Comparative effectiveness of antihypertensive monotherapies in primary prevention of cardiovascular events-a real-world longitudinal inception cohort study.

Introduction: Antihypertensive drugs are used preventatively to lower the risk of cardiovascular disease events. Comparative effectiveness studies on angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), beta-blockers (BBs), calcium channel blockers (CCBs), and thiazides have yielded inconsistent results and given little consideration to patient adherence. Using a longitudinal cohort and considering time-varying adherence and confounding factors, we aimed to estimate the real-world effectiveness of five major antihypertensive drug monotherapies in the primary prevention of cardiovascular events. Methods: Eligible patients for a retrospective inception cohort study were selected using information obtained from the University of Groningen IADB.nl pharmacy prescription database. Cohort 1 comprised adherent patients with a follow-up time exceeding 1 year, and cohort 2 comprised all patients independent of adherence. The exposures were ACEIs, ARBs, BBs, CCBs, and thiazides. The primary outcome was the time to the first prescription for an acute cardiac drug therapy (CDT) measured using valid drug proxies to identify the first major cardiovascular event. A per-protocol analytical approach was adopted with inverse probability of treatment weighted (IPTW), time-varying Cox regression analysis to obtain the hazard ratios (HRs) and 95% confidence intervals (CIs). Results: In cohort 1 (n = 22,441), 1,294 patients (5.8%) were prescribed an acute CDT with an average follow-up time of 4.2 ± 2.8 years. Following IPTW, the hazard measures of ARBs and thiazides were lower than those of BBs (HRs: 0.79 and 0.80, respectively; 95% CIs: 0.64-0.97 and 0.69-0.94, respectively). Among drug-treated diabetic patients, the hazard measures were even lower, with HR point estimates of 0.43 (CI: 0.19-0.98) for ARBs and 0.32 (CI: 0.13-0.82) for thiazides. In cohort 2 (n = 33,427) and sensitivity analysis, the comparative effectiveness results for thiazides and BBs were similar to those for cohort 1. Conclusion: The findings of this real-world analysis suggest that the incidence of CDT associated with long-term thiazide or ARB monotherapy is lower than the incidence of CDT with BBs, notably among high-risk patients. Incidences of CDT associated with ACEIs and CCBs were comparable relative to those associated with BBs.

Do efficacy results obtained from randomized controlled trials translate to effectiveness data from observational studies for relapsing-remitting multiple sclerosis?

BACKGROUND: Randomized controlled trials are considered the gold standard in regulatory decision making, as observational studies are known to have important methodological limitations. However, real-world evidence may be helpful in specific situations. This review investigates how the effect estimates obtained from randomized controlled trials compare to those obtained from observational studies, using drug therapy for relapsing-remitting multiple sclerosis as an example. STUDY DESIGN AND SETTING: A systematic review of randomized controlled trials and observational studies was conducted. The primary outcome was the annualized relapse rate. Using (network) meta-analysis together with posterior predictive distributions, the drug-specific rate ratios from the network of randomized controlled trials were compared with those from the network of observational studies. RESULTS: Effect estimates from 26 observational studies showed greater magnitudes and were less precise compared to estimates obtained from 21 randomized controlled trials. Twenty of the 28 treatment comparisons between designs had similar rate ratios. Seven inconsistencies in observed rate ratios could be attributed to two specific disease-modifying therapies. CONCLUSION: In this case study, estimates from observational studies predominantly agreed with estimates from randomized controlled trials given their posterior predictive distributions. Multiple observational studies together may therefore supplement additional pivotal randomized controlled trials in relapsing-remitting multiple sclerosis, for instance facilitating the extrapolation of trial results to the broader patient population.

Genetic propensity to depression and the role of partnership status.

Social relationships and genetic propensity are known to affect depression risk, but their joint effects are poorly understood. This study examined the association of a polygenic index for depression with time to antidepressant (AD) purchasing and the moderating role of partnership status. We analysed data from 30,192 Finnish individuals who participated in the FINRISK and Health 2000 and 2011 surveys and had register and medication data available. We measured genetic risk with a polygenic index (PGI) for depression. Depression was assessed through antidepressant purchases. We estimated an accelerated failure time model with partnership status as time-varying and different sets of confounder adjustments. The predicted cumulative hazard of antidepressant purchasing varied across PGI and partnership status. At follow-up year 10, being widowed was associated with the largest cumulative hazard of 0.34 (95%CI: 0.28-0.39) in the 80th and 0.20 (95%CI: 0.17-0.23) in the 20th PGI percentile, followed by divorced, single, married and cohabiting. Cohabiting was associated with a cumulative hazard of 0.19 (95%CI: 0.16-0.23) in the 80th and 0.11 (95%CI: 0.1-0.13) in the 20th PGI percentile. We found no evidence for an interaction between the PGI and partnership status. Results were robust to different model specifications, gender stratification, and the choice of PGI. Although antidepressant purchasing correlated with both PGI and partnership status, we found no evidence that partnership status could partially offset or amplify the association between the PGI for depression and antidepressant purchasing incidence.

Childhood obesity's influence on socioeconomic disparities in young adolescents' mental health.

PURPOSE: We investigated whether socioeconomic inequalities in young adolescents' mental health are partially due to the unequal distribution of childhood obesity across socioeconomic positions (SEP), i.e. differential exposure, or due to the effect of obesity on mental health being more detrimental among certain SEPs, i.e. differential impact. METHODS: We studied 4660 participants of the Generation R study, a population-based study in the Netherlands. SEP was estimated by mother's education and household income at age five of the child. We estimated the contribution of the mediating and moderating effects of high body fat percentage to the disparity in mental health. This was done through a four-way decomposition using marginal structural models with inverse probability of treatment weighting. RESULTS: Comparing children with the least to most educated mothers and the lowest to highest household income, the total disparity in emotional problems was 0.98 points (95%CI:0.35-1.63) and 1.68 points (95%CI:1.13-2.19), respectively. Of these total disparities in emotional problems, 0.50 points (95%CI:0.15-0.85) and 0.24 points (95%CI:0.09-0.46) were due to the differential exposure to obesity. Obesity did not contribute to disparities in behavioural problems. CONCLUSION: Addressing the heightened obesity prevalence among children in low SEP families may reduce inequalities in emotional problems in early adolescence.

Association between Incidence of Prescriptions for Alzheimer's Disease and Beta-Adrenoceptor Antagonists: A Prescription Sequence Symmetry Analysis.

BACKGROUND: Alzheimer's disease (AD) is the most common cause of dementia, with a growing number of patients worldwide. The association between AD and treatment with drugs targeting the beta-adrenergic receptor is controversial. The aim of this study is to assess the association between the initiation of AD medication and beta-adrenoceptor antagonists (beta-blockers) in adults. MATERIALS AND METHODS: We conducted a prescription sequence symmetry analysis using the University of Groningen IADB.nl prescription database. We determined the order of the first prescription for treating AD and the first prescription for beta-blockers, with the dispensing date of the first prescription for AD defined as the index date. Participants were adults over 45 years old starting any AD medication and beta-blockers within two years. We calculated adjusted sequence ratios with corresponding 95% confidence intervals. RESULTS: We identified 510 users of both AD and beta-blockers, and 145 participants were eligible. The results were compatible with either a significant decrease in the incidence of AD after using beta-blockers (adjusted sequence ratio (aSR) = 0.52; 95% CI: 0.35-0.72) or, conversely, an increase in beta-blockers after AD medication (aSR = 1.96; 95% CI: 1.61-2.30). CONCLUSIONS: There is a relationship between the use of beta-blockers and AD medications. Further research is needed with larger populations to determine whether drug therapy for AD increases the risk of hypertension or whether beta-blockers have potential protective properties against AD development.