Short-term effect of atorvastatin on ischaemic threshold in hypercholesterolaemic patients with stable ischaemic heart disease.
OBJECTIVE
Hypercholesterolaemia is associated with a loss of endothelium-dependent vasodilation, which may facilitate the occurrence of myocardial ischaemia in patients with coronary artery disease (CAD). The improvement of endothelial dilator function after 4 to 6 weeks of oral lipid-lowering therapy has been documented. Whether this early restoration of endothelial function by statins translates into anti-ischaemic effects is unknown. This study was designed to determine the effect of 4 weeks' treatment with 80 mg atorvastatin daily on exercise-induced ischaemia in patients with stable ischaemic heart disease (IHD) receiving standard anti-anginal drug therapy.


RESULTS
A total of 41 patients with documented CAD, exercise-induced ischaemia and LDL-cholesterol > 130 mg/dl underwent exercise ECG, angina score and lipid level assessment at baseline, after 4 weeks of placebo treatment, and after 4 weeks of therapy with atorvastatin 80 mg. Primary endpoint was the change in time to 1 mm ST-segment depression (= ischaemic threshold) between placebo and treatment period. Atorvastatin treatment resulted in a 55% reduction of low-density lipoprotein (LDL) cholesterol (from mean of 162 (SD 32) to 72 (20) mg/dl). For a comparable rate-pressure product, the average time to 1 mm ST-segment depression was 295 (112) s at baseline, 314 (149) s after placebo and 301 (131) s after atorvastatin, indicating that the ischaemic threshold was not significantly modulated after 4 weeks of atorvastatin treatment. There was also no significant change in global angina score or in time to maximal ST-segment depression.


CONCLUSIONS
High-dose atorvastatin treatment for 4 weeks drastically reduced LDL-cholesterol. However, the present study did not demonstrate a significant effect on the ischaemic threshold in patients with stable IHD already under treatment with anti-ischaemic agents.
Claeys
Marc J
MJ
Cardiology, Hospital Brain l'Alleud, Rue Wayez 35, 1420 Brain l'Alleud, Belgium. marc.claeys@ua.ac.be
Cosyns
Bernard
B
Hoffer
Etienne
E
Carlier
Marc
M
Missault
Luc
L
Cools
Frank
F
De Meester
Antoine
A
Vermeersch
Paul
P
Gobin
Eric
E
Dewit
Brigitte
B
D000368:Aged; D000787:Angina Pectoris; D000069059:Atorvastatin; D008078:Cholesterol, LDL / Q000187:drug effects; D018450:Disease Progression; D005080:Exercise Test; D005260:Female; D006538:Heptanoic Acids / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D006937:Hypercholesterolemia / Q000150:complications / Q000503:physiopathology*; D008297:Male; D017202:Myocardial Ischemia / Q000150:complications / Q000188:drug therapy*; D011758:Pyrroles / Q000494:pharmacology / Q000627:therapeutic use*; D013997:Time Factors
D008078:Cholesterol, LDL; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D000069059:Atorvastatin