Chemoprophylaxis refers to the administration of a medication or natural substance for the purpose of preventing a disease or infection. Before chemoprophylaxis is prescribed, two issues must be considered:
- Benefits of chemoprophylaxis must outweigh any potential harm.
- Chemoprophylaxis must be cost-effective.
There are many common examples of chemoprophylaxis like, fluoridated water to prevent dental caries; statins to prevent cardiovascular and coronary heart disease; trimethoprim-sulfamethoxazole for Pneumocystis pneumonia prophylaxis in AIDS patients with CD4 cell counts under 200; oral hormone contraception to prevent undesired pregnancies; and folic acid use in women of child bearing age to reduce risks of birth defects, especially in those desiring to be pregnant.
Counseling on Indications, Contraindications, and Potential Side Effects
Physicians should be prepared to answer patients’ questions and concerns about various chemoprophylactic agents. Occasionally, patients want to consider chemoprophylactic agents for which there is little evidence for or against their use. Many agents have controversial risk-benefit profiles—hence current recommendations are to have a discussion with the patient about the pros and cons of chemoprophylactic agents, not necessarily to start them.
An Example of Chemoprophylaxis
Aspirin
The use of aspirin in men and women in certain age groups with known cardiovascular disease has been shown to reduce the risk of death and further vascular events (tertiary prevention). The benefits clearly outweigh the risks in patients with established cardiovascular disease. However, the use of aspirin for primary prevention of cardiovascular disease has more balanced risks and benefits depending on several individual factors.
Aspirin carries a risk of intracranial and/or gastrointestinal bleeding. Enteric coated or buffered aspirin does not reduce the risks of gastrointestinal bleeding. In addition, uncontrolled hypertension and concomitant use of other non-steroidal anti-inflammatory agents or anticoagulants increase the risk for serious bleeding. Furthermore, the optimal dosage of aspirin in both primary and secondary prevention of cardiovascular disease has yet to be established. The United States Preventive Services Task Force (USPSTF) makes recommendations that are considered the “gold standard” for clinical preventive services and has weighed in on chemoprophylaxis with aspirin in regards to primary prevention of cardiovascular disease:
- Aspirin to Prevent CVD: Men age 45 to 79 to prevent myocardial infarctions
Grade:A* Specific Recommendations:
The USPSTF recommends the use of aspirin for men age 45 to 79 years when the potential benefit due to a reduction in myocardial infarctions outweighs the potential harm due to an increase in gastrointestinal (GI) hemorrhage. Aspirin does not prevent initial strokes in men. - Aspirin to Prevent CVD: Women age 55 to 79 to prevent ischemic strokes
Grade:A* Specific Recommendations:
The USPSTF recommends the use of aspirin for women age 55 to 79 years when the potential benefit of a reduction in ischemic strokes outweighs the potential harm of an increase in GI hemorrhage.Aspirin does not prevent initial coronary heart disease events in women. - Aspirin to Prevent CVD: Women younger than 55 years of age, to prevent stroke
Grade:D* Specific Recommendations:
The USPSTF recommends against the use of aspirin for stroke prevention in women younger than 55 years, in whom the risk of GI bleeding is much higher than the risk of stroke. - Aspirin to Prevent CVD: Men younger than 45 years of age, to prevent myocardial infarction
Grade:D* Specific Recommendations:
The USPSTF recommends against the use of aspirin for myocardial infarction prevention in men younger than 45 years, in whom the risk of GI bleeding is much higher than the risk of coronary heart disease events. - Aspirin to Prevent CVD: Men and Women age 80 years and older
Grade:I* Specific Recommendations:
The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of aspirin for cardiovascular disease prevention in men and women 80 years or older, in whom the risks of coronary heart disease and GI bleeding are both high.
The “grade definitions” above will be covered later in this module.
Every man older than 45 and woman older than 55, should be assessed for their own personal risk of cardiovascular disease and the harms / benefits of taking aspirin for primary prevention. The first step is calculation of an individual’s 10 year cardiovascular risk, based on the Framingham model, found here (Risk Assessment Tool for Estimating 10-year Risk of Having a Heart Attack (NHLBI)). A woman’s 10-year risk of stroke, not MI, is required to make an informed decision on aspirin (calculator: http://stroke.ucla.edu/body.cfm?id=66). There is no specific USPSTF ‘bleeding calculator’ available, although bleeding risk predictably increases with age. The following table, stratifying aspirin use by age, takes bleeding risk into account. Some organizations are attempting to combine bleeding and CV risk into a single decision aid tool, but these are not fully validated. The Mayo Clinic’s Cardiovascular Primary Prevention Choice website offers several tools useful in shared decision making about the use of aspirin for primary prevention.
Favorable Net Benefit from Aspirin Use:Shared decision-making is recommended with patients at or close to these thresholds |
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Men: 10-year CHD risk (%) | Women: 10-year stroke risk (%) | ||
Age 45 to 59 years | ≥4 | Age 55 to 59 years | ≥3 |
Age 60 to 69 years | ≥9 | Age 60 to 69 years | ≥8 |
Age 70 to 79 years | ≥12 | Age 70 to 79 years | ≥11 |
The table above applies to adults who are not taking NSAIDS and do not have upper GI pain or history of GI ulcers. USPSTF, 2009. |
Tools to discuss these benefits and risks with your patients are available below:
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