Are concomitant treatments confounding factors in randomized controlled trials on intensive blood-glucose control in type 2 diabetes? a systematic review

International audienceBackgroundOpen-label, randomized controlled trials (RCTs) are subject to observer bias. If patient management is conducted without blinding, a difference between groups may be explained by other factors than study treatment. One factor may come from taking concomitant treatments with an efficacy on the studied outcomes. In type 2 diabetes, some antihypertensive or lipid-lowering drugs are effective against diabetic complications. We wanted to determine if these concomitant treatments were correctly reported in articles of RCTs on type 2 diabetes and if they might have influenced the outcome.MethodsWe performed a systematic review using Medline, Embase, and the Cochrane Library (from January 1950 to July 2010). Open-label RCTs assessing the effectiveness of intensive blood-glucose control in type 2 diabetes were included. We chose five therapeutic classes with proven efficacy against diabetes complications: angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor antagonists (AIIRAs), fibrates, statins, and aspirin. Differences between concomitant treatments were considered statistically significant when p ResultsA total of eight open-label RCTs were included, but only three (37.5%) of them published concomitant treatments. In two studies (ACCORD and ADVANCE), a statistically significant difference was observed between the two groups for aspirin (p = 0.02) and ACEIs (p = 0.02).ConclusionsFew concomitant treatments were published in this sample of open-label RCTs. We cannot completely eliminate an observer bias for these studies. This bias probably influenced the results to an extent that has yet to be determined

Effect of intensive glucose lowering treatment on all cause mortality, cardiovascular death, and microvascular events in type 2 diabetes: meta-analysis of randomised controlled trials

Objective To determine all cause mortality and deaths from cardiovascular events related to intensive glucose lowering treatment in people with type 2 diabetes

The Global Risk Approach Should Be Better Applied in French Hypertensive Patients: A Comparison between Simulation and Observation Studies

The prediction of the public health impact of a preventive strategy provides valuable support for decision-making. International guidelines for hypertension management have introduced the level of absolute cardiovascular risk in the definition of the treatment target population. The public health impact of implementing such a recommendation has not been measured.We assessed the efficiency of three treatment scenarios according to historical and current versions of practice guidelines on a Realistic Virtual Population representative of the French population aged from 35 to 64 years: 1) BP≥160/95 mm Hg; 2) BP≥140/90 mm Hg and 3) BP≥140/90 mm Hg plus increased CVD risk. We compared the eligibility following the ESC guidelines with the recently observed proportion of treated amongst hypertensive individuals reported by the Etude Nationale Nutrition Santé survey. Lowering the threshold to define hypertension multiplied by 2.5 the number of eligible individuals. Applying the cardiovascular risk rule reduced this number significantly: less than 1/4 of hypertensive women under 55 years and less than 1/3 of hypertensive men below 45 years of age. This was the most efficient strategy. Compared to the simulated guidelines application, men of all ages were undertreated (between 32 and 60%), as were women over 55 years (70%). By contrast, younger women were over-treated (over 200%).The global CVD risk approach to decide for treatment is more efficient than the simple blood pressure level. However, lack of screening rather than guideline application seems to explain the low prescription rates among hypertensive individuals in France. Multidimensional analyses required to obtain these results are possible only through databases at the individual level: realistic virtual populations should become the gold standard for assessing the impact of public health policies at the national level

Reappraisal of Metformin Efficacy in the Treatment of Type 2 Diabetes: A Meta-Analysis of Randomised Controlled Trials

Catherine Cornu and colleagues performed a meta-analysis of randomised controlled trials of metformin efficacy on cardiovascular morbidity or mortality in patients with type 2 diabetes and showed that although metformin is considered the gold standard, its benefit/risk ratio remains uncertain

Key Learning Outcomes for Clinical Pharmacology and Therapeutics Education in Europe: A Modified Delphi Study.

Harmonizing clinical pharmacology and therapeutics (CPT) education in Europe is necessary to ensure that the prescribing competency of future doctors is of a uniform high standard. As there are currently no uniform requirements, our aim was to achieve consensus on key learning outcomes for undergraduate CPT education in Europe. We used a modified Delphi method consisting of three questionnaire rounds and a panel meeting. A total of 129 experts from 27 European countries were asked to rate 307 learning outcomes. In all, 92 experts (71%) completed all three questionnaire rounds, and 33 experts (26%) attended the meeting. 232 learning outcomes from the original list, 15 newly suggested and 5 rephrased outcomes were included. These 252 learning outcomes should be included in undergraduate CPT curricula to ensure that European graduates are able to prescribe safely and effectively. We provide a blueprint of a European core curriculum describing when and how the learning outcomes might be acquired

The analysis of cardiovascular risk reduction by pharmacological antihypertensive treatment : towards an individualized prescription

Le traitement antihypertenseur (TAH) réduit le risque cardiovasculaire (RCV). Son efficacité est établie à partir de nombreux essais et méta-analyses conduits sur différentes populations. L’effet du TAH suit en moyenne un modèle multiplicatif différent d’une classe médicamenteuse à l’autre et non constant dans le temps. Pour progresser vers une prescription personnalisée du TAH, nous avons suivi 3 objectifs: 1) La modélisation statistique de l’effet du TAH sur le risque d’accidents vasculaires cérébraux (AVC) et d’infarctus (IDM) dans différents sous-groupes de patients, selon le temps et la classe médicamenteuse. 2) La méta-analyse de l’effet du TAH sur le risque d’AVC, d’IDM et de mortalité après 80 ans, situation de prescription fréquente. 3) La mise en place, conduite et coordination de l’essai clinique IDEAL, randomisé en plan croisé et double insu dont l’objectif est d’étudier l’influence des caractéristiques individuelles sur la réponse pressionnelle à 2 classes de TAH. Les 2 premiers travaux ont été réalisés sur la base INDANA, méta-analyse sur données individuelles des essais évaluant le TAH contre placebo. Ils suggèrent sans être définitivement convaincants que la réduction du bénéfice au cours du temps sur le risque d’infarctus est plus nette chez la femme et sous bêtabloquants. Chez les patients très âgés le TAH reste efficace pour réduire le RCV, mais notre analyse de l’absence de réduction de la mortalité nous conduit à recommander d’éviter toute intensification du TAH à cet âge. L’essai IDEAL a inclus 124 patients chez lesquels la régression à la moyenne et l’évolution sous placebo expliquent une baisse de pression de même ordre que le TAH.Antihypertensive treatment (AHT) reduces cardiovascular risk (CVR). Its efficacy is well established from numerous clinical trials and meta-analysis conducted in several populations. The AHT effect follows on average a multiplicative model. This model is different from one drug class to another, and is not constant during follow-up.In order to progress towards a personalized prescription of AHT, we followed 3 objectives: 1) The statistical modelling of AHT effect on stroke (ST) and myocardial infarction (MI) in different sub-groups of patients,depending on time of follow-up and first line drug class. 2) The meta-analysis of AHT effect on the risk of stroke,MI and total mortality in patients ages 80 years and older in whom AHT is frequently prescribed. 3) The set-up,conduct and coordination of the IDEAL study, a cross-over randomized double blind clinical trial in order to assess the influence of individual characteristics on blood pressure (BP) response to two AHT drug classes. The first two analyses were performed on the INDANA database, an individual patient data meta-analysis from trials that evaluated the effect of AHT against placebo. These analyses suggest that the decreased benefit of AHT over timeon MI prevention was mostly apparent in women and with first line beta-blocker. Treatment remained efficient invery old patients in reducing CVR, but the lack of mortality reduction led us not to recommend AHT intensificationin this age group. The IDEAL study included 124 patients for which the regression to the mean and the evolution under placebo phenomena explained a BP reduction similar to the one under AHT

Dual antiplatelet therapy after acute coronary syndrome: a cardiologist-based optimal decision

International audienc

Hazard regression model and cure rate model in colon cancer relative survival trends: are they telling the same story?

Hazard regression models and cure rate models can be advantageously used in cancer relative survival analysis. We explored the advantages and limits of these two models in colon cancer and focused on the prognostic impact of the year of diagnosis on survival according to the TNM stage at diagnosis. The analysis concerned 9,998 patients from three French registries. In the hazard regression model, the baseline excess death hazard and the time-dependent effects of covariates were modelled using regression splines. The cure rate model estimated the proportion of 'cured' patients and the excess death hazard in 'non-cured' patients. The effects of year of diagnosis on these parameters were estimated for each TNM cancer stage. With the hazard regression model, the excess death hazard decreased significantly with more recent years of diagnoses (hazard ratio, HR 0.97 in stage III and 0.98 in stage IV, P 0.5). The two models were complementary and concordant in estimating colon cancer survival and the effects of covariates. They provided two different points of view of the same phenomenon: recent years of diagnosis had a favourable effect on survival, but not on cure