Inclisiran outdoes BPA for LDL-C lowering in high CV risk patients

In the phase IV VICTORION-Challenge trial, inclisiran outperforms bempedoic acid (BPA) for lowering LDL-C in individuals with high and very high cardiovascular (CV) risk.

“Inclisiran achieved superior LDL-C lowering vs BPA, reducing LDL-C by >50 percent from baseline and providing approximately 41 percent greater reduction when added to maximally tolerated statin therapy,” said Dr Ingo Hilgendorf from the Deutsches Herzzentrumder Charité, Berlin, Germany, at ESC 2026.

At day 150, the least-squares mean (LSM) percent change in LDL-C level was –56.31 percent with inclisiran and only –15.35 percent with BPA. Similar patterns were observed in the comparisons between inclisiran and BPA with (LSM percent change, –55.95 percent vs –13.89 percent) and without ezetimibe (LSM percent change, –56.95 percent vs –16.54 percent; p<0.0001 for all).

The LDL-C reduction with inclisiran was consistent across all prespecified subgroups, including individuals with high (LSM difference, –46.57 percent) and very high CV risk (LSM difference, –40.31 percent). [Hilgendorf, I, et al, ESC 2026]

Overall, 78 percent of participants on inclisiran achieved their LDL-C target, compared with only 20 percent in the BPA group (adjusted odds ratio [aOR], 16.4). The greatest benefit was observed among patients who did not receive ezetimibe (75.8 percent vs 13.7 percent; aOR, 23) and those with very high baseline CV risk (77.3 percent vs 18.1 percent; aOR, 17.8; p<0.001 for all).

“[Moreover,] the substantial and clinically meaningful shifts in LDL-C categories with inclisiran were observed as early as day 30. Even from higher baseline LDL-C levels, inclisiran was able to substantially push a majority of patients below the 70 and 55 mg/dL groups, whereas most BPA recipients were not successful in this case,” said Hilgendorf.

More participants on inclisiran than on BPA achieved LDL-C targets across ‘gap-to-goal’ categories (15 to <25 percent: 94.7 percent vs 33.3 percent; aOR, 36.8; p<0.01; 25 to <40 percent: 85.5 percent vs 12.2 percent; aOR, 44.9; p<0.001; ≥40 percent: 64.2 percent vs 16.3 percent; aOR, 9.4; p<0.001). “‘Gap-to-goal’ is defined as the required percent LDL-C reduction from baseline to reach the target,” Hilgendorf noted.

The safety profile of inclisiran aligned with previous evidence, with no new safety signals reported. During the on-treatment phase, the inclisiran group had fewer drug-related treatment-emergent adverse events (TEAEs; 6.4 percent vs 14.6 percent) and serious TEAEs (8.4 percent vs 11.6 percent) than the BPA group. The most common TEAE was nasopharyngitis (10.3 percent and 7.5 percent).

Low LDL-C target attainment

Early and sustained LDL-C lowering is essential for atherosclerotic CV disease (ASCVD) prevention. However, over half of high-risk patients do not meet the ESC/EAS* LDL-C targets (<55/<70 mg/dL). [Am J Prev Cardiol 2024;18:100649; Eur J Prev Cardiol 2021;28:1279-1289; Eur Heart J 2020;41:111-188]

“This is, in part, due to underutilization of adjunctive lipid-lowering therapies beyond statins and ezetimibe,” Hilgendorf said.

In this head-to-head trial, 402 participants (mean age 63.1 years, 64.2 percent men) were randomized 1:1 to SC inclisiran at baseline and day 90 or oral BPA daily on a background of high-intensity statins (atorvastatin 40 mg or rosuvastatin 20 mg) or ezetimibe. Eighty-eight percent of participants had very high CV risk. The mean LDL-C at baseline was 94.4 mg/dL.

“The findings support inclisiran as an effective option for ASCVD patients requiring additional LDL-C lowering when statin therapy alone or in combination with ezetimibe is insufficient to achieve guideline-recommended targets,” Hilgendorf concluded.