Search

Background and purposeClopidogrel is an antiplatelet drug that is metabolized to its active form by the CYP2C19 enzyme. The CHANCE trial (Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events) found a significant interaction between loss-of-function allele status for the CYP2C19 gene and the effect of dual antiplatelet therapy with aspirin and clopidogrel on the rate of early recurrent stroke following acute transient ischemic attack/minor stroke. The POINT (Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke Trial), similar in design to CHANCE but performed largely in North America and Europe, demonstrated a reduction in early recurrent stroke with dual antiplatelet therapy compared with aspirin alone. This substudy was done to evaluate a potential interaction between loss-of-function CYP2C19 alleles and outcome by treatment group in POINT.MethodsOf the 269 sites in 10 countries that enrolled patients in POINT, 134 sites participated in this substudy. DNA samples were genotyped for CYP2C19 *2, *3, and *17 alleles and classified as being carriers or noncarriers of loss-of-function alleles. Major ischemia consisted of ischemic stroke, myocardial infarction, or ischemic vascular death.ResultsNine hundred thirty-two patients provided analyzable DNA. The rates of major ischemia were 6.7% for the aspirin group versus 2.3% for the dual antiplatelet therapy group (hazard ratio, 0.33 [95% CI, 0.09-1.21]; P=0.09) among carriers of loss-of-function allele. The rates of major ischemia were 5.6% for the aspirin group versus 3.7% for the dual antiplatelet therapy group (hazard ratio, 0.65 [95% CI, 0.32-1.34]; P=0.25) among noncarriers. There was no significant interaction by genotype for major ischemia (P=0.36) or stroke (P=0.33).ConclusionsThis substudy of POINT found no significant interaction with CYP2C19 loss-of-function carrier status and outcome by treatment group. Failure to confirm the findings from the CHANCE trial may be because the loss-of-function alleles tested are not clinically important in this context or because the 2 trials had differences in racial/ethnic composition. Additionally, differences between the 2 trials might be due to chance as our statistical power was limited to 50%. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00991029.

BackgroundCombination antiplatelet therapy with clopidogrel and aspirin may reduce the rate of recurrent stroke during the first 3 months after a minor ischemic stroke or transient ischemic attack (TIA). A trial of combination antiplatelet therapy in a Chinese population has shown a reduction in the risk of recurrent stroke. We tested this combination in an international population.MethodsIn a randomized trial, we assigned patients with minor ischemic stroke or high-risk TIA to receive either clopidogrel at a loading dose of 600 mg on day 1, followed by 75 mg per day, plus aspirin (at a dose of 50 to 325 mg per day) or the same range of doses of aspirin alone. The dose of aspirin in each group was selected by the site investigator. The primary efficacy outcome in a time-to-event analysis was the risk of a composite of major ischemic events, which was defined as ischemic stroke, myocardial infarction, or death from an ischemic vascular event, at 90 days.ResultsA total of 4881 patients were enrolled at 269 international sites. The trial was halted after 84% of the anticipated number of patients had been enrolled because the data and safety monitoring board had determined that the combination of clopidogrel and aspirin was associated with both a lower risk of major ischemic events and a higher risk of major hemorrhage than aspirin alone at 90 days. Major ischemic events occurred in 121 of 2432 patients (5.0%) receiving clopidogrel plus aspirin and in 160 of 2449 patients (6.5%) receiving aspirin plus placebo (hazard ratio, 0.75; 95% confidence interval [CI], 0.59 to 0.95; P=0.02), with most events occurring during the first week after the initial event. Major hemorrhage occurred in 23 patients (0.9%) receiving clopidogrel plus aspirin and in 10 patients (0.4%) receiving aspirin plus placebo (hazard ratio, 2.32; 95% CI, 1.10 to 4.87; P=0.02).ConclusionsIn patients with minor ischemic stroke or high-risk TIA, those who received a combination of clopidogrel and aspirin had a lower risk of major ischemic events but a higher risk of major hemorrhage at 90 days than those who received aspirin alone. (Funded by the National Institute of Neurological Disorders and Stroke; POINT ClinicalTrials.gov number, NCT00991029 .).

ObjectiveTo characterize progression of geographic atrophy (GA) associated with age-related macular degeneration in AREDS as measured by digitized fundus photographs.MethodsFundus photographs from 181 of 4757 AREDS participants with a GA area of at least 0.5 disc areas at baseline or from participants who developed bilateral GA during follow-up were scanned, digitized, and evaluated longitudinally. Geographic atrophy area was determined using planimetry. Rates of progression from noncentral to central GA and of vision loss following development of central GA included the entire AREDS cohort.ResultsMedian initial lesion size was 4.3 mm(2). Average change in digital area of GA from baseline was 2.03 mm(2) (standard error of the mean, 0.24 mm(2)) at 1 year, 3.78 mm(2) (0.24 mm(2)) at 2 years, 5.93 mm(2) (0.34 mm(2)) at 3 years, and 1.78 mm(2) (0.086 mm(2)) per year overall. Median time to developing central GA after any GA diagnosis was 2.5 years (95% confidence interval, 2.0-3.0). Average visual acuity decreased by 3.7 letters at first documentation of central GA, and by 22 letters at year 5.ConclusionsGrowth of GA area can be reliably measured using standard fundus photographs that are digitized and subsequently graded at a reading center. Development of GA is associated with subsequent further growth of GA, development of central GA, and loss in central vision.

OBJECTIVE:To estimate the psychometric properties of a vision-targeted measure of health-related quality of life, the National Eye Institute-Refractive Error Quality of Life survey (NEI-RQL), which includes 13 scales designed to assess the impact of refractive error and its correction on day-to-day life. DESIGN:Cross-sectional survey. PARTICIPANTS:The NEI-RQL was self-administered by 667 myopes, 380 hyperopes, and 114 emmetropes recruited from the practices of 6 medical centers. All participants had near and distance visual acuity of 20/32 or better in the worse eye while benefiting from their current method for correction of refractive error (glasses, contact lens, refractive surgery). METHODS:Mean scores, standard deviations, internal consistency reliability, and test-retest intraclass correlations were estimated for the NEI-RQL scales. Item discrimination was assessed by item-scale correlations. Construct validity was evaluated by assessing the sensitivity of scale scores to type of refractive error, type of refractive error correction, and spherical equivalent. Construct validity of the NEI-RQL was compared to those of the Medical Outcomes Study 36-item short-form health survey (SF-36) and the National Eye Institute Vision Functioning Questionnaire (NEI VFQ-25) in a random subsample of respondents. MAIN OUTCOME MEASURES:The 13 NEI-RQL scales-clarity of vision, expectations, near vision, far vision, diurnal fluctuations, activity limitations, glare, symptoms, dependence on correction, worry, suboptimal correction, appearance, and satisfaction with correction. RESULTS:Emmetropes tended to score significantly better on the NEI-RQL scales than myopes and hyperopes. The method of refractive error correction was also associated with NEI-RQL scores. In addition, the NEI-RQL multi-item scales accounted for 29% of the variance in the NEI-RQL satisfaction with correction item beyond that explained by the SF-36 and the NEI VFQ-25. CONCLUSION:These results support the reliability and construct validity of the NEI-RQL. The instrument appears to be useful for comparisons of people with different types of correction for refractive error.

ObjectiveTo identify the content area for a questionnaire designed to measure the vision-targeted, health-related quality of life for persons with well-corrected refractive error.DesignCross-sectional study.ParticipantsFifty-two focus groups were conducted with 414 patients from 5 geographically diverse ophthalmic and optometric sites to identify the content area of a questionnaire for use among persons with myopia and hyperopia.MethodsA standard protocol was used to structure each focus group discussion, and groups were led by centrally trained moderators at each participating site. Results were summarized and analyzed using a standard set of codes. Qualitative and quantitative analyses were conducted.Main outcome measureSelf-reported observations or comments about vision, vision correction, and other aspects of quality of life.ResultsAmong the 414 participants, 9262 mentions of comments were recorded. The most frequent comments reported by participants were about types of vision correction, followed by comments with their own vision and vision-related symptoms. The distribution of comments by topic domain was generally similar across types of correction and type of refractive error. The most frequent specific comments about glasses concerned problems with reading, adjustment between near and far vision, and appearance. The most frequent comments about contact lenses included those on symptoms such as dry eyes, itching and tired eyes, and headaches, and negative comments about ease of use. The most frequent comments among patients with surgical correction concerned fewer driving problems; fewer symptoms; and improvement in vision, recreation, and comfort. Participants provided equal numbers of positive and negative comments about glasses. Twice as many positive as negative comments were given by contact lens wearers, and 4 times as many positive comments were provided by patients who had undergone surgical correction.ConclusionsUsing focus groups, we were able to identify content areas and aspects of visual functioning in persons with refractive error that are not measured by standard visual acuity testing in the clinic or by other vision-targeted, health-related quality of life instruments such as the 25- or 51-item National Eye Institute-Visual Functioning Questionnaire. The similarity of problems mentioned across refractive error type and correction method suggests it will be possible to develop a single questionnaire with adequate content validity to compare the impact of different modes of correction in vision-targeted, health-related quality of life.

Purpose: This study was designed to identify which of 3 treatments for aspiration on thin liquids--chin-down posture, nectar-thickened liquids, or honey-thickened liquids--results in the most successful immediate elimination of aspiration [...]