What is the story here?
This is the full paper publication of an observational study which was first presented as a poster and about which we blogged back in September 2007. We also discussed it in a podcast (13th September). The authors (all employed by Pfizer, which markets atrorvastatin, with a statistician from a contract biostatistics company) analysed the GP records of 2511 patients switched from atorvastatin to simvastatin and matched them with 9009 controls. Records were obtained from a UK primary care database (THIN). Importantly, the last data collection was June 2005.
What does this study claim?
Switching treatment was associated with a statistically significant increase in the risk of death or major cardiovascular events (myocardial infarction (MI), stroke or coronary revascularization) compared with patients who did not switch (Hazard Ratio [HR] 1.30, 95%CI 1.02 to 1.64; P = 0.030). Within this composite endpoint, only stroke occurred statistically significantly more frequently in the switch group: there were no significant differences in rates of MI or revascularisation. There was also no significant difference in the rate of death. Patients who switched were also more likely to stop taking their statin than those who did not switch (adjusted HR for discontinuation 2.15, 95%CI 1.96 to 2.36, P<0.001)
We discussed some of the limitations of this study in our previous blog. Two GPs with a special interest in cardiovascular medicine (Terry McCormack and Rubin Minhas) have written an editorial commenting on the paper, picking up the extra information that is presented over and above that which was available in the poster. They point out that nearly 26% of the switch group ended up taking only 10 mg simvastatin, and a further 39% were taking only 20 mg simvastatin. Only 31% were taking the 40 mg simvastatin dose usually recommended in switch programmes. By contrast, about 42% of control patients were taking atorvastatin 20mg-80 mg. At baseline 60% of patients in the switch group achieved the QoF target for total cholesterol (5mmol/L) compared with 74% of patients in the control group. At one year 65% of switch were achieved the QoF target compared with 72% of controls.
As McCormack and Minhas point out, the timescale of the study means that “It is likely that many people in this study underwent an ‘involuntary’ switch rather than a ‘planned’ switch – a crucial differentiation. People who involuntarily switch will usually do so because of side effects, though in some cases they may be hypo-responders to statins. (The proportion of patients at QoF target at baseline indicates this may well be the case). Being mindful of recent side effects, further treatment is often initiated with a lower-dose statin that is less likely to cause side effects. People that have experienced side effects are less likely to comply with treatment and are more likely to have co-morbidities and to be in a higher risk group.”
We wholeheartedly agree with McCormack and Minhas that this study has little implication for current policy, but does indicate the importance of undertaking statin switching programmes with care. One of many highly successful programmes was discussed at a meeting on this topic held in Yorkshire. Support materials are available on the lipids section of NPC.
Prescribers should continue to choose simvastatin 40 mg daily as first choice drug and dose for most patients who need a statin (bearing in mind contraindications and interactions). Wherever possible, taking into account individual patients’ circumstances and wishes and in the context of a carefully constructed switching programme, there is no good evidence that moving existing patients from standard doses of atorvastatin to simvastatin 40mg would adversely affect cardiovascular risk reduction.