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Statins and coronary heart disease
THE LANCET
Statins and coronary heart disease SIR—From the perspective of a clinician who has enthusiastically used statins since 1981, the essay by Fey and Pearson (May 18, p 1389)1 deserves only a B+. It damns with faint praise what is arguably the most important advance in the prevention and treatment of coronary heart disease (CHD) since aspirin. Although I share their concerns about the cost of these drugs, in the context of CHD prevention they could immediately halve their estimate by substituting simvastatin 20 mg daily (£31 per month) for pravastatin 40 mg daily (£62 per month), which would achieve an equivalent reduction in low-density-lipoprotein cholesterol.2 Use of the Sheffield risk and treatment table may limit the costs of primary prevention but this use would be dubious since the table ignores variations in high-density-lipoprotein cholesterol, which are an integral feature of the Framingham data and, as pointed out by Megnien and colleagues,3 the table uses criteria for intervention that are based on the 4S study, a secondary prevention trial. I agree with these workers3 that a logical if untested approach to primary prevention would be to use drugs only in those at high risk in whom there is subclinical atherosclerosis. Lifestyle changes are important in any population-based approach to primary prevention, but their impact on CHD risk factors is limited, at least in the UK.4 For the present it would make sense to ensure that priority is given to the use of statins in patients with known CHD and raised blood cholesterol, 50% of whom are untreated.5 Gilbert R Thompson Medical Research Council Lipoprotein Team, Royal Postgraduate Medical School, Hammersmith Hospital, London W12 0NN, UK
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Fey R, Pearson N. Statins and coronary heart disease. Lancet 1996; 347: 1389–90. Illingworth DR, Erkelens DW, Keller U, Thompson GR, Tikkanen MJ. Defined daily doses in relation to hypolipidaemic efficacy of lovastatin, pravastatin, and simvastatin. Lancet 1994; 343: 1554–55. Megnien JL, Levenson J, Simon A. Sheffield risk and treatment table for cholesterol lowering in prevention of coronary heart disease. Lancet 1996; 347: 468. Family Heart Study Group. Randomised controlled trial evaluating cardiovascular screening and intervention in general practice: principal results of British family heart study. BMJ 1994; 308: 313–20. ASPIRE Steering Group. A British Cardiac Society survey of the potential for the secondary prevention of coronary disease: ASPIRE (Action on Secondary Prevention through Intervention to Reduce Events). Principal results. Heart 1996; 75: 334–42.
SIR—While agreeing with much of Fey and Pearson’s thoughtful essay1 on perspectives and priorities to be considered following reports of the beneficial effects of statins in CHD, there are two issues that need clarification. First, my comment2 that statins need to be given for life related to starting these drugs in middle rather than old age, since there is no convincing evidence of their benefit in the elderly. If, for cost reasons, statins are discontinued in those judged to need them, there will be a rapid return of plasma cholesterol and low-density lipoproteins to pretreatment levels. For many reasons, this is undesirable. Second, improvements in lifestyle must of course be attempted both before starting, and along with, drug treatment. So far as plasma lipids are concerned, little should be expected from changes in lifestyle. Low-fat diets do not work. No properly controlled randomised trial of the effects of a low-fat diet has shown a significant reduction in CHD, probably because of the minimum effect that these diets have on plasma cholesterol and lipoprotein concentrations.3 Also, long-term compliance is poor4 and inversely related
Vol 348 • July 6, 1996
to the rigour of the diet. If cost-cutting dictates a dietary approach, it must include measures to increase the polyunsaturated/saturated fat ratio, and even then the plasma cholesterol response will be poor relative to that achievable by the statins. While Fey and Pearson are right to debate the wider issues surrounding the use of statins, one matter that is not acceptable is the continuing undertreatment5 in the UK of raised plasma cholesterol concentrations in patients and those at high risk for CHD. M F Oliver National Heart and Lung Institute, London SW3 6LY, UK
1 2 3 4
5
Fey R, Pearson N. Statins and coronary heart disease. Lancet 1996; 347: 1389–90. Oliver MF. Statins prevent coronary heart disease. Lancet 1995; 346: 1378–79. Ramsay LE, Yeo WW, Jackson PR. Dietary reduction of cholesterol concentration: time to think again. BMJ 1993; 303: 953–57. Neil HAW, Roe L, Godlee JW, et al. Randomised trial of lipid lowering dietary advice in general practice: the effects on serum lipids, lipoproteins, and antioxidants. BMJ 1995; 310: 569–73. ASPIRE Steering Group. A British Cardiac Society survey of the potential for the secondary prevention of coronary disease: ASPIRE (Action on Secondary Prevention through Intervention to Reduce Events). Principal results. Heart 1996; 75: 334–42.
SIR—The confusion between science and statistics1 is shown in the response to the West of Scotland Study of the Prevention of Coronary Heart Disease.2 Oliver,3 in The Lancet used the headline “Statins prevent coronary heart disease”, which I would criticise in several ways. First, this title is actually incorrect because the study uses as its endpoints clinical expressions of CHD, not the disease process itself. Second, it acted as a summary for the commentary which might register in the mind of a reader, removing the necessity to read it in full. Third, the message of the title and indeed the commentary itself, was absolutist in its tone, disguising the scientific message of the study. Finally, it seemed to act as a carte blanche to future prescribing. Fey and Pearson’s4 essay provides a balance, and has put the West of Scotland Study into the perspective of clinical practice. The facts of the study are as follows. If 3500 men aged between 45 and 65 with blood cholesterol greater than 6·5 mmol/L are given pravastatin 40 mg daily for 5 years, then there will be 14 fewer deaths than expected, and in addition 60 fewer non-fatal myocardial infarctions (if admitted to hospital, unit cost up to £10 000, total savings up to £600 000) and the need for 20 fewer revascularisation procedures (unit cost up to £10 000, total savings up to £200 000). Fey and Pearson point out that the cost of pravastatin is about £800 per year and so the cost of treatment in the West of Scotland study was in excess of £13 million. Subtraction of the savings leaves rather more than £12 million to be apportioned between the 14 deaths delayed. The prevention is easily prescribed. Advice from the purchasers of health care as to its appropriateness would be welcome. David S Grimes Blackburn Royal Infirmary, Blackburn, Lancs BB2 3LR, UK
1 2
3 4
Charlton BG. Statistical malpractice. J R Coll Phys Lond 1996; 30: 112–14. Shepherd J, Cobbe SM, Ford I, et al. Prevention of coronary heart disease with pravastatin in men with hypercholesterolaemia. N Engl J Med 1995; 333: 1301–07. Oliver MF. Statins prevent coronary heart disease. Lancet 1996; 346: 1378–79. Fey R, Pearson N. Statins and coronary heart disease. Lancet 1996; 346: 1389–90.
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Statins and coronary heart disease SIR—From the perspective of a clinician who has enthusiastically used statins since 1981, the essay by Fey and Pearson (May 18, p 1389)1 deserves only a B+. It damns with faint praise what is arguably the most important advance in the prevention and treatment of coronary heart disease (CHD) since aspirin. Although I share their concerns about the cost of these drugs, in the context of CHD prevention they could immediately halve their estimate by substituting simvastatin 20 mg daily (£31 per month) for pravastatin 40 mg daily (£62 per month), which would achieve an equivalent reduction in low-density-lipoprotein cholesterol.2 Use of the Sheffield risk and treatment table may limit the costs of primary prevention but this use would be dubious since the table ignores variations in high-density-lipoprotein cholesterol, which are an integral feature of the Framingham data and, as pointed out by Megnien and colleagues,3 the table uses criteria for intervention that are based on the 4S study, a secondary prevention trial. I agree with these workers3 that a logical if untested approach to primary prevention would be to use drugs only in those at high risk in whom there is subclinical atherosclerosis. Lifestyle changes are important in any population-based approach to primary prevention, but their impact on CHD risk factors is limited, at least in the UK.4 For the present it would make sense to ensure that priority is given to the use of statins in patients with known CHD and raised blood cholesterol, 50% of whom are untreated.5 Gilbert R Thompson Medical Research Council Lipoprotein Team, Royal Postgraduate Medical School, Hammersmith Hospital, London W12 0NN, UK
1 2
3
4
5
Fey R, Pearson N. Statins and coronary heart disease. Lancet 1996; 347: 1389–90. Illingworth DR, Erkelens DW, Keller U, Thompson GR, Tikkanen MJ. Defined daily doses in relation to hypolipidaemic efficacy of lovastatin, pravastatin, and simvastatin. Lancet 1994; 343: 1554–55. Megnien JL, Levenson J, Simon A. Sheffield risk and treatment table for cholesterol lowering in prevention of coronary heart disease. Lancet 1996; 347: 468. Family Heart Study Group. Randomised controlled trial evaluating cardiovascular screening and intervention in general practice: principal results of British family heart study. BMJ 1994; 308: 313–20. ASPIRE Steering Group. A British Cardiac Society survey of the potential for the secondary prevention of coronary disease: ASPIRE (Action on Secondary Prevention through Intervention to Reduce Events). Principal results. Heart 1996; 75: 334–42.
SIR—While agreeing with much of Fey and Pearson’s thoughtful essay1 on perspectives and priorities to be considered following reports of the beneficial effects of statins in CHD, there are two issues that need clarification. First, my comment2 that statins need to be given for life related to starting these drugs in middle rather than old age, since there is no convincing evidence of their benefit in the elderly. If, for cost reasons, statins are discontinued in those judged to need them, there will be a rapid return of plasma cholesterol and low-density lipoproteins to pretreatment levels. For many reasons, this is undesirable. Second, improvements in lifestyle must of course be attempted both before starting, and along with, drug treatment. So far as plasma lipids are concerned, little should be expected from changes in lifestyle. Low-fat diets do not work. No properly controlled randomised trial of the effects of a low-fat diet has shown a significant reduction in CHD, probably because of the minimum effect that these diets have on plasma cholesterol and lipoprotein concentrations.3 Also, long-term compliance is poor4 and inversely related
Vol 348 • July 6, 1996
to the rigour of the diet. If cost-cutting dictates a dietary approach, it must include measures to increase the polyunsaturated/saturated fat ratio, and even then the plasma cholesterol response will be poor relative to that achievable by the statins. While Fey and Pearson are right to debate the wider issues surrounding the use of statins, one matter that is not acceptable is the continuing undertreatment5 in the UK of raised plasma cholesterol concentrations in patients and those at high risk for CHD. M F Oliver National Heart and Lung Institute, London SW3 6LY, UK
1 2 3 4
5
Fey R, Pearson N. Statins and coronary heart disease. Lancet 1996; 347: 1389–90. Oliver MF. Statins prevent coronary heart disease. Lancet 1995; 346: 1378–79. Ramsay LE, Yeo WW, Jackson PR. Dietary reduction of cholesterol concentration: time to think again. BMJ 1993; 303: 953–57. Neil HAW, Roe L, Godlee JW, et al. Randomised trial of lipid lowering dietary advice in general practice: the effects on serum lipids, lipoproteins, and antioxidants. BMJ 1995; 310: 569–73. ASPIRE Steering Group. A British Cardiac Society survey of the potential for the secondary prevention of coronary disease: ASPIRE (Action on Secondary Prevention through Intervention to Reduce Events). Principal results. Heart 1996; 75: 334–42.
SIR—The confusion between science and statistics1 is shown in the response to the West of Scotland Study of the Prevention of Coronary Heart Disease.2 Oliver,3 in The Lancet used the headline “Statins prevent coronary heart disease”, which I would criticise in several ways. First, this title is actually incorrect because the study uses as its endpoints clinical expressions of CHD, not the disease process itself. Second, it acted as a summary for the commentary which might register in the mind of a reader, removing the necessity to read it in full. Third, the message of the title and indeed the commentary itself, was absolutist in its tone, disguising the scientific message of the study. Finally, it seemed to act as a carte blanche to future prescribing. Fey and Pearson’s4 essay provides a balance, and has put the West of Scotland Study into the perspective of clinical practice. The facts of the study are as follows. If 3500 men aged between 45 and 65 with blood cholesterol greater than 6·5 mmol/L are given pravastatin 40 mg daily for 5 years, then there will be 14 fewer deaths than expected, and in addition 60 fewer non-fatal myocardial infarctions (if admitted to hospital, unit cost up to £10 000, total savings up to £600 000) and the need for 20 fewer revascularisation procedures (unit cost up to £10 000, total savings up to £200 000). Fey and Pearson point out that the cost of pravastatin is about £800 per year and so the cost of treatment in the West of Scotland study was in excess of £13 million. Subtraction of the savings leaves rather more than £12 million to be apportioned between the 14 deaths delayed. The prevention is easily prescribed. Advice from the purchasers of health care as to its appropriateness would be welcome. David S Grimes Blackburn Royal Infirmary, Blackburn, Lancs BB2 3LR, UK
1 2
3 4
Charlton BG. Statistical malpractice. J R Coll Phys Lond 1996; 30: 112–14. Shepherd J, Cobbe SM, Ford I, et al. Prevention of coronary heart disease with pravastatin in men with hypercholesterolaemia. N Engl J Med 1995; 333: 1301–07. Oliver MF. Statins prevent coronary heart disease. Lancet 1996; 346: 1378–79. Fey R, Pearson N. Statins and coronary heart disease. Lancet 1996; 346: 1389–90.
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