METHODS: Nine primary care health clinics across Malaysia participated in this study. 147 statin-naive subjects were selected through convenient sampling and randomised into one of the three arms (after breakfast, after dinner or before bedtime). Differences on percentage reduction of LDL-C from baseline and level of adherence among the three groups at week-16 were compared. The main outcomes measured in this study were the percentage change of lipid parameters and the percentage of high-adherence (MMAS=8) at week-16.
RESULTS: 59.2% of the patients were male. The mean age of the study population was 53.93± 10.85 years. Most of the patients were Malays (69.4%); followed by Indians (22.4%) and Chinese (8.2%). LDL-C decreased from 4.26 (Standard Deviation, SD1.01) to 2.36 (SD0.69)mmol/L at week-16 for patients taking simvastatin before bedtime; an absolute reduction of 44.95%.The differences of LDL-C percentage reduction between three arms were significantly different (p<0.001). The greatest LDL-C reduction was observed when simvastatin was taken before bedtime and revealed 56.2% patients with high-adherence at week-16.
CONCLUSION: Simvastatin showed superior LDL-reduction and higher level of adherence when being instructed to be taken before bedtime.
OBJECTIVES: The authors sought to assess the LDL-C efficacy of rosuvastatin versus placebo in HoFH children, and the relationship with underlying genetic mutations.
METHODS: This was a randomized, double-blind, 12-week, crossover study of rosuvastatin 20 mg versus placebo, followed by 12 weeks of open-label rosuvastatin. Patients discontinued all lipid-lowering treatment except ezetimibe and/or apheresis. Clinical and laboratory assessments were performed every 6 weeks. The relationship between LDL-C response and genetic mutations was assessed by adding children and adults from a prior HoFH rosuvastatin trial.
RESULTS: Twenty patients were screened, 14 randomized, and 13 completed the study. The mean age was 10.9 years; 8 patients were on ezetimibe and 7 on apheresis. Mean LDL-C was 481 mg/dl (range: 229 to 742 mg/dl) on placebo and 396 mg/dl (range: 130 to 700 mg/dl) on rosuvastatin, producing a mean 85.4 mg/dl (22.3%) difference (p = 0.005). Efficacy was similar regardless of age or use of ezetimibe or apheresis, and was maintained for 12 weeks. Adverse events were few and not serious. Patients with 2 defective versus 2 negative LDL receptor mutations had mean LDL-C reductions of 23.5% (p = 0.0044) and 14% (p = 0.038), respectively.
CONCLUSIONS: This first-ever pediatric HoFH statin trial demonstrated safe and effective LDL-C reduction with rosuvastatin 20 mg alone or added to ezetimibe and/or apheresis. The LDL-C response in children and adults was related to underlying genetic mutations. (A Study to Evaluate the Efficacy and Safety of Rosuvastatin in Children and Adolescents With Homozygous Familial Hypercholesterolemia [HYDRA]; NCT02226198).
METHOD: Assessment of utilization (items dispensed) and expenditure of key LLAs (mainly statins) between 2001 and 2015 in Scotland alongside initiatives.
RESULTS: Multiple interventions over the years have increased international nonproprietary name prescribing (99% for statins) and preferential prescribing of generic versus patented statins, and reduced inappropriate prescribing of ezetimibe. This resulted in a 50% reduction in expenditure of LLAs between 2001 and 2015 despite a 412% increase in utilization, increased prescribing of higher dose statins (71% in 2015) especially atorvastatin following generic availability, and reduced prescribing of ezetimibe (reduced by 72% between 2010 and 2015). As a result, the quality of prescribing has improved.
CONCLUSION: Generic availability coupled with multiple measures has resulted in appreciable shifts in statin prescribing behavior and reduced ezetimibe prescribing, resulting in improvements in both the quality and efficiency of prescribing.
METHODS: Using a 2-by-2-by-2 factorial design, we randomly assigned participants without cardiovascular disease who had an elevated INTERHEART Risk Score to receive a polypill (containing 40 mg of simvastatin, 100 mg of atenolol, 25 mg of hydrochlorothiazide, and 10 mg of ramipril) or placebo daily, aspirin (75 mg) or placebo daily, and vitamin D or placebo monthly. We report here the outcomes for the polypill alone as compared with matching placebo, for aspirin alone as compared with matching placebo, and for the polypill plus aspirin as compared with double placebo. For the polypill-alone and polypill-plus-aspirin comparisons, the primary outcome was death from cardiovascular causes, myocardial infarction, stroke, resuscitated cardiac arrest, heart failure, or revascularization. For the aspirin comparison, the primary outcome was death from cardiovascular causes, myocardial infarction, or stroke. Safety was also assessed.
RESULTS: A total of 5713 participants underwent randomization, and the mean follow-up was 4.6 years. The low-density lipoprotein cholesterol level was lower by approximately 19 mg per deciliter and systolic blood pressure was lower by approximately 5.8 mm Hg with the polypill and with combination therapy than with placebo. The primary outcome for the polypill comparison occurred in 126 participants (4.4%) in the polypill group and in 157 (5.5%) in the placebo group (hazard ratio, 0.79; 95% confidence interval [CI], 0.63 to 1.00). The primary outcome for the aspirin comparison occurred in 116 participants (4.1%) in the aspirin group and in 134 (4.7%) in the placebo group (hazard ratio, 0.86; 95% CI, 0.67 to 1.10). The primary outcome for the polypill-plus-aspirin comparison occurred in 59 participants (4.1%) in the combined-treatment group and in 83 (5.8%) in the double-placebo group (hazard ratio, 0.69; 95% CI, 0.50 to 0.97). The incidence of hypotension or dizziness was higher in groups that received the polypill than in their respective placebo groups.
CONCLUSIONS: Combined treatment with a polypill plus aspirin led to a lower incidence of cardiovascular events than did placebo among participants without cardiovascular disease who were at intermediate cardiovascular risk. (Funded by the Wellcome Trust and others; TIPS-3 ClinicalTrials.gov number, NCT01646437.).