The Journal of the American Medical Association has published the results of a retrospective observational study that aimed to assess the rate of death and acute myocardial infarction after stopping clopidogrel in patients with acute coronary syndrome (ACS). Pulse Magazine has reported this study.
The study reviewed data for 3,137 patients with ACS discharged from 127 American hospitals between October 2003 and March 2005. The main outcome was the rate of all-cause mortality or acute myocardial infarction (AMI) after stopping treatment with clopidogrel.
The results were analysed for those patients who were medically treated and those who underwent percutaneous coronary intervention (PCI) separately. Average treatment duration was 302 days (SD 151 days) in medically treated patients and 278 days (SD 169 days) in PCI-treated patients.
Death or AMI occurred in 17.1% of the medically treated patients with 60.8% of these events happening within 90 days of stopping clopidogrel. The same outcome occurred in 7.9% of the PCI-treated patients with 58.9% occurring within the first 90 days.
It has already been suggested that treatment with clopidogrel should be extended, tapered gradually or bridged with alternative antiplatelet therapies. However, the study did not identify reasons for treatment cessation with clopidogrel and examined all-cause mortality rather than cardiovascular mortality and the data may therefore contain some inherent and unexplained bias.
The authors of the study conclude that, "additional studies are needed to confirm the clustering of events" and "to identify strategies to reduce early events after clopidogrel cessation".
Action: Clinicians should continue to follow current NICE and SIGN guidance when reviewing clopidogrel treatment.
The Scottish Medicines Consortium has issued its monthly advice on new medicines.
Mesalazine has been accepted for mild and moderate exacerbations of ulcerative colitis and for maintenance of remission in ulcerative colitis and Crohn's disease.
Valsartan and losartan 100mg/hydrochlorothiazide 12.5mg have been accepted for the treatment of hypertension, the latter when monotherapy with either agent fails.
Glyceryl trinitrate 0.4% ointment (Rectogesic®) was rejected because the economic case was insufficiently robust to gain acceptance. This was the fourth submission to be rejected.
Action: Clinicians should be aware of the recommendations of the SMC. Routine use of rejected medicines should be avoided.
A second study comparing varenicline to nicotine replacement therapy (NRT) has been published in Thorax.
This study was an observational, open label study involving approximately 750 patients so it is larger that the study already reported. The study measured self-reported continuous abstinence rate (CAR) confirmed by a carbon monoxide breath test for the last 4 weeks of treatment. Secondary outcomes included 52 week CAR.
The results of the study are as follows:
- CAR over last 4 weeks was statistically greater with varenicline (55.9%) than with NRT (43.2%) Relative Risk 1.70, [95% CI 1.26 to 2.28, p<0.001] NNT = 9
- CAR at week 52 was greater but not significantly different with varenicline (26.1%) than with NRT (20.3%) Relative Risk 1.40, [95% CI 0.99 to 1.99, p=0.056] NNT = 17 (May not be valid as difference was not statistically different)
- The most frequently reported side effect was nausea (37.2% with varenicline and 9.7% with NRT) NNH = 4
The authors of the paper openly discuss the limitations of the study citing the higher drop out rate and the higher numbers of treatment refusal in the NRT arm. The open label approach in this study may have created a differential in patient motivation that could have biased the results.
The results of this study demonstrate a higher initial efficacy with varenicline however this difference appears to reduce over time. The calculated Numbers Needed to Treat (NNT) shown above show that at the end of a primary course of treatment with varenicline there will be one more quitter but two people with nausea when compared to treatment with NRT.
Action: Clinicians should continue to follow the existing NICE Guidance and prescribe with due regard for the safety warning issued by the MHRA.
The British Medical Journal has published the results of a Welsh survey into GP reporting of adverse drug reactions (ADRs) through the Yellow Card system. The survey found that 63% did not submit a yellow card from 2004 to 2007.
The survey collected data on 1,700 GPs in 22 local health boards. A sample of 224 GPs was questioned more closely to compare those who use the reporting mechanism often with those who had not used the reporting system at all. It was found that good users of the system were generally more aware of the yellow card scheme, more involved in training and study and made the time to report.
Action: The safe use of medicines relies upon effective post marketing surveillance. All clinicians should make time to complete and submit and set themselves a target for submission each month - even if it's only one!
The ACCORD Study has had one study arm halted due to an increased number of deaths in the intensive treatment arm. PharmaTimes and USAToday have already reported this story and it is likely to reach UK media soon.
The study has been designed to evaluate the impact on cardiovascular outcomes of:
- Intensive blood glucose management versus standard treatment
- Intensive lipid management versus standard treatment
- Intensive blood pressure management versus standard treatment
The glycaemic arm of the study has been stopped 18 months early when researchers found that there had been 257 deaths in the intensive treatment group compared with 203 deaths with the standard therapy. Further analysis has, as yet, failed to find a reason for the difference. More rosiglitazone was used in the intensive treatment arm but there were no more deaths in those patients taking rosiglitazone compared to those not taking it so a drug cause cannot be identified.
This study supports a less glucocentric approach to treating diabetes. Clinicians should ensure that smoking cessation and healthy lifestyle encouraged and that cardiovascular risks and blood pressure are managed effectively in combination with blood glucose rather than focussing heavily on blood glucose.
Action: Clinicians should continue to treat diabetes by tackling lifestyle issues as well as blood pressure, blood glucose and cardiovascular risks. The full implications are unclear and more study may be necessary before changes to the management of diabetes can be recommended.