Vorapaxar does not alleviate cardiovascular risk in persons with HIV
In patients with HIV receiving stable antiretroviral therapy, vorapaxar exerts no apparent effect on serum levels of D-dimer and other cardiovascular risk biomarkers, according to a recent study.
“Vorapaxar was safe in people with well treated HIV infection but did not influence D-dimer concentrations or a series of other inflammatory biomarkers associated with adverse outcomes,” said researchers, noting that meaningful changes remained negligible across all timepoints during the trial and that no rebound was observed after vorapaxar treatment was ended.
Researchers enrolled 64 aviraemic patients with HIV, who were randomly assigned to receive vorapaxar (n=33; median age 53 years; 94 percent male) or placebo (n=31; median age 52 years; 90 percent male). The baseline risk for cardiovascular disease within 10 years was 11.4 percent. [Lancet HIV 2018;doi:10.1016/S2352-3018(18)30214-5]
After 12 weeks of vorapaxar treatment, no meaningful and significant change was observed in D-dimer concentrations, which remained unchanged all throughout the trial.
In placebo patients, the mean percent change in D-dimer concentration from baseline to the average of measurements during weeks 8–12 was –8.5 percent. This was not significantly different from that in the vorapaxar group (–10.8 percent; difference in log-transformed data, –0.02; 95 percent CI, –0.10 to 0.05; p=0.056).
There were also no significant between-group changes in D-dimer concentrations from baseline to week 8 (placebo vs vorapaxar: –10.7 percent vs –12.5 percent; difference in log-transformed data, –0.03; –0.10 to 0.05; p=0.52) and week 12 (–8.8 percent vs –10.2 percent; difference in log-transformed data, –0.02; –0.09 to 0.06; p=0.64).
Vorapaxar likewise had no significant effects on other biomarkers. That is, the changes in interleukin-6 levels from baseline to week 8 (placebo vs vorapaxar: –14.3 percent vs –1.1 percent; difference in log-transformed data, 0.04; –0.11 to 0.19; p=0.63) and week 12 (–13.3 percent vs 10.4 percent; difference in log-transformed data: 0.08; –0.05 to 0.21; p=0.22).
The same was true for high-sensitivity C-reactive protein (hsCRP; week 8: –14.2 percent vs –0.5 percent, difference in log-transformed data, 0.02; –0.24 to 0.27; p=0.91; week 12: –28.2 percent vs –24.3 percent; difference in log-transformed data, –0.02; –0.21 to 0.16; p=0.79).
“Vorapaxar had an acceptable safety profile in this HIV-infected population,” said researchers, noting that there were two reports of moderate or severe bleeding in the vorapaxar group. No adverse effects on the control of HIV viraemia were observed.
In the present study, blood samples were collected from the participants at weeks 1, 4, 8 and 12 of the trial. Enzyme-linked immunosorbent assays were performed to measure D-dimer concentrations, which were used as a marker for coagulopathy.
“The lack of effect of vorapaxar on biomarkers associated with cardiovascular risk emphasizes the importance of standard cardiovascular risk reduction measures (including reducing cholesterol, controlling hypertension, stopping smoking) in this high-risk group,” said researchers.
“Improved therapies and targets are needed to reduce cardiovascular disease in this susceptible population,” they added.