Aspirin is used in the treatment of a number of conditions, including fever, pain, rheumatic fever, and inflammatory diseases, such as rheumatoid arthritis, pericarditis, and Kawasaki disease.[17] Lower doses of aspirin have also shown to reduce the risk of death from a heart attack, or the risk of stroke in some circumstances.[18][19][20] There is some evidence that aspirin is effective at preventing colorectal cancer, though the mechanisms of this effect are unclear.[21]

Pain[edit]

Aspirin 325 mg for pain

Uncoated aspirin tablets, consisting of about 90% acetylsalicylic acid, along with a minor amount of inert fillers and bindersAspirin is an effective analgesic for acute pain, but is generally considered inferior to ibuprofen for the alleviation of pain because aspirin is more likely to cause gastrointestinal bleeding.[22] Aspirin is generally ineffective for those pains caused by muscle cramps, bloating, gastric distension, or acute skin irritation.[23] As with other NSAIDs, combinations of aspirin and caffeine provide slightly greater pain relief than aspirin alone.[24] Effervescent formulations of aspirin, such as Alka-Seltzer or Blowfish,[25] relieve pain faster than aspirin in tablets,[26] which makes them useful for the treatment of migraines.[27]

Topical aspirin may be effective for treating some types of neuropathic pain.[28]

Headache[edit]Aspirin, either by itself or in a combined formulation, effectively treats some types of headache, but its efficacy may be questionable for others. Secondary headaches, meaning those caused by another disorder or trauma, should be promptly treated by a medical provider.

Among primary headaches, the International Classification of Headache Disorders distinguishes between tension headache (the most common), migraine, and cluster headache. Aspirin or other over-the-counter analgesics are widely recognized as effective for the treatment of tension headache.[29] Aspirin, especially as a component of an acetaminophen/aspirin/caffeine formulation, e.g., Excedrin Migraine, is considered a first-line therapy in the treatment of migraine, and comparable to lower doses of sumatriptan. It is most effective at stopping migraines when they are first beginning.[30]

Fever[edit]Like its ability to control pain, aspirin's ability to control fever is due to its action on the prostaglandin system through its irreversible inhibition of COX.[31] Although aspirin's use as an antipyretic in adults is well-established, many medical societies and regulatory agencies (including the American Academy of Family Physicians, the American Academy of Pediatrics, and the U.S. Food and Drug Administration (FDA) strongly advise against using aspirin for treatment of fever in children because of the risk of Reye's syndrome, a rare but often fatal illness associated with the use of aspirin or other salicylates in children during episodes of viral or bacterial infection.[32][33][34] Because of the risk of Reye's syndrome in children, in 1986, the FDA required labeling on all aspirin-containing medications advising against its use in children and teenagers.[35]

Swelling and inflammation[edit]Aspirin is used as an anti-inflammatory agent for both acute and long-term inflammation,[36] as well as for treatment of inflammatory diseases, such as rheumatoid arthritis.[17]

Heart attacks and strokes[edit]The first studies of the effect of aspirin on cardiac function and stroke prevention was carried out by Professor Peter Sleight,[37] Emeritus Professor of Cardiovascular Medicine at Oxford University in the early 1970s.[38] Sleight and his research team at Oxford led the way and formed the foundation for the research into the use of aspirin in the prevention of other medical conditions.

For a subset of the population, aspirin may help prevent heart attacks and strokes. In lower doses, aspirin has been known to prevent the progression of existing cardiovascular disease, and reduce the frequency of these events for those with a history of them.[39][40] (This is known as secondary prevention.)

Aspirin appears to offer little benefit to those at lower risk of heart attack or strokefor instance, those without a history of these events or with pre-existing disease. (This is called primary prevention.) Some studies recommend aspirin on a case-by-case basis,[41][42] while others have suggested the risks of other events, such as gastrointestinal bleeding, were significant enough to outweigh any potential benefit, and recommended against using aspirin for primary prevention entirely.[43]

Complicating the use of aspirin for prevention is the phenomenon of aspirin resistance.[44][45] For patients who are resistant, aspirin's efficacy is reduced, which can cause an increased risk of stroke.[46] Some authors have suggested testing regimens to identify those patients who are resistant to aspirin or other antithrombotic drugs (such as clopidogrel).[47]

Aspirin has also been suggested as a component of a polypill[48][49] for prevention of cardiovascular disease.

After surgery[edit]After percutaneous coronary interventions (PCIs), such as the placement of a coronary artery stent, a U.S. Agency for Healthcare Research and Quality guideline recommends that aspirin be taken indefinitely.[50] Frequently, aspirin is combined with an ADP receptor inhibitor, such as clopidogrel, prasugrel, or ticagrelor to prevent blood clots. This is called dual antiplatelet therapy (DAPT). United States and European Union guidelines disagree somewhat about how long, and for what indications this combined therapy should be continued after surgery. U.S. guidelines recommend DAPT for at least 12 months, while EU guidelines recommend DAPT for 612 months after a drug-eluting stent placement.[51] However, they agree that aspirin be continued indefinitely after DAPT is complete.

Cancer prevention[edit]Aspirin reduces the overall risk of both getting cancer and dying from cancer.[52] This effect is particularly beneficial for colorectal cancer (CRC).[21][53][54][55]

Some conclude the benefits are greater than the risks due to bleeding in those at average risk.[52] Other are unclear if the benefits are greater than the risk.[56][57] Given this uncertainty, the 2007 United States Preventive Services Task Force guidelines on this topic recommended against the use of aspirin for prevention of CRC in people with average risk.[58]

Other uses[edit]Aspirin is a first-line treatment for the fever and joint-pain symptoms of acute rheumatic fever. The therapy often lasts for one to two weeks, and is rarely indicated for longer periods. After fever and pain have subsided, the aspirin is no longer necessary, since it does not decrease the incidence of heart complications and residual rheumatic heart disease.[59][60] Naproxen has been shown to be as effective as aspirin and less toxic, but due to the limited clinical experience, naproxen is recommended only as a second-line treatment.[59][61]

Along with rheumatic fever, Kawasaki disease remains one of the few indications for aspirin use in children[62] in spite of a lack of high quality evidence for its effectiveness.[63]

Low-dose aspirin supplementation has moderate benefits when used for prevention of pre-eclampsia.[64][65]

Resistance[edit]For some people, aspirin does not have as strong an effect on platelets as for others, an effect known as aspirin resistance or insensitivity. One study has suggested women are more likely to be resistant than men,[66] and a different, aggregate study of 2,930 patients found 28% were resistant.[67] A study in 100 Italian patients, though, found, of the apparent 31% aspirin-resistant subjects, only 5% were truly resistant, and the others were noncompliant.[68] Another study of 400 healthy volunteers found no subjects who were truly resistant, but some had "pseudoresistance, reflecting delayed and reduced drug absorption".[69]

Dosage[edit]

Coated 325-mg aspirin tabletsAdult aspirin tablets are produced in standardised sizes, which vary slightly from country to country, for example 300 mg in Britain and 325 mg in the United States. Smaller doses are based on these standards, e.g., 75-mg and 81-mg tablets. The 81-mg tablets are called "baby-strength", though they are not intended to be administered to infants and children. No medical significance occurs due to the slight difference in dosage between the 75-mg and the 81-mg tablets. Of historic interest, in the United States, a 325-mg dose is equivalent to the historic 5-grain aspirin tablet in use prior to the metric system.[citation needed]

In general, for adults, doses are taken four times a day for fever or arthritis,[70] with doses near the maximal daily dose used historically for the treatment of rheumatic fever.[71] For the prevention of myocardial infarction (MI) in someone with documented or suspected coronary artery disease, much lower doses are taken once daily.[70]

Recommendations from the USPSTF[72] on the use of aspirin for the primary prevention of coronary heart disease encourage men aged 4579 and women aged 5579 to use aspirin when the potential benefit of a reduction in MI for men or stroke for women outweighs the potential harm of an increase in gastrointestinal hemorrhage.[73] The WHI study said regular low-dose (75- or 81-mg) aspirin female users had a 25% lower risk of death from cardiovascular disease and a 14% lower risk of death from any cause.[73] Low-dose aspirin use was also associated with a trend toward lower risk of cardiovascular events, and lower aspirin doses (75 or 81 mg/day) may optimize efficacy and safety for patients requiring aspirin for long-term prevention.[73]

In children with Kawasaki disease, aspirin is taken at dosages based on body weight, initially four times a day for up to two weeks and then at a lower dose once daily for a further six to eight weeks.[74]

Transient Ischemic Attacks and Ischemic StrokeReduction of the risk of recurrent TIAs or stroke or of death in patients with a history of TIAs or ischemic stroke (secondary prevention).6466828421009cmAlso used in fixed combination with extended-release dipyridamole to reduce the risk of recurrent stroke, death from all vascular causes, or nonfatal MI in patients who have had TIAs or completed ischemic stroke caused by thrombosis.7167387397431009The American College of Chest Physicians (ACCP), the American Stroke Association (ASA), and AHA consider aspirin or the combination of aspirin and extended-release dipyridamole acceptable antiplatelet regimens for secondary prevention of noncardioembolic ischemic stroke and TIAs; other options include cilostazol or clopidogrel.9901009When selecting an appropriate antiplatelet regimen, consider factors such as the patient's individual risk for recurrent stroke, tolerance, and cost of the different agents.990Oral anticoagulation (e.g., dabigatran, warfarin) rather than antiplatelet therapy is recommended in patients with a history of ischemic stroke or TIA and concurrent atrial fibrillation; however, in patients who cannot take or choose not to take oral anticoagulants (e.g., those with difficulty maintaining stable INRs, compliance issues, dietary restrictions, or cost limitations), dual antiplatelet therapy with aspirin and clopidogrel is recommended.1009Also used for acute treatment of ischemic stroke in children.1013Secondary Prevention of Coronary Artery Disease and Myocardial InfarctionRecommended by AHA and the American College of Cardiology Foundation (ACCF) for reduction of the risk of vascular events (e.g., stroke, recurrent MI) inallpatients with CAD, unless contraindicated.992Reduction of the risk of vascular mortality in patients with suspected acute ST-segment-elevation MI (STEMI).579635636646821cmReduction of the risk of stroke and recurrent infarction in patients surviving an MI (secondary prevention).5796356468218421010cmRecommended by American Diabetes Association (ADA) for the prevention of cardiovascular events in diabetic patients who have evidence of large-vessel disease (e.g., history of MI, CABG, stroke or TIA, peripheral vascular disease, claudication, angina).830901Use in conjunction with a P2Y12 platelet adenosine diphosphate (ADP)-receptor antagonist (e.g., clopidogrel, prasugrel, ticagrelor) following an acute coronary syndrome (ACS), including STEMI.9929939941010The addition of warfarin to antiplatelet therapy is recommended in patients with MI who have indications for anticoagulation (e.g., atrial fibrillation, left ventricular dysfunction, cerebral emboli, extensive wall-motion abnormality, mechanical heart valves).99399610071010Primary Prevention of Ischemic Cardiac EventsMay reduce the risk of a first cardiac event (e.g., MI)in certain patient populations (primary prevention).573574575576658659660661666667668670671783785786848851Balance of risks and benefits is most favorable in patients at moderate to high risk of CHD783(based on age and 10-year risk of cardiac event >10%).668832Use of aspirin in such patients is suggested over either warfarin or no antithrombotic therapy.Recommended by ADA for primary prevention in patients with type 1 or type 2 diabetes mellitus who are at high risk for cardiovascular events (i.e., familial history of CHD, smoking, hypertension, obesity, albuminuria, elevated blood cholesterol or triglyceride concentrations) and in whom aspirin is not contraindicated.760830901Benefit appears to be minimal or lacking in women at low risk for CHD, except possibly those 65 years of age; further study needed.846847848849850851Not currently recommended for primary prevention in the general population without known risk factors.646658661674675676783784847ACCP suggests primary prevention with low-dose aspirin in individuals 50 years of age who do not have symptomatic cardiovascular disease.1010Unstable Angina or Non-ST-Segment-Elevation Myocardial InfarctionReduction of the risk of death and/or nonfatal MI in patients with unstable angina or non-ST-segment-elevation MI (NSTEMI).c581613614615616617618619620621682684728736mDual-drug antiplatelet therapy with aspirin and a P2Y12-receptor antagonist (e.g., clopidogrel, prasugrel, ticagrelor) is considered part of the current standard of care for treatment and secondary prevention in patients with ACS.9929939941010Chronic Stable AnginaReduction of the risk of MI and/or sudden death in patients with chronic stable angina.c646680728736822mPercutaneous Coronary Intervention and Revascularization ProceduresReduction of cardiovascular risks (e.g., early ischemic complications, graft closure) in patients with ACS undergoing PCI (e.g., coronary angioplasty, stent implantation)6468668878888899929939941010or CABG.646683687781782Pretreatment with aspirin prior to PCI recommended by ACCF, AHA, and the Society for Cardiovascular Angiography and Interventions (SCAI).994Adjunctive therapy with a P2Y12-receptor antagonist (e.g., clopidogrel, prasugrel, ticagrelor) also recommended in patients undergoing PCI with stent placement.994Continue low-dose aspirin therapy indefinitely as secondary prevention against cardiovascular events following PCI.9939941010Embolism Associated with Atrial Fibrillation/FlutterUsed as an alternative or adjunct to warfarin therapy for reduction of the incidence of thromboembolism in selected patients with chronic atrial fibrillationor atrial flutter.7498809991007ACCP, ACC, AHA, and other experts currently recommend antithrombotic therapy (e.g., warfarin, aspirin) in patients with persistent, permanent, or paroxysmal atrial fibrillation, unless such therapy is contraindicated.9991007Choice of antithrombotic therapy is based on patient's risk for stroke.9991007In general, oral anticoagulant therapy is recommended in patients with high risk for stroke, while aspirin is recommended in low-risk patients or those with contraindications to oral anticoagulant therapy.9991007In patients with atrial fibrillation at increased risk of stroke who cannot take or choose not to take oral anticoagulants for reasons other than concerns about major bleeding (e.g., those with difficulty maintaining stable INRs), combination therapy with clopidogrel and aspirin rather than aspirin alone is recommended.9981007Peripheral Arterial DiseaseHas been used for primary and secondary prophylaxis of cardiovascular events in patients with peripheral arterial disease, including those with intermittent claudication or carotid stenosis and those undergoing revascularization procedures (peripheral artery percutaneous transluminal angioplasty or peripheral arterial bypass graft surgery).1011ACCP suggests the use of low-dose aspirin for primary prevention in patients with asymptomatic peripheral arterial disease.1011For patients with symptomatic peripheral arterial disease or those undergoing revascularization procedures, single-drug antiplatelet therapy with aspirin or clopidogrel generally is recommended.1011Valvular Heart DiseaseRecommended by ACC and AHA for use in selected patients with mitral valve prolapse and atrial fibrillation, and also in symptomatic patients with mitral valve prolapse who experience TIAs.996Prosthetic Heart ValvesUsed for the prevention of thromboembolism in selected patients with prosthetic heart valves.9961008ACCP and ACC/AHA suggest the use of low-dose aspirin for initial (i.e., first 3 months after valve insertion) and long-term antithrombotic therapy in patients with a bioprosthetic heart valve in the aortic position who are in sinus rhythm and have no other indications for warfarin.9961008Aspirin also may be considered after initial (3 months) warfarin therapy in patients with a bioprosthetic heart valve in the mitral position who are in sinus rhythm.1008Addition of an antiplatelet agent such as low-dose aspirin to warfarin therapy recommended in all patients with mechanical heart valves who are at low risk of bleeding.9961008Combination therapy with aspirin and warfarin also recommended in patients with bioprosthetic heart valves who have additional risk factors for thrombosis (e.g., atrial fibrillation, previous thromboembolism, left ventricular dysfunction, hypercoagulable condition).996May be added to therapy with a low molecular weight heparin (LMWH) or heparin (referring throughout this monograph to unfractionated heparin) in pregnant women with prosthetic heart valveswho are at high risk for thrombosis.1012Thrombosis Associated with Fontan Procedure in ChildrenHas been used for prevention of thromboembolic complications following Fontan procedure(definitive palliative surgical treatment for most congenital univentricular heart lesions) in children.1013Thromboprophylaxis in Orthopedic SurgeryHas been used for the prevention of venous thromboembolism in patients undergoing major orthopedic surgery (total-hip replacement, total-knee replacement, or hip-fracture surgery).1003Aspirin generally not considered the drug of choice for this use;1003however, some evidence suggests some benefit over placebo or no antithrombotic prophylaxis in patients undergoing major orthopedic surgery.9539541003ACCP considers aspirin an acceptable option for pharmacologic thromboprophylaxis in patients undergoing major orthopedic surgery.1003When selecting an appropriate thromboprophylaxis regimen, consider factors such as relative efficacy and bleeding risk in addition to other logistics and compliance issues.1003Thromboprophylaxis in General SurgeryHas been used for thromboprophylaxis in patients undergoing general (e.g., abdominal) surgery who are at high risk of venous thromboembolism;1002however, generally recommended as an alternative to LMWHs and low-dose heparin.1002PericarditisDrug of choice for the management of pain associated with acute pericarditisfollowing MI.635821Kawasaki DiseaseTreatment of Kawasaki disease; used in conjunction with immune globulin IV (IGIV).6366376381013Complications of PregnancyHas been used alone or in combination with other drugs (e.g., heparin, corticosteroids, immune globulin) for prevention of complications of pregnancy(e.g., preeclampsia, pregnancy loss in women with a history of antiphospholipid syndrome and recurrent fetal loss).5945955965975996006016056266276286486506516526536547057067077087097107117127137147157268178571012Low-dose aspirin in combination with sub-Q heparin or an LMWH is recommended by ACCP in women with antiphospholipid antibody (APLA) syndromeand a history of multiple (3) pregnancy losses.1012Routine use of aspirin prophylaxis to reduce the incidence and severity of preeclampsia (even in patients at increased risk of preeclampsia) generally not recommended;634705706707712713715can consider prophylaxis in women with prior severe or early-onset preeclampsia, chronic hypertension, severe diabetes, or moderate to severe renal disease.815816817In women at high risk for preeclampsia, ACCP recommends low-dose aspirin during pregnancy, starting from the second trimester.1012(See Pregnancy under Cautions.)Prevention of CancerLimited data (observational studies) suggest that aspirin or other NSAIAs may reduce the risk of various cancers(e.g., colorectal, breast, gastric cancer);864870871872873such results generally not confirmed in randomized controlled trials.864874875876Regular use (e.g., daily) associated with a reduction in the risk of recurrent colorectal adenomas and colorectal cancerin some studies.789790791792793794795796797798799800801802803804805806807808809810811812813814815Beneficial effects of NSAIAs in reducing colorectal cancer risk dissipate following discontinuance of such therapy. Preventive therapy with aspirin currently not recommended because aspirin does not completely eliminate adenomas; aspirin therapy should not be considered a replacement for colorectal cancer screening and surveillance.790793794795796814Aspirin Dosage and AdministrationAdministrationAdminister orally; may administer rectally as suppositories in patients who cannot tolerate oral therapy.aDo not use aspirin preparation if strong vinegar-like odor is present.aOral AdministrationUsually administer orally with food or a full glass of water (240 mL).a836mFilm-coated, extended-release, or enteric-coated may be associated with less GI irritation and/or symptomatic GI disturbances than uncoated tablets.aDo not use delayed-release or extended-release tablets if rapid response is required.aSwallow delayed-release and extended-release tablets whole; do not crush or chew.aPrepare oral solution by dissolving 2 tablets for solution (Alka-Seltzer) in 120 mL of water; ingest the entire solution to ensure adequate dosing.838843844Do not chew aspirin preparations for 7 days following tonsillectomy or oral surgery;841837do not place preparations directly on tooth or gum surface (possible tissue injury from prolonged contact).aRectal AdministrationDo not administer aspirin tablets rectally.aDosageWhen used for pain, fever, or inflammatory diseases, attempt to titrate to the lowest effective dosage.aWhen used in anti-inflammatory dosages, development of tinnitus can be used as a sign of elevated plasma salicylate concentrations (except in patients with high-frequency hearing impairment).aPediatric PatientsDosage in children should be guided by body weight or body surface area.a841Do not use in children and teenagers with varicella or influenza, unless directed by a clinician.841(See Contraindications under Cautions.)PainOralChildren 211 years of age: 1.5 g/m2daily administered in 46 divided doses (maximum 2.5 g/m2daily).aDose may be given every 4 hours as necessary (up to 5 times in 24 hours).841Dosage for Self-medication of Pain in Children