A New HOPE? Lessons from Heart Outcomes Prevention Evaluation-3

Area of Science:

• Cardiology
• Preventive Medicine
• Clinical Trials

Background:

• Lifestyle modification is crucial for preventing atherosclerotic cardiovascular disease (ASCVD).
• Statin therapy is the primary pharmacological intervention when lifestyle changes are insufficient to reduce ASCVD risk.
• The Heart Outcomes Prevention Evaluation-3 (HOPE-3) trial investigated rosuvastatin in a population at lower risk for cardiovascular events.

Purpose of the Study:

• To evaluate the efficacy and safety of rosuvastatin in a diverse, lower-risk population without established ASCVD.
• To explore novel trial design elements, including metabolic risk factor-based inclusion criteria and high adherence strategies.

Main Methods:

• A randomized, double-blind, placebo-controlled trial (HOPE-3) involving a diverse population.
• Inclusion criteria based on easily ascertainable metabolic risk factors, not solely on established ASCVD.
• Moderate-dose rosuvastatin therapy compared against a placebo.
• Strategies to promote high adherence, including a run-in phase and close follow-up.

Main Results:

• Rosuvastatin demonstrated a significant net benefit in reducing cardiovascular risk in a lower-risk population.
• High adherence rates were achieved in the rosuvastatin arm, attributed to trial design and low intolerance.
• While not statistically significant in women alone, meta-analyses including HOPE-3 support statin benefits for women.
• Data suggest a potential legacy effect of statin therapy.

Conclusions:

• Rosuvastatin provides significant cardiovascular risk reduction in individuals without established ASCVD, particularly when using strategies to enhance adherence.
• The HOPE-3 trial highlights the importance of metabolic risk factors in identifying candidates for primary prevention.
• Findings support the continued use of statin therapy for primary prevention, including in women, and suggest a lasting benefit (legacy effect).