Cardiology

Rapid Desensitization Protocols for Patients with Cardiovascular

Disease and Aspirin Hypersensitivity in an Era of Dual
Antiplatelet Therapy

Nathaniel A Page and Walter S Schroeder

ontemporary management of acute

C coronary syndromes (ACS) involves
the administration of dual antiplatelet ther-
apy with the cyclooxygenase-1 (COX-1)
inhibitor aspirin and clopidogrel. Several
studies have demonstrated clear reduc-
tions in adverse cardiovascular events
with the administration of aspirin and
OBJECTIVE: To review the available protocols for rapid desensitization of patients
with aspirin hypersensitivity and apply the data for use in patients with cardio-
vascular disease who would benefit from the dual antiplatelet therapy.
DATA SOURCES: A literature search was conducted via MEDLINE from 1966 to
December 2006. Main search terms included: aspirin sensitivity, aspirin allergy,
aspirin desensitization, aspirin-induced asthma, aspirin therapy, and aspirin
intolerance syndrome.
STUDY SELECTION AND DATA EXTRACTION: Articles describing rapid aspirin de-

clopidogrel to patients with unstable angi-
na, non–ST-segment elevation myocardial
infarction, ST-segment elevation myocar-
dial infarction, or in patients who received
a coronary stent.1-4
Initially, the CURE (Clopidogrel in
Unstable Angina to Prevent Recurrent
Events) trial concluded that dual an-
tiplatelet therapy with aspirin and clopi-
dogrel significantly reduced secondary
cardiovascular events in patients with
ACS without ST-segment elevation ver-
4
sus monotherapy with aspirin. The ab-
solute risk reduction of the composite
endpoint of cardiovascular mortality and
recurrent cardiovascular events was 2.1%
(p < 0.001). A subset of patients in the
CURE trial who received percutaneous
coronary intervention (PCI) also experi-
enced significant reduction in secondary
events when administered dual an-
tiplatelet therapy.1 These results were con-
firmed by the findings of the CREDO
(Clopidogrel for the Reduction of Events During Observa-
tion) trial, along with numerous other studies assessing the
role of dual antiplatelet therapy in the prevention of throm-
Author information provided at the end of the text.
sensitization protocols were selected for review. Literature pertaining to aspirin
hypersensitivity, drug desensitization, and the use of aspirin and dual antiplatelet
therapy was also examined. Three rapid desensitization protocols were identified
and evaluated.
DATA SYNTHESIS: While landmark studies demonstrated that dual antiplatelet
therapy with aspirin and clopidogrel significantly reduces mortality and morbidity in
acute coronary syndromes and coronary stenting, patients with aspirin hyper-
sensitivity are frequently managed with clopidogrel alone with no supporting data.
Approximately 10% of the population experiences hypersensitivity to aspirin,
which can manifest as asthma exacerbations, rhinorrhea, angioedema, urticaria,
and anaphylaxis. The hypersensitivity reaction is mediated through aspirin-
directed antibodies or by excessive leukotriene production. The desensitization
process involved depletion of these mediators, as well as down-regulation of
leukotriene receptors. Two groups of investigators developed rapid protocols to
desensitize patients with aspirin hypersensitivity safely and effectively. The rapid
protocol developed by Wong provides benefits over other protocols with its low
starting dose and completion in less than 3 hours, low incidence of adverse
effects, and high success rate in aspirin desensitization.
CONCLUSIONS: The Wong protocol is an attractive option for the rapid desensi-
tization of patients requiring dual antiplatelet therapy with aspirin and clopidogrel
in the perimyocardial infarction period.
KEY WORDS: aspirin desensitization, myocardial infarction.
Ann Pharmacother 2007;41:61-7.
Published Online, 2 Jan 2007, www.theannals.com, DOI 10.1345/aph.1H437
bosis with bare metal and drug-eluting coronary stents.3,5-7
The outcomes of these pivotal trials resulted in the Class I
recommendation for dual antiplatelet therapy in patients
undergoing PCI by the American College of Cardiology, the
American Heart Association, and the Society for Cardiovas-
cular Angiography and Interventions (ACC/AHA/SCAI)

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NA Page and WS Schroeder
2005 guideline update for percutaneous coronary interven-
tion.8
In addition to the documented efficacy in patients re-
ceiving PCI, dual antiplatelet therapy in patients who expe-
rienced an ST-segment elevation myocardial infarction has
been supported recently by the results from the CLARITY-
TIMI 28 (Clopidogrel as Adjunctive Reperfusion Thera-
py—Thrombolysis in Myocardial Infarction) trial.2 The
absolute risk reduction of the composite endpoint of death,
occluded infarct-related artery, or recurrent myocardial in-
farction with the addition of clopidogrel to aspirin was
6.7% (p < 0.001).
These studies lay the foundation supporting concurrent
use of aspirin and clopidogrel for the prevention of recur-
rent acute cardiovascular events. However, in patients who
experience hypersensitivity to aspirin, alternative an-
tiplatelet options are limited. Often, patients who require
this concurrent therapy are maintained on clopidogrel
monotherapy, for which no data exist to support this treat-
ment strategy. Aspirin desensitization then becomes an im-
portant and often overlooked management strategy in this
population at high risk for recurrent cardiovascular events.
The importance of aspirin desensitization is also highlight-
ed in the ACC/AHA/SCAI 2005 guideline update for PCI.8
The guideline suggests that desensitization may be an op-
tion for patients with aspirin hypersensitivity requiring
dual antiplatelet therapy; however, it makes no specific
recommendations on how to accomplish this.
This article identifies and assesses rapid aspirin desensi-
tization protocols with the goal of selecting those that are
safe and effective. Rapid desensitization protocols may
provide practitioners with a useful option to desensitize pa-
tients with ACS and aspirin hypersensitivity at the time
they are acutely managed for a cardiovascular event.
Aspirin Hypersensitivity
Approximately 10% of patients with asthma experience
respiratory symptoms due to exposure to aspirin.9 Any-
where from 0.07% to 0.2% of the population will experi-
ence urticaria when exposed to aspirin. Up to a third of pa-
tients with chronic idiopathic urticaria will have dermato-
logic exacerbations, such as hives and angioedema, when
exposed to aspirin or a nonsteroidal antiinflammatory drug
(NSAID).
Gollapudi et al.10 established a classification system for
aspirin hypersensitivity. Classification is based on the
mechanism of hypersensitivity, risk factors, and cross-sen-
sitivity to NSAIDs. Types I, II, and III are classified as
pseudoallergic reactions to aspirin.11 A pseudoallergy pre-
sents with the typical signs and symptoms of a true allergic
reaction but is mediated by a pathway different from anti-
gen-directed antibodies. Type I, II, and III reactions are
mediated by an excessive production of leukotrienes by 5-
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lipoxygenase, which results in mast cell degranulation and
the release of histamine and cytokines.10 5-Lipoxygenase
activity is inhibited by prostaglandin E2, which is synthe-
sized by COX-1. When COX-1 is inhibited, the effect of
prostaglandin E2 on 5-lipoxygenase is lost, allowing for the
rapid production of leukotrienes and manifestation of hyper-
sensitivity. Since this hypersensitivity is mediated by the inhi-
bition of COX-1, any drug that inhibits this enzyme may re-
sult in a hypersensitivity reaction.10,12 Type I hypersensitivity
manifests as respiratory symptoms such as rhinitis and asth-
ma. Patients with asthma, nasal polyps, and chronic upper
respiratory conditions are at increased risk for type I hyper-
sensitivity. Type II hypersensitivity is observed in patients
with chronic idiopathic urticaria. Exposure to aspirin mani-
fests as angioedema and an increase in urticaria. Type III hy-
persensitivity exhibits the same symptoms as the type II reac-
tion in patients without chronic idiopathic urticaria.10 Patients
with COX-1–mediated hypersensitivities manifest symptoms
after the first dose of aspirin or an NSAID.10-12
The type IV and V hypersensitivities are mediated via
aspirin-directed immunoglobin (Ig) E antibodies that
rarely cross react with other NSAIDs (Table 1). The type
IV reaction presents as angioedema and urticaria, and type
V presents as the classical anaphylaxis reaction. While
type I–III reactions manifest with the first exposure to as-
pirin, type IV and V reactions require repeated exposure to
promote antibody formation. Many patients exhibit more
than one class of hypersensitivity, which complicates clas-
sification.10,11 Table 1 provides a summary of the 5 types of
hypersensitivity.
The aspirin dose that initiates a hypersensitivity reaction
varies widely. A study of 29 hypersensitive patients demon-
strated a threshold range from 20 to 600 mg of aspirin as a
single dose.13 A second study of 28 hypersensitive patients
identified a threshold range from 30 to 300 mg of aspirin as a
single dose.14 Because the lowest challenge doses of aspirin
in the 2 studies were 20 and 30 mg, respectively, patients
who are sensitive to much lower doses may not be identified.
Because aspirin hypersensitivity is believed to be medi-
ated by either the inhibition of COX-1– or IgE-mediated
antibodies, selective COX-2 inhibitors (eg, celecoxib)
were considered to be a safer alternative for these hyper-
sensitive patients.15 However, at least one case report im-
plicated the COX-2 inhibitor rofecoxib in causing an ana-
phylactoid reaction in a patient with a previous hypersensi-
tivity to the COX-1 inhibitor diclofenac.16 It must be
emphasized that COX-2 inhibitors may not be safe in all pa-
tients who demonstrate hypersensitivity to aspirin and other
COX-1 inhibitors. Furthermore, recent studies demon-
strating an elevated cardiovascular risk in patients receiv-
ing COX-2 inhibitors suggest that this class of drugs
should be avoided in patients with cardiovascular disease,
regardless of aspirin hypersensitivity.17-19
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 Desensitization Protocols for Patients with Cardiovascular Disease and Aspirin Hypersensitivity
Desensitization Mechanism
Desensitization therapy for type I–III (COX-1 mediat-
ed) reactions involves gradual dose escalation of aspirin to
exhaust leukotrienes and downregulate leukotriene recep-
tors.20 Desensitization of type IV and V hypersensitivity
(IgE antibody mediated) is hypothesized to gradually satu-
rate antibody binding sites on granulocytes and deplete in-
flammatory cytokines.10 Upon successful desensitization,
full doses of aspirin (81–325 mg daily) may be used indef-
initely without development of hypersensitivity reactions.
However, a patient will become resensitized to aspirin after
2–7 aspirin-free days. Patients who discontinue aspirin
therapy can be redesensitized at a convenient time with the
goal of reinitiating aspirin therapy.21,22
Desensitization Protocols
A literature search for rapid aspirin desensitization pro-
tocols published between 1966 and December 2006 was
conducted via MEDLINE. Main search terms included as-
pirin sensitivity, aspirin allergy, aspirin desensitization, as-
pirin-induced asthma, aspirin therapy, and aspirin intoler-
ance syndrome. The selected aspirin desensitization proto-
cols could be completed in less than 6 hours and made use
of oral aspirin administration. In general, aspirin desensiti-
zation protocols can be classified as either a rapid protocol
or a traditional protocol. Traditional protocols desensitize
patients over one or more days and were initially devel-
oped to desensitize aspirin-hypersensitive asthmatic pa-
tients.21,23 Due to their length, traditional protocols have limit-
ed utility in the desensitization of cardiovascular patients who
require prompt aspirin and clopidogrel administration.22 In
contrast to the traditional protocol, rapid protocols are com-
pleted in much less time, usually less than 6 hours. Desensiti-
zation must proceed in a well-controlled environment, such
as an intensive care unit or cardiac care unit, in the event that
a severe or life-threatening reaction occurs.21-26 We discuss 3
protocols with documented efficacy in desensitizing a variety
of patients with and without cardiovascular disease (Table 2).
Table 1. Types and Characteristics of Aspirin Hypersensitivity10
Type Reaction Type Risk Factors
I asthma, rhinitis asthma, nasal polyps, chronic upper
respiratory conditions
II angioedema, urticaria chronic idiopathic urticaria
III angioedema, urticaria
IV angioedema, urticaria
V anaphylaxis
IgE = immunoglobulin E; NSAIDs = nonsteroidal antiinflammatory drugs.
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SILBERMAN PROTOCOL
Silberman et al.27 developed a rapid desensitization pro-
tocol based on an initial desensitization of 16 patients who
had an indication for aspirin but had previously demon-
strated hypersensitivity. Thirteen of the patients exhibited
hypersensitivity that manifested as angioedema and ur-
ticaria (type III or IV hypersensitivity); 3 patients present-
ed with increased asthma symptoms upon aspirin exposure
(type I hypersensitivity). Fourteen of the patients received
PCI, 11 of whom also received stent placement. The other
2 patients did not receive PCI, but had an indication for as-
pirin therapy. β-Adrenergic antagonists were withheld for
24 hours before the protocol began, and none of the sub-
jects received pretreatment with antihistamines or cortico-
steroids.
The first 7 patients received a protocol of 8 aspirin doses
given over 3.5 hours. The starting dose was 1 mg, and the
dose was doubled every 30 minutes to a maximum of 100
mg. After completion of the protocol, patients were moni-
tored up to 3 hours for any delayed reaction. Of the 7 pa-
tients, 1 had a severe asthma attack approximately 1 hour
after the 100 mg dose (type I reaction). The patient was
treated with albuterol and recovered. No further attempts at
desensitization were made.27
The second group of 9 patients received a shorter proto-
col in which only 5 doses of aspirin were given every 30
minutes (2.5 h total) with a starting dose of 5 mg (Table 2).
One of these patients developed angioedema 3 hours after
finishing the protocol and responded to corticosteroids and
epinephrine. This patient repeated the protocol without
event 2 days later. Patients were maintained on an aspirin
dose of either 75 or 100 mg/day depending on which de-
sensitization protocol they received.27 The investigators re-
ported successful desensitization of an additional 18 pa-
tients without event. Four of the patients had a previous
anaphylactic (type V hypersensitivity) reaction upon as-
pirin exposure.26,28 The stratification of the patients into 1 of
the 2 desensitization protocols was temporally based; the first
7 patients to be desensitized received the first protocol, while
Cross-
Reaction Reactive Successful
at First with Other Desensitization
Mechanism Exposure NSAIDs Reported
leukotriene production yes yes yes
leukotriene production yes yes no
leukotriene production yes yes yes
aspirin-directed IgE antibodies no no yes
aspirin-directed IgE antibodies no no yes
n 2007 January, Volume 41 n 63
NA Page and WS Schroeder
subsequent patients received the second, shorter protocol.27
The protocols developed by Silberman et al. provide support
for the safe and effective aspirin desensitization of patients
with cardiovascular disease requiring aspirin therapy.
WONG PROTOCOL
Wong et al.22 developed a rapid desensitization protocol
based on their previously developed desensitization proto-
cols for vancomycin and β-lactam antibiotics. The protocol
was performed on 11 patients who experienced urticaria or
angioedema after aspirin therapy. Two of the patients
demonstrated type II hypersensitivity, 2 manifested type III
hypersensitivity, 2 showed type IV hypersensitivity, and
the other 5 patients were classified as having a type II or
IV hypersensitivity. Nine of the patients were pretreated
with loratadine, cetirizine, hydroxyzine, or diphenhy-
dramine. One patient was premedicated with an antihis-
tamine as well as 60 mg of prednisone the night before and
morning of the desensitization secondary to a recent as-
pirin hypersensitivity reaction. One patient did not receive
any pretreatment. Nine of the patients started the protocol
at 0.1 mg, 1 patient started at 1 mg, and another patient
started at 10 mg (Table 2). The length of the protocol var-
ied between 80 and 240 minutes depending on the dosing
interval and the number of doses given.
Of the 11 patients, 2 failed the protocol. The patient who
started with 1 mg experienced chest tightness after taking
10 mg. The tightness was relieved with an albuterol in-
haler. The other patient who failed started the protocol with
0.1 mg and completed the protocol only to experience an-
gioedema 3 hours after completion, which resolved with-
out treatment. No further attempts to desensitize these 2
patients were made. These patients had chronic idiopathic
urticaria independent of aspirin exposure (type II hyper-
sensitivity). The authors attributed these failures to the dif-
ficulty in desensitizing patients with type II hypersensitivi-
Table 2. Summary of Rapid Desensitization Protocols
Hypersensitivity Dosing
Protocol Type Interval
Silberman27
protocol 1 I, III, IV, V 30 min
protocol 2 I, III, IV 30 min
Wong22
protocol 1c I, II, III, IVd 10–20 min
protocol 2 III 20–30 min
protocol 3 II 20–30 min
a
Includes data from Alijotas-Reig et al.24
b
Failure 1: type I hypersensitivity reaction after 100 mg, which was treated with albuterol.
c
Protocol selected to be used in future desensitizations.
d
Success defined as a patient’s being able, ultimately, to tolerate aspirin therapy regardless of previous failed desensitization attempts.
e
Failure 2: angioedema 3 hours after completion of the protocol, which spontaneously resolved.
f
Failure 3: chest tightness after the 10 mg dose, which responded to albuterol.
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ty as opposed to protocol failures. Because these 2 patients
were premedicated with antihistamines, the failures could
not be attributed to lack of pretreatment. The authors stated
that the role of antihistamine as pretreatment was uncer-
tain. They believed that the low toxicity and possible bene-
fit in prevention of a hypersensitivity reaction warranted its
use. The decision to continue antihistamine use after de-
sensitization was left to the patients; however, the authors
believed that it was unnecessary. The investigators opted to
start with a 0.1 mg aspirin dose for subsequent desensitiza-
tion in an attempt to circumvent adverse reactions by ini-
tially exposing patients to a low dose.22
SUPPORT OF THE WONG PROTOCOL
Antiphospholipid syndrome (APS) is a gestational
thrombosis syndrome characterized by the presence of an-
tiphospholipid antibodies that promotes thrombus forma-
tion in the placental and uterine vasculature, leading to pla-
cental infarction.24 The syndrome has a poor prognosis if
left untreated and results in miscarriages and/or serious
complications in the first and second trimesters of preg-
nancy. The condition can be treated using low doses of as-
pirin and heparin. Aspirin hypersensitivity presents a signifi-
cant barrier to treating pregnant women with APS. Alijotas-
Reig et al.24 used the protocol outlined by Wong et al.22 to
desensitize 4 women with a history of APS and aspirin hy-
persensitivity. Aspirin hypersensitivity manifested as respira-
tory symptoms (type I) in 1 of the women, and the other 3
developed angioedema and urticaria upon aspirin exposure
(type III or IV). Three of the women were pregnant and one
was planning to conceive. A starting dose of 0.1 mg was ad-
ministered with a dosing interval of 15 minutes. No pretreat-
ment was administered before the desensitization.
Three of the women completed the protocol without event
and were continued on 100 mg of aspirin. The fourth woman
developed rhino-conjunctivitis after the 40 mg aspirin dose.
Success
Aspirin Dose, mg Rate, n (%)a
1, 2, 4, 8, 16, 32, 64, 100 6/7 (86)b
5, 10, 20, 40, 75 27/27 (100)
0.1, 0.3, 1, 3, 10, 30, 40, 81, 162, 325 11/12 (92)e
10, 20, 40, 81, 162 1/1 (100)
1, 3, 10 0/1 (0)f
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 Desensitization Protocols for Patients with Cardiovascular Disease and Aspirin Hypersensitivity
The protocol was stopped and she received a 2 mg oral dose
of diphenhydramine. She recovered from the reaction and
restarted the protocol the next day with 40 mg. She complet-
ed the protocol and was sustained on aspirin 100 mg/day. All
4 women had uneventful pregnancies while on the aspirin
and enoxaparin therapy. While only 4 patients without car-
diovascular disease were desensitized, this investigation pro-
vides support for the efficacy of rapid aspirin desensitization
in a population for which supporting data are sparse.24
Discussion
Numerous studies have demonstrated and validated the
efficacy of aspirin desensitization protocols in a variety of
patient populations. While limited data exist regarding the
desensitization of hypersensitive patients with cardiovas-
cular disease, the Wong and Silberman protocols may pro-
vide an effective and rapid strategy to desensitize these pa-
tients with the intention of initiating dual antiplatelet therapy.
We acknowledge the limited experience with rapid aspirin
desensitization protocols in patients with cardiovascular dis-
ease. However, a subset of patients who underwent the Sil-
berman protocol had preexisting cardiovascular disease with
an indication for coronary stenting. The success of this proto-
col suggests that desensitization of patients requiring aspirin
as part of dual antiplatelet therapy is possible.
The Wong protocol22 may be associated with a lower
complication rate, as it begins with an aspirin dose of 0.1
mg as opposed to 1 or 5 mg in the Silberman protocols.27
The lower starting dose allows patients who are extremely
sensitive to aspirin to be identified earlier, and the lower
initial doses may reduce the severity with which these pa-
tients may react. The Wong protocol is also shorter and re-
sults in a maintenance dose higher than that achieved with
the Silberman protocol. This allows for greater flexibility
in maintenance dose therapy. While the Wong protocol
used pretreatment with an oral antihistamine, comments
from the authors and the data from Alijotas-Reig et al.24
suggest that this pretreatment may be unnecessary. We be-
lieve that the success and potentially lower risk of adverse
effects of the Wong protocol make it an ideal strategy for
rapid desensitization of patients with type I, III, and IV hy-
persensitivity and an indication for aspirin as a part of dual
antiplatelet therapy.
Treatment failure occurred in 2 patients who presented
with type II hypersensitivity characterized by preexisting
chronic idiopathic urticaria independent of aspirin/NSAID
exposure. The exact mechanism behind the failure is un-
known, although it is hypothesized to be mediated through
leukotriene production. Wong et al.22 suggested that pre-
treatment of these patients with a selective leukotriene re-
ceptor antagonist (montelukast or zafirlukast) and the use
of a longer desensitization protocol may be effective in de-
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sensitizing these patients. Other allergists also support the use
of leukotriene receptor antagonists in attenuating the
leukotriene-mediated reaction.28 Until more data surface re-
garding the desensitization of patients with type II aspirin hy-
persensitivity, rapid desensitization should be avoided.
While limited data exist in desensitizing patients with a
type V anaphylactic reaction, the mechanism of the hyper-
sensitivity suggests that desensitization is possible.10 Steg
et al.26 reported successful desensitization of 4 patients
with aspirin hypersensitivities that presented as anaphylax-
is using the Silberman protocol. While desensitization may
be possible, the procedure poses serious risks. The conse-
quences of a severe anaphylactic reaction may be fatal, and
the risks of desensitization must be weighed against the
possible benefit of aspirin therapy, especially in patients re-
covering from an acute cardiovascular event.
Lastly, the use of β-blockers during desensitization
should be addressed. β-Blocker therapy is essential to pa-
tients in the perimyocardial infarction period. The Silber-
man protocol discontinued therapy with β-blockers prior to
desensitization of patients.27 Despite successful desensiti-
zation of a majority of patients, rescue therapy with a β-ag-
onist may be attenuated in patients concurrently taking β-
blockers. Use of β1-specific antagonists, such as metopro-
lol or atenolol, may reduce the risk of attenuated rescue
therapy should respiratory symptoms develop; however,
this has not been thoroughly investigated.
Summary
Aspirin desensitization can be performed safely in pa-
tients with types I, III, and IV hypersensitivity. Because of
the mentioned benefits and potential for reduced toxicity
associated with the Wong protocol, we recommend this
protocol to desensitize cardiovascular patients with aspirin
hypersensitivity who require dual antiplatelet therapy with
aspirin and clopidogrel. Patients admitted for management
of myocardial infarction are often in an ideal environment
to be closely monitored during the desensitization process
as their aspirin dose is escalated. Since aspirin desensitiza-
tion possesses serious risks, careful evaluation of the pa-
tient’s history and underlying conditions is necessary to
identify whether it is a viable management strategy. Given
the data supporting dual antiplatelet therapy in prevention
of secondary cardiovascular events and the success of
rapid protocols, aspirin desensitization becomes an impor-
tant therapeutic option to ensure optimal pharmacotherapy
to aspirin-hypersensitive patients with an indication for
dual antiplatelet therapy.
Nathaniel A Page, PharmD Student, School of Pharmacy and
Pharmaceutical Sciences, University at Buffalo, Buffalo, NY
Walter S Schroeder PharmD, Clinical Assistant Professor, School
of Pharmacy and Pharmaceutical Sciences, University at Buffalo
The Annals of Pharmacotherapy n 2007 January, Volume 41 n 65
NA Page and WS Schroeder
Reprints: Dr. Schroeder, School of Pharmacy and Pharmaceutical
Science, 317 Cooke Hall, University at Buffalo, Buffalo, NY 14260,
fax 716/645-2886, wss2@buffalo.edu
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pirin sensitivity” (letter). Am J Cardiol 2006;97:294.
EXTRACTO
OBJETIVO: Repasar los protocols disponibles sobre la desensitización
rápida de pacientes con hipersensibilidad al ácido acetilsalicílico (ASA)
con el fin de seleccionar aquellos que son seguros y efectivos y
considerar su uso opcional en la desensitización de pacientes con
síndrome coronario agudo e hipersensibilidad al ASA que requieran de
un tratamiento agudo debido a un evento cardiovascular.
FUENTES DE INFORMACIÓN: MEDLINE (1966– diciembre 2006). Los
términos claves utilizados fueron: sensibilidad a la aspirina, alergia a la
aspirina, desensitización a la aspirina, asma inducida por la aspirina,
terapia con la aspirina, y síndrome de intolerancia a la aspirina.
SELECCIÓN Y MÉTODOS DE EXTRACCIÓN DE INFORMACIÓN: Se seleccionaron
manuscritos describiendo protocolos de desensitización rápida al ASA.
También se examinó la literatura relacionada a la hipersensibilidad al
ASA, desensitización de medicamentos, y el uso del ASA y la terapia
antiplaquetaria dual.
SÍNTESIS: Mientras que los estudios clásicos demuestran que la terapia
antiplaquetaria dual con el ASA y el clopidogrel reducen
significativamente la morbididad y la mortalidad en el síndrome
coronario agudo y “stenting” coronario, los pacientes con
hipersensibilidad al ASA son manajados frecuentemente con el
clopidogrel únicamente sin saber si este tratamiento es una alternativa
adecuada. Aproximadamente el 10% de la población presenta
hipersensibilidad al ASA, la cual se puede manifestar como
exacerbaciones del asma, rinorea, angioedema, urticaria, y anafilaxis. La
reacción de hipersensibilidad al ASA parece ser medida por la
formación de anticuerpos contra el ASA o por la producción excesiva de
leukotriene. El proceso de desensitización involucra el agotamiento de
los mediadores de la reacción así como también la deregulación de los
receptores de leukotriene. En este artículo se repasan 3 protocolos de
desensitización rápida los cuales varían con respecto al intervalo de
dosificación, la dosis inicial, y final de tratamiento.
CONCLUSIONES: Dos grupos de investigadores desarrollaron protocolos
rápidos para desensitizar los pacientes con hipersensibilidad al ASA de
manera segura y efectiva. El protocolo rápido desarrollado por Wong
presenta beneficios sobre otros debido a que comienza con una dosis
baja y termina en menos de 3 horas. Los autores sugieren que este
protocolo puede proveer ventajas específicas sobre los otros debido a su
baja incidencia de efectos adversos, duración corta, y alto grado de éxito
en la desensitización al ASA. Estos factores hacen que el protocolo de
Wong sea una opción atractiva para la desensitización rápida de
pacientes que requieren terapia antiplaquetaria con el ASA y el
clopidogrel durante el período cercano al infarto del miocardio.
Encarnación C Suárez
www.theannals.com
 Desensitization Protocols for Patients with Cardiovascular Disease and Aspirin Hypersensitivity

RÉSUMÉ de données en rapport. Approximativement 10% de la population

OBJECTIF: Faire le point sur les protocoles existants en matière de
désensibilisation rapide des patients hypersensibilisés à l’acide
acétylsalicylique (ASA) et mettre en pratique les données chez les
patients atteints de maladie cardiovasculaire qui bénéficieraient de
traitements antiplaquettaires combinés.
SOURCE DE DONNÉES: Une recherche bibliographique a été menée via
MEDLINE sur la période 1966– décembre 2006. Les principaux termes
de recherche comprenaient: sensibilité à l’aspirine, allergie à l’aspirine,
désensibilisation à l’aspirine, asthme induit à l’aspirine, traitement par
aspirine, et syndrome d’intolérance à l’aspirine.
SÉLECTION DES ÉTUDES ET EXTRACTION DES DONNÉES: Les articles
décrivant des protocoles de désensibilisation rapide à l’aspirine ont été
retenus pour analyse. La littérature relative à l’hypersensibilité à l’ASA,
la désensibilisation aux médicaments, et l’usage de l’ASA et des
traitements antiplaquettaires combinés ont aussi été examinés.
SYNTHÈSE DES DONNÉES: Alors que des études de référence démontrent
que le traitement antiplaquettaire combiné ASA-clopidogrel réduit
significativement la mortalité et la morbidité dans les syndromes
coronariens aigus et le stenting coronaire, les patients hypersensibilisés à
l’ASA sont couramment traités au clopidogrel seul, sans qu’il n’existe
connaît une hypersensibilité à l’ASA qui peut se manifester par
exacerbations d’asthme, rhinorrhées, angioedème, urticaire, et
anaphylaxie. La réaction d’hypersensibilité est produite par des anticorps
directs à l’ASA ou par un excès de production de leucotriènes. Les
procédures de désensibilisation mettent en œuvre la déplétion de ces
médiateurs tout comme la freination des récepteurs aux leucotriènes.
Trois protocoles de désensibilisation rapide sont examinés qui diffèrent
par leurs intervalles d’administration, les doses de départ et de fin.
CONCLUSIONS: Deux groupes d’investigateurs ont développé des
protocoles rapides pour désensibiliser les patients atteints
d’hypersensibilité à l’ASA de manière sûre et efficace. Le protocole
rapide mis au point par Wong apporte des avantages par rapport aux
autres avec sa faible dose de départ et sa réalisation en moins de 3
heures. Nous considérons que ce protocole peut apporter des avantages
spécifiques par rapport aux autres avec sa faible incidence d’effets
indésirables, sa durée courte, et son taux élevé de réussite dans la
désensibilisation à l’ASA. Ces critères font du protocole de Wong une
option attrayante pour la désensibilisation rapide des patients nécessitant
un traitement antiplaquettaire combiné ASA-clopidogrel dans la période
péri-infarctus du myocarde.
Michel Le Duff

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