Effectiveness and efficiency of different guidelines on statin treatment for preventing deaths from coronary heart disease: modelling study

Data sources

Table A. Probabilities of CHD deaths of Ontario patients discharged between 1988-1992 from acute care hospitals after a stay caused by coronary heart disease, cerebrovascular disease, or peripheral arterial disease.

Table B. Description of Guideline criteria applied to CHHS population

Table C. The Number of Lives Saved from CHD Deaths over 5 years, Cumulative Percentage of Total Population Treated and Number Needed to Treat (NNT) with Statin Treatment in Accordance with Different Guidelines for the Management and Treatment of Dyslipidaemia (in Microsoft Excel)

Appendix: Detailed description of methods

Data sources

The study population consisted of respondents to the Canadian Heart Health Survey (CHHS), a cross-sectional, population-based survey that contained biophysical measures including blood pressure, weight, height, and blood lipid levels.¹

The CHHS, conducted between 1990 and 1992, is well suited to estimate the potential effectiveness of statins since this was before they became a standard mode of therapy thus providing an estimate of the risk of coronary heart disease (CHD) outcomes without treatment. Additionally, there is no strong evidence that the CHD risk of Canadians has appreciably changed in the intervening period, given that the incidence of disease is stable² and, except for smoking, risk factors are either unchanged or have shown small prevalence increases.³

The target population of this survey included all Canadian males and females between the ages of 20 and 74 years. The survey was a stratified, two-stage, probability sample and consisted of a home interview, followed by a clinic visit where physical measures, including fasting blood samples, were taken. All blood lipid analyses were done at the Lipid Research Laboratory of the University of Toronto and discussed in detail elsewhere.⁴ The response rate for the home interview was 78% (N = 23,129). We used a subsample of the respondents who were asked questions about their family history (N=9,286). Of these, 6,760 respondents (73% of those interviewed) provided a fasting blood sample during the clinic interview and had completed responses to the questions pertaining to CVD risk.

Baseline CHD mortality risk estimates are necessary for estimations of NNT and population CHD death. Framingham or similar risk models, however, are not available for people with CHD or cardiovascular disease (CVD). For these people, the baseline risks of CHD death was estimated using a population-based prevalence cohort of CVD patients from the Canadian Institutes for Health Information (CIHI) hospital discharge abstract database (table A). These data have been used previously to examine CVD incidence and survival.^5;6 We identified all persons aged 20 to 74 years in Ontario who were discharged from 1988 to 1992 with either ischemic heart disease (International Classification of Diseases, Ninth Revision [ICD-9] codes 410-4), cerebrovascular disease (433-6) or peripheral arterial disease (440, 444) for any reason (most responsible diagnosis, diagnosis contributing to hospital stay or pre-existing condition). Their age-specific 5-year CHD mortality rates were calculated from 1992 and applied to all Canadians with CVD.

Estimating the rates of CHD-related death and of "hard" CHD events on the basis of patients who were discharged within the previous 4 years of the observation period will overrepresent the number of patients who had a recent CVD event. This has a potential to overestimate the mortality rates of CHHS respondents with prevalent CVD. The extent of this potential bias was examined by comparing the 5 year mortality rate (1997-2002) calculated using 4 years (1992-1997) and 9 years (1988-1997) of wash-in data. The rates changed little from 15.5% to 16.2%.

In this study, the number needed to treat (NNT) for CHD death was estimated using a proportion of all-cause mortality, since cause of death is not known for hospitalized patients in Ontario. The proportion of all deaths among people with CVD that were attributed to CHD has been examined in clinical trials for statins.^7-10 The estimate we used (47% proportional mortality of CHD) most closely reflected a population-based CVD prevalence cohort¹⁰. The proportion of deaths attributed to CAD from 4 studies examined ranged from 47% to 74%.^7-10

Analysis

Table B shows the screening criteria set by each guideline recommendation, and those applied to the CHHS respondents. All the guidelines recommended ascertainment of lipid profiles for individuals with history of CVD or diabetes and used a number of risk factors to guide whether a person should be screened. The type of risk factors varied between guidelines but most considered smoking, hypertension, and family history of CVD as risk factors. Risk factors, familial hyperlipidemia, familial hypercholesterolemia or renal diseases could not be identified in the CHHS population. The recommended age at which routine screening commenced differed between guidelines.

Generally, each guideline specified individuals with CVD and/or diabetes to be at the highest risk category. Estimates of the number of individuals with diabetes and CVD generated in this study were based on the proportion of respondents who self-reported having these diseases in the CHHS. Self-reported CVD and diabetes likely under represents physician-diagnosed disease status¹¹ and therefore may underestimate the size and population health benefit of statin therapy in the high-risk population. However, the magnitude of the underestimation is likely to be small since the coefficients for diabetes status in the Framingham equations used to predict CHD risk are relatively small. Estimates of CVD prevalence in the CHHS are similar to estimates of the prevalence of CVD in the Canadian population reported in other studies and therefore potential error is likely small.¹¹

Individuals were assigned to risk groups according to the six guidelines recommendations. For individuals without CVD and/or diabetes, guideline specific risk chart was used to estimate 5 year CVD risk (Australia, New Zealand) or 10 year CHD risk (Canada, United States) or 10 year CVD risk (Joint British Societies, European Societies). The survey sampling weights were applied to generate estimates for all Canadians 20 to 74 years of age.

Individuals were considered treated with statins according to the six guidelines recommendations. Some guidelines had target lipid levels for different risk groups. The NCEP, ATP III guideline also used risk factors to recommend statin therapy. Only people above the appropriate target levels (or with risk factors for the NCEP ATP III guidelines) were considered for statin therapy in our analysis.

The calculation of the NNT with statins for 5 years to prevent one CHD death or event requires an estimate of baseline risk for developing these outcomes. For people without pre-existing CVD, CHD and CVD mortality risk were estimated using the Framingham Risk or SCORE equations.^12;13 The estimation of baseline risks for people with CVD has been described in the earlier section. The relative effectiveness of statins in avoiding a CHD mortality was assumed to be 27% for all risk groups, as reported by La Rosa et al.¹⁴ The number of CHD deaths avoided was calculated by summing, for those recommended treatment, the product of baseline risk and the relative effectiveness of statins. The NNT to prevent one CHD event was estimated as the sum of the number of people treated divided by the sum of the number of CHD events prevented. The results of the analyses for the guidelines are summarized in table C.

Reference List

1. MacLean DR, Petrasovits A, Nargundkar M, Connelly PW, MacLeod E, Edwards A et al. Canadian heart health surveys: a profile of cardiovascular risk. Survey methods and data analysis. Canadian Heart Health Surveys Research Group. CMAJ 1992;146:1969-74.

2. Tu JV, Austin PC, Filate WA, Johansen HL, Brien SE, Pilote L et al. Outcomes of acute myocardial infarction in Canada. Can.J.Cardiol. 2003;19:893-901.

3. Tanuseputro P, Manuel DG, Leung M, Nguyen K, Johansen H. Risk factor for cardiovascular disease in Canada. Can J Cardiol 2003;19:-1249.

4. Connelly PW, MacLean DR, Horlick L, O’Connor B, Petrasovits A, Little JA. Plasma lipids and lipoproteins and the prevalence of risk for coronary heart disease in Canadian adults. Canadian Heart Health Surveys Research Group. CMAJ 1992;146:1977-87.

5. Jackevicius CA, Mamdani M, Tu JV. Adherence with statin therapy in elderly patients with and without acute coronary syndromes. JAMA 2002;288:462-7.

6. Tu JV, Pashos CL, Naylor CD, Chen E, Normand SL, Newhouse JP et al. Use of cardiac procedures and outcomes in elderly patients with myocardial infarction in the United States and Canada. N Engl J Med 1997;336:1500-5.

7. 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. The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group. N Engl J Med 1998;339:1349-57.

8. Lewis SJ, Sacks FM, Mitchell JS, East C, Glasser S, Kell S et al. Effect of pravastatin on cardiovascular events in women after myocardial infarction: the cholesterol and recurrent events (CARE) trial. J Am Coll Cardiol 1998;32:140-6.

9. Sacks FM, Pfeffer MA, Moye LA, Rouleau JL, Rutherford JD, Cole TG et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events Trial investigators. N Engl J Med 1996;335:1001-9.

10. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet 2002;360:7-22.

11. Manuel DG, Leung M, Nguyen K, Tanuseputro P, Johansen KS. Burden of Cardiovascular Disease in Canada. Can J Cardiol 2003;19:997-1004.

12. Anderson KM, Odell PM, Wilson PW, Kannel WB. Cardiovascular disease risk profiles. Am Heart J 1991;121:293-8.

13. Grundy SM, Pasternak R, Greenland P, Smith S Jr, Fuster V. AHA/ACC scientific statement: Assessment of cardiovascular risk by use of multiple-risk-factor assessment equations: a statement for healthcare professionals from the American Heart Association and the American College of Cardiology. J Am Coll.Cardiol 1999;34:1348-59.

14. LaRosa JC, He J, Vupputuri S. Effect of statins on risk of coronary disease: a meta-analysis of randomized controlled trials. JAMA 1999;282:2340-6.

Table A. Probabilities of CHD deaths of Ontario patients discharged between 1988-1992 from acute care hospitals after a stay caused by coronary heart disease, cerebrovascular disease, or peripheral arterial disease.

CHD = Coronary Heart Disease.

Table B. Description of Guideline criteria applied to CHHS population