관상 동맥 질환 입원 환자의 관리

관상 동맥 질환 입원 환자의 관리

연세대학교 세브란스 병원 심장 내과

김 중 선

Definition of Angina

: A pain or discomfort in the chest or

adjacent areas caused by insufficient

blood flow to the heart muscle.

Myocardial O2 demand

Myocardial O2 supply

Pathogenesis of Angina

The ischemic Cascade

Accurate History Taking is the most important Clue to Diagnosis

1. History taking

2. Physical examination 3. ECG

4. Chest X-ray

5. Serum markers

6. Echocardiography, CT, MRI

7. Exercise ECG, Myocardial spect

8. Coronary Angiography

Classification of Chest Pain

Typical angina (definite)

- Substernal chest discomfort with a characteristic quality and duration

- Provoked by exertion or emotional stress and - Relieved by rest or nitroglycerin

Atypical angina (probable)

Meets 2 of the above characteristics Noncardiac chest pain

Meets ≤1 of the typical angina characteristics

61세 남자 환자가 1년전 부터의 운동시

발생하는 흉통을 주소로 내원하였다 . 상기

환자는 60 PY의 heavy smoker 였다.

ECG

BP 140/80 HR : 60/min

TMT : resting

Electrical Conduction System

TMT : stage IV ^{( 11:45 )}

BP 170/90 HR : 133/min THR : 136/min

Chest discomfort

TMT : recovery ^{( 16:03 )}

BP 150/80 HR : 80/min

Total exercise time : 12 min

Chest discomfort during exercise HR achieved 133/min

Target HR 136/min

Tc-99m Myocardial SPECT (MIBI)

A moderate sized, moderate degree,

reversible defect in the inferior wall.

Stress

Rest

Coronary Angiography

CAD(2VD): Near total occlusion of dRCA

Tubular eccentric up to 90% L/N of Big diagnoal br.

Percutaneous Coronary Intervention

PTCA c stent at d-RCA (Nobori 3.5 * 24)

Ischemic Discomfort

Current Concept of Acute Coronary Syndrome

Acute Coronary Syndrome

ST Elevation No ST Elevation

Myocardial Infarction

Non Q MI Q MI

Unstable Angina

NSTEMI

25%

75% 25% 75%

Spectrum of ACS

Definition of Unstable Angina

i) Rest angina (usually prolonged >20 min) ii) New onset angina (within 2 months)

iii) Rapidly increasing or crescendo angina

iv) 정상 범위 심근 효소 수치

Printzmetal’s Variant Angina

젊고 운동과 관련이 없는 환자에서 주로 새벽에 발생하는 흉통일 경우 의심해야 한다.

전날 음주 후 잘 발생하는 경향이 있다.

치료는 Calcium channel blocker와 nitrate를 사용 (alpha-blocker도 사용 가능)

Beta-blocker 및 aspirin은 사용하지 않는 것이 좋다

2002 ACC/AHA UA/NSTEMI Guidelines

IC ergonovine 50 µg 2

dose Baseline

I II III aVR aVL aVF V1 V2

V3 V4 V5 V6

IC NTG 200 µg

안정형 협심증 환자의 진단 방법

Clinical evaluation History and physical ECG and lab. findings

Assessment of ischemia Exercise ECG

or

Pharmacologic stress or Exercise stress imaging

If Unstable syndrome;

ACS management algorithm

Reassess likelihood of ischemia as cause of symptoms

Suspected HF, prior MI, abnormal ECG or clinical exam, HTN or

DM

Echocardiography (or MRI)

to asscess structural or functional heart disease

Evaluate prognosis on basis of clinical evaluation and non-invasive tests

If Ventricular function assess not already performed at this stage

2006 ESC guideline on the management of stable angina

Summary of test characteristics in patients with angina

Diagnosis of CAD

Sensitivity (%) Specificity (%)

Exercise ECG (운동 부하 검사) 68 77

Exercise echo 80~85 84~86

Exercise myocardial

perfusion 85~90 70~75

Dobutamine stress echo

(도부타민 부하 심초음파) 40~100 62~100

Vasodilator stress echo 56~92 87~100

Vasodilator stress

myocardial perfusion (아데노신

부하 심근 관류 스캔 ) 83~94 64~90

Patient with ischemic type discomfort

Assess initial 12-lead ECG

ST elevation ECG strongly suspicious for ischemia

(ST depression, T inversion) Nondiagnostic ECG Rapid triage to “urgent care” room

Aspirin 160-325 mg chewed Baseline cardiac enzymes

Initiate

reperfusion strategy Thrombolysis

Primary PTCA

Admit

Initiate antiischemic therapy Continue evaluation in ER Follow-up cardiac enzymes Echocardiography

Evidence of ischemia/infarction (?)

Yes No

Discharge Admit

Initiate reperfusion strategy if ST elevation develops

Routine Labs

가슴 통증을 주소로 응급실 내원한 환자

Goal = 10 minutes

ATP

Necrotic

myocardium

Ischemic myocardium potentially salvageable by intervention

1 2 3 4 5 6 12 18 24 3 4 5 6 7 8 9 10 6

20 40 60 80 100

% o f p re -is ch em ic st at e

Hours Days

// // // // //

Reversible injury Wks

Irreversible injury

Ischemic myocardium potentially salvageable by reperfusion

Potentially benefits of late reperfusion

“Time is Myocardium !”

Management of STEMI

Pharmacologic reperfusion

Mechanical reperfusion

Thrombolysis

Percutaneous Coronary Intervention

C.C. Chest pain for 3 hours

Risk factor DM(+), HTN(-), Smoking(-)

Lab CK/CK-MB/TnT 116 / 3.43/ < 0.01

=> f/u CK-MB 314.30 ( 6 hour) ECG ST elevation V2~V5

Diagnosis STEMI

M/58 Lee JW

ECG Changes in Anterior Infarction

Reciprocal change

ST elevation

Primary PCI

Guiding : JLG 7-4, GW : Pilot

Balloon predilation : 2.5 x 20mm

ECG Changes in Inferior Infarction

Primary PCI

 Diffuse or multiple intermediate lesions

We need anti-anginal medication

Even in this era of advanced revascularization

Case 1

 M/63

 CC: DOE

 PI

상기 63세 남환 HTN, DM 과거력 있으며 1년전 부터 계단

오를 때 운동시 호흡 곤란 및 흉통을 주소로 타병원에서

촬영한 CT 상 m-LAD 80% stenosis된 소견 보여 전원됨 .

Case 1

Case 1

Case 1

Stable angina Minimal CAD HTN

DM

Case 1

 약물 치료

Aspirin protect 100 mg #1

Plavix 75mg #1 -> 꼭 필요하지 않음.

Concor 2.5 mg #1 – Beta blocker Crestor 10 mg #1 - Statin

Micardis 40 mg #1 - ARB Januvia 100 mg #1

Amaryl 2 mg/T

Case 2

 M/58

 CC

Chest pain

 PI

상기 58세 남환은 고혈압으로 투약 하던 중 2시간 가량의

흉통이 있어 타병원 내원하여 시행한 EKG 상 II, III, aVF ST

분절 상승 소견으로 본원 응급실로 전원됨.

Case 2

Case 2

Case 2

STEMI CAD-1vd

s/p PTCA c stent at dRCA (*Orsiro 3.0*22)

HTN

Case 2

 약물 치료

Aspirin protect 100 mg #1

Plavix 75mg #1 -> Ticagrelor 180 mg #2 or Prasugrel 10 mg #1

Concor 2.5 mg #1 - Beta blocker

Sigmart 10 mg #2 – 혹은 Nitrate

Rousuvastatin 20 mg #1 - Statin

Acertil 2 mg #1 – ACE inhibitor

Case 3

 M/63

 CC

Chest discomfort

 PI

상기 환자는 고혈압, 심방세동으로 투약 중이며 3개월 전

부터 계단 오를 시 흉통 증상이 있었고 최근 악화되는 소

견으로 Coronary CT 시행 후 관상 동맥 협착 소견으로 본원

전원됨.

Case 3

Case 3

Case 3

Unstable angina CAD(3VD)

s/p PTCA c stent p~d LCx (Xience Prime 3.0*38) mRCA (Xience Prime 3.5*23) HTN A.Fib

Old Tb

s/p Cholecystectomy

Case 3

 약물 치료

Warfarin 2.5 mg #1 -> NOAC으로 사용 가능

Aspirin protect 100 mg #1 -> Ischemic risk 와 bleeding risk

Plavix 75mg #1

Amosartan 5/100 1T #1 – CCB and ARB

Dilatrend SR 16 mg #1 – Beta-blocker

Lipitor 80 mg #1 - Statin

Anti-Platelet Agents

Antiplatelet & antithrombotic therapy

Antiplatelet & antithrombotic therapy

Antithrombotic Trialists' Collaboration. BMJ.

Aspirin Meta-analysis of 287 RCT involving 135,000 patients

Dose of Aspirin in ACS – CURRENT-OASIS 7

Mehta SR, et al. N Eng J Med 2010;363:930-42

High dose: 300-325 mg/d vs Low dose: 75-100 mg/d

Increase minor bleeding (5 vs 4.4 %; HR 1.13, 95 %

CI 1.00-1.27, p=0.04)

Antiplatelet & antithrombotic therapy

CLARITY

2005

PCI-CLARITY

2007

COMMIT

2005

CURE

2001

CREDO

2002

CAPRIE

1996

CHARISMA

2006

Occluded artery 36%  D/MI/UR/

RI 20% 

Mortality 46 % 

Mortality 7% 

D/MI/Stroke 20% 

D/MI/Stroke 27% 

D/MI/Stroke Vasc

9% 

D/MI/Stroke Vasc

Benefit in symptomatic

patients

Clopidogrel

Acute STEMI NSTEMI / ACS PCI Post MI High Risk of Event

D, cardiovascular death; MI, myocardial infarction; UR, urgent revascularization; RI, recurrent ischemia.

BMS History of Stent thrombosis

0 2 4 6 8 10 12 14 16

PS

1991

STRESS

1993

Colombo

1995

STARS

1997

St en t t hr om bo si s (% )

16%

3.5%

1.6% 0.8% 0.6%

ISAR

1996

Coumadin High-pressure balloons and Ticlopidine and Clopidogrel

1. Schatz et al. Circulation.1991;83:148; 2. Fischman et al. N Engl J Med. 1994;331496; 3. Colombo et al. Circulation.1995;91:1676;

4. Schömig et al.Circulation.1994,90:2716; 5. Leon et al. N Engl J Med. 1998;339:1665;

0

5 10 15

0 30 60 90 180 270 360 450

HR 0.81 (0.73-0.90) P=0.0004

Prasugrel Clopidogrel

Days

En dp oi nt (% )

12.1 9.9

HR 1.32 (1.03-1.68) P=0.03

Prasugrel

Clopidogrel ^1.8

2.4

138 events

35 events

Balance of Efficacy and Safety

CV Death / MI / Stroke

TIMI Major

NonCABG Bleeds

NNT = 46

NNH = 167

ARR=0.6%

RRR=12%

P=0.045

HR: 0.88 (95% CI, 0.77−1.00)

ARR=1.9%

RRR=16%

NNT=54*

P<0.001

HR: 0.84 (95% CI, 0.77–0.92)

Wallentin L, et al. N Engl J Med. 2009;361:1045–1057.

Both groups included aspirin.

*NNT at one year.

PLATO: Primary Efficacy Endpoint

(Composite of CV Death, MI, or Stroke)

Months After Randomization

C u m u la ti ve In c id en ce ( % )

8,521 8,628

8,362 8,460

8,124 6,6506,743

5,096 5,161

4,047 4,147 8,219

0 2 4 6 8 10 12

12 11 10 9 8 7 6 5 4 3 2 1 0 13

11.7 Clopidogrel

9.8 BRILINTA

0–12 Months 0–30 Days

4.8 5.4

Clopidogrel

BRILINTA

No. at risk ClopidogrelBRILINTA

9,291 9,333

P2Y12 Inhibitors

Clopidogrel Prasugrel Ticagrelor

Class Thienopyridine Thienopyridine Thienopyrimidine Reversibility Irreversible Irreversible Reversible

Activation Prodrug

Limited by metabolism

Prodrug Not limited by

metabolism Active drug

Onset of effect 2-4 h 30 min 30 min

Duration of effect 3-10 days 5-10 days 3-4 days

Withdrawal before

major surgery 5 days 7 days 5 days

Euro Heart J 2011;32:2999-3054

• Diagnosis

Unstable angina CAD (2VD)

S/P PTCA c stent at mLAD (Cypher 3*23), pLCX (Express 4.5*24) (2004.7)

HTN

Brief history

Coronary Angiography

Initial CAG After thrombosuction

항혈소판 제제 사용시 고려 사항

임상 양상 : 안정형 협심증 vs. 급성 관동맥 증후군

스텐트의 종류

동반 질환

Stable angina (모든 환자)

Aspirin 사용은 권고 한다 .

Clopidogrel 은 Aspirin 사용이 어려운 경우 대체로 사용 할 수 있다 .

2013 ESC Guideline

Stable angina (스텐트 시술 환자)

2013 ESC Guideline

Aspirin과 Clopidogrel 복합사용은 권고 한다.

혈소판 기능 검사는 특별한 경우에 한해서 시행 할 수 있다.

Acute coronary syndrome

• Unstable angina

Non ST Elevation myocardial infarction

2014 ESC Guideline

Aspirin 과 Ticagrelor 나 Prasugrel 12 개월 복합사용은 권고

Ticagrelor 나 Prasugrel 사용이 어려울 경우 Clopidogrel 사용 권고

Acute Coronary Syndrome

ST elevation myocardial infarction

2014 ESC Guideline

Aspirin 과 Ticagrelor 나 Prasugrel 12 개월 복합사용은 권고

Ticagrelor 나 Prasugrel 사용이 어려울 경우 Clopidogrel 사용 권고

처음 발견 즉시 P2Y ₁₂ 억제제 사용 권고

Special conditions (Non-valuar atrial fibrillation)

2014 and 2015 ESC Guideline

Stable angina

_HAS-

BLED score

적어도

₁

Triple anti- coagulation

AF에서는 3제 사용시 Ticagrelor 나 Prasugrel 사용은 권고하지 않음

Dual Antiplatelet Therapy

2014 ESC/EACTS Guideline (유럽 지침)

Anti-Anginal Medications

LH Opie, 2001 Reduced Preload

Systemic Circulation

Reduced venous return

Venous capacitance vessels

Arteriolar resistance vessels Ca

Blockers

-Blockers Nitrates ACEi or ARB Reduced Afterload

SA

Nitrate

-Blockers

Verapamil,diltiazem

Inotropic

Nitrates Ca

Blockers

Dilate

Action of Anti-Angina Drugs

Anti-anginal Effect of Beta-blockers

↓↓↓ Heart rate ↓↓ Contractility ↓ BP

↓↓ BP during exercise

↓ Oxygen wastage

↑↑ Diastolic period ↓↓ Paradoxical constriction of coronary

stenotic lesions

↓ Afterload

↓ Wall stress

↓↓↓ Myocardial oxygen demand

↑ Diastolic coronary blood flow

↑ Coronary blood

flow to ischemic area

↑ Coronary Blood flow

Mostly dependent on the slowing heart rate during exercise as well as at rest.

Modified from Bonow: Braunwald’s Heart Disease, 9

ed., 2011

Lipid Lowering Medicaitons

Atherosclerosis Revolution

4S Study

Lancet 1994;344:1383

15

10

5

0 0 1 2 3 4 5 6

Years since randomisation

Pr op or tio n of p at ie nt s de ad

placebo

Simvastatin

risk reduction 30%

p = 0.0003

Miracle Drug !

The end of cholesterol controversy

ASCOT AFCAPS

ASCOT

AFCAPS

WOSCOPS

WOSCOPS 4S

4S

CARE

HPS

LIPID

HPS

CARE LIPID

PROVE-IT

(Atv) PROVE-IT (Pra)

IDEAL (Atv)

IDEAL (Sim)

(Atv 80 mg)TNT

TNT (Atv 10 mg)

The lower, the better

Atv = atorvastatin; Pra = pravastatin; Sim = simvastatin; PROVE-IT = Pravastatin or AtorVastatin Evaluation and Infection Therapy;

IDEAL = Incremental Decrease in Endpoints through Aggressive Lipid Lowering; ASCOT = Anglo-Scandinavian Cardiac Outcomes Trial;

AFCAPS = Air Force Coronary Atherosclerosis Prevention Study; WOSCOPS = West of Scotland Coronary Prevention Study

Adapted from Rosenson RS. Expert Opin Emerg Drugs. 2004;9:269–279; LaRosa JC, et al. N Engl J Med. 2005;352:1425–1435; Pedersen TR, et al. JAMA. 2005;294:2437–2445.

Mean Treatment LDL-C at Follow-up, mg/dL (mmol/L)

Ev en t, %

Statin Placebo

0 30

0 80

(2.1) 140

(3.6) 200

(5.2) 25

20 15 10 5

100 (2.6) 40

(1.0) 120

(3.1) 180

(4.7) 60

(1.6) 160

(4.1)

Secondary Prevention

Primary

Prevention

Relationship Between LDL-C and CV Incidence

Progression Regression

-1.5 -1.0 -0.5 0.0 0.5 1.0 1.5 2.0

40 50 60 70 80 90 100 110 120

Change in Percent Atheroma

Volume*

Achieved LDL-C (mg/dL)

REVERSAL Pravastatin 40mg

REVERSAL Atorvastatin 80mg

ILLUSTRATE Atorvastatin + Placebo ASTEROID

Rosuvastatin 40mg SATURN Atorvastatin 80mg

SATURN Rosuvastatin 40mg

CAMELOT Placebo

STRADIVARIUS Placebo

A-PLUS Placebo

LDL-C & Change in PAV

Definition of high-risk / highest-risk or very high patient:

• ATP I: definite CHD or 2 other CHD risk factors¹

• ATP II: existing CHD or other atherosclerotic disease²

• ATP III and the 2004 update: CHD or CHD risk equivalents^3,4

• 2° AHA/ACC 2006: established coronary and other atherosclerotic disease⁵

• ADA 2010: overt CVD⁶

• ESC/EAS 2011: CVD (MI, ACS, revascularization), ischemic stroke, type 2 DM, moderate to severe CKD, or SCORE ≥10%⁷

 As part of therapeutic lifestyle changes, including diet,

LDL-C treatment goals for high-risk patients have been lowered over time

Optional goal:

<70 mg/dL

1988 ATP I 1993

ATP II 2001

ATP III 2004

ATP III Update

Very-high-risk pts

Goal:

<130 mg/dL

Goal:

100 mg/dL

Goal:

<100 mg/dL

2006 AHA/ACC

Reasonable goal:

<70 mg/dL

2010 ADA

<70 mg/dL

Goal:

<100 mg/dL

Goal:

<100 mg/dL

Goal:

<100 mg/dL

Overt CVD High-risk pts

1. NCEP ATP I. Arch Intern Med. 1988;148:36–69; 2. NCEP ATP II. JAMA. 1993;269:3015–3023; 3. NCEP ATP III. JAMA. 2001;285:2486–2497; 4. Grundy SM et al. Circulation. 2004;110:227–239; 5.

Smith SC Jr et al. Circulation. 2006;113:2363–2372; 6. ADA. Diabetes Care. 2010;33(suppl 1):S11–S61. 7. Reiner Z. et al. European Heart Journal 2011;32:1769-1818

ESC/EAS 2011

<100 mg/dL

Goal:

<70 mg/dL

Very high risk pts

Familial dyslipidemia, severe HTN

CHD: coronary heart disease, CVD: cardiovascular disease, MI: myocardial infarction, ACS: acute coronary syndrome, CKD: chronic kidney disease, HTN: hypertension

LDL-C Goals for High-risk patients have become

More intensive over time

2013 ACC/AHA guideline – 4 statin benefit group

Age <75 y High-intensity statin (Moderate-intensity statin if not)

Age >75 y Moderate-intensity statin

High-intensity statin (Moderate-intensity statin if not)

Moderate-intensity statin

Estimated 10-y ASCVD risk ≥7.5%*

High-intensity statin

Estimate 10-y ASCVD Risk with Pooled Cohort Equations*

Moderate-intensity statin Yes

Yes

Yes

No No

No

Yes Yes

Yes

LDL–C ≥190 ^mg/dL

DM Type 1 or 2 Age 40-75 y

Adults age >21 y and a candidate for statin therapy

≥7.5%

Estimated 10-y ASCVD risk and age 40-75 y secondary prevention

pr im ar y pr ev en tio n

Yes

No

DM with

Clinical ASCVD

Intensity of Statin Therapy

Stone NJ, et al. published online November 12, 2013 Circulation. 2. 2014 NICE LIPID modification Clinical guideline

20 13 A CC /A H A g ui de lin e

20 14 N IC E gu id el in e

Low Intensity Medium Intensity

High Intensity

5 10 20 40 mg 10 20 40 80 mg 10 20 40 mg 10 20 40 80 mg 20 40 80 mg

Intensity High-Intensity Moderate-Intensity Low-Intensity

Reduction %

in LDL-C > 50% reduction of LDL

with daily statin 30-50% reduction of LDL

with daily statin <30% reduction of LDL with daily statin

Statin and dose

Atorvastatin (40)-80 mg

Rosuvastatin 20 (40) mg Atorvastatin 10 (20) mg Rosuvastatin (5) 10 mg Simvastatin 20-40 mg Pravastatin 40 (80) mg Lovastatin 40 mg Fluvastatin XL 80 mg Fluvastatin 40 mg bid Pitavastatin 2-4 mg

Simvastatin 10 mg Pravastatin 10-20 mg Lovastatin 20 mg Fluvastatin 20-40 mg Pitavastatin 1 mg

분류 위험요인 혈중 지질수치 기준 해당 약제

고 저밀도지단백순수 콜레스테롤 (LDL-C)혈증

0~1 개 LDL-C 160 mg/dL 이상

HMG-CoA 환원효소억제제, 담즙산제거제,

Fibrate 계열 중 1종

2 개 이상 LDL-C 130 mg/dL 이상

관상동맥질환 또는 이에 준하는 위험인자가 있는 경우

(당뇨, 말초동맥질환, 복부대동맥류, 증상이 동반된 경동맥질환)

LDL-C 100 mg/dL 이상

급성관상동맥증후군 LDL-C 70 mg/dL 이상

고 트리글리순수 세라이드(TG)혈증

위험요인이 없는 경우 TG 500mg/dL 이상 Fibrate 계열,

Niacin 계열 중 위험요인이 있거나 1종

당뇨병이 있는 경우 TG 200mg/dL 이상

고 LDL-C 및

고 TG혈증 복합형 “순수 고 LDL-C혈증”과 “순수 고 TG혈증”에 해당되는 경우

LDL-C 및 TG에 작용하는 약제별로 각각 1종씩 인정

위험 요인

① 흡연

② 고혈압 (BP≥140/90 mmHg 또는 항고혈압제 복용)

③ 낮은 고밀도지단백콜레스테롤 (HDL-C) (<40 mg/dL)

④ 관상동맥질환 조기 발병의 가족력 (부모, 형제자매 중 남자<55세, 여자<65세에서 관상동맥질환이 발병한 경우)

⑤ 연령 (남자 ≥ 45세, 여자 ≥ 55세)

※ HDL-C≥60 mg/dL은 보호인자로 간주하여 총 위험요인 수에서 하나를 감한다.

2014년 이상지질혈증 새 보험급여기준

시행일자: 2014.1.1 / 보건복지부 고시 제2013-210

 Risk stratification

 Risk factor management ; BP & DM control, stop smoking, exercise, diet, education

약물 치료 정리

CCB, nitrate Anti-anginal

CCB, nitrate Anti-anginal ACE inh/ARB

Beta blocker ACE inh/ARB

Beta blocker Aspirin

Statin Aspirin

Statin

Level of evidence

Strong weak

Thanks for your Attention

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