The New England Journal of Medicine has published the results of a meta-analysis examining the cardiovascular safety of rosiglitazone as an online first article. There is currently free access to full text and PDF versions of the paper.
The study included analysis of 42 papers including data for almost 28,000 patients. Data were collected for outcomes of myocardial infarction and death from cardiovascular causes.
Due to limitations in the published data it was not possible to calculate hazard ratios, however there was a statistically increased risk of myocardial infarction (Odds ratio 1.43, 95% confidence interval [CI], 1.03 to 1.98; P=0.03) and a non significant increase in the risk of cardiovascular death (Odds ratio 1.64, 95% CI, 0.98 to 2.74; P=0.06).
Despite the limitations imposed by a lack of access to original source data the authors of this analysis conclude that clinicians "should consider the potential for serious adverse cardiovascular effects of treatment with rosiglitazone".
Pioglitazone was not studied in this analysis. The PROactive study did contain a secondary endpoint showing some cardiovascular benefit. However, since the primary endpoint in that study did not reach statistical significance the validity of this benefit has been questioned.
Action: Metformin remains the first line hypoglycaemic in all patients with type 2 diabetes. Once the symptoms of diabetes are relieved treatment should focus upon lowering blood pressure and cardiovascular risk, not on lowering blood glucose. Pioglitazone or a sulphonylurea may be suitable choices if additional hypoglycaemic agents are deemed necessary.
The National Prescribing Centre (NPC) has published MeReC Extra 28 that provides a summary of the recently published TORCH study, a discussion of when the benefits outweigh the risks using the combination of aspirin and warfarin and an insight to some future NPC work.
The TORCH study was a randomised controlled trial examining the effects of fluticasone, salmeterol and the combination of these two drugs on mortality in patients with chronic obstructive pulmonary disease (COPD). After three years there was no difference in deaths between the combination arm and the placebo arm of the study. There were some differences in secondary end points, for example there were fewer moderate to severe exacerbations and lung function as measured by FEV1.
Interestingly, in comparison to salmeterol alone, the combination did not reduce the number of hospital admissions. Also, it was noted that pneumonia occurred more frequently in the fluticasone and combination arms. The MeReC calculates that for every 17 people treated with the combination for 3 years as opposed to salmeterol alone, 1 will suffer pneumonia!
The key messages for clinicians about this study are:
- It supports the current NICE Guideline for COPD
- Combination therapies appear to reduce exacerbations but not hospital admissions
- There may be a link between pneumonia and inhaled steroids in COPD patients that requires further investigation
This MeReC also discusses when the additional risk of bleeding caused by the combination of aspirin and warfarin is balanced by clinical benefit. This section covers a recent meta-analysis of 10 trials in patients at high risk of thromboembolism, for example those with mechanical heart valves and atrial fibrillation. The majority of patients in whom the combination might be beneficial will be seen in secondary care. This combination should not be routinely initiated in the primary care setting.
Finally, the article reveals a little more information about NPCi and also reveals the next two MeReC Bulletin topics. These will be the role of newer insulins in diabetes and the management of rheumatoid arthritis. More details of these will be posted when the Bulletins are made available.
Action: As always, the NPC have provided a high quality summary of the latest topical issues. Clinicians will find this publication useful and informative.
The Journal of the American Medical Association has published the results of a trial demonstrating that taking more exercise makes you fitter.
The study recruited 464 sedentary, postmenopausal overweight or obese women. Body mass index ranged from 25 to 43. Baseline systolic blood pressure ranged from 120mmHg to 159.9mmHg. Patients were randomised to a control group or one of three different exercise groups and followed up for 6 months.
Current consensus is that children and adults should aim to undertake at least 30 minutes of moderate-intensity physical activity on most, and preferably all, days of the week. This study assessed the impact upon overall fitness in the three groups by undertaking the equivalent of 15, 30 and 45 minutes of moderate-intensity physical exercise per day.
Unsurprisingly, the study found that the more exercise is undertaken the fitter the individual becomes. The study comments that this finding seems logical, but that few reports have evaluated the activity-fitness dose-response relation. However, it was also found that the even the lowest level of activity was statistically better than a sedentary lifestyle.
Action: The two key messages from this study are that some exercise is better than none and the more exercise you take the better. Using these two key messages, clinicians should advise all patients to increase levels of physical activity, where physically appropriate.
The National Prescribing Centre has revealed plans to launch NPCi, an eLearning environment to support therapeutics and medicines management at a local level.
The interface for NPCi will take the form of a virtual building with each floor offering access to a large variety of learning materials. The content will include therapeutic (cardiovascular, central nervous system, pain management) and medicines management topics (patient safety and risk, patients and their medicines, developing people and organisations) with educational materials available in several forms including quizzes, data-focussed commentaries, slides, case studies, patient decision aids and recorded workshops.
In addition to this there will also be discussion forums, a notice board for hot topics and a library for access existing NPC materials like MeReC and New Medicines.
Action: Clinicians should be aware of the imminent launch of this resource; more details will be made available soon!
According to Tariff Watch, produced by the Medicines Management Network - North West the prices of Category M drugs were increased by 10% in April.
The author of Tariff Watch, Andrew Martin from Bury PCT, estimates that this could mean an additional 2% in expenditure on the entire drug budget if these prices remain unchanged for the year.
Category M was introduced by the Department of Health in April 2005 as part of the Pharmacy Contract. The Pharmaceutical Services Negotiating Committee (PSNC) has produced a summary explaining the key points of the system.
Category M products are available as generics and are quite often the drug of choice within a particular class based upon lower acquisition costs.
Action: Clinicians should ensure that Category M drugs are used wherever possible to offset this potential increase in drugs expenditure. Where possible, the process for setting Prescribing Budgets should take into account changes in Category M price where possible.