A protocol-based strategy was more successful than standard care in reaching guideline-recommended LDL-C targets in patients with acute coronary syndrome (ACS), and the novel agent lepodisiran was associated with sustained reductions in oxidized phospholipids OxPL-apo(a) and OxPL-apoB levels related to Lp(a) lowering, according to two studies presented at ESC Congress 2026 and simultaneously published in JACC.

BRIDGE
In the BRIDGE study, 10 centers in Japan were randomized to either protocol-based or standard lipid management between November 2024 and July 2025. The protocol-based implementation strategy focused on earlier intensive treatment in patients hospitalized for an emergency PCI, and consisted of high-intensity statins, ezetimibe and PCSK9 inhibitors according to a prespecified algorithm based on baseline LLT status and LDL-C levels. LDL-C was assessed at four weeks. The threshold for intensified treatment was LDL-C of 55 mg/dL and <70 mg/dL for both groups. The analysis included 329 patients with a mean age was 69 years and 18% were women. Their median LDL-C level was 110 mg/dL.

Results at six months showed that more patients in the protocol-based group than in the standard care group achieved an LDL-C level <70 mg/dL (86.4% vs. 73.7%; between-group difference, 12.6 percentage points; p=0.005). In a hospital-level analysis, the between-group difference was 12.8 percentage points (p=0.08). Additionally, a similar pattern was found for LDL-C <55 mg/dL (60.8% vs. 34.5%, respectively; between-group difference, 26.3 percentage points; p<0.001).

Of note, use of high-intensity statins, ezetimibe and PCSK9 inhibitors was higher in the protocol-based group at six months.

“These findings support a structured, protocol-based care pathway as a practical and scalable approach to improving the implementation and consistency of guideline-directed lipid management in routine clinical practice after ACS,” concluded Kazuma Oyama, MD, MPH, PhD.

ALPACA
In the post-hoc analysis of the phase 2 ALPACA study, researchers examined the effects of lepodisiran, an extended-duration, small interfering RNA, on OxPL-apo(a) and OxPL-apoB levels and its association with reducing Lp(a) and apoB. The main results of the international multicenter ALPACA study, presented at ACC.25, showed the drug reduced mean serum concentrations of Lp(a) from 60 to 180 days after subcutaneous administration among patients with elevated Lp(a).

This analysis included 213 of the study participants who received placebo or lepodisiran 16, 96 or 400 mg at baseline and again at day 180 and whose OxPL was measured at baseline, day 240 and day 360. The average age for all participants was 63 years, 55% were men and most (85%) were White. Overall, 74% were taking statins and 35% were taking ezetimibe.

The median baseline OxPL-apo(a) and OxPL-apoB levels were 122.0 nmol/L across all participants.

Results showed significant dose-dependent reductions in OxPL-apo(a) and OxPL-apoB, measured as the placebo-adjusted geometric mean percent change, at day 240. This reduction was sustained at day 360. Percent change in OxPL-apo(a) correlated more closely than OxPL-apoB with percent change in Lp(a). No significant correlation was observed between changes in hsCRP and OxPL.

“These OxPL reductions correlated closely with the reductions in Lp(a),” write Steven E. Nissen, MD, MACC, and colleagues. “However, ongoing cardiovascular outcomes trials are needed to provide evidence of the clinical relevance of Lp(a) and OxPL lowering.”

In an accompanying editorial comment published in JACC, Maxim E. Annink, MD, et al., agreed that the trial results are encouraging, but more study is needed. “Ultimately, the authors are appropriately careful to frame their findings as biological rationale rather than proof of benefit of lepodisiran,” they write. “Being able to show that Lp(a) reduction actually reduces cardiovascular events is the main dish; dissecting a potential role of residual OxPLs as an indicator for residual cardiovascular risk could be a future dessert.”

Visit the JACC Journals at ESC Congress 2026 page to see the full list of simultaneous publications.

Keywords: ESC Congress, ESC26