atlantic h 24

The ATLANTIC-HThe ATLANTIC-H2424 Analysis AnalysisEffect of Pre-Hospital Ticagrelor During

the First 24 h After Primary Percutaneous Coronary Intervention in

Patients With STEMI.

J A C C : CARDIOVASCULAR INTERVENTIONS

VOL. 9, NO. 7, 2016

Dr.Vinit KumarMCH, Trivandrum

The aim of this landmark exploratory analysis, ATLANTIC-H, was to evaluate the effects of pre-hospital ticagrelor during the first 24 h after primary PCI in the ATLANTIC Study.

Indications and guideline Indications and guideline recommendationsrecommendations

• ESC STEMI guidelines recommend:[Steg 2012]

– An ADP-receptor blocker in addition to ASA. Options are:

• Prasugrel in clopidogrel-naïve patients, if no history of prior stroke/TIA, age <75 years (Class I, LOE B)

• Ticagrelor (Class I, LOE B)

• Clopidogrel, preferably when prasugrel or ticagrelor are either not available or contraindicated (Class I, LOE C)

• ESC/EACTS myocardial revascularization guidelines recommend:[Kolh 2014]

– An ADP-receptor blocker in addition to ASA for STEMI primary PCI. Options are:

• Prasugrel if no history of prior stroke/TIA, age <75 years (Class I, LOE B)

• Ticagrelor (Class I, LOE B)

• Clopidogrel, only when prasugrel or ticagrelor are not available or contraindicated (Class I, LOE B)

ESC/EACTS treatment guideline ESC/EACTS treatment guideline recommendations for patients with STEMIrecommendations for patients with STEMI

Steg G et al. Eur Heart J 2012;33:2569–2619; Kolh P et al. Eur Heart J August 29 2014; DOI:10.1093/eurheart/ehu278 [Epub ahead of print]

• ACCF/AHA guidelines recommend:[O’Gara 2013]

– A loading dose of a P2Y12 inhibitor should be given as early as possible or at time of primary PCI to patients with STEMI. Options include:

• Clopidogrel 600 mg (Class I; LOE B)

• Prasugrel 60 mg (Class I; LOE B)

• Ticagrelor 180 mg (Class I; LOE B)

ACCF/AHA treatment guideline ACCF/AHA treatment guideline recommendations for patients with recommendations for patients with

STEMISTEMI

O’Gara PT et al. Circulation 2013;127:e362–425

• While pre-hospital initiation of oral antiplatelet treatment is not recommended specifically, the 2012 ESC STE-ACS guidelines acknowledge that it is common practice in Europe[Steg 2012]

– Early administration may be preferable to achieve early efficacy

• The new ESC/EACTS guidelines recommend initiation of DAPT at first medical contact* in STEMI primary PCI[Kolh 2014]

Treatment guidelines: Treatment guidelines: Timing of antiplatelet therapy in STEMITiming of antiplatelet therapy in STEMI

*The point at which the patient is either initially assessed (12-lead ECG) by a paramedic or physician or other medical personnel in the pre-hospital setting, or the patient arrives at the hospital emergency department, and therefore often in the outpatient setting

Steg G et al. Eur Heart J 2012;33:2569–2619.Kolh P et al. Eur Heart J August 29 2014; DOI:10.1093/eurheart/ehu278 [Epub ahead of print]

ATLANTICATLANTIC

AAdministration of dministration of TTicagrelor in the cath icagrelor in the cath LLab or in ab or in the the AAmbulance for mbulance for NNew Sew STT elevation myocardial elevation myocardial

IInfarction to open the nfarction to open the CCoronary arteryoronary artery

A 30-day study to evaluate the efficacy and safetyof pre-hospital versus in-hospital initiation of ticagrelor therapy in STEMI patients planned for PCI

• To evaluate whether earlier, in-ambulance administration of ticagrelor could safely improve coronary reperfusion in patients with acute ST-elevation myocardial infarction (STEMI) transferred for primary percutaneous coronary intervention (PCI)

ATLANTIC: AimATLANTIC: Aim

Montalescot G et al. Am Heart J 2013;165:515–522

• Guidelines’ recommendation to administer antiplatelet therapy as early as possible before angiography is not based on randomized controlled trial (RCT) results

• No clear evidence for benefit of clopidogrel administration pre-hospital versus in-hospital in patients undergoing primary PCI

– No difference in coronary patency or bleeding[Zeymer 2012]

– Ischaemic events may be reduced without excess bleeding, but effectiveness may be limited by slow onset of action and variability of response[Bellemain-Appaix 2012]

Pre-hospital administration of Pre-hospital administration of antiplatelet therapyantiplatelet therapy

; Zeymer U et al. Clin Res Cardiol 2012;101:305–312; Bellemain-Appaix A et al. JAMA 2012;308:2507–2516

• Ticagrelor significantly reduced the risk of CV death, MI or stroke in ACS patients compared with clopidogrel in the PLATO study[Wallentin 2009]

– Results in a subgroup analysis of patients with STE-ACS planned to undergo primary PCI were consistent with the overall study[Steg 2010]

• No specific studies have been conducted to evaluate the potential benefit of treatment with ticagrelor prior to hospitalisation

• Therefore, the primary objective of the ATLANTIC study is to assess the optimal timing of ticagrelor initiation in STEMI patients planned for primary PCI

Study rationaleStudy rationale

Steg PG et al. Circulation 2010;122:2131–2141;Wallentin L et al. N Engl J Med 2009;361:1045–1057

ATLANTICATLANTICStudy design

ATLANTIC study population and designATLANTIC study population and design

Ticagrelor 180 mg loading dose

Placeboloading dosePre-hospital

Placeboloading dose

Ticagrelor 180 mg loading doseIn-hospital

Randomized, double-blind

Ticagrelor 90 mg/bid 30 days

Primary objective

OR

STE-ACS planned for PCIN=1770 (n=1862*)

Written informed consent in mobile care unitSymptoms of acute MI or more than 30 min but less than 6 h

New persistent ST-segment elevation ≥1 mm in two or more contiguous ECG leads

≥70% ST-segment elevation resolution pre-PCI

TIMI flow grade 3 of MI culprit vessel at initial angiography

*Consented and randomized

• Aged ≥18 years• Diagnosed with STEMI (new, persistent ST-segment elevation

≥1 mm in≥2 continuous ECG leads)

• Planned to undergo primary PCI• Symptoms of acute MI >30 minutes but <6 hours in duration• Initially treated by the emergency medical service (ambulance

personnel)

Diagnosis and inclusion into the study are made solely by the ambulance personnel

ATLANTIC: Key inclusion criteriaATLANTIC: Key inclusion criteria

Expected time from qualifying ECG to first PCI balloon inflation in hospital of >120 minutes

Received a loading dose for the index event, or receiving maintenance treatment with ticagrelor, clopidogrel or prasugrel

Concomitant medication that may increase the risk of bleeding administered 24 hours before randomization or strong cytochrome P450 3A inhibitors.

ATLANTIC: Key exclusion criteriaATLANTIC: Key exclusion criteria

16

• Planned surgery during the study period

• Known clinically important thrombocytopenia or anaemia

• Requirement for dialysis

• Any of the following conditions in the absence of a functioning implanted pacemaker: Known sick sinus syndrome, second- or third-degree AV block, or documented syncope of suspected bradycardic origin

• Previous randomization in ATLANTIC or participation in another clinical study with an investigational product or a device study during the previous 30 days and during the study

• To assess the efficacy of pre-hospital administration of ticagrelor compared to an in-hospital administration by comparing percentage of patients not achieving the co-primary endpoints:

ATLANTIC: Primary objectiveATLANTIC: Primary objective

• Percentage of patients not achieving ≥70% ST-segment elevation resolution at pre-PCI

• Percentage of patients not reaching TIMI flow grade 3 in the infarct-related artery at initial (pre-PCI) angiography

ATLANTIC: Co-primary ATLANTIC: Co-primary endpointsendpoints

Complete ST-segment elevation resolution at 60 min post-PCI

TIMI flow grade 3 at end of procedure Definite stent thrombosis alone at 30 days Thrombotic bailout with GPIIb/IIIa inhibitors

ATLANTIC: Pre-specified secondary ATLANTIC: Pre-specified secondary endpointsendpoints

• To assess the safety of pre-hospital versus in-hospital initiation of ticagrelor therapy

ATLANTIC: Safety objectivesATLANTIC: Safety objectives

Bleeding events–Major life-threatening or other minor or major

bleeding events• PLATelet inhibition and patient Outcomes (PLATO)

bleeding definition• Within first 48 h and during first 30 days of treatment

• Excluding CABG-related bleeding events

ATLANTIC study flow chartATLANTIC study flow chart

Administration of in-ambulance GPIIb/IIIa inhibitors discouraged; post-angiogram in-lab use of GPIIb/IIIa inhibitors only if identified as treatment of choice or bail-out option during PCI. Continuation of ticagrelor for 12 months recommended

Secondary endpoints

PCI

R

Ticagrelor 180 mg

Placebo

Placebo

Ticagrelor 180 mg

LD1

ECG 1 Diagnosis

H12 post LD2

Ticagrelor 90 mg BID

ECG 2 Pre-PCI ECG 3 60’ Post-PCI-

LD2

Double-blind period 30-day active treatment period

7 days’ follow-up

Pre-hospital settings Cath lab

STEMI planned for PCIn=1870

Primary endpoints

Secondary endpoints

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• Efficacy analysis based on the modified ITT population analysis set

– Analysis included all patients who received at least one dose of study drug

– Selected because randomization and administration of the first dose of study drug occur simultaneously, in the ambulance

– Each co-primary endpoint analyzed separately using the χ2 test

• Safety population analysis included all randomized patients who received at least one dose of study drug

– Safety endpoints analyzed using descriptive methods

ATLANTIC: AnalysisATLANTIC: Analysis

Baseline patient characteristicsBaseline patient characteristics

Values are n (%)

Ticagrelor pre-hospital

(n=909)

Ticagrelor in-hospital

(n=953) Coronary angiography 890 (97.7) 937 (98.3)

Arterial access (percentage of those undergoing coronary angiography)FemoralRadial

280/890 (31.5)604/890 (67.9)

309/937 (33.0)625/937 (66.7)

Thrombo-aspiration 471 (51.8) 470 (49.3)

PCI With stent

Drug-eluting stents Bare metal stents

Without stent

800 (88.0)760 (83.6)467 (51.4)305 (33.6)40 ( 4.4)

830 (87.1) 776 (81.4)479 (50.3)312 (32.7)54 ( 5.7)

CABG No PCI or CABG

10 (1.1)99 (10.9)

15 (1.6)108 (11.3)

Procedures for index eventProcedures for index event

Montalescot G et al. N Engl J Med September 1, 2014 [Epub ahead of print; DOI: 10.1056/NEJMoa1407024]

Culprit vessel (percentage of those undergoingCulprit vessel (percentage of those undergoingcoronary angiography)coronary angiography)

Reported for the culprit vessel only

Ticagrelor pre-hospital

Ticagrelor in-hospital

Median times to pre- and in-Median times to pre- and in-hospital stepshospital steps

159 min

28 min

31 min73 min 14 min

90 min 63 min

Onset ofsymptoms

ECG Pre-hospital

Randomization

LD1 LD2ECG

Pre-PCI Angiography PCI

ATLANTICATLANTICStudy results

Co-primary and secondary surrogate Co-primary and secondary surrogate endpointsendpoints

Absence of ST-segment elevation ≥70%

• Pre-PCI†

– Pre-hospital n=774– In-hospital n=824

• Post-PCI‡


Pre-PCI Post-PCI

P=NS

P=NS

Pre-hospitalIn-hospital

• Pre-PCI†


• Post-PCI‡


Co-primary and secondary surrogate Co-primary and secondary surrogate endpointsendpoints

Absence of TIMI flow grade 3 in infarct-related artery

P=NS

P=NS


Post-PCI

Absence of ST-segment elevation ≥70% Absence of ST-segment elevation ≥70% AND/ORAND/OR

Absence of TIMI flow grade 3 in infarct-related arteryAbsence of TIMI flow grade 3 in infarct-related artery

• Pre-PCI†


• Post-PCI‡


P=NS

P=NS


Pre-PCI Post-PCI

• Pre-PCI† – Pre-hospital n=719– In-hospital n=751

• Post-PCI‡


P=NS

P=NS


Pre-PCI Post-PCI

Absence of ST-segment elevation ≥70% Absence of ST-segment elevation ≥70% ANDAND

Absence of TIMI flow grade 3 in infarct-related arteryAbsence of TIMI flow grade 3 in infarct-related artery

n (%)

Ticagrelor pre-hosp(n=906)

Ticagrelor in-hosp(n=952)

Odds ratio(95% CI) P value

Difference(95% CI)

Composite of death/MI/stroke/ urgent revascularization/definite acute stent thrombosis

41 (4.5) 42 (4.4) 1.03(0.66, 1.60) 0.9056 0.001

(–0.018, 0.020)

Composite of death/MI/urgent revascularization 39 (4.3) 34 (3.6) 1.22

(0.76, 1.94) 0.4168 0.007 (–0.010, 0.025)

Clinical endpoints at 30 daysClinical endpoints at 30 daysComposites (mITT)

n (%)


Ticagrelor

in-hosp(n=952)


Difference(95% CI)

Definite stent thrombosis (at 30 days)

Early stent thrombosis (within 24 h of index PCI)

2 (0.2)

0

11 (1.2)

8 (0.8)

0.19

(0.04, 0.86)

0.02†

0.008†

–0.009 (–0.017, –0.002)

–0.008 (–0.017, –0.003)§

Acute stent thrombosis (definite or probable at 30 days)

21 (2.3) 20 (2.1) 1.11 (0.60, 2.05)

0.75‡ 0.02 (–0.011, 0.016)

Clinical endpoints at 30 daysClinical endpoints at 30 days

Events occurring up to the date of last study visit (to a maximum of 32 days) are included in the table. Patients could be on study treatment or not when the event occurredmITT analysis: Each event is counted once in each row. A single event may be counted in more than one row. Odds ratios for pre-hospi tal group versus in hospi tal group, two-sided 95% CIs and P values were calculated from a logistic regression model , wi th treatment as the only explanatory variable†Fisher ’s exact test‡Probable stent thrombosis was defined as any death occurring in a stented patient within 30 days§Exact confidence intervalDifference in binomial proportions calculated for pre-hospital – in-hospital ticagrelor

Stent thrombosis (mITT)

2

1

Definite acute stent thrombosis up to 30 Definite acute stent thrombosis up to 30 daysdays

Kaplan–Meier curves

Ticagrelor pre-hospital 2/906 (0.2%) vs ticagrelor in-hospital 11/952 (1.2%) OR 0.19 (95% CI 0.04, 0.86), P=0.02

0 6 12 18 24 302 8 14 20 264 10 16 22 28

Even

t rat

e (K

M %

)

0

Time (days)

Ticagrelor pre-hospitalTicagrelor in-hospital

24 hP=0.008

30 daysP=0.02

n (%)


Ticagrelor in-hosp(n=952)


Difference(95% CI)

Death (all-cause)* 30 (3.3) 19 (2.0) 1.68 (0.94, 3.01)

0.08† 0.013 (–0.001, 0.028)

MI 7 (0.8) 10 (1.1) 0.73 (0.28, 1.94)

0.53† –0.003 (–0.011, 0.006)

Stroke 4 (0.4) 2 (0.2) 2.11 (0.39, 11.53)

0.39† 0.002 (–0.004, 0.009)‡

TIA 0 1 (0.1) Not estimable –0.001 (–0.006, 0.003)‡

Urgent coronary revascularization 5 (0.6) 8 (0.8) 0.66 (0.21, 2.01)

0.46† –0.003 (–0.010, 0.005)

Bail-out with GP IIb/IIIa inhibitors 78 (8.6) 100 (10.5) 0.80 (0.59, 1.10)

0.17 –0.019 (–0.046, 0.008)

Clinical endpoints at 30 daysClinical endpoints at 30 days

*

Almost all causes of death were related to cardiogenic shock, cardiac arrest, or cardiac rupture rather than bleeding or ischaemic events. Patient records have been specifically examined and no treatment related effect can be discerned†Fisher’s exact test‡Probable stent thrombosis was defined as any death occurring in a stented patient within 30 daysEvents occurring up to the date of last study visit (to a maximum of 32 days) are included in the table. Patients could be on study treatment or not when the event occurredmITT analysis: Each event is counted once in each row. A single event may be counted in more than one row. Odds ratios for pre-hospital group versus in hospital group, two-sided 95% CIs and P values were calculated from a logistic regression model, with treatment as the only explanatory variableDifference in binomial proportions calculated for pre-hospital – in-hospital ticagrelor

Other CV and thrombotic bail-out (mITT)

Non-CABG-related bleeding eventsNon-CABG-related bleeding events

Pre-hospital n=908; in-hospital n=950Events occurring up the date of the last visit (to a maximum of 32 days) are included in the table. Patients could be on study treatment or not when the event occurred. Patients may be counted in more than one bleeding event categoryP values were calculated from Chi-square test

PLATO definitions (safety population)

Within 48 h of first dose After 48 h up to 30 d

Major Minor Composite of major

and minor

Major Minor Composite of major

and minor

P=NS

P=NS

P=NS

P=NS

P=NS

P=NS



Pre-hospital n=908; in-hospital n=950Events occurring up the date of the last visit (to a maximum of 32 days) are included in the table. Patients could be on study treatment or not when the event occurred. Patients may be counted in more than one bleeding event categoryP values were calculated from Chi-square test. Statistical tests were not pre-specifiedSTEEPLE, Safety and Efficacy of Enoxaparin in Percutaneous Coronary Intervention (PCI) Patients, an International Randomized Evaluation

TIMI, STEEPLE definitions (safety population)

Major Minor Minimal

TIMI

P=NS

P=NS

P=NS

Major Minor Minimal

STEEPLE

P=NS

P=NS

P=NS



Pre-hospital n=908; in-hospital n=950Events occurring up the date of the last visit (to a maximum of 32 days) are included in the table. Patients could be on study treatment or not when the event occurred. Patients may be counted in more than one bleeding event categoryP values were calculated from Chi-square test. Statistical tests were not pre-specifiedGUSTO, Global Use of Strategies to Open Occluded Arteries; ISTH, International Society on Thrombosis & Haemostasis

GUSTO and ISTH definitions (safety population)

Severe or life-threatening

Moderate Mild

GUSTO

Major Clinically relevant non-major

Unknown

ISTH

P=NS P=NS

P=NSP=NS

P=NS



Pre-hospital n=908; in-hospital n=950Events occurring up the date of the last visit (to a maximum of 32 days) are included in the table. Patients could be on study treatment or not when the event occurred. Patients may be counted in more than one bleeding event categoryP values were calculated from Chi-square test. Statistical tests were not pre-specified BARC, Bleeding Academic Research Consortium

BARC definitions (safety population)

Type 0 Type 1 Type 2 Type 3a Type 3b Type 3c Type 4 Type 5a Type 5b

Unknown

BARC


ATLANTICATLANTICSummary and conclusions

• ATLANTIC was an international, multicentre, randomized, double-blind study in 1862 patients with ongoing STEMI of less than 6 h, comparing pre-hospital (in-ambulance) versus in-hospital (in-catheterization laboratory) treatment with ticagrelor or placebo

• The two co-primary endpoints did not differ between the pre- and in-hospital ticagrelor groups

• Post-PCI ST-segment elevation resolution ≥70% was reported in 57.5% and 52.5% of patients (P=0.055), respectively

ATLANTIC: summary of resultsATLANTIC: summary of results

44

• MACE were not different between the two groups– Mortality was low and there was a numerical imbalance

of deaths in the pre-hospital group vs the in-hospital group (3.3% vs 2.0%). Patient records have been specifically examined and no treatment related effect can be discerned

– Definite stent thrombosis occurred less frequently in the pre-hospital arm (0% vs 0.8% in the first 24 hours; 0.2% vs 1.2% at 30 days)

• Major bleeding event rates at 48 h and 30 days were low and identical between the two study groups whichever bleeding definitions were used

Primary aim of the main ATLANTIC study was to evaluate coronary reperfusion on admission to the catheterization laboratory with pre- versus in-hospital ticagrelor, with 30- day follow-up for clinical outcomes,

The landmark ATLANTIC-H analysis focused on endpoints during the first 24 h after PCI in patients who underwent PCI.Landmark analysis began at the start of the PCI procedure and continued up to 24 h later

Efficacy analyses were performed on the modified intent-to-treat population, defined as all randomized patients who received at least 1 dose of the study drug.

The safety analysis included all patients who received at least 1 dose of the study drug.

MethodsMethodsCoronary reperfusion endpoints were the following: ST-segment elevation resolution measured as the percentage of patients achieving <70% ST-segment elevation resolution 1 h after PCI and the average degree of St segment elevation resolution 1 h after PCI (median %);TIMI flow measured as the percentage of patients reaching TIMI flow grade 3 in the infarct related artery at the end of PCI

Clinical endpoints evaluated over the first 24 h after PCI included the composite endpoint- evaluating death and myocardial ischemic events of myocardial infarction (MI), definite stent thrombosis, urgent revascularization, or per-procedure bail-out use of a glycoprotein IIb/IIIa inhibitor (defined as any use of glycoprotein IIb/IIIa inhibitor after the start of PCI and not including any that were given after coronary angiography but before PCI)

ResultsResultsPLATELET FUNCTION SUBSTUDY-(n - 37) recruited at 5 centersPRU levels showing the biological effect of ticagrelor did not become apparent until 1 h after PCI

PRIVATE-ATLANTICPRIVATE-ATLANTICPLATELET FUNCTION SUBSTUDY-(n - 37) recruited at 5 centers

How PRIVATE-ATLANTIC How PRIVATE-ATLANTIC supports ATLANTICsupports ATLANTIC

Ischaemic events

CV mortalityBleeding

TIMI flowST-segment resolution

VASPVerifyNow PRIVATE-

ATLANTIC

ATLANTIC

Primary objective• To assess platelet inhibition of pre-hospital versus

in-hospital initiation of ticagrelor therapy, when catheterization starts (pre PCI) (T1), measured by VASP-PRI

Secondary objectives• To assess platelet inhibition of pre-hospital versus in-hospital

initiation of ticagrelor therapy, post-PCI (end of procedure) (T2), 1 h post-PCI (T3), 6 h post-PCI (T4), and 12 h post-PCI before the first maintenance dose (T5), measured by VASP-PRI and Verify Now

ObjectivesObjectives

Ticagrelor pre-hospital versus in-Ticagrelor pre-hospital versus in-hospital hospital

for VASP-PRIfor VASP-PRIPre hospital (pre-treatment) In hospital (cath lab) P=NS P=NS P=NS

P=NS

P=NS

T1 (Pre PCI) + 67’

T2 (End of PCI) + 1h44’

T3 (H1 Post PCI) + 2h59’

T4 (H6 Post PCI) + 8h59’

T5 (Before MD)+ 14h25’

LD1 LD2

0

20

40

60

80

100

Pre-PCI TIMI Flow and ST resolution

Post-PCI ST resolution

Primary objective

VASP

-PR

I (%

)

PER-PROCEDURE THROMBOTIC PER-PROCEDURE THROMBOTIC GLYCOPROTEINGLYCOPROTEIN

IIb/IIIa INHIBITOR BAIL-OUT USEIIb/IIIa INHIBITOR BAIL-OUT USE

Bail-out use of glycoprotein IIb/IIIa inhibitors was numerically lower with pre-hospital versus in-hospital administration of ticagrelor (9.4% vs. 12.0%).

POST-PROCEDURE CORONARY POST-PROCEDURE CORONARY REPERFUSIONREPERFUSION

No significant differences between the pre- and in-hospital ticagrelor groups in terms of either post-PCI TIMI flow grade 3 or >70% ST-segment elevation resolution at 1 h.

The degree of ST-segment elevation resolution after PCI was significantly different between the 2 groups

Among the characteristics of the 11 patients who died during the 24 h after PCI, the mean age was much older than that of the 1,618 patients who survived the first 24 h (p < 0.0001), andhigher proportions of female and diabetic patients died than Survived (p - 0.025 and p - 0.022, respectively)A numerically greater percentage of patients who died had an anterior MI compared with those who survived. Significantly more patients who died had a TIMI risk score >6 compared with survivors (p < 0.0001),

average TIMI score of 5.2 versus 2.0, respectively (p < 0.0001), and

Killip class >1 was reported in 27.3% versus 4.6% (p - 0.001).

Patients who died were more likely to have had femoral sheath insertion than those who did not (p ¼ 0.023) and were less likely to have received a drug-eluting stent (p ¼ 0.038

The present exploratory analysis is consistent with the main findings of the ATLANTIC study and demonstrates further that the first hours after PCI are a vulnerable period, with potential benefits of pre-hospital use of ticagrelor in STEMI patients undergoing primary PCI.

It has also been reported that administration of crushed ticagrelor tablets may allow earlier platelet inhibition compared with whole tablets.

STUDY LIMITATIONSSTUDY LIMITATIONS

The exploratory nature of this posthoc Study

A limitation related to the sample size, particularly for the platelet function substudy as numbers were small and

the differences were not statistically significant for all the endpoints.

WHAT IS KNOWNWHAT IS KNOWNThe ATLANTIC study was designed to evaluate the potential effects of pre-hospital oral antiplatelet therapy with ticagrelor

The results showed no significant difference in pre-PCI coronary reperfusion with a pre- versus in-hospital ticagrelor loading dose.

The transfer time was very short and the antiplatelet effects of ticagrelor may not have manifested until after this time

WHAT IS NEWWHAT IS NEWThe ATLANTIC-H24 exploratory analysis confirmed that maximal inhibition of platelet reactivity with pre-hospital ticagrelor occur 1 h after PCI

Significant differences in favor of the pre-hospital ticagrelor group in terms of the degree of ST-segment elevation resolution and the composite ischemic endpoint

WHAT IS NEXTWHAT IS NEXTObservation of the effects of pre- versus in-hospital oral antiplatelet therapy in STEMI patients in a realworld context, where transfer delays are likely longer than we observed, would provide further evidence.

THANKS

atlantic h 24

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