Considering the cost-effectiveness of statins in family practice in Turkey from a payer perspective

doi:10.4236/health.2009.14044

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Vol.1, No.4, 274-280 (2009)

doi:10.4236/health.2009.14044

SciRes

Health

Considering the cost-effectiveness of statins in family

practice in Turkey from a payer perspective

Güvenç Koçkaya1, Albert Wertheimer2, Pınar Daylan Koçkaya3, Ahmet Esen1

1Yeditepe Universitesi PEPI, Istanbul, Turkey

2Temple University, School of Pharmacy, Philadelphia, USA

3Şişli Etfal Education and Research Hospital, Anesthesia Clinic, Istanbul, Turkey

Received 2 October 2009; revised 9 November 2009; accepted 10 November 2009.

ABSTRACT

The percentage of mortality caused by cardio-

vascular events in European Countries and

European Union Countries is respectively 49%

and 42% of all mortality causes. Our estimates

about cardiovascular mortality in Turkey depend

on TEKHARF (Hearth Disease and Risk Factors

in Turkish Adults) which depended on a 12 year

observation. It has been reported that cardio-

vascular mortality rates for Turkey in men and

women were 0.082% and 0.043% respectively. In

Turkey, Atorvastatin, Fluvastatin, Pravastatin,

Rosuvastatin and Simvastatin are the different

alternatives found in the statin market. All stat-

ins are reimbursed by insurance companies.

The aim of this study is to determine the cost-

effectiveness of statins. In conclusion, simvas-

tatin and rosuvastatin comprised the optimal

two statin alternatives.

Keywords: Hypercholesterolemia; Cardiovascular

Disease; Cost-Effectiveness Analysis; Decision

Analysis Mode

1. BACKGROUND

The percentage of mortality caused by cardiovascular

events in European Countries and European Union

Countries is 49% and 42%, respectively of all mortality

causes [1].

Our estimates about cardiovascular mortality in Tur-

key depend on TEKHARF (Hearth Disease and Risk

Factors in Turkish Adults) which was taken from a 12

year observation. In this trial, it was reported that car-

diovascular mortality rates for Turkey, in men and

women, were 0.082% and 0.043% respectively [1].

From this estimation, it can be concluded that every

year 140,000 new cardiovascular patients will be diag-

nosed.

Also in TEKHARF, it was reported that the percent-

age of total cholesterol levels above 200 mg/dL and 249

mg/dL were 25% and 5% respectively [1].

LDL decreasing and HDL increasing can decrease

cardiovascular events. Statins can decrease LDL and

increase HDL [2-8]. Some benefits in cardiovascular

event protection statin use is increasing [9,10].

In Turkey, there is Atorvastatin, Fluvastatin, Pravas-

tatin, Rosuvastatin and Simvastatin in the statin market.

And all statins are reimbursed by health insurance com-

panies [11].

The aim of this study is to consider the cost-effective-

ness of statins which are reimbursed by Social Security

Foundation from a payer perspective.

2. METHODS

A cost-effectiveness analysis was designed from the

perspective of the insurance company view. For insur-

ance company data; SSF (Social Security Foundation)

which is the biggest reimbursement foundation in Tur-

key was chosen. The assumed treatment protocol de-

pended on the one in the Republic of Turkey Health

Ministry Primary Care Diagnosis and Treatment Guide

(THMPCDTG) [12], which was published in 2003. The

initial and maintenance doses of statins were taken from

Benner [13]. Atorvastatin, Fluvastatin, Pravastatin, Ro-

suvastatin, Simvastatin initial and maintanence doses

were assumed as 10-40-80 mg/day, 40-80 mg/day, 20-40

mg/day, 10-20-40 mg/day, 20-40-80 mg/day respectively

depending on Benner [13] and assumed treatment pro-

tocol. The ratios of the effectiveness of the statins which

include LDL-C decrease, HDL-C increase and reaching

ATP II levels were taken from Benner [13]. The costs of

the drugs were taken from Republic of Turkey Drug

Pharmacy General Management Drug List; laboratory

tests and doctor visits were also taken from the Budget

Application Instruction (BAI) [14] from SSF.

As like Benner [13], the analysis employed the payer

perspective, hence only direct medical costs, and time

horizons of 1 and 3 years (a lifetime analysis was not

conducted because longterm clinical data were not yet

G. Koçkaya et al. / HEALTH 1 (2009) 274-280

275

available for all of the treatments used in the model)

[13].

In THMPCDTG, it was reported that for starting and

maintaining statin treatment it is necessary to know the

patients’ lipid levels and hepatic enzymes levels. So in

each doctor visit these laboratory tests will be repeated.

On the other hand, it is also essential to know the

creatinine phosphokinase levels only before initiating the

treatment. Also in the first 3 months visiting the doctor is

essential every 6 weeks and every 3 months in the first

year. After the first year the need to visit the doctor is

every 6 months [12]. In our assumed treatment protocol

depending on THMPCDTG, we assumed that the treat-

ment initiates with initial dosages. In the second visit

(6th week), daily dosage will be titrated to half of

maximum dosage depending on half of reach ATP II

levels and remaining patients will still take the initial

dosage. In the third visit (3rd month), dosage will be

titrated to maximum dosage depending on ATP II levels

and initial dosage and half of the maximum dosage will

be administered to the remaining patients too. Our

treatment protocol was planned as one year because in

the Benner [13] trial the effectiveness of statins was de-

scribed from the 52-weeks’ follow up and estimated as 3

years. The treatment protocol is given in Figure 1. After

52 weeks, last titrated dosages of all statins was assumed

as taken following 2 year and for each year 5% decrease

was taken account in drugs and laboratories costs. Also

practitioner visits was assumed every 6 month in fol-

lowing second and third years and visits costs was as-

sumed increasing 5% each year.

The data for patient population and effectiveness of

statins was taken from Benner [13]. In this trial, the re-

sults of two phase III, randomized clinical studies con-

ducted in Europe and America (Olsson [15] and Brown

[16]) were pooled.

A total of 515 patients (atorvastatin n=116, pravastatin

n=95, rosuvastatin n=202, simvastatin n=102) were in-

cluded in this pooled analysis. 40% of the patients were

male, the mean age was 58, the mean LDL baseline

value was 189 mg/d L and 23% of the patients were in a

high risk group depending on ATP II criteria.

2.1. Statin Effectiveness

The values of the mean effectiveness of statins are

shown in Table 1 depending on Benner [13]. In this co-

hort meta analysis 52 week effectiveness of atorvastatin,

pravastatin, rosuvastatin and simvastatin was calculated.

Because there was no information about fluvastatin and

its effectiveness in Olsson [15], Brown [16] number

from Benner’s [13] analysis dosage of fluvastatin was

considered from the same effectiveness value of provas-

tatin which doubles the potential of fluvastatin. Provas-

tatin was used 20-40 mg daily in the Brown [15] trial so

fluvastatin was assumed as 40-80 mg daily.

3. COSTS

The direct medical costs were used in this trial from the

reimbursement organization perspective. For one year of

treatment; the costs of statin usage, doctor visits and

laboratory tests were added to the calculation: 6 doctor

visits, 6 lipid tests (LDL-K and HDL-K), 6 liver function

tests (AST-ALT); and 1 creatinine phosphokinase test

were added to the calculation depending on assumed

treatment protocol shown in Figure 1. The cost of doctor

visits and laboratory tests was taken from SSF’s BAI for

the year 2009 which was published on www.bumko.gov.tr.

The costs of the drugs were taken from Drug Pharmacy

General Management Drug List of the Republic of Turkey

which was published on 01.06.2009 on www.iegm.gov.tr.

In Turkey, each statin has original and generic brands.

Atorvastatin, pravastatin, rosuvastatin and simvastatin

have 12, 1, 3, 4 generic brands respectively. Fluvastatin

does not have any generic version: there is only an

original brand. The daily treatment cost of each dosage

of each statin which was used in analysis was pooled by

using original and generics costs of daily treatments. In

this calculation, maximum package containers were

chosen for the cost of each dosage. The simvastatin 80

mg dosage form was not available in Turkey’s market so

it was calculated to use the doubled 40 mg dosage form

daily. Then, all costs were changed into US Dollar with

TL/USD rate as 1.50, and calculated in USD.

Compliance with statin therapy was assumed to be

100% in the base-case analysis as Benner [13], because

this study pertained only to patients who completed 52

weeks of follow-up, and because differences in

adherence between the statins have not been documented

[13].

In calculation the results were rounded. The cost

added to calculation is shown in Table 2 and Table 3.

3.1. Alternative Scenarios

In addition, the impacts of two alternative scenarios that

may be reflective for the actual practice were also stud-

ied. In the first scenario, it was assumed that patients

were not titrated to goal, but they completed the year

with initial statin doses. In the second scenario, the pa-

tients started treatment with the maximum dosage and

completed the year with maximum dose.

3.2. Adverse Events and Long-Term

Outcomes

Adverse events were not calculated in the model because

available evidence suggests that treatmentlimiting event

rates do not differ significantly between the statins [13].

Moreover, the average cost of adverse events would be

low, because most events resolve after discontinuation of

the drug [13].

276 G. Koçkaya et al. / HEALTH 1 (2009) 274-280

SciRes

Table 1. Statin effectiveness parameters under Benner study base case.

Statin LDL-C da %

Decrease(mean)

HDL-C da %

Increase (mean)

Reach ATP II

Levels % (mean)

Atorvastatin 10-80 mg 38 0.9 80

Fluvastatin 40-80 mg 30 4.4 60

Pravastatin 20-40 mg 30 4.4 60

Rosuvastatin 10-40 mg 46 7.3 87

Simvastatin 20-80 mg 37 6.1 73

ATP II, National Cholesterol Educaiton Program, Second Adult Treatment Panel; HDL-C, high density lipoprotein cholesterol;

LDL-C, low density lipoprotein cholesterol.

Table 2. Cost parameters (In 2009 US dollars and TL).

BAI Codes Cost

Doctor Visit 520080 6,3 $ (9.5 TL)

Lipid Tests (LDL-K, HDL-K) 902290, 901580 2,7 $ (4,10 TL)

Liver Function Tests (AST-ALT) 900200, 900580 1,4 $ (2,10 TL)

Creatinin Fosfokinaze Test 902180 0,7 $ (1,10 TL)

Table 3. Cost of daily statin treatments.

Also excluded were costs for future clinical outcomes

such as myocardial infarction, stroke, coronary artery

bypass grafting or percutaneous transluminal coronary

angioplasty, even though statin therapy has been shown

to reduce the frequency of these procedures [13].

Excluding these potential cost offsets is consistent

with the short-term time frame of the analysis and gives

a more conservative estimate of the cost-effectiveness of

statin therapy, particularly among the most effective

statins [13].

Short-term time frame of the analysis let us make an

analysis for family practitioners. Because if patients

can’t reach optimum cholesterol levels, they need to go

specialist practitioners like general medicine, cardiology,

etc.

4. RESULTS

4.1. Base Case Analysis

In the base case analysis, the mean reductions in LDL-C

for atorvastatin, fluvastatin, pravastatin, rosuvastatin,

simvastatin were 38, 30, 30, and 46 respectively. Sim-

vastatin had the lowest cost in the first year of therapy

($166), followed by pravastatin ($300), fluvastatin

($365), rosuvastatin ($437) and atorvastatin ($448).

When the drugs were compared for the incremental cost-

effectiveness, simvastatin dominated pravastatin and

fluvastatin, whereas rosuvastatin dominated atorvastatin

(Tables 4-6). The first year incremental cost of rosuvas-

tatin was $271 compared with simvastatin, or $30 per

additional 1% reduction in LDL-C, $225 per additional

1% increase in HDL-C and $1856 per additional patients

to ATP II goal.

When the drugs were compared for cost per HDL-C

increase and LDL-C decrease simvastatin had the least

costs for both criteria (27 and 4, respectively), followed

by rosuvastatin (60 and 9, respectively), pravastatin (68

and 10, respectively), fluvastatin (83 and 12, respec-

tively) and atorvastatin (497 and 12, respectively) (Table

7).

All the dosages of Simvastatin had lower acquisition

Range Mean

10 mg 90 Tablets (1 original + 10 generics) 0,52–0,62 $ (0,79-0,93 TL) 0,57 $ (0,86 TL)

40 mg 90 Tablets (1 original + 10 generics) 1,18-1,33 $ (1,77-1,99 TL) 1,21 $ (1,82 TL)

Atorvastatin

80 mg 90 Tablets (1 original + 6 generics) 1,16-1,39 $ (1,75-2,08 TL) 1,24 $ (1,87 TL)

40 mg 28 Tablets (1 original) 0,78 $ (1,17 TL) 0,78 $ (1,17 TL)

Fluvastatin 80 mg 28 Tablets (1 original) 0,85 $ (1,28 TL) 0,85 $ (1,28 TL)

20 mg 20 Tablets (1 original + 1 generic) 0,36-0,45 $ (0,54-0,68 TL) 0,41 $ (0,61 TL)

Pravastatin 40 mg 30 Tablets (1 original + 1 generic) 0,72-0,85 $ (1,09-1,28 TL) 0,79 $ (1,18 TL)

10 mg 90 Tablets (1 original + 1 generic) 0,75-0,85 $ (1,12-1,28 TL) 0,80 $ (1,20 TL)

20 mg 90 Tablets (1 original + 1 generic) 1,10-1,43 $ (1,66-2,14 TL) 1,26 $ (1,90 TL)

Rosuvastatin

40 mg 90 Tablets (1 original) 1,10 $ (1,66 TL) 1,10 (1,66 TL)

20 mg 28 Tablets (1 original + 4 generic) 0,13-0,16 $ (0,20-0,25 TL) 0,14 $ (0,21 TL)

40 mg 28 Tablets (1 original + 4 generic) 0,27-0,33 $ (0,47-0,50 TL) 0,28 $ (0,43 TL)

Simvastatin

80 mg (40 mg 28 Tablets x 2) (1 original + 4 generic) 0,54-0,66 $ (0,94-1 TL) 0,56 $ (0,86 TL)

G. Koçkaya et al. / HEALTH 1 (2009) 274-280 277

Table 4. 1st year base case cost per 1% reduction in LDL-C in Benner study.

Average cost($) Incremental Cost ($)

Incremental % LDL-C

Incremental

cost-effectiveness ratio

($/I% LDL-C )

Strategy

1 Year 3 Years 1 Year 3 Years

Average

% LDL-C

1 Year 3 Years 1 Year 3 Years

Simvastatin 166 417 - - 37 - - - -

Pravastatin 300 802 Dominated Dominated30 DominatedDominated Dominated Dominated

Fluvastatin 365 970 Dominated Dominated30 DominatedDominated Dominated Dominated

Rosuvatatin 437 1189 271 772 46 9 9 30 85

Atorvatatin 448 1220 Dominated Dominated38 DominatedDominated Dominated Dominated

Cost effectiveness ratios were calculated before cost and effectiveness estimates were rounded. LDL-C, low density lipoprotein cholesterol.

Table 5. 1 year Benner study’s base case cost per 1% increase in HDL-C.

Average Cost($)

Incremental Cost ($)

Incremental % HDL-C

Incremental

cost-effectiveness ratio

($/I% HDL-C )

Strategy

1Year 3Years 1 Year 3 Years

Average

%HDL-C

1 Year 3 Years 1 Year 3 Years

Simvastatin 166 417 - - 6.1 - - - -

Pravastatin 300 802 Dominated Dominated4.4 DominatedDominatedDominated Dominated

Fluvastatin 365 970 Dominated Dominated4.4 DominatedDominatedDominated Dominated

Rosuvastatin 437 1189 271 772 7.3 1.2 1.2 225 643

Atorvastatin 448 1220 Dominated Dominated0.9 DominatedDominatedDominated Dominated

Cost effectiveness ratios were calculated before cost and effectiveness estimates were rounded. HDL-C, high density lipoprotein cholesterol.

Table 6. 1 year Benner study’s base case cost per patients to ATP II goal*.

Average Cost ($) Incremental Cost ($) Incremental Patients to

ATP II Goal

Incremental

cost-efectiveness ratio

($/patients to ATP II

goal)

Strategy

1 Year 3 Years 1 Year 3 Years

Average

Patients

to ATP

II Goal1 Year 3 Years 1 Year 3 Years

Simvastatin 166.000 417.000 - - 725 - - - -

Pravastatin 300.000 802.000 DominatedDominated600 DominatedDominated Dominated Dominated

Fluvastatin 365.000 970.000 DominatedDominated600 DominatedDominated Dominated Dominated

Rosuvastatin 437.000 1.189.000 271.000 772.000 871 146 146 1856 5287

Atorvastatin 448.000 1.220.000 DominatedDominated 800 DominatedDominated Dominated Dominated

*Assuming 1,000 patients treated with each statin

Cost effectiveness ratios were calculated before cost and effectiveness estimates were rounded.

ATP II, National Cholesterol Education Program ,Second Adult Treatment Panel

Table 7. 1 year Benner study’s base case cost per 1% HDL-C increase and 1% LDL-C decrease.

Average 1 Year

Cost ($) Cost per % HDL-C

increase ($)

Cost per %LDL-C decrease ($)

Strategy

1 Year 3 Years

Average

% HDL-C

(1 and 3 Years)

1 Year3 Years

Average

% LDL-C

(1 and 3 Years)

1 Year 3 Years

Simvastatin 166 417 6.1 27 68 37 4 11

Pravastatin 300 802 4.4 68 182 30 10 26

Fluvastatin 365 970 4.4 83 220 30 12 32

Rosuvastatin 437 1189 7.3 60 162 46 9 25

Atorvastatin 448 1220 0.9 497 1355 38 12 32

Cost effectiveness ratios were calculated before cost and effectiveness estimates were rounded. LDL-C, low density lipoprotein cholesterol.

HDL-C, high density lipoprotein cholesterol.

G. Koçkaya et al. / HEALTH 1 (2009) 274-280

278

Openly accessible at

Figure 1. Treatment Protocol : Treatment starts with starting dosage.(Daily Atorvastatin 10 mg, Fluvastatin 40 mg,

Pravastatin 20 mg, Rosuvastatin 10 mg, Simvastatin 20 mg). In the 6th week dosage will be titrated to half of the

maximum dosage depending on ATP II levels (Daily Atorvastatin 40 mg, Fluvastatin 40 mg, Pravastatin 20 mg, Ro-

suvastatin 20 mg, Simvastatin 40 mg). In the 3rd month dosage will be titrated to maximum dosage depending on

reach ATP II levels (Daily Atorvastatin 80 mg, Fluvastatin 80 mg, Pravastatin 40 mg, Rosuvastatin 40 mg, Simvas-

tatin 80 mg).

cost than all other statins. At initial dosage the acquisi-

tion cost is 1/3 of its nearest alternative. So this situation

affects the analysis because none of the statins had a

double or triple effect in all goals when compared with

other statins.

4.2. Alternative Scenarios

When the patients were assumed to remain at their re-

spective initial doses and 12 week effectiveness per-

sisted for the full year, again simvastatin ($116) re-

mained the least costly alternative, followed by pravas-

tatin ($215), fluvastatin ($349), rosuvastatin ($357) and

atorvastatin ($379).

When the patients were assumed to remain at their

respective maximum doses and 12 week effectiveness

persisted for the full year, again simvastatin ($269) re-

mained the least costly alternative, followed by pravas-

tatin ($353), fluvastatin ($375), rosuvastatin ($488) and

atorvastatin ($517).

As like Benner [13], when the base-case scenario was

evaluated using a 3-year time horizon, total costs in-

creased to reflect longer-term statin use (Tables 4-7).

Nevertheless, effectiveness was the same as in the 1-year

analysis because under recommended monitoring and

titration intervals, all titrations occur within the first year

of treatment [13]. Thus, the ICERs in the 3-year analysis

may be interpreted as the cost to maintain a given level

of effectiveness for 3 years [13].

5. DISCUSSION

It was reported that statins have a role in decreasing car-

diovascular risk in some trials [17]. Also it was reported

if 12 mg/dL decrease occurs in LDL-C levels, cardio-

First Visit :

Start Statin Treatment by Initial

Dosage

Second Visit

6th week

ReachATP

II Levels ?

Yes No

Continue Without

Changing Dosage

Continue with Half of

Maximum Dosage

Treatment Continue till

the end of 52 Week

With initial Dosage

Third Visit

3rd Month

Continue with

Maximum Dosage

Yes

Continue Without

g The Dosage Changin

Treatment Continue to

the End of 52 Week

With Initial Dosage

Reach ATP

II Levels ?

G. Koçkaya et al. / HEALTH 1 (2009) 274-280

279

vasculer risk increases by 36% [1].

In this CEA, currently available statins in Turkey in

patients with dyslipidemia from perspective of managed

care payer were compared.

Because simvastatin had a lower acquisition cost than

all statins and its all dosages cost approximately 1/3 of

the nearest alternative statin, in our base case and alter-

native scenarios simvastatin was the least costly alterna-

tive.

Simvastatin dominated pravastatin and fluvastatin,

whereas rosuvastatin dominated over atorvastatin. Com-

pared with simvastatin, the incremental cost of rosuvas-

tatin was $271, or $30 per additional 1% reduction in

LDL-C, $225 per additional 1% increase in HDL-C and

$1856 per additional patient to ATP II goal.

Also simvastatin served the least cost for per 1% de-

crease in HDL-C and 1% increase LDL-C, followed by

rosuvastatin. For per 1% HDL-C increase, need to pay

for simvastatin and rosuvastatin; 27$ and 60$, respec-

tively. For per 1% LDL-C decrease need to pay for sim-

vastatin and rosuvastatin; 4$ and 9$, respectively.

These findings have potentially important implica-

tions for managed care decision-makers. In the light of

the Benner [13] study base case and in each alternative

scenario, pravastatin, fluvastatin and atorvastatin always

dominated. Thus depending on actual acquisition prices

and following costs such as doctor visits and laboratories

the payer may achieve substantial cost savings and

greater effectiveness by using rosuvastatin or simvastatin

instead of these agents in Turkey.

In order to use these findings in a decision-making

context, the analysis may be recalculated without in-

cluding rosuvastatin. The most effective alternative is

atorvastatin, which currently is in many formularies.

Under base-case assumptions atorvastatin, in the absence

of rosuvastatin, has an incremental cost per patient to

reach goal of $75 when compared with simvastatin.

These findings may have some limitations. Because

the objective was to identify the optimal combination of

statins for a managed care formulary, several nonstatin

medications for dislipidemia (e.g., niacin, fibrates and

bile sequestrants) were excluded from the analysis [13].

These products generally have a secondary role in ther-

apy, relatively inexpensive, and were not expected to

influence the relative cost-effectiveness of products in

the statin class [13]. Their exclusion from this analysis

would not be construed to mean that they are not

cost-effective agents in modifying serum lipids [13]. The

effectiveness of atorvastatin, pravastatin, rosuvastatin

and simvastatin were estimated based on data from two

phase III trials [13]. Fluvastatin was also assumed to be

equivalent to pravastatin over the dose ranges specified,

because long-term trials have compared fluvastatin with

rosuvastatin [13]. Although the results of the estimates

for each drug are consistent with numerous other trials

and product labels, and these estimates were varied in

sensivity analyses, the results may not be applied to pa-

tient populations with different characteristics than those

in the Olsson [15] and Brown [16] trials [13]. Moreover,

for the detailed analysis for managed care perspective, it

is essential to study the effectiveness of statins in Turk-

ish patients. The cost associated with adverse drug

events and non-study medications were excluded, but

these were not expected to differ across treatment groups,

and therefore would not have affected the incremental

analysis [13].

In conclusion, the findings of this analysis indicate

that simvastatin is a less costly alternative than other

statins and rosuvastatin is more effective than other stat-

ins. Therefore, simvastatin and rosuvastatin comprise of

the optimal two statin formulary. Formulary desicion

based on these results should be revisited periodically, as

new pricing, outcomes and safety data become available.

6. ACKNOWLEDGEMENTS

Thanks Mrs. Sibel Daylan (MS) from Izzet Baysal University and Mr.

Ruhi Kadaifci (MD) from Medvice Medical Consultansy for their great

help.

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