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Economics of lipid lowering in primary prevention: lessons from the West of Scotland Coronary Prevention Study
Economics of Lipid Lowering in Primary Prevention: Lessons from the West of Scotland Coronary Prevention Study James Shepherd,
MBChB, PhD
On the basis of the clinical benefit and virtual absence of adverse effects observed with statin treatment in major primary and secondary prevention trials, a case could be made for considering statin therapy for all patients meeting the eligibility criteria for these trials. Establishing a risk threshold for statin treatment based on cost is an urgent item on the agenda of modern healthcare systems. An economic analysis using West of Scotland Coronary Prevention Study (WOSCOPS) findings indicates that statin treatment would have prevented 318 events per 10,000 patients in a population similar to that in WOSCOPS (average 1.5% annual risk of a cardiovascular event) at a discounted cost per life-year gained of £20,375 ($31,818). Application of current European treatment guidelines to consider treatment in
patients with risk >2% per year would result in treatment of approximately 40% of the WOSCOPS population; discounted cost per life-year gained in this case would be £13,995 ($21,855). In Scotland, an annual risk threshold of >3% for treatment has been adopted, corresponding to only 8% of the WOSCOPS population; the discounted cost per life-year gained is £9680 ($15,116). Reductions in drug cost, improved compliance, and use of more potent statins could alter cost efficiencies and encourage use of statins in a greater proportion of the primary prevention population that has been shown to benefit from such treatment. 䊚2001 by Excerpta Medica, Inc. Am J Cardiol 2001;87(suppl):19B–22B
he major statin trials provide remarkably consistent evidence of the benefits of cholesterol lowerT ing in both the primary and secondary prevention of
has resulted in benefits with respect to prevention of cardiovascular events across a broad risk range, from an annual risk as low as 0.5% in the AFCAPS/TexCAPS study1 to an annual risk as high as 4.5% in the 4S trial.4 In addition, these benefits have been achieved in populations in the CARE and LIPID studies, in which up to 80% were receiving aspirin treatment, 40 –50% -blocker treatment, 30 – 40% calcium-antagonist treatment, and 15–16% angiotensinconverting enzyme inhibitor treatment.2,3 With demonstration of clinical effectiveness across such a broad risk range, a key question that emerges is where to draw the line on cost-based treatment recommendations. In an attempt to facilitate decisions on which patients should receive treatment, a joint commission of the European Society of Cardiology, European Atherosclerosis Society, and European Society for Hypertension ruled in 1998 that an absolute risk of at least 20% for experiencing a vascular event over the next 10 years (or, broadly, a 2% risk per year) warranted consideration for intervention.6 With reference to Figure 1, this dictum would result in recommendation of treatment for high-risk patients such as those with coronary artery disease and elevated or normal cholesterol, reflecting the patient populations of the 4S, CARE, and LIPID trials, as well as hypercholesterolemic patients with additional cardiovascular risk factors, a profile met by a segment of the WOSCOPS patient population. These patients generally would be considered to have an annual risk of cardiovascular events of ⱖ2%. Patients with lower risk—such as hypercholesterolemic patients who are otherwise “healthy,” normocholesterolemic patients with other risk factors, and normocholesterolemic “healthy” pa-
coronary artery disease.1–5 Indeed, in its broadest sense, interpretation of the findings of these trials would lead to the conclusion that because cholesterol reduction with these agents is virtually devoid of side effects, all patients who meet the entry criteria for the Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS), West of Scotland Coronary Prevention Study (WOSCOPS), Cholesterol and Recurrent Events (CARE), Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID), and Scandinavian Simvastatin Survival Study (4S) trials merit lipid-lowering intervention. Although arguably justifiable in clinical terms, such a liberal treatment strategy is patently impractical in most, if not all, national healthcare systems because of economic factors. Instead, it is more rational to target individuals whose risk of a cardiovascular event exceeds an accepted specified value. How to select such a value or values remains a matter of some contention.
WHO BENEFITS FROM STATIN THERAPY AND WHO SHOULD BE TREATED? To date, clinical endpoint trials of statins have involved the first-generation agents lovastatin, pravastatin, and simvastatin. Treatment with these agents From the Institute of Biochemistry, Royal Infirmary, Glasgow, Scotland, United Kingdom. Address for reprints: James Shepherd, MBChB, PhD, Department of Pathological Biochemistry, Royal Infirmary, 84 Castle Street, Glasgow, G4 0SF, Scotland. ©2001 by Excerpta Medica, Inc. All rights reserved.
0002-9149/01/$ – see front matter PII S0002-9149(01)01451-5
19B
FIGURE 1. Spectrum of risk across which statin treatment has shown benefit as a means of depicting treatment priorities. Trials with populations indicative of risk group are shown at right. AFCAPS/TexCAPS ⴝ Air Force/Texas Coronary Atherosclerosis Prevention Study; CARE ⴝ Cholesterol and Recurrent Events Trial; CAD ⴝ coronary artery disease; RF ⴝ risk factor; 4S ⴝ Scandinavian Simvastatin Survival Study; WOSCOPS ⴝ West of Scotland Coronary Prevention Study.
tients, all of whom have been shown to benefit from statin therapy in WOSCOPS or AFCAPS/TexCAPS— constitute a gray zone in which treatment is not explicitly recommended and clinical judgment must be exercised. It is, in this regard, important to recognize that guidelines are designed to promote treatment uniformity in areas of indecision, that they must not be applied unthinkingly or reflexively, and that clinical judgment should always take precedence over such recommendations.
ECONOMIC ANALYSIS OF WOSCOPS In Scotland, publication of the WOSCOPS results called attention to the potential financial consequences of routinely implementing lipid-lowering therapy as primary prevention of coronary artery disease in individuals matching the WOSCOPS risk profile (a 1.5% average risk of a cardiovascular event). It was calculated that approximately 11.5% of the apparently healthy 35– 64-year-old Scottish population would merit treatment with routine application of these findings. In an attempt to forestall financial disaster, it was hurriedly suggested to practitioners that treatment in primary prevention be limited to those patients with an annual risk of ⱖ4%. Review of the WOSCOPS database, however, revealed that none of the patients in this trial population exhibited cardiovascular risk of such magnitude; indeed, such elevated risk is not likely to be present in individuals without evidence of existing vascular disease.6 A more practical approach to resource allocation was clearly needed. Far less contentious was the cost-effectiveness of treatment to prevent a second myocardial infarction (MI) or reduce the impact of complications. In the secondary prevention setting, the 4S investigators7 calculated from their database that the cost of simvastatin therapy per lifeyear gained after a first MI, discounted at 5% per year, was £5,502 ($8,592)—a value well within the price range normally considered to be cost-effective.8 20B THE AMERICAN JOURNAL OF CARDIOLOGY姞
In an attempt to develop a more practical extension of resources for the at-risk primary prevention population, we performed an economic analysis of prevention of first events among patients in the WOSCOPS trial. To summarize the WOSCOPS findings,5 the study randomized 6,595 Scottish men aged 45– 64 years with a mean cholesterol level of 271 mg/dL (7.0 mmol/L) and no evidence of prior MI to pravastatin or placebo. During an average 4.9-year follow-up, pravastatin treatment yielded a 31% reduction in risk of nonfatal MI or death from coronary disease. To assess the cost-effectiveness of pravastatin treatment in a population similar to that in WOSCOPS, we created an economic model of prevention with a primary premise that an initial cardiovascular event constitutes an irreversible transition from health to sickness, the avoidance of which is considered valuable to society9 (Figure 2). “Transition events” in the WOSCOPS study were defined as fatal or nonfatal MI, silent MI, coronary artery bypass grafting, coronary angioplasty, need for undergoing angiography, stroke or transient ischemic attack, and hospitalization for angina. Event rates for the placebo and pravastatin groups were logged on a monthly basis over 5 years. The cost of treating each transition event was based on the average 1996 cost of initial management of the type of event in the Scottish healthcare system. Costs represented the combined average cost estimates from extracontractual tariffs from a sample of ⬎200 hospital trusts and event-specific average lengths of stay calculated from WOSCOPS. Costs did not include those for management subsequent to the first hospital admission or preadmission management, indirect costs, or costs borne by the patient. To determine the effect of transitions on life expectancy, life-years gained were estimated as the difference between the age- and sex-specific cumulative survival curve for Scotland and the event-specific curves; the event-specific curves were derived from data from the Scottish
VOL. 87 (5A)
MARCH 8, 2001
FIGURE 2. Economic analysis of the West of Scotland Coronary Prevention Study. CABG ⴝ coronary artery bypass grafting; MI ⴝ myocardial infarction; TIA ⴝ transient ischemic attack.
Record Linkage System on ⬎460,000 comparable cardiovascular events recorded between 1981 and 1994. Results of this analysis showed that almost 320 men of 10,000 treated with pravastatin would have avoided the transition to cardiovascular disease over the 5 years of the WOSCOPS study; this included avoidance of immediate cardiovascular death in 33, nonfatal MI in 138, hospital admission for angina in 68, revascularization in 33, and nonfatal stroke or transient ischemic attack in 47. It was calculated that 31.4 patients at the specific level of risk of the WOSCOPS cohort would need to start treatment to prevent 1 transition event (Figure 3)9 and that prevention of transition events by pravastatin treatment resulted in a total of 2,017 hospital-bed-days saved and 2,460 life-years gained. The cost for treating 10,000 men with pravastatin was estimated at £23,340,984
($36,449,280) over 5 years, offset by £529,214 ($826,420) in savings from treatment of prevented disease. Thus, the cost per life-year gained was £8121 ($12,682). At the discounting rate of 6% per year recommended by the United Kingdom Treasury, the discounted cost of treatment for each life-year gained was £20,375 ($31,818). Application of the recent European Joint Committee recommendations to consider treatment in patients with risk of ⬎2% per year would result in treatment of approximately 40% of the WOSCOPS population. Using this threshold, the number of patients who would have to be treated to prevent 1 transition event was calculated at 22.5. The nondiscounted cost of treatment per life-year gained through prevention of events was £5,601 ($8,747); at the discounting rate of 6% per year, the cost was £13,995 ($21,855).
FIGURE 3. Number of men who needed to start pravastatin therapy to prevent 1 transition event as a function of the 5-year risk of an event among untreated men. The “X” indicates the average risk and number needed to be treated to prevent 1 event in the entire West of Scotland Coronary Prevention Study population. (Reprinted with permission from BMJ.9) A SYMPOSIUM: LIPID-LOWERING AGENTS
21B
In Scotland (where reasonable cost is frequently measured in pence rather than pounds), the burden of vascular disease is so onerous that healthcare professionals feel constrained to limit statin intervention for primary coronary artery disease to individuals with a 10-year risk of an event of ⬎30%; this guidance, issued in September 1999, is to be reviewed this year. Using this threshold extends consideration of statin treatment to 1.5% of the “healthy” 35– 64-year-old Scottish population; based on the economic analysis of WOSCOPS, the discounted cost of treatment per life-year saved would be £9680 ($15,116). This cost would be added to that of managing the 7.8% of the 35– 64-year-old Scottish population eligible for secondary prevention; a total of 9.3% of the Scottish 35– 64-year-old population would therefore merit statin treatment.10
CONCLUSION Although widespread use of statins for primary prevention may seem like an unjustified extravagance to impose on already strained healthcare systems, the WOSCOPS results provide good evidence that this intervention, if judiciously applied, would make economic sense (i.e., it achieves clinical benefit at a reasonable cost). Of course, what is considered reasonable varies from one healthcare environment to the next. Limiting treatment to individuals at higher risk may contain costs. Alternatively, a number of factors may mitigate the requirement for cost constraints; these include decreases in the price of treatment, better patient compliance, and the development of statin agents capable of achieving greater cholesterol reductions per unit cost. Such developments may improve cost efficiencies sufficiently to encourage extension of
22B THE AMERICAN JOURNAL OF CARDIOLOGY姞
statin treatment to a greater proportion of those individuals recognized to benefit from such treatment in the primary prevention setting.
1. Downs JR, Clearfield M, Whitney E, Shapiro DR, Beere PA, Langendorfer A,
Stein EA, Kruyer W, Gotto AM Jr, for the AFCAPS/TexCAPS Research Group. Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS. JAMA 1998;279: 1615–1622. 2. The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group. Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. N Engl J Med 1998;339:1349 –1357. 3. Sacks FM, Pfeffer MA, Moye LA, Rouleau JL, Rutherford JD, Cole TG, Brown L, Warnica JW, Arnold JMO, Wun C-C, Davis BR, Braunwald E, for the Cholesterol and Recurrent Events Trial Investigators. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. N Engl J Med 1996;335:1001–1009. 4. Scandinavian Simvastatin Survival Study Group. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 1994;344:1383–1389. 5. Shepherd J, Cobbe SM, Ford I, Isles CG, Lorimer AR, Macfarlane PW, McKillop JH, Packard CJ, for the West of Scotland Coronary Prevention Study Group. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. N Engl J Med 1995;333:1301–1307. 6. Prevention of coronary heart disease in clinical practice: recommendations of the Second Joint Task Force of European and Other Societies on Coronary Prevention. Eur Heart J 1998;19:1434 –1503. 7. Jo¨nsson B, Johannesson M, Kjekshus J, Olsson AG, Pedersen TR, Wedel H, for the Scandinavian Simvastatin Survival Study Group. Cost-effectiveness of cholesterol lowering: results from the Scandinavian Simvastatin Survival Study (4S). Eur Heart J 1996;17:1001–1007. 8. Mark DB. Medical economics in cardiovascular medicine. In: Topol EJ, ed. Textbook of Cardiovascular Medicine. Philadelphia: Lippencott-Raven Publishers; 1998:1033–1061. 9. Caro J, Klittich W, McGuire A, Ford I, Norrie J, Pettitt D, McMurray J, Shepherd J, for the West of Scotland Coronary Prevention Study Group. The West of Scotland Coronary Prevention Study: economic benefit analysis of primary prevention with pravastatin. BMJ 1997;315:1577–1582. 10. Haq IU, Wallis EJ, Yeo WW, Jackson PR, Ritchie LD, Isles CG, Ramsay LE. Population implications of lipid-lowering for primary prevention of coronary heart disease: data from the 1995 Scottish Health Survey [abstract]. Heart 1999;81(suppl 1):28.
VOL. 87 (5A)
MARCH 8, 2001
MBChB, PhD
On the basis of the clinical benefit and virtual absence of adverse effects observed with statin treatment in major primary and secondary prevention trials, a case could be made for considering statin therapy for all patients meeting the eligibility criteria for these trials. Establishing a risk threshold for statin treatment based on cost is an urgent item on the agenda of modern healthcare systems. An economic analysis using West of Scotland Coronary Prevention Study (WOSCOPS) findings indicates that statin treatment would have prevented 318 events per 10,000 patients in a population similar to that in WOSCOPS (average 1.5% annual risk of a cardiovascular event) at a discounted cost per life-year gained of £20,375 ($31,818). Application of current European treatment guidelines to consider treatment in
patients with risk >2% per year would result in treatment of approximately 40% of the WOSCOPS population; discounted cost per life-year gained in this case would be £13,995 ($21,855). In Scotland, an annual risk threshold of >3% for treatment has been adopted, corresponding to only 8% of the WOSCOPS population; the discounted cost per life-year gained is £9680 ($15,116). Reductions in drug cost, improved compliance, and use of more potent statins could alter cost efficiencies and encourage use of statins in a greater proportion of the primary prevention population that has been shown to benefit from such treatment. 䊚2001 by Excerpta Medica, Inc. Am J Cardiol 2001;87(suppl):19B–22B
he major statin trials provide remarkably consistent evidence of the benefits of cholesterol lowerT ing in both the primary and secondary prevention of
has resulted in benefits with respect to prevention of cardiovascular events across a broad risk range, from an annual risk as low as 0.5% in the AFCAPS/TexCAPS study1 to an annual risk as high as 4.5% in the 4S trial.4 In addition, these benefits have been achieved in populations in the CARE and LIPID studies, in which up to 80% were receiving aspirin treatment, 40 –50% -blocker treatment, 30 – 40% calcium-antagonist treatment, and 15–16% angiotensinconverting enzyme inhibitor treatment.2,3 With demonstration of clinical effectiveness across such a broad risk range, a key question that emerges is where to draw the line on cost-based treatment recommendations. In an attempt to facilitate decisions on which patients should receive treatment, a joint commission of the European Society of Cardiology, European Atherosclerosis Society, and European Society for Hypertension ruled in 1998 that an absolute risk of at least 20% for experiencing a vascular event over the next 10 years (or, broadly, a 2% risk per year) warranted consideration for intervention.6 With reference to Figure 1, this dictum would result in recommendation of treatment for high-risk patients such as those with coronary artery disease and elevated or normal cholesterol, reflecting the patient populations of the 4S, CARE, and LIPID trials, as well as hypercholesterolemic patients with additional cardiovascular risk factors, a profile met by a segment of the WOSCOPS patient population. These patients generally would be considered to have an annual risk of cardiovascular events of ⱖ2%. Patients with lower risk—such as hypercholesterolemic patients who are otherwise “healthy,” normocholesterolemic patients with other risk factors, and normocholesterolemic “healthy” pa-
coronary artery disease.1–5 Indeed, in its broadest sense, interpretation of the findings of these trials would lead to the conclusion that because cholesterol reduction with these agents is virtually devoid of side effects, all patients who meet the entry criteria for the Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS), West of Scotland Coronary Prevention Study (WOSCOPS), Cholesterol and Recurrent Events (CARE), Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID), and Scandinavian Simvastatin Survival Study (4S) trials merit lipid-lowering intervention. Although arguably justifiable in clinical terms, such a liberal treatment strategy is patently impractical in most, if not all, national healthcare systems because of economic factors. Instead, it is more rational to target individuals whose risk of a cardiovascular event exceeds an accepted specified value. How to select such a value or values remains a matter of some contention.
WHO BENEFITS FROM STATIN THERAPY AND WHO SHOULD BE TREATED? To date, clinical endpoint trials of statins have involved the first-generation agents lovastatin, pravastatin, and simvastatin. Treatment with these agents From the Institute of Biochemistry, Royal Infirmary, Glasgow, Scotland, United Kingdom. Address for reprints: James Shepherd, MBChB, PhD, Department of Pathological Biochemistry, Royal Infirmary, 84 Castle Street, Glasgow, G4 0SF, Scotland. ©2001 by Excerpta Medica, Inc. All rights reserved.
0002-9149/01/$ – see front matter PII S0002-9149(01)01451-5
19B
FIGURE 1. Spectrum of risk across which statin treatment has shown benefit as a means of depicting treatment priorities. Trials with populations indicative of risk group are shown at right. AFCAPS/TexCAPS ⴝ Air Force/Texas Coronary Atherosclerosis Prevention Study; CARE ⴝ Cholesterol and Recurrent Events Trial; CAD ⴝ coronary artery disease; RF ⴝ risk factor; 4S ⴝ Scandinavian Simvastatin Survival Study; WOSCOPS ⴝ West of Scotland Coronary Prevention Study.
tients, all of whom have been shown to benefit from statin therapy in WOSCOPS or AFCAPS/TexCAPS— constitute a gray zone in which treatment is not explicitly recommended and clinical judgment must be exercised. It is, in this regard, important to recognize that guidelines are designed to promote treatment uniformity in areas of indecision, that they must not be applied unthinkingly or reflexively, and that clinical judgment should always take precedence over such recommendations.
ECONOMIC ANALYSIS OF WOSCOPS In Scotland, publication of the WOSCOPS results called attention to the potential financial consequences of routinely implementing lipid-lowering therapy as primary prevention of coronary artery disease in individuals matching the WOSCOPS risk profile (a 1.5% average risk of a cardiovascular event). It was calculated that approximately 11.5% of the apparently healthy 35– 64-year-old Scottish population would merit treatment with routine application of these findings. In an attempt to forestall financial disaster, it was hurriedly suggested to practitioners that treatment in primary prevention be limited to those patients with an annual risk of ⱖ4%. Review of the WOSCOPS database, however, revealed that none of the patients in this trial population exhibited cardiovascular risk of such magnitude; indeed, such elevated risk is not likely to be present in individuals without evidence of existing vascular disease.6 A more practical approach to resource allocation was clearly needed. Far less contentious was the cost-effectiveness of treatment to prevent a second myocardial infarction (MI) or reduce the impact of complications. In the secondary prevention setting, the 4S investigators7 calculated from their database that the cost of simvastatin therapy per lifeyear gained after a first MI, discounted at 5% per year, was £5,502 ($8,592)—a value well within the price range normally considered to be cost-effective.8 20B THE AMERICAN JOURNAL OF CARDIOLOGY姞
In an attempt to develop a more practical extension of resources for the at-risk primary prevention population, we performed an economic analysis of prevention of first events among patients in the WOSCOPS trial. To summarize the WOSCOPS findings,5 the study randomized 6,595 Scottish men aged 45– 64 years with a mean cholesterol level of 271 mg/dL (7.0 mmol/L) and no evidence of prior MI to pravastatin or placebo. During an average 4.9-year follow-up, pravastatin treatment yielded a 31% reduction in risk of nonfatal MI or death from coronary disease. To assess the cost-effectiveness of pravastatin treatment in a population similar to that in WOSCOPS, we created an economic model of prevention with a primary premise that an initial cardiovascular event constitutes an irreversible transition from health to sickness, the avoidance of which is considered valuable to society9 (Figure 2). “Transition events” in the WOSCOPS study were defined as fatal or nonfatal MI, silent MI, coronary artery bypass grafting, coronary angioplasty, need for undergoing angiography, stroke or transient ischemic attack, and hospitalization for angina. Event rates for the placebo and pravastatin groups were logged on a monthly basis over 5 years. The cost of treating each transition event was based on the average 1996 cost of initial management of the type of event in the Scottish healthcare system. Costs represented the combined average cost estimates from extracontractual tariffs from a sample of ⬎200 hospital trusts and event-specific average lengths of stay calculated from WOSCOPS. Costs did not include those for management subsequent to the first hospital admission or preadmission management, indirect costs, or costs borne by the patient. To determine the effect of transitions on life expectancy, life-years gained were estimated as the difference between the age- and sex-specific cumulative survival curve for Scotland and the event-specific curves; the event-specific curves were derived from data from the Scottish
VOL. 87 (5A)
MARCH 8, 2001
FIGURE 2. Economic analysis of the West of Scotland Coronary Prevention Study. CABG ⴝ coronary artery bypass grafting; MI ⴝ myocardial infarction; TIA ⴝ transient ischemic attack.
Record Linkage System on ⬎460,000 comparable cardiovascular events recorded between 1981 and 1994. Results of this analysis showed that almost 320 men of 10,000 treated with pravastatin would have avoided the transition to cardiovascular disease over the 5 years of the WOSCOPS study; this included avoidance of immediate cardiovascular death in 33, nonfatal MI in 138, hospital admission for angina in 68, revascularization in 33, and nonfatal stroke or transient ischemic attack in 47. It was calculated that 31.4 patients at the specific level of risk of the WOSCOPS cohort would need to start treatment to prevent 1 transition event (Figure 3)9 and that prevention of transition events by pravastatin treatment resulted in a total of 2,017 hospital-bed-days saved and 2,460 life-years gained. The cost for treating 10,000 men with pravastatin was estimated at £23,340,984
($36,449,280) over 5 years, offset by £529,214 ($826,420) in savings from treatment of prevented disease. Thus, the cost per life-year gained was £8121 ($12,682). At the discounting rate of 6% per year recommended by the United Kingdom Treasury, the discounted cost of treatment for each life-year gained was £20,375 ($31,818). Application of the recent European Joint Committee recommendations to consider treatment in patients with risk of ⬎2% per year would result in treatment of approximately 40% of the WOSCOPS population. Using this threshold, the number of patients who would have to be treated to prevent 1 transition event was calculated at 22.5. The nondiscounted cost of treatment per life-year gained through prevention of events was £5,601 ($8,747); at the discounting rate of 6% per year, the cost was £13,995 ($21,855).
FIGURE 3. Number of men who needed to start pravastatin therapy to prevent 1 transition event as a function of the 5-year risk of an event among untreated men. The “X” indicates the average risk and number needed to be treated to prevent 1 event in the entire West of Scotland Coronary Prevention Study population. (Reprinted with permission from BMJ.9) A SYMPOSIUM: LIPID-LOWERING AGENTS
21B
In Scotland (where reasonable cost is frequently measured in pence rather than pounds), the burden of vascular disease is so onerous that healthcare professionals feel constrained to limit statin intervention for primary coronary artery disease to individuals with a 10-year risk of an event of ⬎30%; this guidance, issued in September 1999, is to be reviewed this year. Using this threshold extends consideration of statin treatment to 1.5% of the “healthy” 35– 64-year-old Scottish population; based on the economic analysis of WOSCOPS, the discounted cost of treatment per life-year saved would be £9680 ($15,116). This cost would be added to that of managing the 7.8% of the 35– 64-year-old Scottish population eligible for secondary prevention; a total of 9.3% of the Scottish 35– 64-year-old population would therefore merit statin treatment.10
CONCLUSION Although widespread use of statins for primary prevention may seem like an unjustified extravagance to impose on already strained healthcare systems, the WOSCOPS results provide good evidence that this intervention, if judiciously applied, would make economic sense (i.e., it achieves clinical benefit at a reasonable cost). Of course, what is considered reasonable varies from one healthcare environment to the next. Limiting treatment to individuals at higher risk may contain costs. Alternatively, a number of factors may mitigate the requirement for cost constraints; these include decreases in the price of treatment, better patient compliance, and the development of statin agents capable of achieving greater cholesterol reductions per unit cost. Such developments may improve cost efficiencies sufficiently to encourage extension of
22B THE AMERICAN JOURNAL OF CARDIOLOGY姞
statin treatment to a greater proportion of those individuals recognized to benefit from such treatment in the primary prevention setting.
1. Downs JR, Clearfield M, Whitney E, Shapiro DR, Beere PA, Langendorfer A,
Stein EA, Kruyer W, Gotto AM Jr, for the AFCAPS/TexCAPS Research Group. Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS. JAMA 1998;279: 1615–1622. 2. The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group. Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. N Engl J Med 1998;339:1349 –1357. 3. Sacks FM, Pfeffer MA, Moye LA, Rouleau JL, Rutherford JD, Cole TG, Brown L, Warnica JW, Arnold JMO, Wun C-C, Davis BR, Braunwald E, for the Cholesterol and Recurrent Events Trial Investigators. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. N Engl J Med 1996;335:1001–1009. 4. Scandinavian Simvastatin Survival Study Group. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 1994;344:1383–1389. 5. Shepherd J, Cobbe SM, Ford I, Isles CG, Lorimer AR, Macfarlane PW, McKillop JH, Packard CJ, for the West of Scotland Coronary Prevention Study Group. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. N Engl J Med 1995;333:1301–1307. 6. Prevention of coronary heart disease in clinical practice: recommendations of the Second Joint Task Force of European and Other Societies on Coronary Prevention. Eur Heart J 1998;19:1434 –1503. 7. Jo¨nsson B, Johannesson M, Kjekshus J, Olsson AG, Pedersen TR, Wedel H, for the Scandinavian Simvastatin Survival Study Group. Cost-effectiveness of cholesterol lowering: results from the Scandinavian Simvastatin Survival Study (4S). Eur Heart J 1996;17:1001–1007. 8. Mark DB. Medical economics in cardiovascular medicine. In: Topol EJ, ed. Textbook of Cardiovascular Medicine. Philadelphia: Lippencott-Raven Publishers; 1998:1033–1061. 9. Caro J, Klittich W, McGuire A, Ford I, Norrie J, Pettitt D, McMurray J, Shepherd J, for the West of Scotland Coronary Prevention Study Group. The West of Scotland Coronary Prevention Study: economic benefit analysis of primary prevention with pravastatin. BMJ 1997;315:1577–1582. 10. Haq IU, Wallis EJ, Yeo WW, Jackson PR, Ritchie LD, Isles CG, Ramsay LE. Population implications of lipid-lowering for primary prevention of coronary heart disease: data from the 1995 Scottish Health Survey [abstract]. Heart 1999;81(suppl 1):28.
VOL. 87 (5A)
MARCH 8, 2001