update management of nstemiperkicabangmalang.org/assets/files/2. hm_update... · 2019-07-25 ·...

UPDATE MANAGEMENT OF NSTEMIThe Role of Fondaparinux in ACS

JOHN DOE, MD

SUBTITLE 32 PT ARIAL BOLD ITALICS

Heny Martini, MD, FIHACongenital and Structural Division in

Cardiology and Vascular Department, University of Brawijaya-

Saiful Anwar Hospital, Malang

Admission Chest

Pain

Persistent

ST-elevation

ST/T -

abnormalitiesECG

Normal or

undetermined

ECG

Working

diagnosisAcute Coronary Syndrome

STEMIDiagnosis NSTEMI/ UAP

Troponin

Rise/fall

Troponin

normal

Bio-

chemistry

NSTEMIUnstable

AnginaDiagnosis STEMI

1

2

3

= Unstable

STEMI

1. Revascularisation

2. Anti - Thrombotic

3. Anti - Ischemia

N- STEMI

1. Anti - Ischemia

2. Anti - Thrombotic

3. Revascularisation

Choice of Therapy

Algorithm in Acute Coronary Syndrome

Admission

Working

Diagnosis

ECG

Bio-

Chemistry

Risk

Stratification

Management

Secondary

Prevention

CHEST PAIN

Suspected ACS

Persistent ST

elevationNo Persistent

ST elevation{on serial

ECG}

Performed

in 10 min

Medical Therapy,

coronary angiographyModified from ESC Guideline

Initial Management, ±

revascularization

Risk: High/Low

Troponin,

CKMB (+)Troponin,

CKMB (+)

- ACS Unlikely

- NSTEMI

-STEMI

Paradigm for ACS Management:

Efficacy vs Safety

Acute Coronary Syndrome (ACS) A Major Cause of Mortality and Morbidity

UA/NSTEMI

• In-hospital death and re-infarction: 5-10%1

• Six-month mortality in the GRACE registry2 (from admission to 6 months):

- NSTEMI: 13%

- UA: 8%

STEMI

• 1/3 of STEMI patients will die within 24 h of the onset of ischemia1

• In-hospital death and reinfarction: 8-10%3

• One-month mortality: 6-7%4

1.Grech & Ramsdale. Acute coronary syndrome : unstable angina and non-ST segment elevation myocardial infarction. BMJ 2003;326:1259-61;

2. Fox. et al. An international on acute coronary syndrome care: Insight from the global registry of acute coronary event

Am Heart. Et al J 2004:148:S40-5;

3.Antman et al. ACC/AHA guideline for the management of patiets with ST-Elevation Myocardial infarction. Circulation 2004;110:e82-292;

4.van de Werf et al. Management of acute myocardial infarction in patients presenting with ST-segment Elevation. Eur Heart J 2003;24:28-66

Moscucci et al. Predictor of majaor bleeding in acute coronary syndromes: the Global Registry of Acute Coronary Events (GRACE) Eur Heart J 2003;24:1815-23

GRACE Registry in 24,045 ACS patients

*After adjustment for comorbidities, clinical presentation, and hospital therapies.

**p<0.001 for differences in unadjusted death rates

OR (95% CI) 1.64 (1.18 to 2.28)*

0

Overall ACS UA NSTEMI STEMI

10

20

30

40

**

****

**

5.1

18.6

3.0

16.1

5.3

15.3

7.0

22.8

Inh

osp

ita

ld

eath

(%)

Inhospital major bleeding YesNo

Major Bleeding is Associated with an Increased Risk of Hospital Death in ACS Patients

Inhibition of platelet aggregation

High risk of

ischemic events

High risk of

bleeding events“Sweet spot”

Ischemic risk Bleeding risk

Balancing safety and efficacy

Ferreiro & Angiolillo. Thromb Haemost 2010 (in press)

Ischemic

Complications

► Death

► MI

► Urgent TVR

Evolving Paradigm for Evaluating ACS

Management Strategies

Composite Adverse Event Endpoints

Ischemic

ComplicationsHemorrhage

HIT

► Death

► MI

► Urgent TVR

► Major Bleeding

► Minor Bleeding

► Thrombocytopenia




Periprocedural

ComplicationsClinical

Benefit

►Death

►Major Disability

► Cost

► Ease of Use

► Duration of

Therapy

► Accounting for

Bleeding and

Ischemic Endpoints




Selection of Therapy in the ED

Must Include Consideration of Bleeding Risk

►Age

►Gender

►Renal insufficiency

►Baseline anemia

►Expectation of prolonged medical therapy

Evolution of ACS Therapies

Adapted from White HD et al. Lancet 2008; 372: 570–84

Aspirin

Heparin

1990 1996 1997 2000 2001 2005 2007 2008

Year

Low molecular

weight heparin

IIb/IIIa receptor

antagonist

Early invasive management

CLOPIDOGRELAtorvastatin

Fondaparinux

Bivalirudin

Integrated

strategy

PRASUGREL

Sites of Antithrombotic Drug Action

Tissue factor

Plasma clottingcascade

Prothrombin

Thrombin

Fibrinogen Fibrin

Thrombus

Platelet aggregation

Platelet activation

Collagen

Thromboxane A2

ADP

AT

AT

Aspirin

ClopidogrelPrasugrelCangrelor

EptifibatideAbciximabTirofiban

(GPI)BivalirudinHirudin

Argatroban

FactorXa

Heparin LMWHs

Fibrinolytics

Fondaparinux

AT

Selective Factor Xa Inhibitor in

Management of ACS

UFH LMWH Fondaparinux(Arixtra)

Presence of cofactor required +++ +++ +++

Renal clearance of clinical relevance ± ++ +

Non-specific protein binding +++ + +

Bioavailability by s.c or oral administration +

( for s.c administration )

++ +++

Predictability of pharmacological effect - ++ ++

Inhibition of thrombin generation ++ ++ ++

Inhibition of thrombin activity +++ + -

Inhibition of bound – thrombin - - -

Rebound of thrombin generation after discontinuation +++ ++ -

Platelet Activation +++ + -

Immune thrombocytopenia +++ + -

Decreased bone density +++ + -

Raffaele D.C, et al. Anticoagulants in Heart Disease : Current Status and Perspectives. Eur Heart J 2007 ; 28 : 880-913

A comparison of relevant pharmacological properties of the different anticoagulant in current clinical use

FondaparinuxFondaparinux is a Synthetic and Selective Xa Inhibitor

Fondaparinux Sodium, 2.5 mg/0.5 ml solution for injection,

in pre-filled syringe.

Fondaparinux 2,5 mg does not have clinically relevant affect on

routine coagulations test.

Unlike heparins or LMWH, fondaparinux is a synthetic compound and not derived from animal products.

Has rapid onset of action, 100% bioavailability after SC injection.

Elimination Half life is about 17 hours in healthy young subject and

about 21 hours in health elderly subject

Eliminated mainly by the kidneys, and is contraindicated if CrCl is <20 mL/min1. ArixtraTM PI BPOM 4 October 2010, GDS04/IPI04 (23 January 2007).

2. Jack Hirsh MD, Fondaparinux 2007. Preface

FondaparinuxA Synthetic Inhibitor of Factor Xa

Single chemical entity

No risk of pathogen contamination

Highly selective for its target

Once-daily administration

Rapid onset (Cmax/2=25 min)

No liver metabolism

Does not bind significantly to plasma proteinsother than AT.

No reported cases of HIT

No dose adjustment necessaryin the healty elderly subject.

1.Herbert et al. A Noval Anti-factor Xa antitrombotic Agent . Cardiovasc Drug Rev 1997;15:1-26 2. Van Boeckel et al. The unique antithrombin III binding domain of Heparin: a lead to new Synthetic Antitrombotic. Angew Chem [Int Ed Engl] 1993;32: 1671-90

3. ArixtraTM PI BPOM 4 October 2010, GDS04/IPI04 (23 January 2007).

Fondaparinux Mechanism of Action

1. Olson et al. Role of the antithrombin-binding Pentasaccharide in heparin acceleration of antithrombin-proteinase reaction J Biol Chem 1992;267:12528-38

2. Turpie et al. A synthetic Pentasaccharide for the Prevention of deep-vein trombosis after total hip replacement N Engl J Med 2001;344:619-25

Thrombin

Fibrinogen

Extrinsic

pathway

Intrinsic

pathway

AT

Fondaparinux

XaAT

Antithrombin

Fibrin clot

Xa

Pro-thrombin

Reutilized

Fondaparinux indications


2. Salim Yusuf, et al. Comparison of Fondaparinux and Enoxaprine in Acute Coronary Syndrome.

The fifth organization to assess strategies in Acute Ischemic Syndrome investigator. N Egl J Med 2006:354:1446-76

3. Salim Yusuf. Et al. The OASIS 6 trial. Effect of Fondaparinux on Mortality and Reinfarction in Patients with Acute ST-segment elevation MI.

Jama 2006; 259:1519-30.

4. Turpei Agg, et al. Fondaparinux vs Enoxaparine for the prevention of VTE in MOS.

A meta-analysis of randomized double blind studies. Arch Intern Med 2002;162:1883-40.

5. Cohen AT, et al : Efficacy and Safety Fondaparinux for The Prevention of VTE in older medical patients,

BMJ 2006: 332: 325-9

6. AgnelliG et al. Randomized Clinical Trial of post operative fondaparinux versus perioperative daltaparine of venous

thromboembolism in high risk abdominal surgery. Br J Surg 2005;92:1212-20.

Treatment of ACS Prevention of VTE After MOS & Abdominal Surgery

Treatment of UA/NSTEMI.

Adjuctive Treatment STEMI.

Prevention of VTE in Medical Patients

Hip Fracture.

Knee Replacement Surgery.

Hip Replacement Surgery.

Abdominal Surgery.

Congestive Heart Failure. Acute Respiratory Illness.

Acute Infection Inflammatory diseases

Fondaparinux Study


2. Salim Yusuf, et al. Comparison of Fondaparinux and Enoxaprine in Acute Coronary Syndrome.

The fifth organization to assess strategies in Acute Ischemic Syndrome investigator. N Egl J Med 2006:354:1446-76

3. Salim Yusuf. et al. The OASIS 6 trial. Effect of Fondaparinux on Mortality and Reinfarction in Patients with Acute ST-segment elevation MI.

Jama 2006; 259:1519-30.

4. Turpei Agg, et al. Fondaparinux vs Enoxaparine for the prevention of VTE in MOS.

A meta-analysis of randomized double blind studies. Arch Intern Med 2002;162:1883-40.

5. Cohen AT, et al : Efficacy and Safety Fondaparinux for The Prevention of VTE in older medical patients,

BMJ 2006: 332: 325-9

Treatment of ACS Prevention of VTE After MOS & Abdominal Surgery

OASIS 5 Study : 20,000 patients with UA/NSTEMI.

OASIS 6 Study : 12,000 patients with STEMI.

Prevention of VTE in Medical Patients

Artemis Study : 890 Acutely ill medical

patients.

MOS Meta Analysis Study : 7,344 patients.

a) EPHESUS : Elective Hip Surgery : 2309 patients

b) PENTHATHLON : Total hip Surgery: 2275 patients

c) PENTAMAKS : Major Knee Surgery : 1,049 Patiets.

d) PENTHIFRA : Hip Fracture Surgery : 1,711 Patiets.

PEGASUS Study : 2,048 patient untder going Major

Abdominal Surgery

Study Hypothesis OASIS 5

Fondaparinux 2.5 mg s.c. once dailywill show similar efficacy

to enoxaparin, while improving bleeding

1. Michelangelo OASIS 5 Steering Committee. Am Heart J 2005;150:1107.e1-.e10

2. OASIS 5 Investigators. N Engl J Med 2006;354:1464-76

OASIS 5: An International, Multicenter, Randomized, Double-Blind, Double-Dummy Trial in 41 Countries

1. ArixtraTM PI BPOM 4 October 2010, GDS04/IPI04 (23 January 2007).2. Salim Yusuf, et al. Comparison of Fondaparinux and Enoxaprine in Acute Coronary Syndrome.

The fifth organization to assess strategies in Acute Ischemic Syndrome investigator. N Egl J Med 2006:354:1446-76.

20,078 patients with UA/NSTEMI

Fondaparinux2.5 mg s.c. od up to 8 days

Aspirin, Clopidogrel, anti-GPIIb/IIIa, planned Cath/PCI as per local practice

Randomization

Enoxaparin1 mg/kg s.c. bid for 2-8 days

1 mg/kg s.c. od if ClCr<30mL/min

Vital status ascertained in 20,066 (99.9%) Lost to follow-up at day 9: fondaparinux: n=7 and enoxaparin: n=5

Study Objectives and Outcomes

Objectives

Primary efficacy objective : To demonstrate non-inferiority of fondaparinux compared with enoxaparin

Primary safety objective : To determine whether fondaparinux was superior to enoxaparin in preventing major bleeding

Outcomes (centrally adjudicated)

Primary efficacy : 1st occurrence of the composite of death, MI, or

refractory ischemia (RI) up to day 9

Primary safety : Major bleeding up to day 9

Risk benefit : Death, MI, refractory ischemia, major bleeds up to day 9

Secondary : Above & each component separately at days 30 and 180



Fondaparinux has the same efficacy vs Enoxaparin at Day 9 (Primary Efficacy: death/MI/RI)



Days

Cu

mu

lati

ve

Ha

zard

0.0

0.01

0.02

0.03

0.04

0.05

0.06

0 1 2 3 4 5 6 7 8 9

Enoxaparin

Fondaparinux

HR: 1.01 95% CI: 0.90-1.13

p=0.007 for non-inferiority

Time to event death/MI/RI up to day 9

Fondaparinux: 5.8% (579 events) Enoxaparin: 5.7% (573 events)



Days

Cu

mu

lati

ve

Ha

zard

0.0

0.01

0.02

0.03

0 3 6 9 12 15 18 21 24 27 30

HR: 0.83 95% CI: 0.71-0.97

p=0.02

Enoxaparin

Fondaparinux

0.04

17 %

Fondaparinux Significantly Reduced Mortality vs. Enoxaparin up to Day 30

Fondaparinux Reduced the Rate of the Composite of Death, MI or Stroke up to 6 Months



0.0

Days

0 20 40 60 80 100 120 140 160 180

Cu

mu

lati

ve

Ha

zard

HR: 0.8995% CI: 0.82-0.97

p=0.007

Enoxaparin

Fondaparinux

0.02

0.04

0.06

0.08

0.10

0.12

0.14

11 %

Fondaparinux Significantly reduced Major Bleeding vs Enoxaparine at day 9



Days

Cu

mu

lati

ve

Ha

zard

0.0

0.01

0.02

0.03

0.04

0 1 2 3 4 5 6 7 8 9

HR: 0.52 95% CI: 0.44-0.61 p<0.001

Enoxaparin

Fondaparinux

48 %

Major Bleeding Lower with Fondaparinux Irrespective of Renal Function

Ma

jor

Ble

ed

40 60 80 100 120 140

0.0

20

.04

0.0

60

.08

0.1

0

Enoxaparin(dose adjusted for renal function)

Fondaparinux

GFR mL/min/1.73 m2Fox KAA. Ann Int Med 2007;147:304-310

Low vs. Standard Dose Unfractionated Heparin for

Percutaneous Coronary Intervention

in Acute Coronary Syndromes Patients

treated with Fondaparinux:

the FUTURA/OASIS 8 Randomised Trial

Sanjit S. Jolly on behalf of FUTURA/OASIS 8 Trial Group

FUTURA Trial Study Objectives

• Primary Objective:: To determine whether Low fixed dose vs. Standard ACT guided unfractionated heparin during PCI reduces the composite of peri-PCI* major, minor bleeding and vascular access site complications in ACS patients treated with fondaparinux

• Secondary Objective: To determine if major bleeding rates in FUTURA (with unfractionated heparin added to fondaparinux) are higher than OASIS 5 PCI (with Fondaparinux used alone)

• *Peri-PCI defined within 48 hours following PCI

Study Design

NSTEACSFonda 2.5

mg sc

Angio No PCI

30 Day Follow-Up

Angio with PCI R

Std Dose UFH

(85 U/kg or 60 U/kg with GP IIb/IIIa)

ACT guided*

30 Day Follow-Up

Low Dose UFH

(50 U/kg irrespective of GP IIb/IIIa) –

without ACT

30 Day Follow-UpWith at least 2 of following:

• Age>60

• elevated biomarkers

• ECG changes

Patients were not eligible if

required urgent coronary

angiography (<120 min) due

to clinical instability

Adjunctive therapy

during PCI

Double

Blind

Registry

*ACT Targets consistent with current guidelines

Coronary Angiography/PCI to be

performed within 72 hours

Study Outcome Definitions

Major Bleeding

(OASIS 5)

• Fatal

• Symptomatic ICH

• Retroperitoneal hemorrhage

• Intraocular bleeding leading to significant vision loss

• Requiring surgical intervention

• Hb drop of ≥3 g/dL

• Blood transfusion of > two units RBCs

Minor Bleeding Any other significant bleeding leading to transfusion of one

unit of blood or discontinuation of antithrombotic therapy.

Major Vascular

Access Site

Complications

• Large hematoma (≥5 cm or requiring intervention)

• Pseudoaneurysm requiring treatment

• Arterio-venous fistula

• Other vascular surgery related to the access site

Comparison to OASIS 5 Major Bleeding (<48 h of PCI)

Adjusted

Major bleeding

rate (95% CI)

OASIS 5 PCI

Fondaparinux

Major bleeding

OASIS 5 PCI

Enoxaparin

Major bleeding

FUTURA

standard dose

UFH1.1% (0.6-2.1)

1.5% 3.6%

FUTURA

low dose UFH1.2% (0.6-2.2)

Unfractionated heparin + fondaparinux does not increase peri-PCI major

bleeding with rates apparently lower than when enoxaparin is used.

NSTEMI Guideline

RoffiM, PatronoC EurHeart J.2015 Aug 29. pii: ehv320.41

Recommendations for anticoagulants



Recommendations for anticoagulants in patients with normal and impaired renal function

Pedoman Tatalaksana Sindroma Koroner Akut, PERKI 2018

Conclusions

• No significant difference in major/minor bleeding or vascular complications

between Low fixed dose and Standard dose unfractionated heparin

• While low dose heparin reduced minor bleeding there was a trend towards

reduced efficacy

• The use of unfractionated heparin for PCI on a background of fondaparinux

did not increase major bleeding when compared to fondaparinux alone and

lower than that previously observed with enoxaparin

Implications

• ACS patients treated with fondaparinux can undergo PCI safely with

unfractionated heparin

• No evidence to depart from guideline recommended standard dose

regimen of unfractionated heparin during PCI

• Adding unfractionated heparin during PCI to fondaparinux preserves the

benefits and safety of fondaparinux (ie. reduced bleeding) while

minimizing catheter thrombus

In Management of ACS, we need to consider the efficacy versus safety of

antithrombotic that we use, including anticoagulant

Anticoagulant options in management of UA/NSTEMI:

1. UFH

2. LMWH

3. Fondaparinux

Based on OASIS 5, Fondaparinux (Arixtra®) is a selective factor Xa inhibitor which

offers good efficacy with less bleeding risk compared to enoxaparin for management

UA/NSTEMI

Fondaparinux 2.5 mg SC once daily is recommended by ESC guideline for

UA/NSTEMI patients as having favorable efficacy-safety (Class I)

Adding unfractionated heparin during PCI to fondaparinux preserves the benefits and

safety of fondaparinux (ie. reduced bleeding) while minimizing catheter thrombus.

Take Home Message

THANK YOU

Background: OASIS 5

Randomized trial of Fondaparinux vs. Enoxaparin in NSTEACS (n=20,078)

demonstrated non-inferiority for CV death, MI, Refractory Ischemia

Fondaparinux vs. Enoxaparin reduced major bleeding

by 48% and mortality by 17%

OASIS 5 Investigators. N Engl J Med 2006;354:1464-76

Major Bleeding at 9 days

-

48% relative

risk reduction

Days

0.0

0.01

0.02

0.03

0.04

0 1 2 3 4 5 6 7 8 9

HR: 0.52 95% CI: 0.44-0.61 p<0.0001

Enoxaparin

Fondaparinux

4.1 %

2.2 %

Mortality at 30 days

Fondaparinux: 295 deathsEnoxaparin: 352 deaths

Days

0 3 6 9 12 15 18 21 24 27 30

0.0

0.01

0.02

0.03

HR: 0.83 95% CI: 0.71-0.97

p=0.02

Enoxaparin

Fondaparinux

0.043.5 %

2.9 %

-

17 % RRR

Background: OASIS 5 Fondaparinux vs. Enoxaparin in

ACS patients undergoing PCI (n=6177)

Outcome Day 9Enox

N = 3072

Fonda

N = 3105HR P value

Death, MI or Stroke 6.2 6.3 1.03 0.79

Major Bleeding 5.1 2.4 0.46 <0.00001

Catheter

Thrombosis0.4 0.9 3.59 0.001

Mehta SR., et al .JACC. 2007;50:1742-51

Mehta SR, et al. Circulation, 2008;118:2038-46

• Data from OASIS 5, that unfractionated heparin may prevent catheter thrombosis but optimal dose uncertain

• FUTURA trial was designed to determine the optimal regimen of heparin to prevent catheter thrombus and ischemic events in fondaparinux treated

patients,without increasing bleeding.

Statistical Considerations

• Primary Outcome: Peri-PCI (within 48 hours) major bleeding, minor bleeding or major vascular access site complications

• Key Secondary outcome: Peri-PCI major bleeding, death, MI, or TVR at 30 days

• Study power: Based on a 5% event rate in standard dose group, study had 81% power to detect a 50% RRR in the primary endpoint. (RRR derived from OASIS 5)

• 30 day Follow up complete in 99.9%

Baseline and Procedural Characteristics

Standard Dose UFH

N=1002

Low Dose UFH

N=1024

Age (years) 65.5 65.3

Male (%) 68.5 67.3

Diabetes (%) 27.9 26.1

ECG changes (%) 74.6 75.3

Elevated Troponin I or T (%) 78.8 81.3

Aspirin (%) 96.1 95.4

Clopidogrel (%) 96.3 94.6

Procedural GP IIb/IIIa (%) 26.4 25.8

Femoral Access (%) 62.4 64.2

Any Stents placed (%) 94.0 93.7

Median Times (IQR)

Standard Dose

UFH

N=1002

Low Dose

UFH

N=1024

Symptom onset to PCI (h) 27 (16-42) 28 (17-43)

Last fondaparinux dose to PCI (h) 4:07 (2:43-14:20) 4:26 (2:45-14:44)

Duration of fondaparinux (days) 3 (2-5) 3 (2-5)

Duration of hospitalization (days) 4 (3-7) 4 (3-7)

Primary Outcome at 48 h

Standard Dose UFH (n=1002)

LowDose UFH (n=1024)

OR 95% CI P

Peri-PCI major, minor bleeds and vascular access complications 5.8% 4.7% 0.80 0.54-1.19 0.27

Primary Outcome at 48 h


LowDose UFH (n=1024)

OR 95% CI P

Peri-PCI major, minor bleeds and vascular access complications 5.8% 4.7% 0.80 0.54-1.19 0.27

Components :

Major bleeds 1.2% 1.4% 1.14 0.53-2.49 0.73

Minor bleeds 1.7% 0.7% 0.40 0.16-0.97 0.04

Major vascular access site complications 4.3% 3.2% 0.74 0.47-1.18 0.21

Secondary Outcomes at 30 days


Low Dose UFH (n=1024)

OR 95% CI P

Peri-PCI major bleeding, death, MI, TVR

3.9% 5.8% 1.51 1.00-2.28 0.05

Death, MI, TVR 2.9% 4.5% 1.58 0.98-2.53 0.06

Death 0.6% 0.8% 1.31 0.45-3.78

MI 2.5% 3.0% 1.22 0.72-2.08

TVR 0.3% 0.9% 2.95 0.80-10.9

Stent thrombosis 0.5% 1.2% 2.36 0.83-6.73 0.11

Catheter thrombosis 0.1% 0.5%* 4.91 0.57-42.1 0.15

* One event occurred during coronary angiography after randomization

Outcomes to 30 days

Consistent results by Age, Sex,

GP IIb/IIIa, BMI, CrCl, Arterial access site

Low dose 2.2% vs. Standard dose 1.8%,

HR 1.20 (95% CI 0.64-2.23, p=0.57)

Major Bleed at 30 days

Days

3 6 9 12 15 18 21 24 27 303 6 9 12 15 18 21 24 27 3000

0.0

0.01

0.02

0.03

0.04

0.05

Standard DoseLow Dose

No. at Risk

Standard Dose

Low Dose

1002 986 981 980 980 978

1024 1002 1001 998 997 994

Days

0 3 6 9 12 15 18 21 24 27 300 3 6 9 12 15 18 21 2 27 30

0.0

0.01

0.02

0.03

0.04

0.05Death/MI/TVR at 30 days

Standard DoseLow Dose

No. at Risk

Standard Dose

Low Dose

1002 980 975 975 974 971

1024 997 988 982 981 978

Low dose 4.5% vs. Standard dose 2.9%

HR 1.56 (95% CI 0.98-2.48, p=0.06)

update management of nstemiperkicabangmalang.org/assets/files/2. hm_update... · 2019-07-25 ·...

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