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Effect of aspirin treatment on abacavir-associated platelet hyperreactivity in HIV-infected patients
Emanuela Falcinelli1, Daniela Francisci2, Elisabetta Schiaroli2
1Department of Medicine, Section of Internal and Cardiovascular Medicine, University Perugia, Italy.
Insights
Low-dose aspirin can reduce abacavir-induced platelet activation in HIV patients, but does not normalize it. Further trials are needed to determine if this reduction prevents cardiovascular events.
Area of Science:
- Cardiology
- Virology
- Pharmacology
Background:
- Ischemic cardiovascular events are a major concern for HIV-infected patients.
- Abacavir (ABC), a nucleoside analog reverse transcriptase inhibitor, is linked to increased myocardial infarction risk and platelet hyperreactivity.
- Platelet activation plays a role in cardiovascular risk.
Purpose of the Study:
- To investigate if low-dose aspirin can reduce in vivo platelet activation and hyperreactivity induced by abacavir in HIV-infected patients.
- To assess the efficacy of aspirin in mitigating ABC-associated platelet changes.
Main Methods:
- A randomized, placebo-controlled, cross-over study involving 40 HIV-infected patients with ABC-associated platelet hyperreactivity.
- Patients received either 100 mg aspirin or placebo daily for 15 days, followed by a cross-over.
- In vivo and ex vivo platelet activation markers were measured, including serum TxB2 and urinary 11-dehydro-TxB2.
Main Results:
- Aspirin significantly reduced platelet hyperreactivity in ABC-treated patients (score decreased from 9.3 to 7.5).
- Serum TxB2 and urinary 11-dehydro-TxB2 levels decreased with aspirin, but not to the extent seen in healthy controls.
- Platelet activation markers were reduced but not normalized compared to healthy subjects.
Conclusions:
- Aspirin effectively reduces abacavir-induced platelet activation and hyperreactivity in HIV-infected patients.
- The reduction in platelet activation by aspirin may not be sufficient to normalize levels seen in healthy individuals.
- Prospective trials are necessary to ascertain if this aspirin-induced reduction in platelet activation can prevent cardiovascular events.
Background:
Ischemic cardiovascular events are a relevant cause of morbidity and mortality in HIV-infected patients. Use of abacavir (ABC), a nucleoside analog reverse transcriptase inhibitor, has been associated with increased risk of myocardial infarction (MI) and with platelet hyperreactivity. We explored whether low-dose aspirin reduces in vivo platelet activation and platelet hyperreactivity induced by ABC in HIV-infected subjects.
Methods And Results:
In a randomized, placebo-controlled, cross-over study forty HIV-infected patients with ABC-associated platelet hyperreactivity, defined by a score based on laboratory variables reflecting in vivo platelet activation and ex vivo platelet hyperresponsiveness, were randomized to aspirin 100 mg daily for 15 days with subsequent cross-over to placebo for additional 15 days or placebo for 15 days with subsequent cross-over to aspirin for further 15 days. In vivo and ex vivo platelet activation markers were measured at day 15 and 30. One group of healthy subjects, one of untreated HIV infected-patients and one treated without ABC, were studied concomitantly. Serum TxB2 and urinary 11-dehydro-TxB2 were decreased by aspirin in ABC-treated patients, but not as much as in healthy controls. Aspirin therapy reduced significantly platelet hyperreactivity (score: from 9.3, 95% CIs 8.7 to 10.0, to 7.5, 6.9 to 8.0), however without bringing it back to the levels of healthy controls (score: 4.6, 95% CIs 3.6 to 5.6).
Conclusion:
Aspirin reduces ABC-induced in vivo platelet activation and platelet hyperreactivity in HIV-infected patients, however without normalizing them. Whether the observed reduction of platelet activation is sufficient to prevent cardiovascular events requires a prospective trial.
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