Clinical Knowledge Summaries (CKS) has been updated in April for the following clinical areas:
Action: Clinicians who see patients with any of these conditions may find the updated information useful when reviewing current clinical practice.
The Journal of the American Medical Association has published the results of a study that compared the attainment of aggressive targets with standard targets in patients with type 2 diabetes.
The study recruited 499 American Indian men and women aged 40 years or older with type 2 diabetes and no prior CVD events. The trial was randomised but open label with a follow up of 3 years. Patients were assigned to aggressive targets of 110mmHg systolic blood pressure (SBP) and low-density lipoprotein cholesterol (LDL-C) of 1.8mmol/L or standard targets of 130mmHg SBP and 2.6mmol/L LDL-C. The primary outcome was progression of atherosclerosis measured by common carotid artery intimal medial thickness (C-IMT).
During the last 12 months of follow up mean SBP was 117mmHg (95% CI 115-118) in the aggressive group and 129mmHg (95% CI 128-130) in the standard group. Mean LDL-C was 1.86mmol/L (95% CI 1.78-1.94) and 2.69mmol/L (95% CI 2.61-2.74) respectively. The primary outcome was statistically significant (p<0.001); IMT regressed in the aggressive group and progressed in the standard group. Rates of adverse events related to blood pressure medication occurred more often in the aggressive group and this was statistically significant.
The study was not designed to assess differences in rates of cardiovascular events however the data were collected and analysed and were not different between the two groups. (1.6/100 and 1.5/100 person-years; P = 0.87) The authors conclude that, "further follow-up is needed to determine whether these improvements will result in lower long-term CVD event rates".
It should be noted that the patients recruited to this study are not representative of a broader UK population and that the standard target used in this study was more aggressive than current treatment targets in the UK. Despite these limitations this study again raises questions about the appropriateness of treating individual risk factors to low targets.
Action: Clinicians should continue to follow current targets as defined by the Department of Health and the National Institute of Health and Clinical Excellence. Blood pressure targets are currently 140/85mmHg or 140/80mmHg in patients with diabetes and total cholesterol should be treated to 5mmol/L or a 30% reduction from baseline, whichever is greater.
The Midlands Therapeutics Review and Advisory Committee (MTRAC) has issued updated advice for pioglitazone (Actos®) and rosiglitazone (Avandia®).
The pioglitazone review places this drug as having weaker evidence and having a lower place in therapy. It is suitable for restricted prescribing in primary care because of conflicting evidence in the long-term clinical effects of this drug on cardiovascular outcomes.
The rosiglitazone review recommends that this drug should not be prescribed in primary care because of "inadequate evidence of safety and/or efficacy".
Action: Current recommendations still stand. Metformin continues to be the first choice oral hypoglycaemic with a sulphonylurea added in as second line. This is based upon a proven record of efficacy and safety.
The manufacturer of Sativex®, the cannabinoid oromucosal spray, has announced that a phase III study failed to reach statistical significance for pain relief in patients with central neuropathic pain due to Multiple Sclerosis (MS).
The study recruited 339 patients who had failed to get adequate pain relief with existing therapies. Patients were randomised to active treatment or placebo and were followed up for 14 weeks. The primary outcome was a reduction in pain by 30% measured on a 1-10 scale.
Patients taking the active treatment reported a mean reduction in pain of 50%, however this was not statistically different from the [unreported] pain reduction level in the placebo arm. This finding was reflected throughout all of the secondary outcome endpoints.
The announcement highlights a higher than expected response in the placebo arm of the study and also notes a lower than expected rate of adverse reactions to the active treatment in comparison to previous studies.
Action: Despite the positive spin contained in the press release it is apparent that the benefits of this product are marginal. New patients should not be started on this product until a clearer benefit has been demonstrated in trial conditions.
Thanks to PharmaGossip for highlighting this press release
The Scottish Medicines Consortium has issued its monthly advice on new medicines.
Vildagliptin (Galvus®) has been accepted for restricted use in combination with metformin in patients who are inappropriate for sulphonylureas and have insufficient glycaemic control despite maximal tolerated dose of metformin. This submission did not examine combination use of vildagliptin with sulphonylureas or glitazones.
Insulin glulisine (Apidra®) and insulin glargine (Lantus®) in pre-filled pens (Solostar®) have been accepted for use in patients who require insulin where insulin analogues are appropriate and a pre-filled device offers advantages over a pen and cartridge device. Both of these advisory documents also clarify where the use of insulin analogues is appropriate in relation to established insulin products.
Action: Clinicians should be aware of the recommendations of the SMC. Routine use of rejected medicines should be avoided.