Real-world data on metabolic effects of PCSK9 inhibitors in a tertiary care center in patients with and without diabetes mellitus

Abstract

Background The lipid-lowering and positive cardiovascular effect of proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors was shown in several studies, hence, they are more widely used in the lipid-lowering management of individuals with high cardiovascular risk. As real-world data are still scarce, specifically in patients with type 2 diabetes (T2D), the aim of this retrospective analysis was to investigate the efficacy of PCSK9 inhibitors in lowering low-density lipoprotein cholesterol (LDL-C) in an outpatient clinic of a tertiary care center in routine care. Methods A retrospective analysis of data extracted from the electronic patient record was performed. Patients who were routinely prescribed with PCSK9 inhibitor therapy (alirocumab or evolocumab) during the years 2016 and 2019 were included in the analysis. Characteristics of the patient population, the effects on LDL-C and HbA1c levels as well as subsequent cardiovascular events were assessed over an observation period of 18 months. Results We identified 237 patients treated with PCSK9 inhibitors between January 2016 and September 2019. Almost all patients (97.5%) received PCSK9 inhibitors for secondary prevention. 26.2% of the population had a concomitant diabetes diagnosis. Intolerance to statins (83.1%), ezetimibe (44.7%) or both agents (42.6%) was reported frequently. Three months after initiation of PCSK9 inhibitor therapy, 61.2% of the patients achieved LDL-C levels < 70 mg/dl, and 44.1% LDL-C levels < 55 mg/dl. The median LDL-C was lowered from 141 mg/dl at baseline, to 60 mg/dl after 3 months and 66 mg/dl after 12 months indicating a reduction of LDL-C as follows: 57.5% after 3 months and 53.6% after 12 months. After 3 months of observation, target achievement of LDL-C was higher in patients with T2D compared to non-diabetes patients; < 55 mg/dl: 51% vs. 41.5%; < 70 mg/dl 69.4 vs. 58.5%. After 12 months even more pronounced target LDL achievement in T2D was demonstrated < 55 mg/dl: 58.8% vs. 30.1%; < 70 mg/dl 70.6 vs. 49.6%. Patients with insufficiently controlled T2D (HbA1c > 54 mmol/mol) had a higher reduction in LDL-C but still were more likely to subsequent cardiovascular events. Conclusions Significant reductions in LDL-C and a high percentage of patients achieving recommended treatment targets were observed. The percentage of patients with T2D meeting recommended LDL-C targets was higher than in those without T2D. Still some patients did not achieve LDL-C levels as recommended in current guidelines. Special attention to the characteristics of these patients is required in the future to enable achievement of treatment goals and avoid adverse cardiovascular outcomes.

PCSK9 inhibitors and treatment targets: an audit-based evaluation of a specialist lipid clinic

“…11 A retrospective study of 237 patients receiving PCSK9is in routine care found that 56.2%, 38.6% and 59.5% of patients achieved LDL-C targets of <1.8mmol/L, <1.4mmol/L and >50% reduction, respectively. 12 These lower levels of target attainment are similar to findings of our audit. High baseline LDL-C concentrations in real-world practice often indicate that LDL-C targets of <1.8 and <1.4 mmol/L are unattainable using PCSK9i monotherapy.…”

“…However, the very high baseline cardiovascular risk (10-year risk is usually >20%) in ASCVD patients means their absolute risk may still be high despite lipid modification. 12 Reducing LDL-C to below 1.0mmol/L has been shown to reduce progression, and possibly induce regression, of atherosclerosis and to reduce risk of cardiovascular events. 6,7 Hence, to minimise absolute cardiovascular risk, greater LDL-C reductions to guidelinerecommended targets are needed.…”

Evolocumab on top of empagliflozin improves endothelial function of individuals with diabetes: randomized active-controlled trial

“…Abundant data have shown that evolocumab intensely reduces LDL-C, non-HDL-C, ApoB, Lp(a), and remnant cholesterol in subjects with T2D with and without atherogenic dyslipidemia [ 17 ]. In fact, real-life studies, as well as randomized controlled trials, have shown that PCSK9i therapy increases the achievement of goals in individuals with or without T2DM [ 2 , 18 – 20 ]. Treatment with evolocumab also reduces the plasma concentration of the most atherogenic form of LDL, the small dense particle, and this reduction is associated with attenuation of carotid stiffness in patients with familial hypercholesterolemia [ 21 ].…”

Morphologies and composition changes in nonculprit subclinical atherosclerosis in diabetic versus nondiabetic patients with acute coronary syndrome who underwent long-term statin therapy

“…Similar results were shown in previous studies, which showed similar plaque outcomes detected by IVUS or OCT 14 – 16 . Of course, more intensive LLT combined with PCSK9i leads not only to significant reductions in LDL-C effectively compared with non-DM patients but also to regression in plaque volume in non-DM patients, but there is still a lack of evidence that patients with DM have the same effect as those without DM 58 , 59 , 65 , 66 .…”