Apixaban for Patients With Atrial Fibrillation on Hemodialysis: A Multicenter Randomized Controlled Trial.

BACKGROUND: There are no randomized data evaluating the safety or efficacy of apixaban for stroke prevention in patients with end-stage kidney disease on hemodialysis and with atrial fibrillation (AF). METHODS: The RENAL-AF trial (Renal Hemodialysis Patients Allocated Apixaban Versus Warfarin in Atrial Fibrillation) was a prospective, randomized, open-label, blinded-outcome evaluation (PROBE) of apixaban versus warfarin in patients receiving hemodialysis with AF and a CHA2DS2-VASc score ≥2. Patients were randomly assigned 1:1 to 5 mg of apixaban twice daily (2.5 mg twice daily for patients ≥80 years of age, weight ≤60 kg, or both) or dose-adjusted warfarin. The primary outcome was time to major or clinically relevant nonmajor bleeding. Secondary outcomes included stroke, mortality, and apixaban pharmacokinetics. Pharmacokinetic sampling was day 1, day 3, and month 1. RESULTS: From January 2017 through January 2019, 154 patients were randomly assigned to apixaban (n=82) or warfarin (n=72). The trial stopped prematurely because of enrollment challenges. Time in therapeutic range (international normalized ratio, 2.0-3.0) for warfarin-treated patients was 44% (interquartile range, 23%-59%). The 1-year rates for major or clinically relevant nonmajor bleeding were 32% and 26% in apixaban and warfarin groups, respectively (hazard ratio, 1.20 [95% CI, 0.63-2.30]), whereas 1-year rates for stroke or systemic embolism were 3.0% and 3.3% in apixaban and warfarin groups, respectively. Death was the most common major event in the apixaban (21 patients [26%]) and warfarin (13 patients [18%]) arms. The pharmacokinetic substudy enrolled the target 50 patients. Median steady-state 12-hour area under the curve was 2475 ng/mL×h (10th to 90th percentiles, 1342-3285) for 5 mg of apixaban twice daily and 1269 ng/mL×h (10th to 90th percentiles, 615-1946) for 2.5 mg of apixaban twice daily. There was substantial overlap between minimum apixaban blood concentration, 12-hour area under the curve, and maximum apixaban blood concentration for patients with and without a major or clinically relevant nonmajor bleeding event. CONCLUSIONS: There was inadequate power to draw any conclusion regarding rates of major or clinically relevant nonmajor bleeding comparing apixaban and warfarin in patients with AF and end-stage kidney disease on hemodialysis. Clinically relevant bleeding events were ≈10-fold more frequent than stroke or systemic embolism among this population on anticoagulation, highlighting the need for future randomized studies evaluating the risks versus benefits of anticoagulation among patients with AF and end-stage kidney disease on hemodialysis. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02942407.

Development, validation, and proof-of-concept implementation of a two-year risk prediction model for undiagnosed atrial fibrillation using common electronic health data (UNAFIED).

BACKGROUND: Many patients with atrial fibrillation (AF) remain undiagnosed despite availability of interventions to reduce stroke risk. Predictive models to date are limited by data requirements and theoretical usage. We aimed to develop a model for predicting the 2-year probability of AF diagnosis and implement it as proof-of-concept (POC) in a production electronic health record (EHR). METHODS: We used a nested case-control design using data from the Indiana Network for Patient Care. The development cohort came from 2016 to 2017 (outcome period) and 2014 to 2015 (baseline). A separate validation cohort used outcome and baseline periods shifted 2 years before respective development cohort times. Machine learning approaches were used to build predictive model. Patients ≥ 18 years, later restricted to age ≥ 40 years, with at least two encounters and no AF during baseline, were included. In the 6-week EHR prospective pilot, the model was silently implemented in the production system at a large safety-net urban hospital. Three new and two previous logistic regression models were evaluated using receiver-operating characteristics. Number, characteristics, and CHA2DS2-VASc scores of patients identified by the model in the pilot are presented. RESULTS: After restricting age to ≥ 40 years, 31,474 AF cases (mean age, 71.5 years; female 49%) and 22,078 controls (mean age, 59.5 years; female 61%) comprised the development cohort. A 10-variable model using age, acute heart disease, albumin, body mass index, chronic obstructive pulmonary disease, gender, heart failure, insurance, kidney disease, and shock yielded the best performance (C-statistic, 0.80 [95% CI 0.79-0.80]). The model performed well in the validation cohort (C-statistic, 0.81 [95% CI 0.8-0.81]). In the EHR pilot, 7916/22,272 (35.5%; mean age, 66 years; female 50%) were identified as higher risk for AF; 5582 (70%) had CHA2DS2-VASc score ≥ 2. CONCLUSIONS: Using variables commonly available in the EHR, we created a predictive model to identify 2-year risk of developing AF in those previously without diagnosed AF. Successful POC implementation of the model in an EHR provided a practical strategy to identify patients who may benefit from interventions to reduce their stroke risk.

Treatment and discharge patterns among patients hospitalized with non-valvular atrial fibrillation transitioning from the inpatient to outpatient setting.

OBJECTIVE: To evaluate inpatient oral anticoagulant (OAC) treatment, discharge location, and post-discharge OAC treatment for patients hospitalized with non-valvular atrial fibrillation (NVAF). RESEARCH DESIGN AND METHODS: Retrospective study using claims data linked to hospital electronic health records (EHR). Patients (n = 2,484) were hospitalized with a primary (38%) or secondary (62%) diagnosis of AF without evidence of mitral valvular heart disease or valve replacement between January 2009 and September 2013. Inpatient OAC treatment was identified from EHR data. MAIN OUTCOME MEASURES: Inpatient and post-discharge OAC treatment [direct OAC (DOAC; apixaban, rivaroxaban, dabigatran), warfarin, no OAC] and discharge location (long-term care, home health-care, home self-care). RESULTS: Mean age was 72.6 years, 61.2% were male, and 89.5% had a CHA2DS2-VASc score ≥2. Overall, 6.4% received a DOAC, 38.0% warfarin, and 55.6% no OAC during hospitalization. Compared to other treatment groups, patients receiving DOAC were younger and more likely to be male. The majority (72.2%) were discharged to home health-care, 13.2% home self-care, and 6.0% long-term care. Among patients who were treated with warfarin during hospitalization, 40.3% filled a warfarin prescription within 30 days post-discharge, whereas among patients who were treated with a DOAC, 52.4% filled a DOAC prescription within 30 days post-discharge. Some NVAF patients not treated with an OAC during hospitalization filled a prescription for warfarin (18.0%) or DOAC (1.9%) within 30 days post-discharge. Results were similar among patients with CHA2DS2-VASc score ≥2. CONCLUSIONS: Most patients hospitalized for NVAF were discharged to home support, and the majority did not have OAC treatment during hospitalization or the 30 days post-discharge. Additional investigation should be conducted on trends beyond 30 days post-hospitalization, and the reasons for not receiving anticoagulation therapy in patients at moderate-to-severe risk of stroke or systemic embolism. Helping to avoid preventable strokes is an important goal for public health.

The Efficacy of Continuous Versus Intermittent Celecoxib Treatment in Osteoarthritis Patients with Body Mass Index ≥30 and <30 kg/m(2.).

OBJECTIVE: Characterize the effect of body mass index (BMI) on the efficacy of continuous daily celecoxib treatment compared with intermittent celecoxib treatment. METHODS: Prespecified exploratory analysis of a 24-week, double-blind, parallel-group, randomized, multicenter international study. 858 patients with knee or hip osteoarthritis (OA) were randomized to receive celecoxib 200 mg daily either as continuous or intermittent treatment. Efficacy was measured by Western Ontario and McMaster Universities Arthritis Index (WOMAC) total and subscale scores and the number of flare events. RESULTS: Least squares mean increases (worsening) in WOMAC total scores were significantly less in the continuous treatment group than in the intermittent treatment group in patients with a BMI <30 kg/m(2) (1.33 vs 4.85; p=0.016) and in patients with a BMI ≥30 kg/m(2) (1.84 vs 5.12; p=0.019). There was a greater worsening in patients with a BMI ≥30 kg/m(2) than in those with a BMI <30 kg/m(2) in both the continuous and intermittent groups. Fewer flares were reported in the continuous treatment group than in the intermittent group in patients with a BMI <30 kg/m(2) (0.55 vs 0.88; p<0.0001) and ≥30 kg/m(2) (0.54 vs 0.97; p<0.0001). There were no differences in adverse events in the two BMI groups. CONCLUSIONS: Continuous celecoxib treatment was significantly more efficacious than intermittent use in patients with a BMI <30 kg/m(2) compared with obese patients (≥30 kg/m(2)) as assessed by WOMAC total scores and the number of flares. These data suggest that including weight loss as part of a treatment regimen for obese OA patients could be important.

Healthcare resource utilization and economic impact of a ≥2 g/dL decrease in hemoglobin in osteoarthritis patients.

OBJECTIVE: In non-steroidal anti-inflammatory drug (NSAID) users, chronic occult blood loss may lead to decreases in hemoglobin, which may lead to increased healthcare expenditures. This study, therefore, sought to quantify healthcare resource utilization of ≥2 g/dL hemoglobin decrease in osteoarthritis patients. METHODS: Using a large US managed care database, osteoarthritis patients aged ≥18 years who had exposure to ≥90 days of non-selective or selective COX-2 NSAID use, a hemoglobin value within 6 months before index NSAID, and at least one hemoglobin value 24 months after were evaluated. Resource utilization was evaluated in those with ≥2 g/dL hemoglobin drop vs patients with ≤0.5 g/dL hemoglobin drop (control). RESULTS: Of 1800 NSAID users meeting inclusion criteria, 228 patients [mean (SD) = 59.8 (9.3) years] had ≥2 g/dL hemoglobin drop vs 1572 controls [mean (SD) = 58.3 (8.0) years]. Despite relatively low absolute rates, endoscopic procedures were more commonly observed in the ≥2 g/dL hemoglobin drop group [endoscopy: 37/228 (16.2%) vs 65/1572 (4.1%); adjusted odds ratio (AOR) 3.5, (95% confidence interval [CI] = 2.1-6.0); colonoscopy: 36/228 (15.8%) vs 137/1572 (8.7%); AOR 2.0 (95% CI 1.2-3.2)]. During the 12-month follow-up, patients with ≥2 g/dL hemoglobin drop utilized significantly more healthcare resources [adjusted relative risk (95% CI) for hospitalization, 2.1 (1.5-2.9); outpatient visits, 1.4 (1.3-1.5); physician visits, 1.3 (1.1-1.4)] and charges (total adjusted charges $47,766 vs $23,342) across major categories of healthcare services. LIMITATIONS: This was a retrospective analysis with baseline demographic differences. The source or cause of the hemoglobin drops could not be verified; and it is assumed that they are related to occult gastrointestinal loss. Differences with healthcare utilization and charges were not linked to hemoglobin-associated complications. CONCLUSION: In patients exposed to NSAIDs, those with significant hemoglobin drops experienced higher subsequent healthcare utilization and charges than controls who did not have a significant hemoglobin drop.

The APC and PreSAP trials: a post hoc noninferiority analysis using a comprehensive new measure for gastrointestinal tract injury in 2 randomized, double-blind studies comparing celecoxib and placebo.

BACKGROUND: Previous gastrointestinal (GI) outcomes of nonsteroidal anti-inflammatory drug (NSAID) trials have focused on upper GI events, although recent evidence suggests NSAID-related lower GI effects are important and clinically relevant. OBJECTIVE: We assessed the long-term GI adverse event (AE) profile of celecoxib in a nonarthritis population. The aim of this post hoc analysis was to determine the incidence of serious GI AEs, using a new Clinically Significant Upper and/or Lower GI Events end point. METHODS: Patients from 2 colorectal adenoma recurrence studies were included. Patients received celecoxib 200 mg/400 mg BID, 400 mg once daily, or placebo over 3 years. The analysis measured noninferiority, using a prespecified definition of noninferiority. Celecoxib was predefined to be noninferior to placebo if the upper limit of the 95% CI for the hazard ratio (HR) with celecoxib was <1.25, at any dose, compared with the placebo (calculated using the Cox proportional hazards model). RESULTS: A total of 3588 patients were included; in the primary analysis, the HR for celecoxib (any dose) compared with placebo was 1.22 (95% CI: 0.69-2.18; P = 0.4948). In the secondary dose analyses, the HR associated with a 400-mg daily dose, compared with placebo, was 1.04 (95% CI: 0.55-1.96; P = 0.9149); for 800 mg/d, the HR was 1.79 (95% CI: 0.82-3.89; P = 0.1427). In a third covariate analysis, low-dose aspirin use (HR = 2.33; 95% CI: 1.33-4.08) and age ≥65 years (HR = 1.82; 95% CI, 1.05-3.15) was suggested to have a statistically significant association with increased risk of GI AEs. Study limitations include retrospective evaluation and small sample size of patients with GI AEs. CONCLUSIONS: The noninferiority of celecoxib to placebo was not established because the HR for the time to the first Clinically Significant Upper and/or Lower GI Event was greater than the prespecified upper limit of 95% CI for noninferiority. In addition, HRs associated with daily doses of 400 or 800 mg celecoxib compared with placebo were not significant. However, a significantly increased risk of clinically significant upper and/or lower GI events was observed in low-dose aspirin users (≤162.5 mg average daily use) and in patients ≥65 years of age.

Treatment of osteoarthritis with continuous versus intermittent celecoxib.

OBJECTIVE: To determine whether "continuous" celecoxib is more efficacious than "intermittent" use in preventing osteoarthritis (OA) flares of the knee and/or hip. METHODS: A double-blind, randomized, multicenter international study comparing efficacy and safety of continuous (daily) versus intermittent (as required during predefined OA flare) celecoxib 200 mg/day in 858 subjects, aged 18-80 years. The study consisted of 3 periods: (I) screening/washout visit; (II) open-label run-in with celecoxib; and (III) 22-week blinded treatment. Only subjects whose OA flares resolved in Period 2 (without subsequent flare) were randomized. The primary endpoint, number of flares per time of exposure during Period III (number of flares per month), was compared using analysis of variance with treatment as the independent variable. Acetaminophen was available as rescue medication. RESULTS: Of 875 subjects randomized to treatment, 858 subjects received treatment. At randomization > 70% were female; mean age 58.6 years; mean disease duration 6.5 years; total Western Ontario and McMaster Universities Osteoarthritis Index mean score 25.8; ~45% had hypertension; and ~20% were using aspirin (for cardiovascular prophylaxis). Subjects receiving continuous treatment reported 42% fewer OA flares/month than intermittent users (p < 0.0001) or 2.0 fewer OA flares over 22 weeks. Statistical and clinically meaningful benefits in secondary outcomes were also evident with continuous treatment. There were no differences in adverse events (AE) or new-onset/aggravated hypertension. CONCLUSION: Continuous treatment with celecoxib 200 mg/day was significantly more efficacious than intermittent use in preventing OA flares of the hip and knee, without an increase in overall AE, including gastrointestinal disorders and hypertension, during 22 weeks of treatment. ClinicalTrials.gov identifier NCT00139776.

The cross-sectional relationship of hemoglobin levels and functional outcomes in women with self-reported osteoarthritis: results from the Women's Health Initiative.

OBJECTIVES: Gastrointestinal blood loss is a recognized complication of the use of nonsteroidal anti-inflammatory drugs (NSAIDS) in patients with arthritis. We examined the cross-sectional relationship of patient-reported outcomes of overall health, physical function, vitality, and quality of life to hemoglobin (hgb) levels in postmenopausal women with self-reported osteoarthritis to determine whether hgb levels as potential markers of chronic blood loss were associated with these functional outcomes. METHODS: Postmenopausal women (N = 64,850) with self-reported osteoarthritis (srOA) at baseline in the Women's Health Initiative study, excluding participants with chronic or hemolytic diseases associated with anemia, had hgb levels measured and completed Short-Form Health Surveys. General linear models analysis adjusting for potential confounders was performed. RESULTS: A nonlinear plateauing relationship between hgb levels and functional outcomes was found. Participants with srOA had statistically significantly worse overall health, physical function, and vitality, but not quality of life, for each gram of hgb below 14 g/dL, compared with those with hgb 14 g/dL (P < 0.001). Participants with srOA taking NSAIDS had worse functional outcomes for each level of hgb compared with those not reporting NSAIDS use. CONCLUSIONS: In cross-sectional analyses of postmenopausal women with srOA, differences in hgb levels are related to differences in functional outcomes of overall health, physical function, and vitality at clinically important levels. Prospective studies evaluating whether changes in hgb levels result in changes in functional outcomes in participants with osteoarthritis are needed to confirm of our findings and before any changes in therapeutics based on hemoglogin levels are considered in the care of patients with osteoarthritis.

Valdecoxib is as efficacious as diclofenac in the treatment of acute low back pain.

OBJECTIVE: To compare the efficacy of valdecoxib 40 mg q.d. (with a second dose on day 1) with diclofenac 75 mg b.i.d. in the treatment of acute low back pain. METHODS: This was a multicenter, randomized, double-blind study. Patients with acute low back pain, class 1a or 2a (Quebec Task Force), with a visual analog scale score >/=50 mm (on a 100-mm scale) and moderate to severe pain on a categorical scale, were randomized to valdecoxib 40 mg q.d. (with a second dose on day 1) or diclofenac 75 mg b.i.d. for 7 days (170 patients per group). The primary efficacy end point was change in pain intensity (visual analog scale, mm) from baseline to day 3 for the per-protocol population. RESULTS: Least squares mean reductions in pain intensity from baseline to day 3 were similar for valdecoxib (-42.02 mm) and diclofenac (-41.43 mm). Valdecoxib was comparable to diclofenac as the lower limit of the 95% confidence interval of the estimated difference (0.59 mm; 95% confidence interval, -3.40 to 4.59 mm) was within the prespecified noninferiority margin of -10 mm. The overall incidence of adverse events was similar for valdecoxib (28%) and diclofenac (26%). No statistically different moderate or severe upper gastrointestinal adverse events were reported, although they were numerically greater for diclofenac (8) than for valdecoxib (3). DISCUSSION: Valdecoxib 40 mg q.d. (with a second dose on day 1) provides effective relief for acute low back pain, and was at least as efficacious as diclofenac 75 mg b.i.d., with a nonsignificant but numerically lower incidence of gastrointestinal adverse events.

A multicenter, randomized, double-blind, active-comparator, placebo-controlled, parallel-group comparison of the incidence of endoscopic gastric and duodenal ulcer rates with valdecoxib or naproxen in healthy subjects aged 65 to 75 years.

BACKGROUND: Compared with nonselective NSAIDs, cyclooxygenase (COX)-2-selective inhibitors have been associated with a lower incidence of gastroduodenal ulcers (in short-term endoscopic studies) and ulcer complications (in long-term trials). OBJECTIVE: The aim of this study was to compare the effects of valdecoxib 20 mg BID and naproxen 500 mg BID, administered for 6.5 days, on the upper gastrointestinal (UGI) mucosa of healthy older subjects (aged 65-75 years) as assessed by UGI endoscopy. METHODS: In this multicenter, double-blind, active-comparator, placebo-controlled, parallel-group study, eligible subjects who were free of NSAID or COX-2-selective inhibitor use for 2 weeks and who had normal UGI mucosa (mucosal grading score of 0, based on endoscopic evaluation of both the stomach and duodenum) were randomized. Serologic testing for Helicobacter pylori antibodies was conducted at baseline. No antiulcer medications were permitted. The primary end point was the incidence of gastroduodenal ulcers (gastric or duodenal mucosal grading score of 7, as indicated by any lesion with unequivocal depth > or =3 mm in diameter) after 6.5 days of blinded treatment with valdecoxib, naproxen, or placebo. Secondary end points were incidence of gastric ulcers, duodenal ulcers, and gastroduodenal erosions/ulcers, and the incidence of > or =11 gastroduodenal erosions/ulcers. All documented adverse events were self-reported by subjects or were observed by investigators. RESULTS: Sixty-one patients were randomized to receive valdecoxib, 60 to naproxen, and 60 to placebo. Mean (SD) subject age was 68.8 (3.25) years in the valdecoxib group, 68.6 (2.76) years in the naproxen group, and 68.6 (3.14) years in the placebo group (P = NS). In the valdecoxib and naproxen groups, 47.5% and 58.3% of subjects were female, respectively, compared with 56.7% of the placebo group (P = NS). Valdecoxib and placebo were associated with significantly lower incidences of gastroduodenal ulcers than naproxen (1.6% [1 gastroduodenal ulcer/61 patients] and 1.7% [1/59], respectively, vs 22.0% [13/59]; P < 0.001). Compared with naproxen, both valdecoxib and placebo were associated with significantly lower incidences of gastric (1.6% [1/61] and 1.7% [1/59] vs 15.3% [9/59]; both, P < 0.03) and duodenal ulcers (0% [0/61] and 0% [0/59] vs 8.5% [5/59]; both,P < 0.03). In all cases, the incidence of ulcers with valdecoxib was not significantly different from placebo. Results were similar for any erosions/ulcers, and when analyzed by H pylori status. The number of adverse events was low in each group. CONCLUSION: In these healthy older subjects (aged 65-75 years), valdecoxib 20 mg BID was associated with a significantly lower rate of gastroduodenal, gastric, and duodenal ulcers than naproxen 500 mg BID, even after 6.5 days of therapy.

Valdecoxib for treatment of a single, acute, moderate to severe migraine headache.

OBJECTIVE: To evaluate the analgesic efficacy and safety of a single 20- or 40-mg dose of valdecoxib compared with placebo in treatment of a single, acute, moderate or severe migraine headache, with or without aura. BACKGROUND: Valdecoxib, an oral COX-2 specific inhibitor, is indicated for relief of the signs and symptoms of rheumatoid arthritis and osteoarthritis and treatment of primary dysmenorrhea. This study assessed the optimal dose of valdecoxib for treatment of a single, acute, moderate to severe migraine headache. METHODS: This was a double-blind, randomized, placebo- and active-controlled, multicenter, single-dose (primary end point) and multiple-dose (secondary end point), 56-day study of valdecoxib in the treatment of a single, acute, moderate or severe migraine headache, with or without aura. Migraine headaches were diagnosed according to International Headache Society (IHS) criteria. The primary efficacy end point was headache response (defined as reduction of headache pain intensity from moderate or severe to mild or none) at 2 hours postdose. Patients assessed their headache pain intensity and presence or absence of migraine-associated nausea, vomiting, phonophobia, and photophobia at intervals from 0 to 24 hours postdose. Sumatriptan 50 mg (encapsulated, in standard method, to maintain blinding) was included as a positive control for assay sensitivity. No statistical comparisons were performed between active treatment arms (valdecoxib 20 mg, valdecoxib 40 mg, and sumatriptan 50 mg). Adverse events and safety parameters were monitored throughout the study. RESULTS: In the intent-to-treat population of 570 patients (135 valdecoxib 20 mg, 151 valdecoxib 40 mg, 143 sumatriptan, and 141 placebo), no significant differences in baseline demographics among treatment groups were observed. The headache response rate with valdecoxib 40 mg and sumatriptan 50 mg was significantly greater than that with placebo at all time points from 2 to 24 hours postdose. With valdecoxib 20 mg, headache response rate was significantly greater than placebo from 2 to 4 hours. Significantly fewer patients treated with valdecoxib 40 mg, compared with placebo, experienced nausea, vomiting, and phonophobia at 2 hours postdose. CONCLUSIONS: A single 40-mg dose of valdecoxib is effective and well tolerated in treatment of migraine headache pain and associated symptoms.

Prevalence and burden of illness of migraine in managed care patients.

OBJECTIVE: To determine the 3-month prevalence rate of migraine in a health maintenance organization (HMO) population, using a 2-stage screening process and neurologist exam, and to examine the burden of illness associated with both previously diagnosed and previously undiagnosed migraine in this population METHODS: A migraine assessment was sent to a random sample of 1,000 HMO patients between April 1999 and January 2000. Those screening positive and a random sample of those screening negative for migraine were evaluated by neurologists using a structured diagnostic assessment. Then, those diagnosed to have migraines by the study's neurologists completed a battery of 3 questionnaires, evaluating severity, distress, and impairment RESULTS: Of 1,000 questionnaires sent, 753 (75.3%) were returned. The estimate of prevalence of migraine in this population ranged from 21.4% (adjusted for response bias) to 27.8% (unadjusted for selection bias). Only 48% of respondents had been previously diagnosed with migraine. The typical migraine caused moderate-to-severe distress in 69%, and 66% had definite or extreme interference in their social or occupational functioning. The average migraineur missed 7.6 hours of work due to migraine in the past 3 months. Previously undiagnosed migraine was associated with substantial impairment, with 58% of responders reporting interference with daily activities and 54% reporting moderate or greater distress. There was no significant difference between previously diagnosed and undiagnosed migraineurs on 3 outcome measures: pain, interference, or days of missed work. A higher proportion of previously diagnosed migraineurs (84%) reported moderate or greater distress compared with undiagnosed migraineurs (54%, P=0.002). CONCLUSIONS: Using a neurologist exam, the researchers found that the prevalence of migraine headaches was higher than previously reported. About one half of migraineurs had been previously undiagnosed. Undiagnosed migraine is associated with significant pain, distress, and dysfunction and is similar in these respects to diagnosed migraine. Increased public education and physician education on migraine are warranted.

Effectiveness of eletriptan in acute migraine: primary care for Excedrin nonresponders.

OBJECTIVE: To evaluate the effectiveness of eletriptan as a treatment for acute migraine in patients who were poor responders to Excedrin and had not yet been exposed to a triptan. BACKGROUND: Self-medication with over-the-counter drugs, such as Excedrin, is the most common treatment for migraine. Guidelines, however, recommend that triptans be used as first-line treatment of moderate to severe migraine--the severity affecting approximately 80% of migraineurs. Since over-the-counter medications, such as Excedrin, continue to be used in many patients, it is important that clinicians have information on the efficacy of triptans as first-line treatment and on treatment of migraineurs who have shown poor response to over-the-counter medications. METHODS: One hundred ten patients meeting criteria for migraine who were poor responders to Excedrin received open-label treatment with a 40-mg dose of eletriptan for one migraine attack. Efficacy assessments were made at 1, 2, 4, and 24 hours postdose and consisted of headache and pain-free response rates, absence of associated symptoms, and functional response. RESULTS: At 1 hour, the headache response rate was 44%; at 2 hours, 81%. The pain-free response rate at 1 hour was 14% and at 2 hours, 48%. At 2 hours, relief of baseline-associated symptoms ranged from 74% to 80%. Functional response was achieved by 82% of patients by 2 hours, and 68% of patients achieved relief of migraine that was sustained across 24 hours with no need for a second dose of eletriptan or for rescue medication. Eletriptan was well tolerated with adverse events being transient and mild to moderate in intensity. CONCLUSION: Previous studies have established the efficacy of eletriptan as a first-line treatment for migraine. The results of this open-label trial demonstrate that the 40-mg dose of eletriptan had a high degree of efficacy and tolerability among patients who were poor responders to Excedrin.