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Sex-Related Differences of Coronary Atherosclerosis Regression Following Maximally Intensive Statin Therapy: Insights From SATURN
Study Questions:
Are sex-related differences in coronary atheroma regression observed following high-intensity statin therapy?
Methods:
Data from the SATURN (Study of Coronary Atheroma by Intravascular Ultrasound: Effect of Rosuvastatin Versus Atorvastatin) study were used for the present analysis. SATURN was a randomized controlled study that included patients with angiographically demonstrable coronary disease and low-density lipoprotein cholesterol (LDL-C) <116 mg/dl. Participants were randomized to a 2-week treatment period with atorvastatin 40 mg or rosuvastatin 20 mg daily, and then re-randomized and treated for 24 months with atorvastatin 80 mg or rosuvastatin 40 mg daily. Subjects underwent intravascular ultrasound (IVUS) imaging of a coronary artery at baseline and after 104 weeks of treatment. Serial IVUS measures of coronary atheroma volume in patients treated with rosuvastatin 40 mg or atorvastatin 80 mg for 24 months were obtained.
Results:
A total of 765 men and 274 women were included in the trial. Compared with men, women were older (p < 0.001) and more likely to have hypertension (p < 0.001), diabetes (p = 0.002), and have LDL-C (p = 0.01), high-density lipoprotein cholesterol (HDL-C) (p < 0.001), and C-reactive protein (CRP) (p = 0.004) levels. At follow-up, women had higher HDL-C (p < 0.001) and CRP (p < 0.001), but similar LDL-C (p = 0.46) levels compared with men. Compared with men, women had lower baseline percent atheroma volume (PAV) (34.0 ± 8.0% vs. 37.2 ± 8.2%, p < 0.001) and total atheroma volume (TAV) (122.4 ± 55 mm3 vs. 151.9 ± 63 mm3, p < 0.001) yet demonstrated greater PAV regression (-1.52 ± 0.18% vs. -1.07 ± 0.10%, p = 0.03) and TAV regression (-8.27 ± 0.9 mm3 vs. -6.59 ± 0.50 mm3, p = 0.11) following treatment. Greater PAV regression in women versus men occurred with rosuvastatin (p = 0.004), those with diabetes (p = 0.01), stable coronary disease (p = 0.01), higher baseline LDL-C (p = 0.02), and higher CRP (p = 0.04) levels. On multivariable analysis, female sex was independently associated with PAV regression (p = 0.01), and a sex-treatment interaction was found (p = 0.036). For participants with on-treatment LDL-C levels <70 mg/dl, women achieved greater PAV regression (-1.81 ± 0.22% vs. -1.12 ± 0.13%, p = 0.007) and TAV regression (-10.1 ± 1.1 mm3 vs. -7.16 ± 0.65 mm3, p = 0.023) than men, whereas PAV and TAV regression did not differ by sex, with LDL-C levels ≥70 mg/dl.
Conclusions:
The investigators concluded that women with coronary disease demonstrate greater coronary atheroma regression than men when empirically prescribed guideline-driven potent statin therapy. This benefit appears in the setting of lower on-treatment LDL-C levels.
Perspective:
These data support the use of intensive dose statins for women with coronary artery disease. Often women are resistant to use higher doses of statins. These data can be used to advise women of the benefits associated with statins, in particular intensive dose therapy.
Keywords: Pyrroles, Fluorobenzenes, Cholesterol, C-Reactive Protein, Plaque, Atherosclerotic, Pyrimidines, Heptanoic Acids, Hypertension, Diabetes Mellitus, Sulfonamides
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