Cardiovascular Risk Definition in REPRIEVE
In the REPRIEVE trial, cardiovascular risk was defined as low-to-moderate 10-year atherosclerotic cardiovascular disease (ASCVD) risk, with participants having a median 10-year ASCVD risk score of 4.5% (IQR 2.1-7.0%) based on the 2013 ACC/AHA risk calculator. 1
Specific Enrollment Criteria Based on Risk Stratification
The trial used a tiered approach linking ASCVD risk scores to LDL cholesterol thresholds: 2
- Risk score ≤7.5%: LDL-C <190 mg/dL required for eligibility
- Risk score 7.6-10%: LDL-C <160 mg/dL required for eligibility
- Risk score 10.1-15%: LDL-C <130 mg/dL required for eligibility
The upper limit was capped at 15% 10-year ASCVD risk, explicitly excluding those with high traditional cardiovascular risk. 2
Key Participant Characteristics at Baseline
The enrolled population demonstrated the following cardiovascular profile: 3
- Age range: 40-75 years (median 50 years)
- LDL cholesterol: Median 106 mg/dL (IQR 86-128)
- Viral suppression: 97.8% had HIV-1 viral load <400 copies/mL
- CD4 count: Median 621 cells/μL (IQR 448-827)
- ART duration: Median 9.6 years at study entry
Important Exclusion Context
Participants with known ASCVD at baseline were excluded, making this explicitly a primary prevention trial rather than secondary prevention. 4 This is a critical distinction—the trial specifically targeted people with HIV who had no prior cardiovascular events but were at increased risk due to HIV-related factors beyond traditional risk calculators.
Clinical Significance of the Risk Definition
The median 4.5% 10-year ASCVD risk represents a population that would not typically receive statin therapy under general population guidelines, yet the trial demonstrated a 36% reduction in major adverse cardiovascular events with pitavastatin (HR 0.64,95% CI 0.48-0.84). 1 This finding fundamentally challenged the assumption that traditional ASCVD risk calculators adequately capture cardiovascular risk in people with HIV, as these calculators consistently underestimate risk in this population, particularly for women and Black/African American individuals. 1
The number needed to treat was 53 or below for those with ≥5% 10-year risk versus 149 or higher for those with <5% risk, demonstrating that even within this low-to-moderate risk cohort, higher baseline risk predicted greater absolute benefit. 1