The Cochrane Library has published the results of a meta-analysis that aimed to provide an updated review on the efficacy of tiotropium in patients with COPD.
The review identified 22 studies involving 23,309 participants. 19 studies use the dry powder inhaler while 3 used the soft mist inhaler. The studies were between three months and four years in duration and compared active treatment to placebo.
Based on evaluation of data from the St George's Respiratory Questionnaire (SGRQ) there was a statistically significant improvement in quality of life (mean difference -2.89; 95% CI -3.35 to -2.44), more patients had a clinically significant improvement in quality of life (odds ratio 1.52; 95% CI 1.38 to 1.68) and fewer had a clinically significant deterioration (OR 0.65; 95% CI 0.59 to 0.72).
Tiotropium treatment also resulted in significantly fewer exacerbations (OR 0.78; 95% CI 0.70 to 0.87) corresponding to an NNT of 16 when compared to placebo to prevent one exacerbation in a year. Hospital admissions for exacerbations were also reduced but all-cause hospital admissions remained the same.
All-cause mortality was similar between the placebo and active treatment groups until the two inhaler devices were analysed individually. Treatment with the dry powder device resulted in fewer deaths (non-significant) compared with placebo (Peto OR 0.92; 95% CI 0.80 to 1.05) but treatment with the soft mist inhaler resulted in significantly more deaths (Peto OR 1.47; 95% CI 1.04 to 2.08).
The authors conclude that, "tiotropium improves patients' quality of life, and reduces the risk of exacerbations, including exacerbations leading to hospitalisation". They also advise caution in using the soft mist inhaler.
Action: The findings of this analysis are in keeping with the advice in the current NICE guideline for COPD. As suggested previously, it may be prudent to reserve use of the soft mist inhaler to patients who cannot operate or tolerate the dry powder device.
Thanks to Kevin Ashworth for spotting this article
The Medicines and Healthcare products Regulatory Agency (MHRA) has published Drug Safety Update for July 2012 (PDF).
This issue reminds clinicians of the risk of serious haemorrhage observed with dabigatran (Pradaxa®) and clarifies the contraindications and monitoring requirements.
- Dabigatran is contraindicated in clinical conditions associated with a significant risk of bleeding, such as:
- current or recent gastrointestinal ulceration
- malignant neoplasms
- recent brain or spinal injury
- recent brain, spinal or ophthalmic surgery
- recent intracranial haemorrhage
- oesophageal varices
- arteriovenous malformations
- vascular aneurysms
- major intraspinal or intracerebral vascular abnormalities
- The benefits and risks of starting dabigatran should also be considered carefully for patients who may have other conditions that put them at an increased risk of major bleeding (but in whom treatment with dabigatran is not contraindicated)
- Use of dabigatran is contraindicated with dronedarone, and with other anticoagulants, except when switching treatment to or from dabigatran, or with the use of unfractionated heparin for maintenance of venous or arterial catheter patency
- Concomitant use of antiplatelet agents increases the risk of major bleeding with dabigatran approximately two-fold, therefore a careful benefit-risk assessment should be made prior to initiation of treatment
Renal function should be assessed in all patients before starting dabigatran and at least once a year in patients older than 75 years or those with a suspected decline in renal function. Dabigatran is contraindicated in patients with severe renal impairment (creatinine clearance <30 mL/min)
Action: Clinicians will find this publication to be a useful review of current issues in drug safety.
The National Institute of Health and Clinical Excellence (NICE) has published new guidance for the month of July 2012. This month there are two technology appraisals that impact upon primary care.
The adalimumab (Humira®) for the treatment of moderate to severe ulcerative colitis appraisal has been terminated and the treatment cannot be recommended. No evidence submission was made by the manufacturer or technology sponsor.
Rivaroxaban (Xarelto®) is recommended as an option for the treatment of deep vein thrombosis and prevention of recurrent deep vein thrombosis and pulmonary embolism. This treatment was evaluated against warfarin and low molecular weight heparins (LMWH). It is noted that in the short term this treatment is less expensive than other options. Over longer periods it becomes more expensive but the additional expense is justified by additional benefits in terms of less monitoring compared to warfarin and oral route of administration compared to LMWH.
Action: Clinicians should be aware of this month's new guidance and implement any necessary changes to practice.
The National Institute of Health and Clinical Excellence (NICE) has published new public health guidance for the prevention of type 2 diabetes.
The guidance contains recommendations regarding risk assessment and stratification as well as interventions appropriate to the level of risk.
Initial assessment of the risk of developing type 2 diabetes, using tools like the Diabetes UK Risk Score tool, is recommended for adults aged 40 and over, people of South Asian and Chinese descent aged 25–39, and adults with conditions that increase the risk of type 2 diabetes, other than pregnant women. Blood tests (fasting plasma glucose or HbA1c) are recommended to those with a high risk score or those aged 25 and over of South Asian or Chinese descent whose body mass index (BMI) is greater than 23 kg/m2.
Lifestyle advice, including advice about diet, weight management and physical activity, is recommended in all cases with the intensity increasing with the assessed level of risk.
In addition, metformin is recommended for people who are at high risk and are still progressing towards type 2 diabetes, despite their participation in an intensive lifestyle-change programme or who unable to participate in lifestyle-change programmes. Orlistat is recommended for adults who have a BMI of 28 kg/m2 or more and who are still progressing towards type 2 diabetes.
Action: Clinicians should be aware of this new guidance and implement any necessary changes to practice.
The Scottish Medicines Consortium (SMC) has issued its monthly advice on newly licensed medicines.
Adalimumab (Humira®) has been rejected for use in the treatment of moderately to severely active ulcerative colitis in adult patients who have had an inadequate response to conventional therapy. The manufacturer failed to make a submission.
Azilsartan (Edarbi®) has been rejected for the treatment of essential hypertension in adults. The manufacturer failed to make a submission.
Azithromycin dihydrate (Azyter®) has been rejected for the local antibacterial treatment of conjunctivitis caused by susceptible strains. The manufacturer failed to make a submission.
Eplerenone (Inspra®) has been accepted for use in addition to standard optimal therapy, to reduce the risk of cardiovascular mortality and morbidity in adult patients with NYHA class II (chronic) heart failure and left ventricular systolic dysfunction (LVEF ≤30%).
Golimumab (Simponi®) has been accepted for restricted use for the treatment of active and progressive psoriatic arthritis in adult patients when the response to previous disease-modifying anti-rheumatic drug (DMARD) therapy has been inadequate. It can be used alone or in combination with methotrexate when at least two standard DMARDs have failed to provide a response and at the dose of 50mg only.
Tadalafil (Adcirca®) has been accepted for restricted use in the treatment of adults with pulmonary arterial hypertension (PAH) classified as World Health Organisation functional class (WHO-FC) II and III, to improve exercise capacity. The restriction limits treatment initiations to specialists working in the Scottish Pulmonary Vascular Unit or similar specialists.
Action: Clinicians should be aware of the recommendations of the SMC. Routine use of rejected and restricted medicines should be avoided.