Long-Term Effect of Pravastatin on Carotid Intima-Media Complex Thickness: The J-STARS Echo Study (Japan Statin Treatment Against Recurrent Stroke)

Masatoshi Koga, Kazunori Toyoda, Kazuo Minematsu, Masahiro Yasaka, Yoji Nagai, Shiro Aoki, Tomohisa Nezu, Naohisa Hosomi, Tatsuo Kagimura, Hideki Origasa, Kenji Kamiyama, Rieko Suzuki, Toshiho Ohtsuki, Hirofumi Maruyama, Kazuo Kitagawa, Shinichiro Uchiyama, Masayasu Matsumoto, J-STARS Investigators, Masatoshi Koga, Kazunori Toyoda, Kazuo Minematsu, Masahiro Yasaka, Yoji Nagai, Shiro Aoki, Tomohisa Nezu, Naohisa Hosomi, Tatsuo Kagimura, Hideki Origasa, Kenji Kamiyama, Rieko Suzuki, Toshiho Ohtsuki, Hirofumi Maruyama, Kazuo Kitagawa, Shinichiro Uchiyama, Masayasu Matsumoto, J-STARS Investigators

Abstract

Background and purpose: The effect of statins on progression of carotid intima-media complex thickness (IMT) has been shown exclusively in nonstroke Western patients. This study aimed to determine the effect of low-dose pravastatin on carotid IMT in Japanese patients with noncardioembolic ischemic stroke.

Methods: This is a substudy of the J-STARS trial (Japan Statin Treatment Against Recurrent Stroke), a multicenter, randomized, open-label, parallel-group trial to examine whether pravastatin reduces stroke recurrence. Patients were randomized to receive pravastatin (10 mg daily, usual dose in Japan; pravastatin group) or not to receive any statins (control group). The primary outcome was IMT change of the common carotid artery for a 5-year observation period. IMT change was compared using mixed-effects models for repeated measures.

Results: Of 864 patients registered in this substudy, 71 without baseline ultrasonography were excluded, and 388 were randomly assigned to the pravastatin group and 405 to the control group. Baseline characteristics were not significantly different, except National Institutes of Health Stroke Scale scores (median, 0 [interquartile range, 0-2] versus 1 [interquartile range, 0-2]; P=0.019) between the 2 groups. Baseline IMT (mean±SD) was 0.887±0.155 mm in the pravastatin group and 0.887±0.152 mm in the control group (P=0.99). The annual change in the IMT at 5-year visit was significantly reduced in the pravastatin group as compared with that in the control group (0.021±0.116 versus 0.040±0.118 mm; P=0.010).

Conclusions: The usual Japanese dose of pravastatin significantly reduced the progression of carotid IMT at 5 years in patients with noncardioembolic stroke.

Clinical trial registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00361530.

Keywords: carotid intima-media thickness; dyslipidemias; hydroxymethylglutaryl-CoA reductase inhibitors; pravastatin; ultrasonography.

© 2017 The Authors.

Figures

Figure 1.
Figure 1.
Flow chart of patient enrollment is shown.
Figure 2.
Figure 2.
Temporal trends of total cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, and high-density lipoprotein (HDL) cholesterol by allocated groups for 5 years are shown.
Figure 3.
Figure 3.
Temporal trends of mean intima–media thickness (IMT) by allocated groups for 5 years are shown. Each data indicate the least square mean of the difference from baseline.
Figure 4.
Figure 4.
Temporal trends of maximum intima–media thickness (IMT) by allocated groups for 5 years are shown. Each data indicate the least square mean of the difference from baseline.

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