Dr Roger Boyle, National Director for Heart Disease, has issued a statement that clarifies National Policy on Statin Prescribing.
The statement has been issued following confusion surrounding the recommended targets in the JBS2 Guideline. JBS2 recommends that Total Cholesterol is treated to 4mmol/L and Low-Density Lipoprotein is treated to 2mmol/L.
The statement clarifies that current National Policy is that Total Cholesterol (TC) is treated to 5mmol/L and Low-Density Lipoprotein Cholesterol (LDL-C) is treated to 3mmol/L as determined by the National Service Framework (NSF) for Coronary Heart Disease (CHD). These targets may be revised upon completion of NICE Lipid Modification Guideline due in December 2007.
It is further clarified that the Quality and Outcomes Framework cholesterol target will remain at 5mmol/L for 2007/08 and that the Healthcare Commission will assess delivery of the current NSF and NICE guidance and not JBS2.
Action: Primary and Secondary prevention of CHD involving the prescribing of statins should being with Simvastatin 40mg. Treatment should aim to achieve TC below 5mmol/L and LDL-C below 3mmol/L.
An observational study comparing alendronate and risedronate has been published in Osteoporosis International.
The study retrospectively assessed the medical records of women aged 65 and over who were prescribed monthly preparations of alendronate (21,615 patients) or risedronate (12,215 patients) between July 2002 and September 2004.
Fracture rates were compared for the first year of treatment between the two groups after adjustment for potential differences in baseline fracture risk. In total 109 hip fractures occurred, 29 in the risedronate group and 80 in the alendronate group. Statistical correction of the data produced percentage fracture rates of 0.37% of the risedronate arm and 0.58% of the alendronate arm.
The Numbers Needed to Treat (NNT) is 476. This means 476 patients would need to be treated with risedronate instead of alendronate for a period of one year to prevent one hip fracture. This would be at an approximate cost of £81,500. This also assumes that, as an observational study, there are no biases in the data affecting the conclusion.
Action: This study has produced an interesting hypothesis but should not change current practice without additional research. Alendronate continues to be the first line choice where a bisphosphonate is indicated.
The National Institute of Health and Clinical Excellence (NICE) and Social Care Institute for Excellence (SCIE) jointly published a Clinical Guideline containing recommendations on the treatment and care of people with dementia in health and social care.
At the same time NICE published the widely expected appraisal on donepezil, galantamine, rivastigmine and memantine for the treatment of Alzheimer's disease.
The BBC has reported on the publication highlighting the controversy surrounding these guidelines and the expected legal challenge.
The appraisal of the drugs available for Alzheimer's disease recommends:
Donepezil, galantamine and rivastigmine can be prescribed for moderate Alzheimer's disease only, and if:
- treatment is started by a doctor who specialises in the care of people with dementia
- patients who are started on the drug are checked every 6 months, usually by a specialist team
- the check-up includes a test called the Mini Mental State Examination (MMSE) and assessment of the patient's behaviour and ability to cope with daily life
- the views of carers on the patient's condition are discussed at the start of drug treatment and at check-ups
- the drug is stopped if the patient's MMSE score falls below 10 points, or if the drug isn't working
- the least expensive of these three drugs is prescribed first. However, if this is not suitable for the patient another drug could be chosen
Memantine should not be prescribed for people with moderately severe to severe Alzheimer's disease unless it is being used as part of a clinical trial (research).
Patients already being treated with one of the three drugs recommended in the appraisal should be allowed to continue until the patient, carer and/or specialist decide it is the right time to stop.
Action: Clinicians should be aware of these new recommendations as they are getting substantial media coverage. Audits should be conducted to ensure specialist input is continued and that all four drugs are being used as recommended.
PLoS Clinical Trials has published the results of the Cardiovascular and Cerebrovascular Events in the Randomized, Controlled Alzheimer's Disease Anti-Inflammatory Prevention (ADAPT) Trial.
This study was stopped early in 2004 by the National Institute for Health. A press release stated "data from the ADAPT trial indicated an apparent increase in cardiovascular and cerebrovascular events among participants taking naproxen when compared to placebo".
The trial recruited patients aged 70 and over who had at least one first degree relative with Alzheimer's like dementia. NSAID use was excluded although antiplatelet doses of aspirin were permitted. Patients were then randomised to celecoxib, naproxen or matching placebos.
A composite endpoint including cardiovascular death, myocardial infarction, stroke, transient ischemic attack and heart failure was analysed and revealed a statistically significant increase in the number of events experienced in the naproxen arm of the study. At this point the study was terminated.
The study paper states "these results must be interpreted in the context of a trial that was stopped early, with small numbers of events that were not originally intended as specific outcomes".
An accompanying editorial is critical of the way the study was halted and states "the trial results cannot be reliably interpreted". As recently reported, the European Medicines Agency (EMEA) assessed the safety of all NSAIDS and concluded that a thrombotic risk could not be established for naproxen.
Action: The results of this study are not compelling enough to challenge the findings of the EMEA assessment. As previously recommended, naproxen is a suitable second line choice, after ibuprofen, where NSAIDs are indicated.
The Lancet has recently published the results of the MEDAL study; an analysis of the cardiovascular safety of etoricoxib (Arcoxia®) in comparison to diclofenac.
The study recruited 34,701 patients (24,913 with osteoarthritis and 9,787 with rheumatoid arthritis) and treatment was provided for an average of 18 months. Thrombotic cardiovascular events occurred in 320 patients taking etoricoxib and 323 patients taking diclofenac. There was no statistical difference. Upper gastrointestinal clinical event rates were lower in the etoricoxib arm but there was no difference in the number of complicated events.
PharmaTimes have reported this trial with a headline of "Arcoxia as safe as diclofenac for heart effects".
As recently reported, the European Medicines Agency completed a review of the safety of non-steroidal anti-inflammatories (NSAID) and found that diclofenac carries a thrombotic risk. The study has already drawn criticism for this reason.
Low dose ibuprofen continues to be the first line choice when an NSAID is clinically appropriate. Second line options include naproxen and possibly diclofenac. In patients at risk of gastrointestinal events use lansoprazole or omeprazole to provide gastro-protection.
Action: Use of etoricoxib should be restricted to situations where alternative therapies, including paracetamol based analgesia and the NSAIDs specified above, have failed.