REPRIEVE: Mechanisms behind MACE reduction in HIV population on pitavastatin

A mechanistic substudy of the REPRIEVE trial, investigating the effects of pitavastatin on coronary artery disease (CAD) in patients with HIV, showed a risk reduction in non-calcified plaque volume, a decreased risk of plaque progression, and less evidence of lipid oxidation and arterial inflammation in patients on pitavastatin. According to the investigators, these effects could explain the reduction in major cardiovascular events (MACE) that was observed in the parent trial.

“We know that patients with HIV have an increased risk of cardiovascular disease,” stated Dr Michael Lu (Massachusetts General Hospital, MA, USA) [1]. “Also, the moderate-intensity statin pitavastatin has minimal interaction with the antiretroviral therapy that is used by patients with HIV.” The phase 3 REPRIEVE trial (NCT02344290) randomised 7,769 participants with HIV on antiretroviral therapy with a low-to-moderate 10-year atherosclerotic cardiovascular disease (ASCVD) risk to pitavastatin calcium or placebo [2]. The primary analysis at 5.1 years showed a reduction of 35% in MACE in participants on pitavastatin compared with those who were treated with a placebo. The current analysis, presented by Dr Lu, evaluated the effect of pitavastatin on non-calcified coronary plaque formation and inflammatory and immune biomarkers in 804 participants.

At 24 months, the authors observed a reduction of 7% in non-calcified coronary plaque volume in participants on pitavastatin compared with those on placebo (95% CI -8.6 to -0.1; P=0.044). In participants with plaques at baseline, the corresponding difference was 12%. Furthermore, the risk of non-calcified plaque progression was 33% lower in the pitavastatin group than in the placebo group (95% CI 0.52–0.88; P=0.003).

“We also noted significant reductions in Lp-PLA₂ and oxidised LDL levels in pitavastatin-treated individuals compared with placebo-treated individuals,” added Dr Lu. Changes in other biomarkers, such as MCP-1, sCD14, and IL-6, did not significantly differ between the 2 study groups at 24 months. “The results of REPRIEVE are in a similar ballpark with respect to plaque changes as other trials investigating LDL-reducing agents in higher-risk populations,” according to Dr Lu.

In conclusion, in a primary prevention population of patients with HIV and a low-to-moderate ASCVD risk, 2 years of pitavastatin treatment was associated with reduced non-calcified plaque volumes, a lower risk of plaque progression, and a reduction in relevant biomarkers of lipid oxidation and arterial inflammation, potentially explaining the reduction in MACE that was reported in the primary analysis of this trial.

1. 
   
   1. Lu MT, et al. Effects of pitavastatin on coronary artery disease and inflammatory biomarkers: mechanistic substudy of the REPRIEVE primary prevention trial in HIV. LB06, AHA Scientific Sessions 2023, 11–13 November, Philadelphia, USA.
   2. Grinspoon SK, et al. N Engl J Med 2023;389:687–699.

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Posted on 29 January 202413 June 2024