ESC-update 2015 · STEMI 43.4 44.5 Unstable Angina (UA) 17.4 16.9 ACS to Rand. (days) 72 ±44 72 ±43 Demographics Placebo N = 3034 Lixisenatide N = 3034 CV Medications (%) ACEi/ARB

Diabetes und KHK

Carsten Tschöpe

ESC-update 2015

• TECOS -> Sitagliptin

• ELIXA -> Lixisenatide

• EMPARG -> Empagliflozin

• ALBATROSS -> Aldosteron Inhibition

• ARTS-HF -> Finerenone

• BACC -> Troponin bei ACS

Bellytina64




• ALBATROS -> Aldosteron Inhibition



GLP-1- and GIP-metabolites

DPP-4-

Enzyme

GLP-1

Stimulation of

Incretins

PankreasGI-Trakt

Glucose-dependent

Glucagon

from alpha cells

(GLP-1)

Glucose-dependent

Insulin

from Beta cells

(GLP-1 und GIP)

Regulation of Insulin and Glukagon

via incretins after an oral glucose load

In DM:

GLP-1

GIP function

GLP-1- and GIP-metabolites

DPP-4-

Enzyme

GLP-1/GIP

Stimulation of

Incretins

PankreasGI-Trakt

Glucose-dependent

Glucagon

from alpha cells

(GLP-1)

Glucose-dependent

Insulin

from Beta cells

(GLP-1 und GIP)


via incretins after an oral glucose load

XDPP-4-

Inhibitors

GLP-1 receptor dependent mechanisms and some associated pathways.

Kmok et al Trends Cardiovasc Med, 2014

DPP-IV inhibitors: Beyond glycaemic control?

GLP-1 Receptor

Saxagliptin and Cardiovascular Outcomes in Patients with Type 2 Diabetes Mellitus

Benjamin M. Scirica, M.D., M.P.H., Deepak L. Bhatt, M.D., M.P.H., Eugene Braunwald, M.D., P. Gabriel Steg, M.D., Jaime Davidson, M.D., Boaz Hirshberg,

M.D., Peter Ohman, M.D., Robert Frederich, M.D., Ph.D., Stephen D. Wiviott, M.D., Elaine B. Hoffman, Ph.D., Matthew A. Cavender, M.D., M.P.H., Jacob A. Udell, M.D.,

M.P.H., Nihar R. Desai, M.D., M.P.H., Ofri Mosenzon, M.D., Darren K. McGuire, M.D., Kausik K. Ray, M.D., Lawrence A. Leiter, M.D., Itamar Raz, M.D., for the

SAVOR-TIMI 53 Steering Committee and Investigators

N Engl J MedVolume 369(14):1317-1326

October 3, 2013

Scirica BM et al. N Engl J Med 2013

SAVOR-TIMI 53

Gaps in evidence:

Antidiabetika – DPPI Inhibitoren

Benjamin M. Scirica et al. Circulation. 2014

SAVOR-TIMI 53

Mortalität Hospitalization wegen HF

BNP high

GRR low

History of HF

RF

Metaanalysis of heart failure events

observed in SAVOR and EXAMINE

Schernthaner G, J Diabetes Complications, 2014

Alogliptin

Saxagliptin

Primary Objective

To demonstrate that the risk of cardiovascular events

in patients treated with sitagliptin in addition to usual

care was non-inferior to that in patients treated

without sitagliptin in addition to usual care.

Green JB et al. NEJM 2015

Primary Composite Cardiovascular Outcome

Time to first occurrence of:

• Cardiovascular-related death

• Nonfatal myocardial infarction

• Nonfatal stroke

• Hospitalization for unstable angina

A Clinical Endpoints Committee, blinded to therapy allocation, reviewed all potential CVD endpoints independently.


Consort Diagram

14,735randomized 64 excluded from all analyses

• 11 did not consent

• 53 at one site excluded

for GCP deviations

14,671included in ITT analysis

7332 sitagliptin ITT

7180 (97.9%) VS known

6972 (95.1%) completed

61 (0.8%) LTFU29 (48%) VS known

299 (4.1%) Withdrawn179 (60%) VS known

7339 placebo ITT

7123 (97.0%) VS known

6905 (94.1%) completed

71 (1.0%) LTFU33 (46%) VS known

363 (4.9%) Withdrawn185 (51%) VS known


Glycemic ControlLeast Squares Mean HbA1c ± 1SD

Overall LS Mean difference

-0.29% (-0.32, -0.27), p<0.0001


Estimated Glomerular Filtration Rate (eGFR)Mean ± 1SD

*Mixed model with random intercept & slope, adjusted for baseline value and region

Estimated overall mean difference*:

-1.34 ml/min/1.73m2 (95%CI -1.76, -0.91), p<0.0001


Primary Composite Cardiovascular Outcome* PP Analysis for Non-inferiority

* CV death, nonfatal MI, nonfatal stroke, hospitalization for unstable angina


Primary Composite Cardiovascular Outcome* ITT Analysis for Superiority

* CV death, nonfatal MI, nonfatal stroke, hospitalization for unstable angina


Hospitalization for Heart Failure*ITT Analysis

* Adjusted for history of heart failure at baseline


Summary of Results (1)

• For the primary composite cardiovascular outcome(CV death, nonfatal MI, nonfatal stroke, or hospitalization for unstable angina) sitagliptin, compared with placebo, was noninferior, and not superior

• For the secondary composite cardiovascular outcome(CV death, nonfatal MI, or nonfatal stroke) sitagliptin, compared with placebo, was noninferior, and not superior

• The rate of hospitalization for heart failure did not differ between sitagliptin and placebo treatment groups

• The incidence of severe hypoglycemia did not differ between sitagliptin and placebo treatment groups


Subgroup HR (95% CI) P-Value

SAVOR-TIMI 0.007

EXAMINE 0.235

TECOS

1.27

(1.07–1.51)

1.19

(0.89–1.59)

1.00

(0.84–1.20)1.000

SAVOR-TIMI +

EXAMINE + TECOS1.14

(0.97–1.34)0.102

SAVOR-TIMI 53, EXAMINE, and TECOS*:Hospitalization for Heart Failure

* Unadjusted

Test for heterogeneity for 3 trials:

p=0.16, I2=44.9







GLP-1/GIP

Agonisten

Stimulation of

Incretins

PankreasGI-Trakt

Glucose-dependent

Glucagon

from alpha cells

(GLP-1)

Glucose-dependent

Insulin

from Beta cells

(GLP-1 und GIP)


via GLP1 Agonsits

Localisation of cardiac GLP-1 receptors

Pyke et al., Endocrinology 2014

Human: Sinoatrial node

Ban et al., Circulation 2008

Rodents

Ussher, Circ Res 2014

Potential indirect cardiac effects GLP-1 analogues

Vasculature:

Vasodilation

DPP-4 i

Lixisenatide

Ussher, Circ Res 2014

Evaluation of LIXisenatide in

Acute Coronary Syndrome (ELIXA)

ESC 31 August 2015 Hot Line III -Diabetes mellitus/Pharmacology

Eldrin F. Lewis, MD, MPH Associate Professor of Medicine Harvard

Medical School Brigham and Women’s Hospital

ELIXA Trial Executive Committee:

Rafael Diaz, Kenneth Dickstein, Hertzel Gerstein, Lars Køber, Eldrin Lewis, Aldo

Maggioni, John McMurray, Marc Pfeffer (Chair),

Jeffrey Probstfield, Matthew Riddle, Scott Solomon, Jean-Claude Tardif

on behalf of the ELIXA Investigators

Trial Design

• Randomized, double-blind, placebo-controlled event-driven trial

• Patients with Type 2 DM within 180 days of ACS

• Run-in period of 7 days; trained in self-administration of daily SC

volume-matched placebo

• Lixisenatide or matching placebo (1:1)

– Initial dose 10 µg/day

– Down- or up-titration permitted to maximum of 20 µg/day

• Glucose control managed by site investigators’ judgment

AHJ 2015

Endpoints

• Primary (Composite)

- CV death, Non-fatal MI, Non-fatal stroke, Hospitalization for

unstable angina (UA)

• Secondary and Other

- Primary endpoint + hospitalization for HF

- Primary endpoint + hospitalization for HF + coronary

revascularizatio

- All-cause death

- HF hospitalization

- CV death + HF hospitalization

Variable Placebo

N = 3034

Lixisenatide

N = 3034

Age (years) 60.6 ± 9.6 59.9 ± 9.7

Female (%) 30.9 30.4

Race (%): White 76.4 74.4

Asian 12.1 13.3

Black 3.4 3.9

Other 8.1 8.4

Qualifying ACS Event (%):

NSTEMI 39.0 38.4

STEMI 43.4 44.5

Unstable Angina (UA) 17.4 16.9

ACS to Rand. (days) 72 ± 44 72 ± 43

Demographics

Placebo

N = 3034

Lixisenatide

N = 3034

CV Medications (%)

ACEi/ARB 85 85

Statin 92 93

Anti-Platelet 97 98

Beta-Blocker 85 84

DM Medications (%)

Insulin

Metformin Sulfonylureas

Thiazolidinediones

Other

39

65

33

2

5

39

67

33

1

6

# of DM Med Categories 1.4 ± 0.7 1.5 ± 0.8

Baseline Medications

Results

Biomarker changes with lixisenatide vs placebo

1) HbA1c (absolute value) was 0.27% lower*(with similar hypoglycemia events)

2) Weight change was 0.7kg less*(with more frequent discontinuation due to GI complaints 4.9% vs. 1.2%* )

2) SBP was 0.8 mmHg less*

3) Albuminuria increased less, 24% vs 34%*

4) Heart rate was increased 0.4 bpm*

* p<0.05

1°Outcome (CV Death, MI, Stroke or UA)

Lixisenatide: 406/3034 =

13.4% Placebo: 399/3034 =

13.2%

HR = 1.02 (0.89,

1.17)

No HF

hosp

Post-HF hosp

Hazard Ratio following HF: HR=9.3 (7.2-

11.9)

*76 of 434 deaths (18%) in ELIXA occurred post-HF hosp

Mortality* following HF Hosp

CV Death + Heart Failure Hospitalization (by history of HF)

HR = 0.97 (0.75, 1.24)

Lixisenatide:121/682 = 17.7%

Placebo: 121/676 = 17.9%

Hx HF

No Hx HF

HR = 0.96 (0.75, 1.23)

Lixisenatide:127/2352 = 5.4%

Placebo:132/2358 = 5.6%

Lixisenatide & CVOutcomes

Primary + Heart

Failure Hosp

HR = 0.97 (0.85, 1.10)

Heart Failure Hospitalization

HR = 0.96 (0.75, 1.23)

HR = 0.94 (0.78, 1.13)

All-Cause DeathPrimary + HF Hosp +

Coronary Revasc

HR = 1.00 (0.90, 1.11)

ELIXA Summary

• Demonstrates CV safety of lixisenatide (as defined by FDA

Guidance), but not superiority in reducing CV events

• Additional analyses indicate safety with respect to heart

failure events as well as death

• Neutral effects seen across wide spectrum of heart failure

risk

ELIXA: what does it mean ?

• CV safety of lixisenatide in post ACS patients appears

excellent

• No signal of increase in risk of HF

• Probably does not rule out a genuine CV benefit

– Diabetes is long standing

– Follow up is too short

0 5 10 15 20 25

Years since randomization

Pro

po

rtio

nw

ith

even

t

1.0

0.8

0.6

0.4

0.2

0

Conventional (n = 1138)

Sulfonylurea/Insulin (n = 2729)

0 5 10 15 20 25

Years since randomization

Pro

po

rtio

nw

ith

even

t

1.0

0.8

0.6

0.4

0.2

0

33% reduction

P = 0.005

Holman et al. N Engl J Med. 2008

15% reduction

P = 0.01

In 10-yr post-trial follow-up, between-group A1c differences lost after 1 yr.

Intensive treatment with sulfonylurea and/or insulin also resulted in a persistent 24% reduction in microvascular disease (P = 0.001)

Conventional (n = 411) Metformin (n = 342)

It took more than 10 years to detect the benefit of intensive glucose control on prevention of MI in

UKPDS-80

Myocardial Infarction Myocardial Infarction

CV Mortalität in Diabetes nach 3-4 Jahren

bei Patienten mit guter EF

Saxapliptin Sitagliptin

Lixisenatide

Ist das alles was man von

einer potenten anti-diabetischen Substanz

erwarten kann ?







SGLT-2 Hemmer - Renale Glucose Re-Absorption wird blockiert

Lee YJ, Han HJ. Kidney Int Suppl 2007

Glucose

SGLT-1

SGLT-2

~10%

~90%

In gesunden Individuen filtern die Glomeruli ca. 180 g Glucose pro Tag

Fast die gesamte gefilterte Glucose wird im

proximalen Tubulus durch die sodium glucose co-

transporter SGLT-2 und SGLT-1 re-absorbiert,

wobei SGLT-2 für ca. 90% in dem S1+S2 Segment,

und SGLT-1 für ca. 10% in dem S3 Segment zuständig ist

Mechanismus der SGLT-2 Hemmer

Gerich JE. Review Article. Diabetic Medicine. 2010

SGLT-2 Hemmer reduzieren die Glucose Re-Absorption im proximalen Tubulus, was zu

vermehrter Urin-Glucose-Ausscheidung führt

SGLT-2SGLT-2Inhibitor

SGLT-1

Glucose

Urin Glucose Ausscheidung, Kalorienverlust

Glucose Reupatke Inhibitoren:

Dapagliflozin, Canagliflozin,

Empagliflozin, Ipragliflozin,

Luseogliflozin, Tofogliflozin

-> milde Natriurese/Diurese

-> geringer RR Abfall

Zinman et al, NEJM. 2015

Empagliflozin, inhibitor of sodium–glucose co-transporter 2

N= 7020, type 2 diabetes at high cardiovascular risk;

3.1 years; primary composite outcome: CV death, MI, stroke

EMPA-REG, NEJM 2015

EMPA-REG: HbA1c

adjusted mean HbA1c at week 206 of 7.81% vs 8.16%

EMPA-REG, NEJM 2015

LDL-C

80% Statine

EMPA-REG, NEJM 2015

Systolic Blood Pressure

EMPA-REG, NEJM 2015

Primary composite outcome: CV death, MI, stroke

490 of 4687 (10.5%)

82 of 2333 (12.1%)

14% RRR

EMPA-REG, NEJM 2015

5.7% vs 8.3%

32% relative risk reduction

NNT 39

Death from AnyCause

EMPA-REG, NEJM 2015

3.7% vs 5.9%


Cardiovascular Death

EMPA-REG, NEJM 2015

2.7% vs 4.1%


Hospitalization for Heart Failure

EMPA-REG, NEJM 2015

Adverse events: increased rate of genital infection







Pitt B, et al. N Engl J Med. 1999;

Zannad F, et al. N Engl J Med. 2010

Trials comparing an aldosterone/MR antagonist to placebo (added to an ACE inhibitor) in systolic HF

Underutilization of MRAs and Marked Variability of Use in Heart Failure

All Practices (Baseline Review)

Pe

rce

nt o

f In

dic

ate

d P

atie

nts

(%

)

36%

Fonarow et al, Circ HF 2008

Finerenone combines spironolactone’s

potency with eplerenone’s selectivity

Juurlink et al. New Eng J Med 2004

Finerenone (BAY 94-8862) is a novel non-steroidal MRA that has

greater receptor selectivity than spironolactone and better receptor

affinity than eplerenone in vitro

Results of ARTS-HF:

finerenone versus eplerenone in patients with

worsening chronic heart failure and diabetes

and/or chronic kidney disease

Gerasimos FilippatosStefan D Anker, Michael Böhm, Mihai Gheorghiade, Lars Køber,

Henry Krum, Aldo P Maggioni, Piotr Ponikowski, Adriaan A Voors, Faiez Zannad, So-Young Kim, Christina Nowack, Giovanni Palombo, Peter Kolkhof, Nina Kimmeskamp-

Kirschbaum, Alexander Pieper and Bertram Pitt,

for the MinerAlocorticoid Receptor AnTagonist Study In Heart Failure(ARTS-HF) Committees and Investigators

Study objective

Study objective: to compare the safety and efficacy of different once-

daily oral doses of finerenone with eplerenone in patients who

presented in emergency departments with worsening chronic HFrEF

with type 2 diabetes mellitus and/or chronic kidney disease (CKD)

Pitt B et al. Eur Heart J 2013

Study endpoints

Endpoint Outcome variable

Primary endpoint 1. Proportion of patients with a relative decrease in NT-

proBNP of > 30% from baseline to day 90

Further exploratory

endpoints

1. Composite endpoint of death from any cause, CV

hospitalization or emergency presentation for

worsening chronic heart failure (until day 90)

2. Change in efficacy biomarker levels from baseline (BNP

and NT-proBNP) to days 30, 60 and 90

3. Change in health-related quality of life from baseline to

days 30 and 90

• Kansas City Cardiomyopathy Questionnaire

• 5-dimension EuroQol questionnaire

BNP, B-type natriuretic peptide; CV, cardiovascular; NT-proBNP, N-terminal of prohormone B-type natriuretic peptide

Study design

DMC, Data Monitoring Committee; e.o.d., every other day; o.d. once daily

Pre-specified additional treatment groups introduced

following a recommendation from the DMC

Treatment groups at study start

Initial stabilizationand screening

Safety follow-up

Emergency presentation (in the 7 days before randomization

Finerenone 20 mg o.d.




Eplerenone 25 mg o.d.



Finerenone 15 mg o.d.Finerenone 7.5 mg o.d.


Finerenone 2.5 mg o.d.

Eplerenone 25 mg e.o.d.

Eplerenone 50 mg o.d.

Acute/vulnerable phaseup to day 30

Chronic phase: days 31–90

Up-titration if serum potassium ≤ 5.0 mmol/L

Up-titration/sham up-titration if serum potassium ≤ 5.0 mmol/LRandomization

Day 1 Day 30 Day 90Day 60

Primary endpoint results

• The proportion of patients who had an NT-proBNP decrease of more than 30% at day 90

compared with baseline was similar in the finerenone groups and the eplerenone group

in the full analysis set

Error bars show 90% confidence intervals NT-proBNP, N-terminal of prohormone B-type natriuretic peptide

Pro

po

rtio

n o

f p

atie

nts

wit

h >

30

% r

edu

ctio

nin

NT-

pro

BN

P f

rom

bas

elin

e to

day

90

(%

) 50

30

20

10

0Eplerenone

(n = 207)Finerenone 2.5–5 mg(n = 162)

Finerenone 5–10 mg(n = 157)

Finerenone 7.5–15 mg(n = 158)



37.2

30.932.5

37.3 38.8

34.2

40

Cardiovascular hospitalization

Finerenone 10–20 mg/eplerenoneHR: 0.56; 95% CI: 0.34–0.93

Pooled finerenone/eplerenone HR: 0.70; 95% CI: 0.49–0.98

Finerenone: all-cause death and cardiovascular hospitalization

Pooled finerenone included 5–10 mg, 7.5–15 mg, 10–20 mg and 15–20 mg CI, confidence interval; HR, hazard ratio

All-cause death

Finerenone 10–20 mg/eplerenoneHR: 0.14; 95% CI: 0.02–1.07

Pooled finerenone/eplerenone HR: 0.52; 95% CI: 0.23–1.19

Cu

mu

lati

ve p

rob

abili

ty (

%)

8

0

Cu

mu

lati

ve p

rob

abili

ty (

%)

620

4

102

30

Day 0

0

Day 0 Day 30 Day 60 Day 90 FUDay 30 Day 60 Day 90 FU

Eplerenone (n = 207) Finerenone 10–20 mg (n = 160) Pooled finerenone (n = 633)

Mean change in potassium from baseline

*Statistically significant

ANCOVA with treatment group, comorbidities, MRA use at emergency presentation and region as factors and baseline value as

covariate ANCOVA, analysis of covariance; MRA, mineralocorticoid receptor antagonist

**p = 0.016 p = 0.016

p = 0.030

Eplerenone (n = 143)






0.262

*0.119 0.119

0.134

0.202 0.200

Summary I

• In patients hospitalized for worsening chronic HFrEF with type 2

diabetes mellitus and/or CKD, the proportion of patients with a

relative decrease in NT-proBNP of more than 30% from baseline to

day 90 was similar in the eplerenone group and the finerenone

groups

• The incidence of the clinical composite endpoint (all-cause death,

cardiovascular hospitalization or emergency presentation for

worsening chronic heart failure) at day 90 was lower with all

finerenone doses (except 2.5–5 mg) than with eplerenone, with the

lowest incidence observed in the finerenone 10–20 mg dose group

Summary II

• All doses of finerenone were well tolerated, with a similar

incidence of treatment-emergent adverse events in the

eplerenone group and finerenone groups

• Hyperkalaemia (serum potassium ≥ 5.6 mmol/L) was observed

in 44 patients (4.3%) at any time post-baseline

• FINESSE-HF (3600 Pts. with reduced EF and Diabetes and/or CKD)

• FIGARO-DKD (6400 Pts. With diabetic kidney disease UACR <300mg/g)

• FIDELIO-DKD (4800 Pts. With diabetic kidney disease UACR> 300mg/g)

FINERENONE - Zukunft

Phase III Studienprogramm:







Accurate and Rapid Diagnosis of Myocardial Infarction Using a

High-Sensitivity Troponin I 1-Hour Algorithm

Johannes Tobias Neumann1, Nils Arne Sörensen1, Tjark Schwemer1, Francisco Ojeda1, Rafael Bourry1, Vanessa Sciacca1, Sarina Schäfer1,2, Christoph Waldeyer1, Christoph Sinning1, Thomas Renné3, Martin Than5, Will Parsonage4, Karin Wildi6, Nataliya Makarova1,2, Renate B. Schnabel1,2, Ulf Landmesser7, Christian Mueller6,

Louise Cullen4, Jaimi Greenslade4, Tanja Zeller1,2, Stefan Blankenberg1,2, MahirKarakas1,2, Dirk Westermann1,2

1 Department of General and Interventional Cardiology, University Heart Center Hamburg Eppendorf, Hamburg, Germany2 German Center for Cardiovascular Research (DZHK), Partner Site Hamburg/Kiel/Lübeck, Hamburg, Germany3 Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany4 Royal Brisbane and Women's Hospital, Department of Emergency Medicine, Brisbane 4006, Australia5 Christchurch Hospital, Christchurch, New Zealand6 Department of Cardiology and Cardiovascular Research Institute Basel (CRIB), University Hospital Basel, Switzerland7 Department of Cardiology, Charite Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany

BACC

Background

There is clinical need to rapidly and safely rule-in or rule-out acute myocardial

infarction (AMI) in patients with acute chest pain in order to

1. initiate fast evidence based treatment for patients with AMI

2. limit overuse of scarce medical resources in the emergency room (ER)

discharging patients without acute cardiac conditions.

Guidelines recommend1,2 measuring high sensitivity assayed troponins directly after

admission and after 3 hours detecting elevated levels based on the 99th percentile of

the specific assays together with an increase/decrease.

Recent studies (ADAPT (2-hour)3 and APACE (1- hour)4 cohort) challenge current

guidelines with intervals shorter than 3 hours.

1 Hamm et al. EHJ 2011 2 Thygesen et al. EHJ 2012;

3 Than et al. JACC 2012; 4 Reichlin et al. CMAJ 2015

Aim of the study

To investigate the application of

high sensitivity assayed troponin I (TnI) for

a) a rapid 1-hour rule-out and rule-in compared to a 3-hours

approach

b) a lower and more sensitive cut-off value compared to the 99th

percentile

in the Biomarkers in Acute Cardiovascular Care (BACC) cohort

investigating 1,045 patients with acute chest pain.

0 hour 3 hours

hsTnT hsTnT

BACC (n = 1.045) patients with acute chest pain suggestive of AMI:

Study design

Calculate bestperforming cut-off and

apply it

Validateresults in

other cohorts

Applicate cut-off in general

population

Clinical routine troponin assay and clinical treatment based on ESC guidelines1:

1 hour0 hour

hsTnI hsTnI

3 hours

hsTnI + without adding additional

information

+ clinical judgement, imaging

and ECG to establish final

diagnosis during the complete

hospital stay

(NSTEMI vs. no AMI)

(as recommended by ESC guidelines1)

Hamm et al, EHJ 2011

Cut-offTime after admission

NPV NSTEMI 1(95% CI)

Sensitivity NSTEMI 1

(95% CI)

NPV NSTEMI (95% CI)

Sensitivity NSTEMI (95% CI)

1-hour

99.7(98.6-100.0)

99.1(94.9-100.0)

99.0(97.5-99.7)

97.6(94.1-99.4)

6ng/L

3-hour 100.0(98.5-100.0)

100.0(94.9-100.0)

99.5(98.1-99.9)

98.8(95.8-99.9)

Rule-Out 1-hour vs. 3-hours

p= n.s. vs 1hp= n.s. vs 1h

NPV: negative predictive value; NSTEMI 1: non STEMI type 1

Suggested 1-hour algorithm NSTEMI rule-out:hsTnI < 6 ng/L at 0h and 1h

resulted in 402 out of 1,045 patients being discharged

Criteria to diagnose patient as NSTEMI

PPV NSTEMI 1

(95% CI)

Specificity NSTEMI 1 (95%

CI)

PPV NSTEMI (95% CI)

Specificity NSTEMI (95% CI)

Troponin I 1-hour

> 6 ng/L and absolute delta from 0h 82.8 98.0 87.1 98.0

to 1h (73.2-90.0) (96.7-98.9) (79.6-92.6) (96.7-98.9)

troponin I ≥ 12 ng/L

Troponin I 3-hour

> 6 ng/L and absolute delta from 0h 78.6 96.8 84.6 96.8

to 3h (69.8-85.8) (95.2-97.9) (78.0-89.9) (95.2-97.9)

troponin I ≥ 12 ng/L

BACC Rule-In

PPV: positive predictive value; NSTEMI 1: non STEMI type 1

Suggested 1-hour algorithm NSTEMI rule-in:hsTnI after 1h > 6 ng/L and a delta of 12 ng/L to 0h

Resulted in 116 out 1,046 being identified as NSTEMI after 1 hour

A 1-hour algorithm is safe to rule-out AMI.

A sensitive troponin I cut-off (6 ng/L) performed better compared to

the 99th percentile (27 ng/L) in view of lower follow-up mortality.

Low troponin I values predict mortality in the general population.

Further studies are needed to test the best cut-off for each troponin

assay and to validate a 1-hour algorithm prospectively.

Conclusion

Carsten Tschöpe

Vielen Dank !

Documents

ESC-update 2015 · STEMI 43.4 44.5 Unstable Angina (UA) 17.4 16.9 ACS to Rand. (days) 72 ±44 72 ±43 Demographics Placebo N = 3034 Lixisenatide N = 3034 CV Medications (%) ACEi/ARB