Matt Fisher

An Assessment of the Joint Associations of Aspirin and Statin Use with C-Reactive Protein Concentration

BACKGROUND The use of aspirin alone and statins alone has been shown to reduce markers of inflammation, including C-reactive protein (CRP); however, their combination has been poorly studied. METHODS In a cross-sectional analysis of black and white adults > or =45 years old from the REGARDS cohort, the associations of aspirin and statin use with CRP were examined. Individuals requiring nonsteroidal anti-inflammatory drug therapy or those taking aspirin for reasons other than cardioprotection were excluded from analysis. Participants were classified into 1 of 4 groups: aspirin only (n = 3,673), statin only (n = 1,898), both agents (n = 3,008), or neither agent (n = 7,718). RESULTS Estimated mean CRP was 2.78 mg/L for subjects taking neither drug, 2.73 mg/L with aspirin only, 2.29 mg/L with statins only, and 2.03 mg/L for subjects taking both agents. The combined use of both agents was associated with an apparent synergistically lower CRP; the mean CRP level among these combined users was 0.21 mg/L lower than that anticipated from additive association related to aspirin and statins alone (P for interaction = .01). Associations were larger among participants reporting a history of cardiovascular disease. In addition, among statin users, the use of aspirin for >5 years compared with < or =5 years was associated with apparent significantly lower CRP concentrations (P = .01). CONCLUSIONS The combined use of aspirin and statins was associated with a synergistically lower CRP concentration, especially among participants taking aspirin for >5 years. Given the limitations of this study and the modest associations, randomized controlled trial evidence is needed to confirm the findings.

Assessment of the Efficacy and Safety Profiles of Aspirin and Acetaminophen With Codeine: Results From 2 Randomized, Controlled Trials in Individuals With Tension-Type Headache and Postoperative Dental Pain

BACKGROUND Aspirin is a widely used NSAID that has been extensively studied in numerous conditions. Nonprescription analgesics, such as aspirin, are frequently used for a wide variety of common ailments, including conditions such as dental pain and tension-type headache. OBJECTIVE We sought to compare the efficacy and safety profiles of aspirin, acetaminophen with codeine, and placebo in the treatment of post-operative dental pain and tension-type headache. METHODS These were 2 randomized, double-blind, placebo-controlled, single-dose clinical trials that assigned participants (2:2:1) to receive either aspirin (1000 mg), acetaminophen (300 mg) with codeine (30 mg), or placebo. The primary efficacy end point was the sum of pain intensity differences from baseline (SPID) over 6 hours for the dental pain study and over 4 hours for the tension-type headache study. Other common analgesic measures, in addition to safety, were also evaluated. RESULTS The results of the dental pain study for aspirin and acetaminophen with codeine suggest statistically significant efficacy for all measures compared with placebo at all time points. Aspirin provided statistically significant efficacy compared with acetaminophen with codeine for SPID(0-4) (P = 0.028). In the tension-type headache study, aspirin and acetaminophen with codeine provided statistically significant efficacy compared with placebo for SPID(0-4) and SPID(0-6) (P < 0.001) and for total pain relief (P < 0.001). There were no significant differences between aspirin and acetaminophen with codeine at any evaluation of SPID (P ≥ 0.070), complete relief (P ≥ 0.179), or time to meaningful relief (P ≥ 0.245). Regarding safety, there were no statistically significant differences between treatment groups in the incidence of adverse events in the dental pain and tension-type headache studies. CONCLUSIONS These 2 randomized, double-blind, placebo-controlled studies demonstrate that treatment with aspirin (1000 mg) provides statistically significant analgesic efficacy compared with placebo use and comparable efficacy with acetaminophen (300 mg) with codeine (30 mg) therapy after impacted third molar extraction and in tension- type headache.

The dose of aspirin for the prevention of cardiovascular and cerebrovascular events

ABSTRACT Background: Low dose aspirin (ASA) (75–325 mg daily) is commonly used for the secondary prevention of cardiovascular and cerebrovascular events, as recommended by US national guidelines. Questions remain, however, as to whether there is a difference in the efficacy and safety across this low dose range. Scope: Double-blind controlled studies, meta-analyses, and observational analyses were reviewed to assess the body of evidence regarding the safety and efficacy of aspirin dosing. Findings: Only one double-blind study directly compared two doses of aspirin within the recommended low dose range. No difference in efficacy or safety was observed, although there was a trend toward greater efficacy with ASA 325 mg vs. ASA 81 mg. Three meta-analyses did not find a difference in bleeding events within the low dose range, while one found that higher doses were associated with more events. One meta-analysis found ASA 75–150 mg was as effective as ASA 160–325 mg. Observational analyses of low dose (75–325 mg) ASA from two large controlled trials differed in their results. One study found no difference in the number of cardiovascular/cerebrovascular events, and a significant improvement in mortality with higher doses, while the other found that higher doses were associated with more events. Conclusion: There does not appear to be a difference in safety across the low dose range of 75–325 mg based on randomized controlled trial data. Furthermore, ASA 325 mg daily appears to be at least as effective as 75 mg daily. Since the optimal dose of ASA for primary and secondary prevention of events in the broad population is uncertain, dosing considerations should include an evaluation of a patients individual clinical status as well as an overall cardiovascular and cerebrovascular benefit vs. risk assessment.

Letter by Fisher and Johns Regarding Article, “Variable Platelet Response to Aspirin and Clopidogrel in Atherothrombotic Disease”

To the Editor: We read with great interest the recent review by Maree and Fitzgerald.1 They should be congratulated for their informative summary of a quickly evolving area. However, we are concerned about their comments in the Aspirin Formulation section of the article. In this section, they …

Gastrointestinal Effects of the Addition of Ascorbic Acid to Aspirin

Nonsteroidal anti‐inflammatory drugs (NSAIDs), including aspirin, have been associated with the damage to the gastrointestinal tract. One proposed mechanism of injury to the gastrointestinal mucosa by NSAIDs is oxygen radical‐dependent microvascular injury. There is reasonable evidence to support the benefit of the addition of ascorbic acid, an ingredient with antioxidant properties, to moderate the adverse gastrointestinal (GI) effects of aspirin. Pharmacokinetic data have demonstrated that aspirin and ascorbic acid combination therapy can assist in mitigating the decrease in levels of ascorbic acid secondary to aspirin monotherapy. Endoscopic evaluation has demonstrated that the addition of ascorbic acid to aspirin significantly improves Lanza scores and rates of blood loss when compared to aspirin administration alone. When taken with ascorbic acid, the patient‐reported tolerability of aspirin has been shown to be comparable to paracetamol and placebo. The existing body of evidence is relevant to short‐term therapy with analgesic aspirin doses, and extrapolation to long‐term therapy with low‐dose aspirin is not appropriate. The purported benefit of an aspirin and ascorbic acid combination is a local observance and is not suspected to influence the adverse GI effects experienced as a result of systemic prostaglandin inhibition. Nevertheless, ascorbic acid may be a viable addition to the strategies employed to improve the gastrointestinal tolerability of aspirin.

Comment and Reply on: The dose of aspirin for the prevention of cardiovascular and cerebrovascular events

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