The original NICE lipid modification guideline from 2008 has been updated from new evidence on risk assessment, and to reflect changes in price and availability of generic statins.1 Although concerns about conflicts of interest in the guideline group have been raised, they are unfounded as none of the positive recommendations relate to brand drugs within patent, and the overall cost of these statin drugs to the NHS is likely to continue to fall. The large reduction in cost has resulted in significant changes to the level of risk for recommending treatment, and on the choice and dose of statins, as the cost-effectiveness threshold has altered considerably.
1. Lower risk threshold for statins
Perhaps the biggest change in terms of the scale of treatment is the move from the 20% or greater 10-year risk threshold, to a 10% threshold. To put this scale in context, it is estimated that 80% of men over the age of 50 years, and 50% of women over 60, may now be eligible to be offered treatment (atorvastatin 20mg daily). Although patients may wish to have no intervention, try lifestyle changes in preference to treatment, or amend lifestyle and take a statin at the same time.
This change was felt to be justified by the guideline group by the very low acquisition costs of generic statins and evidence of benefit at low levels of risk. This was set alongside evidence that statin drugs are remarkably safe. This means that the threshold of risk for cost-effectiveness was lower than determined in 2008. The potential to prevent and delay subsequent cardiovascular events on a population basis appears highly cost effective, and for individuals is similar to that in treating mild-to-moderate hypertension. The number needed to treat to prevent a major vascular event or death over five years has been estimated at 50 for those with a 15% 10-year risk, and 74 for those at a 10% level.2
The consultation on the updated lipid guidance early in 2014 showed that this was a highly controversial recommendation, with reactions similar to those for comparable changes recommended in the USA.3,4 The main concerns relate to ‘mass medication’ and to tolerability and safety of statins when used to prevent disease, but recent published evidence from both trial data and observational studies supports the NICE assessment of the good relative safety of statins.5,6
2. Aim for 40% non-HDL cholesterol reduction
In any case, using the nomenclature of the guideline, the recommendation to initiate atorvastatin 20mg daily for primary prevention is simply ‘to offer’. The decision depends on patient preference. The guidance now advises ‘to consider’ increasing the dose if a 40% reduction in non-HDL cholesterol is not seen. It may be that many people might not wish to take a statin but the guideline group believed that, given the evidence, they should be offered the choice.
The recommendation of atorvastatin 20mg daily as the initiation dose for primary prevention was made as this was found to be cost effective, relatively well tolerated and safe, and likely to achieve a 40% reduction in non-HDL cholesterol for many. The evidence to support this came from an analysis provided by the technical team for the guideline group that modelled the effects of low, moderate and high-intensity statin doses. The reduction in cardiovascular events was greatest for high-intensity treatment when a more than 40% reduction in non-HDL cholesterol was achieved. This can be attained with atorvastatin 20mg in many, but a greater effect is seen with atorvastatin 80mg.
Despite its higher cost, atorvastatin 80mg daily also reached conventional thresholds for cost effectiveness, even in primary prevention.
Greater emphasis should be given to increasing the dose up to atorvastatin 80mg daily if the 40% is not achieved, and the patient is judged to be at higher risk because of comorbidities such as diabetes, risk score or clinical judgment.
3. Managing side-effects
The guideline advises that if a person is not able to tolerate a high‑intensity statin, such as atorvastatin 20mg daily or more, you should aim for the maximum tolerated dose. This may require reassurance, so you should advise the patient that any statin, at any dose, reduces CVD risk.
If a patient reports adverse effects from high intensity statins, the guideline recommends the following options:
• Stopping the statin and trying again when symptoms have resolved, to check if symptoms are related to the statin.
• Reducing the dose within the same intensity group.
• Changing to a lower-intensity statin.
In patients intolerant to three different statins and who are at high risk of CVD, such as those with CKD, type 1 diabetes, type 2 diabetes or genetic dyslipidaemias, and those with CVD, the guideline advises seeking specialist advice. This may not require a referral and advice can be sought by telephone or ‘virtual clinic’.
What does NICE mean by ‘high intensity’ statins?
For the purpose of the guideline, statins were grouped into three intensity categories, according to the percentage reduction in LDL cholesterol, based on analysis of the literature. In clinical trials, greatest benefit is seen with the doses of statins that, on average, resulted in a greater than 40% reduction in fasting LDL cholesterol. This is equivalent to a greater than 40% reduction in non-HDL cholesterol.
Atorvastatin 20mg daily comes under this classification as high intensity, and simvastatin 40mg daily as medium intensity. This can cause confusion with patients who may think that the milligram dose describes the strength of treatment and this may need explaining. If a patient appears intolerant of atorvastatin 20mg daily, one option is to change to atorvastatin 10mg daily, and another to simvastatin 40mg daily.
4. Statins in established CVD
Similar considerations were made when looking at established CVD. To give greatest benefit, the guideline recommends atorvastatin 80mg daily. The evidence for statins, and the cost-effectiveness analysis, overwhelmingly supported their use at high-intensity doses, with greater benefit at the 80mg dose of atorvastatin. Following the 2008 guideline, many patients with recent MI, or vascular events, already receive atorvastatin 80mg in the UK, particularly following restrictions in use of high-dose simvastatin.7
The guideline group recommended atorvastatin 80mg, with the possibility of dose reduction, or change of statin, if this is problematic.
For those already on a lesser dose or taking simvastatin, the option of changing or increasing should be discussed at the next medication review.
Dr Martin Duerden is a GP in Wales, and was a member of the development group for the NICE lipid modification guidelines
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