Persistent inflammatory residual risk despite aggressive cholesterol-lowering therapy: what is next?

Area of Science:

• Cardiovascular Medicine
• Inflammation Research
• Pharmacology

Background:

• Atherosclerotic cardiovascular disease (ASCVD) remains a leading cause of mortality.
• Inflammation plays a critical role in the pathogenesis of ASCVD.
• Despite optimal lipid-lowering therapies, a significant residual risk for ASCVD events persists.

Purpose of the Study:

• To review recent evidence on modulating inflammatory processes in ASCVD.
• To discuss the rationale for a new randomized clinical trial.
• To address open questions regarding treatment allocation for a dual-target strategy.

Main Methods:

• Review of recent large-scale clinical trials.
• Analysis of evidence targeting inflammatory pathways (e.g., NLRP3 inflammasome, IL-1β).
• Discussion of potential trial designs for combined lipid and inflammatory risk reduction.

Main Results:

• Targeting the NLRP3 inflammasome and IL-1β pathway shows promise in reducing residual risk in ASCVD patients.
• Novel anti-inflammatory therapies offer new avenues for risk reduction.
• A substantial number of ASCVD patients remain at high risk despite current treatments.

Conclusions:

• A dual-target strategy combining lipid modification and inflammation reduction may enhance patient care for high-risk ASCVD individuals.
• Further research and carefully designed clinical trials are necessary to optimize this integrated approach.
• Key questions regarding the design of a 2x2 factorial trial need resolution.