The Journal of the American Medical Association has published the results of the METEOR Trial. The Full Study is currently available as an Early Release Article.
The study compared therapy with rosuvastatin 40mg against placebo over 2 years in patients with a Framingham risk score of less than 10% in 10 years in terms of the carotid intima-media thickness (CIMT).
CIMT thickening is related to development of coronary atherosclerosis however the relationship is not entirely clear. The European Heart Journal recently published a paper that concluded there was only a modest relationship and that further work is required.
The results of the METEOR Trial were expected to show regression of CIMT in the rosuvastatin arm. While the active arm of the study was statistically different from the placebo arm they were not strong enough to confirm regression, only stabilisation.
This trial does not change current practice. The design of the study was to give top doses of a potent statin to individuals at very low risk of cardiovascular events. This is not recommended in primary care because the cost of treatment compared to the marginal cardiovascular benefits in an already low-risk group makes the intervention economically nonviable. It is also worth remembering that rosuvastatin has no data for reductions in the incidence of deaths, heart attacks and other cardiovascular events.
Action: Simvastatin 40mg remains the statin of choice for lipid lowering therapy as required in the prevention of cardiovascular events.
As reported by the BBC, the budget has cut VAT (Value Added Tax) on smoking cessation products from 17.5% to 5%.
This move has been welcomed by Action on Smoking and Health (ASH), an anti-smoking group and the British Heart Foundation.
The VAT reduction comes into force on 1st July 2007 to coincide with the smoking ban affecting all pubs, clubs, restaurants and other public places in England that will come into effect on the same day.
Action: Healthcare professionals should be aware of the imminent smoking ban and the reduction in VAT on smoking cessation products. These two factors may encourage large numbers of smokers to quit.
The National Prescribing Centre (NPC) has published MeReC Extra 27 that provides a reminder of maximum doses of inhaled steroids in children, an analysis of the consequences of thiazide related diabetes and an analysis of the evidence supporting Grazax®.
Individual sections are available as follows:
The first section reminds clinicians of the licensed doses of inhaled steroids in children. A recent study has identified links between prescribing of high doses inhaled steroids in young children and adrenal suppression. An observational study of GP prescribing is cited that recommends audits are carried out to identify children at high risk of adverse outcomes.
The analysis of the consequences of thiazide-induced diabetes discusses the findings of a post-hoc subgroup analysis of the ALLHAT study. The analysis found no significant association between fasting glucose changes and any of the study endpoints (death, CV disease or end-stage renal disease) in a combined analysis or for thiazides alone. Further investigation is required but this finding adds some weight to a 14-year follow-up of another study that suggests any observed excess in diabetes does not increase cardiovascular risk.
Grazax is only indicated following a positive allergen test to grass pollen (skin prick or specific IgE test). It is recommended that physicians with experience in the treatment of allergic disease initiate treatment. The first dose should also be taken under medical supervision due to the risk of allergic reactions. It is also noted that the absolute benefits of Grazax are modest and have not been compared with subcutaneous allergen immunotherapy.
Action: Clinicians who treat children with asthma, hypertension or grass pollen allergy will find this MeReC useful and informative.
The American Food and Drugs Administration has issued a warning to healthcare professionals after an increased risk of fracture was also seen in the clinical trial database of pioglitazone (Actos®).
The risk appears to be very similar to rosiglitazone. The risk appears to only affect women and the fractures are mainly located in the distal portion of the limbs, e.g. hand, foot, wrist, ankle, forearm, tibia and fibula.
The manufacturer recommends that, "the risk of fracture should be considered in the care of female patients with type 2 diabetes mellitus who are currently being treated with pioglitazone, or when initiation of pioglitazone treatment is being considered".
This analysis strongly suggests that the increased risk of fracture is a class effect of the glitazones. Further investigation is required before the nature and mechanism of this excess risk is understood. Metformin remains the first-line hypoglycaemic and sulphonylureas provide a suitable second-line option as an alternative to the glitazones.
Action: Fracture risk should be considered during medication reviews for female patients already on glitazones. In patients whose type 2 diabetes is poorly controlled the pros and cons of each of the available hypoglycaemic agents should be considered and discussed with the patient before any treatment is started.
The manufacturers of paroxetine (Seroxat®) have announced the launch of a 10mg tablet to "support patients tapering down their medication". As with the current 20mg and 30mg tablets, these are scored allowing for a 5mg dose to be taken.
The Medicines and Healthcare products Regulatory Agency have received over 1,500 reports of withdrawal syndrome with paroxetine as reported in the current Drug Analysis Print.
This new product provides another option to help patients successfully stop taking paroxetine without experiencing severe withdrawal reactions. Alternative strategies include using paroxetine liquid or converting to fluoxetine before carrying out dose reductions.
The costs for each paroxetine presentation are currently:
- 10mg tablets (brand) - £12.32 for 28 tablets
- 20mg tablets (brand) - £13.21 for 30 tablets
- 20mg tablets (generic) - £6.57 for 30 tablets
- 30mg tablets (brand) - £23.18 for 30 tablets
- 30mg tablets (generic) - £8.95 for 30 tablets
- 10mg/5ml suspension - £9.49 for 150ml
Action: Clinicians should already be aware of the withdrawal syndrome associated with paroxetine. Strategies to minimise withdrawal effects should be adopted to aid cessation following a successful treatment course with consideration of cost and patient preference.