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Prescribing Advice for GPs

An NHS Prescribing Advisers' Blog

Smoking cessation approaches

The Cochrane Library has published a review of the available evidence for smoking cessation to investigate the efficacy of a reduction in smoking cigarettes prior to a quit date compared to abrupt cessation.

The review noted that the most common approach to smoking cessation is to stop abruptly on a planned day but that this approach does not work for some individuals. This review identified 10 studies including 3,760 participants. All the studies were randomised controlled trial, five studies offered behavioural support, four offered self help material and the final study offered both. Three of the studies employed pharmacotherapy.

The analysis found no difference in abstinence rates when comparing the two methods (Relative Risk 0.94, 95% CI 0.79 to 1.13). This remained the same whether pharmacotherapy was use or not and was not affected by use of behavioural support or self help materials.

The authors conclude that, "reducing cigarettes smoked before quit day and quitting abruptly produced comparable quit rates, therefore patients can be given the choice to quit in either of these ways".

Action: Clinicians should be aware of this review; advising some smokers to reduce their smoking, perhaps supported with nicotine replacement therapy, may be an effective strategy if abrupt cessation has been unsuccessful in the past.

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MeReC Extra 44

The National Prescribing Centre has published MeReC Extra 44 (PDF) which contains information regarding a recent Cochrane review of combination therapy in asthma and use of antipsychotic drugs in dementia.

Observational data indicate that the addition of long-acting beta-agonists (LABA) is frequently given to steroid naive patients with mild asthma. A review of randomised trials conducted by the Cochrane Collaboration compared LABA and inhaled corticosteroid (ICS) therapy was not associated with a reduction in exacerbations requiring oral steroid or resulting in hospital admission when compared to ICS alone. There were some differences in some measures of lung function, frequency of short-acting beta-agonist use and symptoms.

The authors of the Cochrane review conclude that there is "insufficient evidence to support initiating therapy with a combination of inhaled corticosteroids (ICS) and long-acting ß2-agonist (LABA) rather than with inhaled corticosteroids alone". These results therefore support the current British Thoracic Society step-wise approach to treating asthma.

This MeReC Extra also discusses the results of an independent report on prescribing of antipsychotics in people with dementia. This report identified evidence of over-prescribing of antipsychotic drugs and made recommendations to the government. These recommendations have been accepted and may result in policy change. In the meantime clinicians should consider using non-pharmacological approaches to dealing with anxiety and behavioural problems if these are locally available.

Action: Clinicians who see patients with asthma or dementia will find this information useful and informative.

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BNF 59

The 59th Edition of the British National Formulary is currently being printed and distributed.

New or revised content in this version includes updated advice regarding:

  • Withdrawal of sibutramine
  • Community-acquired pneumonia
  • Safe use of cytotoxic medicines
  • Azathioprine and thiopurine methyltransferase (TPMT) testing
  • Prescribing and dispensing of ciclosporin by brand name

Additionally, in this version prescribing information for hepatic and renal impairment, pregnancy, and breast-feeding is now in-chapter rather than in an appendix and the equivalent doses of morphine sulphate and diamorphine hydrochloride table has been revised to improve clarity.

The web version has already been updated and printed version is available for purchase.

The print version is distributed by the Department of Health to Dentists, Doctors, Nurses and Pharmacists providing NHS services.

The BNF quality management system is now ISO 9001:2008 certified in recognition that the procedures that underpin the production of BNF products are robust and carried out to the highest of standards.

Action: All clinicians should start using BNF 59 as soon as the print version arrives. The web version can be used to access the latest information if necessary.

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Prevention of diabetes

The New England Journal of Medicine has published the results of two studies that aimed to assess the efficacy of medication on the incidence of diabetes and cardiovascular events. The results of these studies have been reported in the general media (BBC).

Although the results are published as two papers the study was a single trial that investigated to interventions. The first intervention compared the effect of valsartan (Diovan®) to placebo. The second intervention compared nateglinide (Starlix®) to placebo.

The study recruited 9,306 participants in 40 countries and followed them for a median period of 5 years for incidence of diabetes. Participants had impaired fasting plasma (glucose between 5.3mmol/L and 7.0mmol/L) and also a risk factor for or overt cardiovascular disease. Treatment was randomly assigned in a 2-by-2 factorial design such that patients could have been taking 2 placebos, only one of the active treatments or both of the active treatments.

The primary outcome measure was either incidence of diabetes or a composite of cardiovascular events including death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, hospital admission for heart failure, arterial revascularisation or hospital admission for unstable angina.

Nateglinide provided no benefit over placebo in prevention of diabetes (Hazard Ratio 1.07, 95%CI 1.00-1.15, p=0.05) or cardiovascular events (HR 0.94, 95%CI 0.82-1.09, p=0.43). Valsartan provided no benefit over placebo on prevention of cardiovascular events (HR 0.96, 95%CI 0.86-1.07, p=0.43) but did provide a modest benefit in progression to diabetes (HR 0.86, 95%CI 0.80-0.92, p<0.001).

The authors conclude that treatment with "nateglinide for 5 years did not reduce the incidence of diabetes or the co-primary composite cardiovascular outcomes" and that "use of valsartan for 5 years, along with lifestyle modification, led to a relative reduction of 14% in the incidence of diabetes but did not reduce the rate of cardiovascular events".

The paper notes that the reduction in diabetes observed with valsartan equates to 38 fewer cases of diabetes per 1,000 patients every 5 years. In addition, the risk reduction observed is less than that seen with alternative strategies including lifestyle modification, metformin and rosiglitazone. The authors therefore note that "lifestyle modification should remain the primary intervention to reduce the risk of diabetes in the general population".

Action: Clinicians should be aware of these studies. Individuals with impaired fasting glucose should be encouraged to make lifestyle modifications to prevent or delay progression to diabetes.

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Episodic hypertension and stroke risk

The Lancet has published the results of an analysis that has identified a correlation between stroke risk and variability or maximal in systolic blood pressure (SBP). This study has been reported in the general media (BBC).

The study noted that guidelines for the treatment and diagnosis of hypertension focus upon assessment of blood pressure over a time period, essentially providing an average over the time the readings are taken. This study aimed to assess stroke risk in comparison to visit-to-visit variability in SBP (expressed in standard deviations) or maximum SBP using data from the UK-TIA and ASCOT-BPLA studies.

The analysis founds that mean SBP, variability in SBP (as standard deviation, coefficient of variation and variation independent of the mean) all positively correlated with stroke risk. The correlations in variability remained after correction for mean SBP.

Additionally, it was noted that the association was strong individuals in the top decile of variability and this association grew stronger after correction for mean SBP, age, sex and other risk factors (Hazard Ratio [HR] 12.08, 95% CI 7.40-19.72, p<0.0001). Maximum SBP was also strongly correlated after correction for mean SBP (HR 15.01, 95% CI 6.56-34.38, p<0.0001).

The authors note that their findings do not prove causality and recommend that consideration be given to how visit-to-visit strong>variability in blood pressure might be integrated into clinical practice. Attention is also drawn to the "false reassurance of a few normal blood-pressure readings ".

Action: Clinicians should be aware of this study. While clinical guidelines are reviewed perhaps it would be prudent to give a little more weight to one-off high blood pressure readings.

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