A meta analysis published in the Archives of Internal Medicines has examined the safety of prescribing combinations of angiotensin converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) in patients with heart failure.
A search strategy revealed four randomised studies involving 17,337 patients that met the pre-defined inclusion criteria. The data were analysed for adverse events including symptomatic hypotension, worsening renal function, hyperkalaemia and treatment discontinuation.
The risk of:
- Treatment discontinuation was 28% higher [95% CI 1.17-1.40] in the combination cohort
- Symptomatic hypotension was 48% higher [95% CI 1.34-1.62] in the combination cohort
- Worsening renal function was 76% higher [95% CI 1.49-2.09] in the combination cohort
- Hyperkalaemia was 246% higher [95% CI 0.68-8.87 Not Significant] in the combination cohort
The authors conclude that, "Combination ARB plus ACE inhibitor therapy was accompanied by marked increases in adverse effects". It is also stated that these results are consistent with HF Guidelines that have expressed reservations about the place in therapy for the combination.
Action: Clinicians should ensure that single agents are used and titrated to maximum tolerated doses before considering combination treatment. It may be appropriate to seek specialist advice before starting combination therapy.
The Lancet has published the results of a prospective study that aimed to quantify the benefits of urgent treatment of transient ischaemic attack (TIA) and minor stroke in preventing recurrent strokes.
The study ran over 2 phases, the first was 'usual care' and the second was a rapid assessment and treatment. The primary outcome was the risk of stroke within 90 days of first seeking medical attention. The study recruited 1278 patients from the Oxford Vascular Study who presented with TIA or stroke. Of these, 591 patients were seen in the study clinic.
Phase 2 of the study reduced assessment time from a median of 3 days to less than 1 day. Median time to first prescription of treatment fell from 20 days to 1 day. Both of these changes were statistically significant (p < 0·0001).
The primary outcome occurred in 10·3% (32/310) of the patients during phase 1 of the study compared to 2·1% (6/281) in phase 2. The adjusted hazard ratio was calculated to be 0·20 (95% CI 0·08-0·49; p=0·0001). This reduction in risk was independent of age or gender and early treatment was did not increase the risk of intracerebral haemorrhage or other bleeding.
The Department of Health already have a National Stroke Strategy that highlights stroke as the third biggest cause of death in the UK and the largest single cause of severe disability. Since 2001, the National Service Framework for Older People has targeted reductions in stroke and the provision of specialist stroke services.
Action: Clinicians should ensure that they are aware of the local specialist stroke service and ensure patients are referred quickly for assessment and treatment when a TIA or minor stroke is suspected.
The Scottish Medicines Consortium has issued its monthly advice on new medicines.
Sitagliptin (Januvia®) has been accepted for restricted use in patients with type 2 diabetes. It is recommended that this agent is used in patients where diet and exercise combined with metformin does not provide adequate glycaemic control and sulphonylureas are contraindicated or not tolerated. They should be considered an alternative to glitazones.
Escitalopram (Cipralex®) has been rejected for the treatment of obsessive compulsive disorder. The economic data submitted was not sufficiently robust to gain acceptance.
Action: Clinicians should be aware of the recommendations of the SMC. Routine use of rejected medicines should be avoided.
A post-hoc analysis of the Treating to New Targets Study (TNT) has been published in the New England Journal of Medicine.
This analysis aimed to assess if the correlation between HDL-C (high density lipoprotein cholesterol) and cardiovascular risk remains, even at low levels of LDL-C (low density lipoprotein cholesterol). The primary outcome used was a composite of death from coronary heart disease, non-fatal myocardial infarction, resuscitation after cardiac arrest and fatal or non-fatal stroke.
Patients were stratified into five groups based on HDL-C levels. A significant difference was detected between those patients in the upper and lower groups. This difference was maintained but was only marginally significant when the analysis stratified for LDL-C.
The authors conclude that, "HDL cholesterol levels were predictive of major cardiovascular events in patients treated with statins" and that this relationship can be observed even in patients with low levels of LDL-C.
The statins are much more effective at lowering LDL-C than at increasing HDL-C. Reducing levels of LDL-C is more important than increasing level of HDL-C however this can be considered when choosing statin therapy. The Summaries of Product Characteristics list the effect of statins on HDL-C as follows:
- Simvastatin increases HDL-C by 13 to 16%
- Atorvastatin increases HDL-C by -3 to 12%
- Rosuvastatin increases HDL-C by 8 to 14%
Action: LDL-C and HDL-C are both important risk factors for preventing cardiovascular morbidity and mortality. Using simvastatin 40mg as first line treatment for lipid management will effectively reduce LDL-C and raise HDL-C to a greater extent than other statins.
The New England Journal of Medicine has published the results of a study that examined the efficacy of donepezil in the treatment of behavioural disturbance in patients with Alzheimer's disease (AD).
The study recruited 272 patients with AD and clinically significant agitation. 259 patients were randomly assigned to treatment with donepezil 10mg per day (n = 128) or placebo (n = 131) for a period of 12 weeks. Patients were assessed for a change in score on the Cohen-Mansfield Agitation Inventory (CMAI).
20.4% (22/108) of patients in the placebo group and 19.5% (22/113) in the donepezil group had a 30% or greater reduction in their CMAI score. The difference was not significant. There were also no significant differences in the several other assessments: Neuropsychiatric Inventory, the Neuropsychiatric Inventory Caregiver Distress Scale and the Clinician's Global Impression of Change.
Action: Neuroleptic drugs are commonly used to treat agitation in AD but have known adverse effects. Donepezil would appear to be ineffective and should not be used as an alternative.
