Clopidogrel Better Inhibitor of Platelet Activation Than Aspirin in Patients With HIV

Results of a randomized controlled trial published in JACC: Basic to Translational Science suggest clopidogrel may more effectively decrease cardiovascular disease (CVD) risk factors compared with aspirin or no treatment among patients with HIV infection.

The Antiplatelet Therapy in HIV trial was an open-label trial conducted in the United States. Patients (N=55) with HIV infection who were on antiretroviral therapy (ART) and had an HIV RNA viral load of less than200 copies/mL for at least 3 months were included in the analysis. Patients were randomly assigned  in a 1:2:2 fashion to receive either no treatment (n=11), a single 325-mg dose aspirin followed by 81 mg of daily aspirin (n=22), or a single 300-mg dose of clopidogrel followed by 75 mg of daily clopidogrel (n=22) for 14 days. Blood samples were collected at baseline and following treatment completion and evaluated for platelet aggregation, platelet function, and gene expression.

Among patients included in the analysis, the median age was 53 (IQR, 50-58) years, 58% were men, 44% were Black, the median BMI was 25.6 (IQR, 23.0-31.2) kg/m², the median duration of ART was 16 (IQR, 10-19) years, and the median CD4⁺ T-cell count was 597.5 (IQR, 417.0-791.8) cells/mm³.  In addition, 14% of patients had hypertension, 13% had hyperlipidemia, 9% were receiving statin therapy, and 32% had a history of AIDS.

Between baseline and day 14, arachidonic acid-induced platelet aggregation was inhibited in patients in the aspirin group (mean difference [MD], -38.8%; 95% CI, -21.5% to -56.1%), with less pronounced changes observed among those in the clopidogrel group (MD, -10.5%; 95% CI, -21.4% to 0.5%). For adenosine diphosphate (ADP)-induced platelet aggregation, inhibitory responses were greater among patients in the clopidogrel group (MD, -37.0%; 95% CI, -20.7% to -53.3%) compared with those in the aspirin (MD, -15.2%; 95% CI, -6.9% to 23.4%) group. No significant changes in arachidonic acid- or ADP-induced platelet aggregation were observed among patients who received no treatment.

After 14 days of treatment, reductions in platelet P-selectin expression in basal-stimulated  (MD, -12.6; 95% CI, -1.1 to -24.1 MFI) and thrombin-stimulated (MD, -215.3%; 95% CI, -7.8 to -422.9 MFI) states were observed among patients in the clopidogrel group. Clopidogrel therapy also was associated with significant reductions in glycoprotein aIIbb3 (PAC-1) expression after ADP stimulation (MD, -86.4; 95% CI, -10.4 to -162.3 MFI) and after arachidonic acid stimulation (MD, -141.7; 95% CI, -52.3 to -231.1 MFI). For patients in the aspirin or no treatment groups, no significant reductions in P-selectin or PAC-1 expression were observed in either basal- or thrombin-stimulated states.

In the gene expression analysis that assessed approximately, 246 immune- and inflammatory-related genes, 103 were down-regulated and 37 were up-regulated following clopidogrel treatment compared with 39 and 106 following aspirin treatment (P <.001), respectively.

The corresponding pathways for genes that were down-regulated among patients in the clopidogrel group included the tumor necrosis factor family, intracellular adhesion, and inflammasome-related mRNA.

Limitations of this study include its open-label design and small sample size.

Based on these findings, the researchers noted that “clopidogrel is more potent than aspirin to inhibit platelet activation as well as proinflammatory and atherogenic endothelial pathways in PWH [patients with HIV].”