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1 Maximizing Hypertension Therapy in Elderly Patients Konkuk University Hospital KyuHyung Ryu, MD, PhD, FACC

2 노인의료비지출 10 년간 8 배증가 국민건강보험공단 건강보험주요통계발간 지난해총 20 조 9,316 억원중 5조 5,989 억원을노인급여비로사용 노인인구 5.8%(1996) 8.6%(2006), 8.6%(2006), 노인급여비지출 13.5%(1996) 26.7%(2006) 매년 1 조원씩증가추세, 고령사회에대비한노인의료대책법제화시급

3 연령증가에따라건강보험재정 ( 건강보험비적용제외 ) 지출크게증가 특히 65 세이상노인은 10 년동안 8.3 배증가 96년 06년 증가지수 - 건강보험급여비 ( 계 ) 4조 9,644억원 20조 9,316억원 4.2배 65 세이상 6,716 억원 5조 5,989 억원 8.3 배 65세미만 4조 2,928억원 15조 3,327억원 3.6배

4 연령대별 2006 년 1 인당건강보험진료비 157, ,893 75,704 43,029 17,916 23,002 29,995 43,665 9 세이하 10 대 20 대 30 대 40 대 50 대 60 대 70 세이상

5 연령증가에따른심장혈관계변화 심장비대 - 좌심실확장기능저하 판막과지지조직의변성 - 대동맥판막협착증, 승모판막폐쇄부전증 동방결절주위의섬유화 - 부정맥 운동에따른맥박수변화 - 조절능력감소 압력수용체반사기능저하 자율신경계장애

6 혈관변화 혈관벽탄성섬유감소 죽상경화증, 석회화 동맥의예비기능감소 수축기고혈압과맥압증가 좌심실비후의주된원인

7 노인성주요심혈관질환 고혈압 심부전 부정맥 ( 심방세동, 동성기능저하 ) 판막질환 허혈성심장질환 뇌졸증

8 고혈압 연령증가에따라증가 국내성인의 30%, 65 세이상 50% 이상 원인 동맥경화 죽상동맥경화성신동맥고혈압 일차성알도스테론혈증 가성고혈압 ( 심한혈관경화 )

9 특징 수축기고혈압 ( 관상동맥질환, 심부전, 뇌졸증등의사망예측지표 ) 맥압증가 ( 혈관의순응도저하 심혈관계합병증의위험지표 ) 아침고혈압, 오후정상혈압 약물에의한기립성저혈압

10 동반질환 ( 당뇨병, 신장기능장애, 만성폐쇄성폐질환 ) 심장의예비능감소 작은부하에쉽게심부전발생

11 치료효과 높은연령일수록사망률과유병율 감소효과가크다. 생활개선요법 ( 염분, 알코올섭취감소, 야채식이요법, 금연, 규칙적인유산소운동 )

12 국내고혈압의성별, 연령별유병률 유병률 (%) 유병률 (JNC 6 기준 ) 년남자 1990 년여자 1998 년남자 1998 년여자 연령군

13 The world population is aging Age Males Females Age Males Females % of population % of population United Nations 1999

14 미국고혈압유병율 Prevalence of High Blood Pressure in USA Age 20 and Older by Age and Sex NHANES IV: Source: Health, United States, 2003, CDC/NCHS.

15 미국고혈압치료율 Extent of Awareness, Treatment and Control of High Blood Pressure by Age NHANES IV: Source: JAMA 2003; 290:

16 노년기고혈압 연령의증가와함께고혈압유병율도증가 55 세에혈압이정상인경우도이후고혈압이발생할확률은 90% 이상 수축기혈압을 140 mmhg 이하로조절하는것은 50 세이상에서심혈관계합병증예방을위해더욱중요

17 옛날이야기 허봉사나리제혈압이 160/90 이라는데어찌해야하나요? 나이가들면당연히윗자리혈압이오르는것이니너무근심치말게

18 Jonit National Committee-7 (JNC-7, 2003) - 노인에서수축기혈압의중요성을강조 - U.S. Department of Health and Human Services New Features & Key massage For persons over age 50, SBP is a more important than DBP as CVD risk factor. National Institutes of Health National Heart, Lung, and Blood Institute Starting at 115/75 mmhg, CVD risk doubles with each increment of 20/10 mmhg throughout the BP range. Persons who are normotensive at age 55 have a 90% lifetime risk for developing HTN. Those with SBP mmhg or DBP mmhg should be considered prehypertensive who require healthpromoting lifestyle modifications to prevent CVD.

19 노인고혈압 -2 가지임상형태 - 수축기고혈압과이완기고혈압의혼합형태 ( 일차성고혈압의연장 ) 고립성수축기고혈압 (ISH, isolated systolic hypertension in old age) 노인에서중요한문제!

20 노인고립성수축기고혈압 -isolated systolic hypertension in old age- 나이가많아질수록 ISH 의유병률은증가한다 과거정상적인반응으로간주 소극적치료 큰수용혈관 (large capacitance vessel) 의신전성 (distensibilty) 과탄성도 (elasticity) 의감소 맥압의상승 미만성동맥경화를시사

21 연령증가에따른유병률의증가 The Natural History of Borderline Isolated Systolic Hypertension Sagie A, et al. N Engl J Med 1993;329 Men Women Borderline isolated systolic hypertension: SBP , DBP <90mmHg Isolated systolic hypertension: SBP 160, DBP <90mmHg

22 기타노인고혈압의특성 기립성저혈압 식사후저혈압 백의효과 (White-coat effect) 가성고혈압 (pseudohypertension)

23 기립성저혈압 Prevalence of Postural Hypotension at Baseline in the Systolic Hypertension in Elderly Patients (SHEP) Cohort Applegate WB, et al. J Am Geriatr Soci 1991;39 4,736 명의참가자 기립성저혈압 : 기상시 SBP 20mmHg 감소 기립후 1 분 : 10.4%, 3 분 : 12% 고혈압과관련 기저혈압이높을수록혈압하강이크다 정맥의저류 자율신경계기능부전 *JNC-7 에서는증상을동반하고 10mmHg 감소하는경우로설정

24 노인고혈압치료의근거 -2 가지의문 - 고혈압 ( 고립성수축기고혈압포함 ) 이 노인에서도위험한가? 치료를하면효과가있는가? - 더해가되는것이아닌가?

25 노인에서수축기혈압과사망률 Systolic Blood Pressure and Mortality Port S, et al. Lancet 2000;355 M F Reduced horizontal-logistic-spline fits : From pooled data of Framingham study cf. Framingam age-adjusted rates for men aged yrs related to SBP (simple linear regression model)

26 노인에서수축기혈압과사망률 Risks of untreated and treated isolated systolic hypertension in the elderly: meta-analysis of outcome trials Staessen JA, et al. Lancet 2000;355 Wide pulse pressure, more harmful!

27 노인수축기고혈압의치료효과 Risks of untreated and treated isolated systolic hypertension in the elderly: meta-analysis of outcome trials TSDH: three smaller trials in systolic and Staessen JA, et al. Lancet 2000;355 diastolic hypertension

28 노인고혈압의치료효과 주요합병증의억제효과 EWPHE MRC SHEP STOP-H Syst-China Syst-Eur 뇌졸중감소 (%) 관동맥질환억제 (%) 심부전감소 (%) -22 NA 복합투여 (%) 35 52/

29 노인고혈압치료의실제 -몇가지의문 - 얼마나혈압을낮추어야하나? 어떤약을써야하나? 부작용은? 주의할점은?

30 노인고혈압의치료가더이득이크다! 5 년의고혈압치료 : 노인 58 명당 1 명의사망을줄인다. 젊은사람 205 명당 1명 치료시작전에이미더큰위험에노출 흡연률이낮다 ( 임상연구에포함된환자들 ) 최근에시행된연구들로 thiazide 등의효과가입증된약제들을사용

31 노인고혈압의치료목표 JNC-7 (2003): 노인도같은기준을적용해야한다 혈압목표치 140/90mmHg 130/80mmHg: 당뇨병이나신장질환이있는경우 노인의경우수축기혈압을목표치까지도달하는것이바람직 이완기혈압이지나치게감소하는경우는?

32 수축기고혈압 BP (mmhg) Systolic BP Women Men 나이에따라 SBP는상승하고DBP는감소한다. SBP는거의일직선으로상승 DBP는완만하게상승하다, 70세이후는천천히감소 80 Diastolic BP Men Women Years Galarza CR et al. Hypertension. 1997;30:

33 Wide Pulse Pressure with Aging BP (mmhg) Systolic BP Women Men Diastolic BP Men Women Years Galarza CR et al. Hypertension. 1997;30:

34 Systolic Hypertension Characteristic finding of elderly HT Young Old

35 노인에서맥압과심혈관사망률 (framingham study) Events/ 1000 patients Vokonas et al 1988 Men SBP years years Events/ 1000 patients Women SBP

36 맥압증가의영향 수축기압증가에의한좌심실비대의유발 ; 산소소모량의증가와동맥경화의촉진 확장기압력의감소에의한심장관류압력의감소 이상에의해서심장의산소요구량은증가되나공급은감소된다.

37 Target organ of Hypertension Endpoints of Clinical Trials Stroke Coronary heart disease Heart failure (fatal or hospitalized) Total cardiovascular events (composite of all above) Declining renal function Cardiovascular mortality Total mortality

38 Treatment of Elderly Hypertension Stroke

39 Strokemore common than MI in11 major hypertensiontrials Incidence (%) 7 STOP-2 Stroke MI 6 SHEP 5 STOP-1 SYST- China NICS STONE SYST- EUR HOT CAPPP NORDIL INSIGHT 1 0 Kjeldsen Blood Press 2001;10(4):190

40 The higher the blood pressure, the greaterthe risk of stroke and CHD Stroke 7 prospective observational studies: 843 events CHD 9 prospective observational studies: 4856 events Relative risk of stroke Relative risk of CHD Baseline DBP category Baseline DBP category Approximate mean usual DBP (mmhg) MacMahon et al 1990

41 Prevention of Stroke, General Population

42 180 LIFE: Comparable Blood Pressure Reductions Atenolol mmhg Systolic Losartan mmhg mmhg Mean Arterial Diastolic Atenolol mmhg Losartan mmhg Losartan 81.3 mmhg Atenolol 80.9 mmhg Study Month Dahlöf B et al Lancet 2002;359:995

43 LIFE: Primary Composite Endpoint Proportion of patients with first event (%) Composite of CV death, stroke and MI Atenolol Losartan Adjusted Risk Reduction 13.0%, p=0.021 Unadjusted Risk Reduction 14.6%, p=0.009 Number at risk 0 Study Month Losartan (n) Atenolol (n) Dahlöf B et al Lancet 2002;359:

44 LIFE: Fatal & Non-fatal stroke 16 Proportion of patients with first event (%) Atenolol Adjusted Risk Reduction Unadjusted Risk Reduction Losartan 24.9%, p= %, p= Number at risk 0 Study Month Losartan (n) Atenolol (n)

45 VALUE: Fatal and Non-fatal Stroke Proportion of Patients With First Event (%) Valsartan-based regimen Amlodipine-based regimen HR = 1.15; 95% CI = ; P = 0.08 Number at risk Valsartan Amlodipine Time (months) Julius S et al. Lancet. June 2004;363.

46 Prevention of Stroke in Elderly Hypertension

47 Is There Evidence for Treatment in Elderly Hypertension?

48 Swedish Trial in Old Patients with Hypertension (STOP-Hypertension),1991 Cohort Age Eligibility Design Therapy Duration BP change 4,736; 43% men yrs old; mean 71.6 yrs old Systolic BP mmhg and Diastolic BP mmhg Double blind; placebo control 3 beta blockers, 1 diuretics 25 months -19.5/8.1mmHg Dahlöf et al Lancet 1991;338(8778):1281

49 STOP Hypertension Survival benefit with antihypertensive treatment in elderly patients % survival Treatment * * p= vs placebo Placebo Years Dahlöf et al Lancet 1991;338(8778):1281

50 The Systolic Hypertension in the Elderly Program, 1991

51 The Systolic Hypertension in the Elderly (SHEP) Program Cohort Age Eligibility Design Therapy Duration BP change 4,736; 43% men 60 yrs old; mean 71.6 yrs old Systolic BP mmhg and Diastolic BP <90 mmhg Double blind; placebo control Chlorthalidone(atenolol as step 2) 4.5 years Systolic BP 12 mmhg SHEP Research Group. JAMA. 1991;265:

52 180 SHEP Change in Blood Pressure Systolic BP 80 Diastolic BP Change in BP (mmhg) Placebo (n=2,371) Active Rx (n=2,365) Placebo (n=2,371) Active Rx (n=2,365) Years Years SHEP Research Group. JAMA. 1991;265:

53 SHEP Average Blood Pressure During Follow-up Blood pressure (mmhg) Months of follow-up SHEP Research Group. JAMA. 1991;265:

54 Cumulative stroke rate per 100 persons SHEP Cumulative Stroke Rate Placebo (n=2,371) Months of follow-up P= Active Rx (n=2,365) SHEP Research Group. JAMA. 1991;265:

55 Relative risk (95% CI) SHEP Cardiovascular Disease Endpoints Active Therapy vs. Placebo Stroke CHD CHF CVD CHD=coronary heart disease; CHF=congestive heart failure; CVD=cardiovascular disease 0.87 Death SHEP Research Group. JAMA. 1991;265:

56 SHEP Conclusions SHEP was the first clinical trial to demonstrate that reduction of blood pressure in patients with isolated systolic hypertension reduced cardiovascular (CV) mortality The relative risk of stroke was reduced by 36% with therapy compared to placebo (P=0.0003) The 5-year absolute benefits were a reduction in 30 strokes and 55 major CV disease events per 1,000 persons SHEP Research Group. JAMA. 1991;265:

57 The Systolic Hypertension in Europe (Syst-Eur) Trial, 1997

58 The Systolic Hypertension in Europe Trial, 1997 Cohort Age Eligibility Design Therapy Duration BP difference 4,695; 67% women 60 yrs old Systolic BP mmhg and diastolic BP <95 mmhg Double blind; placebo control Nitrendipine(enalapril, HCTZ as Step 2) Median 2 yrs (1-97 months) -10/5 mmhg Staessen JA, et al. Lancet. 1997;350:

59 Syst-Eur Mean Sitting Systolic Blood Pressure Systolic BP (mmhg) Placebo (n=2,297) Active treatment (n=2,398) P< Years since randomization Staessen JA, et al. Lancet. 1997;350:

60 Syst-Eur Mean Sitting Diastolic Blood Pressure 85 Diastolic BP (mmhg) P< Placebo (n=2,297) Active treatment (n=2,398) Years since randomization Staessen JA, et al. Lancet. 1997;350:

61 Syst-Eur Primary Endpoint, Fatal and Nonfatal Stroke Events per 100 patients Placebo (n=2,297) Active treatment (n=2,398) P= Years since randomization Staessen JA, et al. Lancet. 1997;350:

62 Percentage relative risk reduction (95% CI) Syst-Eur Cardiovascular Disease Endpoints Stroke 42% P=0.003 Active therapy vs. placebo MI 30% CHF 29% 31% All CVD P<0.001 Death 14% MI=myocardial infarction; CHF=congestive heart failure; CVD=cardiovascular disease Syst-Eur=Systolic Hypertension in Europe Trial Staessen JA, et al. Lancet. 1997;350:

63 Syst-Eur Conclusions Older men and women with isolated systolic hypertension who received active treatment with a dihydropyridinecalcium channel blocker experienced fewer strokes and cardiovascular disease (CVD) events than those receiving placebo. Treatment of 1,000 patients for 5 years with this type of regimen could prevent 29 strokes or 53 major CVD endpoints. Staessen JA, et al. Lancet. 1997;350:

64 Dementia Alzheimer s disease(ad) Vascular dementia(vd) Mixed AD+VD Accounts for 80% of all cases of dementia

65 High blood pressure precedes development of dementia Non-demented SBP (mmhg) Onset of Alzheimer s disease after age 79 years DBP (mmhg) Onset of vascular dementia after age 79 years Age (years) Age (years) Skoog et al 1996

66 Hypertension and cognitive decline: white matter lesions suggest a mechanism Elevated blood pressure causes hyalinisation of vascular walls Hyalinisation coupled with episodes of hypotension may lead to hypoperfusionand ischaemiain vulnerable brain areas,such as deep white matter Subsequent demyelinisationmay lead to disconnection of subcortical-cortical pathways, resulting in cognitive decline and dementia

67 Antihypertensive treatment halves dementia rate in Syst-Eur 2418 patients aged 60 years Median MMSE=29 1 year follow up New cases of dementia (defined as MMSE 23) placebo active treatment / 1000 patient years 3.8 / 1000 patient years p=0.05 Forette et al Lancet 1998;352:1347

68 Study on COgnition and Prognosis in the Elderly (SCOPE)

69 Rationale for SCOPE Hypertension is a risk factor for both CV disease and dementia Antihypertensive treatment reduces CV risk and may reduce risk of dementia However, data are inconclusive with regard to elderly patients with mild-to-moderate hypertension

70 Primary Objectives Major cardiovascular events (cardiovascular death, no n-fatal myocardial infarction, non-fatal stroke) Secondary Cognitive function Dementia Total mortality Cardiovascular mortality Fatal MI Non-fatal MI All MI Fatal stroke Non-fatal stroke All stroke Development of diabetes mellitus Discontinuation of study drug Lithell et al, J Hypertens 2003

71 Inclusioncriteria Men and women, aged years Previously treated or untreated hypertension Previous treatment standardised to HCT 12.5 mg SBP mmhgor DBP mmhg, or both MMSE score 24 Lithell et al, J Hypertens 2003

72 Design Randomisation: Patients untreated or HCT 12.5 mg with SBP mmhg and/or DBP mmhg 16 mg 8 mg Candesartan arm Other antihypertensive drug(s) 1 3 months placebo placebo Other antihypertensive drug(s) Control arm Follow-up visits (months) Every 6 months 60 Step 1: candesartan 8 mg, or placebo, once daily Step 2: If SBP >160 mmhg or DBP >85 mmhg dose doubled Step 3: If SBP remains 160 mmhg or DBP remains 90 mmhg other antihypertensive drug (not ACE inhibitor or AT 1 -receptor blocker) added Lithell et al, J Hypertens 2003

73 SCOPE analysed data from 4937 patients 4964 randomised patients Excluded 13 data quality concerns 14 no study drug dispensed 2477 Atacand arm 2460 control arm 6 lost to follow-up 2 lost to follow-up 2477 available for ITT analysis 2460 available for ITT analysis Lithell et al, J Hypertens 2003

74 Blood pressure reductions mmhg Candesartan Control Difference in BP reduction 3.2/1.6 mmhg (ITT population) Months 48 LVCF* Candesartna(n) Control (n) * LVCF=last value carried forward * LVCF=last value carried forward Lithell et al, J Hypertens 2003

75 First major cardiovascular event Proportion of patients (%) Difference in BP reduction 3.2/1.6 mmhg Control Candesartan Risk reduction=10.9% p= Months Atacand (n) Control (n) Lithell et al, J Hypertens 2003

76 Incidences of significant cognitive decline and dementia Number of patients (events per 1000 patient years) Candesartan Control p value Significant cognitive 113 (13.5) 125 (15.2) >0.20 decline (n=2416) (n=2409) Dementia 62 (6.8) 57 (6.3) >0.20 (n=2477) (n=2460) Lithell et al, J Hypertens 2003

77 SCOPE: Fatal & All stroke Non-fatal stroke 27.8% reduction (p=0.04) All stroke 23.6% reduction (p=0.056)

78 Study on Cognition and Prognosis in the Elderly (SCOPE) Subdata Analysis Isolated systolic hypertension group

79 Fatal or Non-fatal Stroke patients with isolated systolic hypertension(ish) SCOPE:ISH SBP 160mmHg DBP<90mmHg

80 Conclusions Considerable blood pressure reductions achieve d in both treatment groups For major CV events, there was an 11% risk redu ction in the Atacand -based treatment group (p= 0.19) Marked risk reduction of 28% in non-fatal stroke with Atacand (p=0.04) For all stroke, there was a 24% risk reduction in t he Atacand group (p=0.056) Lithell et al, J Hypertens 2003

81 Beta-blocker as 1 st line drug in Elderly Patients The time of withhold?

82 Beta-blocker, No Strong Evidence for Survival Benefit

83 Events (amlodipine based vs atenolol based) ASCOT-BPLA,2005 Fatal & Non-fatal stroke HR(95% CI) Fatal stroke BP difference SBP DBP Non-fatal stroke

84

85 ALLHAT: BP Results by Treatment Group Chlorthalidone Amlodipine Lisinopril 150 BL 6M 1Y 3Y 5Y 90 BL 6M 1Y 3Y 5Y C C mm Hg BP A L mm Hg BP A L Years Compared to chlorthalidone: SBP significantly higher in the amlodipine group (~1 mm Hg) and the lisinopril group (~2 mm Hg) Years Compared to chlorthalidone: DBP significantly lower in the amlodipine group (~1 mm Hg). JAMA 2002;288:

86 ALLHAT : Risk of Stroke.1 RR (95% CI) p value.08 A/C L/C 0.93 ( ) 1.15 ( ) Cumulative Stroke Rate Chlorthalidone Amlodipine Lisinopril Years to Stroke Number at risk: Chlor 15,255 14,515 13,934 13,309 11,570 6,385 3, Amlo 9,048 8,617 8,271 7,949 6,937 3,845 1, Lisin 9,054 8,543 8,172 7,784 6,765 3,891 1,

87 Prevention of Heart Failure in Elderly Hypertension

88 Hypertension, still leading cause of heart failure Effect of hypertension on the risk of heart failure (Framingham Study) Levy D et al. JAMA /392(91%) prior hypertension Men Women Age adjusred annual rate of CHF per 1, Normal(<140/90) Borderline Definite(>160/95) Normal(<140/90) Borderline Definite(>160/95)

89 Underlying cause of CHF in Korea (multicenter survey) Korean J Circ 2003 Hypertesive heart disease 24.8% etc 9.0% Hypertesion 36.4% Ischemic heart disease with HT 11.6% Ischemic heart disease without HT 21.3% Myocardial disease 23.0% Valvular heart disease 12.7%

90 Relative risk (95% CI) SHEP Cardiovascular Disease Endpoints Active Therapy vs. Placebo Stroke CHD CHF CVD CHD=coronary heart disease; CHF=congestive heart failure; CVD=cardiovascular disease 0.87 Death SHEP Research Group. JAMA. 1991;265:

91 Percentage relative risk reduction (95% CI) Syst-Eur Cardiovascular Disease Endpoints Stroke 42% P=0.003 Active therapy vs. placebo MI 30% CHF 29% 31% All CVD P<0.001 Death 14% MI=myocardial infarction; CHF=congestive heart failure; CVD=cardiovascular disease Syst-Eur=Systolic Hypertension in Europe Trial Staessen JA, et al. Lancet. 1997;350:

92 ACE inhibitor, ARB in Heart Failure Prevention

93 Cumulative Event Rate ALLHAT: Doxazosin arm withdrawn Heart Failure Rel Risk % CI z = 10.95, p < doxazosin chlorthalidone Years of Follow-up JAMA. 2000;283:

94 ALLHAT : Heart Failure.15 A/C RR (95% CI) 1.38 ( ) p value <.001 Cumulative CHF Rate L/C 1.19 ( ) Chlorthalidone Amlodipine Lisinopril < Years to HF ALLHAT study group JAMA 2002

95 Proportion of Patients With First Event (%) VALUE: Heart Failure Hospitalisation for HF or death from HF Valsartan-based regimen Amlodipine-based regimen HR = 0.89; 95% CI = ; P = Time (months) Julius S et al. Lancet. June 2004;363.

96 Blood Pressure Lowering Treatment Trialists Collaboration(BPLTT) HEART FAILURE Treatment vs Placebo BP difference (mm Hg) Favours active Favours control RR (95% CI) ACE vs. placebo -5/ (0.69,0.98) CA vs. placebo -8/ (0.93,1.58) More vs. less -4/ (0.59,1.18) Relative Risk BPLTT collaboration group Lancet 2003

97 Blood Pressure Lowering Treatment Trialists Collaboration(BPLTT) BP difference (mm Hg) HEART FAILURE Different Agents Favours first listed Favours second listed RR (95% CI) ACE vs. D/BB CA vs. D/BB ACE vs. CA 2/0 1/0 1/ (0.96,1.19) 1.33 (1.21,1.47) 0.82 (0.73,0.92) 결론적으로 ACEi와 D/BB는비슷 Relative Risk BPLTT collaboration group Lancet 2003

98 Blood Pressure Lowering Treatment Trialists Collaboration Second cycle of overview analyses Institute for International Health

99 Contributing trials Second cycle (29 trials, n= 162,341) AASK ABCD (H) ABCD (N) ALLHAT ANBP2 CAPPP CONVINCE ELSA HOPE HOT IDNT INSIGHT JMIC-B LIFE NICOLE NICS-EH NORDIL PART-2 PREVENT PROGRESS QUIET RENAAL SCAT SCOPE SHELL STOP-2 SYST-EUR UKPDS-HDS VHAS

100 STROKE active treatments vs control BP difference (mm Hg) Favours active Favours control RR (95% CI) ACE vs. placebo CA vs. placebo More vs. less -5/-2-8/-4-4/ (0.64,0.81) 0.62 (0.47,0.82) 0.77 (0.63,0.95) Relative Risk

101 STROKE Comparisons of different active treatments BP difference (mm Hg) Favours first listed Favours second listed RR (95% CI) ACE vs. D/BB CA vs. D/BB ACE vs. CA 2/0 1/0 1/ (1.00,1.18) 0.93 (0.86,1.00) 1.12 (1.01,1.25) Relative Risk

102 CORONARY HEART DISEASE active treatments vs control BP difference (mm Hg) Favours active Favours control RR (95% CI) ACE vs. placebo CA vs. placebo More vs. less -5/-2-8/-4-4/ (0.73,0.88) 0.78 (0.62,0.99) 0.95 (0.81,1.11) Relative Risk

103 CORONARY HEART DISEASE Comparisons of different active treatments BP difference (mm Hg) Favours first listed Favours second listed RR (95% CI) ACE vs. D/BB 2/ (0.91,1.05) CA vs. D/BB ACE vs. CA 1/0 1/ (0.94,1.08) 0.96 (0.88,1.04) Relative Risk

104 Blood Pressure Lowering Treatment Trialists Collaboration(BPLTT) HEART FAILURE Treatment vs Placebo BP difference (mm Hg) Favours active Favours control RR (95% CI) ACE vs. placebo -5/ (0.69,0.98) CA vs. placebo -8/ (0.93,1.58) More vs. less -4/ (0.59,1.18) Relative Risk BPLTT collaboration group Lancet 2003

105 Blood Pressure Lowering Treatment Trialists Collaboration(BPLTT) BP difference (mm Hg) HEART FAILURE Different Agents Favours first listed Favours second listed RR (95% CI) ACE vs. D/BB CA vs. D/BB ACE vs. CA 2/0 1/0 1/ (0.96,1.19) 1.33 (1.21,1.47) 0.82 (0.73,0.92) 결론적으로 ACEi와 D/BB는비슷 Relative Risk BPLTT collaboration group Lancet 2003

106 MAJOR CARDIOVASCULAR EVENTS active treatments vs control BP difference (mm Hg) Favours active Favours control RR (95% CI) ACE vs. placebo -5/ (0.73,0.83) CA vs. placebo -8/ (0.71,0.95) More vs. less -4/ (0.76,0.95) Relative Risk

107 MAJOR CARDIOVASCULAR EVENTS Comparisons of different active treatments BP difference (mm Hg) Favours first listed Favours second listed RR (95% CI) ACE vs. D/BB CA vs. D/BB ACE vs. CA 2/0 1/0 1/ (0.98,1.07) 1.04 (1.00,1.09) 0.97 (0.92,1.03) Relative Risk

108 Pivotal studies demonstrate benefits of treating elderly hypertensive patients Study n Age Inclusion BP (mmhg) (mean) SBP DBP SCOPE (76) SHEP <90 (72) Syst-Eur <95 (70) STOP (76) STOP (76) MRC elderly <115 (69) EWPHE (72)

109 In extremely old age (>80 yrs), high BP should be treated?

110 STOP-2 Cohort Age Eligibility Design Therapy yrs old Systolic BP 180 mmhg, diastolic BP 105 mmhg, or both Double blind; placebo control Conventional antihypertensive drug (beta-blocker+diuretics, n=2,213), ACE inhibitors (n=2,205), or Calcium channel blockers (n=2,196) Hansson L, et al. Lancet. 1999;354:

111 STOP-2 Change in Supine Blood Pressure From Baseline* Change in BP from baseline (mmhg) Calcium channel blockers ACE inhibitors Conventional drugs -40 Systolic Diastolic *Among patients who survived at least 24 months Hansson L, et al. Lancet. 1999;354:

112 STOP-2 Frequency of Events Per 1000 Patient Years Cardiovascular mortality Fatal myocardial infarction Fatal stroke Sudden death Calcium channel blockers ACE inhibitors Conventional drugs Other cardiovascular mortality Diabetes mellitus All myocardial infarction Congestive heart failure P=0.018 P=0.025 Hansson L, et al. Lancet. 1999;354: Events per 1000 patient years

113 No concrete evidence of high BP with survival in extremely old age group

114 Amplification of Benefit Meta-analysis for 61 prospective & observational studies Mean BP 2mmHg 7% mortality Risk reduction By CAD 10% mortality Risk reduction By Stroke LewingtonS et al. Lancet 2002

115 Benefit of Hypertension Treatment in old age EWPHE MRC SHEP STOP-H Syst-China Syst-Eur Stroke (%) CAD (%) Heart Failure (%) -22 NA

116 치료 노년기고혈압 : 반듯이치료해야된다 심혈관질환 : 젊은환자보다 3-4 배높다 수축기고혈압도치료효과유사 남자 / 70 세이상 / 맥압이큰환자 치료효과더욱크다

117 노년기고혈압의치료효과

118 치료 일차목표는수축기혈압과맥압조절에둔다 치료목표 /85 140/85-90 mmhg 이하 중간목표설정 초기혈압이매우높고표적장기손상없으면 일단 160mmHg 이하로조절

119 노년기고혈압의일반적치료원칙 비약물치료법부터시작한다 처음치료의일차약제는저용량이뇨제부터투여한다 환자의동반질병에따라일차약제혹은복합제제를선택한다. 처음사용하는약제는일반용량의반으로시작하여, 천천히증량한다 치료목표는수축기혈압 140 에서 135mmHg 이하로한다 확장기혈압의지나친하강은피한다 (70mmHg 이하 ) 기립성저혈압을유발할정도의지나친치료는피한다

120 비약물치료 초기고혈압치료 치료약제의용량감소 다른위험인자조절효과 처음수축기혈압 <160mmHg/(-) 처음 6 개월은비약물치료 과체중 / 활동이적은환자에서반듯이시행

121 비약물치료 (Lifestyle Modifications) Modification Recommendation Systolic BP Reduction Weight reduction Maintain normal body weight(bmi,18.5 BMI, ) 5-20 mmhg/10-kg Adopt DASH eating plan Dietary sodium reduction Physical activity Moderation of alcohol consumption Consume a diet rich in fruits, vegetables, and low- fat dairy products with a reduced content of saturated and total fat Reduced dietary sodium intake to no more than 100mEq/L (2.4g sodium or 6 g sodium chloride) Engage in regular aerobic physical activity such as brisk walking (at least 30 minutes per day, most days of the week) Limit consumption to no more than 2 drinks per day(1 o or 30 ml ethanol [eg, 24 oz beer, 10 oz wine, or 3 oz 80-proof whiskey]) in most men and no more than 1 drink per day in women and lighter-weight persons 8-14 mm Hg 2-8 mm Hg 4-9 mm Hg 2-4 mm Hg

122 약물치료 일반고혈압치료와동일 동반질환여부 : 당뇨, CAD, HF, BPH 등 단순히고혈압만있는경우 Thiazide 이뇨제를처음사용 기립성저혈압을잘유발하는 clonidine, reserpine 등은피한다

123 어떤약제를선택할것인가? 위약에비해서효과적인것은이뇨제와칼슘차단제이며베타차단제도효과적이나이뇨제보다는못하다 새로운약제들은이뇨제와비슷한효과가있다

124 약물치료 초기용량은절반으로시작 ( 신장기능저하, 약물의감수성증대 ) 이뇨제 - 칼슘길항제 ACE I, ARB 베타차단제는관상동맥질환과심부전에만선택적으로투여 치료목표 : 초기수축기 mmHg 미만

125 고려사항 대부분의연구는건강한노인을대상으로시행 기립성저혈압의출현 저포타슘혈증의출현 : 이뇨제는저용량으로 인지기능의변화에대한고려 : 뇌혈류의저하 정서기능의변화 : 과거의약제들 미각의변화 요량의증가에따른요실금의발생

126 추적과관찰 치료순응도파악 부작용에대한평가 ( 특히기립성저혈압 ) 앙와위와기립혈압측정 자가혈압측정권장 비약물치료법권장 ( 식이요법, 운동 ) 혈압강하제용량결정에주의 Refractory HT 의평가

127 Summary

128

129 Thank for your attention!