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Evevident
Original paper
2023NEJMInfectious Disease

REPRIEVE

Pitavastatin to Prevent Cardiovascular Disease in HIV Infection

RCTHIV cardiovascular prevention

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Overview

Pitavastatin reduced major cardiovascular events in adults with HIV at low-to-moderate traditional risk.

Clinical takeaway

REPRIEVE showed that pitavastatin prevents major cardiovascular events in selected adults with HIV on ART whose calculated ASCVD risk is low-to-moderate, supporting HIV-specific statin prevention beyond usual risk calculators.

Key result

Major adverse cardiovascular events: 4.81 vs 7.32 per 1000 person-years; HR 0.65 (95% CI 0.48-0.90), p=0.002.

Practice impact

Consider statin primary prevention for eligible adults with HIV even when traditional ASCVD risk appears modest.

Evidence

Study design

Phase 3 randomized, double-blind, placebo-controlled trial.

Enrollment

7,769

Follow-up

Median 5.1 years.

Geography

Multinational, 145 sites in 12 countries

Clinical question

Does pitavastatin reduce major adverse cardiovascular events in adults with HIV receiving ART who have low-to-moderate traditional cardiovascular risk?

Population

  • Adults 40-75 years old with HIV infection receiving stable antiretroviral therapy.
  • Low-to-moderate calculated ASCVD risk and no known atherosclerotic cardiovascular disease.
  • Excluded recent statin use and patients with existing statin indications outside the trial criteria.

Intervention

Pitavastatin calcium 4 mg daily.

Comparator

Placebo.

Primary outcome

Major adverse cardiovascular event: cardiovascular death, myocardial infarction, hospitalization for unstable angina, stroke, transient ischemic attack, peripheral arterial ischemia, revascularization, or death from an undetermined cause.

Pitavastatin reduced the primary composite cardiovascular outcome compared with placebo.

Hazard ratio / 0.65 / CI 95% CI 0.48-0.90 / p=0.002

Key results

  • The trial was stopped early for efficacy after a median follow-up of 5.1 years.
  • Major adverse cardiovascular events occurred at 4.81 per 1000 person-years with pitavastatin vs 7.32 per 1000 person-years with placebo; HR 0.65; 95% CI 0.48-0.90; p=0.002.
  • Major adverse cardiovascular event or death from any cause: HR 0.79; 95% CI 0.65-0.96.
  • LDL cholesterol decreased from a median of 107 to 74 mg/dL at 12 months with pitavastatin, compared with 106 to 105 mg/dL with placebo.

Harms

  • Muscle-related symptoms were more frequent with pitavastatin: 91 participants (2.3%) vs 53 (1.4%).
  • Diabetes mellitus was more frequent with pitavastatin: 206 participants (5.3%) vs 155 (4.0%).
  • Myopathy, rhabdomyolysis, and grade 3 or higher liver dysfunction were rare.

Clinical Use

When to cite

  • When deciding whether to offer statin primary prevention to an adult with HIV and modest calculated ASCVD risk.
  • When explaining why traditional ASCVD calculators may underestimate cardiovascular risk in people with HIV.
  • When choosing a statin with fewer antiretroviral drug-interaction concerns.

Practice impact

  • Provides randomized outcomes evidence for statin primary prevention specifically in people with HIV.
  • Supports treating HIV as a cardiovascular risk enhancer when discussing statin therapy.
  • Pitavastatin is clinically relevant because it has fewer interactions with common antiretroviral regimens.

Applicability

  • Most applicable to adults 40-75 years old with HIV on stable ART, no known ASCVD, and low-to-moderate calculated cardiovascular risk.
  • Useful when a patient's calculated pooled-cohort ASCVD risk seems too low to capture HIV-associated inflammatory and immune activation risk.
  • Applies to primary prevention, not secondary prevention in established ASCVD.

Limitations

  • Tested pitavastatin 4 mg daily; do not assume identical evidence for every statin and ART combination.
  • Patients with known ASCVD or clear high-risk statin indications were not the central population.
  • The trial was stopped early for efficacy, which can modestly amplify apparent treatment effect.
  • Implementation still requires shared decision-making around diabetes and muscle-symptom risks.

Common misinterpretations

  • Do not present REPRIEVE as a general statin trial in the overall population; its key contribution is HIV-specific primary prevention.
  • Do not ignore standard statin indications: patients with established ASCVD or very high LDL already have separate reasons for statin therapy.

Related evidence

4S - Same Drug ClassSTART - Same DiseaseHPTN 052 - Same Disease

Citation

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. doi:10.1056/NEJMoa2304146

Participants with HIV infection who received pitavastatin had a lower risk of a major adverse cardiovascular event than those who received placebo over a median follow-up of 5.1 years.