We have read with great enthusiasm the recently published article by
Krasopoulos and coworkers. Platelets have a central role in the
development of arterial thrombosis and subsequent cardiovascular events.
An appreciation of this complex process has made antiplatelet therapy the
cornerstone of cardiovascular disease management. On the other hand,
patients on antiplatelet medication continue to suffer atherothrombotic
complications. Their meta-analysis showed the associatuion between
laboratory and clinical aspirin resistance based on different methods.
This is in concordance with the statement of Wang et al who suggested
that a new era of individualized antiplatelet therapy may arise with
routine measurements of platelet activity in the same way that
cholesterol, blood pressure, and blood sugar are followed, thus improving
the care for millions of people (2).
On the other hand, no clear and generally accepted definition of
aspirin resistance has been achieved up to now. Furthermore, previous
studies found no association between the widely used platelet function
tests (3,4) and thereby these test may are not comperable with each other.
The broad use of statins, angiotensin receptor blockers and selective
serotonin reuptake inhibitors may be in part responsible for the lack of
agreement among the laboratory tests because each of these drug classes
per se inhibits platelets by different pathways (5). Our previous results
showed the effect of different cardiovascular drugs on the laboratory
efficacy of aspirin (6). Based on these results the term aspirin
resistance should be based on the difference of platelet aggregation
between the pre-treated and the aspirin treated stage, not using any other
medications.
Krasopoulos and his coworkers also showed that aspirin resistant
patients did not benefit from other antiplatelet treatment. This result
should be interpreted carefully. A previous in vitro study showed the
association between increased platelet response to ADP and aspirin
resistance (7). Eikelboom et al raised the possibility that the clinical
benefits of adding clopidogrel to aspirin may be greatest in patients
whose platelets are least inhibited by aspirin (8). In another study, the
addition of clopidogrel to aspirin provided greater inhibition of
platelets and could overcome aspirin resistance (9). Pamukcu et al. found
associatin between aspirin resistance and poor clinical otucome in AICS
patients and also showed that the prevalence of major acute cardiac events
in patients who were on clopidogrel treatment for 12 months were
significantly lower compared to those who were on a clopidogrel treatment
for the first six months. In another study, aspirin resistance was also
associated with clinical outcome, but the poor outcome increased just
after cessation of clopidogrel therapy (11).
In conclusion, platelet function tests seem to be important
techniques which are frequently used by hemostaseologists and researchers.
Their widespread clinical use is substantially limited due to complex
preanalytic factors, reduced specificity and reproducibility. The
results of these tests may become more comparable after the
standardization of the different methods. The definition and clinical
importance of aspirin resistance should be based on the results of
randomized, prospective studies. There is also no clear evidence in the
treatment of aspirin resistance.
(1) Krasopoulos G, Brister SJ, Beattie WS, Buchanan MR.Aspirin
"resistance" and risk of cardiovascular morbidity: systematic review and
meta-analysis.BMJ. 2008 Jan 26;336(7637):195-8.
(2) Wang TH, Bhatt DL, Topol EJ.Aspirin and clopidogrel resistance:
an emerging clinical entity.Eur Heart J. 2006 Mar;27(6):647-54.
(3) Harrison P, Segal H, Silver L, Syed A, Cuthbertson FC, Rothwell
PM.Lack of reproducibility of assessment of aspirin responsiveness by
optical aggregometry and two platelet function tests.Platelets. 2008
Mar;19(2):119-24.
(4) Lordkipanidzé M, Pharand C, Schampaert E, Turgeon J, Palisaitis
DA, Diodati JG.A comparison of six major platelet function tests to
determine the prevalence of aspirin resistance in patients with stable
coronary artery disease.Eur Heart J. 2007 Jul;28(14):1702-8.
(5) Malinin AI, Ong S, Makarov LM, Petukhova EY, Serebruany
VL.Platelet inhibition beyond conventional antiplatelet agents: expanding
role of angiotensin receptor blockers, statins and selective serotonin
reuptake inhibitors.Int J Clin Pract. 2006 Aug;60(8):993-1002.
(6) Feher G, Koltai K, Papp E, Alkonyi B, Solyom A, Kenyeres P,
Kesmarky G, Czopf L, Toth K. Aspirin resistance: possible roles of
cardiovascular risk factors, previous disease history, concomitant
medications and haemorrheological variables. Drugs Aging. 2006;23(7):559-
67.
(7) Macchi L, Christiaens L, Brabant S, Sorel N, Allal J, Mauco G,
Brizard A. Resistance to aspirin in vitro is associated with increased
platelet sensitivity to adenosine diphosphate. Thromb Res. 2002 Jul
15;107(1-2):45-9.
(8) Eikelboom JW, Hankey GJ, Thom J, Claxton A, Yi Q, Gilmore G,
Staton J, Barden A, Norman PE. Enhanced antiplatelet effect of clopidogrel
in patients whose platelets are least inhibited by aspirin: a randomized
crossover trial. J Thromb Haemost. 2005 Dec;3(12):2649-55.
(9) Dropinski J, Jakiela B, Sanak M, Wegrzyn W, Biernat M, Dziedzina
S, Plutecka H, Szczeklik A.The additive antiplatelet action of clopidogrel
in patients with coronary artery disease treated with aspirin.Thromb
Haemost. 2007 Jul;98(1):201-9.
(10) Pamukcu B, Oflaz H, Oncul A, Umman B, Mercanoglu F, Ozcan M,
Meric M, Nisanci Y. The role of aspirin resistance on outcome in patients
with acute coronary syndrome and the effect of clopidogrel therapy in the
prevention of major cardiovascular events. J Thromb Thrombolysis. 2006
Oct;22(2):103-10.
(11) Pamukcu B, Oflaz H, Onur I, Oncul A, Ozcan M, Umman B,
Mercanoglu F, Meric M, Nisanci Y.Clinical relevance of aspirin resistance
in patients with stable coronary artery disease: a prospective follow-up
study (PROSPECTAR).Blood Coagul Fibrinolysis. 2007 Mar;18(2):187-92.
Competing interests:
None declared
Competing interests:
No competing interests
20 March 2008
Gergely Feher
MD
Andrea Feher, Gabriella Pusch
Department of Neurology, University of Pecs School of Medicine, Pecs, Hungary, Ret utca 2, Pecs, Bar
Rapid Response:
Aspirin resistance: should we test it or not?
We have read with great enthusiasm the recently published article by
Krasopoulos and coworkers. Platelets have a central role in the
development of arterial thrombosis and subsequent cardiovascular events.
An appreciation of this complex process has made antiplatelet therapy the
cornerstone of cardiovascular disease management. On the other hand,
patients on antiplatelet medication continue to suffer atherothrombotic
complications. Their meta-analysis showed the associatuion between
laboratory and clinical aspirin resistance based on different methods.
This is in concordance with the statement of Wang et al who suggested
that a new era of individualized antiplatelet therapy may arise with
routine measurements of platelet activity in the same way that
cholesterol, blood pressure, and blood sugar are followed, thus improving
the care for millions of people (2).
On the other hand, no clear and generally accepted definition of
aspirin resistance has been achieved up to now. Furthermore, previous
studies found no association between the widely used platelet function
tests (3,4) and thereby these test may are not comperable with each other.
The broad use of statins, angiotensin receptor blockers and selective
serotonin reuptake inhibitors may be in part responsible for the lack of
agreement among the laboratory tests because each of these drug classes
per se inhibits platelets by different pathways (5). Our previous results
showed the effect of different cardiovascular drugs on the laboratory
efficacy of aspirin (6). Based on these results the term aspirin
resistance should be based on the difference of platelet aggregation
between the pre-treated and the aspirin treated stage, not using any other
medications.
Krasopoulos and his coworkers also showed that aspirin resistant
patients did not benefit from other antiplatelet treatment. This result
should be interpreted carefully. A previous in vitro study showed the
association between increased platelet response to ADP and aspirin
resistance (7). Eikelboom et al raised the possibility that the clinical
benefits of adding clopidogrel to aspirin may be greatest in patients
whose platelets are least inhibited by aspirin (8). In another study, the
addition of clopidogrel to aspirin provided greater inhibition of
platelets and could overcome aspirin resistance (9). Pamukcu et al. found
associatin between aspirin resistance and poor clinical otucome in AICS
patients and also showed that the prevalence of major acute cardiac events
in patients who were on clopidogrel treatment for 12 months were
significantly lower compared to those who were on a clopidogrel treatment
for the first six months. In another study, aspirin resistance was also
associated with clinical outcome, but the poor outcome increased just
after cessation of clopidogrel therapy (11).
In conclusion, platelet function tests seem to be important
techniques which are frequently used by hemostaseologists and researchers.
Their widespread clinical use is substantially limited due to complex
preanalytic factors, reduced specificity and reproducibility. The
results of these tests may become more comparable after the
standardization of the different methods. The definition and clinical
importance of aspirin resistance should be based on the results of
randomized, prospective studies. There is also no clear evidence in the
treatment of aspirin resistance.
(1) Krasopoulos G, Brister SJ, Beattie WS, Buchanan MR.Aspirin
"resistance" and risk of cardiovascular morbidity: systematic review and
meta-analysis.BMJ. 2008 Jan 26;336(7637):195-8.
(2) Wang TH, Bhatt DL, Topol EJ.Aspirin and clopidogrel resistance:
an emerging clinical entity.Eur Heart J. 2006 Mar;27(6):647-54.
(3) Harrison P, Segal H, Silver L, Syed A, Cuthbertson FC, Rothwell
PM.Lack of reproducibility of assessment of aspirin responsiveness by
optical aggregometry and two platelet function tests.Platelets. 2008
Mar;19(2):119-24.
(4) Lordkipanidzé M, Pharand C, Schampaert E, Turgeon J, Palisaitis
DA, Diodati JG.A comparison of six major platelet function tests to
determine the prevalence of aspirin resistance in patients with stable
coronary artery disease.Eur Heart J. 2007 Jul;28(14):1702-8.
(5) Malinin AI, Ong S, Makarov LM, Petukhova EY, Serebruany
VL.Platelet inhibition beyond conventional antiplatelet agents: expanding
role of angiotensin receptor blockers, statins and selective serotonin
reuptake inhibitors.Int J Clin Pract. 2006 Aug;60(8):993-1002.
(6) Feher G, Koltai K, Papp E, Alkonyi B, Solyom A, Kenyeres P,
Kesmarky G, Czopf L, Toth K. Aspirin resistance: possible roles of
cardiovascular risk factors, previous disease history, concomitant
medications and haemorrheological variables. Drugs Aging. 2006;23(7):559-
67.
(7) Macchi L, Christiaens L, Brabant S, Sorel N, Allal J, Mauco G,
Brizard A. Resistance to aspirin in vitro is associated with increased
platelet sensitivity to adenosine diphosphate. Thromb Res. 2002 Jul
15;107(1-2):45-9.
(8) Eikelboom JW, Hankey GJ, Thom J, Claxton A, Yi Q, Gilmore G,
Staton J, Barden A, Norman PE. Enhanced antiplatelet effect of clopidogrel
in patients whose platelets are least inhibited by aspirin: a randomized
crossover trial. J Thromb Haemost. 2005 Dec;3(12):2649-55.
(9) Dropinski J, Jakiela B, Sanak M, Wegrzyn W, Biernat M, Dziedzina
S, Plutecka H, Szczeklik A.The additive antiplatelet action of clopidogrel
in patients with coronary artery disease treated with aspirin.Thromb
Haemost. 2007 Jul;98(1):201-9.
(10) Pamukcu B, Oflaz H, Oncul A, Umman B, Mercanoglu F, Ozcan M,
Meric M, Nisanci Y. The role of aspirin resistance on outcome in patients
with acute coronary syndrome and the effect of clopidogrel therapy in the
prevention of major cardiovascular events. J Thromb Thrombolysis. 2006
Oct;22(2):103-10.
(11) Pamukcu B, Oflaz H, Onur I, Oncul A, Ozcan M, Umman B,
Mercanoglu F, Meric M, Nisanci Y.Clinical relevance of aspirin resistance
in patients with stable coronary artery disease: a prospective follow-up
study (PROSPECTAR).Blood Coagul Fibrinolysis. 2007 Mar;18(2):187-92.
Competing interests:
None declared
Competing interests: No competing interests