Karen E. Ramsey

Effect on high-density lipoprotein cholesterol of maximum dose simvastatin and atorvastatin in patients with hypercholesterolemia: Results of the Comparative HDL Efficacy and Safety Study (CHESS)☆

BACKGROUND Previous studies have shown that effects on high-density lipoprotein cholesterol (HDL-C) may differ among statins. METHODS A multicenter, randomized, double-blind, parallel-dose study was conducted in 917 hypercholesterolemic patients to compare the efficacy of 80 mg/d simvastatin versus 80 mg/d atorvastatin on HDL-C and apolipoprotein (apo) A-I for 24 weeks. Efficacy was assessed as the means of weeks 6 and 12 and weeks 18 and 24. Prespecified subgroups analyzed were patients with low HDL-C levels and with the metabolic syndrome. RESULTS Simvastatin increased HDL-C and apo A-I values significantly more than did atorvastatin for the mean of weeks 6 and 12 (8.9% vs 3.6% and 4.9% vs -0.9%, respectively) and the mean of weeks 18 and 24 (8.3% vs 4.2% and 3.7% vs -1.4%). These differences were observed across both baseline HDL-C subgroups (<40 mg/dL, > or =40 mg/dL) and in patients with the metabolic syndrome. Low-density lipoprotein cholesterol and triglyceride reductions were greater with atorvastatin. Consecutive elevations >3x the upper limit of normal in alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) occurred in significantly fewer patients treated with simvastatin than with atorvastatin (2/453 [0.4%] vs 13/464 [2.8%]), with most elevations observed in women taking atorvastatin (11/209 [5.3%] vs 1/199 [0.5%] for simvastatin). CONCLUSIONS Simvastatin (80 mg) increased HDL-C and apo A-I significantly more than did atorvastatin (80 mg) in patients with hypercholesterolemia. This advantage was observed regardless of HDL-C level at baseline or the presence of the metabolic syndrome. Significantly fewer consecutive elevations >3x the upper limit of normal in ALT and/or AST occurred in patients receiving simvastatin.

Efficacy of Rizatriptan 10 mg administered early in a migraine attack.

Objective.—To determine if administration of rizatriptan 10 mg is superior to placebo for the early treatment of acute migraine, while the pain is mild.

Rizatriptan for the acute treatment of ICHD-II proposed menstrual migraine: two prospective, randomized, placebo-controlled, double-blind studies

These are the first prospective studies to use criteria for menstrual migraine proposed in the 2004 revision of the International Classification of Headache Disorders (ICHD-II) to examine the efficacy of rizatriptan for treatment of a menstrual attack. Two identical protocols (MM1 and MM2) were randomized, parallel, placebo-controlled, double-blind studies. Adult women with ICHD-II menstrual migraine were assigned to either rizatriptan 10-mg tablet or placebo in a 2 : 1 ratio. Patients treated a single menstrual migraine attack of moderate or severe pain intensity. The primary end-point was 2-h pain relief and the secondary end-point was 24-h sustained pain relief. A total of 707 patients (MM1 357, MM2 350) treated a menstrual migraine attack. The percentage of patients reporting 2-h pain relief was significantly greater for rizatriptan than for placebo (MM1 70% vs. 53%, MM2 73% vs. 50%), as was the percentage of patients reporting 24-h sustained pain relief (MM1 46% vs. 33%; MM2 46% vs. 33%). Rizatriptan 10 mg was effective for the treatment of ICHD-II menstrual migraine, as measured by 2-h pain relief and 24-h sustained pain relief.

Symptoms of cutaneous sensitivity pre‐treatment and post‐treatment: results from the rizatriptan TAME studies

The presence of cutaneous allodynia may predict response to triptans. Identical randomized double-blind studies were conducted comparing the efficacy of rizatriptan 10 mg or placebo administered within 1 h of headache onset, while pain was mild. The primary endpoint was freedom from pain at 2 h. Presence of symptoms suggesting cutaneous sensitivity (SCS) at baseline and at 2 h post-treatment was recorded. Before treatment, 29% of rizatriptan patients and 22% of placebo patients reported SCS. At 2 h, the percentage of patients with SCS was significantly decreased with rizatriptan. The presence of SCS pre-treatment was not predictive of response to rizatriptan. Most patients with SCS at 2 h were non-responders. Early treatment with rizatriptan significantly reduced the percentage of patients with SCS at 2 h. The presence of SCS at baseline did not predict pain-free response, but presence of SCS at 2 h correlated with lack of a 2-h pain-free response.

Efficacy of Rizatriptan for Menstrual Migraine in an Early Intervention Model: A Prospective Subgroup Analysis of the Rizatriptan TAME (Treat A Migraine Early) Studies

Objective.— A prospective subgroup analysis of the TAME (Treat A Migraine Early) studies examined the efficacy of rizatriptan in patients treating a menstrual migraine attack.

Rizatriptan Efficacy in ICHD-II Pure Menstrual Migraine and Menstrually Related Migraine

Objective.— To examine the efficacy of rizatriptan for the treatment of pure menstrual migraine (PMM).

Rizatriptan 10-mg ODT for Early Treatment of Migraine and Impact of Migraine Education on Treatment Response

Objective.— To examine the efficacy of rizatriptan 10‐mg orally disintegrating tablet (ODT) for treating migraines of mild intensity soon after onset, with or without patient‐specific migraine education.

Total migraine freedom, a potential primary endpoint to assess acute treatment in migraine: comparison to the current FDA requirement using the complete rizatriptan study database.

Objective.— To examine total migraine freedom (TMF), defined as pain freedom and absence of associated symptoms, using rizatriptan clinical trial data and to explore advantages of TMF as a single primary composite efficacy endpoint.

Pharmacokinetic Profile of Rizatriptan 10-mg Tablet and 10-mg Orally Disintegrating Tablet Administered With or Without Water in Healthy Subjects: An Open-Label, Randomized, Single-Dose, 3-Period Crossover Study

This open‐label, 3‐period crossover study compared the plasma concentration profiles of rizatriptan tablet, orally disintegrating tablet with water (ODTc), and ODT without water (ODTs) in 24 healthy volunteers aged 18 to 45 years. At each period, subjects received a single dose of either 10‐mg rizatriptan tablet, 10‐mg rizatriptan ODTs, or 10‐mg rizatriptan ODTc. The authors hypothesized that ODTc has a greater geometric mean AUC0–2h than ODTs and that ODTc has a greater geometric mean AUC0–1h than tablet. A secondary end point was to compare the time of occurrence of the maximum rizatriptan plasma concentration (tmax) of each dosing method. ODTc had a statistically significantly greater geometric mean AUC0–2h compared with ODTs (33.84 h•ng/mL vs 18.83h•ng/mL;P < .001). ODTc had a slightly, but not statistically significantly, greater geometric mean AUC0–1h compared with rizatriptan tablet (17.07h•ng/mL vs 13.32 h•ng/mL). The median tmax was 0.67 hours for ODTc and tablet and 1.33 hours for ODTs. ODTc showed a slightly, but not significantly, faster rate of absorption compared with tablet. ODTs with water had a faster rate of absorption than ODTc. Future studies are needed to determine whether this pharmacokinetic difference produces differential efficacy in a clinical setting.

Elimination of Migraine-Associated Nausea in Patients Treated with Rizatriptan Orally Disintegrating Tablet (ODT): A Randomized, Double-Blind, Placebo-Controlled Study

Objective.— To confirm the efficacy of rizatriptan 10 mg orally disintegrating tablet (ODT) for the elimination of migraine‐associated nausea.