The Medicines and Healthcare products Regulatory Agency (MHRA) has highlighted the results of an international study led by the Hull York Medical School that aimed to assess the cardiovascular risks of non-steroidal anti-inflammatory drugs (NSAIDs).
This study included data from more than 2,700,000 individuals included in 51 studies. The data set allowed analysis of 184,946 cardiovascular events. The relative risks of cardiovascular events for several NSAIDs were calculated as follows:
- Rofecoxib 1.45 (95% CI 1.33 - 1.59)
- Diclofenac 1.40 (1.27 - 1.55)
- Ibuprofen 1.18 (1.11 - 1.25)
- Naproxen 1.09 (1.02 - 1.16)
- Celecoxib 1.26 (1.09 - 1.47) - from a data subset
- Etoricoxib 2.05 (1.45 - 2.88) - from a data subset
- Etodolac 1.55 (1.28 - 1.87) - from a data subset
- Indomethacin 1.30 (1.19 - 1.41) - from a data subset
The authors conclude that, "among widely used NSAIDs, naproxen and low-dose ibuprofen are least likely to increase cardiovascular risk". They also note that the data for indomethacin casts doubt on its continued use.
Action: As noted by the MHRA, the findings presented by this study are not new but the relative risk information may prove useful. Current advice remains the same; Use an NSAID with the lowest risk, for the shortest time and at the lowest dose necessary to control symptoms.
The National Institute of Health and Clinical Excellence (NICE) has published new guidance for the month of September 2011. This month there is one clinical guideline that impacts upon primary care.
The Multiple pregnancy clinical guideline (QRG) offers evidence-based advice on the care of women with multiple pregnancies (twins and triplets) in the antenatal period. This guideline should be read in conjunction with the already published Antenatal care clinical guideline from March 2008.
Action: Clinicians should be aware of this guideline and ensure that women with multiple pregnancies are appropriately referred.
The Department of Health has written (PDF) to NHS colleagues advising that the influenza vaccine Viroflu® should be avoided in children aged under 5 years.
It is already recommend that Enzira® is avoided in this age group due to an increased risk of febrile convulsions. Viroflu uses the same starting antigen as Enzira and although the manufacture process is different evidence has now emerged that Viroflu is associated with a higher rate of fever than other vaccines.
The European regulatory authorities are considering adding the following precaution to the marketing authorisation:
"Due to the risk of high fever, consideration should be given to the use of alternative seasonal influenza vaccines in children under the age of 5 years. In case it is used in children, parents should be advised to monitor for fever for 2 - 3 days following vaccination".
Action: Clinicians should be aware of this precaution and use an alternative vaccine in children aged under 5 years.
The European Medicines Agency (EMA) has recommended that lacosamide (Vimpat®) 15mg/ml syrup is discontinued. This product is licensed for the treatment of partial-onset seizures as an adjunctive therapy in patients with epilepsy aged 16 years and older.
This product was recalled voluntarily in September 2011 due to a quality issue that resulted in an uneven distribution or precipitation of the active ingredient. Changes to the storage recommendations of the product have not remedied this defect.
Patients are advised to continue taking their medication but to consult with their doctor. A license application for a 10mg/ml liquid product has been submitted. This product is not affected by this quality issue and is already available in the United States.
Clinicians should consider using lacosamide film coated tablets where appropriate. It may be possible to obtain the lower strength liquid product on a named patient basis where tablets will not be an option.
Action: Clinicians should be aware of this recommendation. The number of affected individuals should be small but changes to treatment will need careful planning.
NHS Evidence has published Eyes on Evidence for September 2011. This issue includes the results of a meta-analysis into the risks and benefits of aspirin treatment for the primary prevention of cardiovascular disease.
This most recent study was published in the American Heart Journal. Nine trials involving 102,621 patients that ran for an average of 6.9 years were reviewed. Aspirin treatment was associated with a reduction in the composite primary outcome of major cardiovascular events (risk ratio [RR] 0.90, 95% CI 0.85-0.96, P<0.001) but there was no significant reduction for the individual outcomes of myocardial infarction, stroke, ischaemic stroke or all-cause mortality.
Conversely, there was an increased risk of haemorrhagic stroke (RR 1.35, 95% CI 1.01-1.81, P=0.04) and major bleeding (RR 1.62, 95% CI 1.31-2.00, P<0.001).
The authors also summarise this data over a 5 year period noting that for every 1,000 patients treated aspirin would prevent 2.9 major cardiovascular events but cause 2.8 major bleeds.
The authors conclude that, "the evidence provides only modest support for a benefit of aspirin in patients without clinical cardiovascular disease, which is offset by its risk".
NHS Evidence also notes that current 'PolyPill' trials have explicitly not included aspirin in the studies, instead opting for a combination of statins and antihypertensive agents. It is also noted that secondary prevention is a different matter as aspirin is linked with a 15% reduction in subsequent events in such patients.
Action: Clinicians should be aware of UK policy to not use aspirin for primary prevention. Eyes on Evidence may also be a useful resource in maintaining up to date knowledge.
Thanks to Kevin Ashworth for spotting this article