Headache
Aspirin is one of the first-line drugs used in the treatment of migraine, bringing relief in 50–60% of the cases.[26] It is as effective as a newer triptan medication sumatriptan (Imitrex)[27] and other painkillers such as paracetamol (acetaminophen)[28] or ibuprofen.[29] The combination of aspirin, paracetamol (acetaminophen) and caffeine (Excedrin) is even more potent. For the treatment of migraine headache, this formulation works better than any of its three components taken separately,[28] better than ibuprofen[30] and better than sumatriptan. Similarly to all other medications for migraine, it is recommended to take aspirin at the first signs of the headache, and it is the way these medications were used in the comparative clinical trials.[31]
Aspirin alleviates pain in 60–75% of patients with episodic tension headaches.[32][33] It is equivalent to paracetamol (acetaminophen) in that respect, except for the higher frequency of gastrointestinal side effects.[33] Comparative clinical trials indicated that metamizole and ibuprofen may relieve pain faster than aspirin, although the difference becomes insignificant after about 2 hours. The addition of Caffeine in a dose of 60–130 mg to aspirin increases the analgesic effect in headache.[32][34] The combination of aspirin, paracetamol (acetaminophen) and caffeine (Excedrin) is still more effective, but at the cost of more stomach discomfort, nervousness and dizziness.[35]
Pain
In general, aspirin works well for dull, throbbing pain; it is ineffective for pain caused by most muscle cramps, bloating, gastric distension and acute skin irritation.[36] The most studied example is pain after surgery such as tooth extraction, for which the highest allowed dose of aspirin (1 g) is equivalent to 1 g of paracetamol (acetaminophen), 60 mg of codeine and 5 mg of oxycodone. Combination of aspirin and caffeine, generally, affords greater pain relief than aspirin alone. Effervescent aspirin alleviates pain much faster than aspirin in tablets (15–30 min vs. 45–60 min).[37]
Nevertheless, as a post-surgery painkiller, aspirin is inferior to ibuprofen. Aspirin has higher gastrointestinal toxicity than ibuprofen. The maximum dose of aspirin (1 g) provides weaker pain relief than an intermediate dose of ibuprofen (400 mg), and this relief does not last as long.[37] A combination of aspirin and codeine may have a slightly higher analgesic effect than aspirin alone; however, this difference is not clinically meaningful.[38] It appears that ibuprofen is at least equally, and possibly more, effective than this combination.[39]
According to a meta-analysis of clinical trials for menstrual pain, aspirin demonstrated higher efficacy than placebo but lower one than ibuprofen or naproxen, although maximum doses of aspirin were never used in these trials. The authors concluded that ibuprofen has the best risk-benefit ratio.[40]
Aspirin did not ease pain during cycling exercise,[41] while caffeine, surprisingly, was very effective.[42][43] Similarly, aspirin, codeine or paracetamol (acetaminophen) were not better than placebo for muscle soreness after exercise.[44]
Prevention of heart attacks and strokes
There are two distinct uses of aspirin for prophylaxis of cardiovascular events: primary prevention and secondary prevention. Primary prevention is about decreasing strokes and heart attacks in the general population of those who have no diagnosed heart or vascular problems. Secondary prevention concerns patients with known cardiovascular disease.[45]
Low doses of aspirin are recommended for the secondary prevention of strokes and heart attacks. For both males and females diagnosed with cardiovascular disease, aspirin reduces the chance of a heart attack and ischaemic stroke by about a fifth.[citation needed] This translates to an absolute rate reduction from 8.2% to 6.7% of such events per year for people already with cardiovascular disease.[citation needed] Although aspirin also raises the risk of hemorrhagic stroke and other major bleeds by about twofold, these events are rare, and the balance of aspirin's effects is positive. Thus, in secondary prevention trials, aspirin reduced the overall mortality by about a tenth.[45]
For persons without cardiovascular problems, the benefits of aspirin are unclear. In the primary prevention trials aspirin decreased the overall incidence of heart attacks and ischaemic strokes by about a tenth. However, since these events were rare, the absolute reduction of their rate was low: from 0.57% to 0.51% per year. In addition, the risks of hemorrhagic strokes and gastrointestinal bleeding almost completely offset the benefits of aspirin. Thus, in the primary prevention trials aspirin did not change the overall mortality rate.[45] Further trials are in progress[update].[45]
The expert bodies diverge in their opinions regarding the use of aspirin for primary prevention, such as can be accomplished by including aspirin in a polypill for the general population. The US Government Preventive Services Task Force recommended making individual case by case choice based on the estimated future risk and patient's preferences.[46][47] On the other hand, Antithrombotic Trialists’ Collaboration argued that such recommendations are unjustified since the relative reduction of risk in the primary prevention trials of aspirin was same for persons in high- and low-risk groups and did not depend on the blood pressure. The Collaboration suggested statins as the alternative and more effective preventive medication.[45]
Coronary and carotid arteries, bypasses and stents
The coronary arteries supply blood to the heart. Aspirin is recommended for 1 to 6 months after placement of stents in the coronary arteries and for years after a coronary artery bypass graft.
The carotid arteries supply blood to the brain. Patients with mild carotid artery stenosis benefit from aspirin. Aspirin is recommended after a carotid endarterectomy or carotid artery stent.
After vascular surgery of the lower legs using artificial grafts which are sutured to the arteries to improve blood supply, aspirin is used to keep the grafts open.
Other uses
Although aspirin has been used to combat fever and pains associated with common cold for more than 100 years, only recently its efficacy was confirmed in controlled clinical trials on adults. 1 g of aspirin, on average, reduced the oral body temperature from 39.0 °C (102.2 °F) to 37.6 °C (99.7 °F) after 3 hours. The relief began after 30 minutes, and after 6 hours the temperature still remained below 37.8 °C (100.0 °F). Aspirin also helped with "achiness", discomfort and headache,[48] and with sore throat pain, for those who had it.[49] Aspirin was indistinguishable from paracetamol (acetaminophen) in any respect, except for, possibly, slightly higher rate of sweating and gastrointestinal side effects.[48]
Fever and joint pain of acute rheumatic fever respond extremely well, often within three days, to high doses of aspirin. The therapy usually lasts for 1–2 weeks; and only in about 5% of the cases it has to continue for longer than six months. After fever and pain have subsided, the aspirin treatment is unnecessary as it does not decrease the incidence of heart complications and residual rheumatic heart disease.[50] In addition, the high doses of aspirin used cause liver toxicity in about 20% of the treated children,[51][52] who are the majority of rheumatic fever patients, and increase the risk of them developing Reye's syndrome.[50] Naproxen was shown to be as effective as aspirin and less toxic; however, due to the limited clinical experience, naproxen is recommended only as a second-line treatment.[50][53]
Along with rheumatic fever, Kawasaki disease remains one of the few indications for aspirin use in children, although even this use has been questioned by some authors.[54] In the United Kingdom, the only indications for aspirin use in children and adolescents under 16 are Kawasaki disease and prevention of blood clot formation.
Aspirin is also used in the treatment of pericarditis, coronary artery disease, and acute myocardial infarction.[55][56][57]
There have been suggestions that taking aspirin before air travel in cramped conditions may decrease the risk of deep-vein thrombosis (DVT). The reason for taking aspirin is the long period of sitting without exercise, not air travel in itself. A large, randomized, controlled trial in 2000 of aspirin against placebo in 13,000 patients with hip fractures found "a 29% relative risk reduction in DVT with 160 mg of aspirin taken daily for 5 weeks. Although there are obvious problems with extrapolating the data to long-distance travelers, this is the best evidence we could find to justify aspirin use".[58]
Experimental
Aspirin has been theorized to reduce cataract formation in diabetic patients, but one study showed it was ineffective for this purpose.[59] The role of aspirin in reducing the incidence of many forms of cancer has also been widely studied. In several studies, aspirin use did not reduce the incidence of prostate cancer.[60][61] Its effects on the incidence of pancreatic cancer are mixed; one study published in 2004 found a statistically significant increase in the risk of pancreatic cancer among women,[62] while a meta-analysis of several studies, published in 2006, found no evidence that aspirin or other NSAIDs are associated with an increased risk for the disease.[63] The drug may be effective in reduction of risk of various cancers, including those of the colon,[64][65][66][67][68] lung,[69][70] and possibly the upper GI tract, though some evidence of its effectiveness in preventing cancer of the upper GI tract has been inconclusive.[71][71][72] Its preventative effect against adenocarcinomas may be explained by its inhibition of PTGS2 (COX-2) enzymes expressed in them.[73]
In a 2009 article published by the Journal of Clinical Investigation it was found that aspirin might prevent liver damage. In their experiment, scientists from Yale University and The University of Iowa induced damage in certain liver cells called hepatocytes using excessive doses of acetaminophen. This caused hepatoxicity and hepatocyte death which triggered an increase in the production of TLR9. The expression of TLR9 caused an inflammatory cascade involving pro–IL-1β and pro-IL-18. Aspirin was found to have a protective effect on hepatocytes because it led to the "downregulation of proinflammatory cytokines".[74]
In another 2009 article published by the Journal of the American Medical Association, it was found that men and women who regularly took aspirin after colorectal cancer diagnosis had lower risk of overall and colorectal cancer death compared to patients not using aspirin.[75][76]
A 2010 article in the Journal of Clinical Oncology has suggested that aspirin may reduce the risk of death from breast cancer.[77] While the information has been well-circulated by the media,[78][79] official health bodies and medical groups have expressed concern over the touting of aspirin as a "miracle drug".[80]
