Coronary Adjunctive Pharmacotherapy

Contemporary Antiplatelet Strategies in the Treatment of STEMI using

Primary Percutaneous Coronary Intervention
Sri R av e e n Ka n d a n a n d Th o m a s W J o h n s o n

Bristol Heart Institute, Bristol, UK

Abstract
Reperfusion therapy for patients presenting with an acute ST-segment elevation myocardial infarction (STEMI) involves primary
percutaneous coronary intervention (PPCI) and concomitant oral antiplatelet and intravenous antithrombotic pharmacotherapy.
There is a conflict between the desire to reduce the time between first medical contact and coronary re-canalisation and achieving
effective platelet inhibition with oral antiplatelet agents. This review outlines the currently available antiplatelet treatments, and their
place within the therapeutic timeline of a patient presenting with STEMI. Additionally, we focus on current challenges associated with
effective antiplatelet treatment, including acute stent thrombosis (AST), the effect of morphine, platelet function assessment and
concomitant anticoagulant therapy.

Keywords
Primary percutaneous coronary intervention, antiplatelet therapy, ST-elevation myocardial infarction

Disclosure: Dr. Kandan has no conflicts of interest to declare. Dr. Johnson has received consultancy and speaker fees from AstraZeneca, Daiichi-Sankyo and Correvio.
Received: 16 December 2014 Accepted: 4 February 2015 Citation: Interventional Cardiology Review, 2015;10(1):2631
Correspondence: Thomas W Johnson, BSc, MBBS, MD, FRCP, Bristol Heart Institute, Upper Maudlin Street, Bristol BS2 8HW, UK. E: tom.johnson@uhbristol.nhs.uk

Antiplatelet Therapy Clopidogrel

Current guidelines support the early administration of oral antiplatelet
agents upstream of angiographic assessment and intervention.1
Aspirin is commonly given by the first medical contact and additional
oral antiplatelet drugs are administered on arrival in hospital (see
Figure 1).
Aspirin
The efficacy of aspirin in acute ST-segment elevation myocardial
infarction (STEMI) was first demonstrated in the Second International
Study of Infarct Survival (ISIS-2).2 In ISIS-2, 17,187 patients were
randomised within 24 hours of an acute STEMI to receive oral aspirin
160 mg/day for 30 days, intravenous streptokinase, both agents
or neither drug. Compared with placebo, aspirin therapy resulted
in a highly significant reduction in vascular mortality (23 % odds
reduction [OR]), equivalent to streptokinase monotherapy (25 % OR).
The combination of aspirin and streptokinase offered even greater
benefit (42% OR). Aspirin therapy was also associated with significant
reductions in the incidence of non-fatal re-infarction (1.0 versus 2.0%)
and stroke (0.3 versus 0.6 %) with no increase in the risk of major
bleeding or haemorrhagic stroke.
Aspirin has excellent bioavailability and this is enhanced by use of
uncoated aspirin, administered chewed or crushed to establish a high
blood level quickly (time to peak concentration [Tmax] 2030 minutes).3
Interestingly, there is a significant geographic variation in the dosing of
aspirin. In Europe, the recommended oral loading dose is 150300mg
(or intravenous [i.v.] 80150 mg) followed by 75100 mg by mouth (p.o.)
daily.1 US STEMI guidelines recommend 162325 mg loading followed by
81325 mg daily.4
Clopidogrel is a thienopyridine a pro-drug requiring two cytochrome-
p450 dependent steps to generate an active metabolite which binds
irreversibly to the P2Y12 adenosine diphosphate (ADP) receptor on
platelets (see Figure 2). Genetic polymorphisms in the cytochrome
P450 (CYP) enzymes can lead to lower levels of the active clopidogrel
metabolite, diminished platelet inhibition and a higher rate of major
adverse cardiovascular events (MACE), including stent thrombosis.
Approximately 30% of healthy subjects have been shown to be carriers
of a reduced function CYP2C19 allele.5
Use of clopidogrel in STEMI patients has evolved from initial trials in
acute coronary syndrome (ACS) patients undergoing percutaneous
coronary intervention (PCI) (Clopidogrel in Unstable Angina to Prevent
Recurrent Events Trial [PCI-CURE])6 and patients with STEMI treated
with fibrinolysis before PCI (PCI-clopidogrel as adjunctive reperfusion
therapy trial [PCI-CLARITY]).7 In PCI-CURE, ACS patients undergoing
PCI benefited from combined treatment with clopidogrel and aspirin,
achieving a 31 % reduction in cardiovascular death and MI at 30
days. In PCI-CLARITY, clopidogrel pre-treatment in STEMI patients
undergoing fibrinolysis led to a 46 % reduction in the 30-day rate of
cardiovascular death, recurrent MI or stroke compared with placebo,
without an increase in bleeding.
The recommended clopidogrel loading dose in STEMI patients is
600 mg. Results from the Intracoronary stenting and antithrombotic
regimen: Choose between 3 high oral doses for immediate clopidogrel
effect (ISAR-CHOICE) trial8 showed that in patients undergoing PCI,
loading with 600 mg of clopidogrel (compared with 300 mg) resulted
in higher plasma concentrations of the active metabolite and lower

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 Contemporary Antiplatelet Strategies in the Treatment of STEMI using PPCI

values for ADP-induced platelet aggregation 4 hours after drug Figure 1: Timeline of a STEMI Patient Requiring PPCI and
administration. The clinical benefit of a 600 mg loading dose in STEMI Pharmacotherapy Options
patients undergoing PPCI was demonstrated in the Antiplatelet
therapy for reduction of myocardial damage during angioplasty Symptom Onset

(ARMYDA)-6 MI,9 Clopidogrel and aspirin optimal dose usage to

reduce recurrent events seventh organisation to assess strategies Aspirin (Morphine,
First Medical
in ischemic symptoms (CURRENT-OASIS) 7 10 and Harmonising Contact Oxygen Therapy)
outcomes with revascularisation and stents in acute myocardial
CTB Time*

}
infarction (HORIZONS-AMI)11 trials. In ARYMDA-6 MI, high dose loading Diagnosis and Antiplatelet Therapy 113 mins
Decision for PPCI pre-PPCI
reduced infarct size with improved cardiac function, and 30-day
MACE rates. Similarly, in subgroup analyses of the CURRENT-OASIS Clopidogrel or Prasugrel
7 and HORIZONS-AMI trials, STEMI patients loaded with clopidogrel Arrival at PPCI or Ticagrelor
Centre
600 mg, prior to PPCI, had a significant reduction in stent thrombosis DTB Time*
and myocardial infarction, without any increase in bleeding events. Heparin or Bivalirudin +/- GP
39 mins
PPCI IIb/IIIa Inhibitor
Prasugrel
Aspirin + Clopidogrel or
Prasugrel is a third-generation thienopyridine, sharing the same active Prasugrel or Ticagrelor
Post PPCI
metabolite as clopidogrel (see Figure 2), and despite partial reliance on (Warfarin and (N)OACs)
CYP2C19, achieves faster and more potent platelet inhibition (a 60 mg *Median times based on British Cardiovascular Intervention Society Audit Returns 2013.
CTB = call to balloon; DTB = door to balloon; GPIIb/IIIa = glycoprotein IIb/IIIa; (N)OAC = non-
loading dose of prasugrel reaches maximal plasma concentration at 30 vitamin K antagonist oral anticoagulants; PPCI = primary percutaneous coronary intervention.
minutes in healthy volunteers).12 Prasugrel has a very low rate of non-
responders in comparison with clopidogrel.13 Figure 2: Molecular Targets of Drug Therapy on the
Activated Platelet
The clinical superiority of prasugrel over clopidogrel in ACS was
demonstrated in the TRial to assess Improvement in Therapeutic Prasugrel Clopidogrel
Outcomes by optimising platelet inhibitioN Thrombolysis in Myocardial
CP450
Infarction-38 (TRITONTIMI 38) study.14 Prasugrel, administered
following angiography, reduced the composite primary endpoint CP450 CP450
(cardiovascular death, non-fatal MI or stroke) in patients undergoing
PCI for STEMI or moderate-high risk ACS. In the pre-specified STEMI active
subgroup (3,534 patients), the risk reduction was 21% (prasugrel 10% metabolite
versus clopidogrel 12.4%) at 15 months, without a significant increase
in non-coronary artery bypass graft (CABG)-related bleeding.15 The risk Ticagrelor

of stent thrombosis was also significantly lower. P2Y12 GPIIb/IIIa Inhibitors

2
Y1
P2

Prasugrel is contraindicated in patients with prior stroke/transient

ischaemic attack (TIA), and is not recommended in patients aged 75 Abxicimab
Platelet Activation Eptifibatide
years or in patients with lower body weight (<60 kg), as there was no net Tirofiban
clinical benefit in these subsets. A reduced maintenance dose of 5mg AA TXA2
could be considered in these patients. COX-1

Ticagrelor
A new chemical class called CycloPentylTriazoloPyrimidine is partly
formed by Ticagrelor, which, in contrast to thienopyridines, causes
reversible inhibition of the P2Y12 receptor and does not require
hepatic metabolism for its activity (see Figure 2).16 Similar to prasugrel,
ticagrelor provides more rapid, potent and consistent platelet inhibition
over clopidogrel.
In the PLATelet inhibition and patient Outcomes (PLATO) trial,17 ticagrelor
(compared with clopidogrel) reduced the composite primary endpoint
(cardiovascular death, non-fatal MI or stroke) and also reduced
cardiovascular mortality in STEMI and moderatehigh risk ACS patients.
In the STEMI subgroup, this primary endpoint was reduced from 10.8%
in the clopidogrel group to 9.4% in the ticagrelor group (relative risk [RR]
reduction of 13%). In addition, overall mortality was reduced from 6 %
to 4.9% without a higher risk of major bleeding.
Dyspnoea is a frequently reported side effect of ticagrelor. In PLATO,
13.8% of patients on ticagrelor reported dyspnoea compared with 7.8%
Aspirin
AA = arachidonic acid; COX-1 = cyclooxygenase-1; CYP450 = cytochrome P450;
P2Y12 = purinergic receptor P2Y; GPIIb/IIIa = glycoprotein IIb/IIIa; TXA2 = thromboxane A2.
treated with clopidogrel.17 However few patients (0.9%) discontinued the
drug because of dyspnoea; importantly, there were no associated lung
abnormalities and the mortality benefit persisted in this group.18 Contrary
to the PLATO experience, a recent study of ticagrelor compliance in ACS
patients demonstrated that dyspnoea was the commonest reason for
drug discontinuation, occurring in 9.1% of cases.19
The European Society of Cardiology (ESC) and American College
of Cardiology Foundation/American Heart Association (ACCF/AHA)
recommendations for antithrombotic strategies in patients with STEMI
undergoing primary PCI are summarised in Table 1. Prasugrel, ticagrelor
and clopidogrel (600 mg loading dose) are all class I, level B options in
both guidelines, but the ESC expresses a clear preference for the newer
antiplatelet agents, stating that clopidogrel should only be used when
prasugrel or ticagrelor are either not available or contraindicated.

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 Coronary Adjunctive Pharmacotherapy

Table 1: Recommendations for Antithrombotic Treatment Strategies in Patients with STEMI Undergoing Primary PCI

Recommendations Class of Recommendation

ESC1 ACCF/AHA3
Antiplatelet Therapy
Aspirin
Recommended in all patients regardless of initial treatment strategy I I
In Europe: Loading dose 150300mg oral (or 80150mg i.v.), maintenance dose 75100mg daily long term I
In America: Loading dose 162325mg oral, maintenance 81325mg daily long term (81 mg preferred with I
Ticagrelor Class IIa)
P2Y12 Inhibitor
Recommended in addition to aspirin and maintained over 12 months I I
Give at time of first medical contact (ESC); as early as possible or at time of PCI (AHA/ACCF) I I
Options:
Prasugrel (60 mg loading dose, 10 mg daily dose) if no contraindication (i.e. prior stroke/TIA) I I
Ticagrelor (180 mg loading dose, 90 mg twice daily dose) if no contraindication I I
Clopidogrel (600 mg loading dose, 75 mg daily dose). ESC: only when prasugrel or ticagrelor are not I I
available or contraindicated
GPIIb/IIIa Inhibitor
Should be considered for bail-out or evidence of no re-flow or a thrombotic complication IIa IIa
Upstream use may be considered for high-risk patients undergoing transfer for primary PCI IIb IIb
Options are: abxicimab, eptifibatide (with double bolus) or tirofiban (with a high bolus dose)

Anticoagulant Therapy
Recommended in all patients in addition to antiplatelet therapy I I
Options:
Unfractionated heparin (70100 U/kg i.v. bolus when no GPIIb/IIIa inhibitor is planned; 5070 U/kg i.v. I I
bolus with GPIIb/IIIa inhibitor)
Bivalirudin 0.75 mg/kg i.v. bolus followed by i.v. infusion of 1.75 mg/kg/h for up to 4 hours post procedure IIa I
Bivalirudin is preferred over UFH with GPIIb/IIIa receptor antagonist in patients at high risk of bleeding IIa
Enoxaparin i.v. 0.5 mg/kg with or without GPIIb/IIIa inhibitor IIa

Antiplatelet Therapy after PCI in Patients Requiring Oral Anticoagulation

In patients with a firm indication for oral anticoagulation (e.g. atrial fibrillation with CHA2DS2-VASc score 2, I
venous thromboembolism, LV thrombus or mechanical valve prosthesis), oral anticoagulation is recommended
in addition to antiplatelet therapy
In patients with ACS and atrial fibrillation at low bleeding risk (HAS-BLED 2), initial triple therapy of (N)OAC and IIa
ASA (75100 mg/day) and clopidogrel 75 mg/day should be considered for a duration of 6 months irrespective of
stent type followed by (N)OAC and aspirin 75100 mg/day or clopidogrel (75 mg/day) continued up to 12 months
In patients requiring oral anticoagulation at high bleeding risk (HAS BLED 3), triple therapy of (N)OAC and ASA IIa
(75100 mg/day) and clopidogrel 75 mg/day should be considered for a duration of 1 month irrespective of stent
type followed by (N)OAC and aspirin 75100 mg/day or clopidogrel (75 mg/day) continued up to 12 months
The use of ticagrelor and prasugrel as part of initial triple therapy is not recommended III
ACCF/AHA = American College of Cardiology Foundation/American Heart Association; ACS = acute coronary syndrome; ASA = acetylsalicylic acid; CHA2DS2-VASc = Cardiac failure,
Hypertension, Age 75 [Doubled], Diabetes, Stroke [Doubled] Vascular disease, Age 65 74 and Sex category [Female]); ESC = European Society of Cardiology; GPIIb/IIIa = glycoprotein
IIb/IIIa; HAS-BLED = hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile INR, elderly, drugs/alcohol; INR = international normalized ratio; LV = left
ventricular; (N)OAC = (non-vitamin K antagonist) oral anticoagulant; PCI = percutaneous coronary intervention; STEMI = ST elevation myocardial infarction; TIA = transient ischaemic attack;
UFH = unfractionated heparin.

Glycoprotein IIb/IIIa Inhibitors
Glycoprotein IIb/IIIa inhibitors (GPIs) provide rapid, potent platelet
inhibition. Their use in PPCI has spanned the evolution of PCI and
pharmacological therapies; consequently, it is challenging to relate the
data to current practice with more potent oral antiplatelet therapies.
Initial data supported the combined role of stenting and abciximab
administration to minimise target vessel revascularisation,20 and pre-
angiographic commencement of therapy appeared advantageous.21
However, in the dual antiplatelet therapy (DAPT) era, early use of
abciximab resulted in an increased rate of bleeding.22 Subsequent
analysis has demonstrated a continued benefit in early administration
of GPIs in high-risk patients,23 particularly if presenting early or to a
non-interventional centre.24 Contemporary trials provide conflicting
results, the ONgoing Tirofiban in Myocardial infarction Evaluation 2
(ON-TIME 2) trial,25 utilising pre-hospital initiation of high bolus dose
tirofiban, in addition to aspirin, heparin and high-dose clopidogrel,
reduced MACE at 30 days with no significant increase in major
bleeding. However, the HORIZONS-AMI26 trial demonstrated superiority
of bivalirudin versus unfractionated heparin (UFH) and GPI in terms of
a composite of major bleeding and MACE. Consequently, current
guidelines1,4 suggest restricting GPI use for bailout in the event of
angiographic evidence of massive thrombus, slow-/no-reflow or a
thrombotic complication.
Adjunctive Antithrombotic Pharmacotherapy
during PPCI
In addition to the array of oral antiplatelet therapy options in PPCI, there
is continued debate regarding the optimal combination of antithombotic

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 Contemporary Antiplatelet Strategies in the Treatment of STEMI using PPCI
therapy. UFH and bivalirudin are most commonly used and the European
guidelines for STEMI support their use with a Class I indication.27
The evidence supporting use of bivalirudin derived from HORIZONS-
AMI,26 which demonstrated that bivalirudin compared with UFH and
routine use of GPIs was associated with a reduction in mortality
and major bleeding at 30 days, with a survival benefit that extended
to 3 years. Further support for bivalirudins bleeding safety was
demonstrated in the open-label European Ambulance ACS Angiography
(EUROMAX) trial,28 comparing pre-hospital administration of bivalirudin
versus UFH or low-molecular-weight heparin (LMWH) with optional use
of GPI (58.5% routine use). However, both trials were associated with
an increased rate of AST with the use of bivalirudin and the elevated
bleeding rate observed in the UFH arm of both studies has been
attributed to the high rates of GPI use.
The recently published How Effective are Antithrombotic Therapies in
primary percutaneous coronary intervention (HEAT-PPCI) trial29 was
designed to specifically address the criticisms levelled at previous
bivalirudin trials, specifically the efficacy of bivalirudin monotherapy
against UFH with GPI use restricted to true bail-out (13 % and 15 %,
respectively). The study demonstrated a primary efficacy outcome (all-
cause mortality, cerebrovascular accident, re-infarction or unplanned
target lesion revascularisation) of 8.7% in the bivalirudin group versus
5.7% in the heparin group (RR 1.52, 95% confidence interval [CI] 0.9
2.13). This reduction in major adverse ischaemic events with heparin
was not associated with an increase in bleeding complications. Definite
or probable stent thrombosis occurred more often with bivalirudin (3.4
versus 0.9 %, RR 3.91, 95% CI 1.619.52). In the light of these new data,
the most recent ESC guidelines on revascularisation have downgraded
their recommendation for the use of bivalirudin to Class IIa1.
Acute Stent Thrombosis
The increased rate of AST observed with bivalirudin therapy has been
attributed to the relatively short half life of bivalirudin (t1/2=25minutes),30
resulting in a waning effect of the drug within 2 hours of withdrawal.
The risk of AST is further exacerbated by the observed delay in
platelet inhibition observed in STEMI patients treated with oral P2Y12
inhibitors. The Rapid Activity of Platelet Inhibitor Drugs (RAPID) Primary
PCI study31 evaluated 50 patients with STEMI undergoing PPCI with
bivalirudin monotherapy, randomised to prasugrel or ticagrelor at
standard loading doses. There was no significant difference in residual
platelet reactivity between both drugs but the study showed that
effective platelet inhibition within 2 hours of loading was only achieved
in half of patients. Four hours were required to achieve effective
platelet inhibition in the majority of patients.
Morphine Effect on Platelet Activity
The RAPID investigators assessed the effect of opiate use on platelet
reactivity. The use of morphine significantly affected the activity
of prasugrel and ticagrelor, independently predicting high residual
platelet reactivity 2 hours post-loading dose (odds ratio 5.29;
p=0.012).31 The effect has been confirmed in a randomised controlled
trial of 24 healthy subjects receiving 600 mg of clopidogrel with
placebo or 5 mg of intravenous morphine. Morphine was shown to
delay clopidogrel absorption, decrease plasma levels of the active
metabolite and delayed the maximal inhibition of platelet aggregation
by 2 hours.32 Furthermore, the opiate effect on platelet inhibition
does not appear restricted to patients experiencing opiate-related
nausea/vomiting.33
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Johnson_FINAL.indd 29
The negative interaction between morphine and oral antiplatelet
agents is also supported by the Administration of ticagrelor in the
cathlab or in the ambulance for new STEMI to open the coronary
artery (ATLANTIC) trial,34 which demonstrated that the primary end
point of ST-segment resolution was significantly improved with pre-
hospital administration of ticagrelor in opiate-nave patients. These
findings challenge current guidance to administer analgesia early, on
first medical contact.27
Methods to Enhance Platelet Inhibition
Studies to overcome the potential delay in platelet inhibition, associated
with immediate pre-procedural loading of oral antiplatelet therapy,
have been undertaken. The ATLANTIC investigators addressed this
question by randomising 1,862 patients presenting within 6 hours
of STEMI onset to pre-hospital versus in-hospital treatment with
ticagrelor.34 Pre-hospital ticagrelor did not improve pre-PCI coronary
perfusion but appeared to be safe and was associated with a reduction
in post-procedural AST. The median time between the two loading
doses (pre-hospital versus in-hospital) was 31 minutes.
Alternatives to upstream administration of an oral antiplatelet therapy
include manipulation of the pharmacokinetic properties of oral
agents or use of an intravenous platelet inhibitor. The Mashed Or
Just Integral Tablets of ticagrelOr (MOJITO) study35 tested the effect of
crushing ticagrelor to accelerate drug absorption and demonstrated
a significant enhancement of platelet inhibition 1 hour following
drug ingestion. A larger scale trial with clinical endpoints would be
necessary to validate these results. Cangrelor is an intravenous
adenosine triphosphate (ATP) analogue, which reversibly inhibits the
P2Y12 receptor without requiring hepatic conversion.36 The attraction
of cangrelor is therefore its very rapid onset of action and short half-
life (35 minutes) allowing rapid platelet inhibition and quick reversal.
Two early trials (Cangrelor versus standard therapy to achieve optimal
management of platelet inhibition [CHAMPION]-PCI37 and CHAMPION-
PLATFORM38) evaluating cangrelor in patients undergoing PCI failed
to show clinical superiority over clopidogrel. The more recent
CHAMPION-PHOENIX39 trial randomised 11,145 patients undergoing
urgent or elective PCI to intravenous cangrelor or clopidogrel 600
or 300 mg loading (56% stable angina/18% STEMI). At 48 hours the
rate of composite primary efficacy endpoint (death, MI, ischaemia-
driven revascularisation or stent thrombosis) occurred less in the
cangrelor group (4.7% versus 5.9%) and the rate of stent thrombosis
was significantly lower (0.8 % cangrelor versus 1.4 % clopidogrel).
Although the study demonstrated benefit with use of cangrelor, there
were significant limitations in the trial design, favouring the study drug
arm. The control group only received clopidogrel once the anatomy
was delineated, and 30 % of the cohort were administered the drug
post-PCI. Consequently, the higher rate of peri-procedural MI in the
control group is not surprising.
Antiplatelet Strategies in Patients on
Oral Anticoagulation
A significant proportion of patients undergoing PPCI may already be
anticoagulated on a vitamin K antagonist (VKA) or a non-vitamin K
antagonist oral anticoagulants ((N)OAC) at the time of the procedure.
These patients are at increased risk of bleeding and often the
international normalized ratio (INR) levels are not available. There is
no clear evidence on the optimal antithrombotic pharmacotherapy
for these patients. The 2014 ESC/EACTS guidelines on myocardial
revascularisation1 recommends that PPCI in this setting should be
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 Coronary Adjunctive Pharmacotherapy

performed via a radial approach with use of additional parenteral
anticoagulation regardless of the timing of the last dose of oral
anticoagulant. Bivalirudin may be preferred due to its short half-life and
should be discontinued immediately after PPCI. GPIs should generally be
avoided unless for bail-out situations.
Duration of Dual Antiplatelet Therapy post-PPCI
DAPT (aspirin + a P2Y12 inhibitor) is recommended for 1 year in patients
undergoing PPCI for STEMI. This recommendation is based on the early
CURE study40 (clopidogrel) and is supported by more recent results from
TRITON-TIMI 38 (Prasugrel)15 and PLATO (Ticagrelor).17 Regardless of stent
type, extended DAPT for 1 year reduces the risk of stent thrombosis,
re-infarction and cardiovascular mortality6 with the more potent DAPTs
associated with the greatest post-ACS clinical benefit.41 Recent data
have highlighted that extended DAPT confers further protection against
ischaemic events but at the expense of additional bleeding risk.42 In stark
contrast, the Global-Leaders trial (NCT01813435) is currently enrolling
patients to either 1 month DAPT with aspirin and ticagrelor, and then
ticagrelor monotherapy for 23 month or 12 months DAPT with aspirin
and ticagrelor/clopidogrel with aspirin monotherapy between 12 and 24
months. We await the results with interest.
Antiplatelet Therapy after PCI in Patients
Requiring Oral Anticoagulation
A proportion of patients on DAPT post-PPCI will have a firm indication
for long-term anticoagulation (atrial fibrillation with Cardiac failure,
Hypertension, Age 75 [Doubled], Diabetes, Stroke [Doubled]
Vascular disease, Age 65 74 and Sex category [Female]) [CHA2DS2-
VASc] score 2, venous thromboembolism, left ventricular [LV]
thrombus, mechanical valve prosthesis). Triple therapy with an oral
anticoagulant, aspirin 75100 mg and clopidogrel 75 mg should be
limited in duration depending on the clinical setting, thromboembolic
risk (CHA2DS2-VASc score) and bleeding risk (HAS-BLED score). The
WOEST trial43, which randomised 573 patients either to dual therapy
or triple therapy, showed that in patients on oral anticoagulants the
use of clopidogrel without aspirin was safe. TIMI bleeding and all-
cause mortality was lower in the dual therapy group with no increase
in the rate of thrombotic events. The 2014 ESC/EACTS guidelines on
myocardial revascularisation1 recommends 1 month of triple therapy
for ACS patients at high bleeding risk (HAS-BLED >3) and 6 months
for patients at lower bleeding risk, followed by dual therapy (oral
anticoagulant and clopidogrel or aspirin) for a minimum of 12 months
(see Table 1). The use of prasugrel and ticagrelor as part of triple
therapy should be avoided44 and gastric protection with a proton
pump inhibitor should be implemented.
Conclusion
Successful revascularisation of patients presenting with STEMI requires
rapid transfer to a PCI capable unit and concomitant treatment with
antiplatelet and antithrombotic drugs. A delicate balance exists
between thrombosis and bleeding and a perfect combination of agents
is yet to be found. An intimate relationship between the intravenous
antithrombotic and oral antiplatelet agents exists and these must be
considered in the selection/tailoring of treatment. Oral antiplatelet
therapies provide long-term platelet inhibition but are hampered by
delayed onset of action in acutely unwell patients. Future strategies
may include upstream administration of drugs by the first medical
contact or acute treatment with an intravenous platelet inhibitor. n

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