High-Dose Statins Have Substantial Effects on Soluble P-Selectin in Advanced CAD

High-dose statins have significant effects on platelet-derived proteins among patients with advanced coronary artery disease (CAD) who fail to reach treatment goals on standard treatment, according to results of a study published in the International Journal of Cardiology.

Patients (N=130) with advanced CAD who failed to reach low-density lipoprotein cholesterol (LDL-C) targets after 6 to 12 months with 10 mg/day rosuvastatin (n=62), 20 mg/day atorvastatin (n=23), 20 mg/day simvastatin (n=21), 10 mg/day atorvastatin (n=17), or 5 mg/day rosuvastatin (n=7) were recruited at the Jagiellonian University Medical College in Poland. Plasma soluble P-selectin (sP-selectin), fibrin clot permeability (Ks), clot lysis time (CLT), thrombin generation, and fibrinolysis proteins were evaluated at baseline and after switching to high-dose therapy. Elevated sP-selectin was defined as being more than 37.9 ng/mL.

The patients had a median age of 64 (IQR, 59-70) years, 48.5% were men, 33.8% were obese, 74.6% had a previous myocardial infarction, 59.2% had arterial hypertension, 91.5% were taking aspirin, 43.1% were taking beta-blockers, and 40% were taking angiotensin-converting enzyme inhibitors.

At baseline, 77 patients had elevated sP-selectin. The patients with elevated sP-selectin also had elevated alanine transaminase (median, 24 vs 19 IU/L; P =.04) and CLT (median, 91 vs 85 min; P =.006) and depressed Ks (median, 6.6 vs 7.6 10^-9cm²; P <.001) compared with patients who had normal sP-selectin, respectively.

After failing to reach treatment goals, the patients were switched to 80 mg/day (n=76) or 40 mg/day (n=54) atorvastatin.

At a median follow-up of 7 months, total cholesterol decreased by 14%, LDL-C by 24.5%, and C-reactive protein by 42.8%. Levels of sP-selectin were also decreased by 32.6% (P <.001), at which point all patients were observed to have levels within the normal range.

Significant associations were observed for Ks with fibrinogen (β, -0.44; P <.001) and sP-selectin (β, -0.27; P =.002); CLT with sP-selectin (β, 0.21; P =.034); the change in Ks with change in fibrinogen (β, -0.39; P <.001), change in sP-selectin (β, -0.29; P <.001), age (β, -0.17; P =.033), change in LDL-C (β, -0.15; P =.038), and hypertension (β, 0.21; P =.003); and the change in CLT with the change in fibrinogen (β, 0.20; P =.041), age (β, 0.21; P =.031), and change in sP-selectin (β, 0.24; P =.012).

The major limitation of this study is that it remains unclear which aspects of these trends are causal.

“…we found that high-dose statins can exert a substantial antiplatelet action, as evidenced by reduced sP-selectin, and these actions could improve fibrin clot structure and functions, independent of LDL-C lowering,” the study authors wrote. “The current findings provide new insights into additional effects of high-dose statins, which might contribute to reduction in thromboembolic events in CAD patients receiving such therapy.”