Aspirin or acetylsalicyclic acid (ASA) is commonly used for aches, pains, and headache occaisionally and long term if recommended by a physician for the prevention of heart attack, stroke, or blood clots if the patient is a candidate and the benefit of aspirin outweighs the risk of its use. It may cause an increase in the risk of bleeding by inhibiting thromboxane synthesis in platelets. Aspirin can reduce the prostaglandins which serve as a protective layer in the gastrointestinal tract placing patients at risk for gastric ulcers resulting in bleeding in the stomach. Aspirin use in children has been associated with Reyes Syndrome characterized by rash, vomiting and liver damage that may occur while taking aspirin with a viral illness. Ringing in the ears may occur in high doses.
Aspirin for prevention of cardiovascular disease and stroke, U.S. Preventive Services Task Force (USPSTF) (1):
Ideal dose of aspirin:
According to the USPSTF, the ideal dose of aspirin is not known, but a dose of 75 mg per day appears as effective as higher doses and may have less risk of gastrointestinal bleeding.
The USPSTF recommendation for prevention of cardiovascular disease in men:
Men younger than 45 years: For myocardial infarction prevention in men younger than 45 years the USPSTF recommends against the use of aspirin since the benefit for prevention of cardiovascular events are small.
Men age 45 to 79 years: The USPSTF strongly recommends the use of aspirin when the potential benefit due to a reduction in myocardial infarctions is more beneficial than the potential harm due to gastrointestinal hemorrhage.
The USPSTF recommendation for prevention of cardiovascular disease for the elderly: Men and Women 80 years of age and older: According to the USPSTF, there is insufficient evidence to determine the risk verses benefit of taking aspirin by men and women over 79 years of age for the prevention of cardiovascular disease.
Aspirin and prevention of ischemic stroke in women:
Cardiovascular events were not reduced in women by aspirin and therefore they are not believed to benefit from aspirin for heart disease but women do benefit from aspirin in the prevention of ischemic stroke.
Women age 55 to 79 years: The USPSTF strongly recommends aspirin when the potential benefit due to a reduction in ischemic strokes (which occur when an artery to the brain is blocked) is more beneficial than the potential harm due greater gastrointestinal hemorrhage.
Women 55 years old or younger: The USPSTF recommends against the use of aspirin for stroke prevention since the benefit for prevention of ischemic stroke is small.
A calculator for the risk of stroke (2):
http://www.westernstroke.org/PersonalStrokeRisk1.xls Western States Stroke Consortium, Neurocritical Care and Stroke Division, University of Southern California, 1100 N. State St., Clinic Tower A4E111, Los Angeles, CA 90033, Tel: 323-409-7381 Fax: 323-441-8093 Link is also available at: Aspirin for the Prevention of Cardiovascular Disease, Topic Page. December 2009. U.S. Preventive Services Task Force. http://www.uspreventiveservicestaskforce.org/uspstf/uspsasmi.htm
Aspirin use for the prevention of cancer:
Aspirin, non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs) and cancer: In a study by Bardia A et al, regular aspirin use was associated with a lower cancer incidence and cancer mortality, but non-aspirin non-steroidal anti-inflammatory drug (NSAID) use was not. The beneficial effects of aspirin were stronger in former and never smokers than current smokers. Among 22,507 cancer-free postmenopausal women age 55-69 who provided information on aspirin and NSAID use, those who said they regularly used aspirin had a 16% reduced risk of developing cancer more than a decade later. There was also a 13% reduced risk of dying from cancer over this same time period, compared to women who did not use aspirin. Aspirin use decreased the risk of mortality from coronary artery disease by 25% and reduced the risk of all-cause mortality by 18%. Ever use of aspirin was associated with a lower risk of cancer than those women who never used aspirin. Aspirin use greater than 6 times per week was compared to aspirin use 2-5 times per week, over 1 time per week, ever use , and never use. The higher the frequency of aspirin use, the lower the incidence of cancer. Also the higher the frequency of aspirin use, the lower the cancer mortality. The women with the lowest all-cause mortality took aspirin 2-5 times per week. There was no statistically significant impact on cancer incidence or mortality among women who used non-aspirin NSAIDs, compared to those who did not. (3)
Aspirin and colorectal cancer according to the U.S. Preventive Services Task Force (USPSTF):
For the prevention colorectal cancer in individuals at average risk for colorectal cancer the recommends against the routing use of aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs). According to the USPSTF, aspirin is required in higher doses than cardiovascular and ischemic stroke prevention. The higher doses of aspirin and NSAIDs required to prevent polyps and colorectal cancer poses a risk of severe bleeding episodes. Therefore, the USPSTF has determined that the risk of hemorrhagic stroke with aspirin outweighs the benefit of colorectal cancer prevention. The risk of gastrointestinal bleeding and hemorrhage with NSAIDs outweigh the benefits of colorectal cancer prevention. (4)
The USPSTF recommends against aspirin for prevention of colorectal cancer because it requires higher doses in order to accomplish this, but if aspirin is recommended for cardiovascular disease or stroke prevention, there would still be benefit obtained in the prevention of cancer, since according to the study by Bardia A et al, cancer incidence and cancer mortality was reduced even in patients that used aspirin infrequently compared to those that never used it (3).
Aspirin recommendations for diabetes patients from the American Heart Association (AHA) and the American Diabetes Association (ADA) (5):
Diabetes patients without history of vascular disease:
Diabetic patients without history of vascular disease but at increased risk of cardiovascular disease may benefit from the use of aspirin at a dose of 75–162 mg per day for primary prevention of cardiovascular disease. This would include men with diabetes over 50 and women with diabetes over 60 with additional risk factors of hyperlipidemia, family history of premature heart disease, high bp, smoking, and albuminuria only if there is no increased risk of bleeding or using other medications that can affect bleeding. Aspirin should not be used for diabetics without history of vascular disease in men under 50 years old or women under 60 years old and with a low risk of cardiovascular disease.
Diabetes patients with a history of vascular disease:
Low dose aspirin (75–162 mg per day) may be considered for primary prevention of cardiovascular disease in diabetic young patients with one or more risk factors or older patients without risk factors until further research is available.
Aspirin recommendations of the American Heart Association and American Stroke Association Stroke Council (6):
The use of aspirin for primary prevention of cardiovascular disease: The use of aspirin for primary prevention of cardiovascular disease is recommended in patients with a high enough risk of cardiovascular disease or 6-10% 10-year risk of cardiovascular events if the benefit of aspirin outweighs the risk of harm from aspirin use.
Stroke prevention:
For stroke prevention, men are not recommended to use aspirin but women with a risk of ischemic stroke are recommended to use aspirin if the benefit outweighs the risk of harm.
Aspirin as analgesia:
Aspirin relieves headaches better in combination with other analgesics than using aspirin alone: A double-blind, randomized clinical study with nonprescription pain medication for the treatment of headaches compared the effectiveness of a fixed combination of acetylsalicylic acid (ASA), paracetamol (PAR, also known as acetaminophen), and caffeine (CAF) or placebo (PL) over single substances in 1734 patients. Study participants were randomized to one of 5 treatments (2 tablets of 250 mg ASA + 200 mg PAR + 50 mg CAF) or (2 tablets of 250 mg ASA + 200 mg PAR) or (2 tablets of 500 mg ASA) or (2 tablets of 500 mg PAR) or (2 tablets of 50 mg CAF) or placebo (2 tablets of PL). Prior to randomized treatment phase, headache episodes treated with patients usual nonprescription drug (open-label pre-phase) were recorded. Pain intensity was measured on a 100-mm visual analog scale. Pain intensity difference (PID) from start of study to after treatment was compared. Results show caffeine was not effective when used alone for headaches but was effective in combination with other analgesics mentioned. The other agents (ASA and PAR) were approximately equal in relieving headache although not as well as the triple combination. A similar time course of PID from baseline to randomized study drug was reported. For patients who took ASA+PAR+CAF combination, there was overall better pain improvement and was all around superior to the single agent therapies. The combination also took less time to reach 50% pain relief than PAR, ASA, or CAF. (7)
Aspirin adverse reactions and interactions:
Aspirin interactions with drugs and herbal agents: Abebe W. reported the following possible aspirin interactions and concerns (9):
Dong Quai has antiplatelet effects and may interact with non-steroidal anti-inflammatory drugs (NSAIDs) and aspirin to increase risk of bleeding.
Feverfew has antiplatelet effects and may interact with non-steroidal anti-inflammatory drugs (NSAIDs), warfarin (Coumadin), heparin, and aspirin to increase risk of bleeding.
Garlic has antiplatelet effects and may interact with non-steroidal anti-inflammatory drugs (NSAIDs) and aspirin to increase risk of bleeding and with an increased anticoagulation (reduce blood clotting) effect when combining with aspirin, warfarin, or ticlopidine should be avoided because of the potential increased risk of bleeding.
Ginger has antiplatelet effects and may interact with non-steroidal anti-inflammatory drugs (NSAIDs), warfarin (Coumadin), heparin, and aspirin to increase risk of bleeding.
Ginkgo has antiplatelet effects and may interact with non-steroidal anti-inflammatory drugs (NSAIDs), warfarin (Coumadin), heparin, and aspirin to increase risk of bleeding.
Ginseng has antiplatelet effects and may interact with non-steroidal anti-inflammatory drugs (NSAIDs), warfarin (Coumadin), heparin, and aspirin to increase risk of bleeding.
Horse Chestnut: Esculin in horse chesnut may interact with non-steroidal anti-inflammatory drugs (NSAIDs), warfarin (Coumadin), heparin, and aspirin to increase risk of bleeding.
Meadowsweet has antiplatelet effects and may interact with non-steroidal anti-inflammatory drugs (NSAIDs) and aspirin to increase risk of bleeding.
Turmeric has antiplatelet effects and may interact with non-steroidal anti-inflammatory drugs (NSAIDs) and aspirin to increase risk of bleeding.
Willow has antiplatelet effects and may interact with non-steroidal anti-inflammatory drugs (NSAIDs), warfarin (Coumadin), heparin, and aspirin to increase risk of bleeding.
Acetaminophem was reported as a potential cause of kidney damage when taken with willow which contains salicylate and is chemically similar to aspirin.
The Agency for Healthcare Research and Quality reported the following possible aspirin interactions and concerns (10): Fenugreek may be associated with an increased anticoagulation (reduce blood clotting) effect. Consumption should be avoided when taking anticoagulants like aspirin, warfarin, or ticlopidine because of the potential increased risk of bleeding. Ginkgo biloba may be associated with an increased anticoagulation (reduce blood clotting) effect. Consumption should be avoided when taking anticoagulants like aspirin, warfarin, or ticlopidine because of the potential increased risk of bleeding.
Consumption of large amounts of garlic in food or garlic supplements should be avoided when taking anticoagulants.
Fish oil may be associated with an increased anticoagulation (reduce blood clotting) effect. Consumption should be avoided when taking anticoagulants like aspirin, warfarin, or ticlopidine because of the potential increased risk of bleeding.
Saw Palmetto may be associated with an increased anticoagulation (reduce blood clotting) effect. Consumption should be avoided when taking anticoagulants or drugs with anti-platelet effects like aspirin, warfarin, or ticlopidine because of the potential increased risk of bleeding.
Garlic has been shown to increase the PT INR when combined with Coumadin (warfarin) and increase the risk of bleeding after surgery (11). Avoid combining the use of aspirin with these agents.
Ginkgo biloba related bleeding occurred when combined with warfarin or aspirin (acetylsalicylic acid). (8)
Use of ginkgo biloba extract has been associated with excessive bleeding in 20 cases including 8 cases of bleeding in the brain, 4 of the eye, and several occurring after surgery. In the 3 cases where it was reported, discontinuation of ginkgo reduced bleeding time by lab tests. About one-third of these patients were found to also be taking drugs that prevent clotting of the blood (anticoagulants [warfarin], antiplatelets [aspirin], nonsteroidal, anti-inflammatory drugs [ibuprofen]). A study of 12 healthy individuals taking 120mg of ginkgo extract for 3 months showed a slight antiplatelet effect. Yet, 2 other studies showed no significant antiplatelet/anticoagulation effect in 32 healthy individuals taking either 120 mg, 240 mg (2x the normal dose), or 480 mg ginkgo daily for 2-weeks or in 50 healthy individuals taking 240 mg of ginko for one week. (12)
In a systematic review by Izzo AA, et al Ginkgo (Ginkgo biloba) was noted to interact with aspirin (acetylsalicylic acid) to increase risk of bleeding. (13)
Policosanol reduced fibrinogen significantly and should not be taken 2 weeks prior to surgery, anyone with a bleeding disorder or fibrinogen deficiency, anyone with a history of major bleeding in the past, anyone taking aspirin, NSAIDs, warfarin, or any type of heparin. Monitoring by a physician should be done with a coagulation profile and fibrinogen every month until stable. If no monitoring occurs policosanol may not be safe. Fibrinogen under 150 is associated with an increased risk of bleeding. (14)
Vitamin E was found to enhance aspirin\’s ability to prevent blood clots. Research reported that vitamin E (50 and 100 μM) inhibited aggregation of platelets. In addition, vitamin E was associated with an 80% reduction in platelet adhesion to collagen (a protein). Platelet adhesion to collagen is fundamental during blood clotting. (15)
Assessment and Plan: Aspirin
- The primary physician may take into consideration age, medical history, and risk factors for cardiovascular disease or stroke to determine whether or not aspirin will benefit you for prevention of stroke or cardiovascular disease.
- Avoid herbs, supplements or medications which may have an interaction with aspirin to increase risk of bleeding.
- For a history of headaches without history of gastrointestinal bleeding or contraindications to aspirin, aspirin combined with caffeine and acetaminophen (Tylenol) is more effective than any of these agents taken alone for headache..
References:
1.Aspirin for the Prevention of Cardiovascular Disease, Topic Page. December 2009. U.S. Preventive Services Task Force. http://www.uspreventiveservicestaskforce.org/uspstf/uspsasmi.htm
2.Western States Stroke Consortium, Neurocritical Care and Stroke Division, University of Southern California, 1100 N. State St., Clinic Tower A4E111, Los Angeles, CA 90033
3.Bardia A, Ebbert JO, Vierkant RA, et al. Association of aspirin and nonaspirin nonsteroidal anti-inflammatory drugs with cancer incidence and mortality. J Natl Cancer Inst 2007 Jun 6;99 (11):881–9. http://www.ncbi.nlm.nih.gov/pubmed/17551148
4.Routine Aspirin or Nonsteroidal Anti-inflammatory Drugs for the Primary Prevention of Colorectal Cancer, Topic Page. March 2007. U.S. Preventive Services Task Force. http://www.uspreventiveservicestaskforce.org/uspstf/uspsasco.htm
5.Pignone M, Alberts MJ, Colwell JA, Cushman M, Inzucchi SE, Mukherjee D, Rosenson RS, Williams CD, Wilson PW, Kirkman MS; American Diabetes Association; American Heart Association; American College of Cardiology Foundation. Aspirin for primary prevention of cardiovascular events in people with diabetes: a position statement of the American Diabetes Association, a scientific statement of the American Heart Association, and an expert consensus document of the American College of Cardiology Foundation. Diabetes Care. 2010 Jun;33(6):1395-402. http://www.ncbi.nlm.nih.gov/pubmed/20508233
6.Goldstein LB, Adams R, Alberts MJ, Appel LJ, Brass LM, Bushnell CD, Culebras A, DeGraba TJ, Gorelick PB, Guyton JR, Hart RG, Howard G, Kelly-Hayes M, Nixon JV, Sacco RL. Primary prevention of ischemic stroke: a guideline from the American Heart Association/American Stroke Association Stroke Council: cosponsored by the Atherosclerotic Peripheral Vascular Disease Interdisciplinary Working Group; Cardiovascular Nursing Council; Clinical Cardiology Council; Nutrition, Physical Activity, and Metabolism Council; and the Quality of Care and Outcomes Research Interdisciplinary Working Group. Circulation. 2006 Jun 20;113(24):e873-923. http://www.ncbi.nlm.nih.gov/pubmed/16785347
7.Pfaffenrath V, Diener HC, Pageler L, Peil H, Aicher B. OTC analgesics in headache treatment: open-label phase vs randomized double-blind phase of a large clinical trial. Headache 2009;49(5):638–45. http://www.ncbi.nlm.nih.gov/pubmed/19472437
8.Hu Z, Yang X, Ho PC, Chan SY, Heng PW, Chan E, Duan W, Koh HL, Zhou S. Herb-drug interactions: a literature review. Drugs. 2005;65(9):1239-82. http://www.ncbi.nlm.nih.gov/pubmed/15916450
9.Abebe W. Herbal medication: potential for adverse interactions with analgesic drugs. J Clin Pharm Ther. 2002 Dec;27(6):391-401. http://www.ncbi.nlm.nih.gov/pubmed/12472978
10.Agency for Healthcare Research and Quality. Comparative Effectiveness of Dietary Supplement Versus No Dietary Supplement Use in Adults Taking Cardiovascular Drugs. April 2012. http://www.effectivehealthcare.ahrq.gov/ehc/products/223/596/DietarySupplement_Amended_Protocol_20110428.pdf
11.Rai J. Adverse interactions between low-dose aspirin/warfarin and garlic/ginseng/Ginkgo biloba. Indian Heart J 2004;56:176.
12.All patients at risk of bleeding should avoid Ginkgo biloba extracts. Haemorrhage due to Ginkgo biloba? Prescrire Int. 2008 Feb;17(93):19.
13.Izzo AA, Ernst E. Interactions between herbal medicines and prescribed drugs: an updated systematic review. Drugs, 2009, 69(13): 1777-1798. http://www.ncbi.nlm.nih.gov/pubmed/19719333
14.Castano, G., Mas, R., Gamez, R., Fernandez, L., and Illnait, J. Effects of policosanol and ticlopidine in patients with intermittent claudication: a double-blinded pilot comparative study. Angiology 2004;55(4):361-371. http://www.ncbi.nlm.nih.gov/pubmed/15258682
15.Celestini A, Pulcinelli FM, Pignatelli P, Lenti L, Frati G, Gazzaniga PP, Violi F. Vitamin E potentiates the antiplatelet activity of aspirin in collagen-stimulated platelets. Haematologica. 2002 Apr; 87(4): 420-6. http://www.ncbi.nlm.nih.gov/pubmed/11940487