Lack of effect of 8 weeks atorvastatin on microvascular endothelial function in patients with systemic sclerosis.

OBJECTIVE

The aim of this study was to test the hypothesis that statin therapy confers benefit on the microvasculature, including improving endothelial function, in patients with SSc.

METHODS

This was a randomized, parallel group, double-blind study, with assessments at baseline, 4 and 8 weeks. Thirty-six patients were randomly assigned to receive 8 weeks treatment with atorvastatin 20 mg/day or placebo. The primary end-point was endothelial-dependent vasodilation, as assessed by response to iontophoresis with acetylcholine chloride (ACh) as measured by laser Doppler imaging. Secondary end-points included endothelial-independent vasodilation, microvascular structure as assessed by videocapillaroscopy, von Willebrand factor, high-sensitivity CRP and plasma cholesterol.

RESULTS

Eighteen patients were randomly assigned to atorvastatin and 18 to placebo. Eight weeks treatment resulted in no statistically significant differences in any of the outcome measures (other than cholesterol) between atorvastatin and placebo groups. The median area under the curve for ACh iontophoresis at baseline was 1569 perfusion units (PU).time in the atorvastatin group and 1450 PU.time in the placebo group, and at 8 weeks 2146 and 1822 PU.time, respectively. Mean difference (95% CI) at 8 weeks was 355 (-835, 1544) PU.time.

CONCLUSION

Atorvastatin 20 mg/day, given for 8 weeks, was not associated with changes in microvascular function or structure. The large variation in outcome scores means that it is not possible to rule out an effect on the basis of this trial. Future studies should be of longer duration and include patients with early disease who are unlikely to have irreversible structural vascular disease.

TRIAL REGISTRATION

EudraCT, https://eudract.emea.europa.eu/, 2005-003775-21.