Chau, J

Cheung, BMY

Kumana, CR

Lau, CP

Lauder, IJ

McGhee, SM

Hong Kong Medical Journal

HKU Scholars Hub

Title Cost-effectiveness of statins for coronary heart disease patientswith hypercholesterolaemiaAuthor(s) Cheung, BMY; Chau, J; McGhee, SM; Lauder, IJ; Lau, CP;Kumana, CRCitation Hong Kong Medical Journal, 2006, v. 12 n. 2 Supp 1, p. 20-23Issued Date 2006URL http://hdl.handle.net/10722/45481Rights Creative Commons: Attribution 3.0 Hong Kong License20      Hong Kong Med J Vol 12 No 2 Supplement 1 April 2006RESEARCH DISSEMINATION REPORT—CARDIOVASCULAR DISEASESHong Kong Med J 2006;12 (Suppl 1):S20-3Cost-effectiveness of statins forcoronary heart disease patients withhypercholesterolaemia○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○University of Hong Kong:Department of MedicineBMY CheungJ ChauCP LauCR KumanaDepartment of Community MedicineSM McGheeDepartment of Statistics and ActuarialScienceIJ LauderHSRF project number: 611006Principal applicant and corresponding author:BMY CheungDepartment of MedicineQueen Mary Hospital102 Pokfulam RoadHong Kong SAR, ChinaTel: (852) 2855 4768Fax: (852) 2904 9443E-mail: mycheung@hkucc.hku.hkBMY Cheung  J Chau SM McGhee IJ Lauder CP Lau  CR Kumana  IntroductionThere is a strong association between blood cholesterol and the development ofischaemic heart disease (IHD). The Scandinavian Simvastatin Survival Study(4S) was the first of several large-scale clinical trials of an HMG-CoA reductaseinhibitor (statin) on cardiovascular events and mortality in patients with knowncoronary heart disease.1 Treatment with simvastatin resulted in a 37% reductionin non-fatal myocardial infarction (MI), a 37% decrease in revascularisationprocedures, and a 42% reduction in deaths attributable to IHDs. Overallmortality was reduced by 30%. Subsequent large clinical trials such as theCholesterol And Recurrent Events (CARE) Trial2 and Long-term Interventionwith Pravastatin In Ischaemic Disease (LIPID) study,3 showed that lower-riskpatients also benefited from statins.Diet modification alone is insufficient to reduce cholesterol level in themajority of patients. For these patients, statins are needed as they are efficaciousand reasonably safe. We set out to study coronary heart disease patientsrequiring lipid-lowering therapy and to analyse the costs, benefits andcost-effectiveness of treating hypercholesterolaemia with statins in thesepatients.MethodsEffect of diet and statin therapyPatients were recruited from the Cardiac Clinic at Sai Ying Pun betweenNovember 1996 and January 1997. Patients were included if they had not hadtheir cholesterol checked in the previous 2 years and were diagnosed as havingIHD, by virtue of a clinical diagnosis of IHD or angina, a history of MI, positiveexercise ECG or thallium scan, coronary angiography showing any significantstenosis, or prescription of nitrates as anti-anginal therapy. Subjects were seenand plasma lipid profile was measured at the time of recruitment, after dietaryclass, and 3 and 6 months after statin prescription.Cost-effectiveness of dietary intervention in lowering serum cholesterolThe cost-effectiveness of dietary intervention was assessed in those patientswho were started on cholesterol-lowering therapy for the first time. Drug therapywould be started if the plasma total cholesterol (TC) exceeded 5.2 mmol/L anddietary modification for at least 3 months had failed.4 We used this period toassess the effectiveness of diet. All hypercholesterolaemic patients were asked toattend an afternoon dietary class (3 hours) run by dieticians. The cost in terms ofdietician time and the cholesterol-lowering effect of the dietary intervention wereused to calculate a cost-effectiveness ratio.Cost-effectiveness of statins in lowering plasma cholesterolAssessment of costsPatients were assumed to receive 40 mg daily of pravastatin, as in theCARE study.2 The acquisition cost of a 20 mg tablet of pravastatin was HK$7.67for hospitals in the Hong Kong Hospital Authority. A telephone survey of10 local private clinics indicated that the market price of a full lipid profilewas $440.Key Messages1. These results suggest that aperiod of non-pharmacologicalintervention including dietaryclasses lowers the blood choles-terol of patients with coronaryheart disease. The use of statinscan improve the lipid profiles ofthese patients further.2. For Hong Kong patients withmyocardial infarction andaverage cholesterol levels onstatin therapy, the gross costper event prevented or perquality-adjusted life year gainedis substantial; the potentialbenefits  and savings mayoutweigh the costs.Hong Kong Med J Vol 12 No 2 Supplement 1 April 2006      21Cholesterol reduction in patients with coronary heart diseaseAssessment of benefitsWe assessed the benefits of treating a hypothetical cohortof Hong Kong patients with the same demographicsand prognosis as in the CARE study. As there were nolocal data on the long-term benefit of statins, we usedthe outcome data of the CARE study. Patients inCARE were American and Canadian men (n=3583)and post-menopausal women (n=576), aged 21 to 75 years,who had an acute MI 3 to 20 months previously. Theentry criteria included plasma TC levels <240 mg/dL(6.2 mmol/L), low-density lipoprotein (LDL) cholesterollevels of 115 to 174 mg/dL (3.0 to 4.5 mmol/L), fastingtriglyceride levels of <350 mg/dL (4.0 mmol/L), fastingglucose levels of no more than 220 mg/dL (12.2 mmol/L),left ventricular ejection fractions of no less than 25%, andno symptomatic congestive heart failure. The patients wererandomised to double-blind treatment with either placebo(n=2078) or pravastatin (n=2081) for a median period of 5years.Benefits evaluated included (i) benefits to the hospital:the prevention of IHD (costs of hospitalisation, clinicattendance, cardiac investigations, cardiac interventionprocedures, rehabilitation), and other cardiovascular diseases(eg stroke, peripheral vascular disease), and (ii) patientbenefits: reduction in loss of earnings. We used data fromthe CARE study to estimate the number of cardiac eventsprevented by treatment with statins.Cost-effectiveness analysisThe cost-effectiveness in terms of reduction in cardiacevents and mortality was analysed from the perspective ofa hospital-based cardiological service providing in-patientand out-patient care, specifically the diagnosis, treatment,rehabilitation, follow-up and secondary prevention ofIHD.Cost-utility analysisIn our cost-utility analysis, the endpoint was gross costper quality-adjusted life year (QALY) gained. In the 4Sstudy, the quality of life (QOL) in their population ofpost-MI patients was 0.88. Other studies reported theQOL as between 0.8 and 0.9. We therefore used 0.85.Based on official statistics, the remaining average lifeexpectancy was estimated to be 16.7 and 22.3 yearsrespectively in males and females. We assumed that at age59 a prior MI decreased life expectancy by half, as observedin the 4S study.Cost-benefit analysisBenefits and savings arose from life years gained,prevention of MIs, strokes and procedures. The life yearsgained was translated to earnings according to theemployment pattern for the working population aged 55 to59 years. Prevention of non-fatal MIs would lead to fewerhospitals admissions. The average cost of an admission toQueen Mary Hospital for an acute MI patient was $46 720.The median cost of a percutaneous transluminal coronaryangioplasty (PTCA) procedure was $35 000 and the me-dian price for a stent was $12 000. Calculation of benefitsdue to stroke prevention was based on the assumption ofequal numbers of severe and mild disabilities prevented.Severe disabilities was assumed to require attendance at aday hospital with supervised daily training ($1430 perattendance). Mild disabilities were assumed to require com-munity nursing services (twice per week at $360 per visit).ResultsEffect of diet and statin therapyThere were 106 males and 95 females (mean age, 71±10years) recruited. Results of lipid profiles are shown inTables 1 to 3. For those patients who had raised cholesterollevels in their first blood test, they were asked to attenddiet class and have their second blood test measured 3months later.Cost-effectiveness of dietary intervention and statintherapy in lowering serum cholesterolThe cost of the dietary intervention was $55.44 per patient.The mean reductions in TC and LDL cholesterol after thedietary intervention were 0.24 mmol/L and 0.22 mmol/L,respectively. Therefore, the cost per mmol/L reduction wasestimated as $231 for TC and $252 for LDL cholesterol.The mean cost of statin therapy was $8.41 per patientper day. The average LDL cholesterol level of patientswho had received statin treatment until the end of the studydecreased from 4.58±0.77 to 3.59±0.86 (P=0.003). Themean reduction due to statin treatment was 0.99 mmol/Lper patient. The cost-effectiveness of statin therapy was$8.49 per patient per day per mmol/L reduction in LDLcholesterol.Cost-effectiveness of statins in lowering plasmacholesterolCosts and benefits of lipid-lowering therapy with a statinThe cost of the lipid measurements and prescription ofTable 1.  Lipid profileProfile* Blood test 1 (n=143) Blood test 2 (n=40) Blood test 3 (n=30) Blood test 4 (n=16)Mean ± SD (mmol/L) Mean ± SD (mmol/L) Mean ± SD (mmol/L) Mean ± SD (mmol/L)TC 5.30 ± 0.99 5.80 ± 0.87 5.53 ± 0.95 5.52 ± 0.94TG 1.39 ± 0.92 1.60 ± 1.10 1.57 ± 1.21 1.48 ± 0.65HDL 1.17 ± 0.38 1.25 ± 0.42 1.20 ± 0.34 1.20 ± 0.32LDL 3.51 ± 0.89 3.93 ± 0.82 3.60 ± 1.05 3.63 ± 0.84* TC denotes total cholesterol, TG triglycerides, HDL high-density lipoprotein cholesterol, and LDL low-density lipoprotein cholesterolCheung et al22      Hong Kong Med J Vol 12 No 2 Supplement 1 April 200640 mg pravastatin daily for 2081 patients was estimated tobe $12 818 960 and $58 258 635.5, respectively. Totalundiscounted cost was $71 077 596. The cost-effectivenessratios are set out in Table 4. Total undiscounted benefits andsavings would be $90 144 231 (Table 5). As the potentialbenefits and savings exceed the costs, there is a net benefitof $19 066 635 before discounting. After discounting at 6%,benefits and savings ($75 944 058) are still larger thanthe discounted costs ($60 512 876), resulting in a netbenefit of $15 431 182. Pravastatin treatment for 5 yearsresulted in 343.12 QALYs gained. Net cost per QALYgained was $71 032 ([$71 077 596 - $46 704 975]/343.12)and after discounting at 6%, $73 218 ([$60 512 876 -$39 347 668]/289.07) [Table 6].Cost-effectiveness of statins under differentcircumstancesThe cost-effectiveness of statins was also estimated forother types of patient population. In a patient populationsimilar to 4S, drugs and biochemical monitoring would cost$8331.23 per patient per year. It would cost $524 867.49 toprevent one coronary event and $1 357 990.49 to preventone death. In a patient population similar to WOSCOPstudy,5 drugs and biochemical monitoring would cost$7359.10 per patient per year. It would cost $1 596 924.70to prevent one coronary event and $4 054 864.10 to preventone death. In a patient population similar to AFCAPS/TexCAPS study,6 drugs and biochemical monitoringwould cost $5707.48 per patient per year. It would cost$1 461 114.88 to prevent one coronary event. In this study,there was no significant reduction in mortality.DiscussionDietary classThese results suggest that dietary classes help to lowerthe cholesterol level of patients with coronary heart disease.Table 2.  Effect of diet class on lipid profiles (n=40)Profile* Before class After class Change in meanMean ± SD Mean ± SD (mmol/L)(mmol/L) (mmol/L)TC 6.04 ± 0.72 5.80 ± 0.87 -0.24†TG 1.63 ± 1.16 1.60 ± 1.10 -0.03†HDL 1.21 ± 0.42 1.24 ± 0.42 -0.03†LDL 4.15 ± 0.56 3.93 ± 0.82 -0.22†* TC denotes total cholesterol, TG triglycerides, HDL high-density lipoproteincholesterol, and LDL low-density lipoprotein cholesterol† P<0.05Table 3.  Effect of statin on lipid profiles (n=16)Profile* Before statin Blood test 3 Blood test 4 ChangeMean ± SD Mean ± SD Mean ± SD in mean(mmol/L) (mmol/L) (mmol/L) (mmol/L)TC 6.33 ± 0.73 5.62 ± 1.20 5.52 ± 0.94 -0.81†TG 1.57 ± 0.84 1.59 ± 1.31 1.48 ± 0.65 -0.09†HDL 1.14 ± 0.34 1.25 ± 0.31 1.23 ± 0.30 -0.09†LDL 4.58 ± 0.77 3.64 ± 1.25 3.59 ± 0.86 -0.99†* TC denotes total cholesterol, TG triglycerides, HDL high-density lipoproteincholesterol, and LDL low-density lipoprotein cholesterol† P<0.05Table 4.  Cost-effectiveness of statin treatmentEvent* No. prevented HK$ cost/event preventedMean (95% CI)No discounting 6% discountingDeaths 16 4 442 350 3 782 055(1 537 736 to undefined†) (1 309 173 to undefined†)CHD deaths 23 3 090 330 2 630 995(1 584 785 to undefined†) (1 349 228 to undefined†)Non-fatal MI 38 1 870 463 1 592 444(1 103 094 to 10 755 162) (939 134 to 9 156 554)Fatal or confirmed non-fatal MI 50 1 421 552 1 210 258(911 251 to 4 442 350) (775 806 to 3 782 055)CHD deaths or non-fatal MI 62 1 146 413 976 014(764 275 to 3 057 101) (650 676 to 2 602 704)Procedures 97 732 759 623 844(534 716 to 1 318 966) (455 238 to 1 122 919)Fatal and non-fatal strokes 24 2 961 566 2 521 370(1 822 502 to 23 692 532) (1 551 612 to 20 170 959)All events (deaths + non-fatal MIs + non-fatal 179 397 082 338 061strokes + procedures)* CHD denotes coronary heart disease, and MI myocardial infarction† The upper limit is undefined as the 95% confidence interval crosses zeroTable 5.  Cost-benefit analysisSource of benefits and savings* Amount (HK$)BenefitsPotential increase in earnings due to life 36 596 390years gainedSavingsAcute admission from non-fatal MI 21 495 692preventionPTCA procedures prevented 21 385 868Deployment of stents prevented 22 475 155Community nursing services for mild 22 408 876disabilities prevented from strokeGeriatric day hospital for severe disabilities 33 582 077prevented from strokeTotal discounted benefits and savings 75 944 058* MI denotes myocardial infarction, and PTCA percutaneous transluminalcoronary angioplastyTable 6.  Gross and net cost per QALY gainedAmount (HK$)No discounting 6% discountingGross cost/QALY gained 207 151 209 336Net cost/QALY gained 271 032 273 218Hong Kong Med J Vol 12 No 2 Supplement 1 April 2006      23Cholesterol reduction in patients with coronary heart diseaseThe use of statins can improve the lipid profiles of thesepatients but at a considerable cost. Dietary intervention isless effective than drug treatment in lowering cholesterolbut it is inexpensive. Since a proportion of patientsrespond to dietary modification, long-term prescription ofexpensive lipid-lowering drugs might be avoided in thesepatients.Cost-effectiveness of lipid-lowering therapyPrevious clinical trials suggest that all at-risk patients willbenefit from treatment with statins, regardless of the levelof their risk. The cost-effectiveness of statins depends onthe risk of coronary heart disease. For patients at high risktreatment with a statin has been shown to be cost-effective.In our analysis of a patient population similar to that in theCARE study, the gross cost per QALY gained is substantial.Care should be taken in the prescription of statins andin deciding whom to treat. Cholesterol per se is a weakindicator of future coronary risk. The majority of coronaryevent patients have average cholesterol levels. To be morecost-effective, statins should be prescribed according to thebaseline risk of individual patients.Treatment with statins can also reduce the risk of stroke,the second leading cause of death. We therefore includedstroke in our analysis and found that its inclusion increasesthe cost-effectiveness of statin therapy. Prevention ofheart attacks and strokes result in other benefits andsavings that ultimately outweigh the costs of statins.These include increased life expectancy and earnings, aswell as avoidance of costs due to acute hospitalisation,more frequent out-patient follow-up, procedures, andrehabilitation.ConclusionsIf coronary heart disease patients in Hong Kong derive asmuch benefit from statin therapy as patients in clinical trials,statin therapy may be economically sound. Although theshort-term costs appear high, there are long-term benefitsin terms of lower mortality, fewer hospitalisations andcardiac catheterizations, angioplasties and coronary arterybypass operations, especially if stroke reduction is alsoconsidered. Therefore, our analysis supports the use ofstatins in addition to dietary intervention for patients withcoronary heart disease. Cholesterol-lowering therapy inpatients with coronary heart disease should be enthusiasti-cally implemented and allocated appropriate resources.AcknowledgementsThis study was supported by the Health Services ResearchFund (#611006). Dr CM Yu and Dr K Busche contributedto this research project. The help from the staff and medicalofficers of the Sai Ying Pun Cardiac Clinic, and the dieti-cians of Queen Mary Hospital is gratefully acknowledged.References1. Randomised trial of cholesterol lowering in 4444 patients withcoronary heart disease: the Scandinavian Simvastatin Survival Study(4S). Lancet 1994;344:1383-9.2. Sacks FM, Pfeffer MA, Moye LA, et al. The effect of pravastatin oncoronary events after myocardial infarction in patients with averagecholesterol levels. Cholesterol and Recurrent Events Trial Investigators.N Engl J Med 1996;335:1001-9.3. Prevention of cardiovascular events and death with pravastatin inpatients with coronary heart disease and a broad range of initialcholesterol levels. The Long-term Intervention with Pravastatinin Ischemic Disease (LIPID) Study Group. N Engl J Med 1998;339:1349-57.4. Wong SP, et al. Guide to plasma lipids and lipoproteins for Hong Kongdoctors. J Hong Kong Cardiol 1996;4:81-9.5. Shepherd J, Cobbe SM, Ford I, et al. Prevention of coronary heartdisease with pravastatin in men with hypercholesterolemia. Westof Scotland Coronary Prevention Study Group. N Engl J Med 1995;333:1301-7.6. Downs JR, Clearfield M, Weis S, et al. Primary prevention ofacute coronary events with lovastatin in men and women withaverage cholesterol levels: results of AFCAPS/ TexCAPS. Air Force/Texas Coronary Atherosclerosis Prevention Study. JAMA 1998;279:1615-22.

Cost-effectiveness of statins for coronary heart disease patients with hypercholesterolaemia

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Cost-effectiveness of statins for coronary heart disease patients with hypercholesterolaemia

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