Aspirin resistance: possible roles of cardiovascular risk factors, previous disease history, concomitant medications and haemorrheological variables.
OBJECTIVE
Recent studies have described the incidence (approximately one in eight high-risk patients will experience a further atherothrombotic event over a 2-year period) of aspirin (acetylsalicylic acid) resistance and its possible background. The aim of this study was to compare the characteristics (risk profile, previous diseases, medications and haemorrheological variables) of patients in whom aspirin provided effective platelet inhibition with those in whom aspirin was not effective in providing platelet inhibition.


METHODS
599 patients with chronic cardio- and cerebrovascular diseases (355 men, mean age 64 +/- 11 years; 244 women, mean age 63 +/- 10 years) taking aspirin 100-325 mg/day were included in the study. Blood was collected between 8:00am and 9:00am from these patients after an overnight fast. The cardiovascular risk profiles, history of previous diseases, medication history and haemorrheological parameters of patients who responded to aspirin and those who did not were compared. Platelet and red blood cell (RBC) aggregation were measured by aggregometry, haematocrit by a microhaematocrit centrifuge, and plasma fibrinogen by Clauss' method. Plasma and whole blood viscosities were measured using a capillary viscosimeter.


RESULTS
Compared with aspirin-resistant patients, patients who demonstrated effective aspirin inhibition had a significantly lower plasma fibrinogen level (3.3 g/L vs 3.8 g/L; p < 0.05) and significantly lower RBC aggregation values (24.3 vs 28.2; p < 0.01). In addition, significantly more patients with effective aspirin inhibition were hypertensive (80% vs 62%; p < 0.05). Patients who had effective platelet aggregation were significantly more likely to be taking beta-adrenoceptor antagonists (75% vs 55%; p < 0.05) and ACE inhibitors (70% vs 50%; p < 0.05), whereas patients with ineffective platelet aggregation were significantly more likely to be taking HMG-CoA reductase inhibitors (statins) [52% vs 38%; p < 0.05]. Use of statins remained an independent predictor of aspirin resistance even after adjustment for risk factors and medication use (odds ratio 5.92; 95% CI 1.83, 16.9; p < 0.001).


CONCLUSIONS
The mechanisms underlying aspirin resistance are multifactorial. Higher fibrinogen concentrations increase RBC aggregation and can also result in increased platelet aggregation. The higher rate of hypertension in patients with effective platelet aggregation on aspirin could explain the differences in beta-adrenoceptor antagonist and ACE inhibitor use between these patients and aspirin-resistant patients. Furthermore, an additive effect of these drugs may contribute to effective antiplatelet therapy. It is also possible that drug interactions with statins might reduce aspirin bioavailability and/or activity, thereby reducing platelet inhibition in aspirin-resistant patients.
Feher
Gergely
G
First Department of Medicine, Medical School, University of Pecs, Pecs, Hungary. gergely.feher@aok.pte.hu
Koltai
Katalin
K
Papp
Elod
E
Alkonyi
Balint
B
Solyom
Alexander
A
Kenyeres
Peter
P
Kesmarky
Gabor
G
Czopf
Laszlo
L
Toth
Kalman
K
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D001241:Aspirin / Q000627:therapeutic use*; D001809:Blood Viscosity / Q000187:drug effects; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000453:epidemiology; D002449:Cell Aggregation / Q000187:drug effects; D004336:Drug Antagonism; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D004912:Erythrocytes / Q000187:drug effects / Q000502:physiology; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D006400:Hematocrit; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D012307:Risk Factors
D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010975:Platelet Aggregation Inhibitors; D005340:Fibrinogen; D001241:Aspirin