Postponement of Death by Statin Use: a Systematic Review and Meta-analysis of Randomized Clinical Trials.

BACKGROUND: The average postponement of the outcome (gain in time to event) has been proposed as a measure to convey the effect of preventive medications. Among its advantages over number needed to treat and relative risk reduction is a better intuitive understanding among lay persons. OBJECTIVES: To develop a novel approach for modeling outcome postponement achieved within a trial's duration, based on published trial data and to present a formalized meta-analysis of modeled outcome postponement for all-cause mortality in statin trials. METHODS: The outcome postponement was modeled on the basis of the hazard ratio or relative risk, the mortality rate in the placebo group and the trial's duration. Outcome postponement was subjected to a meta-analysis. We also estimated the average outcome postponement as the area between Kaplan-Meier curves. Statin trials were identified through a systematic review. RESULTS: The median modeled outcome postponement was 10.0 days (interquartile range, 2.9-19.5 days). Meta-analysis of 16 trials provided a summary estimate of outcome postponement for all-cause mortality of 12.6 days, with a 95% postponement interval (PI) of 7.1-18.0. For primary, secondary, and mixed prevention trials, respectively, outcome postponements were 10.2 days (PI, 4.0-16.3), 17.4 days (PI, 6.0-28.8), and 8.5 days (PI, 1.9-15.0). CONCLUSIONS: The modeled outcome postponement is amenable to meta-analysis and may be a useful approach for presenting the benefits of preventive interventions. Statin treatment results in a small increase of average survival within the duration of a trial. SYSTEMATIC REVIEW REGISTRATION: The systematic review was registered in PROSPERO [CRD42016037507] .

Effect of Allopurinol on Cardiovascular Outcomes in Hyperuricemic Patients: A Cohort Study.

BACKGROUND: Hyperuricemia and gout have been associated with increased cardiovascular risk. Allopurinol is an effective urate-lowering drug. Whether lowering of urate by allopurinol improves the cardiovascular risk in hyperuricemic patients remains to be established. OBJECTIVE: Our objective was to investigate the effect of allopurinol on cardiovascular outcomes in hyperuricemic patients in an observational setting. METHODS: We had access to a study population consisting of all patients from Funen County, Denmark with high urate levels (≥6 mg/dL) from 1992 to 2010. We linked 4 registries; all blood samples, all in- and outpatient contacts in hospitals, all reimbursed prescriptions and causes of death. We identified all incident allopurinol users and matched them 1:1 to nonusers of urate-lowering therapy, with similar urate levels, by using propensity scores. Hazard ratios were calculated using competing risk regression model, with respect to Antiplatelet Trialists' Collaboration composite outcome (myocardial infarction, stroke, or cardiovascular death) and all-cause mortality. RESULTS: Among 65,971 patients with hyperuricemia, we found 7127 patients on allopurinol treatment. In the propensity score-matched cohort we found a hazard ratio of 0.89 (95% confidence interval, 0.81-0.97) for the main outcome among allopurinol treated compared with nonusers of allopurinol. The corresponding hazard ratio for all-cause mortality was 0.68 (95% confidence interval, 0.62-0.74). CONCLUSION: Allopurinol treatment is associated with a decreased cardiovascular risk among hyperuricemic patients.

Is urate crystal precipitation a predictor of cardiovascular risk in hyperuricemic patients? A Danish cohort study.

INTRODUCTION: There is increasing evidence that both hyperuricemia and gout increase the risk of cardiovascular morbidity and mortality. Whether urate crystal precipitation confers a particular risk above what is already inherent in having hyperuricemia is not well established. We conducted this cohort study to establish whether the presence of monosodium urate crystal precipitation per se is associated with increased risk of cardiovascular diseases among hyperuricemic patients. METHODS: We identified hyperuricemic individuals who had joint fluid examinations for urate crystals. Individuals with intra-articular urate crystals were matched by propensity score to individuals without crystals and compared with respect to a composite cardiovascular endpoint. Included in the propensity score model were potential confounders retrieved from four different health care registries. RESULTS: We identified 862 hyperuricemic patients having urate crystal examination. After propensity score matching, we could include 317 patients with urate crystals matched 1:1 to patients without urate crystals. We found no difference between the two groups with respect to cardiovascular outcomes (hazard ratios = 0.86; 95 % confidence interval (CI) 0.52 - 1.43) or death (hazard ratio 0.74; CI 0.45 - 1.21). CONCLUSION: The presence of urate crystal precipitations does not seem to confer a particular cardiovascular risk in hyperuricemic patients.

SearCh for humourIstic and Extravagant acroNyms and Thoroughly Inappropriate names For Important Clinical trials (SCIENTIFIC): qualitative and quantitative systematic study.

OBJECTIVES: To describe the development of acronym use across five major medical specialties and to evaluate the technical and aesthetic quality of the acronyms. DESIGN: Acronyms obtained through a literature search of Pubmed.gov followed by a standardised assessment of acronym quality (BEAUTY and CHEATING criteria). PARTICIPANTS: Randomised controlled trials within psychiatry, rheumatology, pulmonary medicine, endocrinology, and cardiology published between 2000 and 2012. MAIN OUTCOME MEASURES: Prevalence proportion of acronyms and composite quality score for acronyms over time. RESULTS: 14,965 publications were identified, of which 18.3% (n=2737) contained an acronym in the title. Acronym use was more common among cardiological studies than among the other four medical specialties (40% v 8-15% in 2012, P<0.001). Except for within cardiology, the prevalence of acronyms increased over time, with the average prevalence proportion among the remaining four specialties increasing from 4.0% to 12.4% from 2000 to 2012 (P<0.001). The median combined acronym quality score decreased significantly over the study period (P<0.001), from a median 9.25 in 2000 to 5.50 in 2012. CONCLUSION: From 2000 to 2012 the prevalence of acronyms in trial reports increased, coinciding with a substantial decrease in the technical and aesthetic quality of the acronyms. Strict enforcement of current guidelines on acronym construction by journal editors is necessary to ensure the proper use of acronyms in the future.

Use of exenatide and liraglutide in Denmark: a drug utilization study.

PURPOSE: The purpose of this study was to characterise the utilization of the glucagon-like peptide-1 (GLP-1) analogues exenatide and liraglutide in Denmark. METHODS: From the Danish National Prescription Registry, we extracted all prescriptions for either liraglutide or exenatide twice-daily in the period 1 April 2007 to 31 December 2012. Using descriptive statistics, we calculated incidence rates, prevalence proportions, daily consumption, and concomitant drug use. For a subset of users we included data from other registries and characterised the baseline characteristics of incident users of GLP-1 analogues. RESULTS: We identified 21,561 and 2,354 users of liraglutide and exenatide respectively. From market entry in 2009 liraglutide showed an increasing prevalence reaching 2.4 per thousand inhabitants in 2012. Exenatide ranged between 0.01 and 0.25 per thousand inhabitants from 2007 to 2012. Treatment intensity showed geographical variation ranging from 1.84per thousand inhabitants to 3.22 per thousand inhabitants for liraglutide. Average doses were 1.34 mg/day (liraglutide) and 16.4 µg/day (exenatide). Treatment initiation was most often performed by a hospital physician and was not associated with any changes in concomitant treatment with antihypertensives, cholesterol-lowering drugs or anticoagulants. Of liraglutide and exenatide users, 38 % and 43 % also used insulin. Low kidney function (eGFR < 30 ml/min) was found in 10.1 % and 9.0 % of users of liraglutide and exenatide respectively. CONCLUSIONS: The preferred GLP-1 analogue in Denmark is liraglutide. Certain aspects of the utilization of GLP-1 analogues, such as large regional differences and concomitant use of GLP-1 analogues and insulin, warrant further investigation.