- What is aspirin
- How Does Aspirin Work ?
- What Is the Dose of Aspirin ?
- What Are the Side Effects of Aspirin ?
- Who Should Take Aspirin ?
- Conditions Where Aspirin Is Proven to Be Effective or Routinely Recommended
- Coronary Artery Disease (Have Experienced Angina or a Heart Attack, or Have Undergone an Angioplasty With or Without Stent Placement)
- Cerebral Vascular Disease (Have Experienced a Stroke or Transient Ischemic Attack [Ministroke])
- Have Undergone Coronary Artery Bypass Graft Surgery
- Have Undergone Surgery for Fractured Hip to Prevent Blood Clots in the Legs or Lungs
- Have Never Experienced a Heart Attack or Stroke But are >50 Years of Age (ie, Primary Prevention)
- Diagnosed With Peripheral Artery Disease (Have Experienced Claudication [Leg Pain While Walking] or Rest Pain That Is Caused by Blockages in the Leg Blood Vessels)
- Diabetes Mellitus But Have Never Experienced a Heart Attack or Stroke
- Have Had a Blood Clot in the Leg or Lungs
- Currently Taking Warfarin
- Should You Stop Aspirin Before Undergoing Surgery ?
- Aspirin uses
- Aspirin overdose
What is aspirin
Aspirin also known as acetylsalicylic acid is one of the most widely used medical treatments worldwide. Following the advent of synthetic salicylate, Felix Hoffman, working at the Bayer company in Germany, made the acetylated form of salicylic acid in 1897 1). This drug was named “Aspirin” and it was not until 1971 when Vane discovered the mechanism by which aspirin exerts its anti-inflammatory, analgesic and antipyretic actions. He proved that aspirin and other non-steroid anti-inflammatory drugs (NSAIDs) inhibit the activity of the enzyme now called cyclooxygenase (COX) which leads to the formation of prostaglandins (PGs) that cause inflammation, swelling, pain and fever. However, by inhibiting this key enzyme in prostaglandin (PG) synthesis, the aspirin-like drugs also prevented the production of physiologically important prostaglandins (PGs) which protect the stomach mucosa from damage by hydrochloric acid, maintain kidney function and aggregate platelets when required.
Since then clinical trials involving tens of thousands of patients have since demonstrated that aspirin is effective for the prevention and treatment of heart attack and stroke 2). In patients who are at high risk because they already have occlusive vascular disease, long-term antiplatelet therapy (eg, with aspirin) reduces the yearly risk of serious vascular events (non-fatal myocardial infarction, non-fatal stroke, or vascular death) by about a quarter 3), 4). This decrease typically corresponds to an absolute reduction of about 10–20 per 1000 in the yearly incidence of non-fatal events, and to a smaller, but still definite, reduction in vascular death.
Aspirin and Prevention of Heart Attack
Most heart attacks and strokes occur when the blood supply to a part of your heart muscle or brain is blocked. This usually starts with atherosclerosis, a process in which deposits of fatty substances, cholesterol, cellular waste products, calcium and other substances build up in the inner lining of an artery. This buildup is called plaque.
Plaque usually affects large and medium-sized arteries. Plaques can grow large enough to significantly reduce the blood’s flow through an artery. But most of the damage occurs when a plaque becomes fragile and ruptures. Plaques that rupture cause blood clots to form that can block blood flow or break off and travel to another part of the body. This is called an embolism.
- If a blood clot blocks a blood vessel that feeds the heart, it causes a heart attack.
- If a blood clot blocks a blood vessel that feeds the brain, it causes a stroke.
Aspirin helps prevent blood clots from forming and helps prevent heart attack and stroke.
Certain patients will be prescribed aspirin combined with another antiplatelet drug (such as clopidogrel, prasugrel or ticagrelor) – also known as dual antiplatelet therapy (DAPT).
- However, taking aspirin isn’t advised during a stroke, because not all strokes are caused by blood clots. Most strokes are caused by clots, but some are caused by ruptured blood vessels. Taking aspirin could potentially make these bleeding strokes more severe.
How Does Aspirin Work ?
Aspirin is a noncompetitive and irreversible irrecyclooxygenase-1 (COX-1) inhibitor 5) that prevents platelet aggregation and reduces the risk of heart attacks and strokes by preventing blood clots (due to aspirin’s anti-platelets effect, which works by preventing blood platelets from sticking together) from forming on the surface of ruptured atherosclerotic plaques. Atherosclerotic plaques build up along the lining of blood vessels over many years in response to injury caused by high blood pressure, abnormal blood sugar levels, high blood cholesterol levels, and toxins contained in tobacco smoke. Platelets stick to ruptured atherosclerotic plaques to form blood clots that block blood flow and thereby reduce oxygen delivery to tissues. Clots that block blood flow to heart muscle cause heart attacks, and clots that block blood flow to the brain cause strokes.
Noncoated aspirin acts within minutes of ingestion to stop platelets from forming blood clots. Enteric-coated aspirin takes longer to work but acts just as quickly as uncoated aspirin if chewed. Aspirin reduces the severity of heart attacks and strokes and prevents future heart attacks and strokes. The platelet-inhibitory effects of aspirin last for the life of the platelet (5 to 10 days), but patients need to take aspirin every day to inhibit new platelets that are constantly being released into the circulation.
What does anti-platelet mean ?
Blood platelets are actually fragments of cells – meaning they don’t contain all the necessary cellular equipment. When a person gets a cut or scratch, platelets release thromboxane, a chemical that signals other platelets to “help out.” Without the release of thromboxane, the platelets won’t come (stick) together, no clot will form, and the cut will continue to bleed. If you have a wound, thromboxane is an indispensable self-sealing material; but if you’re a stroke survivor, thromboxane’s ability to round up “help” to form a blood clot becomes potentially life-threatening.
Antiplatelet agents, including aspirin, clopidogrel, dipyridamole and ticlopidine, work by inhibiting the production of thromboxane. Aspirin is highly recommended for preventing a first stroke, but it and other antiplatelets also have an important role in preventing recurrent strokes.
According to a statement by the American Heart Association, taking aspirin within two days of an ischemic stroke reduces the severity of the stroke. In some cases, it prevents death. For long-term (meaning for the rest of your life unless otherwise specified by your physician) prevention, antiplatelet therapy is recommended primarily for people who have had a transient ischemic attack (TIA or “mini” stroke) or acute ischemic stroke.
Despite the potential benefits, antiplatelet therapy is not for everyone. People with a history of liver or kidney disease, gastrointestinal disease or peptic ulcers, high blood pressure, bleeding disorders or asthma may not be able to take aspirin or may require special dosage adjustments.
Is aspirin a blood thinner
No. Aspirin is an anti-platelet that keeps blood clots from forming by inhibiting the production of thromboxane, which prevents blood platelets from sticking together.
Blood thinners are also called anticoagulants. Anticoagulants target blood clotting factors, which are other agents that are crucial to the blood-clotting process. Clotting factors are proteins made in the liver. These proteins can’t be created in the liver without Vitamin K – a common vitamin found in cabbage, cauliflower, spinach and other leafy green vegetables. Anticoagulants, such as warfarin (Coumadin) and heparin, slow clot formation by competing with Vitamin K. This inhibits the circulation of certain clotting factors with the exotic names of factors II, VII, IX and X. Blood thinner decreases the clotting (coagulating) ability of the blood, although they do not actually thin the blood. They do NOT dissolve existing blood clots. Blood thinners are used to treat certain blood vessel, heart and lung conditions.
Blood thinners (anticoagulants) uses:
- Helps to prevent harmful clots from forming in the blood vessels.
- May prevent the clots from becoming larger and causing more serious problems.
- Often prescribed to prevent first or recurrent stroke.
Commonly prescribed blood thinners (anticoagulants) include:
- Rivaroxaban (Xarelto)
- Dabigatran (Pradaxa)
- Apixaban (Eliquis)
- Heparin (various)
- Warfarin (Coumadin)
Aspirin helps prevent clotting in patients who have had a heart attack, unstable angina, ischemic strokes, TIA (transient ischemic attacks, or “little strokes”) and other forms of cardiovascular disease. Usually prescribed preventively when atherosclerotic plaque buildup is evident but there is not yet a major obstruction in the artery. Certain patients will be prescribed aspirin combined with another antiplatelet drug – also known as dual antiplatelet therapy. For example, patients who have had heart attacks, patients who are treated with stents in their coronary arteries, and some patients who undergo coronary artery bypass graft surgery (CABG) are treated at the same time with two types of antiplatelet agents to prevent blood clotting. One antiplatelet agent is aspirin. Almost everyone with coronary artery disease, including those who have had a heart attack, stent, or CABG are treated with aspirin for the rest of their lives. A second type of antiplatelet agent, called a P2Y12 inhibitor [e.g. Clopidogrel (Plavix®), Dipyridamole, Prasugrel (Effient), Ticagrelor (Brilinta)], is usually prescribed for months or years in addition to the aspirin therapy. The type of medication and the duration of your treatment will vary based on a discussion with your healthcare provider weighing the risks of potential bleeding complications.
Is ibuprofen aspirin ?
Although ibuprofen is also a nonsteroidal anti-inflammatory drugs (NSAIDs) and have similar function (reduce pain, decrease fever or decrease inflammation) and side effects (increased risk of stomach ulcers) just like aspirin, but ibuprofen is NOT recommended for people with a heart attack, unstable angina, ischemic strokes, TIA (transient ischemic attacks, or “little strokes”) and other forms of cardiovascular disease. The term nonsteroidal distinguishes these drugs from steroids, which, among a broad range of other effects, have a similar eicosanoid-depressing, anti-inflammatory action. First used in 1960, the term served to distance these medications from steroids 6).
People who take nonsteroidal anti-inflammatory drugs [common brands include Advil (ibuprofen); Motrin (ibuprofen); Aleve (naproxen)] (other than aspirin) such as ibuprofen may have a higher risk of having a heart attack or a stroke than people who do not take these medications. Studies estimate that a person’s relative risk of heart attack and stroke increases 10 percent to 50 percent when they regularly take an NSAID, depending on the particular drug and the dose being used, according to the Food and Drug Administration 7). Side effects affecting the kidneys, heart or the stomach also can occur when NSAIDs are taken at too high a dose, for too long, or in combination with another NSAID. Aspirin also is considered an NSAID but is not included in the warnings. Low-dose aspirin has been shown in clinical trials to reduce the risks of cardiovascular events in patients who have cardiovascular disease or who have already had a heart attack or stroke.
- Do NOT take an NSAID such as ibuprofen if you have recently had a heart attack, unless directed to do so by your doctor.
- Stop taking NSAIDs and seek medical help if you experience symptoms that might signal heart problems or stroke, such as chest pain, trouble breathing, sudden weakness in one part or side of the body, or sudden slurred speech 8).
Nonsteroidal anti-inflammatory drugs (NSAIDs) work to block enzymes called cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) that are responsible for manufacturing substances called postglandins (PGs), chemical messengers that can cause inflammation, pain and fever. These postglandins, however, also help regulate blood clotting, protect the lining of the stomach and intestine and help with kidney function 9). It is thought that inhibiting cyclooxygenase-2 (COX-2) leads to the anti-inflammatory, analgesic and antipyretic effects and that those NSAIDs also inhibiting COX-1 [COX-1 generated prostaglandins required to maintain physiological functions such as protection of the gastric mucosa, platelet aggregation], particularly aspirin, may cause gastrointestinal bleeding and ulcers in large doses 10).
Prescription ibuprofen is used to relieve pain, tenderness, swelling, and stiffness caused by osteoarthritis (arthritis caused by a breakdown of the lining of the joints) and rheumatoid arthritis (arthritis caused by swelling of the lining of the joints). It is also used to relieve mild to moderate pain, including menstrual pain (pain that happens before or during a menstrual period). Nonprescription ibuprofen is used to reduce fever and to relieve minor aches and pain from headaches, muscle aches, arthritis, menstrual periods, the common cold, toothaches, and backaches.
Is it safe to take aspirin during pregnancy ?
Generally, aspirin isn’t recommended during pregnancy unless you have certain medical conditions 11).
Low-dose aspirin — 60 to 100 milligrams daily — is sometimes recommended for pregnant women with recurrent pregnancy loss, clotting disorders and preeclampsia.
However, use of higher doses of aspirin poses various risks depending on the stage of pregnancy. During the first trimester, use of higher doses of aspirin poses a concern for pregnancy loss and congenital defects. Taking higher doses of aspirin during the third trimester increases the risk of the premature closure of a vessel in the fetus’s heart. Use of high-dose aspirin for long periods in pregnancy also increases the risk of bleeding in the brain of premature infants.
If you need to take aspirin during your third trimester of pregnancy, your health care provider will likely closely monitor you and your baby.
If you need to take a pain reliever during pregnancy, talk to your health care provider about the options. He or she might suggest occasional use of acetaminophen (Tylenol, others) instead of aspirin.
What Is the Dose of Aspirin ?
If rapid and complete platelet inhibition is required (eg, if a person is having a heart attack), the first dose of aspirin should be 160 to 325 mg 12). If noncoated aspirin is unavailable, enteric-coated tablets can be used but should be chewed to achieve a rapid effect.
For long-term prevention of cardiovascular disease, the recommended dose of aspirin is 75 to 325 mg once daily 13). Some guidelines recommend only baby aspirin (75 to 100 mg) for long-term prevention, based on evidence that higher doses cause more gastrointestinal bleeding but do not provide additional protection against heart attack and stroke 14).
What Are the Side Effects of Aspirin ?
Aspirin’s most common side effect is upper abdominal pain resulting from gastric irritation. This side effect might be avoided by taking aspirin with food. Enteric-coated aspirin is popular but is more expensive than noncoated aspirin and has not been shown to reduce symptoms of gastric irritation 15).
Aspirin causes gastrointestinal bleeding (an excess of up to 1 event for every 1000 patients treated for 1 year) 16). Risk of gastric irritation and bleeding can be reduced by the use of a proton pump inhibitor (eg, omeprazole) in combination with aspirin.
One to two percent of patients have an allergy to aspirin that can result in asthma or rarely, life-threatening allergy (anaphylaxis). Allergic patients can undergo a desensitization procedure. After undergoing desensitization, patients should not miss any doses of aspirin because this may lead to recurrence of the allergy.
Liver injury from high doses of aspirin is usually mild and self-limited 17). Symptoms attributable to liver injury (as opposed to the other side effects of aspirin itself) are common but generally nonspecific and mild. Typically, alanine transaminase (ALT) elevations fall to normal within days of stopping. No convincing cases of acute liver failure or chronic liver injury or chronic vanishing bile duct syndrome due to aspirin have been published. Reye syndrome induced by aspirin, on the other hand, is a serious and potentially life threatening condition that should be managed with emergency intensive care.
A special form of aspirin hepatotoxicity is Reye Syndrome, the development of lactic acidosis, microvesicular fat and hepatic dysfunction with encephalopathy and coma. Serum aminotransferase levels are usually markedly increased while serum bilirubin is minimally or only moderated elevated despite signs of hepatic failure such as hyperammonemia and encephalopathy. Reye syndrome usually occurs in children or young adults developing a few days to a week after a prodromal febrile illness, typically influenza B or varicella. It is often rapidly fatal, but in milder cases recovery is rapid. Reye syndrome was first reported in Australia in 1963, but subsequently was reported from around the world with increasing frequency and peaking in incidence in the 1970s and 1980s. Subsequently, case reports followed by careful epidemiological surveys linked the occurrence of Reye syndrome to receipt of aspirin during the prodromal viral illness. With medical recognition of this association, followed by wide scale public warnings, the use of aspirin in children with fever decreased markedly and the frequency of Reye syndrome fell dramatically. In the United States, reported cases of Reye syndrome fell from more than 500 cases per year before 1986 to less 2 cases per year thereafter. Occasional rare case reports of Reye syndrome still appear. Reye syndrome can also occur in adults.
The mitochondrial failure of Reye syndrome is rapidly reversible and the major focus of management should be clinical support during the acute phase. Infusions of 20% glucose may help sustain hepatic and brain function during the temporary mitochondrial failure. Recurrence of Reye syndrome has been reported in children who have recovered and were then treated again with aspirin during an acute febrile illness. Children who require long term therapy with aspirin or other mitochondrial inhibitors should receive influenza and varicella vaccine and parents should be alert to the signs and symptoms of Reye syndrome.
The National Institute for Clinical Excellence in the UK have defined aspirin intolerance as either a proven hypersensitivity to aspirin or a history of severe indigestion caused by low-dose aspirin 18). The prevalence of aspirin intolerance is between 6% and 20% with ‘true’ aspirin hypersensitivity occurring in 0.6–2.4% of the general population 19). Aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) are contraindicated in patients with a history of hypersensitivity including asthma, angioedema, urticaria, or rhinitis. However, in patients with a definitive need for aspirin, desensitization may offer a viable option for delivery of treatment.
Hypersensitivity reactions to aspirin have either a pharmacological or immunological basis, although patients may present with mixed reactions. Pharmacological reactions are dependent on inhibition of the cyclooxygenase-1 (COX-1) pathway while immunological/allergic reactions are mediated by drug-specific immunoglobulin E (IgE) production against aspirin 20). This is the basis for the difference between an anaphylactoid and anaphylactic reaction. Anaphylactic reactions are IgE mediated whereas anaphylactoid reactions can resemble anaphylactic symptoms but are not IgE mediated. Furthermore, aspirin may induce a pharmacological reaction at one time but an immunological reaction at another time in the same patient 21).
There are three basic clinical types of hypersensitivity reaction to aspirin: respiratory, cutaneous and systemic 22). While systemic reactions can be the most serious, respiratory and cutaneous reactions comprising urticaria and or angioedema are the most common.
Type 1: Aspirin-exacerbated respiratory disease
Aspirin-exacerbated respiratory disease (AERD) consists of asthma and rhinitis/nasal polyps. Aspirin-exacerbated respiratory disease is also commonly referred to as aspirin-sensitive, aspirin-induced or aspirin-intolerant asthma. The prevalence of aspirin-intolerant asthma is uncertain, but it has been estimated to affect about 1–20% of people with asthma 23). Respiratory reactions to aspirin begin within minutes to hours after ingestion. Classic symptoms of asthma are often accompanied by rhinitis, conjunctival irritation and facial flushing. In addition, abdominal cramping may occur 24). Aspirin-exacerbated respiratory disease most commonly occurs in patients between 30 and 40 years old, often after respiratory tract infection and is more common in women but is very uncommon in children 25). Most patients with aspirin-exacerbated respiratory disease can successfully undergo aspirin desensitization therapy.
Type 2: Cutaneous reactions
Aspirin-induced cutaneous disease consists of urticaria and angioedema. Cutaneous and systemic reactions to aspirin are less well characterized than aspirin-exacerbated respiratory disease. Urticaria occurs either separately or simultaneously with angioedema. Patients with chronic idiopathic urticaria are more sensitive to aspirin, urticaria being aggravated in 21–30% 26). When urticaria is active, patients are more likely to react to aspirin than if quiescent. Leukotriene-receptor antagonists can block NSAID-induced urticaria and angioedema reactions. Mixed reactions consisting of a combination of respiratory and cutaneous symptoms may also occur. Patients with chronic idiopathic urticaria are not thought to be suitable for aspirin desensitization 27).
Type 3: Systemic reactions
Systemic reactions occur within minutes of ingesting aspirin and consist of hypotension, swelling, laryngeal oedema, generalized pruritis, tachypnoea and lapses in consciousness. Angioedema with hypotension is generally considered a ‘systemic’ rather than a cutaneous reaction to aspirin. Some authors report successful desensitization where systemic reactions have occurred 28) while others do not 29). Because systemic reactions are potentially fatal, many authors recommend avoiding desensitization in these patients 30). It should be noted that terminology regarding the type of hypersensitivity reactions is inconsistent in the published literature and standardization in this area is essential if aspirin desensitization is to be implemented safely.
Who Should Take Aspirin ?
Guideline recommendations for aspirin use are summarized in the Table 1. Aspirin is recommended in patients with angina, previous heart attack or stroke (ie, secondary prevention), but it is not clear whether patients who have not previously experienced angina, heart attack or stroke benefit from aspirin (ie, primary prevention).
Table 1. Common Conditions in Which Aspirin Is Proven to Be of Benefit for the Prevention of Major Cardiovascular Events (Heart Attack, Stroke, Death) or Venous Thromboembolism (Blood Clots in the Legs or Lungs) or Is of Uncertain Benefit
|Aspirin of Proven Benefit||Aspirin of Uncertain Benefit|
|Angina/heart attack||Peripheral artery disease*|
|Coronary artery stents|
|Stroke||Diabetes (no previous heart attack or stroke)*|
|Following coronary artery bypass graft surgery||Primary prevention (ie, no angina, previous heart attack or stroke)|
|Prevention of blood clots in patients undergoing surgery for hip fracture||Prevention of recurrent deep vein thrombosis and pulmonary embolism in patients who have completed treatment with warfarin|
Note: The American College of Cardiology/American Heart Association Guidelines recommend aspirin for patients with peripheral artery disease and diabetes despite lack of conclusive evidence that it is beneficial.[Source 31)]
Conditions Where Aspirin Is Proven to Be Effective or Routinely Recommended
Aspirin reduces the risk of major cardiovascular events (heart attack, stroke, cardiovascular death) by ≈25% (36 fewer events for every 1000 patients treated for 2 years) in patients with a recent heart attack 32). The American College of Cardiology/American Heart Association guidelines recommend aspirin at a dose of 75 to 325 mg once daily for patients with a history of heart attack 33). Patients with a recent heart attack and those who have undergone angioplasty and stenting are usually prescribed a second antiplatelet drug, clopidogrel, prasugrel, or ticagrelor, in combination with baby aspirin. The combination of 2 antiplatelet drugs further increases the risk of major bleeding (10 additional events for every 1000 patients treated for 1 year) in comparison with aspirin alone 34).
Cerebral Vascular Disease (Have Experienced a Stroke or Transient Ischemic Attack [Ministroke])
Aspirin reduces the risk of major cardiovascular events by ≈22% (36 fewer events for every 1000 patients treated for 2 years) in patients with a recent stroke 35). The American Heart Association/American Stroke Association guidelines recommend aspirin at a dose of 50 to 325 mg once daily for patients with a history of stroke 36). Not all stroke patients should take aspirin; ≈1 in 6 strokes is caused by blood clots that arise in the heart; in such patients, the anticoagulants warfarin, dabigatran, and rivaroxaban are more effective than aspirin and are generally preferred. Aspirin is not known to benefit patients with stroke caused by bleeding into the brain.
Have Undergone Coronary Artery Bypass Graft Surgery
Aspirin reduces the risk of coronary artery bypass graft failure by ≈30% in patients who have recently undergone coronary artery bypass graft surgery. By preventing graft failure, it is logical to expect that aspirin will also prevent heart attacks resulting from a blocked graft, but this is unproven. The American College of Cardiology/American Heart Association guidelines recommend aspirin at a dose of 75 to 162 mg once daily for patients who have undergone coronary artery bypass graft surgery 37).
Have Undergone Surgery for Fractured Hip to Prevent Blood Clots in the Legs or Lungs
The pulmonary embolism prevention study has shown in patients undergoing surgery for hip fracture that aspirin given at a dose of 160 mg once daily reduces the risk of developing blood clots in the legs (deep vein thrombosis) or lungs (pulmonary embolism) by ≈30% (9 fewer events for every 1000 patients treated for 35 days) 38). Many physicians prefer to use other treatments (eg, heparin, enoxaparin, fondaparinux, rivaroxaban) over aspirin for prevention of deep vein thrombosis and pulmonary embolism in patients undergoing hip fracture surgery.
Conditions Where a Benefit of Aspirin Is Uncertain or Unknown
Have Never Experienced a Heart Attack or Stroke But are >50 Years of Age (ie, Primary Prevention)
Primary prevention trials involving a combined total of 100 000 patients have shown that aspirin reduces the risk of a first heart attack by ≈20% (1 fewer event for every 1000 patients treated for 1 year) 39). In low-risk patients, the benefit of aspirin may be outweighed by the increase in bleeding (up to 1 more event per 1000 patients treated for 1 year). Calculators are available (http://www.mdcalc.com/framingham-cardiac-risk-score) to estimate the risk of major cardiovascular events in the next 10 years in patients who have not previously experienced a heart attack or stroke. If the risk exceeds 10% over 10 years, aspirin is likely to be associated with a net benefit. The American Heart Association guidelines recommend aspirin at a dose of 75 to 160 mg once daily if used for primary prevention 40).
Despite having an increased risk of heart attack and stroke, patients with peripheral artery disease have not been shown to benefit from aspirin. Nevertheless, most guidelines recommend aspirin for patients with peripheral artery disease. The dose of aspirin recommended by the American College of Cardiology/American Heart Association guidelines for patients with peripheral artery disease is 75 to 325 mg once daily 41).
Diabetes Mellitus But Have Never Experienced a Heart Attack or Stroke
The risk of heart attack in patients with diabetes mellitus who have never experienced a heart attack is similar to the risk of a recurrent heart attack in patients without diabetes mellitus who have already had a heart attack. Primary prevention trials have not shown a benefit of aspirin in patients with diabetes mellitus, but most guidelines recommend that adult patients with diabetes mellitus should be treated with aspirin. The dose recommended by the American Diabetes Association/American Heart Association/American College of Cardiology Foundation guidelines is 75 to 162 mg daily 42).
Have Had a Blood Clot in the Leg or Lungs
There is currently no evidence that aspirin is effective for prevention of recurrent deep vein thrombosis or pulmonary embolism, but studies are ongoing to address this issue.
Currently Taking Warfarin
The combination of aspirin and warfarin is more effective than warfarin alone in patients who have a mechanical heart valve and is more effective than aspirin alone in patients with a recent heart attack, but will increase the risk of bleeding 43). Triple therapy, with the combination of aspirin, clopidogrel, and warfarin may be of benefit in patients with a recent heart attack or coronary stent who also have atrial fibrillation 44). To minimize the risk of bleeding when aspirin is combined with warfarin, the dose of aspirin should not exceed 100 mg once daily.
Should You Stop Aspirin Before Undergoing Surgery ?
Aspirin increases the risk of bleeding if it is continued during surgery, but it is not known whether continuing aspirin will also protect against the risk of heart attack or stroke. Studies are presently ongoing to address this issue. Current guidelines recommend that aspirin should be stopped 7 to 10 days before surgery to avoid an increase in risk of bleeding 45). The exception is patients with coronary stents, who should always check with their clinicians before stopping either aspirin or any of the other antiplatelet agents—clopidogrel, prasugrel, or ticagrelor—used to prevent stent thrombosis.
The current interest in aspirin stems from the fact that many animal experiments and human epidemiological studies now link aspirin (and other non-steroidal anti-inflammatory drugs) with beneficial effects in various cancers, including breast, ovarian, oesophageal, and colorectal cancer 46). Recent meta-analyses supported the idea that the overall relative risk of colorectal cancer is reduced in people taking long term aspirin 47). Another meta-analysis of observational data confirmed a protective effect in oesophageal cancer and provided evidence of a relation with dose and duration of treatment, and other studies showed a beneficial effect in ovarian cancer 48). How aspirin or other non-steroidal anti-inflammatory drugs produce this effect is not entirely clear, but the synthesis or activity of COX 2 is increased in many tumours, and inhibition could activate apoptotic mechanisms or suppress angiogenesis 49). It has even been suggested that the link between diet and the prevention of colorectal cancer is attributable to the presence of salicylic acid in plant and vegetable foodstuffs 50).
Evidence from longitudinal studies of long term users of non-steroidal anti-inflammatory drugs originally pointed to a reduced risk of Alzheimer’s disease 51) and these findings are supported by other, more recent data 52), where an inverse relation was found between taking aspirin (and other non-steroidal anti-inflammatory drugs) and Alzheimer’s disease, but not other forms of dementia. The mechanism is uncertain—Alzheimer’s has an inflammatory component and therefore COX 2 may be the target, although other mechanisms have been suggested 53).
The US Preventive Services Task Force 54) recommends initiating low-dose aspirin use for the primary prevention of cardiovascular disease and colorectal cancer in adults aged 50 to 59 years who have a 10% or greater 10-year cardiovascular disease risk, are not at increased risk for bleeding, have a life expectancy of at least 10 years, and are willing to take low-dose aspirin daily for at least 10 years
Table 1. US Preventive Services Task Force Recommendation Summary
|Adults aged 50 to 59 years with a ≥10% 10-year CVD risk||The USPSTF recommends initiating low-dose aspirin use for the primary prevention of cardiovascular disease (CVD) and colorectal cancer (CRC) in adults aged 50 to 59 years who have a 10% or greater 10-year CVD risk, are not at increased risk for bleeding, have a life expectancy of at least 10 years, and are willing to take low-dose aspirin daily for at least 10 years.||B|
|Adults aged 60 to 69 years with a ≥10% 10-year CVD risk||The decision to initiate low-dose aspirin use for the primary prevention of CVD and CRC in adults aged 60 to 69 years who have a 10% or greater 10-year CVD risk should be an individual one. Persons who are not at increased risk for bleeding, have a life expectancy of at least 10 years, and are willing to take low-dose aspirin daily for at least 10 years are more likely to benefit. Persons who place a higher value on the potential benefits than the potential harms may choose to initiate low-dose aspirin.||C|
|Adults younger than 50 years||The current evidence is insufficient to assess the balance of benefits and harms of initiating aspirin use for the primary prevention of CVD and CRC in adults younger than 50 years.||I|
|Adults aged 70 years or older||The current evidence is insufficient to assess the balance of benefits and harms of initiating aspirin use for the primary prevention of CVD and CRC in adults aged 70 years or older.||I|
Grade B: The USPSTF recommends the service. There is high certainty that the net benefit is moderate or there is moderate certainty that the net benefit is moderate to substantial.
Grade C: The USPSTF recommends selectively offering or providing this service to individual patients based on professional judgment and patient preferences. There is at least moderate certainty that the net benefit is small.
Grade I: The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of the service. Evidence is lacking, of poor quality, or conflicting, and the balance of benefits and harms cannot be determined.[Source 55)]
However, questions remain about safety, side effects and dosage of aspirin for its an exciting therapeutic prospects. For example, what is the minimum dose required to achieve these effects and how can scientists and doctors assess the relative risk and benefit of a preventive treatment that will entail treating healthy people for many years with a drug known to have gastric and other side effects ? To better answer questions about safety and who is most likely to benefit from aspirin, researchers are awaiting the results of several ongoing clinical trials that are testing aspirin.
Aspirin overdose remains a significant public health threat with more than 20,000 exposures reported annually in the United States 56). In adult Emergency Department patients with acute aspirin poisoning, independent predictors of severe outcome were older age and increased respiratory rate, as well as initial serum lactate. Mortality increases with the measured serum salicylate level.
The variation of presenting symptoms of aspirin overdose contributes to inconsistent treatments in the emergency department. Patients with severe aspirin overdose require a high minute ventilation. Early in the course of an overdose, a patient will require hyperventilation. If they become too fatigued to compensate, mechanical ventilation may be needed. It can be impossible to recreate such a high minute ventilation with mechanical ventilation. This places patients at a high risk for decompensation and death. Hemodialysis is an effective elimination technique for salicylate overdose and should be considered early. In a review 57) of aspirin overdose that were reported to the Illinois Poison Center from 2003–2014, it was found that timely hemodialysis for intubated salicylate overdose patients decreases mortality.
References [ + ]
|1.||↵||Vane JR. Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nat New Biol. 1971;231:232–235. https://www.ncbi.nlm.nih.gov/pubmed/5284360|
|2.||↵||Aspirin. Circulation. 2012;125:e439-e442. https://doi.org/10.1161/CIRCULATIONAHA.111.046243 http://circ.ahajournals.org/content/125/10/e439.full|
|3.||↵||Collaborative overview of randomised trials of antiplatelet therapy–I: Prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories of patients. Antiplatelet Trialists’ Collaboration. BMJ : British Medical Journal. 1994;308(6921):81-106. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2539220/pdf/bmj00422-0015.pdf|
|4.||↵||Collaboration AT. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ : British Medical Journal. 2002;324(7329):71-86. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC64503/|
|6.||↵||Origins and impact of the term ‘NSAID’. Inflammopharmacology. 2014 Oct;22(5):263-7. doi: 10.1007/s10787-014-0211-2. Epub 2014 Jul 27. https://www.ncbi.nlm.nih.gov/pubmed/25064056|
|7, 8.||↵||FDA Drug Safety Communication: FDA strengthens warning that non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) can cause heart attacks or strokes. https://www.fda.gov/Drugs/DrugSafety/ucm451800.htm|
|9.||↵||Flower R. What are all the things that aspirin does?: This fascinating but simple and cheap drug has an assured future. BMJ : British Medical Journal. 2003;327(7415):572-573. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC194070/|
|10.||↵||Clive P. Page, Michael J. Curtis, Morley Sutter, Michael Walker, Brian Hoffman. Farmacología integrada (in Spanish). Published by Elsevier España, 1998. ISBN 84-8174-340-2|
|11.||↵||Is it safe to take aspirin during pregnancy? https://www.mayoclinic.org/healthy-lifestyle/pregnancy-week-by-week/expert-answers/aspirin-during-pregnancy/faq-20058167|
|12, 13.||↵||CURRENT-OASIS 7 Investigators, Mehta SR, Bassand JP, Chrolavicius S, Diaz R, Eikelboom JW, Fox KA, Granger CB, Jolly S, Joyner CD, Rupprecht HJ, Widimsky P, Afzal R, Pogue J, Yusuf S. Dose comparisons of clopidogrel and aspirin in acute coronary syndromes. N Engl J Med. 2010;363:930–942. http://www.nejm.org/doi/full/10.1056/NEJMoa0909475|
|14, 33, 34.||↵||2011 ACCF/AHA Focused Update of the Guidelines for the Management of Patients With Unstable Angina/ Non–ST-Elevation Myocardial Infarction (Updating the 2007 Guideline). A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines https://doi.org/10.1161/CIR.0b013e31820f2f3e http://circ.ahajournals.org/content/123/18/2022|
|15, 31.||↵||Aspirin. Circulation. 2012;125:e439-e442. https://doi.org/10.1161/CIRCULATIONAHA.111.046243 http://circ.ahajournals.org/content/125/10/e439.full|
|16, 35.||↵||Antithrombotic Trialists’ (ATT) Collaboration, Baigent C, Blackwell L, Collins R, Emberson J, Godwin J, Peto R, Buring J, Hennekens C, Kearney P, Meade T, Patrono C, Roncaglioni MC, Zanchetti A. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet. 2009;373:1849–1860. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2715005/|
|18.||↵||National Institute for Health and Clinical Excellence (2005) Clopidogrel and modified release dipyridamole in the prevention of occlusive vascular events. NICE technology appraisal guidance 90. London: National Institute for Health and Clinical Excellence; https://www.nice.org.uk|
|19.||↵||Aspirin desensitization in aspirin intolerance: update on current standards and recent improvements.Pfaar O, Klimek L. Curr Opin Allergy Clin Immunol. 2006 Jun; 6(3):161-6. https://www.ncbi.nlm.nih.gov/pubmed/16670507|
|20.||↵||Desensitization for drug allergy. Castells M. Curr Opin Allergy Clin Immunol. 2006 Dec; 6(6):476-81. https://www.ncbi.nlm.nih.gov/pubmed/17088655/|
|21, 28.||↵||Rapid desensitization procedure for patients with aspirin hypersensitivity undergoing coronary stenting. Silberman S, Neukirch-Stoop C, Steg PG. Am J Cardiol. 2005 Feb 15; 95(4):509-10. https://www.ncbi.nlm.nih.gov/pubmed/15695141/|
|22.||↵||Management options for patients with aspirin and nonsteroidal antiinflammatory drug sensitivity. Knowles SR, Drucker AM, Weber EA, Shear NH. Ann Pharmacother. 2007 Jul; 41(7):1191-200. https://www.ncbi.nlm.nih.gov/pubmed/17609236/|
|23.||↵||Systematic review of prevalence of aspirin induced asthma and its implications for clinical practice. Jenkins C, Costello J, Hodge L. BMJ. 2004 Feb 21; 328(7437):434. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC344260/|
|24.||↵||Aspirin sensitivity: the role for aspirin challenge and desensitization in postmyocardial infarction patients. Schaefer OP, Gore JM. Cardiology. 1999; 91(1):8-13. https://www.ncbi.nlm.nih.gov/pubmed/10393393|
|25.||↵||Approach to “aspirin allergy” in cardiovascular patients. Ramanuja S, Breall JA, Kalaria VG. Circulation. 2004 Jul 6; 110(1):e1-4. http://circ.ahajournals.org/content/110/1/e1.long|
|26.||↵||Aspirin sensitivity and urticaria. Grattan CE. Clin Exp Dermatol. 2003 Mar; 28(2):123-7. https://www.ncbi.nlm.nih.gov/pubmed/12653694|
|27, 29.||↵||Aspirin sensitivity: implications for patients with coronary artery disease. Gollapudi RR, Teirstein PS, Stevenson DD, Simon RA. JAMA. 2004 Dec 22; 292(24):3017-23. https://www.ncbi.nlm.nih.gov/pubmed/15613671/|
|30.||↵||Aspirin sensitivity: the role for aspirin challenge and desensitization in postmyocardial infarction patients. Schaefer OP, Gore JM. Cardiology. 1999; 91(1):8-13. https://www.ncbi.nlm.nih.gov/pubmed/10393393/|
|32.||↵||Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ 2002; 324 doi: https://doi.org/10.1136/bmj.324.7329.71 http://www.bmj.com/content/324/7329/71|
|36.||↵||Furie KL, Kasner SE, Adams RJ, Albers GW, Bush RL, Fagan SC, Halperin JL, Johnston SC, Katzan I, Kernan WN, Mitchell PH, Ovbiagele B, Palesch YY, Sacco RL, Schwamm LH, Wassertheil-Smoller S, Turan TN, Wentworth D. American Heart Association Stroke Council, Council on Cardiovascular Nursing, Council on Clinical Cardiology, and Interdisciplinary Council on Quality of Care and Outcomes Research. Guidelines for the prevention of stroke in patients with stroke or transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2011;42: 227–276. http://stroke.ahajournals.org/content/42/1/227|
|37.||↵||AHA/ACC National Heart, Lung, and Blood Institute. AHA/ACC guidelines for secondary prevention for patients with coronary and other atherosclerotic vascular disease: 2006 update: endorsed by the National Heart, Lung, and Blood Institute. Circulation. 2006;113: 2363–2372. http://circ.ahajournals.org/content/113/19/2363|
|38.||↵||Prevention of pulmonary embolism and deep vein thrombosis with low dose aspirin: Pulmonary Embolism Prevention (PEP) trial. Lancet. 2000;355:1295–1302. https://www.ncbi.nlm.nih.gov/pubmed/10776741|
|39.||↵||Antithrombotic Trialists’ (ATT) Collaboration. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet. 2009;373(9678):1849-1860. doi:10.1016/S0140-6736(09)60503-1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2715005/|
|40.||↵||AHA Guidelines for Primary Prevention of Cardiovascular Disease and Stroke: 2002 Update. Circulation. 2002;106:388-391. http://circ.ahajournals.org/content/106/3/388|
|41.||↵||2011 ACCF/AHA Focused Update of the Guideline for the Management of Patients With Peripheral Artery Disease (Updating the 2005 Guideline). A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2011;124:2020-2045. http://circ.ahajournals.org/content/124/18/2020|
|42.||↵||Aspirin for Primary Prevention of Cardiovascular Events in People With Diabetes. Circulation. 2010;121:2694-2701. http://circ.ahajournals.org/content/121/24/2694|
|43.||↵||Eikelboom JW, Hirsh J. Combined antiplatelet and anticoagulant therapy: clinical benefits and risks. J Thromb Haemost. 2007;5 (suppl 1): 255–263. https://www.ncbi.nlm.nih.gov/pubmed/17635734|
|44.||↵||Faxon DP, Eikelboom JW, Berger PB, Holmes DR Jr., Bhatt DL, Moliterno DJ, Becker RC, Angiolillo DJ. Antithrombotic therapy in patients with atrial fibrillation undergoing coronary stenting: a North American perspective: executive summary. Circ Cardiovasc Interv. 2011;4:522–534. http://circinterventions.ahajournals.org/content/4/5/522|
|45.||↵||AHA/ACC, National Heart, Lung, and Blood Institute. AHA/ACC guidelines for secondary prevention for patients with coronary and other atherosclerotic vascular disease: 2006 update: endorsed by the National Heart, Lung, and Blood Institute. Circulation. 2006;113: 2363–2372. http://circ.ahajournals.org/content/113/19/2363|
|46.||↵||Aspirin and colorectal cancer: the promise of precision chemoprevention. Nature Reviews Cancer 16, 173–186 (2016). doi:10.1038/nrc.2016.4. https://www.nature.com/articles/nrc.2016.4|
|47.||↵||Bosetti C, Gallus S, La Vecchia C. Aspirin and cancer risk: an update to 2001. Eur J Cancer Prev 2002;11: 535-42. https://www.ncbi.nlm.nih.gov/pubmed/12457105|
|48.||↵||Corley DA, Kerlikowske K, Verma R, Buffler P. Protective association of aspirin/NSAIDs and esophageal cancer: a systematic review and meta-analysis. Gastroenterology 2003;124: 47-56. https://www.ncbi.nlm.nih.gov/pubmed/12512029|
|49.||↵||Thun MJ, Henley SJ, Patrono C. Nonsteroidal anti-inflammatory drugs as anticancer agents: mechanistic, pharmacologic, and clinical issues. J Natl Cancer Inst 2002;94: 252-66. https://www.ncbi.nlm.nih.gov/pubmed/11854387|
|50.||↵||Paterson JR, Lawrence JR. Salicylic acid: a link between aspirin, diet and the prevention of colorectal cancer. QJM 2001;94: 445-8. https://www.ncbi.nlm.nih.gov/pubmed/11493722|
|51.||↵||Stewart WF, Kawas C, Corrada M, Metter EJ. Risk of Alzheimer’s disease and duration of NSAID use. Neurology 1997;48: 626-32. https://www.ncbi.nlm.nih.gov/pubmed/9065537|
|52.||↵||Broe GA, Grayson DA, Creasey HM, Waite LM, Casey BJ, Bennett HP, et al. Anti-inflammatory drugs protect against Alzheimer disease at low doses. Arch Neurol 2000;57: 1586-91. https://www.ncbi.nlm.nih.gov/pubmed/11074790|
|53.||↵||Gao F, Bales KR, Dodel RC, Liu J, Chen X, Hample H, et al. NF-kappaB mediates IL-1beta-induced synthesis/release of alpha2-macroglobulin in a human glial cell line. Brain Res Mol Brain Res 2002;105: 108-14. https://www.ncbi.nlm.nih.gov/pubmed/12399113|
|54, 55.||↵||Aspirin Use to Prevent Cardiovascular Disease and Colorectal Cancer: Preventive Medication. US Preventive Services Task Force. https://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/aspirin-to-prevent-cardiovascular-disease-and-cancer|
|56.||↵||Acute salicylate poisoning: risk factors for severe outcome. Rachel M. Shively, Robert S. Hoffman & Alex F. Manini. Clinical Toxicology Vol. 55 , Iss. 3,2017. http://www.tandfonline.com/doi/full/10.1080/15563650.2016.1271127|
|57.||↵||The association of hemodialysis and survival in intubated salicylate-poisoned patients. The American Journal of Emergency Medicine , Volume 35 , Issue 6 , 899 – 903.|