The Medicines and Healthcare products Regulatory Authority has released a safety message on Long-Acting Beta-2 Agonists (LABAs) following concerns in America.
As previously reported, the results of the SMART Study have raised concerns over the use of LABAs in Asthma in the United States. LABAs can be issued without a steroid in America, however in the UK this would not occur if the BTS Guidelines are followed.
The MHRA message reminds prescribers that:
- patients given salmeterol or formoterol should always be prescribed an inhaled corticosteroid
- patients with acutely deteriorating asthma should not be initiated on salmeterol or formoterol
- patients should be monitored closely during the first 3 months of treatment
Action: Clinicians involved in the treatment of asthma should ensure that they are following the current BTS Guideline. Audits should be conducted to ensure that patients who are prescribed LABAs are also prescribed inhaled steroids.
The National Prescribing Centre has published a MeReC Bulletin that reviews Non-Drug Therapies for Depression in Primary Care.
The review is based on the NICE Guideline for Depression but summarises the following recommendations:
- There is little evidence of different efficacy between non-drug interventions. Choice should be based on patient preference and past experience, and local availability.
- For most people with mild depression general advice including exercise and watchful waiting may be sufficient. Guided self help based on cognitive based therapy (CBT) or short-term psychological therapies (counselling, problem solving and brief CBT) may be considered for those requiring treatment. Antidepressants are not recommended initially for mild depression.
- More extensive psychological therapies (16-20 sessions over 6-9 months) such as CBT or interpersonal therapy are appropriate for patients with moderate depression who do not respond to, or prefer not to take, antidepressants. They should be used with antidepressants in severe depression.
Action: Clinicians who diagnose and treat any form of depression should be aware of the place of non-drug therapies in treatment. Clinicians should also be aware of the services they are able to access at local level.
1/ Benzodiazepines in Older People
A paper recently published in the BMJ reviewed 24 trials of sedatives in older people with insomnia. This study calculated an NNT of 13 for improved sleep quality against an NNH of 6 for any adverse event. This indicates that an adverse event is twice as likely as improved sleep. There are limitations in this study as there were no corrections for dose, half life or potency of the sedative, however it does make clear that the benefits of sedatives in older people are marginal and are outweighed by the risks.
Action: Review sedative prescribing for insomnia in older people and encourage patients to consider stopping treatment whenever possible.
The blood pressure lowering arm of the ASCOT study was recently published and reported in the general media. The trial did not reach statistical significance for the primary outcome and there were blood pressure differences between the two arms that could account for all of the differences noted in the secondary and post-hoc tertiary end points. Despite this the study is being heralded as a landmark trial.
It certainly aids our understanding of hypertension management and rightly, NICE and BHS have agreed to work together to clarify the position of all antihypertensive agents to aid clinicians. In the meantime this study should not negate 40 years of experience in hypertension. Clinicians should continue to follow current guidelines, preferably the NICE Guideline of Hypertension Management, until the new Guidance becomes available.
Action: Continue to follow Hypertension Guidelines to aid prescribing in Hypertension. The NICE Guideline for Hypertension is recommended.
3/ NICE Primary Prevention with Statins
NICE have published the Final Appraisal Determination for Statins in Prevention of Cardiovascular Events. This document gives the clearest indication yet of the direction of the final appraisal. There is no mention of cholesterol targets in the document but it seems likely that the Primary Prevention risk threshold for treatment will be rolled back to 15% CHD risk (or 20% CVD) as originally detailed in the National Service Framework for CHD. The cost models produced by NICE are based upon using Simvastatin 20mg and 40mg. Simvastatin is currently the most evidence-based and cost-effective statin.
Action: Clinicians should be aware of the imminent NICE Guidance. Simvastatin should be used as the statin of choice wherever possible.
The American Heart Association carries a story about what appears to be the first sub-group study from ASCOT.
The Conduit Artery Function Evaluation (CAFE) study used an FDA approved non-invasive Sphygmocor system to estimate central aortic pressure by examining blood pressure variables at the wrist. This was done in a cohort of 2,199 people from the original 19,257 individuals in the ASCOT Study.
This study found that aortic systolic blood pressure was lower by 4.3mmHg in the amlodipine arm compared to the atenolol arm, despite arm blood pressures that were "virtually the same". The authors conclude that treating hypertension with an amlodipine based treatment is therefore favourable. One of the authors states, "The assumption has been that all types of blood pressure treatments are equally effective. We show that this assumption is untrue."
From what we already know about ASCOT there were blood pressure differences between the two arms of the study of 2.7/1.9mmHg on average over the duration of the study. Articles in the Lancet and BMJ that have already been covered on this website have also raised this discrepancy and it has been estimated that this difference could account for half to all of the differences found between the two arms in the original ASCOT Study.
There is no indication that these differences have been corrected for in the sub-group study, although using statements that blood pressures were "virtually the same" intimates that no corrections were made. It is unknown what the results of this study would have shown if the blood pressures in the two arms of the study had been identical. It is also unclear exactly what the place of aortic blood pressure estimation should be in the treatment of hypertension.
This study is perhaps of academic interest to those who are at the very cutting edge of hypertension diagnosis, management and innovation. It does not apply to current management on hypertension in primary care. It does however continue the ASCOT hype.
Action: Clinicians should continue to follow NICE Guidelines to diagnose and manage hypertension in primary care.
Tiotropium (Spiriva) is a long acting anticholinergic bronchodilator licensed for use in Chronic Obstructive Pulmonary Disease (COPD). It has been shown to maintain FEV1 in patients with COPD, but how does this equate to patient outcomes like exacerbations and hospital admissions?
A recent study in the Annals of Internal Medicine investigated the impact that tiotropium had on COPD exacerbation and hospital admission compared to placebo over a period of 6 months. The study has also been reported as an InfoPOEM in the Pharmaceutical Journal.
The study was conducted in 26 Veterans Affairs medical center so 99% of the patients were male. Patients had moderate to severe COPD with a mean baseline FEV1 of 36%. Patients received usual care, excluding use of other anticholinergic bronchodilators (ipratropium).
The study found that there was a statistically significant decrease in the number of exacerbations, but the actual difference was slight. The NNT was 23 to prevent on exacerbation in 6 months, but the confidence intervals extend to between 12 and 456. The impact on hospital admissions did not reach statistical significance although there were fewer admissions for COPD in the tiotropium arm. There was no impact on all-cause hospital admission.
The responses to this study point out that usual care in general practice would involve ipratropium and they are therefore critical of the design of the study. Knowing this exclusion however, allows the study to be put into context. The benefits of tiotropium in this study appear to be clinically marginal. As practice in primary care would not exclude the use of ipratropium this may have the effect of diluting the effect further.
Tiotropium treatment does decrease COPD exacerbations over 6 months but it does not decrease hospital admissions. Using the NNT of 23 this would equate to treating one patient for 11 years to prevent one exacerbation.
Action: The NICE COPD Guideline recommends that long acting bronchodilators are used in patients who remain symptomatic on short-acting agents. This study backs this advice.