Background
People with HIV (PWH) are at increased risk for atherosclerotic cardiovascular diseases (ASCVD) and accelerated aging, including frailty. REPRIEVE demonstrated a 36% reduction in the hazard of major adverse cardiovascular events (MACE) for pitavastatin vs placebo among PWH, but little is known about statins for ASCVD prevention among PWH with frailty. The goal of this post-hoc analysis was to examine whether frailty is associated with MACE among PWH, and whether statins prevent MACE across a spectrum of frailty.
Methods
REPRIEVE randomized PWH aged 40-75 without ASCVD to pitavastatin 4mg vs placebo. Frailty was measured with a 32-item cumulative deficit frailty index (FI) and classified as non-frail (<0.1), pre-frail (0.1-0.2) and frail (>0.2-1) using Rockwood approach. Cox proportional hazards models were used to estimate cause-specific hazard ratio (HR) of MACE by frailty status, stratified by treatment group. Modification of pitavastatin effect by frailty was assessed via interaction with treatment. Fractional polynomials were used to evaluate pitavastatin effect continuously across the FI.
Results
Of 7769 REPRIEVE participants, 7740 (>99%) had sufficient data to calculate FI at study entry. Median age was 50 years (Q1, Q3: 45, 55), ASCVD risk score 4.5 (2.1, 7.0)%, 31% were female, and 65% non-White. FI ranged from 0 to 0.44, with 68% classified as non-frail, 28% pre-frail and 4% frail. Frailty status showed good predictive validity for mortality: adjusted for age and sex, HR of death was 1.63 (95% CI: 1.27, 2.09) among pre-frail, 1.47 (95% CI: 0.83, 2.60) among frail compared to non-frail participants (p=0.0005 for overall effect of frailty status). Over median 5.6 years of follow up, MACE incidence rate (IR) was 4.51/1000 person-years (PY) among non-frail, 9.88/1000PY among pre-frail, and 14.39 among frail participants (HR=1.72 among pre-frail, and 2.15 among frail compared to non-frail, adjusted for age, sex and ASCVD risk score; p<0.0001, Figure panel A). There was no evidence that pitavastatin effect differed by frailty status (p=0.39; Figure panel B), but with uncertainty in the frail category due to small numbers. Further analysis using continuous FI suggested consistent pitavastatin effect across the spectrum of frailty.
Conclusions
Frailty was associated with markedly higher incidence of MACE, but did not appear to modify the protective effects of pitavastatin seen in the REPRIEVE primary analysis.