A review on low-dose aspirin for the prevention of atherosclerotic cardiovascular disease (CVD) highlights the following important issues to keep in mind.
The use of medium-dose (75–325 mg/day) aspirin for the prevention of vascular events was supported by an overview of 145 randomized trials of prolonged antiplatelet therapy published by the Antiplatelet Trialists’ Collaboration thirty years ago. These trials were conducted to prevent death, myocardial infarction (MI), and stroke (vascular events).
Because of its short half-life and the rapid resynthesis of any acetylated COX-2 in nucleated cells, aspirin at low doses completely blocks platelet cyclooxygenase (COX)-1 activity while largely sparing clinically relevant sites of COX-2 activity (e.g., renal cells and endothelial cells of the vasculature).
The pharmacokinetics of aspirin are very straightforward, requiring minimal metabolic activation, with an oral bioavailability of around 50% and a half-life of 15 to 20 minutes. However, inadequate platelet inhibition may ensue, especially in heavier persons, from decreased bioavailability of some enteric-coated preparations of low-dose aspirin and poor absorption from the higher pH environment of the small intestine.
Once-daily dosing with low-dose aspirin (162.5 mg) initiated within 24 hours of the onset of symptoms of a suspected MI resulted in highly significant reductions in nonfatal stroke by 46%, nonfatal reinfarction by 49%, and 5-week vascular mortality (the primary endpoint) by 23% in over 17,000 patients in the Second International Study of Infarct Survival.
Long-term (2–3 years) aspirin therapy delivers clear net benefit on the risk of subsequent MI, stroke, or vascular death among subjects at high risk of vascular complications, as shown by a significant number of placebo-controlled randomized clinical trials (RCTs).
P2Y12 inhibitors (ticlopidine, clopidogrel, or ticagrelor) or aspirin were randomly assigned to 42,108 patients in nine RCTs. The meta-analysis found that patients who received P2Y12 inhibitors had a marginally lower risk of MI than those who received aspirin (odds ratio, 0.81; 95% confidence interval [CI], 0.66–0.99). There was no difference in the risks of stroke, all-cause death, and vascular death between those treated with a P2Y12 inhibitor and those taking aspirin.
Low-dose aspirin administration did not significantly reduce the incidence of CVD compared to placebo in the ASPREE study, which included 19,114 healthy elderly people (median age, 74 years) without known CVD (hazard ratio [HR], 0.95; 95% CI, 0.83–1.08).
Because aspirin has a short half-life and acetylated COX isozymes resynthesis quickly in nucleated epithelial cells, low-dose aspirin appears to spare COX-1 and COX-2 function in the gastrointestinal (GI) mucosa. When low-dose aspirin is used chronically, there is an absolute excess of gastrointestinal difficulties. This excess can range from 6 per 10,000 in a young individual without a history of GI problems to 600 per 10,000 in an elderly person who has had a complex ulcer in the past. Proton-pump inhibitors, in example, are gastro-protectant treatments that lower the risk of peptic ulcer disease and associated complications in a variety of clinical settings, although their usage in patients on antiplatelet medications is still relatively limited.
Both COX inhibitors and conventional nonsteroidal anti-inflammatory medications have COX-2-dependent renal effects that have the potential to acutely lower renal function and impede blood pressure regulation. Because of its relative COX-1 selectivity, low-dose aspirin does not worsen blood pressure regulation, affect renal function, or raise the risk of heart failure.
Aspirin has been shown to have a chemopreventive impact on cancer, especially gastrointestinal tract cancers, according to several lines of evidence. These comprise meta-analyses of post hoc, long-term follow-up of aspirin RCTs for primary and secondary prevention of CVD, as well as observational studies indicating a consistent relationship between regular aspirin usage and decreased risk of gastric, esophageal, and colorectal cancer.
Highlights of the Summary:
Given the lack of a regulatory superiority claim and the recommendations of current cardiovascular treatment guidelines, it is unlikely that currently available P2Y12 inhibitors will replace aspirin in the current therapeutic armamentarium due to the lack of convincing evidence of their superiority over low-dose aspirin.
Even with the abundance of data supporting the safety and effectiveness of low-dose aspirin as an antithrombotic drug, aspirin use for secondary prevention is still generally lacking, especially in low-income nations. Instead of switching out one antiplatelet medication for another, efforts to meet this unmet therapeutic need would have a significantly greater impact on worldwide CVD prevention.
Those with a moderate-to-high risk of cardiovascular disease (CVD) are more likely to experience cardiovascular events if they discontinue their aspirin treatment or do not comply with guidelines. Therefore, patients who are prescribed antiplatelet therapy should be encouraged to continue it for as long as the benefit/risk profile is deemed favorable.
