C Basic & Clinical Pharmacology & Toxicology 2006, 99, 283–286.Printed in Denmark . All rights reserved

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MiniReview

The Established and Emerging Uses of AspirinGareth Morgan

Welsh Aspirin Group, 41 Ffordd Beck, Gowerton, Swansea, Wales, U.K. SA4 3GE

(Received January 2, 2006; Accepted March 17, 2006)

Abstract: In this paper, summary narratives on the established and emerging uses of aspirin are presented. On the former,aspirin is used to treat conditions such as headache and also reduce the risks associated with cardiovascular disease andalso with pre-eclampsia. On the latter, aspirin might be taken more widely by individuals over 50 years, used as a dietarysupplement to possibly reduce cancer risk and used post-transplant to improve organ survival. Aspirin will continue tobe an important therapeutic agent and to generate considerable interest among the research community for the foreseeablefuture.

Aspirin (acetylsalicylate) is an inexpensive, relatively safeand widely used medicine (Trinder et al. 2003). It waslaunched onto the market over 100 years ago by Bayer,possibly heralding the start of the modern pharmaceuticalindustry. Subsequent work has also contributed to the for-mation of at least two classes of medicines namely the non-steroidal anti-inflammatory drugs (NSAIDs) and the sali-cylates such as 5 amino-salicylic acid. Furthermore, evenafter more than one century, we are still discovering moreabout the pharmacology (Flower 2003) and health benefitsof the drug (Elwood 2001). This MiniReview presents sum-mary narratives on the established and emerging uses ofaspirin (fig. 1). Box 1 also provides a brief discussion on theclinical use and pharmacology of aspirin in terms of dosageconsideration, risk/benefit assessment, pharmacokineticsand drug interactions.

Aspirin, either alone or in combination with otheragents, is used to treat a variety of conditions associatedwith pain, inflammation and fever (Flower 2003). These in-clude headache and the common cold. Most adults havetaken aspirin at some stage in their lives for one or moreof these conditions and domestic medicine cabinets oftencontain aspirin or a medicinal preparation containing it.These products are often from over-the-counter sales and inWales an estimated 3 million products are purchased perannum. This is approximately equivalent to one product perhead of population although each product will containmultiple preparations.

The pharmacological basis of the benefit against theseconditions is believed to be related, at least in part, to theinhibition of the cyclooxygenase enzyme leading to a re-duced synthesis of pro-inflammatory prostaglandins (PG’s)

Author for correspondence: Gareth Morgan, 41 Ffordd Beck,Gowerton, Swansea, Wales, U.K. SA4 3GE (e-mail morgan/fforrdbeck.fsnet.co.uk).

(Flower 2003). Yet, cyclooxygenase inhibition also leads toa reduction in the synthesis of protective prostaglandins inthe gastrointestinal tract contributing to the undesirable ef-fects of irritation and bleeding (Pirmohamed et al. 2004).

Box 1: Summary narratives on aspirin clinical use and phar-

macology

Aspirin doses vary according to the effect required in respect ofthe condition being treated. For cardiovascular disease patientsrequiring an anti-platelet effect, an oral low-dose of 75–325 mgonce per day is used. The pain (analgesic) and fever (antipyretic)relieving effects of aspirin are higher than the anti-platelet dose.For example, an adult may require a total daily oral intake of4g built up by an oral dose every 6 hr. For the antiinflammatoryeffect, more than 5g per day may be required taken orally in 4or more divided doses.

As with all other medications, the therapeutic dose of aspirinthat is used will vary according to the specific patient character-istics. However, there is a direct relationship between the doseof aspirin that is taken and the risk of undesirable effects suchas gastrointestinal irritation and bleeding. Each clinical situ-ation in which aspirin may be considered therefore presents arisk versus benefit assessment. There are strategies available toreduce the risk of the undesirable effects including the coatingof tablets and instructing patients to take tablets with plenty ofwater.

For completeness and to put this paper in a wider context,some pharmacokinetic and drug interaction aspects of aspirinfollow. In respect of the former, aspirin is rapidly absorbed fromthe gastrointestinal tract following ingestion which is usuallyoral. The major metabolite is salicylate and this is excreted bythe kidneys. Aspirin also interacts with other drugs and for ex-ample it can reduce the effect of diuretics. The drug can alsoincrease the effect of anticoagulation drugs such as warfarin.These effects also need to be factored into the risk versus benefitassessment in the clinical use of aspirin.

Aspirin is also used by patients with cardiovascular disease.Meta-analyses of randomised trials suggest that low-dose

284 GARETH MORGAN MiniReview

Fig. 1. Summary of the established (solid lines) and emerging (dotted lines) uses of aspirin.

(75–150 mg per day) aspirin users benefit from a reducedrisk of cardiovascular disease morbidity of at least 25%,reduced risks of cardiovascular disease mortality of between20–50% depending on the clinical history of the patient anda reduced risk of all-cause mortality by as much as 20%(Antithrombotic Trialists’ Collaboration 2002; Hayden et

al. 2002; van Walraven et al. 2002; Weisman & Graham2002). In Wales, about 1.5 million prescriptions for aspirinare dispensed per annum with around 90% of these done soin primary care settings. However, further efforts to pro-mote aspirin appear to be needed since it is not taken by asmany as 50% of patients at risk of suffering cardiovascularevents such as heart attack and ischaemic stroke (Carroll et

al. 2003; Elwood et al. 2005a).

The pharmacological basis of the benefit against cardio-vascular disease is believed to be related, at least in part, tocyclooxygenase inhibition leading to a reduced synthesis ofthromboxanes that aggregate platelets in the blood. Al-though there is also a relationship between long-term low-grade inflammation and increased coronary heart diseaserisk (Danesh et al. 2000), it seems unlikely that aspirin in-fluences this process.

There is good evidence that low-dose aspirin may also behelpful in some pregnancies by reducing the risks associatedwith pre-eclampsia and increasing the birth weight of babies(Coomarasamy 2003). Aspirin is contraindicated in thethird trimester of pregnancy and there are restrictions forthe use in the first two trimesters so it should only be con-

285ESTABLISHED AND EMERGING USES OF ASPIRINMiniReview

sidered in women with historical risk factors. Furthemore,since low-birth weight predisposes to coronary heart diseaseand other illnesses later in life (Barker et al. 2002), perhapsthis indication for aspirin might prove to be of public healthimportance.

The pharmacological basis of the benefit against preg-nancy complications is not well understood. Perhaps benefitmight be related to the antihypertensive properties of as-pirin (Hermida et al. 2003). In addition, perhaps aspirinhelps to improve blood supply to the developing foetus, viaeffects upon the vascular system and platelets, thus ac-counting for the effect on birth weight.

The emerging uses of aspirin include the suggestion thata low-dose might be taken by individuals over the age of 50years without a contraindication (Morgan 2003a; Elwoodet al. 2005b). The cardiovascular benefits alone support thissuggestion but the matter is highly controversial and othershave challenged this view on the basis of the undesirableeffects of the drug (Baigent 2005). However, there may beadditional bonuses to those individuals who take aspirinnamely reduction in the risk of chronic diseases such ascancer (Baron 2003; Morgan 2004b) and possibly againstneurological conditions such as Alzhiemer’s disease (Entmi-nan et al. 2003) and Parkinson’s disease (Chen et al. 2003).The public health implication of wider aspirin use is far-reaching, particularly given that the ‘Western population’ isageing and increased aspirin use might reduce populationmortality by approximately 10% (Morgan 2005a; Ratnas-inghe et al. 2004).

There may be multiple pharmacological mechanismsthrough which aspirin may confer a broad range of benefitsto older people over 50 years of age. The anti-platelet effectis certainly of relevance and with respect to possible cancerreduction, induction of programmed cell death (apoptotis)has been suggested as one of the mechanisms of action (Dinet al. 2004).

Human populations have two important sources of sali-cylate. The first is through the use of aspirin (acetylsalicyl-ate) and the second is by eating fresh fruits and vegetablesgrown in natural conditions. It has been suggested that itmay be legitimate to re-classify salicylate as vitamin S(Morgan 2004a). Whether or not this suggestion becomesadopted, the apoptotic properties of salicylate plus the in-verse association between fruit and vegetable intake andcancer risk suggest that salicylate might possibly confer acertain degree of protection against cancer.

The pharmacological basis for the controversial sugges-tion of aspirin for cancer reduction is that ‘Western popula-tions’ may now be salicylate-deficient (Morgan 2003b). Thedeficiency, which may be related to changes in food produc-tion and consumption patterns, is possibly a substantialthreat to public health. Therefore, more ‘nutriceutical’ re-search on the matter of salicylates in human health anddisease is required as a matter of urgency to end speculationon this topic.

Renal insufficiency is another contraindication for as-pirin yet in low-doses the drug could exert a range of bene-

fits in kidney transplant patients (Grotz et al. 2004). Thisraises another risk/benefit assessment issue but the possi-bility that a low-dose could lead to an increase in transplantefficacy is worthy of further clinical study in renal and otherorgan transplant situations. The national and Europeantransplant registers, some of which are rich sources of data,would appear to be reasonable starting points for suchstudy.

The pharmacological basis for suggesting aspirin as apost-transplant agent is another area that requires furtherstudy. The anti-platelet effects of aspirin may prove to beimportant. An alternative productive line for inquiry mightbe the effect of aspirin on cyclooxygenase-1 and -2 systemsin host and transplanted tissues. Perhaps these systems playkey roles in inflammatory and immunological reactionspost-transplant.

It is likely that the use of aspirin for the alleviation ofhuman disease will increase. Possibly, other indications forit may be identified or new aspirin formulations, such asthe ‘Polypill’ (a statin, folic acid, blood pressure-reducingagents and 75 mg aspirin), may be marketed. The searchfor new formulations on aspirin that improve therapeuticefficacy and reduce the risk of undesirable effects is a keyresearch avenue to ensure optimum benefit/risk in all of thetreatments for which aspirin is used.

There is another dimension that cannot be excluded andthat is cost. Recent economic analyses have highlighted thevalue of aspirin in treating cardiovascular disease (Pignoneet al. 2006) and have questioned the cost-effectiveness ofthe ‘Polypill’ (Franco et al. 2006). Further economic analy-ses are required but what is beyond reasonable doubt is thataspirin will continue to be an important therapeutic agentthat will continue to generate considerable interest, researchand publications for the foreseeable future. In contributionto this, the Welsh Aspirin Group is currently engaged indiscussions about taking forward a number of initiatives inWales (Morgan 2005b).

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