Cardiovascular disease, the leading cause of death in North

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CLINICAL STUDIES

Application of the 1998 Canadian cholesterol guidelines to a military population: Health benefits and cost effectiveness of improved cholesterol management Johanna N Spaans MSc1, Douglas Coyle MA MSc2, George Fodor MD3, Rama Nair PhD1, Régis Vaillancourt BPharm PharmD4, Steven A Grover MD MPA5, Louis Coupal MSc5

JN Spaans, D Coyle, G Fodor, et al. Application of the 1998 Canadian cholesterol guidelines to a military population: Health benefits and cost effectiveness of improved cholesterol management. Can J Cardiol 2003;19(7):790-796. OBJECTIVE: To determine whether statins are underprescribed in the Canadian military. The cost effectiveness of statin therapy in patients identified by the 1998 Canadian cholesterol interim guidelines was also explored. METHODS: Charts of 1424 Canadian military personnel (age 45 or older) were reviewed at 11 Canadian bases. Risk factors and cholesterol values were used to identify drug therapy candidates. Cost effectiveness ratios and health benefits in terms of years of life saved for statin therapy were estimated for the candidates using a validated cardiovascular disease life expectancy model. RESULTS: Of the 1313 personnel not on lipid lowering medication, 172 were identified as drug therapy candidates. An average of 2.89 years of life saved was forecast for the identified personnel, at an average cost of less than $10,000 per year of life saved. CONCLUSIONS: The health benefits of statin therapy in this population are substantial and the cost effectiveness is acceptable. Statin therapy warrants greater attention as a preventive strategy for coronary artery disease.

Application des lignes de conduite canadiennes en matière de cholestérol à une population militaire : avantages pour la santé et rentabilité de la gestion améliorée du cholestérol OBJECTIF : Déterminer si les statins sont prescrits en quantité suffisante aux militaires canadiens. On a également exploré la rentabilité des statins chez les patients identifiés par les lignes directrices intérimaires canadiennes de 1998 en matière de cholestérol. MÉTHODES : On a examiné les dossiers de 1 424 militaires canadiens (âgés de 45 ans ou plus) dans 11 bases canadiennes. On a utilisé des facteurs de risques et des valeurs de cholestérol pour identifier les candidats à un traitement aux médicaments. On a évalué les rapports coût-efficience et les avantages pour la santé à l’aide d'un modèle validé d’espérance de vie des maladies coronariennes. RÉSULTATS : Sur les 1 313 militaires qui ne suivaient pas un traitement hypolipidémiant, on a identifié 172 candidats admissibles à un traitement médicamenteux. On a prévu qu’on prolongerait de 2,89 ans la vie de ces personnes, et ce, à un coût moyen inférieur à 10 000$ par année de vie sauvée. CONCLUSIONS : Les avantages pour la santé du traitement aux statins dans cette population sont substantiels et le rapport coût-efficacité est acceptable. Le traitement aux statins justifie une plus grande attention comme stratégie préventive des coronaropathies que les autres méthodes.

Key Words: Cholesterol; Drugs; Health economics

ardiovascular disease, the leading cause of death in North America, accounted for 37% of all Canadian deaths in 1995 (1). Coronary artery disease (CAD) causes a significant portion of these deaths. Elevated cholesterol has repeatedly and consistently been shown to be an independent risk factor of CAD (2-4). Most randomized, controlled trials have demonstrated a reduction in coronary events with the use of cholesterol lowering medication (5-7). The acceptance of cholesterol lowering medication in clinical practice as an effective

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means to reduce the risk of CAD, however, was initially hampered by a lack of observed relative risk reduction in overall mortality in some of the early clinical trials with cholesterol lowering medication such as fibric acid derivatives and bile acid sequestrants (5,6). The low coronary event rate in primary prevention, combined with the excess mortality due to other diseases such as stroke and cancer that were sometimes observed in the experimental group, was even occasionally found to increase overall mortality in some trials (8).

1Department

of Epidemiology and Community Medicine, University of Ottawa; 2Ottawa Health Research Institute, Ottawa Hospital; 3Division of Cardiology, University of Ottawa Heart Institute; 4Directorate of Medical Policy, Pharmacy Policies and Standards, Canadian Forces Medical Services, Ottawa, Ontario; 5Centre of the Analysis of Cost Effective Care, the Montreal General Hospital, and Department of Epidemiology and Biostatistics, McGill University, Montréal, Québec Correspondence: Ms Johanna N Spaans, 130 Sherwood Drive, Ottawa, Ontario. Telephone 613-724-4542, email [email protected] Received for publication April 3, 2002. Accepted August 27, 2002

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Several milestone randomized controlled trials on the newer statin drugs for cholesterol reduction have been instrumental in redefining the role of cholesterol lowering pharmacotherapy as a preventive strategy for CAD. By lowering cholesterol levels, statins have recently been shown to reduce not only the risk of coronary events, but also overall mortality in people with elevated cholesterol. In primary prevention, the 4.9-year West of Scotland Coronary Prevention Study (WOSCOPS), published in 1995 (9), found a 31% relative risk reduction in coronary events (P=0.001) and a 22% reduction in overall mortality with the use of pravastatin (P=0.05). In secondary prevention, even greater relative risk reductions in coronary events and mortality have been observed with the use of statin therapy. Specifically, in the Scandinavian Simvastatin Survival Study (4S) (10), major coronary events were reduced by 34% (P=0.00001) and overall mortality by 30% (P=0.0003) with the use of simvastatin over a mean of 5.4 years of follow-up. If evidence-based medicine is to translate into improved population health, the results of clinical trials must be incorporated into routine clinical practice. Preliminary evidence from a 1995 survey, undertaken to examine prescription patterns of cholesterol lowering medication in the Canadian primary clinical setting following the publication of the 4S and the WOSCOPS studies, found that a gap existed between actual and desirable cholesterol screening and management (11). This survey, in which 503 physicians supplied data for 21,470 adult patients, found that total cholesterol (TC) had been assessed in only 54% of men over 40 years of age (11). Also, less than one-third of all patients with elevated cholesterol who were candidates for lipid lowering drug therapy had been prescribed lipid lowering drugs (11). Even more disturbing was the low rate of prescription of lipid lowering medication (36%) in drug therapy candidates at the highest risk level (previous CAD or at least four CAD risk factors) (11). Based on the results of this survey, publication of the results of the 4S and the WOSCOPS had little effect on screening and management of cholesterol in the Canadian clinical setting. The short time interval between the publication of the 4S and WOSCOPS studies and this survey cannot, however, be discounted as the reason for the poor integration of the findings into routine clinical practice. Since the initial statin trials, several other randomized controlled trials have been published that support the initial findings (12-14). Some of these trials have shown that the beneficial effects of statin therapy on the risk of developing CAD also extend to patients with only moderate cholesterol levels. In one 5.2-year primary prevention study, the use of lovastatin 20 to 40 mg daily in patients with moderate cholesterol levels (4.65 to 6.83 mmol/L) reduced the risk of fatal and nonfatal coronary events by 25% (P=0.006) (12). Similar results have been obtained in secondary prevention in patients with comparable cholesterol levels (13,14). Finally, published overviews of randomized, controlled trials of statin therapy, such as that by Hebert et al (15), have provided clear evidence of the benefit of statin therapy on total mortality. When compared with the earlier fibric acid derivative and bile acid sequestrant drug studies, overviews of statin therapy have also provided evidence of the benefit of statin therapy on the risk of stroke (15). Statins are now considered the drug of choice for cholesterol management in most clinical populations.

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The overwhelming evidence supporting the beneficial effect of statin therapy that was available in 1998 resulted in the publication of an interim report of a revised set of Canadian cholesterol guidelines developed by a working group at Health Canada (16). The 1998 publication was designed to update the 1988 Canadian cholesterol guidelines (17) and to assist both primary and secondary prevention strategies in the clinical setting by synthesizing the recent literature that had emerged on statin therapy using an evidence-based approach. It is unclear whether the amount of time that has elapsed since the initial publications on statin therapy in 1994 and 1995 and the overwhelming amount of literature published supporting the results of these earlier studies (in addition to the publication of the revised 1998 Canadian cholesterol interim guidelines) have resulted in better screening and management of cholesterol in the Canadian clinical setting. To answer this question, a study on cholesterol management in the Canadian military was undertaken in 1998, the results of which are presented here. This study was initiated not only because of the recent developments with respect to appropriate cholesterol management, but also because of the potentially negative implications of untreated asymptomatic heart disease on military operations. Furthermore, it was also of interest to determine how well cholesterol is managed in a closely monitored patient population that undergoes routine medical testing, because this would have implications for the feasibility of appropriate cholesterol management in less well monitored civilian populations. Because of increasing financial constraints and mounting interest in health care expenditures, the potential health benefits and cost effectiveness of improved cholesterol management with statin therapy in the sample population were estimated in a complementary step in this investigation, using a validated life expectancy model (18). This step was carried out to determine whether the revised 1998 Canadian cholesterol interim guidelines identify patients for whom drug therapy for cholesterol reduction is a cost effective risk management strategy for CAD. The modelling of life expectancy and cost effectiveness was required in this investigation because of the absence of any clinical data on the long term benefits and cost effectiveness of statin therapy. While diet and exercise are recommended as the initial approach to cholesterol reduction in the revised 1998 Canadian cholesterol interim guidelines (16), the benefits of these risk reduction strategies in terms of cholesterol reduction are typically small and of short duration, often due to poor adherence to dietary changes (19,20). Diet and exercise studies have also failed to consistently show any statistically significant decrease in mortality from such lifestyle modifications (21,22). For example, a recent review that considered the efficacy of different cholesterol lowering dietary and drug interventions found no statistically significant reduction in either CAD mortality or overall mortality with diet therapy, based on the weighted average risk ratio of 16 randomized controlled dietary trials (21). Of course, it should be remembered that no single diet trial can claim to be an a priori test of diet on CAD mortality. Similarly, multiple risk factor interventions for CAD have also not proved to be effective long term risk management strategies (22). A recent systematic review published by Ebrahim and Smith (22) that considered randomized controlled trials of multiple risk factor interventions reported that the pooled effects of these interventions on mortality were insignificant and that any

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changes in risk factors observed were related to the amount of pharmacological treatment received. Because nonpharmacological cholesterol reducing interventions have not been found to be effective CAD risk reduction strategies, they were not considered in the present investigation. Finally, while the 1998 Canadian cholesterol interim guidelines was the latest available reference at the time this study was initiated, an update to this set of guidelines has since been published (23) to take into account recent developments in cholesterol research. The potential effect of the updated guidelines on the results of this investigation will be considered in the discussion section.

METHODS Survey A cross-sectional chart review of military personnel in the Regular Forces posted to 11 bases across Canada was undertaken between July and November 1998. This ‘convenience sample’ was based on all charts available for military personnel over the age of 45 during a site visit at each of the 11 bases. Age was the only eligibility criterion for inclusion into the study. Age 45 was chosen because it is at this time that age itself becomes a risk factor for CAD in men, according to the revised 1998 Canadian cholesterol interim guidelines (16). Chart reviews of this patient population are particularly attractive because of the availability of complete and comprehensive medical records. Specifically, all Regular Force personnel are required to have routine medical examinations, which occur on a biannual basis starting at age 40. Values from the most recent fasting lipid profile, as well as data on nonlipid risk factors for coronary disease identified by the revised 1998 Canadian cholesterol interim guidelines (16), were abstracted from the medical charts. The CAD risk factors considered were age (men 45 years or older and women 55 years or older), diabetes, hypertension (greater than 140 mmHg systolic or greater than 90 mmHg diastolic blood pressure) or taking antihypertensive medication, smoking and a family history of premature CAD in a first-degree relative (CAD at an age less than 55 years in men and less than 65 years in women). Patient history of coronary events and the use of lipid lowering medication was also considered. Left ventricular hypertrophy, although identified as a risk factor for CAD (16), was conservatively assumed not to be present in any of the personnel included in this study because it is not routinely assessed during medical examinations in the military.

Classification In this study, candidates for cholesterol lowering pharmacotherapy were identified based on CAD risk and the cholesterol levels appearing in the revised 1998 Canadian cholesterol interim guidelines (16). Patients not taking lipid lowering drugs but meeting the criteria for drug therapy outlined in the revised 1998 Canadian cholesterol interim guidelines were considered to be drug therapy candidates. Using these guidelines, patients exceeding the recommended low density lipoprotein cholesterol (LDL-c) target level by 1 mmol/L or the ratio of TC to high density lipoprotein cholesterol (TC:HDL-c) target level by greater than 1 for their CAD risk level were identified as drug therapy candidates. These patients were considered most likely to benefit from statin therapy. While triglyceride target values for each risk level were also identified in the revised 1998 Canadian cholesterol interim guidelines, exceeding this target value by 1 mmol/L in the absence of other lipid imbalances does not warrant drug therapy

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initiation according to the guidelines. Personnel exceeding only this target value were identified but were not considered drug therapy candidates in the present study. When abstracting the data from the medical charts, imputation was not used in the event of missing data. Missing values were conservatively assumed not to contribute to the patient’s overall risk of CAD. Missing nonlipid risk factors were not considered part of the overall risk profile and missing cholesterol values were similarly assumed not to exceed the recommended target values. In the absence of recent lipid profiles (less than five years), outdated profiles were considered but were recorded as outdated in the final analysis. Economic analysis: A validated life expectancy model (18) was used to estimate the potential health benefits and cost effectiveness of improved cholesterol management with statin therapy in the study population. A complete description of this model has been described elsewhere (18). Briefly, the validated Markov (state-transition) model estimates life expectancy based on simulations of a cohort of 1000 patients with a defined risk profile. States identified in this model include death from coronary disease, stroke or other diseases and the nonfatal events of coronary insufficiency, myocardial infarction, transient ischemic attack and stroke. The transition probabilities between the states are determined using the multiple regression coefficients derived from the lipid research clinics trial (6) and the cohort risk factor data. The total number of years of life accrued by the cohort (based on the simulations), divided by the size of the cohort (1000), is used to determine the average life expectancy of the cohort. The model estimates the long term health benefits of one therapy over its alternative by comparing the life expectancies generated by the model under these two scenarios. In the present investigation, the potential health benefits of statin therapy for the drug therapy candidates over the alternative of ‘usual care’ were estimated using the model, and the data were collected in the chart review. All the health benefit estimates of statin therapy in model simulations, in terms of reductions in LDL-c, HDL-c and TC, were based on the results obtained in the 4S study (10). Specifically, when estimating the health benefits in drug therapy candidates, the model assumed reductions in TC and LDL-c of 25% and 35%, respectively, and an increase in HDL-c of 8% with the use of statin therapy. It should be noted that this model assumes that the new CAD risk level of a statin-treated patient is equal to that of an untreated person with the same endogenous cholesterol levels after a oneyear lag. To determine the cost effectiveness of statin therapy, the life expectancy model considers direct treatment, surgical and intervention costs, and the life expectancies of alternative treatment strategies (18). Using this model, the incremental cost of a new therapy is determined based on the lifetime medical cost estimates both with and without the new therapy. In this study, the cost effectiveness ratios were determined based on the difference in life expectancy and incremental cost estimates for statin therapy versus ‘usual care’ in all drug therapy candidates identified. Because hypertension was coded as a dichotomous variable during data abstraction, the missing systolic and diastolic blood pressures were imputed in the estimation process for all subjects using simple linear regression developed from the 1993 Canadian Heart Health Survey. Predictor variables used in the regression analysis for this imputation were age, sex, hypertension, body mass index, smoking and a previous history of cerebrovascular disease. In all estimates of life expectancy and cost effectiveness, model simulations conservatively assumed that while statin therapy would be

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TABLE 1 Drug therapy candidates* by risk category

TABLE 2 Baseline coronary artery disease risk factors for drug therapy candidates*

Number of nonlipid risk factors†

n

Drug therapy candidates

Percentage

Low

≤1

763

33

4.3

Moderate

2

470

95

20.2

High

3

70

37

52.9

Risk level

Very high Total

≥4 or CAD

10

7

70.0



1313‡

172

13.1

n†

Risk factor

CAD Coronary artery disease. *Drug therapy candidates were patients not taking lipid lowering drugs but meeting the criteria for drug therapy outlined in the 1998 Canadian cholesterol lowering guidelines; patients must exceed the recommended low density lipoprotein cholesterol target level by 1 mmol/L or the target ratio of total cholesterol to high density lipoprotein cholesterol by greater than 1 for their CAD risk level. †Risk factors were age (men 45 years or older, women 55 years or older), diabetes, smoking, premature heart disease in a first-degree relative (ie, CAD occurring at less than 55 years in men or less than 65 years in women), hypertension (systolic blood pressure of 140 mmHg or greater, or diastolic blood pressure of 90 mmHg or greater) or taking antihypertensive medication. ‡Number excludes patients already on lipid lowering therapy

lifelong, patients would not derive any benefit from the therapy after age 75 because the effect of statin therapy in the elderly is not well understood. All results generated by the model were discounted at a rate of 3%, as recommended by the Panel on Cost Effectiveness in Health and Medicine (24). All cost estimates in the results section are presented in 1996 Canadian dollars (25).

RESULTS Sample demographics A total of 1424 Regular Force Canadian military personnel (n=1348, 76 women) were included in the investigation. This is approximately one-quarter of all Canadian military Regular Force personnel over the age of 45 in 1998. Eighty-four per cent of the study sample had a complete and recent (less than five years) fasting lipid profile. Missing nonlipid risk factor information was limited to data on family history of premature CAD in military personnel who were adopted (n=30). The prevalence of nonlipid risk factors was as follows: smokers, n=417; diabetics, n=34; hypertensives or people on antihypertensive medication, n=148; premature CAD in a first-degree relative, n=161; and history of CAD, n=26.

Percentage

Smoking

102

62.2

Hypertension

37

21.5

Diabetes

12

7.0

Coronary artery disease

2

1.2

Family history

39

22.7

*See definition of drug therapy candidates in Table 1 legend; †The subject count does not add up to 172 because subjects are listed multiple times

Classification A total of 111 military personnel in the study were taking cholesterol lowering medication. Of the 1313 study participants not receiving cholesterol lowering medication, 35% exceeded one or more of the target cholesterol values identified by the revised 1998 Canadian cholesterol interim guidelines for their level of CAD risk. The number of personnel not on lipid lowering medication but meeting the criteria for drug therapy is presented, by risk category, in Table 1. As shown, 172 (13.1%) of the study population were identified as drug therapy candidates among those not currently on lipid lowering medication. Furthermore, the proportion of personnel who met the criteria for drug therapy increased by level of risk. Specifically, 70.0%, 52.9% and 20.2% of the personnel not on lipid lowering medication at very high, high and moderate risk levels, respectively, were identified as candidates for drug therapy. The baseline CAD risk factors for the 172 drug therapy candidates are summarized in Table 2. Estimates for years of life saved (YOLS) and incremental cost effectiveness of statin therapy were generated using the life expectancy model for these drug therapy candidates. These results are presented in Table 3 in both undiscounted and discounted form. Over one-third of the personnel included in this study exceeded target cholesterol levels for one or more of the lipid parameters. While drug therapy was not warranted in all personnel with elevated cholesterol identified in this study, the numbers presented in Table 1 show that a number of people in the Canadian military could benefit from cholesterol lowering drug therapy, particularly those at higher risk levels of CAD. Of the 80 study participants at high or very high risk of CAD, 44 (55%) had cholesterol levels that would qualify them for cholesterol lowering drug therapy.

TABLE 3 Forecasted health benefits and incremental cost effectiveness of lifetime statin therapy

CAD Risk level

n

Total YOLS (undiscounted)

Mean YOLS (undiscounted)

Mean incremental C/E (undiscounted)

Total YOLS (discounted)*

Mean YOLS (discounted)*

Mean incremental C/E (discounted)* $11,800.00

Low

33

90.18

2.73

$9,500.00

42.99

1.30

Moderate

95

273.76

2.88

$7,700.00

139.46

1.47

$9,200.00

High

37

111.86

3.02

$7,400.00

59.56

1.61

$8,400.00

7

21.15

3.02

$7,400.00

12.09

1.73

$7,700.00

172

496.95

2.89

$8,000.00

254.09

1.48

$9,300.00

Very high Total

C/E Cost effectiveness in 1996 Canadian dollars per year of life saved; CAD Coronary artery disease; YOLS Years of life saved. *Discount rate 3%

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Economic analysis Based on estimates derived by the life expectancy model, the mean incremental increase in life expectancy with lifetime statin therapy over ‘usual care’ was 2.89 years (1.48 years discounted at 3%), with average YOLS between 2.73 and 3.02 years based on CAD risk level. Statin therapy becomes more cost effective for higher risk levels of CAD (Table 3). For cases with low CAD risk level, the cost per life-year saved discounted at 3% was $11,800, while for very high CAD risk levels the ratio was $7700.

DISCUSSION Based on the results obtained in the present investigation, the prevalence of hypercholesterolemia in the Canadian military is comparable with that of the Canadian population (26). The increased physical fitness and the greater emphasis placed on good health in the military, in addition to the close medical monitoring of this population, does not appear to be protecting military personnel from a disease that killed just over 79,000 Canadians in 1995 (1). Because of the potentially negative consequences of untreated, asymptomatic heart disease on military operations, appropriate screening and management of high cholesterol in this population are paramount. Compared with the survey results discussed previously (11), cholesterol is more often screened in the Canadian military than in other primary care settings. More than eight of every 10 people over the age of 45 included in this study had a complete lipid profile done in the previous five years. These are unlike the results obtained by Fodor (11) in which TC had been assessed in only just over half of men over 40. The results presented here suggest, however, that improvements are warranted with respect to the management of elevated cholesterol in the Canadian military. A number of personnel in the study who were not currently on lipid lowering medication were identified as drug therapy candidates based on the revised 1998 Canadian cholesterol interim guidelines (16). According to the estimates of the validated cardiovascular disease life expectancy model, better identification and management of patients with elevated cholesterol in the military has the potential to substantially extend the lives of these people at a cost that falls well within the range of currently accepted medical interventions (27). Despite the overwhelming evidence in the medical literature regarding the efficacy of statin therapy in reducing the risk of CAD in patients with elevated cholesterol, the results of this investigation suggest that patients who would benefit from this therapy are sometimes not receiving it. Particularly disturbing in the results presented here is that there is a higher proportion of drug therapy candidates among personnel at higher levels of risk. Patients who stand to benefit most from statin therapy have a greater chance of not receiving it. This is likely the result of several factors. First, the ‘clustering’ effect of risk factors for CAD has been well documented (28,29). People who already have multiple risk factors for CAD are more likely to have elevated cholesterol. Second, because the revised 1998 Canadian cholesterol interim guidelines (16) take into account the multifactorial nature of heart disease, lower target cholesterol levels are recommended in people with multiple risk factors. As a result, only moderately elevated cholesterol levels in high risk patients qualify them for drug therapy. Finally, these results may be a reflection of inefficient strategies in the military to target and treat elevated cholesterol in personnel at high risk for CAD, perhaps due to 794

factors such as frequent postings and deployments. Difficulty in clinical practice guideline implementation is not unique to the Canadian military. Strategies to implement such guidelines in individual American military facilities have also been reported to be rarely successful in the long term (30). In addition to the survey mentioned earlier and the results presented here, limited use of lipid lowering medication among high risk patients has also been reported elsewhere (31). In a recent survey conducted in England, only 3% of patients with elevated TC (5 mmol/L or more) and a 10-year CAD risk of 30% or greater were receiving lipid lowering drugs for primary prevention (31). Despite some reported improvements in the proportion of patients with high cholesterol being prescribed lipid lowering drugs (32), actual overall use remains low and cholesterol levels remain elevated. A comparison of the results obtained in two European surveys, conducted in 1995 to 1996 and again in 1999 to 2000, revealed that while the proportion of patients with elevated cholesterol had decreased and that lipid lowering drug use had increased, elevated TC continued to be a health concern (32). Over 55% of the survey population in the second survey had elevated TC (5 mmol/L or more) (32). There are numerous potential obstacles that have hindered the acceptance and integration of results of randomized controlled trials on statin therapy in the clinical setting. The recent explosion of literature available to primary care physicians is making it increasingly difficult to identify high quality studies and to assimilate incongruent findings. Poor dissemination of results to primary care physicians by leading health care authorities could also be a factor slowing the integration of the findings into routine clinical care. Finally, the willingness of primary care physicians to place too great an emphasis on lifestyle modifications as the primary (and often the only) risk management strategy for CAD is still likely hindering appropriate cholesterol management in the clinical setting. To date, studies of dietary and other lifestyle modification strategies to reduce lipid and nonlipid risk factors for CAD on free-living subjects have failed to consistently show any long term health benefits in terms of significant decreased mortality or CAD morbidity. Even in populations such as the military, where higher levels of fitness and exercise would be expected to have a positive effect on cholesterol levels and the risk of developing CAD, there is a high prevalence of hypercholesterolemia, as shown by the results of the present investigation. Several caveats to the results of the present investigation deserve mention. First, recent and complete fasting lipid profiles were not available for all personnel included this study. The identification of drug therapy candidates, however, was based solely on information available in the medical charts. Any missing risk factor data or cholesterol values were assumed not to contribute to the overall risk profile. The ultimate effect of this decision was to potentially underestimate the prevalence of hyperlipidemia in the study population. The second caveat relates to the modelling undertaken as part of the economic evaluation component of this investigation. Because of the absence of any clinical data on the long term efficacy of statin therapy in reducing the risk of heart disease, economic modelling was used in the present investigation to determine the potential health benefits and cost effectiveness of this CAD risk management strategy. The estimates derived in this investigation were based on model simulations and were not directly observed. Also, there was a loss in the accuracy of the estimates generated by the model because Can J Cardiol Vol 19 No 7 June 2003

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imputation of blood pressure values was required. The deviation of the imputed blood pressure values from the true values is not known. However, because of the lesser role of blood pressure in determining overall 10-year CAD risk as compared with other CAD risk factors using the Framingham method (23), the overall effect of imputation on the model estimates is likely to be small. Furthermore, the simple linear regressions used to generate the blood pressure values were based on six predictor variables and generated from a large Canadian database. When long term efficacy results of statin therapy become available, the results derived by the model in this investigation may be shown to over- or underestimate the true cost effectiveness and long term health benefits of statin therapy in this population. However, models should be seen as representations of our current knowledge, not necessarily as predictors of future knowledge. The results of the present investigation were derived from a life expectancy model that has been validated against the results of nine clinical trials (18). As mentioned previously, since the completion of this investigation, an update to the 1998 Canadian cholesterol interim guidelines has been published (23). While the format of the guidelines has remained similar in structure, the changes to the recommendations, such as the classification of patients with diabetes mellitus as very high risk and the use of target values as drug initiation values, would likely increase the number of patients qualifying for drug therapy in the clinical setting. The publication of the more recent guidelines further emphasizes the importance of appropriate cholesterol screening and management. One promising next step in research on

the cost effectiveness and health benefits of statin treatment would be further study based on the newer, more rigorous Canadian cholesterol guidelines. An advantage of such further study would be the opportunity to calculate the effects of the newer guidelines on cost efficacy. Future efforts in cholesterol management should be directed at identifying patients who stand to benefit most from cholesterol-reducing drug therapy. Once identified, these patients need to be followed up and monitored appropriately to ensure that the maximum benefit of therapy is achieved. This will include both appropriate titration of the medication and ensuring maximum patient compliance with the therapy. Interventions to improve adherence to cholesterol guidelines have recently been proposed in the United States in the executive summary of the Third Report of the National Cholesterol Education Program (NCEP) (33). The proposed interventions include implementation of lipid clinics and case management by nurses (33). Specifically, lipid clinics have been shown to be effective with patients who have dyslipidemia and can help them achieve their LDL-c goals (34). To this end, the Canadian Forces has initiated pharmacist-coordinated lipid clinics on some of the larger bases in Canada to improve the attainment of cholesterol goals and to ensure appropriate follow-up. Given the cost effectiveness and potential health benefits of statin therapy as a preventive health strategy to reduce the risk of CAD, financial resources invested in improving the screening and monitoring of patients with high cholesterol would be money well spent. Preventive medicine is both a clinical and financial imperative in an era of spiraling health care costs and limited health care resources.

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