Inclisiran: a breakthrough in LDL-C reduction for indian ASCVD patients

Abstract Background Achieving guideline-recommended LDL-C goals in larger proportion of patients with ASCVD and ASCVD risk-equivalent remains challenging despite the available oral lipid lowering therapies (LLTs). Inclisiran, a novel PCSK9 synthesis inhibitor, complements the oral LLTs by improving the clearance of LDL-C with proven safety. Aim To evaluate Inclisiran's efficacy among Indian patients with ASCVD and ASCVD risk-equivalent. Methodology This real-world prospective study (March – December 2024) conducted in four tertiary care centers from South India. It included patients with ASCVD and ASCVD risk-equivalent, who did not achieve their LDL-C goals despite being on oral LLTs. Inclisiran was administered initially, at 3 months, and every 6 months. The LDL-C was measured at Inclisiran initiation and repeated every 3 months. Results Inclisiran was initiated in 80 patients (Mean Age 57 ± 10 y, 23% females, 67% diabetics, 59% hypertensives, and 43% smokers). Data was analyzed from 65 patients who had LDL-C values both at baseline (day 0) and at 3 months. Despite being on oral LLTs, the mean baseline LDL-C was 120.64 ± 43.53 mg/dL. At three months, inclisiran reduced the LDL-C to 32.83 ± 14.65 mg/dL, demonstrating a significant 70.64 ± 12.72% reduction from baseline. In very high-risk (VHR, N=44) and extremely high-risk (EHR, N=21) patients, the percentage of LDL-C reductions were 72.84 ± 14.28 and 69.64 ± 11.72 respectively; Among VHR patients (N=37), 84% achieved LDL-C 55 mg/dL, while 85.7% of EHR patients (N=18) reached LDL-C 40 mg/dL. Additionally, data from 18 out of these 65 patients (28%) received second dose of inclisiran on day 90, showed a greater reduction of 80.44 ± 14.90% in LDL-C at six months from baseline. Conclusion Inclisiran significantly reduced the LDL-C by 70% at three months among Indian ASCVD patients, with greater reductions in VHR patients. A second dose further enhanced the LDL-C lowering to 80% at six months. These findings need validation through larger studies in the Indian population.