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Vol. 68. Issue 10.
Pages 899-903 (October 2015)
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Vol. 68. Issue 10.
Pages 899-903 (October 2015)
Scientific letter
DOI: 10.1016/j.rec.2015.06.011
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Use of Antihypertensive Drugs in Spain: National Trends From 2000 to 2012
Uso de medicamentos antihipertensivos en España: tendencias nacionales en el periodo 2000-2012
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Virginia Grecianoa,b, Diego Macías Saint-Geronsa, Diana González-Bermejoa, Dolores Monteroa, Ferrán Catalá-Lópeza,c,
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ferran_catala@hotmail.com

Corresponding author:
, César de la Fuente Honrubiaa
a División de Farmacoepidemiología y Farmacovigilancia, Agencia Española de Medicamentos y Productos Sanitarios (AEMPS), Madrid, Spain
b Servicio de Farmacia de Atención Primaria, Dirección Asistencial Este, Servicio Madrileño de Salud, Alcalá de Henares, Madrid, Spain
c Fundación Instituto de Investigación en Servicios de Salud, Valencia, Spain
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Rev Esp Cardiol. 2015;68:119110.1016/j.rec.2015.08.009
Carlos Escobar, Vivencio Barrios
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Tables (1)
Table. Use of Antihypertensive Drugs in Spain According to Treatment Subgroup and Active Ingredient. Data Expressed as Defined Daily Doses per 1000 Inhabitants per Day
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To the Editor,

Hypertension is a major global public health problem, mainly because of its contribution to the risk of cardiovascular events.1,2 Epidemiological studies2,3 have reported that hypertension control in Spain continues to be suboptimal and that, on occasions, targets (arterial blood pressure < 140/90mmHg) are met in less than half of the hypertensive individuals under treatment.2 A number of previous studies4 have called attention to important changes in the patterns of use of antihypertensive drugs in recent decades.

Following the methodology described by the Observatory for the Use of Medicines of the Spanish Agency of Medicine and Medical Devices,5 we examined the pattern of antihypertensive drug use in Spain from 2000 to 2012. We selected the treatment subgroups of the Anatomical Therapeutic Chemical Classification (ATC): antihypertensive agents (C02), diuretics (C03), beta-blockers (C07), calcium channel blockers (C08), and drugs that act on the renin-angiotensin system (C09), such as angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and direct renin inhibitors (aliskiren). The analytical measure was the number of defined daily doses (DDD) dispensed per 1000 inhabitants per day (DID).5 We used the consumption data provided by the Directorate-General of the Basic Service Portfolio of the Spanish Health and Pharmacy System, whose database compiles prescriptions for the medications covered by the Spanish Health System.

The patterns of use of antihypertensive drugs in Spain are shown in the Table (according to treatment subgroup and active ingredient). The use of antihypertensive medications in Spain increased from 2000 to 2012, and those most widely consumed were angiotensin receptor blockers and angiotensin-converting enzyme inhibitors. More specifically, the total used of antihypertensive drugs was 165.5 DID in the year 2000 and 299.0 DID in 2012. By group, angiotensin receptor blockers (18.2 DID and 93.8 DID in 2000 and 2012, respectively), angiotensin-converting enzyme inhibitors (62.2 DID and 86.4 DID, respectively), diuretics (32.8 DID and 44.8 DID, respectively), and calcium channel blockers (33.4 DID and 38.8 DID) were the most widely used antihypertensive drugs. Enalapril (42.7 DID), amlodipine (20.7 DID), furosemide (16.4 DID), ramipril (15.1 DID), valsartan (14.3 DID), and candesartan (12.5 DID) were the most widely used active ingredients in 2012.

Table.

Use of Antihypertensive Drugs in Spain According to Treatment Subgroup and Active Ingredient. Data Expressed as Defined Daily Doses per 1000 Inhabitants per Day

  2000  2001  2002  2003  2004  2005  2006  2007  2008  2009  2010  2011  2012 
Antihypertensive drugs (C02)
Clonidine  0.01  0.01  0.01  0.01  0.01  0.01  0.01  0.01  0.01  0.01  0.01  0.01  0.01 
Doxazosin  4.27  5.15  6.08  7.10  7.74  7.98  8.19  8.42  8.54  8.87  8.88  8.64  9.05 
Hydralazine  0.04  0.04  0.05  0.05  0.05  0.05  0.06  0.07  0.07  0.07  0.08  0.08  0.08 
Methyldopa (racemic)  0.04  0.04  0.03  0.03  0.03  0.02  0.02  0.02  0.02  0.02  0.02  0.02  0.02 
Minoxidil  0.01  0.01  0.01  0.01  0.01  0.01  0.01  0.01  0.01  0.01  0.01  < 0.01  < 0.01 
Moxonidine  0.22  0.25  0.25  0.29  0.32  0.33  0.35  0.38  0.40  0.43  0.42  0.39  0.38 
Prazosin  0.07  0.06  0.05  0.05  0.04  0.03  0.03  0.02  0.02  0.02  0.02  0.01  0.01 
Rauwolfia serpentina alkaloidsa  0.07  0.05  0.04  0.02  0.01  0.01  < 0.01             
Reserpine and diureticsb  0.07  0.06  0.03  0.03  0.02  < 0.01               
Reserpine and diuretics, combinations with othersb  0.14  0.12  0.10  0.08  0.07  0.05               
Total C02  4.95  5.77  6.65  7.66  8.30  8.50  8.67  8.92  9.06  9.43  9.43  9.16  9.56 
Diuretics (C03)
Bumetanide  0.02  0.03  0.03  0.03  0.03  0.03  0.03  0.03  0.03  0.03  0.03  0.03  0.03 
Chlorthalidone  5.17  5.12  5.01  5.02  5.21  5.20  5.23  5.19  5.11  5.10  4.89  4.61  4.82 
Chlorthalidone/spironolactone  0.15  0.14  0.11  0.10  0.10  0.09  0.09  0.09  0.09  0.09  0.08  0.08  0.08 
Eplerenone            < 0.01  0.03  0.08  0.23  0.31  0.36  0.48  0.62 
Spironolactone  2.02  2.12  2.16  2.23  2.11  2.20  2.17  2.14  2.12  2.17  2.15  2.14  2.20 
Furosemide  7.75  8.13  8.43  8.24  9.21  9.77  10.66  11.50  12.28  13.30  14.08  14.86  16.42 
Furosemide-xanthinol/triamterene  1.24  1.15  1.03  0.94  0.85  0.74  0.67  0.60  0.54  0.51  0.46  0.42  0.38 
Hydrochlorothiazide  4.22  4.73  5.23  5.80  6.56  7.12  7.81  8.38  8.90  9.25  9.46  9.42  9.40 
Hydrochlorothiazide/potassium sparing diuretics  3.97  3.83  3.63  3.49  3.34  3.16  3.01  2.84  2.63  2.53  2.33  2.16  2.06 
Indapamide  4.65  4.75  4.80  5.03  5.10  4.95  4.89  4.71  4.52  4.43  4.12  3.79  3.77 
Piretanide  0.03  0.03  0.02  0.02  0.02  0.01  0.01  0.01  0.01  0.01  0.01  0.01  < 0.01 
Torasemide  2.47  3.07  3.72  4.34  4.72  4.82  4.93  4.93  4.97  5.16  5.05  4.79  4.72 
Xipamide  0.74  0.66  0.59  0.53  0.47  0.41  0.37  0.33  0.30  0.28  0.25  0.22  0.20 
Spironolactone/altizide  0.36  0.36  0.35  0.33  0.31  0.29  0.27  0.26  0.24  0.24  0.23  0.13  0.13 
Mebutizide/ potassium sparing diureticsc  0.03                         
Spironolactone/bendroflumethiazided  0.01  < 0.01  < 0.01  < 0.01  < 0.01  < 0.01  < 0.01  < 0.01  < 0.01  < 0.01  < 0.01     
Total C03  32.82  34.12  35.11  36.09  38.01  38.79  40.16  41.08  41.96  43.39  43.50  43.14  44.84 
Beta blockers (C07)
Acebutolola  0.06  0.05  0.04  < 0.01  < 0.01  < 0.01  < 0.01             
Acebutolol/thiazidea  0.01  0.01  0.01  0.01  < 0.01  < 0.01  < 0.01             
Atenolol  6.38  6.64  6.78  6.84  7.38  7.33  7.64  7.65  7.48  7.51  7.32  7.10  7.22 
Atenolol/bendroflumethiazide  0.05  0.04  0.04  0.04  0.03  0.02  0.02  0.02  0.02  0.02  0.02  0.02  0.02 
Atenolol/chlorthalidone  1.16  1.13  1.04  0.53  1.07  1.03  1.01  0.97  0.91  0.87  0.84  0.78  0.76 
Atenolol/hydrochlorothiazide/amiloride  0.06  0.06  0.06  0.05  0.05  0.05  0.04  0.04  0.04  0.04  0.04  0.04  0.04 
Atenolol/hydralazine/bendroflumethiazidee  < 0.01  < 0.01  < 0.01  < 0.01  0.01  0.01  0.01  0.01  0.01  0.01  0.01  < 0.01   
Bisoprolol  2.14  2.46  2.78  3.06  3.38  3.63  3.97  4.31  4.63  5.17  5.61  6.05  6.92 
Bisoprolol/hydrochlorothiazide  0.39  0.46  0.51  0.57  0.64  0.67  0.70  0.71  0.71  0.75  0.73  0.70  0.71 
Carteololf  0.01  < 0.01  < 0.01  < 0.01  < 0.01  < 0.01  < 0.01  < 0.01  < 0.01  < 0.01       
Carvedilol  1.11  1.30  1.53  1.78  2.04  2.28  2.52  2.69  2.83  3.04  3.11  3.13  3.38 
Celiprolol  0.09  0.08  0.07  0.06  0.06  0.05  0.05  0.04  0.04  0.04  0.04  0.03  0.03 
Labetalol  0.02  0.02  0.02  0.02  0.02  0.02  0.02  0.02  0.02  0.02  0.03  0.03  0.03 
Metoprolol  0.34  0.36  0.38  0.39  0.40  0.39  0.40  0.40  0.40  0.42  0.42  0.42  0.45 
Metoprolol/felodipine  0.52  0.55  0.52  0.48  0.48  0.48  0.47  0.46  0.45  0.45  0.41  0.37  0.36 
Metoprolol/thiazideb  0.01  0.01  < 0.01  < 0.01  < 0.01  < 0.01               
Nadolol  0.08  0.08  0.08  0.09  0.09  0.09  0.10  0.10  0.05  0.04  0.06  0.07  0.08 
Nebivolol  0.43  0.75  1.00  1.20  1.29  1.32  1.46  1.70  2.03  2.52  2.70  2.71  2.83 
Oxprenolol  0.05  0.04  0.04  0.03  0.03  0.02  0.02  0.02  0.02  0.02  0.02  0.02  0.01 
Oxprenolol/chlorthalidone  0.08  0.07  0.06  0.06  0.05  0.04  0.04  0.03  0.03  0.03  0.02  0.01  0.01 
Propranolol  0.62  0.62  0.62  0.63  0.63  0.62  0.64  0.65  0.68  0.74  0.74  0.74  0.79 
Propranolol/other antihypertensive drugsf  0.06  0.05  0.05  0.04  < 0.01  < 0.01  < 0.01  < 0.01  < 0.01  0.00       
Sotalol  0.17  0.17  0.17  0.17  0.17  0.17  0.16  0.16  0.16  0.18  0.17  0.14  0.15 
Nebivolol/hydrochlorothiazide                      0.05  0.24  0.33 
Total C07  13.84  14.97  15.81  16.06  17.82  18.24  19.27  20.00  20.50  21.85  22.31  22.59  24.10 
Calcium channel blockers (C08)
Amlodipine  11.95  13.06  13.97  14.71  15.21  15.62  16.23  16.95  17.78  18.69  18.79  19.09  20.76 
Barnidipine    < 0.01  0.23  0.40  0.69  0.78  0.84  0.96  1.33  1.43  1.38  1.34  0.95 
Diltiazem  4.85  4.77  4.70  4.64  4.55  4.42  4.35  4.28  4.18  4.18  4.00  3.76  3.72 
Felodipine  0.88  0.74  0.64  0.55  0.47  0.40  0.33  0.28  0.25  0.23  0.20  0.18  0.17 
Lacidipine  1.57  1.37  1.18  1.03  0.90  0.78  0.69  0.62  0.55  0.50  0.44  0.38  0.36 
Lercanidipine  1.06  1.40  1.58  1.67  1.84  2.24  2.67  3.03  3.22  3.36  3.27  3.13  3.24 
Manidipine        0.13  0.81  1.23  1.66  2.21  2.80  3.33  3.59  3.57  3.89 
Nicardipine  1.16  1.04  0.96  0.90  0.84  0.75  0.67  0.59  0.53  0.49  0.44  0.39  0.36 
Nifedipine  6.83  6.33  5.97  5.63  5.25  4.91  4.68  4.45  4.22  4.04  3.73  3.44  3.34 
Nimodipine  1.02  0.93  0.83  0.72  0.61  0.51  0.45  0.39  0.34  0.30  0.26  0.22  0.20 
Nisoldipine  0.25  0.19  0.16  0.13  0.11  0.09  0.07  0.06  0.05  0.05  0.04  0.03  0.03 
Nitrendipine  0.68  0.57  0.49  0.43  0.38  0.33  0.30  0.27  0.25  0.23  0.20  0.18  0.17 
Verapamil  3.19  3.04  2.89  2.75  2.59  2.42  2.30  2.18  2.05  2.00  1.85  1.70  1.61 
Total C08  33.45  33.43  33.61  33.67  34.23  34.46  35.24  36.29  37.55  38.82  38.20  37.42  38.79 
Agents acting on the renin-angiotensin system (C09)
ACE inhibitors and associations
Benazepril  0.50  0.41  0.35  0.30  0.25  0.21  0.18  0.16  0.15  0.15  0.13  0.11  0.10 
Benazepril/hydrochlorothiazide                  < 0.01  < 0.01  < 0.01  < 0.01  < 0.01 
Captopril  7.98  7.53  6.93  6.09  5.69  4.77  4.63  4.08  3.52  3.16  2.70  2.29  2.11 
Captopril/hydrochlorothiazide  1.76  1.63  1.47  1.30  1.24  1.11  1.00  0.90  0.80  0.73  0.64  0.57  0.52 
Cilazapril  1.95  1.64  1.34  1.12  0.94  0.77  0.65  0.55  0.46  0.41  0.34  0.28  0.24 
Cilazapril/hydrochlorothiazide  0.45  0.41  0.36  0.32  0.28  0.25  0.22  0.20  0.17  0.16  0.14  0.12  0.11 
Enalapril  26.39  28.25  29.25  29.81  32.15  31.48  35.13  35.80  37.67  38.72  39.14  39.61  42.73 
Enalapril/hydrochlorothiazide  4.59  4.81  4.94  5.19  5.80  6.18  7.25  8.00  8.67  9.33  9.82  10.30  11.64 
Enalapril/calcium channel blockers      0.1  0.47  0.8  0.89  0.89  0.96  1.70  1.80  2.52  2.84  2.99 
Spiraprilg  0.22  0.22  0.24  0.26  0.25  0.23  0.19  0.15  0.12  0.06  < 0.01  < 0.01  < 0.01 
Fosinopril  1.78  1.66  1.54  1.46  1.26  1.07  0.94  0.82  0.72  0.64  0.56  0.48  0.45 
Fosinopril/hydrochlorothiazide  0.47  0.50  0.51  0.53  0.49  0.44  0.40  0.38  0.34  0.33  0.30  0.26  0.26 
Imidapril          < 0.01  0.06  0.15  0.22  0.27  0.48  0.63  0.77  1.16 
Lisinopril  4.52  4.50  4.32  4.01  3.78  3.54  3.47  3.40  3.39  3.50  3.57  3.64  3.94 
Lisinopril/hydrochlorothiazide  1.62  1.64  1.56  1.50  1.42  1.33  1.33  1.32  1.32  1.37  1.41  1.46  1.62 
Perindopril  0.57  0.58  0.62  0.71  0.81  0.82  0.76  0.71  0.66  0.57  0.52  0.48  0.48 
Perindopril/indapamide        0.01  0.18  0.33  0.48  0.54  0.60  0.70  0.69  0.66  0.66 
Quinapril  4.11  3.93  3.76  3.60  3.13  2.61  2.23  1.93  1.67  1.49  1.29  1.11  1.01 
Quinapril/hydrochlorothiazide  1.08  1.01  0.94  0.89  0.80  0.69  0.62  0.55  0.48  0.44  0.39  0.34  0.30 
Ramipril  2.87  3.24  4.32  5.61  7.31  8.33  9.12  9.72  10.58  11.84  12.58  13.16  15.15 
Ramipril/felodipine              0.03  0.05  0.04  0.04  0.03  0.03  0.04 
Ramipril/hydrochlorothiazide                  < 0.01  0.04  0.10  0.18  0.30 
Trandolapril  0.50  0.44  0.38  0.35  0.31  0.26  0.24  0.21  0.18  0.15  0.13  0.11  0.09 
Trandolapril/verapamil  0.83  0.99  0.97  0.94  0.93  0.89  0.83  0.80  0.76  0.74  0.66  0.57  0.52 
Total ACE inhibitors and associations  62.20  63.38  63.90  64.48  67.81  66.27  70.74  71.43  74.29  76.84  78.29  79.37  86.42 
ARB and associations
Candesartan  4.59  5.47  5.79  6.03  7.10  6.28  8.26  10.01  11.39  12.77  12.80  12.55  12.52 
Candesartan/hydrochlorothiazide    0.54  0.94  1.15  1.28  2.51  2.59  2.63  2.68  2.83  3.16  3.54  3.73 
Eprosartan    0.68  1.62  2.07  2.60  2.50  2.26  2.16  2.16  2.20  2.02  1.73  1.57 
Eprosartan/hydrochlorothiazide            0.13  0.52  0.62  1.47  1.73  1.71  1.57  1.57 
Irbesartan  3.01  3.64  4.36  5.31  5.88  5.99  6.22  6.35  6.41  6.62  6.54  6.13  6.04 
Irbesartan/hydrochlorothiazide  0.55  1.25  1.79  2.35  2.97  3.19  3.50  3.97  4.28  4.71  4.77  4.55  4.54 
Losartan  1.99  2.11  2.40  2.78  3.38  4.28  5.09  5.78  6.20  6.65  6.89  7.10  8.05 
Losartan/hydrochlorothiazide  1.09  1.55  2.14  2.63  3.04  3.25  3.43  3.64  3.73  3.85  3.89  4.02  4.55 
Olmesartan          0.69  2.65  3.87  3.01  5.23  5.98  6.25  6.42  6.82 
Olmesartan/amlodipine                    0.26  1.70  2.39  2.65 
Olmesartan/amlodipine/hydrochlorothiazide                        0.14  1.08 
Olmesartan/ hydrochlorothiazide                0.10  0.52  0.96  1.30  1.92  2.68 
Telmisartan  2.77  3.88  4.80  4.74  4.62  4.56  4.81  5.34  5.93  6.59  6.82  7.00  7.39 
Telmisartan/amlodipine                        0.14  0.34 
Telmisartan/hydrochlorothiazide            0.45  0.62  1.15  2.40  2.98  3.43  3.72  4.07 
Valsartan  3.39  4.86  6.88  8.73  9.98  9.85  9.81  10.23  12.15  14.60  14.74  14.08  14.34 
Valsartan/amlodipine                  0.41  1.80  2.46  2.53  2.48 
Valsartan/amlodipine/hydrochlorothiazide                      0.09  0.84  1.28 
Valsartan/hydrochlorothiazide  0.83  1.19  1.61  2.17  2.88  4.08  5.45  6.57  7.35  7.79  8.07  7.85  8.07 
Total ARB and associations  18.22  25.16  32.32  37.96  44.42  49.72  56.44  61.56  72.33  82.32  86.64  88.20  93.76 
Renin inhibitors
Aliskiren                  0.05  0.83  1.39  1.92  1.26 
Aliskiren/hydrochlorothiazide                      0.17  0.41  0.32 
Total renin inhibitors                  0.05  0.83  1.55  2.32  1.57 
Total C09  80.40  88.50  96.20  102.50  112.20  116.00  127.20  133.00  147.40  160.70  167.10  170.40  181.70 
Total antihypertensive drugs  165.50  176.80  187.40  196.00  210.60  216.00  230.50  239.30  256.50  274.20  280.60  282.70  299.00 

ACE, angiotensin-converting enzyme; ARB, angiotensin receptor blockers.

Footnotes concerning the approval of some of the above agents:

a

Overturned in 2006.

b

Overturned in 2005.

c

Overturned in 2000.

d

Overturned in 2010.

e

Overturned in 2011.

f

Overturned in 2009.

g

Overturned in 2012.

Note: The values represented in the table have been rounded to two decimals.

The upward trends in use had been observed in an earlier study performed in Spain for the period from 1995 to 2001.5 In the present report, the series was extended to cover 2000 to 2012, revealing continued growth, with an increase of 80.7%. This continued growth occurred even though there have been no important changes in the marketing of new antihypertensive medications with respect to the existing groups. It is important to mention the introduction of aliskiren in 2008, of imidapril in 2004, of olmesartan in 2004, and of eplerenone in 2005. The consumption of antihypertensive drugs has increased all over Europe,6 and the growth in Spain is similar to the European average. Germany in central Europe, Finland among the Nordic countries, and Italy in the Mediterranean area were the countries with the widest use in absolute terms. The consumption of antihypertensive drugs in Spain is higher than in other countries such as France and Portugal, and lower than in the United Kingdom and the central European and Nordic countries, with the exception of Luxemburg and Iceland.6

Whether the increase in the intensity of antihypertensive therapy in Spain has contributed to improving blood pressure control is, at best, controversial. Although the results of the various studies may appear to disagree, the evidence suggests that, despite the increase in the consumption of antihypertensive drugs, blood pressure control in Spain continues to be inadequate. The growth observed could be related to the increase in the prevalence of treated hypertension and population aging.1,2 One of the limitations of this study is that it does not enable us to determine whether the reason for the increment in medication use is the increase in the number of hypertensive patients being treated (including mild forms), the increase in the duration of the treatments, or both. In addition, estimation of drug use was based on the DDD, which is a unit of measure that does not necessarily coincide with the dose actually used in clinical practice. Moreover, true consumption of these drugs could be higher than that reflected here since prescriptions issued by private physicians were excluded.

With the recent publication of new clinical practice guidelines recommending less ambitious or more flexible targets for arterial blood pressure levels, the patterns of use could change, resulting in better rates of blood pressure control in the years to come.

FUNDING

Virginia Greciano was the recipient of a grant for training in the Spanish Agency of Medicine and Medical Devices during the course of the present study.

Acknowledgments

We wish to thank the Directorate-General of the Basic Service Portfolio of the Spanish Health and Pharmacy System for providing us with the information on the consumption of medications used in the present report.

References
[1]
S.S. Lim, T. Vos, A.D. Flaxman, G. Danaei, K. Shibuya, H. Adair-Rohani, et al.
A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010.
Lancet., 380 (2012), pp. 2224-2260
[2]
F. Catalá-López, G. Sanfélix-Gimeno, C. García-Torres, M. Ridao, S. Peiró.
Control of arterial hypertension in Spain: a systematic review and meta-analysis of 76 epidemiological studies on 341632 participants.
J Hypertens., 30 (2012), pp. 168-176
[3]
J.M. Baena-Díez, F.J. Félix, M. Grau, A. Cabrera de León, H. Sanz, M. Leal, et al.
Tratamiento y control de los factores de riesgo según el riesgo coronario en la población española del estudio DARIOS.
Rev Esp Cardiol., 64 (2011), pp. 766-773
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J. García del Pozo, E. Ramos Sevillano, F.J. De Abajo, R. Mateos Campos.
Utilización de antihipertensivos en España (1995-2001).
Rev Esp Cardiol., 57 (2004), pp. 241-249
[5]
Agencia Española de Medicamentos y Productos Sanitarios. Metodología utilizada (updated July 2009). Available at: http://www.aemps.gob.es/medicamentosUsoHumano/observatorio/metodologia.htm
[6]
The Organisation for Economic Co-operation and Development (OECD). Health at a Glance 2013: OECD Indicators. Available at: http://www.oecd.org/els/health-systems/Health-at-a-Glance-2013.pdf

The opinions expressed in this report are the responsibility of the authors and, thus, do not necessarily reflect the point of view of the organisms in which they work.

Copyright © 2015. Sociedad Española de Cardiología
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