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LETTERS: Stuart J Laurie NICE’s simplified approach to lipids will not work BMJ 2008; 336: 1324 [Full text]

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Evidentially Cost-INeffective

L Sam Lewis   (13 June 2008)

Keep it simple

Peter D Burrill   (13 June 2008)

NICE's simplified approach can't not work

Magnus I Hird   (18 June 2008)

Simvastatin 40 mg - a baseline of acceptable practice

William E Moody   (24 June 2008)

Evidentially Cost-INeffective 13 June 2008
L Sam Lewis, GP Surgery, Newport, pembrokeshire, SA42 0TJ Send response to journal: Re: Evidentially Cost-INeffective	Stuart Laurie seems to pay no regard to the need, espoused by many in the NHS including NICE, to maximise cost-effectiveness. His proposal to pursue an LDL target of 2mmol/L is very cost- INeffective. It has been shown that benefits can accrue by reducing LDL cholesterol down to at least 2mmol/L, and perhaps further. But it is increasingly cost-ineffective , ie: the diminishing returns law obtains. The first 10mg of Simvastatin saves three-quarters of the lives that can be saved by the highest-dose Atorvastatin regimen in high-risk groups (refs: 1, 2, 3, 4, 5 ). This may be due to the cholesterol-lowering plateauing dose-response curve, and differing potencies of different Statins. Simvastatin 10mg costs just 36 pence for 28 tablets, compared to Atorvastatin 80mg at £28.21. If one accepts that the three-quarters-as- effective evidence ( in terms of coronaries prevented ) extrapolates from secondary to primary prevention then FIFTY times as many coronaries can be prevented if Laurie were to adopt the NICE advice. Is this why Liverpool has such high prescribing costs, and such poor coronary prevention statistics ? 1 LaRosa JC, Grundy SM, Waters DD, Shear S, Barter P, Fruchart J, et al. Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N Engl J Med 2005;352:1425-35. 2 Ravnskov U, Rosch PJ, Sutter MC. Intensive lipid lowering with atorvastatin in coronary disease. N Engl J Med 2005;353:94. 3 LaRosa JC, Grundy SM,Waters DD. Intensive lipid lowering with atorvastatin in coronary disease. N Engl J Med 2005;353:96-7. 4 Pedersen TR, Faergeman O, Kastelein JJ, Olsson AG, Tikkanen MJ, Holme I, et al. High-dose atorvastatin vs usual-dose simvastatin for secondary prevention after myocardial infarction: the IDEAL study: a randomized controlled trial. JAMA 2005;294:2437-45. Competing interests: Time and Money
Keep it simple 13 June 2008
Peter D Burrill, Specialist Pharmaceutical Adviser for Public Health Derbyshire County PCT, Chesterfield, S41 7PF Send response to journal: Re: Keep it simple	I trust that readers have heard of the acronym KISS? If you want things to be implemented successfully, keep them as simple as possible. Adding more steps or other types of complications is likely to put up barriers to successful implemenation. To maximise health gain, all our interventions in the NHS need to meet the criteria of being effective (with POO evidence), cost-effective and affordable. Fire-and-forget with simvastatin 40mg daily meets all these criteria. The use of atorvastatin 40mg daily meets none of these criteria. Show me the patient-orientated outcome evidence for the C&M cardiac network advice. Do they have to suffer the financial consequences of their advice? What about the opportunity cost? Which patients are not receiving effective treatments (usually non-drug e.g. pulmonary rehab) as a result of wasteful expenditure on atorvastatin 40mg? The same applies to chasing lipid targets of 4 & 2. Non-evidence based and unachievable. A recent HTA report (1) clearly states that there is an absence of strong and conclusive evidence on the exact relationship between cholesterol lowering and clinical endpoints. In the IDEAL study (2) atovastatin 80mg was compared directly with simvastatin 20-40mg (mean 25mg/day)in patients with a previous MI. There was no difference in the primary endpoint of major coronary events. In those taking atrovastatin 80mg daily, only about half achieved an LDL-C level below 2. Let's keep it simple and follow the evidence base, which means offering simvastatin 40mg to the high-risk patients and encouraging them to take it, and not trying to achieve non evidence-based targets. 1. HTA vol 11, no. 14. www.hta.ac.uk/project/1409.asp 2. JAMA 2005; 295: 2437-45 Competing interests: I believe that the NHS is a cash-limited organisation and we must make best use of our scarce resources to maximise health gain.
NICE's simplified approach can't not work 18 June 2008
Magnus I Hird, Pharmacist Practitioner Bloomfield Medical Centre Send response to journal: Re: NICE's simplified approach can't not work	Dr Laurie writes that a proportion of patients started on simvastatin 40mg for secondary prevention will not achieve total and LDL cholesterols less than 4 and 2mmol/L respectively(1). He is quite right: even in the trials of the most aggressive statin treatment about half of patients do not reach these levels, a point emphasised by NICE in their recent guideline (2). He suggests starting with an alternative statin in patients with baseline cholesterol levels above a threshold derived from the point at which the average reduction achieved with simvastatin 40mg will not reach the 4&2 levels. Unfortunately this misses several vital points: firstly that cholesterol levels can vary significantly, as NICE note, and thus the point estimate on today's test may not be correct. Secondly that the 37% reduction is an average, not an absolute for every patient, so individual responses may achieve different reductions. Thirdly, atorvastatin is not licensed to start at 40mg (3) and as a result he could be personally liable for any adverse effects that occurred to the patients he decides to treat in this manner. Fourthly for each patient that takes a little longer to have their treatment optimised there may be several who suffer adverse effects due to these clinical short cuts. These patients often decline any further treatment out of fear and remain sub-optimally treated forever: an opportunity cost seemingly uncounted. Yet all this is moot: For the reason already mentioned NICE make it clear that 4&2 are not a treatment goal for all patients and that titration from simvastatin 40mg should stop at the 80mg dose as progressing beyond this in stable secondary prevention patients is simply not cost-effective (and as other respondents have noted there is significant debate about whether it is even clinically effective in this group (4)). Thus the point about starting with atorvastatin at whatever dose is irrelevant: it shouldn't be being used in this circumstance. It then follows that there is also no need for the extra tests and clinician time he laments. It seems like this approach will work after all. (1) Laurie SJ. BMJ,2008; 336: 1324 (2) NICE. Clinical Guideline 67: Lipid modification (ful guideline). May 2008 (3) Anon. Lipitor SPC, accessed 17 June 2008 at http://emc.medicines.org.uk/ (4) Burrill P. Rapid Response to (1) 13 June 2008 Competing interests: I am paid by the National Prescribing Centre as a trainer and author although this response is made personally and may not represent their views. My consultancy provides training and writing to other clients which may include lipid topics.
Simvastatin 40 mg - a baseline of acceptable practice 24 June 2008
William E Moody, ST1 CMT trainee, Heart of England NHS Foundation Trust Birmingham Heartlands Hospital Send response to journal: Re: Simvastatin 40 mg - a baseline of acceptable practice	In our recent departmental audit drawn from a large central teaching hospital in the West Midlands, nearly a third of all patients with established coronary risk factors admitted with chest pain were being treated with low dose atorvastatin 10 mg or 20 mg rather than simvastatin 40 mg (1). This practice persists despite the call from James Moon, now more than 2 years ago, to switch statins to generic simvastatin as first line in an attempt to produce the largest single drug saving in NHS history(2). Most clinical trials concentrate on low-density lipoprotein (LDL) lowering as being central to the beneficial effects of statins on morbidity and mortality. Epidemiological studies together with data from fibrates suggest that raising HDL also plays a critical role. Whilst simvastatin 40 mg is slightly inferior to atorvastatin 20 mg for LDL lowering, it increases HDL more than any other dose of atorvastatin (3). A 28 day supply of simvastatin 40 mg daily costs our Trust £1.32, whilst a 28 day supply of atorvastatin 10 mg daily and atorvastatin 20 mg daily costs £18.50 and £26.32, respectively. As controlled dosing studies have proven (STELLAR and CURVES), simvastatin is not merely the cheapest option in terms of absolute cost but it is also cheapest in terms of %LDL reduction (4, 5). Laurie rightly states that there will be a proportion of patients in whom simvastatin is insufficiently potent to meet the increasingly aggressive latest targets set by the JBS-2 (6). Primary care performance will always be measured in terms of achieving such targets. From a secondary care perspective, we strongly advocate the approach of regarding the relative reduction in cholesterol and LDL levels as being more important than any achieved absolute levels. Intensive lipid therapy should be reserved for patients at highest risk such as those following an acute coronary syndrome. Recent guidelines estimate roughly 1 in 4 of the population between the ages of 30 and 75 are eligible for statin therapy. With such huge numbers implicated, I concur with Burrill’s adoption of the KISS acronym (7). The importance of keeping our strategy simple is paramount. In order to avoid the sort of prescribing practice highlighted by our audit and in keeping with latest NICE recommendations (8), simvastatin 40 mg should be considered as the baseline of acceptable practice. At the same time, atorvastatin 10 mg and 20 mg should not be made available from pharmacies. 1. Moody WE, Beattie J. Your money or your statin! Audit examining the statin prescribing practice for in-patients at Birmingham Heartlands Hospital, December 2007. 2. Moon JC. Switching statins. BMJ 2006;332:1344-5. 3. Moon JC. More on switching statins. BMJ 2006;333:655-656. 4. Jones P, Kafonek S, Laurora I, Hunninghake D. Comparative dose efficacy study of atorvastatin versus simvastatin, pravastatin, lovastatin, and fluvastatin in patients with hypercholesterolaemia (the CURVES study). Am J Cardiol 1998;81:582-587. 5. Jones PH, Davidson MH, Stein EA, Bays HE, McKenney JM, Miller E, et al. Comparison of the efficacyand safety of rosuvastatin versus atorvastatin, simvastatin, and pravastatin across doses (STELLAR Trial) Am J Cardiol 2003;92:152-60. 6. Laurie SJ. NICE’s simplified approach to lipids will not work. BMJ 2008; 336:1324. 7. Burrill PB. NICE’s simplified approach can’t not work. BMJ Rapid Response to (6), 13 June 2008. 8. NICE. Clinical Guideline 67: Lipid modification (full guideline). May 2008 Competing interests: Acting cardiac network representative Birmingham Sandwell and Solihull PCT, NHS Heart Improvement Programme October 2006.