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UDC 615.225:339.13:338.517
PHARMACOEPIDEMIOLOGIC AND PHARMACOECONOMIC ASPECTS
OF ANGIOTENSIN II RECEPTOR BLOCKERS CONSUMPTION
IN PHARMACEUTICAL MARKET OF UKRAINE
O. Ya. Mishchenko, V. Yu. Adonkina,
National University of Pharmacy, Kharkiv
Keywords: hypertension, angiotensin ІІ receptor blockers (ARBs ІІ), affordability, indicator of paying capacity adequacy, consumption, АТС/DDDmethodology
The article highlights the results of the analysis of the range, affordability
and consumption of angiotensin II receptor blockers (ARBs II) compared to ACE
inhibitors during 2008-2013 and rationale for the choice of the most optimal trade
names (TNs) on the results of pharmacoeconomic analysis “cost minimization”
and the rate of missed opportunities. During the study period there was an increase in the range of ARBs II in pharmaceutical market of Ukraine mainly due to
foreign drugs. ARBs II drugs are characterized by low availability for the average
citizen of Ukraine compared to ACE inhibitors. In the dynamics of years the consumption of ARBs II increased, but was far less than the consumption of ACE inhibitors. During the study period the leaders of consumption were losartan, valsartan and candesartan, which were mostly generics. As a result of pharmacoeconomic analysis and calculation of the rate of missed opportunities, some offers of less
expensive ARBs ІІ drugs, the use of which allows treating a number of patients
compared to more expensive ones, were determined.
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Treatment of hypertension (HTN) is the most cost-effective strategy for reducing the number of cardiovascular events, including the most dangerous: myocardial infarction and stroke [7, 8, 10, 11, 13, 14]. Angiotensin ІІ receptor blockers
(ARBs II) or sartans belong to the first-line drugs for pharmacotherapy of patients
with HTN. In medical practice drugs of this group are considered as an alternative
to ACE inhibitors. Based on the results of large multicenter clinical trials it can be
said about the presence of class effects in all sartans, and among them the main
ones are antihypertensive, that is a stable and long-term control of blood pressure
(BP), and organoprotective [7, 8, 10, 11, 14]. The presence of cardioprotective,
nephroprotective, neuroprotective effects and the ability to improve glycemic control in patients with diabetes mellitus has been proven so far [9, 12, 15, 16]. The
latest guidelines of the European Society of Cardiology and the European Society
of Hypertension focused on situations when the most appropriate thing was to administer sartans: heart failure; postinfarction period; microalbuminuria; proteinuria; diabetic nephropathy; renal insufficiency; left ventricular hypertrophy;
metabolic syndrome; intolerance to ACE inhibitors [13]. Absolute contraindications to sartans are pregnancy, hyperkalemia and bilateral renal artery stenosis
[13]. So, today ARBs II are positioned as effective and safe antihypertensive
agents (AHAs) with organoprotective action, but the amount of their consumption
is lower than for other AHAs [4]. In view of the above, study of the appropriateness of choice of ARBs ІІ on the basis of pharmacoeconomic component requires
further development and is valid.
The purpose of this paper is to conduct marketing research of the range, affordability and amounts of consumption of ARBs ІІ drugs compared to ACE inhibitors during 2008-2013 and rationale for the choice of the most optimal trade
names (TNs) on the results of pharmacoeconomic analysis.
Material and methods
Marketing analysis of ARBs ІІ, their affordability and amounts of consumption was conducted during 2008-2013 on the basis of Morion research and retrieval
system data on the range, price and the number of drug packages sold over a year.
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To analyse the social and economic affordability of ARBs II, the indicator of paying capacity adequacy (Са.s.), which shows the share of wages spent on the purchase of a drug package, was calculated by the formula [2, 5]: Ca.s. = P/ Wa.w.Х 100
%, where Ca.s. is the indicator of paying capacity adequacy; P is the weighted average price of a drug package per year; Wa.w. is the average salary for the year. The
value of the average salary in Ukraine for the years studied was found on the website: www.ukrstat.gov.ua. All trade names (TNs) of ARBs II were divided into
three categories: highly available, the indicator of paying capacity adequacy (Ca.s.)
of which was less than 5%, of average availability (Ca.s. was more than 5% and
less than 15%) and low availability (Ca.s. was more than 15%) [3, 5]. The analysis
of ARBs II consumption was conducted with the help of the АТС/DDD methodology [1]. The drug consumption was expressed in the index DDDs/1000
inhabitants/day (DIDs), which was calculated by the formula: DIDs = DDDs
1000 / the number of inhabitants
Х
Х
365, where DDDs is the number of standard
doses (DDD, defined daily dose), which were taken by seriously ill patients in
Ukraine for the year. The values of DDD for the analysed drugs were found on the
website of WHO by the respective АТС code.
To determine ARBs II drugs with a minimum value of annual treatment of
HTN, the method of “cost minimization” was used to analyze generics of certain
INN, assuming that comparable drugs have the same clinical efficacy as a condition of their registration is a proven clinical efficacy that meets the efficacy of the
comparator [6]. The calculation was performed by the formula: СМА = DC1− DC2,
where: СМА is the cost difference of the compared treatment regimens; DC1 − direct costs for the first treatment regimen; DC2 − direct costs for the second treatment regimen [6]. At the final stage of the study, the rate of missed opportunities
(Q), which shows the number of patients who may be treated when switching from
the drug with a maximum value to the drug with a minimum value of the treatment
course, was calculated by the formula: Q = СМА / Clow, wherе: СМА is the cost
difference (UAH) of the compared treatment regimens; Clow – costs (UAH) for the
treatment with a less expensive drug.
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Results and discussion
During the study period the pharmaceutical market consisted of 17 INN of
ARBs ІІ (7 INN of single entity drugs and 10 INN of fixed dose combinations
(FDC) with hydrochlorothiazide and/or amlodipine) (Table 1). The number of TNs
of ARBs ІІ taking into account different pharmaceutical forms and dosages kept
growing from 88 TNs in 2009 to 156 TNs in 2013. During the study period the
bulk of 82.1% TNs of ARBs, presented in the market of Ukraine, is of foreign
pharmaceutical manufacturers, and 17.9% – of domestic ones. Over the study period, a stable dominance of the range of foreign ARBs ІІ with a slight gradual increase of a segment of drugs of home manufacture was observed in the market. In
2009, domestic manufacturers presented 11.4 % TNs, and in 2010 compared to
2009 the range of domestic ARBs ІІ increased only by three drugs and amounted
to 13.5 %. In 2011-2013 compared to data from 2010 the specific share of drugs of
home manufacture increased to 23.3% (2011), 21.6 % (2012) and 19.6% (2013).
Thus, increase in the number of ARBs ІІ in the market was due to foreign drugs,
the number of which exceeded the number of domestic ones by 3-8 times. The
largest number of drugs by TN is characteristic of losartan, valsartan and
candesartan.
Results of estimates of ARBs ІІ affordability compared to ACE inhibitors on
the basis of the indicator of paying capacity adequacy (Са.s.) are shown in Table 2.
During the study period, the share of highly available drugs from ARBs ІІ group
was 65.6% - 85.4% that is less than the share of highly available drugs from ACE
inhibitors group. There was a tendency to its increase, and respectively the share of
drugs of average and low availability in ARBs ІІ group decreased. This tendency
can be explained by the significant share of both original and foreign generic single
entity and combination drugs in this group.
According to evidence-based medicine, ARBs II and ACE inhibitors are two
groups of drugs that affect the renin–angiotensin system (RAS) and one of the
most effective drugs for the treatment of HTN and prevention of cardiovascular
events [13, 15]. Angiotensin ІІ receptor blockers are positioned as an alternative to
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ACE inhibitors with missing ability to cause such side effects as a cough. Results
of the study of consumption of drugs that affect RAS, in terms of DIDs, are shown
in Fig. 1.
The amount of consumption of ACE inhibitors exceeds the amount of consumption of ARBs II by almost 8-26 times. This difference in the amounts of consumption of two groups of drugs can probably be explained by quite less availability of ARBs II drugs and stereotype approaches to the choice of AHAs.
The analysis of consumption patterns in a group of ARBs II drugs showed
that consumption growth is mainly due to losartan and valsartan (Fig. 2). These are
drugs of the earliest generations. The undisputed leader of consumption during the
study period is losartan as the first drug of sartans, which is more widely presented
by generics compared to other drugs. The second position in terms of consumption
amount is taken by valsartan – the drug of later generation. Furthermore, high
amounts of consumption of this drug can be explained by the fact that it is now positioned as effective and safe and is the most appropriate as to the price characteristics [12]. The third position in terms of consumption amount is taken by candesartan.
Thus, the larger amounts of consumption are inherent to those ARBs ІІ
drugs, which are presented by generics to the largest extent and characterized by
more affordability.
In order to justify the best offers of ARBs ІІ on the criterion “cost of the annual course of treatment” of HTN, the pharmacoeconomic analysis “cost minimization” and the calculation of the rate of missed opportunities were conducted.
Results of “cost minimization” analysis showed that among all TNs of ARBs
ІІ Losartin (coated tabl. 50 mg No30, Zdorovie LLC, Ukraine) is the least expensive. The cost of treatment with this drug is 262.80 UAH, which is less compared
to other TNs. The most expensive of all TNs of ARBs ІІ is Aprovel®, (Sanofi,
France) with the cost of the annual treatment course of 4139.10 UAH.
The most rational drugs of individual INN from the pharmacoeconomic
point of view are as follows: for losartan (C09C A01) - Losartin (coated tabl. 50
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mg No30, Zdorovie LLC, Ukraine), the cost of treatment was 262.80 UAH; for
valsartan (C09C A03) - Vazar (coated tabl. 160 mg blister, No90, Actavis Group,
Iceland), the cost of treatment was 219.00 UAH; for candesartan (C09C A06) Casark (tabl. 8 mg No30, Arterium (Ukraine, Kyiv), the cost of treatment is 609.50
UAH; for irbesartan (C09C A04) – Irbetan (tabl. 300 mg, No20, Kyiv Vitamin
Factory OJSC (Ukraine, Kyiv), the cost of treatment is 584.00 UAH; for olmesartan (C09C A08) – Olmesar 20, (coated tabl. 20 mg, No28, Macleods Pharmaceuticals Ltd (India), the cost of treatment is 912.50 UAH; for telmisartan (C09C A07) Miocaris®, (tabl. 80 mg, No28, Boehringer Ingelheim (Germany), the cost of
treatment is 1219.10 UAH; for eprosartan (C09C A02) – Teveten®, (film-coated
tabl. 600 mg blister, No14, Abbott Products GmbH, Germany), the cost of treatment is 3701.10 UAH. So, the cost of the annual course of treatment with different
ARBs ІІ varies considerably.
In order to prove the rationale of cost-effective use of ARBs ІІ for the treatment of HTN based on the results of cost minimization analysis, the rate of missed
opportunities (Q) when switching from the generic with a maximum value to the
generic with a minimum value of the treatment course was calculated (Table 3).
The rate of missed opportunities shows how many patients can be treated
additionally when switching from more expensive to less expensive drug in the
treatment of HTN. As a result of the analysis, TNs of ARBs ІІ, treatment of HTN
with which is less expensive, have been selected. Using these less expensive drugs
compared to more expensive ones for 100 patients during a year, the following
number of patients can be treated additionally: 136 patients – when switching from
Lorista (KRKA, Slovenia) to Losartin (Zdorovie LLC, Ukraine); 58 patients when
switching from Valzap (Sanofi, France) to Vazar (Actavis Group, Iceland); 13 patients when switching from Candesar (Ranbaxy, India) to Casark (Arterium,
Ukraine).
Thus, the results of the study indicate that ARBs ІІ have less affordability
which probably causes the low level of consumption. In this regard, to justify the
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choice of drugs with the best value pharmacoeconomic analysis results are appropriate.
Conclusions.
1. During 2009 - 2013 the range of ARBs ІІ increased in the pharmaceutical market of Ukraine mainly due to foreign drugs.
2. ARBs ІІ are characterized by low availability for the average citizen of Ukraine
compared to other antihypertensive medications, including ACE inhibitors.
3. In the dynamics of years the consumption of ARBs ІІ is increasing but is far less
than the consumption of ACE inhibitors. During the study year, leaders of consumption in ARBs ІІ group are losartan, valsartan and candesartan.
4. As a result of pharmacoeconomic analysis and calculation of the rate of missed
opportunities, some offers of less expensive ARBs ІІ drugs, the use of which allows treating a number of patients compared to more expensive ones, were determined.
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Table 1
No
1.
2.
3.
4.
5.
6.
7.
ARBs ІІ range in the pharmaceutical market of Ukraine
Domestic/foreign TNs
ATC code
INN
2009 2010 2011 2012 2013
Single entity drugs
3/25
3/25
7/26
7/25
7/29
FDC with HCTZ /
Aml
1/10
1/10
4/14
5/16
5/16
Losartan
Total 4/35
4/35 11/40 12/41 12/45
Single entity drugs
0/10
0/10
2/10
2/15
2/17
FDC with HCTZ /
Aml
3/12
3/14
3/15
7/21
7/28
Valsartan
Total 3/22
3/24
5/25
9/36
9/45
Single entity drugs
0/1
0/1
0/1
0/1
0/1
FDC with HCTZ
0/1
0/1
0/1
0/1
0/0
Eprosartan
Total 0/2
0/2
0/2
0/2
0/1
Single entity drugs
1/2
1/2
1/2
1/2
2/10
FDC with HCTZ
0/0
0/0
0/0
0/2
0/4
Irbesartan
Total 1/2
1/2
1/2
1/4
2/14
Single entity drugs
2/5
5/5
4/5
5/5
6/5
FDC with HCTZ
0/3
0/3
0/3
2/5
2/5
Candesartan
Total 2/8
5/8
4/8
7/10
8/10
Single entity drugs
0/3
0/3
0/3
0/3
0/3
FDC with HCTZ
0/3
0/3
0/4
0/3
0/3
Telmisartan
Total 0/6
0/6
0/7
0/6
0/6
Single entity drugs
0/3
0/4
0/4
0/4
0/4
FDC with HCTZ
0/0
0/2
0/2
0/2
0/2
Olmesartan
Total 0/3
0/6
0/6
0/6
0/6
Total in the group 10/78 13/83 21/90 29/105 31/127
88
96
111
134
Notes: 1. FDC – fixed drug combination; 2. HCTZ – hydrochlorthiazide;
3.Aml – amlodipine.
158
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Table 2
Distribution of study drugs by different categories of affordability according
to the indicator of paying capacity adequacy
Years of study
2009
ATC
group
2010
Drug category
highly available, Са.s.<5%
2011
2012
2013
% drug
65.6
75.3
82.1
82.4
85.4
5%<Са.s.<15%
30.0
24.7
17.9
17.6
14.6
of low availability, Са.s.>15%
4.4
─
─
─
─
highly available, Са.s.<5%
99
100
99
98.9
98.5
of average availability,
ARBs II
of average availability,
ACE in-
5%<Са.s.<15%
1.0
─
1.0
1.1
1.5
hibitors
of low availability, Са.s.>15%
─
─
─
─
─
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DDDs/1000/day
47,62
2008
47,38
2009
50,00
2010
41,31
45,00
40,00
2011
37,47
32,79
2012
31,70
35,00
2013
30,00
25,00
20,00
15,00
10,00
4,31
1,25
5,00
1,69
6,62
7,96
2,83
0,00
ACE inhibitors
Angiotensin II receptor antagonists
Fig. 1. Dynamics of consumption of drugs that affect RAS, in DDDs/1000/day
(DIDs) during 2008-2013 in Ukraine
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Fig. 2. Dynamics of ARBs ІІ drugs consumption in DIDs during 2008-2013
in Ukraine
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Table 3
Offers of ARBs ІІ drugs for optimization of costs for the treatment of patients with HTN based on the results of “cost
minimization” analysis and the rate of missed opportunities
Cost of
Trade name,
manufacturer of the drug
the
Pharmaceutical form
with a minimum value
treatment
course,
UAH
Trade name,
manufacturer of the
drug with a maxi-
No 30
treatment
course,
UAH
Difference of
the cost of
treatment of
100 patients
(thous.UAH)
Rate of
missed
opportunities (Q)
coated tabl. 50 mg,
262.80
Lorista, KRKA
coated tabl. 80 mg,
Vazar, Actavis Group
Pharmaceutical form
mum value
coated tabl. 50 mg,
Losartin, Zdorovie LLC
Cost of the
No 90
620.80
35.77
136
No 28
565.75
20.81
58
tabl. 8 mg, No 10
693.50
8.39
13
coated tabl. 80 mg,
No 90
357.70
Valzap, Sanofi
tabl. 8 mg, No 30
609.50
Candesar, Ranbaxy
Casark,
Arterium Corporation
Notes: 1. Q – additional number of patients, which can be treated with drugs with a minimum value per the money spent for the
course of treatment with drugs with a maximum value; 2. ARBs ІІ treatment course – 1 year.
15
About the Authors
Oksana Mishchenko Yakivna - D. Pharmacy, professor of pharmacoeconomic department of National University of Pharmacy (Kharkiv).
e-mail: [email protected]
Tel.: 658 895; Tel. mob .: 0666666849.
Adonkina Victoria Yuriivna - K. Pharm. Science.
e-mail: [email protected]
Tel. Mob .: 0667272323.