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Objective: British clinical guidelines recommend statins as first-line lipid-modifying treatment (LMT) for patients at high risk of cardiovascular disease (CVD). We undertook an observational study to assess total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels in high-risk patients who were treated with atorvastatin monotherapy by UK general practitioners., Methods: This retrospective database study included patients with a prescription for atorvastatin monotherapy between November 30, 2008, and November 30, 2011, with the index date defined as the first atorvastatin prescription during this period. Eligible high-risk patients with evidence of coronary heart disease (CHD), atherosclerotic vascular disease (AVD), diabetes mellitus (DM), or familial hypercholesterolemia (FH) were required to have ≥1 TC and LDL-C measurement between 3 and 12 months after the index date, and continuous enrollment 1 year before and 1 year after the index date. Cholesterol levels were assessed using the National Institute for Health and Care Excellence (NICE) guidelines: TC <4.0 mmol/L or LDL-C <2.0 mmol/L., Results: Of 2999 high-risk patients (60.2% men; mean [SD] age = 67.9 [10.6] years) meeting selection criteria, 23.9% 28.2%, 36.2%, and 11.6% received prescriptions for atorvastatin 10, 20, 40, and 80 mg, respectively (percentages do not sum to 100 because of rounding). Across all doses, the mean (SD) follow-up TC was 4.08 (0.80) mmol/L and LDL-C 2.08 (0.65) mmol/L. A large proportion of patients (88.8%) had TC < 5.0 mmol/L. However, only 45.8% had TC < 4.0 mmol/L, and 46.5% had LDL-C < 2.0 mmol/L. Although a larger proportion of patients with CHD/AVD + DM reached guideline-recommended lipid levels, only 63.7% of such patients had TC < 4.0 or LDL-C < 2.0 mmol/L, which are the current targets for this subgroup as recommended by NICE., Conclusions: Less than half of UK high-CVD-risk patients receiving atorvastatin monotherapy achieved guideline-recommended treatment targets for TC, and less than two-thirds of patients with CHD/AVD + DM had values below TC (4.0 mmol/L) or LDL-C (2.0 mmol/L) targets. More effective lipid-lowering strategies may be warranted to optimize cholesterol lowering and target attainment in high-risk patients. Limitations of this study include its retrospective, observational nature.

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. TRIAL REGISTRATION (BASE STUDY): ClinicalTrials.gov identifier: NCT00190957.

Background: Levels of cholesterol are regulated by its synthesis, absorption, and elimination. Plasma levels of phytosterols (e.g., sitosterol, campesterol) and ratios of these sterols to total cholesterol (TC) are reported to correlate with efficiency of intestinal cholesterol absorption, whereas levels of certain cholesterol precursor sterols (e.g., desmosterol, lathosterol) and their ratios to TC correlate with cholesterol biosynthesis. However, there is a paucity of published data concerning the effects of combined treatment using HMG-CoA reductase inhibitors (statins) and a cholesterol absorption inhibitor (ezetimibe) on these parameters., Objectives: To characterize the effects of ezetimibe co-administered with statins, compared with each treatment alone, on cholesterol precursor sterols and plasma phytosterol levels., Methods: A post-hoc analysis was performed to determine the effects of treatment with ezetimibe 10 mg, simvastatin (10-80 mg), and atorvastatin (10-80 mg), alone or in combination, on these non-cholesterol sterols using plasma samples from two randomized controlled trials involving patients with primary hypercholesterolemia (low-density lipo protein [LDL-C] = 145-250 mg/dL; triglycerides < or = 350 mg/dL; N = 975) but without a recent (< or = 6-month) history of coronary heart disease (CHD) or either uncontrolled or newly diagnosed diabetes mellitus., Results: Ezetimibe monotherapy significantly reduced plasma sitosterol and campesterol concentrations from baseline compared with placebo (both p < 0.001), whereas statins significantly lowered desmo sterol and lathosterol levels (p < 0.001 vs. placebo). Co-administration of ezetimibe and statins significantly decreased plasma levels of all of these sterols (p < 0.001)., Conclusions: 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.

Objective: The use of Framingham equations to determine 10-year absolute coronary risk ('global risk') represents an accepted strategy to target coronary prevention measures and enhance clinical outcomes. The aim of this study was to determine the effects of providing global risk scores to physicians on the prescription of lipid-lowering therapy for patients at increased coronary risk., Research Design and Methods: This prospective, randomized controlled trial enrolled 368 primary-care patients without a history of coronary heart disease and not on therapy with a hydroxymethylglutaryl coenzyme A reductase inhibitor (i.e. statin). The study was conducted in the general medical clinics of an academic US teaching hospital. In the intervention group (n = 186) patients' charts were reviewed, 10-year absolute coronary risk computed, and this information conveyed via a simple educational tool appended to charts. In the control group (n = 182), charts were accompanied by a form with general information on coronary prevention goals and strategies., Main Outcome Measure: The primary endpoint was the proportion of high-risk patients receiving a new statin prescription. Secondary and tertiary endpoints included (1) the proportion of moderate-risk patients receiving a statin prescription; and (2) the proportion of patients in the whole cohort who had other coronary prevention measures recommended., Results: There was no significant difference in statin prescription to high-risk individuals in the intervention group (40.0%) compared with the control group (37.9%; p = 0.86). Moderate-risk individuals who were not eligible for treatment according to the National Cholesterol Education Program Adult Treatment Panel II guidelines were more likely to receive a statin prescription in the intervention group versus the control group (28.8% vs. 12.5%. p = 0.036), Conclusions: 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.