Abstract
The selection of optimum statin intensity is inconclusive, and the association of plasma exposure of statins and metabolites with major adverse cardiovascular events (MACEs) is unclear. This study sought to compare the effect of low (quartile 1), intermediate (quartiles 2 and 3), and high (quartile 4) plasma exposure of statins and metabolites on MACE, re-ischemia events and death in patients with coronary artery disease (CAD) at 5 years. A total of 1,644 patients in atorvastatin (AT) cohort and 804 patients in rosuvastatin (RST) cohort were included, and their plasma concentration of statins and metabolites was categorized as low-, mid-, or high-group. The association between the plasma levels of statins and metabolites and the incidence of primary endpoint in patients was assessed by Cox proportional hazard models. Intensive AT exposure (Q4 > 5.32 ng/ml) was significantly associated with increased risk of death compared with low (hazard ratio [HR]: 1.522; 95% confidence interval [CI]: 1.035–1.061; P = 0.0022) or moderate exposure (HR: 2.054; 95% CI: 1.348–3.130; P = 0.0008). This association was also found in AT’s five metabolites (all P < 0.01). In patients with RST treatment, moderate RST concentration (0.53–4.29 ng/ml) versus low concentration had a significantly lower risk of MACE and re-ischemia events. (HR: 0.532, 95% CI: 0.347–0.815, P = 0.0061 and HR: 0.505, 95% CI: 0.310–0.823, P = 0.0061, respectively). A higher plasma exposure of AT and metabolites has a significantly higher risk of death, and moderate RST exposure has a significantly lower risk of MACE and re-ischemia events in Chinese patients with CAD. The harms of high plasma exposure should be considered when prescribing statins to patients because it may be a risk factor for having poor prognosis in patients with CAD.
Highlights
Statin therapy is extensively used in the primary and secondary prevention of coronary artery disease (CAD). It is effective in reducing the rates of major adverse cardiovascular events (MACEs) by approximately a quarter and improving longterm survival compared with placeb (Cholesterol Treatment Trialists C, et al, 2010; Fitchett et al, 2015; Silverman et al, 2016)
We recruited 1,644 patients taking AT in stage I to evaluate the impact of statin exposure on MACE, re-ischemia, and death, and 804 patients taking RST in stage II to further confirm the idea
We grouped patients into patients with low (< 0.53 ng/ ml), moderate (0.53–4.29 ng/ml) and high (> 4.29 ng/ml) RST concentration, and we found that patients with moderate RST concentration versus low concentration had a significantly lower risk of MACE, with hazard ratios (HRs) = 0.532 (0.347–0.815), P = 0.0038
Summary
Statin therapy is extensively used in the primary and secondary prevention of coronary artery disease (CAD) It is effective in reducing the rates of major adverse cardiovascular events (MACEs) by approximately a quarter and improving longterm survival compared with placeb (Cholesterol Treatment Trialists C, et al, 2010; Fitchett et al, 2015; Silverman et al, 2016). The USPSTF guideline (Force et al, 2016) recommends to initiate low- to moderate-dose statin treatment for adults aged 40–75 years who have no history of cardiovascular disease (CVD), have one or more CVD risk factors, and have a calculated 10-year CVD event risk of 10% or greater. We assessed the impact of high-statin concentrations on the occurrence of MACE, re-ischemia events, and death in 2,448 Chinese patients with CAD
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