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.”
Siudut J, Pudlo J, Konieczyńska M, Polak M, Jawień J, Undas A. Therapy with high-dose statins reduces soluble P-selectin: the impact on plasma fibrin clot properties. Int J Cardiol. Published online November 18, 2022. doi:10.1016/j.ijcard.2022.11.026