BMJ 1996;312:1443-1448 (8 June)

Papers

Cost effectiveness of lowering cholesterol concentration with statins in patients with and without pre-existing coronary heart disease: life table method applied to health authority population

P D P Pharoah, W Hollingworth, health economist a

a Health Services Research Group, Department of Community Medicine, Institute of Public Health, University of Cambridge, Cambridge CB2 2SR

Cambridge and Huntingdon Health Commission, Fulbourn Hospital, Cambridge CB1 5EF PDP Pharoah, senior registrar in public health. Correspondence to: Dr PDP Pharoah, Department of Community Medicine, Institute of Public Health, Cambridge CB2 2SR.

Abstract

Objectives: To estimate the cost effectiveness of statins in lowering serum cholesterol concentration in people at varying risk of fatal cardiovascular disease and to explore the implications of changing the criteria for intervention on cost and cost effectiveness for a purchasing authority.
Design: A life table method was used to model the effect of treatment with a statin on survival over 10 years in men and women aged 45-64. The costs of intervention were estimated from the direct costs of treatment, offset by savings associated with a reduction in coronary angiographies, non-fatal myocardial infarctions, and revascularisation procedures. The robustness of the model to various assumptions was tested in a sensitivity analysis.
Setting: Population of a typical district health authority.
Main outcome measure: Cost per life year saved.
Results: The average cost effectiveness of treating men aged 45-64 with no history of coronary heart disease and a cholesterol concentration >6.5 mmol/l for 10 years with a statin was £136 000 per life year saved. The average cost effectiveness for patients with pre-existing coronary heart disease and a cholesterol concentration >5.4 mmol/l was £32 000. These averages hide enormous differences in cost effectiveness between groups at different risk, ranging from £6000 per life year in men aged 55-64 who have had a myocardial infarction and whose cholesterol concentration is above 7.2 mmol/l to £361 000 per life year saved in women aged 45-54 with angina and a cholesterol concentration of 5.5-6.0 mmol/l.
Conclusions: Lowering serum cholesterol concentration in patients with and without pre-existing coronary heart disease is effective and safe, but treatment for all those in whom treatment is likely to be effective is not sustainable within current NHS resources. Data on cost effectiveness data should be taken into account when assessing who should be eligible for treatment.

Key messages

  • Treatment of all who would benefit from intervention would be prohibitively expensive for the NHS

  • Cost effectiveness of lowering cholesterol con- centration varies greatly according to patient risk factors, treatment being most efficient in those at highest risk

  • The marginal cost effectiveness of treatment increases greatly as lower risk groups are included in this preventive regimen

Introduction

The results of the Scandinavian simvastatin survival study provide robust evidence for the effectiveness of lowering cholesterol concentration with simvastatin in patients aged 35-70 years who have a history of coronary heart disease and a serum cholesterol concentration >5.4 mmol/l.1 More recently, the west of Scotland coronary prevention study has provided convincing evidence for the benefit and safety of pravastatin in middle aged men without coronary heart disease and a moderately raised cholesterol concentration (initial value >6.4 mmol/l).2

Given this evidence for the effectiveness of statins, can the NHS afford to treat all who might benefit? A typical health commission with a population of 500 000 will have around 50 000 men aged 45 to 64, of whom some 20 000 will have a cholesterol concentration over 6.4 mmol/l and therefore would probably benefit from treatment. The current cost of statins at typical daily doses is around £540 a year,3 and to treat all who might benefit would cost £10.8m per annum. In addition, up to 2000 adults in this age group with cholesterol concentrations between 5.5 and 6.4 mmol/l and pre-existing coronary heart disease would also benefit from treatment.

Cost effectiveness studies of lowering cholesterol with statins have used estimates of the likely changes in serum lipid concentrations to predict the benefits of intervention on morbidity and mortality.4 5 6 7 Various estimates of the cost effectiveness of secondary prevention based on the results of the Scandinavian trial have been reported, suggesting an average cost of £85 000 to £136 000 per life saved8 9 or £23 110 to £32 440 per life year saved.10

The Scandinavian trialists reported that the relative risk reduction with treatment is the same whatever the initial cholesterol concentration.11 Because serum cholesterol concentration is an independent risk factor for fatal coronary events,12 13 14 15 16 17 18 19 the absolute risk reduction will depend on the patient's cholesterol value before treatment. Also, the relative risk reduction is likely to be the same for patients in different absolute risk groups because of other independent risk factors such as age, sex, and the nature of the patient's pre-existing coronary heart disease. This assumption is supported by the fact that the relative risk reductions reported in the Scottish trial were similar to those in the Scandinavian trial, although the study populations were dissimilar. The various combinations of risk factors will therefore result in widely differing risks of fatal cardiovascular disease, and so the cost effectiveness of lowering cholesterol concentration will also vary widely.

We estimated the cost effectiveness of statins in lowering serum cholesterol concentration in people at varying risk of fatal cardiovascular disease on the basis of published estimates of the benefits of intervention. We also explored the cost and cost effectiveness implications for a typical purchasing authority of changing the criteria at which treatment of hypercholesterolaemia might be recommended.

Methods

The benefits of lowering cholesterol concentration have been assumed to be a reduction in the numbers of deaths from cardiovascular disease and in the numbers of non-fatal acute coronary events, coronary angiographies, and revascularisation procedures.

We used a life table method to estimate the life years gained by lowering serum cholesterol concentration in the population of this health commission. The method is illustrated in table 1, which is the life table for an imaginary cohort of 1000 men with pre-existing coronary heart disease aged 45-54 (average age at start 50 years). The method for deriving the numbers in each column in table 1 are as follows: 


Table 1--Survival of imaginary cohort of 1000 men aged 45-54 with pre-existing coronary heart disease according to treatment for raised cholesterol
concentration
---------------------------------------------------------------------------------------------------------------------------------------------------
                                         Mortality per 1000 population
---------------------------------------------------------------------------------------------------------------------------------------------------
                                               Patients with pre-existing coronary heart      No of deaths          No surviving at
                            General population                  disease                         expected              end of year
---------------------------------------------------------------------------------------------------------------------------------------------------
                                                No treatment            With treatment
---------------------------------------------------------------------------------------------------------------------------------------------------
                   Average         Coronary  Coronary                Coronary
                     age     All     heart     heart    All            heart        All       No        With        No        With
             Year  (years)  cause   disease   disease  cause          disease      cause  treatment  treatment  treatment  treatment
---------------------------------------------------------------------------------------------------------------------------------------------------
Column No*:     1      2     3        4         5       6               7           8          9         10          11         12
---------------------------------------------------------------------------------------------------------------------------------------------------
                1     50     3.45     0.78      2.41    5.07            1.40        4.06       5         4          995        996
                2     51     3.82     0.88      2.72    5.66            1.58        4.51       6         4          989        991
                3     52     4.24     1.00      3.07    6.31            1.78        5.02       6         5          983        986
                4     53     4.69     1.13      3.47    7.04            2.01        5.58       7         6          976        981
                5     54     5.20     1.28      3.92    7.85            2.28        6.20       8         6          968        975
                6     55     5.77     1.44      4.43    8.76            2.57        6.89       8         7          960        968
                7     56     6.39     1.63      5.01    9.77            2.90        7.67       9         7          951        961
                8     57     7.08     1.84      5.66   10.90            3.28        8.52      10         8          940        953
                9     58     7.85     2.08      6.39   12.16            3.71        9.48      11         9          929        944
               10     59     8.70     2.35      7.22   13.57            4.19       10.54      13        10          916        934
---------------------------------------------------------------------------------------------------------------------------------------------------
             Total                                                                            84        66         9650       9721
---------------------------------------------------------------------------------------------------------------------------------------------------
*See Methods for explanation.

Columns 3 and 4 are the age specific death rates from all causes and from cardiovascular disease in one year age bands for the general population, estimated from a log-linear regression of published death rates in five year age bands.20 Cardiovascular disease includes codes 401-405, 410-414, 430-438 of the ninth revision of the International Classification of Diseases (ICD-9).

Column 5 shows the death rates from cardiovascular disease for men with pre-existing coronary heart disease, estimated with the formula r/ (pr + (1 - p), where r is the mortality ratio of those with pre-existing coronary heart disease to those without and p is the proportion of the population with pre-existing coronary heart disease. We assumed that r = 3.4.14

Column 6 shows the death rate from all causes for those with pre-existing coronary heart disease, or column 3 minus column 4 plus column 5, given that the death rate from non-cardiovascular causes in those with pre-existing coronary heart disease is the same as in the general population.

Column 7 shows the mortality from cardiovascular disease in men with pre-existing coronary heart disease receiving treatment with a statin; the rate is 0.58 x column 5, given that that treatment with statin reduces cardiovascular mortality by 42%.1

Column 8 shows the death rate from all causes in men with pre-existing coronary heart disease, or column 3 minus column 4 plus column 7, given that the reduction in all cause mortality after treatment is entirely due to a reduction in deaths from cardiovascular disease.

Column 9 shows the expected number of deaths without statin treatment, or the number surviving at start of year x column 6.

Column 10 shows the expected number of deaths with treatment, or the number surviving at start of year x column 8.

Column 11 shows the number surviving at end of year without treatment, or number surviving at start of year x (1 -- column 6).

Column 12 shows the number surviving at end of year with treatment, or the number surviving at start of year x (1 - column 8).

Total shows the life years survived by the cohort, or the sum of the number surviving at the end of each year + 0.5 x total number of deaths.

A similar life table can be constructed for men and women in the two age bands without previous coronary heart disease, with angina, and with previous myocardial infarction, and within these categories for subjects with cholesterol values in different fifths. The assumptions about the relative risk of fatal cardiovascular disease for these different categories of patient are given in table 2. 


Table 2--Values of uniformly distributed parameters used in model
----------------------------------------------------------------------------------------------------------------------------
                                                               Mid-
                                                               point
Parameter                                                     estimate   Minimum Maximum  References
----------------------------------------------------------------------------------------------------------------------------
Prevalence of angina:
  Men aged 45-54                                               0.02       0.01     0.03   White et al21
  Women aged 45-54                                             0.02       0.01     0.03
  Men aged 55-64                                               0.05       0.04     0.06
  Women aged 55-64                                             0.05       0.04     0.06
Prevalence of previous myocardial
  infarction:
  Men aged 45-54                                               0.0125     0.005    0.02   White et al21
  Women aged 45-54                                             0.0125     0.005    0.02
  Men aged 55-64                                               0.05       0.04     0.06
  Women aged 55-64                                             0.02       0.01     0.03
Proportion of non-fatal myocardial                             0.28       0.18     0.38   Scandinavian Simvastatin
  infarctions prevented to life years                                                       Survival Study Group,1
  saved                                                                                     Shepherd et al2
Proportion of coronary angiographies                           0.4        0.3      0.5    Shepherd et al2
  prevented to life years saved
Proportion of revascularisation                                0.38       0.28     0.48   Scandinavian Simvastatin
  procedures prevented to life years                                                        Survival Study Group,1
  saved                                                                                     Shepherd et al2
Discount rate                                                  0.05       0.0      0.1
Cost of non-fatal myocardial infarction (£)    4300       3800     4800   Sawitz et al,22 local data
Cost of revascularisation procedure (£)        5000       4500     5500   Sculpher et al,23 local data

Estimating the numbers of non-fatal myocardial infarctions, coronary angiographies, and revascularisation procedures prevented in each risk group is difficult because the age-sex specific rates of these events and their relative risks for different patient categories are not known. However, the results of the Scandinavian and Scottish trials can be used to estimate the numbers of events prevented. There were 0.28 non-fatal myocardial infarctions and 0.38 revascularisation procedures prevented for every life year saved in the Scandinavian trial,10 with broadly similar results in the Scottish trial, which also reported that for every life year saved 0.4 coronary angiographies were avoided. The cost of a non-fatal myocardial infarction and revascularisation procedure are about £430022 and £5000.23 These published figures are similar to local contract prices for these procedures.

The costs of the treatment have been limited to drug costs. Given that in the Scandinavian trial two thirds of the patients required 20 mg daily and one third 40 mg daily, the average cost at current prices is £540 a year.3 The Department of Health traditionally discounts future costs and savings at 5-6%,24 though the validity of this procedure has recently been questioned.25 In the model we used a discount rate of 5% and a range of values from 0-10% in the sensitivity analysis.

The results of the model depend on assumptions made about the values of various input parameters. We carried out a sensitivity analysis with a range of potential values for each input parameter. The model was recalculated 1000 times using the Latin hypercube sampling technique to ensure that each input parameter was sampled across the complete range of its putative distribution.26 The values used for each input parameter and the sampling distribution used are given in table 3. 


Table 3--Mean (SD) values of normally distributed parameters used in model
--------------------------------------------------------------------------------------------------
                                                          Mean (SD)   Reference
--------------------------------------------------------------------------------------------------
Relative risk of fatal coronary heart disease:
 Patient with angina                                      2.4 (0.4)   Shaper et al14
 Patient with previous myocardial infarction              6.0 (0.8)   Shaper et al14
 Patient in cholesterol fifth:
    1                                                     1.0 (0.0)   Martin et al13
    2                                                     1.5 (0.15)
    3                                                     1.8 (0.2)
    4                                                     2.4 (0.2)
    5                                                     3.8 (0.3)
Patient with pre-existing disease treated with statin     0.58(0.06)  Scandinavian Simvastatin
                                                                        Survival Study Group1
Patient without pre-existing disease treated with statin  0.67(0.08)  Shepherd et al2

Results

In Cambridge and Huntingdon the values for the cholesterol fifths are roughly <5.5 mmol/l, 5.5-6.0 mmol/l, 6.1-6.5 mmol/l, 6.6-7.2 mmol/l, and >7.2 mmol/l. Thus those in the lowest fifth would have cholesterol concentrations below those in the Scandinavian trial, and only those in the top two fifths would qualify for treatment in the Scottish trial. Of 95 800 resident men and women aged 45-64 years, 3795 had pre-existing coronary heart disease and a cholesterol concentration >5.4 mmol/l and some 18 100 men without coronary heart disease had a cholesterol concentration >6.4 mmol/l.

Table 4 shows the benefits of treatment for 10 years for patients with pre-existing coronary heart disease, stratified by age, sex, type of coronary heart disease, and cholesterol fifth. Table 5 shows the costs of treatment for the same groups. Table 6 shows the benefits and costs of treating men without a history of coronary heart disease. The values given in these tables are the results when middle values of the input parameters were entered in the model. In those with pre-existing coronary heart disease, 35 619 treatment years would save 442 life years and prevent 137 deaths, 128 non-fatal myocardial infarctions, 164 revascularisation procedures, and 177 coronary angiographies at a net cost of £14.1m--an average cost of £103 000 per life and £32 000 per life year saved. The cohort of men without coronary heart disease would undergo 174 364 treatment years to save 512 life years and prevent 90 deaths, 153 non-fatal myocardial infarctions, 207 revascularisation procedures, and 218 coronary angiographies at a net cost of £74.6m--an average cost of £0.8m per life saved and £147 000 per life year saved. 


Table 4--Benefits of treating hypercholesterolaemia in patients with pre-existing coronary heart disease
-----------------------------------------------------------------------------------------------------------
                                              Cholesterol fifth (value (mmol/l))
-----------------------------------------------------------------------------------------------------------
                             2 (5.5-6.0)    3 (6.1-6.5)     4 (6.6-7.2)    5 (>/=7.3)     2-5 (>/=5.5)
-----------------------------------------------------------------------------------------------------------
No treated (n = 3795)
Men aged 45-54:
 Angina                         115             115             115            115            461
 Myocardial infarction           72              72              72             72            288
Men aged 55-64:
 Angina                         194             194              19            194            774
 Myocardial infarction          194             194             194            194            774
Women aged 45-54:
 Angina                         113             113             113            113            453
 Myocardial infarction           71              71              71             71            283
Women aged 55-64:
 Angina                         113             113             113            113            453
 Myocardial infarction           77              77              77             77            309
No of life years of treatment (n = 35619)
Men aged 45-54:
 Angina                        1122            1121            1118           1112           4472
 Myocardial infarction          695             693             689            680           2757
Men aged 55-64:
 Angina                        1807            1802            1790           1763           7162
 Myocardial infarction         1764            1750            1721           1658           6893
Women aged 45-54:
 Angina                        1112            1111            1110           1107           4440
 Myocardial infarction          692             691             689            685           2758
Women aged 55-64:
 Angina                        1076            1074            1070           1060           4281
 Myocardial infarction          724             721             714            699           2858
No of expected deaths from    coronary h   eart disease    (n = 627)*
Men aged 45-54:
 Angina                           7               8               9             11             36
 Myocardial infarction            7               8               9             12             36
Men aged 55-64:
 Angina                           5               5               6              7             22
 Myocardial infarction           46              51              60             79            237
Women aged 45-54:
 Angina                          31              33              37             47            149
 Myocardial infarction            4               4               5              7             20
Women aged 55-64:
 Angina                          13              14              16             19             63
 Myocardial infarction           13              14              16             22             64
No of discounted lives sav   ed (n = 137   )+
Men aged 45-54:
 Angina                           1               1               2              3              6
 Myocardial infarction            2               2               2              4             10
Men aged 55-64:
 Angina                           4               5               7              1             27
 Myocardial infarction           10              12              16             22             60
Women aged 45-54:
 Angina                           0               1               1              1              3
 Myocardial infarction            1               1               1              2              4
Women aged 55-64:
 Angina                           2               2               3              4             11
 Myocardial infarction            3               3               4              6             16
No of discounted life year   s saved (n    = 442)+
Men aged 45-54:
 Angina                           3               4               5              8             20
 Myocardial infarction            5               6               8             12             30
Men aged 55-64:
 Angina                          14              17              22             34             87
 Myocardial infarction           34              40              52             78            203
Women aged 45-54:
 Angina                           1               2               2              3              8
 Myocardial infarction            2               2               3              5             13
Women aged 55-64:
 Angina                           5               6               8             13             32
 Myocardial infarction            8               9              12             19             49
-----------------------------------------------------------------------------------------------------------
*On the basis of current death rates.20
+For economic analysis, lives saved in the future are worth less than those saved today. Discount rate used
is 5%.


Table 5--Costs and cost effectiveness of treating hypercholseterolaemia in patients with
pre-existing coronary heart disease
----------------------------------------------------------------------------------------
                                         Cholesterol fifth (value (mmol/l))
----------------------------------------------------------------------------------------
                         2 (5.5-6.0)  3 (6.1-6.5)  4 (6.6-7.2)  5 (>/=7.3) 2-5 (>/=5.5)
----------------------------------------------------------------------------------------
Discounted net costs (£000s); total £14 141 000
Men aged 45-54:
 Angina                      483          480          475        463         1900
 Myocardial infarction       288          284          276        258         1106
Men aged 55-64:
 Angina                      747          735          712        659         2853
 Myocardial infarction       661          633          580        464         2337
Women aged 45-54:
 Angina                      483          482          479        474         1918
 Myocardial infarction       296          295          291        283         1165
Women aged 55-64:
 Angina                      456          451          443        423         1772
 Myocardial infarction       291          285          271        242         1089
Net cost per life saved (£000s); average £103 000
Men aged 45-54:
 Angina                      465          387          289        180          293
 Myocardial infarction       182          151          112         68          114
Men aged 55-64:
 Angina                      167          138          102         62          105
 Myocardial infarction        63           52           37         21           39
Women aged 45-54:
 Angina                     1046          871          652        410          660
 Myocardial infarction       415          345          258        161          261
Women aged 55-64:
 Angina                      268          222          165        102          168
 Myocardial infarction       112           92           68         41           70
Net cost per life year saved (£000s); average £32 000
Men aged 45-54:
 Angina                      154          128           95         59           97
 Myocardial infarction        60           49           36         22           37
Men aged 55-64:
 Angina                       53           44           32         19           33
 Myocardial infarction        20           16           11          6           11
Women aged 45-54:
 Angina                      361          300          225        141          227
 Myocardial infarction       143          118           88         55           89
Women aged 55-64:
 Angina                       90           74           55         34           56
 Myocardial infarction        37           30           22         13           22


Table 6--Benefits, cost, and cost effectiveness of treating hypercholesterolaemia in
patients without pre-existing coronary heart disease
--------------------------------------------------------------------------------------
                         Cholesterol fifth (value (mmol/l))
--------------------------------------------------------------------------------------
                4 (6.6-7.2)  5 (>/=7.3) 4 and 5 (>/=6.6)
--------------------------------------------------------------------------------------
No treated (n = 18 110)
Men aged 45-54      5 570     5 570         11 141
Men aged 55-64      3 485     3 485          6 969
Life year treatment (n = 174 364)
Men aged 45-54     54 484    54 352        108 836
Men aged 55-64     32 874    32 654         65 528
No of expected deaths from coronary heart disease (n = 1748)
Men aged 45-54        314       361            675
Men aged 55-64        499       573          1 073
No of discounted lives saved (n = 96)
Men aged 45-54         17        20             36
Men aged 55-64         27        32             59
No of discounted life years saved (n = 546)
Men aged 45-54         79       125            205
Men aged 55-64        133       208            341
Discounted net cost (£000s; total £74 611)
Men aged 45-54     23 643    23 439         47 082
Men aged 55-64     13 938    13 591         27 529
Net cost per life saved (£000s; average £778 000)
Men aged 45-54      1 424     1 178          1 290
Men aged 55-64        515       420            464
Net cost per life year saved (£000s; average £136 000)
Men aged 45-54        297       187            230
Men aged 55-64        105        65             80
----------------------------------------------------------------------------------------
*On the basis of current death rates.[20]

These averages hide large variations in cost effectiveness for different groups of patients at different degrees of risk. Treatment of hypercholesterolaemia is most cost effective in men aged 55-64 who have previously had a myocardial infarction and whose cholesterol concentration is above 7.2 mmol/l. Treatment costs £6000 per life year saved compared with £361 000 per life year saved in women aged 45-54 with angina and a cholesterol concentration of 5.5-6.0 mmol/l.

Table 7 shows the results of the sensitivity analysis for several key results of the model. For patients with pre-existing coronary heart disease the estimated average cost effectiveness ranged from £15 000 to £70 000. Rank correlation of the inputs and outputs in the sensitivity analysis showed that the effectiveness of treatment was the parameter having the greatest influence on the result (r=0.76). Correlation coefficients for all other input variables were <0.5. For men without coronary heart disease, average cost effectiveness ranged from £70 000 to £424 000, with the effectiveness of treatment again being the parameter having the greatest influence (r=0.95). The sensitivity analysis also shows that even if the "best case" scenario for the lowest risk group is compared with the "worst case" scenario for the highest risk group, treatment is still seven times more costly per life year saved in the lowest risk group. 


Table 7--Results of sensitivity analysis for key output variables
--------------------------------------------------------------------------------------------------------------------------
                                                                                                             Interquartile
Output variable                                                                   Median  Minimum   Maximum      range
--------------------------------------------------------------------------------------------------------------------------
Patients with pre-existing coronary heart disease
No treated                                                                         3 797   3 008      4 552    3 621-3 792
No of lives saved                                                                    136      70        218     120-153
No of life years saved                                                               438     195        835     366-517
Patients without pre-existing coronary heart disease
No treated                                                                        18 111  17 837     18 931  18 029-18 152
No of lives saved                                                                     95      66        221      79-109
No of life years saved                                                               541     346      1 325     436-636
Net cost per life year saved (£000s)
All patients aged 45-64 with coronary heart disease and cholesterol >/=5.5 mmol/l     32      15         70      27-39
Men aged 45-64 without coronary heart disease but with cholesterol >/=6.6 mmol/l     137      70        424     115-170
Men aged 55-64 with previous myocardial infarction and cholesterol >/=7.3 mmol/l       6       0.7       23       4-8
Women aged 45-54 with angina and cholesterol 5.5-6.0 mmol/l                          360     154        914     297-448

In deciding which patients should be treated, while taking into account cost effectiveness data, the effect of changing criteria for intervention on the total cost of treatment, average cost effectiveness, and marginal cost effectiveness should be considered. The following are five groups of patients at decreasing risk of coronary heart disease, all of whom fulfil the criteria for intervention of the Scandinavian or Scottish trial:

* Group 1--men aged 45-64 and women aged 55-64 with previous myocardial infarction and a cholesterol concentration >5.4 mmol/l

* Group 2--men aged 45-64 and women aged 55-64 with angina and a cholesterol concentration >5.4 mmol/l

* Group 3--men aged 55-64 with no history of coronary heart disease and cholesterol >6.5 mmol/l

* Group 4--women aged 45-54 with angina or previous myocardial infarction and a cholesterol concentration >5.4 mmol/l

* Group 5--men aged 45-54 with no history of coronary heart disease and a cholesterol concentration >6.5 mmol/l.

The cost implications for Cambridge and Huntingdon Health Commission of expanding the indications for cholesterol lowering treatment to include each successive risk group is shown in table 8. If only those patients in the highest risk group are treated, 1371 patients would require treatment at a net cost of £4.5m (over 10 years) and a benefit of 282 life years saved at £16 000 per life year. If the next highest risk group is also treated an additional 1688 patients will require treating at an additional cost of £11.1m and an additional benefit of 138 life years saved at a marginal cost of £47 000 per life year gained. The average cost effectiveness of treating both groups is £26 000 per life year saved. For treating the fifth risk group the marginal cost per life years saved is £230 000 compared with an average cost of £92 000. 


Table 8--Cost implications of expanding indication for lowering cholesterol concentration in Cambridge and Huntingdon Health Commission
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                                                                    Marginal cost                  Average cost
                 Additional      Total     Additional cost             Total cost                Additional life  Total life years   per life year                  per life year
Groups treated*  No to treat  No to treat     (£000s)   (£000s)  years saved          saved         saved (£000s)  saved (£000s)
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
1                  1 371         1 371           4 533                    4 533                      282               282                16                            16
1 and 2            1 688         3 059           6 526                   11 059                      138               420                47                            26
1-3                6 969        10 028          27 529                   38 588                      341               761                81                            51
1-4                  736        10 764           3 082                   41 670                       21               781               143                            53
1-5               11 141        21 905          47 082                   88 752                      205               967               230                            92
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
*See Results for definition of groups.

Discussion

Lowering cholesterol has been shown to be safe and effective for patients with and without pre-existing coronary heart disease, but the cost of treating all those in whom treatment is likely to be effective is not sustainable within current NHS resources. In addition, other equally effective secondary prevention interventions, such as antiplatelet treatment27 and dietary intervention,28 29 are cheaper. We have estimated the cost effectiveness of lowering cholesterol concentration in various at risk patient groups to identify groups in which intervention will be most efficient.

Although the validity of several assumptions was explored in a sensitivity analysis, no attempt was made to account for other assumptions. In particular, although the benefits of lowering cholesterol concentration were derived from large trials, our model assumes that they occur immediately treatment is started, whereas not much effect was apparent in the Scandinavian or Scottish trial for six months to two years.1 2 Taking this into account would result in the intervention becoming less cost effective. The population on which this model is based is affluent compared with the rest of the United Kingdom. In an area with higher mortality from coronary heart disease the absolute benefits would be greater and thus the intervention would become more cost effective. Other than drug costs, costs of managing hypercholesterolaemia in the population have not been included in the model. This is reasonable in patients with pre-existing coronary heart disease, since the drug will simply be added to standard treatment and will incur few additional costs associated with doctor time. In patients without coronary heart disease there would be additional costs associated with measuring cholesterol concentrations in a large healthy population group, and in those subsequently treated there will be costs from increased use of doctor time.

The model does not account for several direct and indirect benefits that might accrue from lowering cholesterol concentration. For example, treatment may reduce morbidity from angina or congestive heart failure. This would reduce direct costs through reduction in need for other treatment and a reduction in patient consultations. Measuring these benefits is, however, difficult without published information about such outcomes, and the benefits are likely to be small in comparison to the total cost of drugs. Indirect societal costs, such as preventing illness related job losses, are also relevant but are, again, difficult to account for. We also did not assess the differing utility of preventing death or morbidity in the different risk groups as this type of analysis was beyond the scope of this study.

CONCLUSIONS

We have shown that the cost effectiveness of treatment of hypercholesterolaemia with statins varies greatly between different risk groups. Statin treatment should be reserved for patients who will get the most benefit--that is, those in whom intervention is most cost effective. If data on cost effectiveness are to be used in determining who should be eligible for treatment, our results emphasise the importance of considering the marginal cost effectiveness rather than the average cost effectiveness when assessing the impact of moving from one health care strategy to another.

Funding: None.

Conflict of interest: None.

  1. Scandinavian Simvastatin Survival Study Group. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandanavian simvastatin survival study. Lancet 1994;344:1383-9. [Medline]
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(Accepted 29 February 1996)


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