Randomized Trial to Prevent Vascular Events in HIV - REPRIEVE

Feb 26, 2024
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Author/Summarized by Author:
Anthony A. Bavry, MD, MPH, FACC
Trial Sponsor:
National Institutes of Health
Date Presented:
11/12/2023
Date Published:
02/21/2024
Date Updated:
02/26/2024
Original Posted Date:
07/25/2023
References

Contribution To Literature:

Highlighted text (the mechanistic substudy) has been updated as of February 26, 2024.

The REPRIEVE trial showed that pitavastatin treatment lowers the risk of adverse cardiovascular events among individuals with HIV and low-to-moderate risk of cardiovascular disease.

Description:

The goal of the trial was to evaluate pitavastatin compared with placebo among individuals with human immunodeficiency virus (HIV) infection and low-to-moderate risk of cardiovascular disease.

Study Design

  • Randomized
  • Parallel
  • Placebo
  • Stratified

Individuals with HIV and low-to-moderate risk of cardiovascular disease were randomized to pitavastatin 4 mg daily (n = 3,888) vs. placebo (n = 3,881).

  • Total number of enrollees: 7,769
  • Duration of follow-up: median 5.1 years
  • Mean patient age: 50 years
  • Percentage female: 31%

Inclusion criteria:

  • Individuals with HIV infection 40-75 years of age
  • Stable anti-retroviral therapy

Exclusion criteria:

  • Statin use within the last 90 days
  • Known atherosclerotic cardiovascular disease

Other salient features/characteristics:

  • Median screening low-density lipoprotein cholesterol (LDL-C): 108 mg/dL
  • Median CD4 count: 621 cells/mm3
  • HIV RNA value below quantification: 5,250 of 5,997 participants (87.5%)

Principal Findings:

The primary outcome, incidence of major adverse cardiovascular events, occurred in 4.81 per 1,000 person-years in the pitavastatin group vs. 7.32 per 1,000 person-years in the placebo group (p = 0.002).

Secondary outcomes:

  • Cardiovascular death: 0.64 per 1,000 person-years in the pitavastatin group vs. 0.85 per 1,000 person-years in the placebo group (p = not significant [NS])
  • Nonfatal serious adverse event: 4.16 per 1,000 person-years in the pitavastatin group vs. 4.13 per 1,000 person-years in the placebo group (p = NS)
  • Myalgia, muscle weakness, or myopathy grade ≥3, or treatment-limiting: 0.49 per 1,000 person-years in the pitavastatin group vs. 0.28 per 1,000 person-years in the placebo group (p < 0.05)

Mechanistic substudy (n = 804):

  • Change in noncalcified plaque volume at 2 years: -1.7 mm3 with pitavastatin vs. 2.6 mm3 with placebo (p = 0.044)
  • Change in LDL-C: -29 mg/dL with pitavastatin vs. 0 with placebo
  • Change in Lp-PLA2: -10.1 ng/dL with pitavastatin vs. 19.3 with placebo (p < 0.001)
  • Change in oxLDL: -14.9 U/L with pitavastatin vs. -6.45 with placebo (p < 0.001)
  • Change in hs-CRP: -0.1 mg/L with pitavastatin vs. 0.1 with placebo (p = 0.09)

Interpretation:

Among individuals with HIV infection and low-to-moderate risk of cardiovascular disease, pitavastatin treatment was beneficial. Pitavastatin vs. placebo was associated with a reduction in major adverse cardiovascular events. This benefit may be mediated by decreased risk of plaque progression, decreased lipid oxidation, and decreased arterial inflammation. The results were the same in various tested subgroups (gender, geographic region, CD4 level, etc.). The benefit observed with pitavastatin was more than predicted by the degree of LDL-C lowering. Pitavastatin treatment was safe with similar incidence of nonfatal serious adverse events; however, muscle-related symptoms were more common vs. placebo.

References:

Lu MT, Ribaudo H, Foldyna B, et al. Effects of Pitavastatin on Coronary Artery Disease and Inflammatory Biomarkers in HIV: Mechanistic Substudy of the REPRIEVE Randomized Clinical Trial. JAMA Cardiol 2024;Feb 21:[Epublished].

Editorial Comment: Feinstein MJ. Statins, Inflammation, and Tissue Context in REPRIEVE. JAMA Cardiol 2024;Feb 21:[Epublished].

Presented by Dr. Michael Lu at the American Heart Association Scientific Sessions, Philadelphia, PA, November 12, 2023.

Grinspoon SK, Fitch KV, Zanni MV, et al., on behalf of the REPRIEVE Investigators. Pitavastatin to Prevent Cardiovascular Disease in HIV Infection. N Engl J Med 2023;389:687-99.

Editorial: Freiberg MS. HIV and Cardiovascular Disease — An Ounce of Prevention. N Engl J Med 2023;389:760-1.

Presented at the 2023 International AIDS Society Meeting on July 23 in Brisbane, Australia.

Clinical Topics: Stable Ischemic Heart Disease, Vascular Medicine

Keywords: Biomarkers, HIV, Vascular Diseases, AHA23


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