Aspirin: Promise and Resistance in the New Millennium

Abstract

Abstract-Although conceived at the end of the 19th century, aspirin remains the gold standard of antiplatelet therapy.Approximately 100 randomized clinical trials have established its efficacy and safety in the prevention of myocardial infarction, ischemic stroke, and vascular death among high-risk patients treated for a few weeks, at one end of the spectrum, and in low-risk subjects treated up to 10 years at the other. Despite this wealth of data, several issues continue to be debated concerning the use of aspirin as an antiplatelet agent, and novel opportunities appear on the horizon for this 110-year-old drug. These issues include: (1) the optimal dose for cardiovascular prophylaxis; (2) the uncertain threshold of cardiovascular risk for its use in primary prevention; (3) the apparent gender-related difference in its cardioprotective effects; (4) the increasingly popular theme of aspirin "resistance"; (5) the opportunities of chemoprevention in colorectal cancer; and (6) the renewed interest in aspirin as an analgesic agent in osteoarthritic patients at high cardiovascular risk. The aim of this review is to address these issues by integrating our current understanding of the molecular mechanism of action of the drug with the results of clinical trials and epidemiological studies of aspirin as an antiplatelet drug. A lthough conceived at the end of the 19th century, aspirin remains the gold standard of antiplatelet therapy. Approximately 100 randomized clinical trials have established its efficacy and safety in the prevention of myocardial infarction, ischemic stroke, and vascular death among highrisk patients treated for a few weeks, at one end of the spectrum, and in low-risk subjects treated up to 10 years at the other. 1,2 Despite this wealth of data, several issues continue to be debated concerning the use of aspirin as an antiplatelet agent, and novel opportunities appear on the horizon for this 110-year-old drug. These issues include: (1) the optimal dose for cardiovascular prophylaxis; (2) the uncertain threshold of cardiovascular risk for its use in primary prevention; (3) the apparent gender-related difference in its cardioprotective effects; (4) the increasingly popular theme of aspirin "resistance"; (5) the opportunities of chemoprevention in colorectal cancer; and (6) the renewed interest in aspirin as an analgesic agent in osteoarthritic patients at high cardiovascular risk.The aim of this review is to address these issues by integrating our current understanding of the molecular mechanism of action of the drug with the results of clinical trials and epidemiological studies of aspirin as an antiplatelet drug. The Optimal Dose of AspirinPlacebo-controlled randomized trials have shown that aspirin is an effective antithrombotic agent when used long term in doses ranging between 50 and 100 mg/d, and there is a suggestion that it is effective in doses as low as 30 mg/d. 2,3 Aspirin in a dose of 75 mg/d was shown to be effective in reducing the risk of acute myocardial infarction (MI) or death in pati...

Platelet Response to Aspirin in Chinese Stroke Patients is Independent of Genetic Polymorphisms of COX-1 C50T and COX-2 G765C

“…In our study, the prevalence of AR and ASR by the historical gold standard of OPA was 20.4% and 4.4%, respectively, somewhat lower than that found in other studies 35,36) . OPA was performed to evaluate AR, which is a widely available method routinely used to assess platelet function.…”

Urinary 11‐Dehydro‐Thromboxane B 2 as a Predictor of Acute Myocardial Infarction Outcomes: Results of Leukotrienes and Thromboxane In Myocardial Infarction (LTIMI) Study

“…Further, intense thrombotic and concomitant acute inflammatory processes present in AMI induce TX synthesis from sources other than platelets, mostly inflammatory (monocytes and macrophages) and endothelial cells 22. These cells produce TX mainly via the COX‐2 pathway and stimulate platelets despite their inhibition by aspirin 23. Aspirin in small doses blocks irreversibly COX‐1–dependent TX production; however, inhibition of COX‐2 pathway requires much higher doses of aspirin 2…”

Effects of policosanol on the recovery of ischemic stroke: a randomized controlled study

“…Several studies and meta-analyses support the merits of antiplatelet drugs in stroke prevention by lowering platelet function, which reduces thrombotic complications of atherosclerosis [5][6][7][8]. Aspirin (AS) remains the gold standard of antiplatelet therapy for stroke prevention, whereas extended release dypiridamole + AS has yielded the best results among combination therapy schemes [5][6][7][8].…”

“…Aspirin (AS) remains the gold standard of antiplatelet therapy for stroke prevention, whereas extended release dypiridamole + AS has yielded the best results among combination therapy schemes [5][6][7][8]. Policosanol, a mixture of 8 high molecular weight sugarcane wax alcohols, has reduced platelet aggregation in experimental and clinical studies [9][10][11][12][13].…”