Michael Voelker

Efficacy and safety of 1,000mg effervescent aspirin: individual patient data meta-analysis of three trials in migraine headache and migraine accompanying symptoms

Migraine is often associated with health consequences including impaired quality of life, and the cost of treating migraine headaches places a significant financial burden on patients who suffer from migraines. Nonsteroidal anti-inflammatory drugs (NSAIDs) and triptans are commonly used for the treatment of acute migraine attacks. Aspirin is widely accepted as a treatment option for migraine pain relief and could provide an alternative not only for treatment of moderate migraine attacks, but also for severe migraine attacks. The efficacy and safety of 1,000 mg effervescent aspirin (eASA) was evaluated in comparison to 50 mg sumatriptan and placebo in an individual patient data meta-analysis of three randomized, placebo-controlled, single- dose migraine trials. Pain-relief at 2 h, pain-free at 2 h and sustained pain-free up to 24 h were calculated. For eASA, the response rates were 51.5 % (95 % CI: 46.6-56.5 %), 27.1 % (95 % CI: 22.6-31.4 %), and 23.5 % (95 % CI: 19.3-27.7 %). For sumatriptan, the response rates were 46.6 % (95% CI: 40.0-3.2 %), 29% (95 % CI: 23.0-34.9 %), and 22.2 % (95 % CI: 16.7-27.6 %). The corresponding rates for placebo were 33.9 % (95% CI: 29.1-38.6 %), 15.1 % (95 % CI: 11.5-18.7 %), and 14.6 % (95 % CI: 11.0-18.1 %). The treatment effect of eASA and sumatriptan were significantly different from placebo (p < 0.001), but differences between eASA and sumatriptan were not significant. The remission of accompanying symptoms and the subgroup analyses of patients with moderate or severe migraine pain at baseline revealed no significant differences between eASA and sumatriptan. Safety was evaluated based on the frequency of reported adverse events, and treatment with eASA was associated with lower incidence of adverse events than was with sumatriptan. This individual patient data meta-analysis provided evidence that eASA 1,000mg is as effective as sumatriptan 50mg for the treatment of acute migraine attacks and has a better side effect profile. This is also true for patients with moderate as well as severe headache at baseline. Patients therefore should be advised to use eASA first for migraine attacks and use a triptan in case of no response.

Aspirin in the treatment of acute migraine attacks

Acetylsalicylic acid (aspirin or ASA) has been used for many years as an analgesic, antipyretic and anti-inflammatory drug. In recent years, evidence for its effectiveness in migraine headache has been demonstrated in several clinical trials. The effervescent highly buffered preparation of aspirin was shown to be effective, safe and well tolerated compared with placebo or other treatment options. The effervescent aspirin preparation is at least as effective as the combination of aspirin plus metoclopramide, but has fewer side effects. This review summarizes and analyzes clinical data of aspirin in the treatment of acute migraine attacks with respect to the different galenic formulations.

Serum fibrosis markers as predictors of an antifibrotic effect of interferon alfa in children with chronic hepatitis B.

Objective Interferon alfa (IFN-&agr;) may retard hepatic fibrogenesis in adults with chronic hepatitis C. We evaluated prospectively four selected serum fibrosis markers before, immediately after and 12 months after IFN treatment of children with chronic hepatitis B (CHB). Methods Forty-seven children (mean age 8 years, range 4–16) with CHB underwent IFN-&agr; treatment (3 MU t.i.w.) for 5 months. Fibrosis and inflammation were assessed blindly before and 12 months after the end of treatment. Serum laminin-2, collagen IV, MMP-2 and MMP-9/TIMP-1 complex were determined using automated assays. Results Twelve months after treatment had been discontinued levels of laminin-2, collagen IV and MMP-2 were decreased, and serum MMP-9/TIMP-1 complex was increased. Levels did not differ between sustained responders (42.5%) and non-responders. Similarly, fibrosis did not progress in both groups, whereas histological inflammation improved only in responders. Conclusions A 5 month IFN-&agr; treatment has no marked effect on histological liver fibrosis in children with CHB, irrespective of virological response. The evolution of serum fibrosis markers suggests they may be more sensitive to detect minor antifibrotic effects than semiquantitative follow-up histology.

Short-Term Acetylsalicylic Acid (Aspirin) Use for Pain, Fever, or Colds —Gastrointestinal Adverse Effects: A Meta-Analysis of Randomized Clinical Trials

AbstractBackground and Aim: Acetylsalicylic acid (ASA [aspirin]) is a commonly used over-the-counter drug for the treatment of pain, fever, or colds, but data on the safety of this use are very limited. The aim of this study was to provide data on the safety of this treatment pattern, which is of interest to clinicians, regulators, and the public. Methods: A meta-analysis of individual patient data from 67 studies sponsored by Bayer HealthCare was completed. The primary endpoints were patient-reported gastrointestinal (GI) adverse events (AEs); the secondary endpoints were the incidence of patient-reported non-GI AEs. Event incidence and odds ratios (ORs) based on Cochran-Mantel-Haenszel estimates are reported. In total, 6181 patients were treated with ASA, 3515 with placebo, 1145 with acetaminophen (paracetamol), and 754 with ibuprofen. Exposure to ASA was short term (82.5% of patients had a single dose). Results: GI AEs were more frequent with ASA (9.9%) than with placebo (9.0%) [OR 1.3; 95% CI 1.1, 1.5]. Dyspeptic symptoms were infrequent (4.6% in placebo subjects). The ORs for ASA were 1.3 (95% CI 1.1, 1.6) versus placebo; 1.55 (95% CI 0.7, 3.3) versus ibuprofen; and 1.04 (95% CI 0.8, 1.4) versus acetaminophen. There were very few serious GI AEs (one ASA case; three placebo cases). No differences were found for non-GI AEs and no cases of cerebral hemorrhage were reported. Conclusion: Short-term, mostly single-dose exposure to ASA for the treatment of pain, fever, or colds was associated with a small but significant increase in the risk of dyspepsia relative to placebo.No serious GI complications were reported.

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.

Aspirin is First‐Line Treatment for Migraine and Episodic Tension‐Type Headache Regardless of Headache Intensity

Objectives.— (1) To establish whether pre‐treatment headache intensity in migraine or episodic tension‐type headache (ETTH) predicts success or failure of treatment with aspirin; and (2) to reflect, accordingly, on the place of aspirin in the management of these disorders.

Demonstration of the Analgesic Efficacy and Dose-Response of Acetylsalicylic Acid With Pseudoephedrine

To determine acute analgesia by acetylsalicylic acid (ASA) when combined with pseudoephedrine (PSE) in patients with upper respiratory tract infection (URTI), we used the sore throat pain model to measure single‐dose effects of ASA 500 mg/PSE 30 mg, ASA 1000 mg/PSE 60 mg, and acetaminophen (APAP) 1000 mg/PSE 60 mg (serving as a positive control). Under double‐blind, randomized, placebo‐controlled conditions, 640 adult patients with confirmed acute pharyngitis and rhinosinusitis associated with URTI rated throat pain intensity and relief at intervals over 6 hours. Efficacy was demonstrated for both doses of ASA/PSE compared with placebo for all end points, including total pain relief and summed pain intensity differences, beginning at 20 minutes on both scales (all P < .05), and the efficacy of APAP/PSE compared with placebo was confirmed (P < .01). Greater differences in pain relief and intensity were also demonstrated between the higher and lower doses of ASA/PSE (P < .05), in particular, among 329 patients with severe pain, as well as between ASA 1000 mg/PSE 60 mg and APAP 1000 mg/PSE 60 mg (P < .05). No serious adverse events were reported. This study demonstrates that ASA is a well‐tolerated and effective analgesic in 500‐ and 1000‐mg doses when combined with pseudoephedrine.

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.