Potent anti-ischaemic effects of statins in chronic stable angina: incremental benefit beyond lipid lowering?

Abstract

Aims: 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.

Methods and 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.

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

Clinical trial registration information: National clinical trial number: NCT00159718, protocol number A0531031 listed on http://clinicaltrials.gov/.

Figure 1

Study design. AECG, ambulatory electrocardiogram; ET, exercise test.

Figure 2

Flow of participants through the trial. MITT, modified intent-to-treat.

Figure 3

Median number of transient myocardial ischaemia episodes/week, recorded by ambulatory electrocardiographic 48 h monitoring. **P < 0.001 vs. baseline. TMI, transient myocardial ischaemia.

Figure 4

Twenty-four-hour circadian patterns during ambulatory electrocardiographic monitoring for the three treatment groups.

Figure 5

(A) Mean angina attacks/week and (B) mean number of nitroglycerin tablets/week, based on patients' diaries. **P < 0.001 vs. baseline; ^†P < 0.05 change from baseline between groups.

Figure 6

Change from baseline in high-sensitivity C-reactive protein by treatment group. *P < 0.05 vs. baseline; **P < 0.001 vs. baseline; ^†P < 0.001 for change from baseline between treatment groups.

Figure 7

Change in number of transient myocardial ischaemia episodes during ambulatory electrocardiographic monitoring and high-sensitivity C-reactive protein in the three groups. TMI, transient myocardial ischaemia; AECG, ambulatory electrocardiogram.