Lipid management strategies in Europe during the study period were dominated by statin monotherapy. Even after prolonged follow-up on lipid-modifying therapy, approximately 60% of Europeans studied did not achieve guideline recommended cholesterol goals. Future emphasis must be placed on subsequent lipid panel monitoring, as well as the use of more efficacious, well-tolerated lipid-modifying therapies such as dual cholesterol inhibitors to enable more European patients to attain their recommended cholesterol goals.

BackgroundThe relatively short durations of the initial pivotal randomized placebo-controlled trials involving atomoxetine HCl for the treatment of attention-deficit/hyperactivity disorder (ADHD) provided limited insight into the time courses of ADHD core symptom responses to this nonstimulant, selective norepinephrine reuptake inhibitor. The aim of this analysis was to evaluate time courses of treatment responses or remission, as assessed by attainment of prespecified scores on the ADHD Rating Scale-IV-Parent Version: Investigator Administered and Scored (ADHDRS-IV-PI) and the Clinical Global Impressions-ADHD-Severity (CGI-ADHD-S) scales, during up to 1 year of atomoxetine treatment in children with ADHD.MethodsUsing pooled data from three Canadian open-label studies involving 338 children ages 6-11 years with ADHD who were treated with atomoxetine for 3, 6 and 12 months, and survival analysis methods for interval-censored data, we estimated the time to: 1) improvement and robust improvement defined by ≥25% and ≥40% reductions from baseline ADHDRS-IV-PI total scores, respectively; and 2) remission using two definitions: a final score of ADHDRS-IV-PI ≤18 or a final score of CGI-ADHD-S ≤2.ResultsThe median time to improvement was 3.7 weeks (~1 month), but remission of symptoms did not occur until a median of 14.3 weeks (~3.5 months) using the most stringent CGI-ADHD-S threshold. Probabilities of robust improvement were 47% at or before 4 weeks of treatment; 76% at 12 weeks; 85% at 26 weeks; and 96% at 52 weeks. Probabilities of remission at these corresponding time points were 30%, 59%, 77%, and 85% (using the ADHDRS-IV scale) and 8%, 47%, 67%, and 75% (using the CGI-ADHD-S scale). The change from atomoxetine treatment month 5 to month 12 of -1.01 (1.03) was not statistically significant (p = .33).ConclusionsReductions in core ADHD symptoms during atomoxetine treatment are gradual. Although approximately one-half of study participants showed improvement at 1 month of atomoxetine treatment, remission criteria were not met until about 3 months. Understanding the time course of children's responses to atomoxetine treatment may inform clinical decision making and also influence the durations of trials comparing the effects of this medication with other ADHD treatments.Trial Registrationsclinicaltrials.gov: NCT00191633, NCT00216918, NCT00191880.

Background Attention-deficit/hyperactivity disorder (ADHD) and substance use disorder are often comorbid in adults. The effects of ADHD treatment on comorbid alcohol use disorder have not been extensively studied. Objective To assess correlates of ADHD and alcohol use outcomes in ADHD with comorbid alcohol use disorders, via a post-hoc exploratory subgroup analysis of a previously conducted, randomized, double-blind, placebo controlled study of recently abstinent adults. Methods Adults who had ADHD and alcohol use disorders and were abstinent for 4–30 days were randomized to daily atomoxetine 25–100 mg (mean final dose=89.9 mg) or placebo for 12 weeks. Changes in ADHD symptoms from baseline to endpoint were assessed using the ADHD Investigator Symptom Rating Scale (AISRS) total score, alcohol use by the timeline followback method, and alcohol cravings by the Obsessive Compulsive Drinking Scale. Results Of 147 subjects receiving atomoxetine (n=72) or placebo (n=75) in the primary study, 80 (54%) completed 12 weeks (n=32 atomoxetine; n=48 placebo). Improvements in ADHD symptoms on the AISRS correlated significantly with decreases in alcohol cravings (Pearson’s r=0.28; 95% confidence interval [CI]=0.11–0.43; p=0.002), and the correlation was most notable with atomoxetine (r=0.29; CI [0.04 – 0.51]; p=0.023) rather than with placebo (r=0.24; CI [0.00–0.46]; p=0.055). On-treatment drinking levels correlated with AISRS scores (r=0.12; CI [0.05 –0.19]; p=0.001). Relapse to alcohol abuse significantly correlated with worse ADHD symptoms on 15 of 18 items of the AISRS in the placebo group (p<0.05 for each). Conclusions No baseline predictor (other than degree of sobriety) of alcohol use or ADHD outcomes emerged. ADHD symptom improvements correlated significantly with reductions in alcohol cravings, and relapse to alcohol abuse correlated significantly with worsening of most ADHD symptoms in the placebo group, but not in the atomoxetine group. This post-hoc subgroup analysis is of a hypothesis-generating nature, and the generalizability of the findings may be limited by exclusion of adults with common ADHD comorbidities from the base study. Further, prospective clinical trials in larger and more heterogeneous patient populations are warranted to confirm or reject these preliminary associations.

Although a simple global risk educational tool did not improve the targeting of statin therapy to patients at high absolute coronary risk, it may be of benefit in targeting moderate-risk individuals who do not have markedly elevated low-density lipoprotein cholesterol (LDL-C) levels. Future research should evaluate the effects of physicians performing their own Framingham risk calculations on statin prescribing and on cholesterol goal attainment.

The observed effects of co-administration of ezetimibe and statins on non-cholesterol sterols are consistent with net inhibition of sterol absorption (driven by ezetimibe) in conjunction with net inhibition of cholesterol synthesis (driven by statins). The potential influence of treatment-induced changes in phytosterols on cardiovascular risk warrants further investigation in long-term, prospective, randomized controlled trials. This post-hoc study was by nature exploratory, and, because data from such analyses are not customarily adjusted for multiple comparisons, some associations may have emerged as statistically significant by chance. Future prospective randomized controlled studies may help to confirm our findings and address other research issues, such as the generalizability of our findings to patients with CHD or diabetes mellitus and possible dose:response relationships between escalating statin (or ezetimibe-statin) doses and circulating non-cholesterol levels.