Community - based study

Transcription

1 : T M Community - based study HIG H (Hy za a r In G ro u p o f Hy p e rt e ns iv e p a t ie nt s ) =A b s t r a c t = S a f e t y an d e f f ic a c y s tu dy o f H y z a ar in p atie n t s w it h h y p e rte n s i on : a c om m u n ity - b a s e d s t u dy HIGH ST UDY GROUP B ackg round : T his study was designed to evaluate efficacy and safety of losartan/ hydrochlorothiazide combined tablet (Hyzaar ) under usual practice condition. Meth ods : In HIGH (Hyzaar In Group of Hypertensive patients) study, patients diagnosed as hypertension were on losartan (50 mg)/ hydrochlorothiazide (12.5 mg) combined tablet (Hyzaar ) once daily for more than 8 weeks. Blood pressure was measured at least twice; prior to administering Hyzaar and 8 weeks after. Blood pressure at week 4 was also measured when possible. Adverse experience was investigated throughout and 14 days following the treatment. Re s ult s : A total of 2428 patients (male : female=4:6, mean age; ) were assessed. On week 8 of treatment, systolic blood pressure and diastolic blood pressure measured were mmhg, mmhg, respectively. These denote 2.1 mmhg, 12.4 mmhg decrease from the baseline levels, respectively. After 8 weeks of treatment, blood pressure in 79% of patients either reached the goal (SBP<140 mmhg and DBP<90 mmhg) or was under control (reduction of diastolic blood pressure 10 mmhg). Gender, presence of diabetes mellitus, body mass index and co- medication of other antihypertensive agents did not affect the degree of blood pressure reduction by Hyzaar treatment. Decrease of diastolic blood pressure in younger age groups under 40 and years- old were significantly greater compared to that of elderly patients over 70 years- old (p <0.05, p <0.01, respectively). Greater decrease of blood pressure (p <0.001) was seen in patients with higher baseline blood pressure. Clinical adverse experience was seen in 26 patients (1.1%) and any specific adverse experience did not exceed 1%. Conclus ion : T reatment of losartan (50 mg)/ hydrochlorothiazide (12.5 mg) is highly effective in lowering blood pressure with few adverse experience in hypertension patients.(korean J Med 62:25-4, 2002) Key W ords : Hyzaar, Losartan, Angiotensin II receptor antagonist, Hypertension T M angiotensin II receptor (losartan) 50 mg (hydrochlorothiazide) 12.5 mg. Angiotensin II receptor 1999 WHO/ ISH : : :, 50, (15-710) E -mail : wonrolee@smc.samsung.co.kr T M post m arketing surv eillance (PMS ) MSD

2 Korean Journal of Medicine : Vol. 62, o. 1, ) angiotensin II receptor angiotensin II receptor AT 1 (angiotensin receptor type 1) angiotensin converting enzyme,. 2 ) ). JC (Joint ational Committee) VI 4 )..., 5-9 ). T M T M T M T M 8,,,. 1. T M. T M. T M, , ,428 8 T M. 2. T M. T M, body mass index (BMI). T M T M. T M T M 8, , , ( 9.6 ) 6, 8 ( 87.2 ) 12. T M 14.. T M 95%, t- test. T M AOVA. p - value

3 HIGH ST UDY GROUP : Safety and efficacy study of Hyzaar in patients with hypertension : a community- based study , %, 40.0% T able 1. B as eline characteris tic s of patient s Sex Female Male Age (years) < Mean (SD) Characteristics Duration of hypertension (years) (n=1052) < Mean (SD) SBP at baseline (mmhg) DBP at baseline (mmhg) BMI (kg/ m 2 ) (n=1449) =2, (60.2%) 966 (9.8%) 14 (5.6%) 459 (18.9%) 809 (.%) 649 (26.7%) 77 (15.5%) 57.5 (11.) 21 (22.0%) 511 (48.6%) 195 (18.5%) 115 (10.9%).8 (4.) (20.1) * 96.6 (12.) * 24.6 (.0) * * Values expressed as mean S.D.; SiSBP, Sitting Systolic Blood Pressure; SiDBP, Sitting Diastolic Blood Pressure; BMI, Body Mass Index ( 1) mmhg, mmhg BMI kg/ m % (15.2%) (5.5%), (4.5%) ( 2). 2. 1) 4, 6, 8, 12 T able 2. Frequency of concomitant disease umber (frequency) =2,428 o. of patients with secondary diagnosis 144 (55.4%) o. of concomitant disease ( 1.0 %) Diabetes mellitus 70 (15.2%) Hyperlipidemia 14 (5.5%) Ischemic heart disease 109 (4.5%) Gastritis 50 (2.1%) Cerebral infarction 49 (2.0%) Fatty liver 48 (2.0%) Osteoporosis 48 (2.0%) Chronic gastritis 45 (1.9%) Cerebrovascular accident 2 (1.7%) T able. Me an chang e in BP at e ach w eek Week Baseline At F ollow - up Visit Change 4 SBP (mmhg) (- 20.5, ) * DBP (mmhg ) (- 10.7, - 9.5) * 6 SBP (mmhg) (- 2.6, ) * DBP (mmhg ) (- 11.8, - 9.4) * 8 SBP (mmhg) (- 24., ) * DBP (mmhg ) (- 1.2, ) * 12 SBP (mmhg) (- 24., ) * DBP (mmhg ) (- 1.1, ) * * p <0.001 within group; SBP, Sitting Systolic Blood Pressure; DBP, Sitting Diastolic Blood Pressure

4 : Figure 1A Figure 1B Fig ure 1. Effect of losartan and hydrochlorothiazide on (A) sitting systolic blood pressure and (B) sitting diastolic blood pressure in patients with hypertension. Each p value denotes comparison to the blood pressure of the previous week. S : not significant, *** : p < / 10.1 mmhg, 21.4/ 10.6 mmhg, 2.1/ 12.4 mmhg, 2.2/ 12. mmhg (, 1). 0 4 (p <0.001), (p <0.001), plateau 8 2, ) JC VI SBP<140 mmhg, DBP<90 mmhg ( ), ( DBP 10 mmhg ), (, ) 79%. SBP< 10 mmhg, DBP<85 mmhg 29 72% ( 4). ),,, BMI,,, BMI ( 5). BMI,. (p <0.01) post hoc ( p <0.05, p <0.01). 4) (Isolated S BP) SBP 160 mmhg, DBP<90 mmhg ( 6). T able 4. Mag nitude of antihy pertensiv e effect T arget SBP (mmhg ) / DBP (mmhg ) ormalized * Controlled ot Controlled T otal All patients SBP < 140 and DBP <90 Patients with DM SBP < 10 and DBP <85 92 (4.9%) 77 (2.4%) 740 (4.9%) 161 (48.9%) 451 (21.2%) 91 (27.7%) *achieved target BP, not normalized and DBP reduction is 10 mmhg, neither normalized nor controlled; SBP, Sitting Systolic Blood Pressure; DBP, Sitting Diastolic Blood Pressure; DM, diabetes mellitus

5 HIGH : TM Community-based study T able 5. Mean chang e in BP after 8 w eeks by g ender, ag e, presence of DM, BMI SBP (mmhg) Sex * Female Age * Male < DM * DM+ BMI (kg/ m 2 ) * < DBP (mmhg) Sex * Female Male Age < DM * DM- DM- DM+ BMI (kg/ m 2 ) * < Baseline After 8 weeks Change (- 24.0, ) (- 24.9, ) (- 27.7, ) (- 26.5, ) (- 24.1, - 21.) (- 25.2, ) (- 2.7, - 19.) (- 24.2, ) (- 24.9, ) (- 24.1, - 21.) (- 24.1, ) (- 27.8, ) +1.0 (- 29.0, +1.0) (- 12.4, ) - 1. (- 14.2, ) (- 17.0, ) (- 14.9, ) (- 1.2, ) (- 12.9, ) (- 11.9, - 9.1) (- 1.1, ) (- 12.6, ) (- 1.1, ) (- 12.8, ) (- 1., - 7.5) (- 14.6, 0.0) * not significant, p <0.01 between groups; SBP, Sitting Systolic Blood Pressure; DBP, Sitting Diastolic Blood Pressure; DM+, presence of diabetes mellitus; DM-, absence of diabetes mellitus; BMI, Body Mass Index 5) ( 7). 6) T M T M

6 Korean Journal of Medicine : Vol. 62, o. 1, 2002 T able 6. Me an chang e in BP after 8 w eeks by ag e in patients w ith is olated s y s tolic hy perten s ion * SBP (mmhg) DBP (mmhg ) Baseline After 8 weeks Change (- 1., - 2.9) (- 48.4, -.6) (- 4.1, - 2.1) (- 2.7, ) (- 4., ) (- 4.4, - 0.8) (- 14.6, - 0.1) (-.4, +2.8) (- 6.8, - 2.0) (- 4.7, +2.) * isolated systolic hypertension defined as DBP < 90 mmhg and SBP 160 mmhg, not significant between groups; SBP, Sitting Systolic Blood Pressure; DBP, Sitting Diastolic Blood Pressure T able 7. Me an chang e in BP after 8 w eeks by deg ree of hy pertens ion * SBP (mmhg) DBP (mmhg ) Baseline After 8 weeks Change (- 0., +4.1) (- 12.9, ) (- 24.9, ) - 9. (- 40.9, - 7.) +1.4 (0.0, +2.8) (- 7.0, - 5.4) (- 1.4, ) (- 21.9, ) * 0: SBP < 140 mmhg and DBP < 90 mmhg 1: 140 mmhg SBP < 160 mmhg or 90 mmhg DBP < 100 mmhg 2: 160 mmhg SBP < 180 mmhg or 100 mmhg DBP < 110 mmhg : 180 mmhg SBP or 110 mmhg DBP p <0.001 between groups; SBP, Sitting Systolic Blood Pressure; DBP, Sitting Diastolic Blood Pressure T able 8. Me an chang e in BP after 8 w eeks by c o - antihy pertentiv e drug Baseline After 8 weeks Change SBP * (mmhg) Hyzaar alone (- 2.9, ) Hyzaar + other antihypertensive (- 25.5, ) DBP * (mmhg) Hyzaar alone (- 12.7, ) Hyzaar + other antihypertensive (- 14.0, ) *not significant between groups; SBP, Sitting Systolic Blood Pressure; DBP, Sitting Diastolic Blood Pressure - 0 -

7 HIGH ST UDY GROUP : Safety and efficacy study of Hyzaar in patients with hypertension : a community- based study T able 9. Mean chang e in BP after 8 w eek by patient Baseline After 8 weeks Change SBP * (mmhg) old patient new patient DBP * (mmhg) old patient new patient (- 21.8, ) (- 1.8, ) (- 11.6, ) (- 17.4, ) * p <0.001 between groups; SBP, Sitting Systolic Blood Pressure; DBP, Sitting Diastolic Blood Pressure T able 10. Drug - related clinic al adv ers e ex periences o. of patients with one or more adverse experience o. of total adverse experience Headache Dizziness Cough Facial flushing Erectile dysfunction ausea Palpitation Polyuria Muscle cramping Chest discomfort eck stiffness ( 8). 2% atenolol 6.1%, amlodipine 5.6%, nifedipine.0%, diltiazem 2.2% (data not shown).. (p <0.001) ( 9). umber (Frequency %) =2, (1.1%) 1 (1.28%) 8 (0.%) 7 (0.29%) 5 (0.21%) 2 (0.08%) 2 (0.08%) 2 (0.08%) 1 (0.04%) 1 (0.04%) 1 (0.04%) 1 (0.04%) 1 (0.04%).,, 1% % ( 10). community- based study,. Communitybased study, - 1 -

8 : community- based study,, 10 ).,,. (bias) community- based study / 12.4 mmhg. 8 plateau 8 8, 9 ) % / 140/ 90 mmhg 10 mmhg mg 55% / 140/ 90 mmhg 11).,, BMI. 40, ) 1 )... / 140/ 90 mmhg ( ). 12 ). 12 ) mmhg 90 mmhg.. T M

9 HIGH : TM Community-based study,. 11) 1%. 50 mg 12.5 mg T M 1 1. :. : 50 mg 12.5 mg : 2,428 ( : =4:6, ; ) mmhg, mmhg 2.1 mmhg, 12.4 mmhg. 8 (SBP< 140 mmhg DBP<90 mmhg) 79%.,, BMI, ( p <0.05, p <0.01) (p <0.001). 1.1% 1%. : 50 mg 12.5 mg 1 1. ACKOWLEDG EMET Major Study Centers & Investigators of HIGH STUDY GROUP :, ;,,, ;, ; ; ; ; ; ;, ; ; ;, ; ;, ; ;, ; R E F E R E C E S 1) 1999 World Health Organization- International Society of Hypertension. Guidelines f or the management of Hyp ertension. J Hyp ertens 17:151-18, ) Laragh JH. H istorical p ersp ective on renin system blockade in the treatment of hypertension. A m J Hyp ertens 5:207S -208S, 1992 ) MacKay JH, Arcuri KE, Goldberg AI, Snapinn SM, Sweet CS. Losartan and low- does hydrochlorothiaz ide in patients with essential hyp ertension. A rch Intern M ed 156: , ) Joint ational Committee on Prevention, Detection. E valuation and Treatment of H igh B lood P ressure. The sixth report of the Joint ational Committee on P revention, D etection, E valuation and T reatment of H igh B lood Pressure (J C VI). A rch Intern M ed 157: , ) Owens P, Kelly L, allen R, Ryan D, Fitzgerald D, O'Brien E. Comparison of antihyp ertensive and metabolic effects of losartan and losartan in combination with hydrochlorothiaz ide: a randomiz ed controlled trial. J Hyp ertens 18:9-45, ) Ruilope LM, Simpson RL, T oh J, Arcuri KE, Goldberd AI, Sweet CS. Controlled trial of losartan - -

10 Korean Journal of Medicine : Vol. 62, o. 1, 2002 given concomitantly with diff erent doses of hydrochlorothiazide in hypertensive patients. B lood Press 5:2-40, ) Oparil S, Barr E, Elkins M, Liss C, Vrecenak A, Edelman J. Eff icacy, tolerability, and effects on quality of life of losartan, alone or with hydrochlorothiazide, versus amlodipine, aloe or with hydrochlorothiaz ide, in patients with essential hyp ertension. Clin Ther 18: , ) Weir MR, Elkins M, Liss C, Vrecenak AJ, Barr E, Edelman JM. Eff icacy, tolerability, and eff ects on quality of lif e of losartan, alone or with hydrochlorothiaz ide, versus nif edip ine GI TS in patients with essential hyp ertension. Clin Ther 18: , ) Conlin PR, Elkins M, Liss C, Vrecenak AJ, Barr E, Edelman JM. A study of losartan, alone or with hydrochlorothiaz ide vs nif edip ine GI TS in elderly patients with diastolic hypertension J Hum Hyp ertens 12:69-699, ) Moore MA, Edelman JM, Gazdick LP, Vrecenak AJ, DeLucca P, Flaherty JT. Choice of initial hyp erten sive medication may inf luence the extent to which patients stay on therapy:a community based study of a losartan- based regimen vs usual care, H igh B lood P ress 7: , ) Goldberg AI, Dunlay MC, Sweet CS. Saf ety and tolerability of losartan p otassium, an angiotensin II recep tor antagonist, compared with hydrochlorothiaz ide, atenolol, felodip ine ER, and angiotensinconverting enzyme inhibitors f or the treatment of systemic hyp ertension. A m J Cardiol 75:79-795, ),,,,,,,,,,,,,,,,,,,,,,,,,,,,. Losartan. 6: , ),,,,,,,,,,.,. 28:19-20,