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Pfizer UK Response to BMJ Switching Editorial
- Kate Lloyd (26 June 2006)
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Kate Lloyd, Medical Director Pfizer Ltd, KT20 7NS
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Editor, James Moon and Richard Bogle1 present a contentious claim that all statins are the same except for the cost. Their article fails to address the need to select statin treatment based on the patient’s starting cholesterol level, the importance of new nationally agreed targets2 and is selective in its use of data. The financial pressures to switch patients from atorvastatin to simvastatin are recognised but there are patients for whom switching is not clinically appropriate. Clinical practice thus demands a more sophisticated approach to initial selection, switching and combination of statins to manage cardiovascular risk most effectively. Achievement of lower cholesterol targets has been shown to improve cardiovascular outcomes. This can reduce costly inpatient hospital admissions, progression to long term conditions and the need for invasive percutaneous or surgical procedures. A recently published economic analysis3 stated that CVD cost the NHS about £15.7 billion in 2004, representing 21% of overall NHS expenditure. Hospital inpatient care was the largest component of CVD-related healthcare costs, representing £9.93 billion (63%). This was significantly larger than drug expenditure on CV disease which accounted for £2.77 billion (18%). This highlights the need to consider all health related costs and benefits in any economic analysis. The Second Joint British Society Guidelines2 (JBS 2) reviewed the latest clinical trial evidence and concluded that TC < 4mmol/L should be the optimal target for patients with CVD, diabetes or high risk primary prevention and that the original JBS target of TC < 5mmol/L should now be superseded. Modelling using data from the CURVES study shows that only 33% of patients would achieve the JBS 2 targets using simvastatin 40mg alone4 . Patients may be intolerant of simvastatin; may not be close to target on current therapy, may have contraindications or dosing restrictions with simvastatin, such as patients taking potent CYP 3A4 inhibitors, grapefruit juice, amiodarone, verapamil and diltiazem and patients with severe renal impairment5. A study in South Africa6 looked at patients switching from atorvastatin 20mg to simvastatin 40mg and found that cholesterol levels increased significantly in these patients. An increase in atorvastatin dose is therefore more likely to assist in meeting the target cholesterol level than switching to a less potent statin, such as simvastatin or pravastatin. The authors use the CURVES4 and STELLAR7 lipid efficacy studies to suggest that atorvastatin 10mg and 20mg are as effective as simvastatin 40mg However, both studies show that atorvastatin 20mg is more efficacious than simvastatin 40mg in cholesterol reduction. The large systematic review in the BMJ 2003 by Law et al8 showed that the LDL-C efficacy for atorvastatin 20mg was similar to simvastatin 80mg and that the LDL-C efficacy for atorvastatin 10mg was similar to simvastatin 40mg. The Cholesterol Treatment Trialists Collaboration meta-analysis9 in over 90,000 patients demonstrated a 19% reduction in coronary mortality and a 26% reduction in non-fatal MI per mmol/L LDL-C reduction. Even a relatively small absolute difference in cholesterol, such as the 4% quoted by the authors, can make a large impact at a population level on cardiovascular morbidity and mortality. Quoting their unpublished in-house meta-analysis 10 the authors argue that the CV outcomes data is similar for atorvastatin 10mg and simvastatin 40mg. However, the atorvastatin trials, ASCOT11 and CARDS12, are primary prevention studies in hypertension and diabetes, 4S13 is high risk secondary prevention, HPS14 is secondary prevention and diabetes and the Mohler study15 is a short 12 month study in 354 patients with PVD with walking distance as the primary endpoint and clearly underpowered for CV events. The ASCOT and CARDS studies were stopped early due to the benefits seen (median 3.3 years and 3.9 years respectively) whereas 4S and HPS ran for 5 years. Combining trials with such marked heterogeneity in design, duration, patient population and outcomes in a meta-analysis is highly questionable; the amalgamation of such a mixed collection of studies cannot reasonably be used to generate guidance for the management of individual patients in clinical practice. The authors also refer to the 3T study16 comparing atorvastatin and simvastatin.. The study was designed to evaluate lipid lowering not CV events. More patients achieved target cholesterol level on atorvastatin than simvastatin. The authors inexplicably claim there was no difference though they admit that the study was underpowered for analysis of CV events. Their claim of no difference in this comparison is therefore statistically invalid. The claim that switching patients to simvastatin should be a proactive national decision fails to recognise the resources and costs that such a program would add. Any change in therapy may affect patient tolerability, side effects and compliance17. A loss of cholesterol control may require dose titration or switching back to the more potent statin. Therefore suggestions of wholesale, unthinking switching of treatments, based purely on acquisition cost in this or any clinical condition are inappropriate. Yours faithfully Kate Lloyd
References (1) Moon et al, BMJ 2006;332:1344-5 (2) JBS2 2005, Heart 91: (supplement V) 1-52 (3) The cost of cardiovascular disease in the UK, Luengo-Fernandez et al, Heart 2006 (4) CURVES Study, Jones et al, Am J Cardiology 1998; 81:582-587 (5) Simvastatin Summary of Product Characteristics, June 2006 (6) Raal et al, Cardiovascular J of South Afr 2004; 15:118-123 (7) STELLAR Study, Jones et al, Am J Cardiology 2003; 92:152-160 (8) Law et al, BMJ 2003;326:1423 (9) Cholesterol Treatment Trialists’ (CTT) Collaborators, Lancet 2005; 366:1267-78 (10) www.uclh.nhs.uk/NR/rdonlyres/OA09D988-OCAB-4CFC-BB58- BEC5212F6D19/34496/statinprescribingguidelines1.pdf (accessed 15th June 2006) (11) ASCOT-LLA Study, Sever et al, Lancet 2003; 361:1149-58 (12) CARDS Study, Colhoun et al, Lancet 2004; 364:685-96 (13) 4S Study (14) Heart Protection Study, Lancet 2002; 360 :7-22 (15) Mohler et al, Circulation 2003 ; 108 :1481-6 (16) 3T Study, Olsson et al, Clin Ther 2003 ; 25 :119-38 (17) Thiebaud et al, Am J Manag Care 2005; 11:670-674 Competing interests: I am Medical Director for Pfizer in the UK |
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