A dose-specific meta-analysis of lipid changes in randomized controlled trials of atorvastatin and simvastatin.

BACKGROUND: The available statins exhibit differences in the potency with which they alter serum lipid levels. OBJECTIVE: Meta-analyses were conducted to assess the relative potency of atorvastatin and simvastatin (the 2 most commonly prescribed statins) across all possible dose combinations in terms of changes in total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), and high-density lipoprotein cholesterol (HDL-C). METHODS: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, National Health Service (NHS) Centre for Reviews and Dissemination database, NHS Economic Evaluation Database, and Database of Abstracts of Reviews of Effects were searched for randomized, head-to-head trials of atorvastatin and simvastatin in patients aged >or=18 years with elevated levels of serum TC and LDL-C. Reference lists of the identified articles, letters, and editorials also were reviewed. The manufacturers of atorvastatin and simvastatin products were contacted for relevant unpublished data. All studies were reviewed and rated for quality by 2 independent reviewers. The maximum quality score was 4 points; trials with a score of <2 points were considered to be of poor quality and were excluded from analysis. Dose comparisons were abstracted in pairs from each trial. Meta-analyses were conducted on the fixed-dose pairs for each lipid parameter. Weighted mean differences in the change in TC, LDL-C, TG, and HDL-C were estimated using the Der Simonian and Laird random-effects model. RESULTS: Seventeen published trials and 1 unpublished study were included in the meta-analyses. Atorvastatin treatment was associated with significantly greater reductions in TC, LDL-C, and TG in the majority of dose comparisons with simvastatin. The potency of atorvastatin and simvastatin was comparable at dose ratios between 1:2 and 1:4. Higher doses of simvastatin were more effective in increasing HDL-C levels than atorvastatin, with no apparent dose-equivalence point. The HDL-C advantage of simvastatin was greatest when simvastatin 80 mg was compared with atorvastatin 80 mg (weighted mean difference, -4.35%; 95% CI, -5.64 to -3.08, P < 0.001). CONCLUSIONS: In these meta-analyses, atorvastatin was 2 to 4 times as potent as simvastatin in reducing TC, LDL-C, and TG, indicating that the dose equivalence of atorvastatin and simvastatin lay between 1:2 and 1:4. In contrast, simvastatin was more effective than atorvastatin in increasing HDL-C, but without any indication of a point of dose equivalence.

Development of a quality use of medicines coding system to rate clinical pharmacists' medication review recommendations.

OBJECTIVE: To develop a 'quality use of medicines' coding system for the assessment of pharmacists' medication reviews and to apply it to an appropriate cohort. METHOD: A 'quality use of medicines' coding system was developed based on findings in the literature. These codes were then applied to 216 (111 intervention, 105 control) veterans' medication profiles by an independent clinical pharmacist who was supported by a clinical pharmacologist with the aim to assess the appropriateness of pharmacy interventions. The profiles were provided for veterans participating in a randomised, controlled trial in private hospitals evaluating the effect of medication review and discharge counselling. The reliability of the coding was tested by two independent clinical pharmacists in a random sample of 23 veterans from the study population. MAIN OUTCOME MEASURE: Interrater reliability was assessed by applying Cohen's kappa score on aggregated codes. RESULTS: The coding system based on the literature consisted of 19 codes. The results from the three clinical pharmacists suggested that the original coding system had two major problems: (a) a lack of discrimination for certain recommendations e.g. adverse drug reactions, toxicity and mortality may be seen as variations in degree of a single effect and (b) certain codes e.g. essential therapy were in low prevalence. The interrater reliability for an aggregation of all codes into positive, negative and clinically non-significant codes ranged from 0.49-0.58 (good to fair). The interrater reliability increased to 0.72-0.79 (excellent) when all negative codes were excluded. Analysis of the sample of 216 profiles showed that the most prevalent recommendations from the clinical pharmacists were a positive impact in reducing adverse responses (31.9%), an improvement in good clinical pharmacy practice (25.5%) and a positive impact in reducing drug toxicity (11.1%). Most medications were assigned the clinically non-significant code (96.6%). In fact, the interventions led to a statistically significant difference in pharmacist recommendations in the categories; adverse response, toxicity and good clinical pharmacy practice measured by the quality use of medicine coding system. CONCLUSION: It was possible to use the quality use of medicine coding system to rate the quality and potential health impact of pharmacists' medication reviews, and the system did pick up differences between intervention and control patients. The interrater reliability for the summarised coding system was fair, but a larger sample of medication regimens is needed to assess the non-summarised quality use of medicines coding system.