The European Medicines Agency has announced a review of the benefits and risks of aliskiren (Rasilez®) after the ALTITUDE Study was terminated early.
ALTITUDE was terminated on the recommendation of the data monitoring committee after a higher rate of adverse events was noted among the study participants. The study recruited 8,606 patients with type 2 diabetes at high risk of adverse heart and kidney events. In most patients, blood pressure was adequately controlled before participation in the study. Aliskiren at a dose of 300mg daily or placebo was added into existing therapy with either an angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB). The primary outcome for the study was a composite endpoint of cardiovascular death, resuscitated death, myocardial infarction, stroke, unplanned hospital admission for heart failure, onset of end-stage renal disease or doubling of baseline serum creatinine concentration.
The interim analysis found no benefit from treatment with aliskiren and a higher incidence of non-fatal stroke, kidney complications, hyperkalaemia and hypotension. Regulatory agencies have made the following interim recommendations:
- Clinicians should not prescribe aliskiren-containing medicines to diabetic patients in combination with ACE inhibitors or ARBs
- Clinicians should review the treatment of patients taking aliskiren at a routine appointment, and if patients are diabetic and are also taking ACE inhibitors or ARBs, aliskiren should be stopped and alternative treatments considered
- Patients are advised to discuss their treatment with their doctor at their next scheduled appointment
- Patients in clinical trials with aliskiren should contact their study site for guidance on their medication
- Patients who have any questions or concerns about their treatment should speak to their doctor or pharmacist at a routine appointment
Action: Clinicians should be aware of this review and implement the interim recommendations. Further details will be published as the review progresses. Clinicians should report any adverse events related to aliskiren through the Yellow Card reporting system.
The National Prescribing Centre has published a MeReC Bulletin (PDF) that focuses on the adoption of evidence into practice.
This bulletin takes evidence and ideas from educational theory, decision-making theory, information management and implementation science and brings them together in one place. It notes that directives issued 'from above' may be resisted and that there are no fool-proof solutions.
However, it is suggested that a strategic approach that is adaptable and flexible may prove more useful in addressing the concerns of potential adopters. Deploying a wide range of interventions in a sensitive and appropriate manner can then lead to important improvements in care.
Finally, this bulletin lists some key principles for more successful implementation of evidence into practice:
- Aim for adoption of the change in practice, not its imposition
- Consider the concerns and questions of potential adopters
- Make it easier for people to do the right thing
- Support effective foraging, hunting and hot-synching
- Recognise and support the communities of practice in which potential adopters work
- Allow potential adopters to experiment with and adapt the change in practice to their situation
- Plan carefully but be flexible and adaptable
Action: This MeReC Bulletin will be a worthwhile read for any clinicians who are also involved in encouraging evidence-based, clinically effective practice.
The manufacturer of Becodisks® has announced that this product will be discontinued in 2012. Ventodisks® were discontinued in 2006.
The letter cites "low and declining demand" and the availability of appropriate alternatives as the reasons for the decision to discontinue this product.
A from February 2012 the Becodisk Diskhaler packs in 100microgram, 200microgram and 400microgram with no longer be available in the UK. The Refill packs will no longer be available from May 2012.
Action: Clinicians should be aware of this announcement. Patients who are currently prescribed this medication should be identified and offered appropriate alternatives.
The National Institute of Health and Clinical Excellence (NICE) has published new guidance for the month of December 2011. This month there is one clinical guideline that impacts upon primary care.
The anaphylaxis clinical guideline offers advice on the care of adults, young people and children following emergency treatment for suspected anaphylaxis.
The recommendations include documenting acute clinical features in cases of suspected anaphylaxis including the time of onset and any circumstances immediately before the onset of symptoms in order to aid accurate diagnosis.
After treatment for suspected anaphylaxis referral to a specialist allergy service is recommended with an adrenaline injector issued as an interim measure pending assessment by the specialist service.
Action: Clinicians should be aware of this guideline and implement any necessary changes to practice.
The New England Journal of Medicine has published the results of the AIM-HIGH study. This study aimed to assess the cardiovascular benefits of extended-release niacin (nicotinic acid) added to simvastatin to raise low levels of HDL cholesterol.
The study recruited 3,414 patients who were at least 45 years old, had a history of cardiovascular disease, low levels of HDL and high levels of triglycerides. All participants received simvastatin at a dose of 40mg or 80mg per day with ezetimibe 10mg daily added in to achieve a target LDL cholesterol of 1.03 to 2.07 mmol/L. Participants were then randomly assigned to extended-release niacin, 1500 to 2000 mg per day, or matching placebo. The primary outcome of the study was a composite of death from coronary heart disease, nonfatal myocardial infarction, ischemic stroke, hospital admission for an acute coronary syndrome, or symptom-driven coronary or cerebral revascularisation.
The trial was stopped after a mean follow-up period of 3 years owing to a lack of efficacy. At two years, treatment with extended-release niacin had significantly increased the median level of HDL from 0.91mmol/L to 1.08mmol/L. Triglyceride levels were also significantly reduced from 1.85mmol/L to 1.38mmol/L. Despite these favourable changes there was no significant difference in the primary outcome which was found to have a hazard ratio of 1.02 (95% confidence interval 0.87 - 1.21, P=0.79).
The authors of the study conclude that, "Among patients with atherosclerotic cardiovascular disease and LDL cholesterol levels of less than 1.81 mmol/L, there was no incremental clinical benefit from the addition of niacin to statin therapy".
Action: In patients with stable cardiovascular disease, intensifying treatment with niacin to increase HDL confers no cardiovascular benefits. In such patients any decision to intensify treatment should take into account current guidelines, patient preference and a consideration of the risks and benefits.