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Randomized controlled trials remain the gold standard study design and yield the highest level of scientific credence. However, recognition of the limitations of the randomized controlled trial is important. This [...]

BACKGROUND Adherence to study medications is crucial to evaluating treatment effects in clinical trials. To assess whether in the SPRINT trial, adherence and cardiovascular outcomes are associated regardless of intervention assignment. METHODS This study included 9,361 participants aged ≥50 years, recruited from 102 clinics. Participants were randomized to a Standard Treatment Group (targeted systolic blood pressure [SBP] <140 mm Hg) or an Intensive Treatment Group (targeted SBP <120 mm Hg) and followed for incident cardiovascular events until the study was halted early for benefit. The 8-item Morisky Medication Adherence Scale (MMAS-8) was administered at baseline, and at the 12- and 48-month (or close out) visit. RESULTS Adjusting for covariates, there was no association between the baseline 8-item MMAS-8 and the likelihood of the primary composite endpoint, any of the secondary endpoints, or blood pressure (BP) control. Low adherence was associated with a higher body mass index, SBP, diastolic BP, and Patient Health Questionnaire, and high adherence was associated with a higher Montreal Cognitive Assessment. There was no difference in the MMAS-8 over time by treatment arm assignment. For the primary outcome (a composite of myocardial infarction, other acute coronary syndromes, stroke, heart failure, or death from cardiovascular causes), baseline odds ratios (95% confidence intervals) for the Low vs. Medium and vs. High; and, for Medium vs. High MMAS-8 were 1.02 (0.82–1.28), 1.07 (0.85–1.34), and 1.05 (0.88–1.250). CONCLUSIONS In SPRINT, medication adherence as measured using the MMAS-8 was not associated with outcomes or BP control. [ABSTRACT FROM AUTHOR]

Controlled clinical trials, especially those that use a placebo (inert substance or 'sugar pill') against which to compare the action of a drug, are thought to offer the most efficient and clear-cut evidence for usefulness of new drugs. However, this method cannot ethically be used if an effective therapy already exists, especially if it affects survival or illness. In the case of angina, therapy relieves the chest pain, but does not change the chances of survival or the course of related disease. There is increasing reluctance to approve research designs using a placebo for the study of angina, although there is no evidence of undue risk. Trials of 12 antianginal drugs using a placebo for comparison were evaluated for the frequency and type of adverse heart problems. A total of 3,161 patients were included. Heart-related problems leading to dropout were uncommon, and the placebo was not associated with increased risk when compared with the active drugs. Assignment to the group receiving the active drugs did not reduce the frequency of heart problems. There was a significant increased risk with the use of calcium antagonists, so in this case assignment to the placebo group would have been preferable. The Food and Drug Administration guidelines for the study of antianginal drugs specify symptom-limited exercise testing to measure effectiveness, and short-term placebo-controlled trials of one to four weeks, using patients who are not receiving any type of antianginal therapy. Long-term placebo-controlled trials of patients receiving background therapy are also recommended because they would provide useful information for labeling. (Consumer Summary produced by Reliance Medical Information, Inc.)

Abstract Background Postprandial lipemia (PPL) is likely a risk factor for cardiovascular disease but these changes have not been well described and characterized in a large cohort. We assessed acute changes in the size and concentration of total and subclasses of LDL, HDL, and VLDL particles in response to a high-fat meal. Participants (n = 1048) from the Genetics of Lipid-Lowering Drugs and Diet Network (GOLDN) Study who ingested a high-fat meal were included in this analysis. Lipids were measured at 0 hr (fasting), 3.5 hr, and 6 hr after a standardized fat meal. Particle size distributions were determined using nuclear magnetic resonance spectroscopy. Analyses were stratified by baseline triglycerides (normal vs. elevated) and gender. The effect of PPL on changes in lipoprotein subclasses was assessed using repeated measures ANOVA. Results Postprandially, LDL-C, HDL-C, VLDL-C, and triglycerides increased regardless of baseline triglyceride status, with the largest increases in VLDL-C and TG; however, those with elevated triglycerides demonstrated larger magnitude of response. Total LDL particle number decreased over the 6-hour time interval, mostly from a decrease in the number of small LDL particles. Similarly, total VLDL particle number decreased due to reductions in medium and small VLDL particles. Large VLDL particles and chylomicrons demonstrated the largest increase in concentration. HDL particles demonstrated minimal overall changes in total particle number. Conclusions We have characterized the changes in LDL and VLDL particle number, and their subclass patterns following a high-fat meal.

Abstract Background Inflammation is implicated in causing diabetes. We tested whether transcription factor 7 like-2 (TCF7L2) gene polymorphisms (rs12255372 and rs7903146), consistently associated with type 2 diabetes, are associated with plasma concentrations of inflammatory markers before and after three weeks of daily treatment with fenofibrate. Methods Men and women in the Genetics of Lipid-Lowering Drugs and Diet Network study (n = 1025, age 49 ± 16 y) were included. All participants suspended use of lipid-lowering drugs for three weeks and were then given 160 mg/day of fenofibrate for three weeks. Inflammatory markers and lipids were measured before and after fenofibrate. ANOVA was used to test for differences across TCF7L2 genotypes. Results Under the additive or dominant model, there were no significant differences (P > 0.05) in the concentrations of inflammatory markers (hsCRP, IL-2, IL-6, TNF-α and MCP-1) across TCF7L2 genotypes in the period before or after treatment. For both rs12255372 and rs7903146, homozygote T-allele carriers had significantly higher (P < 0.05) post-fenofibrate concentrations of MCP-1 in the recessive model. No other significant associations were detected. Conclusion Overall these data show no association between TCF7L2 polymorphisms and the inflammatory markers suggesting that the effects of TCF7L2 on diabetes may not be via inflammation.