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Is NICE too obsessed with simvastatin?

Dr Stuart Laurie argues that NICE is preoccupied with promoting the use of the cheapest statin rather than the one that will best lower LDL, but Dr John Ashcroft says NICE guidance is right to focus on 40mg simvastatin first line, and should go further

Dr Stuart Laurie argues that NICE is preoccupied with promoting the use of the cheapest statin rather than the one that will best lower LDL, but Dr John Ashcroft says NICE guidance is right to focus on 40mg simvastatin first line, and should go further

Yes

NICE has advised that in secondary prevention of CVD first-line statin therapy should be simvastatin 40mg. This can be titrated to simvastatin 80mg or a drug of similar efficacy and acquisition cost if targets of less than 4mmol/l for total cholesterol and 2mmol/l for LDL cholesterol are not met. As there are no other statins of equal or greater efficacy with a similar acquisition cost, NICE has effectively made simvastatin 80mg maximal statin therapy.

I simply don't believe that this advice is supported by the evidence.

Guidelines produced by the Joint British Societies support treating to a target of less then 2mmol/l for LDL cholesterol. The US National Cholesterol Education Program ATP III guidance adopts similar targets. The evidence supporting cholesterol lowering in secondary prevention of CVD is strong and the benefits seem independent of pre-treatment lipid levels.

It has been shown that, for every 1mmol/l reduction in LDL cholesterol, over five years there is a 21% reduction in major coronary events, coronary revascularisation and stroke combined. In fact NICE itself acknowledges that only 37% of patients will be treated to a target of less than 4mmol/l total cholesterol with simvastatin 80mg.

There is good evidence that higher-intensity statins have superior clinical efficacy compared with low-intensity statins, and again NICE acknowledges this. The PROVE-IT, TNT and IDEAL trials all showed the significantly superior efficacy of atorvastatin 80mg over lower-intensity statins, although results were not significant across all endpoints. A meta-analysis of these trials and one other trial found intensive lipid lowering provided a 16% odds reduction of coronary death or any cardiovascular event when compared with less intensive lipid lowering.

NICE has advised using simvastatin 80mg first line in patients with acute coronary syndrome (ACS) based on the PROVE IT trial, but this trial also showed the superiority of atorvastatin 80mg over pravastatin 40mg after ACS. It also seems strange to say that patients who have a new episode of ACS should be treated differently from those who have suffered ACS in the past and now have stable coronary heart disease.

The LDL lowering ability of different statins is well documented and meta-analysis has shown that simvastatin 40mg reduces LDL by an average of 37%, simvastatin 80mg by 42%, atorvastatin 40mg by 49%, atorvastatin 80mg by 55% and rosuvastatin 20mg by 48%. There's an argument for using high-intensity statins first line for secondary prevention in patients with an LDL above a certain threshold. Even taking into account variable individual response to statins and variability in laboratory results, I'd argue there is a case for using atorvastatin 40mg first line when the pre-treatment LDL is greater than 4mmol/l. It seems far simpler to get things right first time.

The international consensus and evidence strongly suggests that we should be trying to get LDL cholesterol levels to less than 2mmol/l using a statin of appropriate intensity to achieve this. NICE has essentially restricted the use of statins more potent than simvastatin 80mg based solely on cost-effectiveness analysis. Although cost-effectiveness is important and we should use the least expensive effective treatment, I would struggle to tell a patient with CVD that they were receiving optimal therapy if they were taking simvastatin 80mg and had an LDL of greater than 2mmol/l.

NICE seems to be not seeing the wood for the trees by focusing on the therapy - simvastatin - rather than the actual point of the whole exercise - lowering LDL. Admittedly NICE has left the door open for 2011 when the patent expires on atorvastatin and no doubt costs will fall.

I know that if I had CVD I would want treatment to an LDL target of less than 2mmol/l or as near as possible with a higher-intensity statin than simvastatin 80mg if needed. It is an uneasy position, being told by NICE to treat my patients in a way I would not want to be treated myself.

Dr Stuart Laurie is a GP in Liverpool

No

A number of NICE guidelines recommend using simvastatin for cardiovascular risk reduction. Different guideline groups with different members have largely arrived at the same conclusion - simvastatin is best.

The latest - CG 67 on lipid modification - advises that patients assessed as having a 10-year CVD risk higher than 20% should be started on 40mg of simvastatin with a 'fire-and-forget' strategy, with no need to monitor cholesterol.

For sometime in Derbyshire County PCT we have had a fire-and-forget policy for all patients, including those on secondary prevention, provided 40mg of simvastatin is used. In some ways it is good to see this approach being adopted by NICE, but it doesn't go far enough in recognising that the interests of both patients and taxpayers are best served by the virtually exclusive prescribing of simvastatin at a 40mg dose.

But the new guidance asks clinicians to consider increasing doses of simvastatin to 80mg in patients with existing CVD if total cholesterol remains above 4.0, or LDL above 2.0, and in ACS to give 80mg of simvastatin from the onset. It even suggests atorvastatin 80mg as an alternative.

Although we may consider it, I feel we must reject this approach. Though lowering of LDL cholesterol down to 2.0 and total cholesterol to 4.0 has been shown to give some benefit, there remains no evidence that lowering it with anything more than 40mg of simvastatin is additionally effective. And this isn't just a case of absence of evidence. In the IDEAL study, atorvastatin 80mg was compared directly with simvastatin 20-40mg (mean dose 25mg) in patients with previous MI. No difference was found in the primary endpoint of major coronary events.

For those who still feel that something more must be done, it is important to remember just how much is already being done. A patient with pre-existing heart disease may have a 40-50% risk of a cardiovascular event over the next 10 years, but the Heart Protection Study shows that 40mg of simvastatin will reduce this by 36% over the first five years. Aspirin will reduce the remaining risk by a further 25%, and a ß-blocker and ACE-inhibitors by 20% each, acting incrementally on the remaining risk, with diminishing returns. If patients take their treatment, with four drugs, their ongoing 10-year risk of CVD will be on average only 12-15%.

Many additional interventions to lower the risk further have been suggested, of which further lowering LDL is only one, with others including greater rehabilitation, more aggressive revascularisation, drugs to increase HDL, fish oils, anti-arrhythmics such as amiodarone, or thrombolytic therapies such as warfarin or clopidogrel. But all fall foul of the law of diminishing returns and this is certainly the case for further lowering of LDL or total cholesterol.

Even if we assume that increasing simvastatin to 80mg delivers the expected returns, and this outweighs extra side-effects, it would reduce relative risk by a further 10% but absolute risk by only 1-1.5% over 10 years.

Paradoxically, as the cheapest way to prescribe 80mg of simvastatin is to give two 40mg tablets, if we give the second 40mg simvastatin to another patient who doesn't have heart disease but has a similar level of 10-year risk as the compliant patient with heart disease, then we will get nearly four times the absolute benefit.

And yet NICE has advised that the NHS cannot afford to treat such patients, even with generic simvastatin which costs the pharmacist little more than 50p per pack. If NICE believes this, it is inconceivable that the switch from simvastatin to atorvastatin could ever be justified.

On this basis NICE should revisit guidelines with a fire-and-forget policy of simvastatin 40mg for all patients, with the aim of getting patients down to a cardiovascular risk of 10%. Doctors should be aiming at 90% or more of their statin prescribing being simvastatin 40mg.

Dr John Ashcroft is a GP in Ilkestone and vascular lead for Derbyshire County PCT

yes quote

I am uneasy treating patients differently from how I'd treat myself

no quote

Lowering LDL any further is a case of diminishing returns

Is NICE too obsessed with simvastatin? Simvastatin

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