El documento resume las principales guías de tratamiento de la hipertensión arterial. Indica que la monoterapia rara vez es suficiente y que generalmente se requieren combinaciones de dos o más fármacos antihipertensivos para lograr los objetivos de presión arterial. Las combinaciones fijas simplifican el tratamiento y pueden mejorar el cumplimiento. Estudios demuestran que la combinación de bloqueadores del sistema renina-angiotensina con calcioantagonistas o diuréticos son efectivas en pacientes de alto riesgo cardiovascular.
2. 35-64 60-69 70-79 > 79 * Banegas JR, et al. Hypertension 1998; 32: 998-1002 (datos de 35-64 años) † Banegas JR, et al. Hypertension 2002; 20: 2157-64 (datos en > 60 años) Prevalencia de HTA en España ( 140/90 mmHg) % Años * † † †
3. Prevalencia de la hipertensión arterial y porcentaje de hipertensos tratados JAMA. 2003;289:2363-2369 46,8 26,8 37,7 32 55,3 26 27,8 52,5 Edad 35-64 años, ambos sexos
4. Riesgo mortalidad CV PAS/PAD (mm Hg) 0 1 2 3 4 5 6 7 8 115/75 135/85 155/95 175/105 El riesgo de mortalidad CV se duplica con cada incremento de 20/10mm Hg de presión arterial * Lewington S et al. Lancet. 2002;360:1903-1913. Chobanian AV et al. JAMA. 2003;289:2560-2572. CV, cardiovascular; PAS, presión arterial sistólica; PAD, presión arterial diastólica. *Individuos de 40-69 años de edad, empezando en PA 115/75 mm Hg.
5.
6. Objetivos de PA en las diferentes guías DM ERC, CV < 130/80 DM ERC, CV < 130/80 DM < 130/80 DM ERC < 130/80 Poblaciones especiales < 140/85 PAS < 140 < 140/90 < 140/90 General BHS IV 2004 WHO-ISH ESH/ESC 2007 JNC 7
11. La monoterapia es inadecuada en el 40-60% de pacientes hipertensos Materson et al. Am J Hypertens. 1993;8:189-192. 0 20 40 60 80 ACA BB Diurético Alfa 1 antagonista IECA Alfa 2 agonista Placebo 50% respuesta Respuesta: PAD < 95 mm Hg después de un año de tratamiento Porcentaje respuesta
12. Más de 2 fármacos necesarios para lograr los objetivos de presión arterial AASK PAM <92 PA objetivo (mmHg) Número de antihipertensivos 1 UKPDS PAD <85 ABCD PAD <75 MDRD PAM <92 HOT PAD <80 Ensayo 2 3 4 PAM: Presión arterial media IDNT PAS <135/PAD <85 ALLHAT PAS <140/PAD <90 Bakris et al. Am J Kidney Dis 2000;36:646–61 Lewis et al. N Engl J Med 2001;345:851–60 Cushman et al. J Clin Hypertens 2002;4:393–404
13. Cifras de presión objetivo y número de fármacos necesarios 2,3 137/78 53% 60% 32% DM <140/90 (<130/80) 164/95 ASCOT 4 140/77 NR ≤ 135/85 159/87 IDNT 3.75 140/74 NR <140/90 153/82 RENAAL PAM <92 PAM<107 PAD 90 PAD 85 PAD 80 PAM<92 PAD<75 PAD<85 <140/90 PA objetivo (mmHg) (en DM) 3.04 2.4 3.25 3.6 2.75 2.6 2 Nº fármacos 128/78 141/85 143/85 141/83 140/81 PAD 93 132/78 144/82 135/75 PA lograda 52 39 19 NR NR 56 66 % pacientes con PA objetivo 152/95 170/105 PAD 95 155/98 159/94 157/90 145/83 PA inicial (mmHg) AASK HOT MDRD ABCD UKPDS ALLHAT Ensayo
14.
15. Elegir entre: Elevación considerable de la PA R CV alto/muy alto Objetivo de reducción de PA Elevación leve de la PA RCV bajo o moderado Objetivos convencionales de PA Combinación de 2 Fa dosis bajas F único a dosis bajas Si no se alcanza el objetivo de PA Si no se alcanza el objetivo de PA Añadir un tercer F a dosis bajas F anterior a dosis máxima Combinación anterior a dosis máxima Cambiar a otro F a dosis bajas Monoterapia a dosis máxima Combinación de 2-3 F a dosis máxima Combinación de 2-3 F a dosis máxima ESH-ESC 07: Elección entre monoterapia y combinación ESH Guidelines. J Hypertens 2007;25:1105-1187.
16.
17. Efecto de las combinaciones fijas sobre el cumplimiento Am J Med 2007;120:713-719 11925 pacientes con combinaciones fijas vs 8317 con componentes libres Las fijas reducen en un 24% el no cumplimiento respecto las libres (p<0,001)
18.
19. Calcioantagonista o tiazida añadidos al bloqueo del SRA en pacientes de riesgo elevado. Estudio ACCOMPLISH Jamerson et al. N Engl J Med 2008;359:2417-28. N=11506 Edad media 68 años Seguimiento 3 años AML TZ PA inicial 145/80 145/80 PA final 131/73 132/74
20. Calcioantagonista o tiazida añadidos al bloqueo del SRA en pacientes de riesgo elevado. Estudio ACCOMPLISH Jamerson et al. N Engl J Med 2008;359:2417-28.
21. Efectos complementarios entre IECA o ARAII y calcioantagonistas Vasodilatador Arterial > venular Activación del SRAA Edemas Efecto diurético natriurético Vasodilatador Arterial venular Calcioantagonista ARAII o IECA Efecto antihipertensivo Inhibición Aldo Natriuresis/diuresis Calcioantagonista ARAII o IECA
22. Valsartán Irbesartán Candesartán Telmisartán Eprosartán Olmesartán Losartán Placebo Cambio en PAS (mmHg) Cambio en PAD (mmHg) Superioridad de Olmesartán frente a otros ARAII en el control de la PA de 24 horas Fabia et al. J Hypertens 2007;25:1327–36 Revisión sistemática de la literatura 0 -2 -4 -6 -8 -10 -12 -14 0 -2 -4 -6 -8 -10
23. Eficacia de Olmesartán en el control de la presión arterial a < 130/80mmHg GilesTD, et al J Clin Hypertens (Greenwich) 2007; 9: 187-95 Smith DH et al Am J Cardiovasc Drugs 2005; 5: 41-50 PA <140/90 PA < 130/80 Olmesartán 20 mg Losartán 50 mg Valsartán 80 mg Irbesartán 150 mg Pacientes que consiguen objetivos de PA (%)
24. Eficacia de Olmesartán/HCTZ durante las 24 horas J Clin Hypertens 2009;11:411–421 . N=178, > 65 años, PA 165/87. Titulación OLM 20 a 40 más HCTZ 12,5 a 25 mg hasta PA < 120/70 PAS PAD Ultimas horas del intervalo de dosis 6 horas 4 horas 2 horas Día (8am-4pm) Noche (10pm-6am) 24 horas Cambio de PA ambulatoria (mmHg) a la semana 12 respecto al basal
25. Eficacia de la combinación fija Olmesartán/amlodipino: estudio COACH Chrysant SG et al. Clin Ther 2008;30:587-604 N=1940, edad media 54 años. PAD basal entre 95-120 mmHg 8 semanas Máximo efecto sobre la PA observado a las 2 semanas Cambio de PA en sedestación a la semana 8 (mm Hg)
26. Eficacia de la combinación fija Olmesartán/amlodipino: estudio COACH Chrysant SG et al. Clin Ther 2008;30:587-604 % de pacientes consiguen umbral PA a la semana 8 (mm Hg) Rango Presión Arterial (mm Hg)
27. Eficacia de la combinación Olmesartán/amlodipino en pacientes no controlados con amlodipino en monoterapia Sanford M & Kean SJ Drugs 2009;69:717-729 Volpe et al Clin Drug Invest 2009;29:11-25 N=755 no controlados con 5 mg amlodipino: adición de placebo a olmesartán 8 semanas. Pacientes con PA >140/90 se realizó titulación de dosis 8 semanas más. * p<0,0001 Estudio VOLPE PAS PAD
28. Mourad. Clin Drug Invest 2009;29:419–25 140 – <150 150 – <160 160 – <170 170 – <180 180 – <190 190 – <200 120 140 160 180 200 PASse a la Semana 0 y fin tratamiento (mmHg) Semana 0 Fin tratamiento -54.5 -47.7 -38.9 -32.1 -23.2 -14.4 (n=60) (n=112) (n=258) (n=96) (n=44) (n=8) 144.9 130.5 154.4 131.2 163.6 131.5 173.9 135.0 184.0 136.3 193.8 139.3 Estudio VOLPE Eficacia de la combinación Olmesartán/amlodipino en pacientes no controlados con amlodipino (post hoc estudio VOLPE)
29. Reducción del edema periférico con Olmesartán/amlodipino Sanford M & Kean SJ Drugs 2009;69:717-729
30. La adición de Olmesartán a Amlodipino 10 mg reduce la incidencia y severidad del edema proporcional a la dosis Pacientes con edema* (%) Tasa ajustada para el placebo * P = 0,032; ** P = 0,011 frente a monoterapia amlodipino 10 mg *** P = 0,009 para el aumento de la dosis de olmesartán * ** *** Chrysant y cols. Clin Ther 2008;30:587–604 AML OLM/AML Reducción del edema periférico con Olmesartán/amlodipino Estudio COACH
31. Efecto de Olmesartán/amlodipino sobre la inflamación Martínez-Martin FJ et al. 18th Meeting ESH, Berlin 14-19 June 2008 Estudio OLAS; N=120 pacientes con síndrome metabólico, entre 28 y 75a Aleatorizados a Olmesartán/amlodipino (OA 20/5) u Olmesartán/HCTZ (OH 20/12,5) 24 semanas
32. Efecto de Olmesartán/amlodipino sobre la resistencia a la insulina Estudio OLAS; N=120 pacientes con síndrome metabólico, entre 28 y 75a Aleatorizados a Olmesartán/amlodipino (OA 20/5) o Olmesartán/HCTZ (OH 20/12,5) 24 semanas Martínez-Martin FJ et al. 18th Meeting ESH, Berlin 14-19 June 2008
33.
34.
35.
Notas del editor
BP Reductions as Small as 2 mmHg Reduce the Risk of CV Events by Up to 10% Data from a meta-analysis of 61 prospective, observational studies have also provided powerful evidence that throughout middle and old age, BP is strongly and directly related to vascular mortality. 7 Perhaps most striking are the practical implications of these data: even a small, 2 mmHg fall in mean systolic BP would be associated with large absolute reductions in premature deaths and disabling strokes. 7 As shown here, a 2 mmHg lower mean systolic BP could lead to a 7% lower risk of ischemic heart disease (IHD) death and a 10% lower risk of stroke death. Throughout middle and old age, usual blood pressure is strongly and directly related to vascular (and overall) mortality, without any evidence of a threshold down to at least 115/75 mm Hg 7 Prospective Studies Collaboration. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet. 2002;360:1903-1913.
Possible combinations between some classes of antihypertensive drugs. The preferred combinations in the general hypertensive population are represented as thick lines. The frames indicate classes of agents proven to be beneficial in controlled intervention trials.
ASCOT=Anglo-Scandinavian cardiac outcomes trial; ALLHAT= Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial; UKPDS=United Kingdom Prospective Diabetes Study; ABCD= Appropriate Blood Pressure Control in Diabetes trial; MDRD=Modification of Diet in Renal Disease; HOT=Hypertension Optimal Treatment; IDNT=Irbesartan Diabetic Nephropathy Trial; RENAAL=Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan; AASK=African American Study of Kidney Disease; PA= presión arterial; PAS=presión arterial sistólica; PAD=presión arterial diastólica; PAM= presión arterial media; DM= diabetes mellitus Dahlöf B et al Lancet 2005:366:895-906; ALLHAT JAMA 2002;288:2981-2997; UK Prospective Diabetes Study Group BMJ 1998;317:713-720; Estacio RO NEJM 1998;338:645-652; Peterson JC Ann Intern Med. 1995;123:754; Hansson L et al LAncet 1998;351:1755-1762; Wright JT et al JAMA 2002;288:2421-2431; Lewis EJ et al N Engl J Med 2001;345:851-60; Brenner BM et al N Engl J Med 2001;345:861-9;
Aquí tenéis el algoritmo de las Guías ESH/ESC para elegir el tratamiento inicial de un paciente hipertenso: - recomienda comenzar con una monoterapia o con un tratamiento combinado a dosis bajas - si el tratamiento elegido no es eficaz, se incrementarán las dosis o se modificará el tratamiento o se añadirá otro - si ni siquiera estas intervenciones consiguen reducir la tensión arterial hasta el valor buscado, será necesario iniciar un tratamiento combinado con dos o tres fármacos.
La evidencia sugiere que la mayoría de los pacientes hipertensos necesitan combinaciones de antihipertensivos para alcanzar los objetivos óptimos de cifras de presión arterial. La adherencia baja a la medicación contribuye al hiato entre la práctica y los resultados, en el que se implementan las guías, pero los beneficios esperados no se alcanzan. Las combinaciones fijas aportan un arsenal potente en el manejo de las enfermedades crónicas. El riesgo de no cumplimiento al régimen terapéutico se reduce entre un 24 y un 26% con las combinaciones fijas respecto a los componentes libres.
Background The optimal combination drug therapy for hypertension is not established, although current U.S. guidelines recommend inclusion of a diuretic. We hypothesized that treatment with the combination of an angiotensin-converting–enzyme (ACE) inhibitor and a dihydropyridine calcium-channel blocker would be more effective in reducing the rate of cardiovascular events than treatment with an ACE inhibitor plus a thiazide diuretic. Methods In a randomized, double-blind trial, we assigned 11,506 patients with hypertension who were at high risk for cardiovascular events to receive treatment with either benazepril plus amlodipine or benazepril plus hydrochlorothiazide. The primary end point was the composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, hospitalization for angina, resuscitation after sudden cardiac arrest, and coronary revascularization. Results The baseline characteristics of the two groups were similar. The trial was terminated early after a mean follow-up of 36 months, when the boundary of the prespecified stopping rule was exceeded. Mean blood pressures after dose adjustment were 131.6/73.3 mm Hg in the benazepril–amlodipine group and 132.5/74.4 mm Hg in the benazepril–hydrochlorothiazide group. There were 552 primary-outcome events in the benazepril–amlodipine group (9.6%) and 679 in the benazepril–hydrochlorothiazide group (11.8%), representing an absolute risk reduction with benazepril–amlodipine therapy of 2.2% and a relative risk reduction of 19.6% (hazard ratio, 0.80, 95% confidence interval [CI], 0.72 to 0.90; P<0.001). For the secondary end point of death from cardiovascular causes, nonfatal myocardial infarction, and nonfatal stroke, the hazard ratio was 0.79 (95% CI, 0.67 to 0.92; P = 0.002). Rates of adverse events were consistent with those observed from clinical experience with the study drugs. Conclusions The benazepril–amlodipine combination was superior to the benazepril–hydrochlorothiazide combination in reducing cardiovascular events in patients with hypertension who were at high risk for such events. (ClinicalTrials.gov number, NCT00170950.)
Background The optimal combination drug therapy for hypertension is not established, although current U.S. guidelines recommend inclusion of a diuretic. We hypothesized that treatment with the combination of an angiotensin-converting–enzyme (ACE) inhibitor and a dihydropyridine calcium-channel blocker would be more effective in reducing the rate of cardiovascular events than treatment with an ACE inhibitor plus a thiazide diuretic. Methods In a randomized, double-blind trial, we assigned 11,506 patients with hypertension who were at high risk for cardiovascular events to receive treatment with either benazepril plus amlodipine or benazepril plus hydrochlorothiazide. The primary end point was the composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, hospitalization for angina, resuscitation after sudden cardiac arrest, and coronary revascularization. Results The baseline characteristics of the two groups were similar. The trial was terminated early after a mean follow-up of 36 months, when the boundary of the prespecified stopping rule was exceeded. Mean blood pressures after dose adjustment were 131.6/73.3 mm Hg in the benazepril–amlodipine group and 132.5/74.4 mm Hg in the benazepril–hydrochlorothiazide group. There were 552 primary-outcome events in the benazepril–amlodipine group (9.6%) and 679 in the benazepril–hydrochlorothiazide group (11.8%), representing an absolute risk reduction with benazepril–amlodipine therapy of 2.2% and a relative risk reduction of 19.6% (hazard ratio, 0.80, 95% confidence interval [CI], 0.72 to 0.90; P<0.001). For the secondary end point of death from cardiovascular causes, nonfatal myocardial infarction, and nonfatal stroke, the hazard ratio was 0.79 (95% CI, 0.67 to 0.92; P = 0.002). Rates of adverse events were consistent with those observed from clinical experience with the study drugs. Conclusions The benazepril–amlodipine combination was superior to the benazepril–hydrochlorothiazide combination in reducing cardiovascular events in patients with hypertension who were at high risk for such events. (ClinicalTrials.gov number, NCT00170950.)
La vasodilatación y, en parte el efecto natriurético de los calcioantagonistas activan el SRAA, lo cual limita su efecto antihipertensivo al constituir esta activación un mecanismo contrarregulador a la reducción de la presión arterial. El bloqueo del SRAA mediante IECA o ARAII elimina este efecto, además de contribuir a la inhibición de la aldosterona y por tanto favorecer la natriuresis. Asimismo, la vasodilatación predominante arteriolar de los calcioantagonistas favorece la aparición de edemas maleolares, efecto que se reduce al añadir IECA o ARAII, sobre todo éstos últimos gracias a su capacidad de dilatación tanto arteriolar como venular.
Proportion of patients achieving combined systolic blood pressure (BP)/diastolic BP (DBP) goal in comparative trials of angiotensin II type 1 receptor antagonists (Giles et al.[14] and Smith et al.[42]). ( a ) Proportion of patients achieving the BP goal of <140/ 90 mmHg (cuff measurement) was assessed in a double-blind, randomized, forced-titration study[14] in which patients with primary hypertension (cuff DBP between 100 and 115 mmHg) initiated therapy with olmesartan medoxomil (OLM) 20 mg/day, losartan (LOS) 50 mg/day or valsartan (VAL) 80 mg/day, uptitrated at predetermined intervals to OM 40 mg/day, LOS 100 mg/day and VAL 160 or 320 mg/day by the end of the 12-week active treatment period. ( b ) Proportion of patients achieving the BP goal of <130/80 mmHg (ambulatory BP monitoring [ABPM] measurement) was assessed in a double-blind, parallel-group, randomized study in which patients with essential hypertension (cuff DBP between 100 and 115 mmHg) received OM 20 mg/day, LOS 50 mg/day, VAL 80 mg/day or irbesartan (IRB) 150 mg/day for 8 weeks (reproduced from Smith et al.,[42] with permission). * p < 0.05 vs LOS and VAL.
This study examined the effect of olmesartan medoxomil (OM) hydrochlorothiazide (HCTZ) on mean 24-hour ambulatory blood pressure, mean seated cuff (Se) blood pressure (BP), and SeBP goal achievement in elderly (65 years and older) patients with hypertension. After a 2- to 3-week placebo run-in period, patients received OM 20 mg, up-titrated to OM 40 mg, and then added HCTZ 12.5 mg to 25 mg in a stepwise manner at 3-week intervals if SeBP remained 120 ⁄ 70 mm Hg. The primary end point was change from baseline in mean 24-hour ambulatory systolic BP. At study end, mean 24-hour ambulatory BP had decreased by 25.7 ⁄ 12.3 mm Hg (n=150) and mean SeBP by 25.4 ⁄ 10.5 mm Hg (n=176; all P < .00001 vs baseline). Drug-related treatment-emergent adverse events, most commonly dizziness (3.4%), hypotension (2.2%), and headache (1.1%), were observed in 11.8% of patients. An OM-based treatment algorithm effectively lowers BP in an elderly patient population throughout the 24-hour dosing interval without compromising tolerability. J Clin Hypertens (Greenwich). 2009;11:411–421. ª 2009 Wiley Periodicals, Inc.
Background: Hypertension guidelines recommend the use of 2 agents having complementary mechanisms of action when >1 agent is needed to achieve blood pressure (BP) goals. Objective: The aim of this study was to compare the efficacy and tolerability of combinations of olmesartan medoxomil (OM) and amlodipine besylate with those of the component monotherapies in patients with mild to severe hypertension. Methods: This was a multicenter, randomized, doubleblind, placebo-controlled, factorial study. Patients who were naive to antihypertensive therapy or who underwent a washout of previous antihypertensive therapy for up to 2 weeks and had a seated diastolic BP (SeDBP) of 95 to 120 mm Hg were randomized to receive 1 of the following for 8 weeks: OM 10, 20, or 40 mg; amlodipine (AML) 5 or 10 mg; each possible combination of OM and AML; or placebo. The primary end point was the change from baseline in SeDBP at week 8, with secondary end points including the change in seated systolic blood pressure (SeSBP), the proportion of patients reaching the BP goal (<140/90 mm Hg; <130/80 mm Hg for patients with diabetes), and the proportions of the intention-to-treat population reaching BP thresholds of <120/80, <130/80, <130/85, and <140/90 mm Hg. Safety and tolerability were also evaluated, with a particular focus on the incidence and severity of edema. Results: Of the 1940 randomized patients, 54.3% were male. The mean age of the study population was 54.0 years and 19.8% were aged >65 years. The mean baseline BP was 164/102 mm Hg, and 79.3% of patients had stage 2 hypertension. Combination therapy with OM and AML was associated with dosedependent reductions in SeDBP (from -13.8 mm Hgwith OM/AML 10/5 mg to -19.0 mm Hg with OM/AML 40/10 mg) and SeSBP (from -3.6 mm Hg with OM/AML 20/5 mg to -30.1 mm Hg with OM/AML 40/10 mg) that were significantly greater than the reductions with the corresponding component monotherapies (P < 0.001). At week 8, the number of patients achieving the BP goal ranged from 57 of 163 (35.0%) to 84 of 158 (53.2%) in the combinationtherapy groups, from 32 of 160 (20.0%) to 58 of 160 (36.3%) in the OM monotherapy groups, and from 34 of 161 (21.1%) to 53 of 163 (32.5%) in the AML monotherapy groups (P < 0.005, combination therapies vs component monotherapies), compared with 14 of 160 (8.8%) in the placebo group. Achievement of the BP thresholds was highest in the combinationtherapy groups, with 56.3% and 54.0% of patients achieving a BP <140/90 mm Hg with OM/AML 20/10 and 40/10 mg, respectively. Combination therapy was generally well tolerated, and no unexpected safety concerns emerged in the course of the study. The most common adverse events were edema (ranging from 9.9% [OM 20 mg] to 36.8% [AML 10 mg], compared with 12.3 % with placebo) and headache (ranging from 2.5% [OM/AML 10/5 mg] to 8.7% [OM 20 mg], compared with 14.2% with placebo). Conclusion: The combination of OM and AML was effective and well tolerated in this adult population with hypertension.
Background: Hypertension guidelines recommend the use of 2 agents having complementary mechanisms of action when >1 agent is needed to achieve blood pressure (BP) goals. Objective: The aim of this study was to compare the efficacy and tolerability of combinations of olmesartan medoxomil (OM) and amlodipine besylate with those of the component monotherapies in patients with mild to severe hypertension. Methods: This was a multicenter, randomized, doubleblind, placebo-controlled, factorial study. Patients who were naive to antihypertensive therapy or who underwent a washout of previous antihypertensive therapy for up to 2 weeks and had a seated diastolic BP (SeDBP) of 95 to 120 mm Hg were randomized to receive 1 of the following for 8 weeks: OM 10, 20, or 40 mg; amlodipine (AML) 5 or 10 mg; each possible combination of OM and AML; or placebo. The primary end point was the change from baseline in SeDBP at week 8, with secondary end points including the change in seated systolic blood pressure (SeSBP), the proportion of patients reaching the BP goal (<140/90 mm Hg; <130/80 mm Hg for patients with diabetes), and the proportions of the intention-to-treat population reaching BP thresholds of <120/80, <130/80, <130/85, and <140/90 mm Hg. Safety and tolerability were also evaluated, with a particular focus on the incidence and severity of edema. Results: Of the 1940 randomized patients, 54.3% were male. The mean age of the study population was 54.0 years and 19.8% were aged >65 years. The mean baseline BP was 164/102 mm Hg, and 79.3% of patients had stage 2 hypertension. Combination therapy with OM and AML was associated with dosedependent reductions in SeDBP (from -13.8 mm Hgwith OM/AML 10/5 mg to -19.0 mm Hg with OM/AML 40/10 mg) and SeSBP (from -3.6 mm Hg with OM/AML 20/5 mg to -30.1 mm Hg with OM/AML 40/10 mg) that were significantly greater than the reductions with the corresponding component monotherapies (P < 0.001). At week 8, the number of patients achieving the BP goal ranged from 57 of 163 (35.0%) to 84 of 158 (53.2%) in the combinationtherapy groups, from 32 of 160 (20.0%) to 58 of 160 (36.3%) in the OM monotherapy groups, and from 34 of 161 (21.1%) to 53 of 163 (32.5%) in the AML monotherapy groups (P < 0.005, combination therapies vs component monotherapies), compared with 14 of 160 (8.8%) in the placebo group. Achievement of the BP thresholds was highest in the combinationtherapy groups, with 56.3% and 54.0% of patients achieving a BP <140/90 mm Hg with OM/AML 20/10 and 40/10 mg, respectively. Combination therapy was generally well tolerated, and no unexpected safety concerns emerged in the course of the study. The most common adverse events were edema (ranging from 9.9% [OM 20 mg] to 36.8% [AML 10 mg], compared with 12.3 % with placebo) and headache (ranging from 2.5% [OM/AML 10/5 mg] to 8.7% [OM 20 mg], compared with 14.2% with placebo). Conclusion: The combination of OM and AML was effective and well tolerated in this adult population with hypertension.
Contrariamente a otros estudios en el COACH se hizo una búsqueda activa del edema. Se hizo una graduación de la intensidad en una escala numérica. Para evaluar si la tasa de edema se relacionaba on la dosis se hizo“ post hoc“ un análisis de la tendencia (Cochran-Armitage).La mayor incidencia y severidad de edema se observaron con la dosis más alta de AML. Tanto la severidad como la incidiencia de edema se redujeron cuando estas dosis de AML se asociaron a OLM,comprobándose un reduccion significativa a mayores dosis de OLM
Mientras que la combinación olmesartan/hctz era capaz de reducir significativamente los niveles de PCR e ICAM1, la combinación olmesartan/amlodipino reducía los niveles de todos los parámetros estudiados. Las dosis se duplicaron en aquellos pacientes con PAS >139 mmHg
En ambos grupos se consiguió una reducción equivalente de la presión arterial sistólica y diastólica y de la excreción urinaria de albúmina. Las dosis se duplicaron en aquellos pacientes con PAS >139 mmHg