Alan Morrison

Objective: To investigate the effects of continued use of non-selective NSAIDs (nsNSAIDs) on blood pressure and hypertension.Research design and methods: This was a systematic review of randomized clinical trials of oral nsNSAIDs used for at least a 4-week duration. Searches were conducted of PubMed and the Cochrane Database of Systematic Reviews, using key terms for nsNSAIDs and blood pressure or hypertension, to identify articles published in the English language peer-reviewed literature through March 2007.Main outcome measures: Change from baseline to end of study in systolic blood pressure (SBP) and diastolic blood pressure (DBP), and the incidence of hypertension. Pooled statistics were computed using fixed and random-effects analyses.Results: Thirty-two articles were included. The mean change (95% confidence interval [CI]) in blood pressure (in mmHg) from baseline to end of study for five trials of ibuprofen was 3.54 (2.70, 4.39) for SBP and 1.16 (0.68, 1.64) for DBP ( p < 0.001 for both cha...

Research into the relationship between genetics and drug response has focused on polymorphisms in genes that encode drug-metabolizing enzymes, particularly the genes of cytochrome P450 superfamily 2, which affect the clearance of the anticoagulant warfarin, proton pump inhibitors, tricyclic antidepressants, and many other clinically relevant drugs. Much of this work has targeted East Asians, a genetically distinguishable and populous group. Researchers have identified polymorphisms that inactivate gene function, compared polymorphism frequencies in East-Asian and Caucasian populations, and determined the effects on the pharmacokinetic parameters of drugs. Detection in an individual of polymorphisms known to inactivate a drug-metabolizing enzyme is predictive of poor metabolism of drugs processed by that pathway, which itself may be predictive of an atypical drug response. Genetic tests can be used to screen for individuals with poor metabolizer phenotypes, with the ultimate goal of predicting the clinical effects of drugs.

OBJECTIVE: To examine the cost-effectiveness of statins in relation to different measures of effectiveness, differences in efficacy among individual statins, and the risk of coronary heart disease. Efficacy is defined here as the magnitude of the effect produced by a given amount of drug, as demonstrated in placebo control trials; i.e., the effectiveness per unit dose. DATA SYNTHESIS: Treatment guidelines categorize patients by their risk of coronary events and set lower target cholesterol levels for patients at higher risk. Statins vary in their efficacy. If effectiveness is expressed as percent lowering in low-density lipoprotein cholesterol (LDL-C) and relatively little cholesterol lowering is required as in low-risk patients even statins of low efficacy provide adequate cholesterol lowering, and drug price is the determining factor of cost effectiveness. For patients at high risk the primary target group, which has been expanded in recent guidelines high-efficacy statins are required to meet the more ...