SYMPOSIUM  Evolving role of antiplatelet therapy

Overview of advances in cardiovascular disease

treatment and prevention:
The evolving role of antiplatelet therapy

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Robert L. Talbert

A
ccording to the American Heart As-
sociation (AHA), an estimated 80.7
million Americans—about one in
three—have at least one type of cardiovas-
cular disease (CVD).1
Coronary heart disease (CHD) con-
tributes to more than half of all adverse
cardiovascular events in American men and
women under age 75, making it the lead-
ing cause of CVD morbidity and mortal-
ity.1 The lifetime risk for developing CHD
after age 40 is 49% for men and 32% for
women, with the average age for first MI of
66 years in men and 70 years in women. In
2004, CHD accounted for 52% of all CVD
deaths—three times greater than deaths
due to stroke and more than eight times
greater than deaths due to high blood pres-
sure or heart failure (Figure 1).
Acute coronary syndrome (ACS) is a
term that encompasses acute myocardial
infarction (MI) and unstable angina.1 A
patient who presents with ACS is clas-
sified into one of three categories: ST-
elevation MI (STEMI), non-ST-elevation
MI (NSTEMI), or unstable angina. In both
categories of MI, the patient presents with
classical symptoms and abnormal eleva-
tions of myocardial biomarkers; however,
only patients with STEMI—about 20% of
all patients with ACS—show ST-segment
elevation on electrocardiogram (ECG).
In unstable angina, defined as chest pain
that accelerates in frequency or severity
and may occur at rest, symptoms are not
accompanied by positive ECG findings or
elevated myocardial biomarkers.
Each year, an estimated 500,000 new
MIs and 300,000 recurrent MIs are re-
ported; 175,000 of these first MIs are silent.1
Purpose. The role of antiplatelet therapy
in preventing and treating cardiovascular
disease is reviewed.
Summary. Cardiovascular disease, espe-
cially coronary heart disease, contributes
to substantial morbidity and mortality in
the United States and raises healthcare
costs. Current guidelines from the Ameri-
can College of Cardiology and the Ameri-
can Heart Association, in conjunction with
the Society for Cardiovascular Angiogra-
phy and Interventions, recommend per-
cutaneous coronary intervention (PCI) and
stent placement to improve cardiovascular
outcomes in patients with acute coronary
syndrome, which encompasses unstable
angina and myocardial infarction. Fol-
lowing stent placement, dual antiplatelet
therapy with aspirin and a thienopyridine
(clopidogrel or ticlopidine) significantly
reduces the incidence of early major
adverse cardiac events and mortality com-
pared with aspirin alone or in combination
with warfarin, and is the current standard
of care for patients undergoing PCI. Main-
The incidence of acute MI increases with
age and is generally higher among black
men and women than among white men
and women. In 2005, 772,000 men and
women were discharged from hospital for
ACS; including secondary discharge diag-
noses, ACS accounted for about 1.5 million
discharges.
Current guidelines and strategies
The American College of Cardiol-
ogy (ACC) in conjunction with the AHA,
has issued a series of guidelines for the
tenance therapy should be continued
for at least one month after placement
of a bare-metal stent, and at least three
months or six months after placement of
a sirolimus- or paclitaxel-eluting stent;
ideally, therapy should be continued for
one year following PCI. Even utilizing this
standard, however, adverse clinical events
do occur. In addition, treatment is often
discontinued within the first year after
stent placement by either the healthcare
provider or the patient.
Conclusion. Premature discontinuation of
antiplatelet therapy is associated with an
increased risk of adverse outcomes and can
be avoided through better understanding
of these risks by healthcare professionals
and improved patient education.
Index terms: Aspirin; Cardiovascular
diseases; Clopidogrel; Combined therapy;
Mortality; Platelet aggregation inhibitors;
Protocols; Stents; Ticlopidine
Am J Health-Syst Pharm. 2008; 65(Suppl
5):S1-5
management of ACS, including recom-
mendations for invasive and conservative
treatment strategies, and antithrombotic
drug therapy.2-4 These recommendations
are classified according to evidence ranging
from limited to multiple population risk
evaluations.2 Class I recommendations cor-
respond to procedures or treatments that
should be performed or administered, and
Class II recommendations to procedures or
treatments that are reasonable to perform
or administer (IIa) or may be considered
(IIb). Class III recommendations are for

Robert L. Talbert, Pharm.D, FCCP, BCPS, is a Professor, College
of Pharmacy, University of Texas-Austin and Professor, School of
Medicine, University of Texas Health Science Center at San Antonio
Pharmacotherapy and Education Research Center MSC 6220, Uni-
versity of Texas Health Science Center at San Antonio, 7703 Floyd
Curl Drive, San Antonio, TX 78229-3900 (talbert@uthscsa.edu).
Based on the proceedings of a symposium held December 4, 2007,
during the ASHP Midyear Clinical Meeting and Exhibition in Las Ve-
gas, NV, and supported by an educational grant from Daiichi Sankyo,
Inc. and Eli Lilly and Company. Dr. Talbert received an honorarium
for his participation in the symposium and for the preparation of
this article. Dr. Talbert reports serving on the advisory board and
speakers’ bureau for AstraZeneca and Novartis and on the advisory
board for Abbott.
Copyright © 2008, American Society of Health-System Pharma-
cists, Inc. All rights reserved. 1079-2082/08/0701-00S1$06.00.
DOI 10.2146/ajhp080129

Am J Health-Syst Pharm—Vol 65 Jul 1, 2008  Suppl 5 S1

 SYMPOSIUM  Evolving role of antiplatelet therapy
Figure 1. Specific causes of cardiovascular disease-related deaths in the U.S. (2004).
Reprinted with permission from reference 1.
Rheumatic
Fever/Rheumatic
Other
Heart Disease
13%
0.4%
Congenital
Cardiovascular
Defects
0.5%
CAD
4%
High Blood Pressure
6%
Heart Failure
6%
Stroke
17%
CHD = coronary heart disease; CAD = coronary artery disease
those procedures or treatments that should
not be performed or administered because
they may be harmful or not helpful.2
Current Class I guidelines for the man-
agement of unstable angina (UA) or non-ST-
elevation myocardial infarction (NSTEMI)
prior to hospitalization call for the use of
aspirin, 162 to 325 mg, to be chewed if
not taken previously.2 In addition, a single
dose of sublingual nitroglycerin should be
taken; if the patient does not experience
relief, emergency medical services should
be notified. For the patient hospitalized
with unstable angina or NSTEMI, early
Class I hospital care includes sublingual
nitroglycerin at a dose of 0.4 mg every five
minutes for persistent ischemic discomfort,
or intravenous (i.v.) nitroglycerin in the
first 48 hours for patients with persistent
ischemia, heart failure, or hypertension.
Early hospital care may also include use
of antihypertensive agents, such as an
oral beta blocker within the first 24 hours
in the absence of contraindications, a
calcium channel blocker (CCB) for con-
tinuing or frequently occurring ischemia,
an angiotensin-converting enzyme (ACE)
inhibitor in the first 24 hours for symp-
tomatic heart failure or a left ventricular
ejection fraction < 0.40 (or an angiotensin-
receptor blocker if intolerant). Nonsteroi-
dal antiinflammatory agents other than as-
pirin should be avoided. Recommendations
for Class IIa early hospital care include ad-
ministration of oxygen; an i.v. beta blocker,
CCB, or ACE inhibitor; and i.v. morphine.
S2 Am J Health-Syst Pharm—Vol 65 Jul 1, 2008  Suppl 5
CHD
52%
After hospital admission, clinicians may
choose to manage the patient with an initial
invasive strategy or a conservative strategy.2
The invasive strategy includes administra-
tion of clopidogrel and aspirin, followed by
anticoagulation therapy with enoxoparin
or unfractionated heparin (or bivalirudin
or fondaparinux). Prior to angiography,
the patient should receive antiplatelet ther-
apy with clopidogrel and/or a glycoprotein
(GP) IIb/IIIa inhibitor, depending on risk
status, due to their different 1mechanisms
of action. Factors favoring administration
of both clopidogrel and GP IIb/IIIa in-
hibitor include delay to angiography, high
risk features or early recurrent ischemic
discomfort. Clopidogrel should be given
as a loading dose (300-600 mg) followed
by 75 mg/day due to a lag time in onset of
antiplatelet activity, whereas the GP IIb/IIIa
inhibitors have a rapid onset of activity.
Alternatively, the conservative strategy may
be considered based on the condition of the
patient, the availability of a catheterization
laboratory, or any potential delay in the
procedure. The same anticoagulant therapy
is recommended, and i.v. eptifibatide or
tirofiban may be considered as an adjunct
to clopidogrel therapy.
The recommendations for medica-
tions prescribed at hospital discharge for
patients with UA or ST-elevation myo-
cardial infarction (STEMI) are based on
in-hospital medical management.2 Patients
who received only medical therapy should
continue the use of low-dose aspirin in-
definitely (75-162 mg per day). Those who
received bare-metal stents should be in-
structed to take high-dose aspirin (162-325
mg per day) for one month, followed by
a lower dose indefinitely. After placement
of a drug-eluting stent, high-dose aspirin
therapy is recommended for three to six
months, followed by low-dose aspirin
indefinitely. Regardless of in-hospital treat-
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ment, all patients should be treated with
clopidogrel for at least one month, and
ideally for one year; any patient with an in-
dication for anticoagulation therapy should
receive warfarin.
Guidelines for antithrombotic
therapy for percutaneous coronary
intervention
The AHA and ACC, in conjunction with
the Society for Cardiovascular Angiogra-
phy and Interventions (SCAI) have issued
separate guidelines for antithrombotic
therapy following percutaneous coronary
intervention (PCI).3 The Class I recom-
mendations include aspirin and a loading
dose of clopidogrel prior to the procedure.
Clopidogrel maintenance therapy should
be continued for at least one month after
placement of a bare-metal stent, and at least
three months or six months after place-
ment of a sirolimus- or paclitaxel-eluting
stent; ideally, clopidogrel therapy should be
continued for one year after PCI. Class IIa
recommendations include the addition of a
GP IIb/IIIa inhibitor to clopidogrel prior to
the procedure. For patients with an absolute
contradiction to aspirin, a 300-mg loading
dose of clopidogrel six hours prior to PCI
and administration of a GP IIb/IIIa inhibi-
tor at the time of the procedure is a reason-
able approach; the efficacy and safety of a
higher loading dose of clopidogrel (>600
mg) have not been established. Finally, pa-
tients undergoing brachytherapy should be
treated with clopidogrel and aspirin indefi-
nitely. Platelet aggregation studies should
be considered, and the maintenance dose of
clopidogrel increased to 150 mg, for those
patients in whom subacute thrombosis
would be catastrophic or fatal.
The use of a GP IIb/IIIa inhibitor is rec-
ommended for those patients with unstable
angina or NSTEMI undergoing PCI wheth-
er or not they have been pretreated with
clopidogrel, as well as patients undergoing
elective stent placement.3 Patients admitted
with STEMI should be treated with abcix-
imab as early as possible, and treatment
with eptifibatide or tirofiban may be con-
sidered for patients with STEMI undergo-
 SYMPOSIUM  Evolving role of antiplatelet therapy

ing PCI. Additional ACC/AHA guidelines
address the management of patients who
have experienced STEMI (Table 1).4
Role of antiplatelet agents in acute
coronary syndromes
PCI has become a widely successful
procedure in patients with unstable an-
gina and those experiencing MI.5 More
to continue therapy with both aspirin and
clopidogrel for one month after placement
of a bare-metal stent, for three months
after sirolimus DES placement, and for
six months after placement of a paclitaxel
DES are based on the time expected for
stents to become adequately protected by
endothelial tissue and reduce the risk for
thrombosis and on the timeframe reported
tion of aspirin plus ticlopidine. Overall,
the combination of aspirin and ticlopidine
was more effective than aspirin alone or in
combination with warfarin, and in some
studies, the treatment differences were sta-
tistically significant.5,8,9
Unfortunately, and despite current
recommendations and the proven benefits
of combination antiplatelet therapy, treat-

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than 70% of elective PCIs are done with from clinical trials.8 ment is often discontinued within the first
stent placements, due to their high effi- Combination therapy with aspirin ther- year after stent placement by either the
cacy rate in avoiding early vessel closure.5 apy and a thienopyridine (clopidogrel or healthcare provider or the patient.8 Drug
Drug-eluting stents (DES) represent an ticlopidine) significantly reduces the inci- cost, instructions by healthcare providers
important advance in PCI in that they dence of early major adverse cardiac events to discontinue antiplatelet therapy prior to
substantially reduce restenosis compared after stent placement compared with aspi- procedures, and inadequate education and
with bare-metal stents; consequently, they rin alone or in combination with warfarin.8 understanding of the importance of con-
are used in the majority of PCI procedures.6 In addition, the use of a thienopyridine in tinuing treatment have been cited as factors
However, DES are not without limitations. combination with aspirin for at least one contributing to premature discontinuation.
Subacute thrombosis has been reported in year after NSTEMI decreases the incidence Both physicians and patients should be
1–4% of stenting procedures, resulting in of ischemic events. These findings form the aware of the serious adverse consequences,
MI or death in the majority of patients.5 basis of the ACC/AHA recommendations including death, associated with discon-
In a recent analysis of DES versus bare for patients undergoing PCI and those who tinuing antiplatelet therapy that have been
metal stents, Applegate and colleagues 7 have experienced NSTEMI.8 demonstrated in clinical trials.
found that target vessel revascularization, The benefits of combination therapy Premature discontinuation of thien-
non-fatal MI or death and all-cause death with an antiplatelet agent and aspirin were opyridine therapy is an independent pre-
were reduced with DES compared to bare underscored in four randomized trials dictor of stent thrombosis.10 In one study
metal stents for both “on-label” and “off- that compared combination therapy with of more than 2200 patients, premature
label” indications. Stent thrombosis was aspirin and ticlopidine (250 mg twice daily discontinuation of antiplatelet therapy
less common with DES early on but by two for 4 weeks) or aspirin and coumadin— within nine months of successful DES im-
years there was little difference. Premature ISAR (Intracoronary Stenting and Anti- plantation conferred statistically significant
discontinuation of thienopyridine therapy thrombotic Regimen), FANTASTIC (Full hazard ratios for any stent thrombosis, as
has been found to be the leading risk factor Anticoagulation Versus Aspirin and Ticlo- well as for subacute and late stent thrombo-
for stent thrombosis.6 The risk after bare- pidine After Stent Implantation), STARS sis (p < 0.001 for each), with no differences
metal stent placement decreases rapidly (Stent Anticoagulation Restenosis Study), between sirolimus- and paclitaxel-eluting
after 2–4 weeks due to endothelial tissue MATTIS (Multicenter Aspirin and Ticlopi- stents.10 In addition, the cumulative in-
coverage; however, the risk is prolonged dine Trial after Intracoronary Stenting).5,8 cidence of stent thrombosis (29%) was
following DES placement, due to a delay in An additional study by Hall and colleagues9 substantially higher than that reported in
endothelial coverage.6 Thus, the guidelines compared aspirin alone with the combina- earlier clinical trials.
In the Prospective Registry Evaluating
Myocardial Infarction: Events and Recovery
(PREMIER) study,6 nearly 1 in 7 patients
Table 1. (13.6%) discontinued thienopyridine
Guidelines for Antithrombotic Therapy in ST-Elevation Myocardial therapy within 30 days after DES placement
following MI, resulting in a significant
Infarction.a Reprinted with permission from reference 4.
increase in mortality over the following
Class I ASA should be chewed if patient with STEMI has not taken ASA 11 months compared with patients who
ASA dose 162–325 mg (buccal administration may result in more rapid continued therapy (7.5% versus 0.7%,
absorption) p < 0.0001; Figure 2), as well as a greater
Continue ASA indefinitely at 75–162 mg/day risk for rehospitalization (23% versus
Patients taking ASA should take 75–325 mg before PCI is performed 14%, p = 0.08). Patients who discontinued
Clopidogrel should be given if ASA cannot be used thienopyridine therapy were also less likely
Stop clopidogrel at least 5 days prior to CABG to have received medication instructions
If diagnostic catheterization with PCI is planned, clopidogrel should be or referral for cardiac rehabilitation at dis-
started and continued: charge, indicating a need to develop strate-
For at least 1 mo with a bare-metal stent gies to improve the use of thienopyridines
For at least 3 mo with a sirolimus-eluting stent and optimize outcomes following DES
For at least 6 mo with a paclitaxel-eluting stent placement.
Up to 12 mo if not at high risk of bleeding A third observational study corrobo-
a
ASA = aspirin; STEMI = ST-elevation myocardial infarction; PCI = percutaneous coronary intervention;
rated the need to continue antiplatelet
CABG = coronary artery bypass grafting therapy for patients with DES.11 In this five

Am J Health-Syst Pharm—Vol 65 Jul 1, 2008  Suppl 5 S3

 SYMPOSIUM  Evolving role of antiplatelet therapy
year study, clopidogrel use continued to
predict 24-month outcomes significantly
among patients with DES, providing lower
rates of mortality (p < 0.004) and death or
MI (p < 0.001). These results have impor-
tant implications in clinical practice for the
use of thienopyridine therapy in patients
with DES, although the precise duration of
therapy has not been determined.
Joint recommendations for dual
anticoagulation therapy following
stent placement
The results of these observational stud-
ies prompted the promulgation of recom-
mendations to eliminate premature dis-
continuation of thienopyridine therapy in a
2007 joint science advisory from the AHA,
ACC, SCAI, American College of Surgeons,
and American Dental Association, with
representation from the American College
of Physicians.8 These recommendations
are summarized as follows 1) prior to stent
implantations, physicians should explain
the need for dual antiplatelet therapy to
the patient; for those patients who may
not comply with 12 months of therapy,
DES stents should be avoided; 2) use of a
bare-metal stent rather than a DES should
be considered in patients undergoing PCI
who are likely to require invasive surgical
procedures within 12 months; 3) healthcare
professionals must make a greater educa-
tional effort prior to patient discharge re-
Figure 2. Kaplan-Meier curves comparing mortality from 1 to 12 months after drug-
eluting stent placement in patients continuing thienopyridine therapy with those dis-
continuing therapy within 1 month. Reprinted with permission from reference 6.
15
10
Mortality (%)
5 Myocardial Infarction). Circulation. 2004;
0
0 1
No. at Risk
Continued 431
Discontinued 68
S4 Am J Health-Syst Pharm—Vol 65 Jul 1, 2008  Suppl 5
garding the risks associated with premature
discontinuation of antiplatelet therapy; 4)
patients should be given specific instruc-
tions prior to discharge to contact their car-
diologists before discontinuing antiplatelet
therapy; 5) healthcare professionals who
perform invasive or surgical procedures
and are concerned about peri- or post-
procedural bleeding should contact the
patient’s cardiologist prior to discontinuing
antiplatelet therapy and discuss optimal
strategies; 6) elective surgical procedures
should be deferred until patients have com-
pleted 12 months of antiplatelet therapy
after DES implantation and a minimum
of 1 month after bare-metal stent place-
ment; 7) patients with DES undergoing
procedures that require discontinuation
of thienopyridine therapy should continue
aspirin therapy and resume thienopyridine
therapy as soon as possible; and, 8) the
healthcare industry, insurers, and Congress
should work together to ensure that the
cost of thienopyridine therapy does not
contribute to premature discontinuation
of therapy.
Conclusion
CVD, and particularly CHD, is highly
prevalent in the U.S. and contributes
to significant morbidity, mortality, and
healthcare costs. Current guidelines recom-
mend PCI and stent placement to improve
cardiovascular outcomes in patients with
unstable angina or MI; however, there is
Continued
p<0.001
Discontinued
2 3 4 5 6 7 8 9 10 11 12
Months
431 431 431 430 429 420
68 67 66 65 65 62
risk for stent thrombosis within one month
of placement of a bare-metal stent and
within 12 months of DES placement. Anti-
thrombotic therapy, especially antiplatelet
therapy, plays an important role in the pre-
vention and treatment of CVD. Specifically,
combination antiplatelet therapy with aspi-
rin and a thienopyridine reduces the risk of
major adverse coronary events and mortal-
Downloaded from https://academic.oup.com/ajhp/article-abstract/65/13_Supplement_5/S1/5128232 by guest on 27 May 2019
ity in patients with ACS undergoing PCI.
Premature discontinuation of antiplatelet
therapy is associated with an increased risk
of adverse outcomes and can be avoided
through better understanding of these risks
by healthcare professionals and improved
patient education.
References
1. Rosamond W, Flegal K, Furie K et al.
Heart disease and stroke statistics 2008
update. A report from the American
Heart Association Statistics Commit-
tee and Stroke Statistics Subcommittee.
Circulation. 2008; 117:e25-e146.
2. Anderson JL, Adams CD, Antman EM
et al. ACC/AHA 2007 Guidelines for the
Management of Patients With Unstable
Angina/Non-ST-Elevation Myocardial
Infarction: Executive Summary. A report
of the American College of Cardiology/
American Heart Association Task Force
on Practice Guidelines (Writing Com-
mittee to Revise the 2002 Guidelines for
the Management of Patients With Unsta-
ble Angina/Non-ST-Elevation Myocardial
Infarction). Circulation. 2007; 116:803-77.
3. Smith SC Jr, Feldman TE, Hershfeld JW
et al. ACC/AHA/SCAI 2005 Guideline
Update for Percutaneous Coronary
Intervention—Summary Article. A
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Cardiology/American Heart Associa-
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(ACC/AHA/SCAI Writing Committee to
Update the 2001 Guidelines for Percuta-
neous Coronary Intervention. Circula-
tion. 2005; 113:1156-75.
4. Antman EM, Anbe DT, Armstrong PW
et al. ACC/AHA 2007 Guidelines for
the Management of Patients With ST-
Elevation Myocardial Infarction. A report
of the American College of Cardiology/
American Heart Association Task Force
on Practice Guidelines (Committee
to Revise the 1999 Guidelines for the
Management of Patients With Acute
110:e82-e293.
5. ten Berg JM, Thijs Plokker HW, Verheug
FWA. Antiplatelet and anticoagulant
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6. Spertus JA, Kettelkamp R, Vance C et al.
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registry. Circulation. 2006; 113:2803-09.
 SYMPOSIUM  Benefits andEvolving
SYMPOSIUM  limitations ofof
role antiplatelet therapies
antiplatelet therapy

7. Applegate RJ, Sacrinty MT, Kutcher MA
et al. “Off-label” stent therapy 2-year
comparison of drug-eluting versus
bare-metal stents. J Am Coll Cardiol. 2008;
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with representation from the American
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9. Hall P, Nakamura S, Maiello L et al. A
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ticlopidine and aspirin therapy versus
aspirin therapy alone after successful in-
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10. Iakovou I, Schmidt T, Bonizzoni E et al.
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Benefits and limitations of current
antiplatelet therapies
Jean Nappi

A
cute coronary syndromes (ACS),
which include angina and non-ST seg-
ment elevation myocardial infarction
(NSTEMI), share a common pathophysi-
ologic process in which plaque rupture is
the most likely cause.1 Interaction between
a clot rich in platelets and the tissue factor
at the site of the plaque leads to a sudden
decrease in the vessel lumen diameter, trig-
gering clinically relevant ischemia (unstable
angina) or necrosis (NSTEMI). For the last
few decades, researchers in cardiovascular
medicine have focused on pharmacologic
interventions to prevent platelet aggrega-
tion, thus disrupting the pathophysiologic
process leading to ischemia. Antiplatelet
agents, including aspirin, thienopyridines,
and platelet glycoprotein (GP) IIb/IIIa re-
ceptor inhibitors, have become the founda-
tion of antithrombotic therapy.1,2
Aspirin: The cornerstone of
antiplatelet therapy
Aspirin therapy, recognized for many
years as an effective agent for the man-
agement of patients with atheroscle-
rosis, has become the cornerstone of
antiplatelet therapy in cardiovascular
Purpose. The benefits and limitations of
current antiplatelet therapies in the man-
agement of patients experiencing acute
coronary syndrome (ACS) are reviewed.
Summary. Antiplatelet agents, including
aspirin, thienopyridines, and platelet glyco-
protein (GP) IIb/IIIa receptor inhibitors, have
become the foundation of antithrombotic
therapy in the management of patients
experiencing ACS. Despite aspirin’s ability
to reduce the risk for adverse thrombotic
events in a broad range of patients, it has
variable antiplatelet activity in individual
patients. The term “aspirin resistance” de-
scribes the inability of aspirin to produce
an anticipated effect on one or more tests
of platelet function. Because a substantial
proportion of patients are “resistant” to the
antiplatelet effects of aspirin, and other
pathways for platelet aggregation are not
inhibited by aspirin, current guidelines rec-
ommend a dual antiplatelet regimen with
a thienopyridine or GP IIb/IIIa inhibitor in
addition to aspirin for patients with ACS, in-
cluding patients undergoing percutaneous
coronary intervention and stent placement.
These guidelines are based on observational
and randomized clinical trials support-
ing the effectiveness of dual antiplatelet
therapy in reducing mortality, nonfatal myo-
cardial infarction, and the need for urgent
revascularization compared with placebo,
aspirin therapy alone, or an anticoagulant
regimen. Studies in small numbers of pa-
tients have also revealed that some patients
may be resistant to a thienopyridine, with
some suggestion of a genetic etiology. Ad-
ditional studies are needed to provide more
definitive answers.
Conclusion. Improved awareness by
healthcare professionals of the benefits and
limitations of various antiplatelet therapies
should aid in the development of strategies
to ensure patient compliance and thereby
reduce the morbidity and mortality associ-
ated with premature discontinuation of
dual antiplatelet therapy.
Index terms: Acute coronary syndrome;
Aspirin; Combined therapy; Mechanism
of action; Mortality; Platelet aggregation
inhibitors; Protocols; Thienopyridines
Am J Health-Syst Pharm. 2008; 65(Suppl
5):S5-10

Jean Nappi, Pharm.D., FCCP, BCPS, is a Professor of Clinical Phar-
macy and Outcome Sciences, South Carolina College of Pharmacy
and Professor of Medicine, Medical University of South Carolina, QE
213, 43 Sabin Street, Charleston, SC 29425 (nappijm@musc.edu).
Based on the proceedings of a symposium held December 4, 2007,
during the ASHP Midyear Clinical Meeting and Exhibition in Las Ve-
gas, NV, and supported by an educational grant from Daiichi Sankyo,
Inc. and Eli Lilly and Company. Dr. Nappi received an honorarium
for her participation in the symposium and for the preparation
of this article. Dr. Nappi reports serving on the advisory board for
Arca Discovery and sanofi-aventis and the speakers’ bureau for
AstraZeneca, Scios, The Medicines Company, and Pfizer, Inc.
Copyright © 2008, American Society of Health-System Pharma-
cists, Inc. All rights reserved. 1079-2082/08/0701-00S5$06.00.
DOI 10.2146/ajhp080156

Am J Health-Syst Pharm—Vol 65 Jul 1, 2008  Suppl 5 S5