Understanding Aspirin

Aspirin is the most comprehensively studied and least expensive of all antiplatelet medications.¹ It is among the most widely used over-the-counter (OTC) medications in the United States as a single agent or as an ingredient in popular combination pain relievers. Aspirin belongs to the family of drugs known as the salicylates, and most dental hygienists are already familiar with the abbreviation for aspirin, ASA, which stands for acetylsalicylic acid.² Aspirin is best known for its nonsteroidal anti-inflammatory, analgesic, and antipyretic properties, and is a drug of choice for mild-to-moderate pain, such as that caused by rheumatoid arthritis or osteoarthritis, menstrual cramps, or headache. Aspirin produces these effects by blocking the formation of prostaglandins. It inhibits the enzyme cyclooxygenase, which then prevents the conversion of arachidonic acid to prostaglandins (see Figure 1).

When a person experiences injury or trauma (eg, surgery) to the body, the target of aspirin therapy is to block the formation of prostaglandins that mediate inflammation and pain. Decreased swelling and analgesia are the desired therapeutic effects. Aspirin also works in the heat-regulating center of the hypothalamus that mediates fever, another desired indication for this drug.

However, aspirin also blocks the formation of another set of prostaglandins—cytoprotective mediators—which help ensure the health and function of the kidneys and gastrointestinal (GI) tract as well as other cells and organs. Most clinicians know that chronic use of aspirin leads to GI ulceration and bleeding because of the lack of formation of the cytoprotective mucous barrier that separates the hydrochloric acid from the thin, vulnerable epithelial lining of the stomach. This well-known and predictable side effect of chronic exposure to aspirin is a limiting factor for its long-term use. Chronic use of aspirin also is toxic to the kidneys, which may result in decreased renal function over time.

Aspirin also inhibits the formation of thromboxane A2, a substance associated with platelet aggregation. Inhibiting thromboxane A2 prevents platelets from clumping together, which is why aspirin is used for cardioprotection in patients with increased risk for or a history of adverse thrombotic events, including myocardial infarction (MI) and stroke. Thromboxane A2 is synthesized by the platelets themselves, and because platelets are anucleated, they do not have the ability to synthesize new thromboxane A2. For this reason, the effect of aspirin exposure on a platelet is permanent and will last for the life of the platelet, approximately 7 days to 10 days. This permanent antiplatelet effect explains why a patient may be advised to discontinue aspirin therapy a week before an invasive surgery. This timeframe allows for normal platelet turnover to occur and for platelet aggregation to return.

CARDIOPROTECTIVE EFFECTS OF ASPIRIN

Aspirin is used for primary prevention of MI and for secondary prevention of ischemic events, such as stroke.³ Patients take 81 mg low dose aspirin for prevention of stroke and adverse thrombotic events. A recent metaanalysis of six randomized trials found that in patients with stable cardiovascular disease, low-dose aspirin was associated with a significant (21%) reduction in risk of cardiovascular events (nonfatal MI, nonfatal stroke, and cardiovascular death) and a 13% reduction in risk of all-cause mortality. However, patients treated with aspirin were also significantly more likely to experience bleeding.⁴

ADVERSE EVENTS WITH ASPIRIN

Aspirin users demonstrate an increased risk for hemorrhagic stroke, although the cardioprotective benefits of the drug outweigh this risk when used appropriately in at-risk patient populations.^3,5 Many adverse events caused by aspirin are dose-related and are extremely rare with low-dose therapy. Bleeding risk increases with concurrent use of other medications that alter hemostasis, including nonsteroidal anti-inflammatory drugs (NSAIDS), warfarin, and alcohol.² There is no evidence to support the discontinuation of low-dose aspirin therapy prior to dental procedures or dental surgery because the risk for an adverse cardiovascular event outweighs the risk for intraoperative and post-operative bleeding in dental patients.^2,6,7

There is growing evidence about aspirin resistance, also known as hypo-responsiveness to the effects of aspirin. Individuals who are resistant to aspirin may experience a first MI or suffer a second adverse event while taking aspirin. Platelet aggregation studies of these individuals reveal no biochemical activity of aspirin. A metabolite of thromboxane known as 11-dehydrothromboxane B2 is found in the urine, and can be used as a marker to identify potentially aspirin-resistant individuals. Patients who are aspirin resistant may require additional antiplatelet therapies for risk reduction.^8,9

DOSING

Full strength aspirin, 325 mg, is used as a pre-hospital admission drug during acute MI. All dental offices should have full strength aspirin in their medical emergency kits for this indication. The patient is instructed to chew the aspirin tablet and swallow it. Four 81 mg aspirin tablets may be substituted. The fibrinolytic properties of aspirin may help to reperfuse the ischemic myocardium.¹⁰ Use of aspirin during acute MI helps to reduce mortality.¹¹ Aspirin is dosed at or up to 325 mg prior to and after acute MI, coronary stent implantation, carotid endarterectomy, and during acute stroke.^2,12

CONTRAINDICATIONS

Contraindications for aspirin use include allergy to salicylates or other NSAIDS, asthma, nasal polyps, or in individuals who have inherited or acquired bleeding disorders. Caution should be used when administering aspirin to a patient with compromised renal function, and to patients taking other NSAIDS or anticoagulant medications. Aspirin is contraindicated in children who have a viral infection, such as influenza or chicken pox, due to the increased risk of the potentially fatal Reye’s Syndrome, a condition characterized by severe vomiting, liver complications, and encephalopathy.²

INTERACTIONS WITH ASPIRIN AND IBUPROFEN

In 2006, the Food and Drug Administration (FDA) issued an informational statement to health care professionals stating that “ibuprofen can interfere with the antiplatelet effect of low-dose aspirin (81 mg per day), potentially rendering aspirin less effective when used for cardioprotection and stroke prevention. Health care professionals should advise consumers and patients regarding the appropriate concomitant use of ibuprofen and aspirin.”¹³ The concern is that concurrent use of these medications can increase risk for adverse cardiac events. Thus, the FDA issued the following considerations:

•  “Counseling patients about the appropriate timing of ibuprofen dosing if they are also taking aspirin for cardioprotective effects.
• With occasional use of ibuprofen, there is likely to be minimal risk from any attenuation of the antiplatelet effect of low-dose aspirin, because of the long-lasting effect of aspirin on platelets.
• Patients who use immediate release aspirin (not enteric coated) and take a single dose of ibuprofen 400 mg should dose the ibuprofen at least 30 minutes or longer after aspirin ingestion, or more than 8 hours before aspirin ingestion to avoid attenuation of aspirin’s effect.
• Recommendations about the timing of concomitant use of ibuprofen and entericcoated low-dose aspirin cannot be made based on available data.
• Other nonselective OTC NSAIDs should be viewed as having the potential to interfere with the antiplatelet effect of low-dose aspirin unless proven otherwise.
• Prescribing analgesics that do not interfere with the antiplatelet effect of lowdose aspirin for high risk populations.”¹³

Dental hygienists will most likely encounter the potential for this interaction, as many patients self-medicate with NSAIDS, and because NSAIDS are frequently used analgesics for orofacial and postoperative dental pain. Patients should be taught how to time their dosing of aspirin with NSAIDS to reduce the risk of this interaction.

ASPIRIN DISCONTINUATION AND RISK FOR MI

Compliance with taking medications is problematic, even with the use of OTC aspirin. Research shows that discontinuing the use of aspirin increases mortality risk.¹⁴ One large clinical trial examined patients who were admitted to the hospital with an acute coronary syndrome, grouped by those who had never taken an oral antiplatelet agent, those with a prior history of use, and those who had recently discontinued use of the drug. Among patients who had recently discontinued aspirin, mostly due to physician recommendation prior to surgery, there was a higher 30-day rate of death or MI and adverse bleedings than among prior users, despite a similar cardiovascular risk profile between the groups. There was no difference in the incidence of death or MI at 30 days between nonusers and prior users. This study concluded that patients who had recently withdrawn the use of oral antiplatelet medications displayed worse clinical outcomes than nonusers.¹⁵ A metaanalysis reviewing data from more than 50,000 patients showed that aspirin nonadherence/ withdrawal was associated with a three-fold higher risk for major adverse cardiac events. Risk was even greater among patients with coronary stents.¹⁶

Dental hygienists must be aware that just as their patients will choose to self-medicate with aspirin, they will also decide if and when to discontinue their aspirin therapy. It is important to assess aspirin use during the pharmacologic history review, including whether or not the patient’s physician recommended its use, dosing schedule, frequency, and compliance. Patients should not stop their own aspirin therapy prior to a dental procedure, although many individuals do so, fearing bleeding complications afterward. Patient education should include a discussion about the risks and benefits of aspirin therapy while undergoing dental treatment, and reassurance given that postoperative bleeding can be managed with local hemostatic agents. The dental hygienist must ensure the availability of these agents at chairside in order to manage patients safely.

REFERENCES

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13. US Food and Drug Administration. Information for Healthcare Professionals: Concomitant Use of Ibuprofen and Aspirin. Available at: www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm125222.ht m. Accessed March 22, 2010.
14. Ho PM, Spertus JA, Masoudi FA, et al. Impact of medication therapy discontinuation on mortality after myocardial infarction. Arch Intern Med. 2006;166:1842-1847.
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From Dimensions of Dental Hygiene. April 2010; 8(4): 22, 24, 26.