일차진료에서고혈압치료 - 맞춤처방 / 선우성 일차진료에서고혈압치료 - 맞춤처방 선우성울산대학교의과대학서울아산병원가정의학과 Hypertension is a key modifiable risk factor for cardiovascular disease (CVD) Modifiable risk factors Hypertension Dyslipidemia Diabetes Cigarette smoking Obesity Physical inactivity 4 3 2 1 1. The Lower the BP, the Lower the Risk 1. Diastolic BP (mmhg) Systolic BP (mmhg) 1.3 1.19 1.18 1.31 1.24 1.39 1.31 1.56 1 2 3 4 5 6 7 8 9 1 Lowest 1% Highest 1% 1.4 Decile of Blood Pressure 1.75 1.62 1.78 1.81 2.31 1.99 2.71 2.9 3.82 Grundy et al, Circulation, 1998; Grundy et al, Circulation, 1999. CV Mortality Doubles With Each 2/1 mmhg Increase in BP Benefits of Therapy RR = X8 Hypertension Increasing CV Mortality * RR = X1 RR = X2 135/85 RR = X4 155/95 175/15 Silent Killer Lowering of DBP and SBP by 5 1 mmhg : Reduction of stroke by 4% 115/75 SBP/DBP, mmhg and CV death by 2% BP=Blood Pressure, RR=Relative Risk *Individuals aged 4 69 years (N=1 million) Lewington S et al. Lancet. 22;6:193 1913. 133
고혈압유병률의연도별변화 고혈압유병률의연령별변화 * 고혈압전단계유병률 ( 만 3 세이상 ) 전체 23.4%, 남자 28.4%, 여자 18.7% * 평생고혈압유병률 9%(29 JSH) 고혈압관리현황 고혈압관리현황 한국 미국 인지율 66.1% 78% 치료율 59.4% 68% 조절률 42.4% 64% 남성 여성 인지율 56.9% 74.5% 치료율 48.3% 69.9% 조절률 33.9% 5.4% * 28년국민건강영양조사만3세이상, 25표준인구표준화 * 미국 (NHANES 25-26, 만18세이상 ) 28년국민건강영양조사 특히, 남자 3~4대의관리현황이인지율 27~36%, 치료율 14~23%, 조절률 ( 유병자기준 ) 1-18% 로다른연령대에비해낮은수준이었다 권고사항 1 권고사항 2 일차의료에서고혈압은매우흔한건강문제이므로, 일차의료의사는이에대한선별검사, 진단, 치료및상담에대한능력을갖춰야한다. 18세이상모든성인은 1-2년마다혈압을측정해야한다. 134
일차진료에서고혈압치료 - 맞춤처방 / 선우성 권고사항 3 일차의료의사는고혈압을진단할때 1주이상에서걸쳐서 2회이상측정한혈압을근거로신중하게결정해야한다. 혈압의측정과고혈압의진단 진료실에서혈압 (office BP monitoring) 을측정할때는혈압측정의원리를적용하여정확하게측정해야한다. 백의고혈압 (white coat hypertension), 혹은가면고혈압 (masked hypertension) 이의심되는등진료실에서측정한혈압만으로결론을내리기힘들때는가정자기혈압측정 (home BP monitoring), 혹은 24 시간활동혈압측정 (24h ambulatory BP monitoring) 을활용해야한다. 혈압의분류 진료실혈압 백의고혈압 지속성고혈압 14/9 정상혈압 가면고혈압 (Masked Hypertension) 활동혈압 135/85 대한고혈압학회. 혈압모니터지침 27 U.S. Department of Health and Human Services, National Institutes of Health, National Heart, Lung, and Blood Institute. JNC7(7th Joint National Committee) 24 Suggested Values for the Upper Limit of Normal Ambulatory Pressure Optimal Normal Abnormal Daytime <13/8 <135/85 >14/9 Nighttime <115/65 <12/7 >125/75 24-hour <125/75 <13/8 >135/85 한국고혈압지침서일일평균 125/8 mmhg 주간평균 135/85 mmhg 야간평균 12/75 mmhg * 29 JSH 기준도같음 Pickering TG. Hypertension. 25;45:142 135
권고사항 4 일차의료의사는고혈압을진단한후, 병력, 진찰, 검사실검사를통해서다음사항을평가해야한다. o 위험요인및교정이필요한생활습관 o 동반질환 o 표적장기질환손상여부 o 2차고혈압유무 고혈압예후에미치는영향요인 1. 위험요인 o 수축기혹은이완기혈압수준 o 고령에서는맥압 (pulse pressure) 수준 o 연령 ( 남 >55 세, 여 >65) o 흡연 o 이상지질혈증 (TC>19mg/dl, LDL-C>115, TG>15, HDL-C 남 <4, 여 <46) o FBS>12 mg/dl o AC 남 >12cm, 여 >88 o 조기심혈관질환의가족력남 <55 세, 여 <65 U.S. Department of Health and Human Services, National Institutes of Health, National Heart, Lung, and Blood Institute. JNC7(7th Joint National Committee) 24 ESH/ESC Practice Guideline for the Management of Arterial Hypertension 27 고혈압예후에미치는영향요인 2 2. 당뇨병 3. 전임상기표적장기질환 o 심전도상좌심실비대 o 심에코상좌심실비대 o 경동맥 IMT>.9 mm, or plaque 존재 o Ankle/Brachial BP index<.9 o Creatinine 미세한증가 ( 남 1.3-1.5mg/dl, 여 1.2-1.4) o egfr<6ml/min/1.73m 2 o Microalbuminuria 3-3mg/24h, albumin creatinine ratio 남 >=22 여 >=31 고혈압예후에미치는영향요인 3 4. 확증된심혈관혹은신장질환 o 심혈관질환 ( 뇌졸중, TIA) o 신장질환 o 말초혈관질환 o 진행된고혈압성망막질환 고혈압평가에서 항상포함시킬정례적검사 CBC 혈청칼륨 (potassium), 요산, 갑상선자극호르몬 (TSH) 지질검사 (Total cholesterol, high-density and lowdensity lipoprotein cholesterol, triglycerides) 크레아티닌, 또는추정사구체투과률 (estimated GFR) 공복시혈당 요분석 ( 단백뇨, 혈뇨, 현미경적검사 ) 심전도 Old targets: BP levels A New Treatment Paradigm Measure and treat levels Goal is normal levels Based on epidemiologic and observational data New target: Atherosclerosis Find patients at risk Goal is reducing a life-long risk Based on randomized clinical trial evidence ESH/ESC Practice Guideline for the Management of Arterial Hypertension 27 Adapted from Fonarow GC, et al. Am J Cardiol. 2;85:1A-17A. 136
일차진료에서고혈압치료 - 맞춤처방 / 선우성 ( 선별검토 ) 고혈압평가에포함시켜야하지만비 용등다른요인에따라달라질수있는검사 Echocardiography Carotid Ultrasound(Carotid intima-media thickness) Arterial stiffness(pulse wave velocity) Ankle-brachial index 노인 : 인지검사 > Brain MRI, 우울증선별 미세단백뇨 안저검사 권고사항 5 고혈압에대한관리는전고혈압단계부터시작되어야한다. 수개월내목표혈압 (<12/8mmHg) 에도달하지못하는경우, 당뇨병, 임상적심혈관계질환혹은신장질환이있는경우는약물요법을시작한다. 권고사항 6 고혈압치료에서비약물요법은매우중요하다. 표적장기질환이없는 1 단계고혈압의경우는고혈압진단과동시에약물요법을시작하기보다는수주간비약물요법으로혈압을정상화할수있는시도를한다. 권고사항 7 항고혈압제적응증 (29JSH) 목표기간이내에목표혈압에도달하지못하면항고압제에의한약물요법을시작한다. 항고혈압제의선택은표적장기질환의유무및종류, 동반질환에따라선택한다. 각약물의적응증과금기증이고혈압환자의상태에맞는지를점검한다. 137
항고혈압제의금기증 (29JSH) 권고사항 8 항고혈압제복합제투여는초기부터적극고려한다. 권고사항 9 일차의료의사는다음과같은경우에는고혈압전문가에게의뢰를고려한다. o 2차성고혈압이의심될때 o 고혈압의합병증이의심되어추가적인정밀검사가필요할때 o 항고혈압제로혈압이조절이안되어 4가지이상의약제를써야할때 권고사항 1 일차의료의사는고혈압환자의복약순응도수준을평가하고이를높이기위한상담을제공해야한다. Barriers to Adherence in HT Control Reasons for Antihypertensive Drug Discontinuation % 6 Lack of knowledge 5 48.4 Noncompliance with therapy Medication side effects 4 3 2 3.1 2 16.8 Complexity of regimens 1 4.9 Inadequate BP control Side Effects Patient Dissatisfaction Non- Compliance Cost Mancia G, et al. AJH 23;16:166-73 138
일차진료에서고혈압치료 - 맞춤처방 / 선우성 Adherence (medication possession ratio) ARBs are associated with higher adherence rates compared with other antihypertensive drug classes.8.7.6.5.4.3.2.1 A retrospective cohort study analysing claims from 62,754 patients in the German Sickness Fund ARB ACEI CCB Diuretic β-blocker Compliance Decreases as the Number of Medications Increases Number of pre-existing prescription medications 1 2 3 5 6 Unadjusted odds ratio for compliance (>8%) to both antihypertensive therapy and LLT (95% CI; p value) 1.73 (1.56 1.9; p<.1) 1.25 (1.13 1.39; p<.1).96 (.86 1.6; p=.41).87 (.79.94; p<.1).65 (.59.71; p<.1).5 1 1.5 2 2.5 Decreased compliance Increased compliance Mean (95% CI) medication possession ratio: ARBs.697 (95% CI:.686.77); ACEIs.556 (.55.562); β-blockers.385 (.382.388); CCBs.54 (.531.548); diuretics.533 (.525.541) Adapted from Höer et al. J Hum Hypertens 27;21:744 6 Retrospective cohort study of MCO population. N=8,46 patients with hypertension who added antihypertensive therapy and LLT to existing prescription medications within a 9-day period. Compliance to concomitant therapy: sufficient antihypertensive and LL prescription medications to cover 8% of days per 91-day period CI=confidence interval; LLT = lipid-lowering therapy Chapman et al. Arch Intern Med 25;165:1147 52 Multiple Antihypertensive Agents are Needed to Reach Blood BP Goal Trial (SBP achieved) MDRD (132 mmhg) 1 HOT (138 mmhg) 1 RENAAL (141 mmhg) 1 AASK (128 mmhg) 1 ABCD (132 mmhg) 1 IDNT (138 mmhg) 1 UKPDS (144 mmhg) 1 ASCOT-BPLA (136.9 mmhg) 2 ALLHAT (138 mmhg) 1 ACCOMPLISH (132 mmhg) 3, 4 Initial 2-drug combination therapy 1 2 3 4 Average no. of antihypertensive medications 1 Bakris, et al. Am J Med 24;116(5A):3S 8; 2 Dahlöf, et al. Lancet 25;366:895 96 SBP = systolic blood 3 Jamerson, pressure et al. Blood Press 27;16:8 6; 4 Jamerson, et al. N Engl J Med 28;359:2417 28 Improved Compliance with Single-pill Combination (SPC) Therapy Compared with Free-combination Therapy SPC (amlodipine/benazepril) (n=2,839) Free combination (ACEI + CCB) (n=3,367) Defined as the total number of days of therapy for medication d ispensed/365 days of study follow-up ACEI = angiotensin-converting enzyme inhibitor; CCB = calcium channel blocker 69% 88% p<.1 % 2% 4% 6% 8% 1% Medication possession ratio (MPR) Gerbino, Shoheiber. Am J Health System Pharm 27;64:1279 83 Initiating therapy with SPC is associated with improved BP control and lower risk of developing a CV event vs switching to combination therapy Retrospective (real-world), matched-cohort study (2,432 patients in each of the single-pill combination (SPC) and switcher/add-on cohorts); mean blood pressure (BP) at baseline in each study group: 149/83 mmhg More patients achieved BP control* in the SPC vs switcher/add-on cohort at months 3 (24.7% vs 2.4%), 6 (46.6 % vs 42.4%, and 12 (72.% vs 69.1%), resulting in a shorter median time to BP goal: 6.5 vs 7. months, respectiv ely; log-rank p=.367 No. of patients with event SPC (n=2,432) Switch (n=2,432) Incidence rate (No. of patients with an event p er 1 person-years) SPC Switch (n=2,432) (n=2,432) Conditional Poisson [Ref: Switcher/Add-on] IRR (95% CI) p value Acute MI 82 129 1.29 1.79.45 (.32.64) <.1 Stroke 357 426 6.14 6.53.85 (.7 1.2).814 Hospitalization for HF 83 135 1.3 1.87.46 (.33.64) <.1 EX-FAST Efficacy of the combination of amlodipine and valsartan in patients with hypertension uncontrolled with previous monotherapy: the Exforge in Failure after Single Therapy Overall 454 573 8. 9.13.72 (.61.84) <.1 Overall (with death) 473 587 8.34 9.36.74 (.63.86).1 IRR = incidence rate ratio of cardiovascular (CV) events (incidence rate of CV event [SPC cohort]/incidence rate of CV event [Switcher/Add-on cohort]. SPC or free co mbinations = angiotensin-converting enzyme inhibitor (ACEI)/calcium channel blocker (CCB), angiotensin receptor blocker (ARB)/CCB, ACEI/diuretic, ARB/diuretic. *<14/9 mmhg, or <13/8 mmhg for patients with compelling indications. SPC = patients initiated on SPC therapy for at least 6 days. Switchers/add-on = patients initiated on monotherapy for at least 6 days, subsequently switched to combination therapy/added a second agent for at least 6 days. HF = heart failure; MI = myocardial infarction Gradman et al. Poster presented at the American Society of Hypertension, New York, 21 24 May 211 Allemann Y, Fraile B, Lambert M,et al.j Clin Hypertens,(Greenwich) 28;1:185-194 139
EX-FAST Efficacy of the combination of amlodipine and valsartan in patients with hypertension uncontrolled with previous monotherapy: the Exforge in Failure after Single Therapy 목적 기존항고혈압제단일요법으로조절되지않는고혈압환자를대상으로, 엑스포지투여후목표혈압 * 에도달한환자비율평가 * BP level < 14/9 mm Hg or 13/8 mm Hg for diabetics 대상환자 단일요법으로혈압이조절되지않은고혈압환자 894 명 ( 14/9 mm Hg 또는당뇨병환자의경우 13/8 mm Hg, 평균연령 59 세, SBP 18 mm Hg 및당뇨병환자의경우 16 mm Hg 인경우는제외 ) amlodipine and valsartan 은단일제제로혈압이조절되지않았던환자에서추가적인혈압강하효과를나타내었습니다 Result at 8 week in patients with HTN not controlled by antihypertensive monotherapy EX-FAST 시험디자인 - 이중맹검, 무작위배정, 평행군, 다국가, 다기관임상시험 (washout 기간없이단일요법에서엑스포지투여로전환 ) - 엑스포지 5/16 mg (n=443) 또는 1/16 mg (n=451) 으로무작위배정, 8 주후혈압이조절되지않는경우비맹검으로 HCTZ 12.5 mg 추가 ; 12 주후여전히혈압이조절되지않는경우 HCTZ 용량을 25 mg 으로적정 Allemann Y, Fraile B, Lambert M,et al.j Clin Hypertens,(Greenwich) 28;1:185-194 *p=.1 (Exforge 1/16 mg vs 5/16 mg) MSSBP / MSDBP was 149.8/9.8 mmhg in 5/16 mg and 15.4/9.6mmHg in 1/16 mg groups, respectively at baseline ACEI=Angiotensin converting enzyme inhibitor; ARB=Angiotensin receptor blocker; B-blocker=beta blocker; BP=Blood pressure; CCB=Calcium channel blocker; DBP=Diastolic blood pressure; HTN=Hypertension; MSSBP=Mean sitting systolic blood pressure; SBP=Systolic blood pressure Allemann Y, Fraile B, Lambert M,et al.j Clin Hypertens,(Greenwich) 28;1:185-194 Amlodipine/Valsartan : Up to 9 Out of 1 Patients Reach BP Goal <14/9 mmhg Tolerability and risk factor modification: CCB-induced peripheral edema minimized by the ARB 1 8 All patients Non-diabetic patients Diabetic patients 84.4 85.2 77.1 78.4 8. 69.7 Complementary mechanism of ARB and CCB 1 Amlodipine/Valsartan 1/16mg significantly decreased Ankle Edema compared to 2 Amlodipine 1mg/Olmesartan 2mg Patients (%) 6 4 n=44 n=369 n=71 n=449 n=375 n=74 2 Amlodipine/Valsartan 5/16 mg Amlodipine/Valsartan 1/16 mg Diabetic patients with BP <13/8 mmhg at Week 8 were 47.% and 49.2% for 5/16 mg and 1/16 mg doses, respectively Data shown are at Week 8 No hydrochlorothiazide add-on was permitted until after Week 8 Randomized, double-blind, multinational, parallel-group, 16-week study Adapted from Allemann et al. J Clin Hypertens 28;1:185 94 Copyright 28, with permission from Blackwell Publishing 1 Messerli F et al. Am J Hypertens. 21;14:978-9 2 Fogari R et al. Adv Ther. 21;27:48-55 Summary 고혈압은아직도인지, 발견, 치료율이낮은편이라일차의료에서적극적인발견과치료를요한다. 적절히조절되지않는고혈압환자에서는흔히여러약물의사용이복합제재가순응도유지에유리하다. CCB 와 ARB 의복합은이상적인고혈압치료약제중의하나이다. 좀더알아보야할문제들 : 혈압의일중변동 / 백의고혈압 14