Low Dose Aspirin. Aleem M A., Hakkim A M . BMJ 2018;363:k5108

British Medical journal  - BMJ

Research

Clopidogrel plus aspirin versus aspirin alone for acute minor ischaemic stroke or high risk transient ischaemic attack: systematic review and meta-analysis

BMJ 2018; 363 doi: https://doi.org/10.1136/bmj.k5108 (Published 18 December 2018)

Cite this as: BMJ 2018;363:k5108

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Re: Clopidogrel plus aspirin versus aspirin alone for acute minor ischaemic stroke or high risk transient ischaemic attack: systematic review and meta-analysis

Low Dose Aspirin

Antiplatelet drugs inhibit platelet activation and aggregation, an early step in the clotting process. Several classes of antiplatelet drugs inhibit platelet aggregation and activation at a different point in platelet metabolism.

The most common antiplatelet drug is aspirin. It inhibits the enzyme cyclooxygenase (COX), which is responsible for synthesizing thromboxane A2 . Thromboxane A2 is a factor secreted by platelets to recruit other platelets to the site of injury during the initial stages of the clotting process. The cyclooxygenase inhibitory effect of aspirin is permanent for the life of the platelet (about 7–10 days).

Aspirin has been shown effective in preventing stroke even in low dose. 
Interestingly, aspirin also inhibits the COX enzyme in endothelial cells, but does not exert an irreversible action here. Unlike platelets, endothelial cells contain DNA and RNA and can therefore synthesize new COX enzymes even after aspirin has bound to existing COX enzymes. This dichotomy of aspirin action in platelets versus endothelial cells is significant because the COX enzyme is critical for the synthesis of the anti-platelet, vasodilatory compound prostacyclin (PGI2). Healthy endothelial cells secrete prostacyclin to counteract the action of TXA2 and ensure that a clot does not continue to grow and occlude the blood vessel.
The difference between endothelial cell biology and platelet biology also explains why low-dose aspirin is cardioprotective. Low-dose aspirin does not impair endothelial secretion of prostacyclin because these cells quickly synthesize new COX enzymes and overwhelm low concentrations of aspirin. However, platelets do not synthesize new COX so that aspirin, even in low concentrations, suppresses platelet-derived TXA2 until new platelets arise from the bone marrow. Thus, low-dose aspirin is effective for reducing the risk of pathologic blood clot formation while maintaining optimal endothelial function.

A second group of commonly prescribed antiplatelet drug is Clopidogrel, which is more effective than aspirin in its ability to reduce the aggregation of platelets.
Clopidogrel activity can be enhanced when combined with aspirin and this combination has been tested for its efficacy, safety, and cost effectiveness in stroke.

The combined clopidogrel and aspirin resulted in a significant  reduction in  stroke risk , as compared to aspirin alone .

Other clinically important oral antiplatelets include dipyridamole  and cilostazol which are platelet phosphodiesterase inhibitors. These drugs are used less frequently as large-scale clinical trials have not proved them to be more effective than aspirin and clopidogrel 

Competing interests: No competing interests

15 January 2019

M.A. Aleem

Emeritus Professor of Neurology * Visiting Specialist in Neurology ** Consultant Neurologist ***

A.M.Hakkim

The Tamilnadu Dr.M.G.R. Medical University * Dhanalakshami Srinivasan Medical College ** ABC Hospital ***

Chennai 600032* Perambalure 621212** Trichy 620018*** Tamilnadu India

@drmaaleem