Effect of Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Inhibitors on Lipid Profile and Cardiovascular Events in High-Risk Diabetic Patients.

Background Type 2 diabetes mellitus (T2DM) significantly increases the risk of atherosclerotic cardiovascular disease (ASCVD), and optimal lipid control is essential for reducing major adverse cardiovascular events (MACE). However, despite the widespread use of statins, many high-risk diabetic patients fail to reach target low-density lipoprotein cholesterol (LDL-C) levels. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have emerged as effective adjunctive agents for lipid lowering. This study was conducted to evaluate the effect of PCSK9 inhibitors on lipid profile and cardiovascular outcomes in high-risk diabetic patients. Methods A prospective, observational study was conducted at Kakatiya Medical College/Mahatma Gandhi Memorial (MGM) Hospital Warangal over 18 months. A total of 100 patients with T2DM (age, 40-75 years), having established ASCVD or multiple cardiovascular risk factors and LDL-C >100 mg/dL despite maximal statin therapy, were included. All participants received proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors (alirocumab 75 mg or evolocumab 140 mg subcutaneously every two weeks) in addition to standard care. Lipid profile parameters were assessed at baseline, three months, and 12 months. MACE (non-fatal myocardial infarction, stroke, or cardiovascular death) was recorded and compared with a matched historical control group (n = 100) on statin therapy alone. Results At the end of 12 months, the PCSK9 inhibitor group (n = 100) showed a significant reduction in mean LDL-C from 138.5 ± 17.6 mg/dL to 64.3 ± 12.9 mg/dL (p < 0.001). An increase in high-density lipoprotein cholesterol (HDL-C) was observed from 40.8 ± 5.3 mg/dL to 45.1 ± 5.6 mg/dL (p = 0.04), and triglycerides reduced from 178.7 ± 25.2 mg/dL to 149.5 ± 19.8 mg/dL (p < 0.01). MACE occurred in seven out of 100 patients (7%) in the PCSK9 group, compared to 16 out of 100 patients (16%) in the control group (HR: 0.41; 95% CI: 0.17-0.98; p = 0.044). Specifically, non-fatal myocardial infarction occurred in three (3%) vs. seven (7%), stroke in two (2%) vs. five (5%), and cardiovascular death in two (2%) vs. four (4%) in the PCSK9 and control groups, respectively. No serious adverse drug reactions were reported among the PCSK9 users. Conclusion PCSK9 inhibitors significantly improve lipid parameters and reduce cardiovascular event rates in high-risk diabetic patients who are inadequately controlled with statins alone. These findings support their role as an effective and safe adjunctive therapy for secondary cardiovascular prevention in diabetes.