EBM BLS: Pitavastatin Reduces Cardiovascular Events in People Living with HIV With Low-to-Moderate Cardiovascular Risk

Source Article: Grinspoon SK, Fitch KV, Zanni MV, et al. Pitavastatin to Prevent Cardiovascular Disease in HIV Infection. N Engl J Med. 2023;389(8):687–699. 10.1056/NEJMoa2304146.

WHY THIS IS IMORTANT

• People living with HIV (PLWH) are at elevated risk for cardiovascular disease (CVD), now a leading cause of non-HIV-related mortality.¹

• Guidelines now recommend statin therapy for PLWH aged 40-75 years, regardless of lipid levels or Atherosclerotic Cardiovascular Disease (ASCVD) risk, with the strongest recommendation for those with a 10-year ASCVD risk ≥ 5%. High-intensity statins are advised for risk > 20%, and moderate-intensity statins for lower-risk groups. These recommendations were directly shaped by the REPRIEVE trial.²

• Prior to REPRIEVE, 68% of statin-eligible PLWH were not on statins despite meeting criteria.³

INTERVENTION

• REPRIEVE was a randomized, double-blind, placebo-controlled trial.

• Participants were randomized in 1:1 ratio to pitavastatin (4 mg daily) or placebo.

• Primary Outcome: major adverse cardiovascular events (MACE), defined as the occurrence of any of the following: cardiovascular death, myocardial infarction (MI), hospitalization for unstable angina, stroke, transient ischemic attack (TIA), peripheral arterial ischemia, revascularization of a coronary, carotid, or peripheral artery, or death from an undetermined cause Fig. 1.

Figure 1.

Incidence of MACE over 5.1 years in adults with HIV receiving pitavastatin vs placebo.

RESULTS

• Median screening CD4 count: 621 cells/mm³ with 87.5% having HIV RNA below quantification, confirming viral suppression. Participants had a median age of 50 years; 41.3% were Black, 34.8% White, and 14.6% Asian. All were on antiretroviral therapy, with a median duration of 9.6 years. The median 10-year ASCVD risk was 4.5%.

• Over a median follow-up of 5.1 years, pitavastatin reduced MACE by 35% (4.81 vs. 7.32 events per 1,000 person-years; HR 0.65, 95% CI 0.48–0.90, p = 0.002); trial was stopped early for efficacy.

• Individual MACE components were numerically lower with pitavastatin, although the trial was not powered for these comparisons: MI/cardiac ischemia (1.40 vs 2.51 events per 1,000 person-years), stroke/TIA (1.56 vs 2.36), and cardiovascular mortality (0.64 vs 0.85).

• Muscle-related symptoms (2.3% vs. 1.4%, IRR: 1.74, 95% CI: 1.24—2.45) and incident diabetes mellitus (5.3% vs. 4.0%, IRR: 1.35, 95% CI: 1.09-1.66) were significantly more frequent in the pitavastatin group.

STUDY DESCRIPTION

Setting

• Participants were PLWH aged 40–75 years on stable ART with no clinical ASCVD (MI, angina, stroke, TIA, PAD, revascularization), and at low-to-moderate (≤ 15%) 10-year ASCVD risk.

• The study was conducted across 145 sites in 12 countries.

Exclusion Criteria

• Baseline diabetes with LDL ≥ 70, clinical ASCVD, ASCVD risk > 15%, most active cancer diagnoses, cirrhosis, recent fungal/viral infection, or recent use of statins, PCSK9 inhibitors, or specific immunosuppressants.

Methods

• Participants received standardized counseling on lifestyle modifications at baseline in addition to pitavastatin or placebo.

• MACE were adjudicated by blinded reviewers.

STUDY QUALITY AND APPLICATION TO PATIENTS

• The USPSTF quality rating for this study is good.

• Strengths include a diverse population (65.2% non-White, 31.1% women).

• Limitations include few older adults enrolled.

• Traditional risk calculators underestimate ASCVD risk in PLWH: the median estimated 10-year ASCVD risk was 4.5%, yet the observed MACE rate in the placebo group was 7.3%. REPRIEVE used the Pooled Cohort Equations, which—like the newer PREVENT calculator—underestimate risk in this population.⁴

• Guidelines now support statin use for primary CVD prevention in PLWH.

• Pitavastatin was chosen for its minimal drug–drug interactions. Most first-line ART regimens recommended by the U.S. Department of Health and Human Services lack significant statin interactions; notable interactions occur primarily with protease inhibitor–based regimens.

• REPRIEVE enrolled PLWH aged 40–75 on stable ART, most (87%) with suppressed viremia and without ASCVD, liver disease, or recent statin use; thus, findings apply primarily to lower-risk, well-controlled individuals with sufficient life expectancy to realize long-term cardiovascular benefit.

Author Contributions

All authors contributed to the conception and design of this manuscript.

Funding

We have no funding related to this submission.

Data Availability

Data supporting the findings of this study are available in the published source article.

Declarations

Human Ethics and Consent to Participate

Not applicable. The manuscript is a summary and analysis of a previously published journal article. No original research involving human subjects was conducted, and therefore IRB approval is not required. There are no potential ethical issues associated with this submission.

Conflicts of interest

We have no conflicts of interest to disclose.