Clopidogrel may reduce inflammation, thrombogenicity in HIV
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The increased risk for CVD in patients with HIV was associated with higher thrombogenicity that interacted with immune and inflammatory activation markers, which improved with clopidogrel compared with aspirin or placebo, according to a study published in Science Advances.
“This study shows benefits of clopidogrel in HIV patients that could reduce cardiovascular events among this vulnerable and aging population,” Juan J. Badimon, PhD, professor of cardiology and director of the Atherothrombosis Research Unit at the Cardiovascular Institute at the Icahn School of Medicine at Mount Sinai, told Cardiology Today.
Meagan P. O’Brien, MD, assistant professor of medicine at the Icahn School of Medicine at Mount Sinai, and colleagues analyzed data from 15 patients with HIV who were on suppressive antiretroviral therapy (mean age, 46 years; 53% men) and 14 sex- and age-matched controls (mean age, 44 years; 50% men). Once enrolled, measurements were taken for platelet reactivity, thrombus kinetics and markers of inflammation, in addition to undergoing the Badimon perfusion study to assess thrombogenicity.
Patients were assigned 75 mg once-daily clopidogrel, 81 mg once-daily aspirin or placebo for 24 weeks.
Blood samples were taken at 12 weeks to measure inflammatory markers. At 24 weeks, patients underwent all assessments that were performed at baseline. At all time points, patients underwent safety assessments including blood collection for serum and plasma specimen storage for batched assays, safety laboratory testing, clinical evaluations and detailed bleeding questionnaires.
All study drugs were safe and well tolerated with no serious adverse events.
Compared with patients without HIV, those with HIV had higher thrombus formation at low (6,349 µm2/mm vs. 5,237 µm2/mm; P = .006) and high shear rates (9,256 µm2/mm vs. 7,421 µm2/mm; P = .013).
There were significant positive associations between high shear rate thrombus and soluble tumor necrosis factor (TNF) receptor 1 (r = 0.75; P = .005), soluble TNF receptor 2 (r = 0.61; P = .037), D-dimer (r = 0.67; P = .017) and nonclassical monocytes (r = 0.62; P = .031). There was also a significant negative association between high shear thrombus and classical monocytes (r = –0.71; P = .005). There were no significant links between thrombus size at low shear rate and other variables.
Clopidogrel decreased blood thrombus at low shear rate by 11.3% (P = .047). There was a 19.6% reduction in thrombogenicity at high shear rate, although it did not reach statistical significance (P = .176). There were also reductions in plasma soluble CD14 levels with clopidogrel at 12 weeks (16.3%; P = .01) and 24 weeks (9%; P = .049). Aspirin and placebo did not reduce thrombogenicity or soluble CD14.
“It is premature to recommend dual antiplatelet therapy for our patients with HIV at risk for cardiovascular disease,” Judith A. Aberg, MD, FIDSA, FACP, Dr. George Baehr Professor of Medicine at Mount Sinai, told Cardiology Today. “However, this study supports our clinical observations that our patients with HIV are at risk for major adverse cardiac events and should be screened accordingly and offered preventive therapies as indicated.” – by Darlene Dobkowski
For more information:
Judith A. Aberg, MD, FIDSA, FACP, can be reached at One Gustave L. Levy Place, Box 1090, New York, NY 10029; email: judith.aberg@mssm.edu.
Juan J. Badimon, PhD, can be reached at Atran Berg Laboratory Building, Floor 6, Room 20, 1428 Madison Ave., New York, NY 10029; email: juan.badimon@mssm.edu.
Disclosures: Aberg reports she received clinical research support from Gilead Sciences and GlaxoSmithKline/ViiV Healthcare and scientific advisory board fees from Gilead Sciences, Janssen, Merck and ViiV Healthcare unrelated to the present study. The other authors report no relevant financial disclosures.
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