REPRIEVE Substudy: Pitavastatin reduces non-calcified coronary plaque in people with HIV

Avatar
By Inbar McCarthy on

Key Points

  • The REPRIEVE trial recently demonstrated that pitavastatin reduced major adverse cardiovascular events by 35% among individuals with HIV at low-moderate risk predicted risk for cardiovascular disease. However, little is known regarding the mechanism of benefit. 
  • The mechanistic sub-study of REPRIEVE enrolled 804 participants from the overall trial from 31 U.S. sites and randomized them to daily pitavastatin at a dose of 4mg or placebo. 
  • At 2 years follow-up, pitavastatin reduced non-calcified plaque volume by 7% relative to placebo and reduced the risk of plaque progression by 33%.  

Approximately 39 million individuals worldwide are living with HIV. People with HIV have a 50% higher relative risk of cardiovascular disease as compared to the general population. The REPRIEVE trial recently enrolled 7,769 people with HIV on antiretroviral therapy with low-moderate 10-year predicted atherosclerotic cardiovascular disease risk and randomized them to pitavastatin or placebo. The trial found pitavastatin reduced major adverse cardiovascular events by 35% as compared to placebo over 5 years. This mechanistic sub-study was undertaken to better understand the mechanisms of cardiovascular risk reduction in the study population. 

The REPRIEVE mechanistic sub-study enrolled 804 men and women aged between 40 and 75 years of age with HIV and on antiretroviral therapy who were at low to moderate traditional cardiovascular disease risk. Participants for the study were enrolled from 31 sites in the United States and were randomized in a 1:1 ratio to either 4mg pitavastatin or placebo daily. The primary outcomes were 2-year change in non-calcified coronary plaque volume and non-calcified plaque progression as assessed by coronary computed tomography angiography (CCTA). The average age of the study population was 51 years and 17% were women. The median ASCVD risk score at baseline was approximately 4.5%. 

There was a 29% greater reduction in LDL cholesterol in the pitavastatin arm over the 2 year as compared to placebo. At 2-years, there was a decrease in non-calcified coronary plaque volume in the pitavstatin arm relative to placebo (difference – 4.3 mm3; 95% CI, -8.6, -0.01; p=0.044). This equated to a 7% relative reduction in non-calcified plaque volume in the pitavastatin arm as compared to placebo. Progression of non-calcified plaque occurred less frequently in the pitavastatin arm as compared to the placebo arm (18% vs 28%; p=0.003). There were also significant reductions in oxidized LDL and Lipoprotein-Associated Phospholipase A2 in those randomized to pitavastatin as compared to placebo. 

In conclusion, pitavastatin reduced non-calcified plaque volume by 7% relative to placebo among people with HIV at low-moderate risk of cardiovascular disease. The investigators noted that these changes may contribute to 35% reduction in major adverse cardiovascular events with pitavastatin observed in the overall REPRIEVE trial.