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Hydroxychloroquine's Efficacy as an Antiplatelet Agent Study in Healthy Volunteers: A Proof of Concept Study
S Achuthan1, J Ahluwalia2, N Shafiq1
1Department of Pharmacology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.
Insights
Hydroxychloroquine (HCQ) demonstrates antiplatelet properties, particularly through the arachidonic acid pathway, and may enhance aspirin's effects. Further research could explore HCQ as a novel antiplatelet therapy for cardiovascular disease.
Area of Science:
- Cardiovascular Pharmacology
- Immunology
- Hematology
Background:
- Atherosclerosis is increasingly viewed through an inflammatory lens, highlighting the therapeutic potential of anti-inflammatory drugs for cardiovascular disease (CVD).
- Hydroxychloroquine (HCQ) has shown protective effects against thrombovascular events in lupus erythematosus and improved cardiovascular risk factors in rheumatoid arthritis patients.
- Preliminary data suggest HCQ may possess antiplatelet activity.
Purpose of the Study:
- To investigate the antiplatelet activity of hydroxychloroquine (HCQ) when administered alone and in combination with aspirin (ASA).
- To compare the antiplatelet effects of HCQ plus ASA with ASA alone and with ASA plus clopidogrel (CLOP) in healthy volunteers.
Main Methods:
- Part 1 involved 8 volunteers receiving HCQ for 7 days.
- Part 2 randomized 12 volunteers to compare ASA, ASA plus CLOP, and ASA plus HCQ over two treatment periods with a 14-day washout.
- Inhibition of platelet aggregation (IPA) was quantified using light transmission aggregometry.
Main Results:
- HCQ alone significantly reduced platelet aggregation induced by arachidonic acid (AA) (P = .03).
- The combination of ASA plus HCQ showed a synergistic increase in IPA compared to ASA alone (P = .002), specifically with AA as the agonist.
- HCQ alone or with ASA also led to significant reductions in fibrinogen and erythrocyte sedimentation rate.
Conclusions:
- HCQ exhibits antiplatelet effects, potentially via the AA pathway downstream of thromboxane A2 production.
- The findings suggest HCQ may offer additional benefits beyond its effects on traditional cardiovascular risk factors.
- Larger clinical trials are warranted to explore the potential of HCQ as an antiplatelet agent in cardiovascular disease management.
Background:
With the inflammatory model of atherosclerosis taking center stage, anti-inflammatory drugs hold a promising place in the therapy of cardiovascular disease (CVD). Recent studies showed that hydroxychloroquine (HCQ) was protective against thrombovascular events in lupus erythematosus and traditional cardiovascular risk factors in patients with rheumatoid arthritis. Some preliminary experimental data have shown that it may prevent platelet activation too.
Objective:
To evaluate the antiplatelet activity of HCQ when given alone and in combination with aspirin (ASA) and compare it with ASA alone and ASA plus clopidogrel (CLOP) in healthy human volunteers.
Methods:
In part 1 of the study, 8 volunteers were given HCQ for 7 days. In part 2, 12 volunteers were randomly assigned in a 1:1:1 ratio to the 3 groups in which 2 of the 3 treatments, ASA, ASA plus CLOP, and ASA plus HCQ, were given in the 2 treatment periods separated by a 14-day washout period using the incomplete block design. Inhibition of platelet aggregation (IPA) was measured by light transmission aggregometry.
Results:
When arachidonic acid (AA) was used as agonist, HCQ given alone showed a significant reduction in platelet aggregation (11.0% ± 4.2%, P = .03). The IPA was significantly increased when ASA plus HCQ was compared with ASA alone (31.2% ± 8.1%, P = .002). This synergistic effect was not seen with adenosine diphosphate and collagen as agonists. Levels of serum 11-dehydrothromboxane B2, a stable marker of thromboxane A2 production, were not significantly different between the groups. There was also a significant decrease in fibrinogen and erythrocyte sedimentation rate values when HCQ was used alone or in combination with ASA.
Conclusion:
This study suggests that HCQ has antiplatelet properties possibly through the AA pathway (downstream to thromboxane A2 production). With possible additional beneficial effects over the traditional CVD risk factors, larger studies in the future might explore HCQ's potential as an antiplatelet agent.
