Inhibition of Clinical Benefits of Aspirin on First Myocardial Infarction by Nonsteroidal Antiinflammatory Drugs

Kurth, Tobias; Glynn, Robert J.; Walker, Alexander M.; Chan, K. Arnold; Buring, Julie E.; Hennekens, Charles H.; Gaziano, J. Michael

doi:10.1161/01.cir.0000087593.07533.9b

Cited by 232 publications

(103 citation statements)

References 30 publications

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“…20,21,32,33 Additionally, the concomitant administration of ibuprofen seems to antagonize the irreversible platelet inhibition induced by aspirin 34 and may also be associated with increased thrombotic complications. 35,36 Clopidogrel offers added antiplatelet efficacy to aspirin in patients with acute coronary syndromes 3 or after stent implantation. 6 It is possible, however, that the clinical benefit of clopidogrel is more complementary than additive.…”

Section: Discussionmentioning

confidence: 99%

Contribution of Hepatic Cytochrome P450 3A4 Metabolic Activity to the Phenomenon of Clopidogrel Resistance

et al. 2004

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Background-Interindividual variability of platelet inhibition after aspirin or clopidogrel administration has been described. Additionally, aspirin resistance and clopidogrel resistance occur in some individuals. Because the prodrug clopidogrel is activated by hepatic cytochrome P450 (CYP) 3A4, we hypothesized that interindividual variability in clopidogrel efficacy might be related to interindividual differences in CYP3A4 metabolic activity. Methods and Results-Platelet aggregation was measured before and after clopidogrel treatment in 32 patients undergoing coronary artery stent implantation and in 35 healthy volunteers. The erythromycin breath test was used to measure CYP3A4 activity in vivo in 25 of the healthy volunteers. Individual platelet aggregation was studied in 10 healthy volunteers after the coadministration of clopidogrel and rifampin (a CYP3A4 inducer). Clopidogrel nonresponders, low responders, and responders were defined by a relative inhibition of adenosine diphosphate (20 mol/L)-induced platelet aggregation of Ͻ10%, 10% to 29%, and Ն30%, respectively. Among patients, 22% were clopidogrel nonresponders, 32% were low responders, and 47% were responders. Among volunteers, 16% were nonresponders, 12% were low responders, and 72% were responders. Percent platelet aggregation after clopidogrel inversely correlated with CYP3A4 activity (rϭϪ0.6, Pϭ0.003). Improved platelet inhibition in volunteers resistant to clopidogrel was observed with the coadministration of clopidogrel and rifampin. Conclusions-Clopidogrel administration results in interindividual variability in platelet inhibition, which correlates with CYP3A4 metabolic activity. Measurement of antiplatelet drug efficacy with a point-of-care device and alternative antithrombotic strategies for aspirin or clopidogrel nonresponders and low responders could reduce the incidence of thrombotic events that continue to occur despite oral antiplatelet therapy. Key Words: drugs Ⅲ platelets Ⅲ pharmacology C lopidogrel, a thienopyridine derivative similar to ticlopidine, is an inhibitor of platelet aggregation induced by adenosine diphosphate (ADP). 1 Clopidogrel was approved by the United States Food and Drug Administration (FDA) in 1997 for the reduction of myocardial infarction, stroke, and vascular death in patients with recent stroke, recent myocardial infarction, or established peripheral arterial disease after the Clopidogrel versus Aspirin in Patients at Risk of Ischemic Events (CAPRIE) trial 2 showed superior reduction of these events with clopidogrel compared with aspirin (annual risk, 5.3% versus 5.8%; Pϭ0.04). Dual antiplatelet therapy (aspirin plus clopidogrel) for acute coronary syndromes was approved by the FDA in 2002 on the basis of the Clopidogrel in Unstable angina to prevent Recurrent ischemic Events (CURE) trial 3 results, which showed a significant reduction in the 9-month composite end point of cardiovascular death, nonfatal myocardial infarction, or stroke versus aspirin monotherapy (9.3% versus 11.4%, PϽ0.001). Additionally, the c...

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Section: Discussionmentioning

confidence: 99%

Contribution of Hepatic Cytochrome P450 3A4 Metabolic Activity to the Phenomenon of Clopidogrel Resistance

et al. 2004

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“…In healthy volunteers, ibuprofen, but not diclofenac or rofecoxib, impaired aspirin's effect on thromboxane inhibition and platelet aggregation (19). Further evidence emerged from a subanalysis of the Physician's Health Study indicating that nonselective NSAIDs reduce the cardioprotective effect of aspirin in primary prevention of myocardial infarction (20). Moreover, a retrospective study from the United Kingdom concluded that concomitant aspirin and ibuprofen use was associated with an increased risk of cardiacrelated and all-cause mortality (21).…”

Section: Discussionmentioning

confidence: 99%

Effect of cardiovascular comorbidities and concomitant aspirin use on selection of cyclooxygenase inhibitor among rheumatologists

Greenberg

Bingham

Abramson

et al. 2005

Arthritis & Rheumatism

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“…In contrast, sustained exposure to diclofenac, rofecoxib or acetaminophen did not influence the effects of aspirin on platelet function. 94,95 To add to the controversy, another study on the effect of ibuprofen in aspirin-treated healthy adult volunteers showed no clinically meaningful loss of cardioprotection of aspirin when over-the-counter doses of ibuprofen were administered. 96 The gastroprotective benefit of COX-2 inhibitors is partially or, in some patients, totally lost if aspirin is used for cardiovascular prophylaxis.…”

Section: Drug Interactions Of Nsaidsmentioning

confidence: 99%

An Evidence-Based Update on Nonsteroidal Anti-Inflammatory Drugs

Ong¹,

Lirk²,

Tan³

et al. 2007

Clinical Medicine & Research

491

286

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Nonsteroidal anti-inflammatory drugs (NSAIDs), including both traditional nonselective NSAIDs and the selective cyclooxygenase (COX)-2 inhibitors, are widely used for their anti-inflammatory and analgesic effects. NSAIDs are a necessary choice in pain management because of the integrated role of the COX pathway in the generation of inflammation and in the biochemical recognition of pain. This group of drugs has recently come under scrutiny because of recent focus in the literature on the various adverse effects that can occur when applying NSAIDs.This review will provide an educational update on the current evidence of the efficacy and adverse effects of NSAIDs. It aims to answer the following questions: (1) are there clinically important differences in the efficacy and safety between the different NSAIDs, (2) if there are differences, which are the ones that are more effective and associated with fewer adverse effects, and (3) which are the effective therapeutic approaches that could reduce the adverse effects of NSAIDs. Finally, an algorithm is proposed which delineates a general decision-making tree to select the most appropriate analgesic for an individual patient based on the evidence reviewed. Keywords: Analgesics; COX-2 specific inhibitors; NSAIDs; Pain Nonst eroidal anti-inflammatory drugs (NSAIDs) are among the most widely used medications in the world because of their demonstrated efficacy in reducing pain and inflammation. 1 Their efficacy has been documented in a number of clinical disorders, including osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, gout, dysmenorrhea, dental pain and headache. [2][3][4][5][6][7][8] The basic mode of action is inhibition of the pro-inflammatory enzyme cyclooxygenase (COX). NSAIDs as a class comprise both traditional nonselective NSAIDs (tNSAIDs) that nonspecifically inhibit both COX-1 and COX-2, and selective COX-2 inhibitors. Although effective at relieving pain and inflammation, tNSAIDs are associated with a significant risk of serious gastrointestinal adverse events with chronic use. 9 Therefore, specific inhibitors of the COX-2 isoenzyme were developed, thus opening the possibility to provide antiinflammatory and analgesic benefits, while theoretically leaving the gastroprotective activity of the COX-1 isoenzyme intact. However, important concerns have recently been raised regarding the potential cardiovascular toxicity of COX-2 inhibitors. 10This review will provide an educational update of the scientific evidence for the efficacy and adverse effects of NSAIDs in view of the emerging new information for this class of drugs. It is composed deliberately to be a classic, pragmatic review and draws on the results of published systematic reviews and studies regarding the topic. It aims to answer the following questions: (1) are there clinically important differences in the efficacy and safety between the different NSAIDs, (2) if there are differences, which are the ones that are more effective and associated with fewer adverse effects, and (3) which are...

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Inhibition of Clinical Benefits of Aspirin on First Myocardial Infarction by Nonsteroidal Antiinflammatory Drugs

Abstract: Background-There is clear evidence from numerous randomized trials and their meta-analyses that aspirin reduces risks of first myocardial infarction (MI). Recent data also suggest that other nonsteroidal anti-inflammatory drugs (NSAIDs) may interfere with this benefit of aspirin.

Cited by 232 publications

References 30 publications

Contribution of Hepatic Cytochrome P450 3A4 Metabolic Activity to the Phenomenon of Clopidogrel Resistance

Contribution of Hepatic Cytochrome P450 3A4 Metabolic Activity to the Phenomenon of Clopidogrel Resistance

Effect of cardiovascular comorbidities and concomitant aspirin use on selection of cyclooxygenase inhibitor among rheumatologists

An Evidence-Based Update on Nonsteroidal Anti-Inflammatory Drugs

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