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Prescribing Advice for GPs

An NHS Prescribing Advisers' Blog

One third obese by 2012

According to projections made in a paper published in the Journal of Epidemiology and Community Health, about a third of all adults will be obese by 2012 if historical trends continue. This information has been reported in the general media (BBC).

The study examined and extrapolated prevalence trends from 1993 to 2004. The prevalence of obesity was noted to increase over this time period from 13.6% to 24.0% among men and from 16.9% to 24.4% among women. Three projection models were applied to this data and estimated that obesity prevalence could be 32.1% (95%CI: 30.4; 34.8) in men and 31.0% (95%CI: 29.0; 33.1) in women by 2012.

The impact of recent strategies including the child measuring scheme and Change4Life are not included in these projections however it is estimated that 9,000 adults die early every year because of obesity-related illness.

Action: Clinicians should continue to support anti-obesity strategies by providing diet and lifestyle advice and through appropriate use of anti-obesity drugs.

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SMC December Update

The Scottish Medicines Consortium (SMC) has issued its monthly advice on new medicines.

Flecainide modified release 200mg capsules (Tambocor XL®) have been accepted for use in treating a variety of cardiac arrhythmias including AV nodal reciprocating tachycardia, Wolff-Parkinson-White Syndrome and atrial fibrillation in patients with disabling symptoms. It is also noted that the once-daily product has a lower acquisition cost than a twice-daily product at equivalent doses.

Action: Clinicians should be aware of the recommendations of the SMC. Routine use of rejected and restricted medicines should be avoided.

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Glitazones doubled fracture risk in women

The Journal of the Canadian Medical Association (CMAJ) has published the results of a systematic review and meta-analysis that aimed to quantify the fracture risk associated with glitazone therapy. There is also an accompanying editorial. This study has also reached the general media (BBC).

The analysis examined data from 10 studies involving 13,715 patients. The trials varied in duration from one to four years, collected data on fracture rates and were all double blind randomised trials. The overall risk of fracture was significantly increased by glitazone therapy with an odds ratio of 1.45 (95% confidence interval 1.18 - 1.79). When analysed separately it was found that there was no significant increase in risk among men but remained significant among women; odds ratio 2.23 (95% CI 1.65 - 3.01).

The authors note that the findings of this study have several limitations. None of the included trials were designed to measure the risk of fractures and a number of trials were excluded from the final analysis because they did not report fracture data.

Despite these limitations the rates of fractures reported were consistent with those observed in observational epidemiologic studies. The authors conclude that, "the relatively modest benefits of thiazolidinediones (glitazones) must be balanced against their significant long-term effects on bone and the cardiovascular system". In addition the authors quote the current NICE guideline recommendations that advise clinicians to "not commence or continue a thiazolidinedione (glitazone) in people who have evidence of heart failure, or who are at higher risk of fracture".

Action: This new analysis further confirms the current third line position for glitazones after metformin and sulphonylureas.

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Which antihypertensive combination?

The New England Journal of Medicine has published the results of a study that aimed to compare two combination drug therapies for hypertension to find the optimal approach.

The ACCOMPLISH Study recruited 11,506 participants with hypertension who were at high risk for cardiovascular events. They were randomly assigned to treatment with a fixed dose combination of amlodipine 5mg/benazepril 20mg or hydrochlorothiazide 12.5mg/benazepril 20mg. After 1 month, benazepril was titrated to 40 mg in both arms and thereafter the dose of the other agent was doubled. After 3 months additional antihypertensive medication could be added to attain blood pressure targets of <140/90 mmHg, or <130/80 mmHg in patients with diabetes or renal insufficiency.

The primary end point was the composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, hospital admission for angina, resuscitation after sudden cardiac arrest and coronary revascularisation.

The study found a 20% reduction in the primary endpoint in the amlodipine/benazepril arm (Event rate 9.6%) compared with the hydrochlorothiazide/benazepril arm (Event rate 11.8%) (p<0.001). There was a significant reduction in the rate of fatal and nonfatal myocardial infarction (2.2% versus 2.8%, p=0.04) although rates of cardiovascular mortality, stroke, and resuscitated sudden death were similar between the two groups.

The incidence of adverse effects was similar between the two groups for outcomes such as hypotension, cough and angioedema although peripheral oedema was much more common in the amlodipine arm (31.2% vs. 13.4%).

The authors of this study conclude that, "the benazepril/amlodipine combination was superior to the benazepril/hydrochlorothiazide combination in reducing cardiovascular events". However, it should be noted that there was a small but statistically significant difference in blood pressure that favoured the benazepril/amlodipine arm of the study and that these findings are contrary to those from the ALLHAT study that found no difference between amlodipine and chlorthalidone (another thiazide diuretic).

Action: This study needs evaluation in conjunction with the established evidence base and may require a revision of current guidelines. Clinicians should continue to implement the existing guidelines until advisory organisations have reviewed the current advice.

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