006538:Heptanoic Acids / Q000627:therapeutic use; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D006949:Hyperlipidemias / Q000188:drug therapy; D006973:Hypertension / Q000188:drug therapy; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000188:drug therapy*; D011758:Pyrroles / Q000627:therapeutic use; D055815:Young Adult
D000959:Antihypertensive Agents; D004338:Drug Combinations; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents; D011758:Pyrroles; C487936:amlodipine, atorvastatin drug combination; D017311:Amlodipine; D000069059:Atorvastatin