Aspirin, Beta Blockers, and Ace Inhibitors
Heart Attack Prevention Series
Medical Author Revision: Dennis Lee, M.D.,
Daniel Kulick, M.D.
Medical Editor: William C. Shiel Jr., MD, FACP, FACR
Additional Heart Attack Prevention Series Information (related articles)
What is aspirin?
Aspirin (known chemically
as acetyl salicylic acid and often abbreviated as ASA) belongs to a class of
medications called non-steroidal anti-inflammatory drugs, or NSAIDs. Aspirin and
other NSAIDs, for example, ibuprofen (e.g., Motrin, Advil) and naproxen (e.g.,
Aleve), are widely used to treat fever, pain, and inflammatory conditions such
as arthritis, tendonitis, and bursitis. In addition to its effects on pain,
fever, and inflammation, aspirin also has an important inhibitory effect on
platelets in the blood. This antiplatelet effect is used to prevent blood clot
formation inside arteries, particularly in individuals who have atherosclerosis
of their arteries or are otherwise prone to develop blood clots in their
arteries.
What are antiplatelet agents?
Antiplatelet agents are medications that block the formation of blood clots
by preventing the clumping of platelets. There are three types of antiplatelet
agents; aspirin, the thienopyridines, and the glycoprotein IIb/IIIa inhibitors.
These agents differ in the way they work, their potency (how strongly they
prevent clumping), how rapidly they work, and their cost.
What are platelets?
Platelets are particles (actually, remnants of cells) circulating in the
blood that are needed in order for blood clots to form. Platelets initiate the
formation of blood clots by sticking together (clumping), a process called
platelet aggregation. Clumps of platelets then are further bound together by a
protein (fibrin) formed by clotting factors present in the blood. The clumps of
platelets and fibrin make up the blood clot.
Blood clots are important because they stop us from
bleeding when we get cut. However, if a blood clot forms inside an artery, it
blocks the flow of blood to the tissue that the artery supplies, which can
damage the tissue. For example, a blood clot that forms in a coronary artery
supplying blood to the muscle of the heart causes a heart attack, and a blood clot that forms in an artery supplying
blood to the brain causes a stroke.
How do antiplatelet agents work?
Aspirin prevents blood from clotting by blocking the production by platelets
of thromboxane A-2, the chemical that causes platelets to clump. Aspirin
accomplishes this by inhibiting the enzyme cyclo-oxygenase-1 (COX-1) that
produces thromboxane A-2. While other NSAIDs also inhibit the COX-1 enzyme,
aspirin is the preferred NSAID for use as an antiplatelet agent because its
inhibition of the COX-1 enzyme lasts much longer than the other NSAIDs (aspirin's
antiplatelet effect lasts days while the other NSAIDs' antiplatelet effects last
only hours).
In addition to thromboxane A-2, platelets also produce adenosine diphosphate
(ADP). When ADP attaches to receptors on the surface of platelets, the platelets
clump. The thienopyridines, for example, ticlopidine (Ticlid) and clopidogrel
(Plavix), block the ADP receptor. Blocking the ADP receptor prevents ADP from
attaching to the receptor and the platelets from clumping.
The glycoprotein IIb/IIIa inhibitors, such as abciximab (Reopro) and
eptifibatide (Integrilin), prevent clumping by inhibiting a different receptor
on the surface of platelets, the receptor for glycoprotein IIb/IIIa. The
glycoprotein IIb/IIIa inhibitors that are approved by the FDA must be given
intravenously.
What is the relative potency of the antiplatelet agents?
Since aspirin blocks only one of the several pathways by which platelet
aggregation can occur, aspirin is a weak antiplatelet agent because platelet
aggregation can be stimulated via another pathway. Since glycoprotein IIb/IIIa
inhibitors block the final common pathway for platelet aggregation (platelet
aggregation is blocked regardless of the nature of the initial stimuli),
glycoprotein IIb/IIIa inhibitors are the most potent antiplatelet agents. The
maximal antiplatelet effect of glycoprotein IIb/IIIa inhibitors is approximately
9 times that of aspirin. The maximal antiplatelet effect of thienopyridines is
in between that of aspirin and the glycoprotein IIb/IIIa inhibitors.
How quickly do antiplatelet agents work?
When aspirin is given in low doses (75 mg/day), the complete inhibition of
the COX-1 enzyme and hence maximal antiplatelet effect may take several days. At
a dose of 160-325 mg/day, the maximal antiplatelet effect of aspirin occurs
within 30 minutes. Thus, aspirin at low doses (75-150 mg/day) is used for the
long term prevention of heart attacks and strokes, whereas moderate doses
(160-325 mg/day) of aspirin are given in situations where an immediate
anti-clotting effects are needed (such as in the treatment of acute heart
attacks and unstable angina).
Like aspirin, the onset of action of clopidogrel (Plavix) is dose related.
Maximal antiplatelet effect occurs several days after initiation of clopidogrel
(75 mg/daily), but can occur within hours after larger doses of 300 or 600 mg.
Therefore, larger doses of clopidogrel are used initially when immediate
antiplatelet actions are needed while the lower doses are used as maintenance.
The glycoprotein IIb/IIIa inhibitors have a rapid onset of action. Their
maximal antiplatelet effect occur within minutes after an intravenous infusion.
What are the costs of the antiplatelet agents?
Aspirin is the least expensive antiplatelet agent, costing approximately 4
-12 cents daily, while Clopidogrel is more expensive at $4/day and glycoprotein
IIb/IIIa inhibitors are the most expensive, costing between $ 600-$2,000 per
infusion.
What is Dipyridamole?
Dipyridamole is another medication that
decreases platelet aggregation, though the exact mechanism of its antiplatelet
action is not well understood. Dipyridamole is not commonly used in heart attack prevention although it is sometimes used with aspirin to lessen the chance of stroke.
Next: When is aspirin used for preventing and treating heart attacks and strokes? »
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