The British Medical Journal has published the results of a systematic review and meta-analysis of studies assessing the efficacy of treatments for irritable bowel syndrome (IBS). The results have also been reported in the general media (BBC).
The review identified 35 studies that were of the required quality and provided the data necessary for the analysis. These studies included trials of antispasmodics, fibre supplements and peppermint oil.
Fibre reduced the risk of persistent symptoms however the effect was limited to ispaghula (Hazard Ratio 0.78, 95% CI 0.63 to 0.96). Studies of antispasmodics revealed consistent evidence of efficacy for hyoscine (HR 0.63, 95% CI 0.51 to 0.78) but the evidence for mebeverine was poor based on a single study of 80 patients. Peppermint oil was also found to be beneficial (HR 0.43, 95% CI 0.32 to 0.59).
The authors conclude that, "fibre, antispasmodics, and peppermint oil were all more effective than placebo in the treatment of irritable bowel syndrome".
Action: Clinicians will be reassured by the results of this review of IBS treatments. In particular, it appears that ispaghula, hyoscine and peppermint oil offer the most effective treatment options.
The Scottish Medicines Consortium (SMC) has issued its monthly advice on new medicines.
Quetiapine fumarate (Seroquel XL®) has been accepted for use in the the treatment of schizophrenia and manic episodes associated with bipolar disorder based on similar or lower costs compared to immediate-release quetiapine.
Insulin glulisine (Apidra®) has been restricted to use in the treatment of adolescents and children, 6 years or older with diabetes mellitus, where treatment with insulin is required and for whom soluble human insulin is inappropriate. This medicine has previously accepted with the same restrictions for use in adults.
Insulin lispro (Humalog KwikPen®, Mix25 KwikPen®, Mix50 KwikPen®) have all been accepted (KwikPen, Mix 25 and 50) for the treatment of patients with diabetes mellitus who require insulin for maintenance of normal glucose homeostasis, for whom either a short-acting insulin analogue or a biphasic insulin analogue is appropriate.
Action: Clinicians should be aware of the recommendations of the SMC. Routine use of rejected and restricted medicines should be avoided.
The Clinical Trial Service Unit at the University of Oxford have announced the summary results (PDF) of the SEARCH study. Publication of the full results is expected in 2009.
The study aimed to assess the impact of intensive lipid lowering with simvastatin 80mg versus standard therapy with simvastatin 20mg and folic acid supplementation in patients who have had a heart attack.
The study recruited 12,000 participants with 6,000 being randomly assigned to treatment with intensive or standard statin therapy. The study ran for an average of 6.7 years. The intensive treatment produced a reduced level of low-density lipoprotein cholesterol (LDL-C) by 0.35mmol/L. This reduction was associated with a 6% reduction in heart attacks, stroke and revascularisation procedures although this was not statistically significant. The study also found that there was no benefit from folic acid or vitamin B12 supplementation in the prevention of heart attacks or strokes.
The press release states that the study results, although not statistically significant, are consistent with data from meta-analysis showing a 0.35mmol/L reduction in LDL-C is associated with a relative risk reduction of 6-7% and therefore supports the assertion at lower LDL-C is better.
However, it is also notable that during the study 3 patients treated with simvastatin 20mg developed myopathy while 53 developed this adverse drug reaction while taking simvastatin 80mg. This is a relative risk increase of 1667%.
Action: Clinicians should consider the absolute benefit that an individual patient could expect to achieve from additional cholesterol lowering before increasing statin therapy. This absolute benefit should be balanced against the increased risk of side effects and the potential benefits of other interventions (for example smoking cessation, lifestyle changes and blood pressure reduction).
The New England Journal of Medicine has published the results (PDF) of the JUPITER study. This study has been reported in the general media (BBC) with an indication that treatment recommendations may need to be revised based on the findings.
The study was a primary prevention study in patients at high risk of cardiovascular events with risk defined by age and blood levels of high-sensitivity C-reactive protein (CRP) but low-density lipoprotein levels (LDL-C) below 3.4mmol/L.
The study recruited 17,802 patients and randomly assigned them to treatment with rosuvastatin 20mg or placebo. The primary endpoint of the study was a combination of myocardial infarction (MI), stroke, arterial revascularization, hospitalization for unstable angina and death from cardiovascular causes.
The study found a statistically significant relative risk reduction of 44% in the primary outcome (Hazard Ratio = 0.56; 95% CI, 0.46 to 0.69; P<0.00001). There were similar risk reductions for stroke and MI when analysed as secondary outcomes. Treatment reduced LDL-C by 50% and CRP by 37%.
The study was originally designed to be event driven, reaching adequate statistical power when 520 primary events had occurred. The study was stopped early when the benefits became clear however only 393 primary events had occurred. This may impact on the overall validity of the results.
An accompanying editorial (PDF) points out that absolute risk reductions are an important consideration before implementing changes to practice. Absolute benefits must be weighed against the associated risks and costs of the treatment in deciding if the intervention is clinically appropriate.
The editorial also notes that evidence already exists that statins reduce the risk of cardiovascular events in those at high risk. Guidelines that recommend a threshold level of cardiovascular risk before starting treatment are based on economic evaluations; this new evidence will almost certainly initiate a review of the current guidelines to balance the benefits of treatment and its long-term safety and cost.
Action: The results of this study need careful analysis before changes are made to national guidelines and current practice. Clinicians should continue to implement existing guidance.
The Medicines and Healthcare products Regulatory Agency (MHRA) has published Drug Safety Update for November 2008 (PDF).
This issue provides a safety update regarding adverse psychiatric reactions linked to varenicline use. There is also a hot topic discussion regarding the possible increased risk of cancer associated with ezetimibe. Finally, the stop press section reminds clinicians about the withdrawal of rimonabant, recent concerns regarding inhaled anticholinergics and paracetamol in infants.
Action: Clinicians will find this publication to be a useful review of current issues in drug safety.