BMJ Open has published the results of an observational study that has link the use of hypnotics with an increased risk of mortality. This study has been reported in the general media (BBC).
The study reviewed electronic medical records for 10,531 patients who were prescribed hypnotics and 23,674 matched controls in an American healthcare database system between 2002 and 2007. Data were available for each individual for an average of 2.5 years.
After correction for several variables including age, gender, smoking, body mass index, ethnicity, marital status, alcohol use and prior cancer it was found that there was an increased risk of death among users of hypnotics compared to non-users, even at low levels of use. Among those prescribed hypnotics there were 638 deaths (6.06%) whereas among non-users there were 295 deaths (1.25%). For individuals prescribed up to 18 doses per year the hazard ratio was 3.60 (95% CI 2.92 to 4.44), for 18–132 doses per year this increased to 4.43 (95% CI 3.67 to 5.36) and for more than 132 doses per year it was 5.32 (95% CI 4.50 to 6.30).
The authors note that there are limitations to this study. The data relating to hypnotics covers the issuing of prescriptions. It is not known for sure that these prescriptions were dispensed and subsequently taken. Additionally, the data did not contain and could not be corrected for social and psychological problems as these are protected by privacy laws. Finally, despite the corrections made there may be residual confounding in the data.
The authors conclude that, "receiving hypnotic prescriptions was associated with greater than threefold increased hazards of death" and that "poor health did not explain the observed excess mortality".
National advice recommends only using hypnotics to treat insomnia when it is severe, disabling or causing the patient extreme distress.
Action: Clinicians should be aware of this study and continue to implement national recommendations. The absolute risk of death remains small and the association cannot be described as causal from this study.
MTRAC has issued two new Commissioning Support reviews in February 2012. The reviews cover buprenorphine and fentanyl transdermal patches.
The review for buprenorphine states that it is suitable for restricted prescribing under defined conditions in chronic non-cancer pain. The review came to this conclusion stating that the evidence for efficacy is relatively weak and the acquisition costs compared to oral sustained release morphine are unfavourable.
The review for fentanyl also states that it is suitable for restricted prescribing under defined conditions in chronic non-cancer pain. This review arrived at the same conclusion as above; that the evidence for efficacy is relatively weak and the acquisition costs compared to oral sustained release morphine are unfavourable.
Both reviews recommend that specific conditions are identified where transdermal products may be advantageous, for example patients who cannot tolerate tablet formulations, or have difficulty swallowing.
Action: Clinicians should be aware of these reviews and compare current practice to the recommendations, making changes where appropriate.
The National Institute of Health and Clinical Excellence (NICE) has published new guidance for the month of February 2012. This month there is one technology appraisal that impact upon primary care.
Exenatide prolonged release (Bydureon®) has been reviewed in a technology appraisal and is approved for use in combination with oral therapies when glycaemic control is inadequate (HbA1c > 7.5% or 59mmol/mol) and:
- BMI ≥ 35kg/m2 and psychological or medical problems associated with high body weight
- BMI < 35kg/m2 and insulin therapy would have significant occupational implications or weight loss would benefit obesity-related comorbidities
It is also advised the treatment is reviewed at 6 months and discontinued if:
- there has not been a reduction in HbA1c of 1% or 11mmol/mol if used in dual therapy
- there has not been a reduction in HbA1c of 1% or 11mmol/mol and a weight loss of at least 3% of initial body weight
Action: Clinicians should be aware of this new guidance and implement any necessary changes to practice.
The European Medicines Agency (EMA) has completed a review of aliskiren (Rasliez®) by recommending new contraindications and warnings. It is expected that prescribing information will be updated to reflect this new advice.
The ALTITUDE Study was recently stopped early due to a higher rate of adverse events occurring in the treated study participants. Initially, the EMA recommended against using aliskiren in combination with angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARB) in patients with diabetes.
This advice has now been extended to include a contraindication in patients with moderate to severe renal impairment and a warning that the combination of aliskiren and ACEI or ARB should be carefully considered in all other patients.
Action: Clinicians should be aware of this extended advice and implement any necessary change in practice. Patients should be reviewed where appropriate and alternative treatments considered.
The National Prescribing Centre has published MeReC Extra 52 (PDF) which discusses the results of the recently published SATURN study and recent safety warnings issued for citalopram, escitalopram and dabigatran.
The SATURN Study compared two high intensity statins in 1,385 patients with cardiovascular disease and assessed atherosclerotic plaque volume. At the end of the 2 year study there was no difference in this primary outcome with atorvastatin 80mg reducing plaque volume by 0.99% (95% CI −0.63 to -1.19) and rosuvastatin 40mg by 1.22% (95% CI -0.90 to -1.52). It is unknown whether this reduction in plaque volume would lead to a reduction in the risk of cardiovascular events. It is therefore suggested that clinicians continue to follow national guidance and use simvastatin 40mg for the majority of individuals here statin therapy is required.
The recently reported safety warnings regarding a dose dependent prolongation QT interval with citalopram and escitalopram and the new requirement to assess renal function before starting treatment with dabigatran and during therapy in some patients are also discussed.
Action: Clinicians who prescribe, or who see patients who are prescribed, any of these drugs will find this information useful and informative.