Education in Heart Pharmacology before, during and after percutaneous oO OPEN ACCESS (Cardology Feeman Hostal and Newcastle Unversty, ‘Newcaseupon Tne UK *ercoony, ames Cook Uniersty Hosp Midlestorough UK Correspondence to PreesorasforG Zaman Freeman Hostal Newcase Upon ye NE? TON, UK: afatzamantens.iet Published Onin Fist 4 November 2020| ® check or updates © Authors) (or tee employes) 2021. Rese permite under CCBYNC. No ‘Commerc se See gs ‘and permissions Published ye To ate: Zaman AG, Aeon @ Hear 2021107 385-592 coronary intervention Azfar G Zaman © ,' Qaiser Aleem? INTRODUCTION Coronary intervention initiates thrombin genera sion through endothelial damage and plaque diseup- ‘ion. The subsequent thrombotic risk! can persist tor several weeks and dissipates, but not disappear, alter stent endotheliaisation. Adjunctive antithrom= botie pharmacology, therefore, isa key determinant of acute and long-term outcomes with the range of available options improving outcomes but adding complexity to the decision making process. This review will focus on antithrombotic phar macology before, during and alter percutaneous coronary intervention (PCI) with stent deployment, The major tials of antithrombotic deugs ate listed in table 1 and those of extended and shortened duration in tables 2 and 3, respectively PHARMACOLOGY BEFORE INTERVENTION Pretreatment refers to pharmacology given (jn ambulance or Emergency Department) betore coro- nary anatomy is defined, Given the pathophysi- ology of coronary revascularisation, pretreatment with P2V12 inhibitors would be expected to reduce ischaemic events. However, this benefit has to be balanced with increased bleeding isk in patients who have nou-obstrictive disease of those referred for surgical revascularisation, The evidence base for patient benctit of pretreatment with oral P2Y12 inhibitors is limited but all patients should be given ‘loading dose of aspirin, Stable angina The evidence for pretreatment arose from the CREDO trial? which demonstrated benefit it patients received clopidogrel 300mg loading at least Ghours betore PCI . However, closer analysis of patient inclusion revealed that most were selected alter coronary angiography. The only tial designed {o test pretreatment was PRAGUE-8 which failed to show ischaemic benefit between prehospital 600mg clopidogeel compared with in-aboratory treatment bur with a higher risk of minor bleeding.” The study finding was consolidated by a meta-analysis showing no mortality benefit from pretreatment” The “absence of benelit from pretreatment loading is reflected in guidelines: The European Society of Cardiology (ESC) giving « Ib C recom ‘menclation for prettearment loading. only ‘i high chance of PCI” and the American Heart Assacia- tion/American College of Cardiology (AHA/ACC) questioning ies benetit without giving, a recommen- ation.” Neither prasugrel nor ticagrelor have been tested in patients with stable angina. There is no evidence of patient benefit for glyco- protein inhibitors (GPI) in pretreatment, Cangrelor > To understand the risks and benefits of antithrombotic drug combinations in coronary intervention in different clinical settings. > To provide a state-of-the-art review of relevant cal studies of pharmacology for coronary intervention, >> To understand options for managing high bleeding risk patients. is approved bur has not been tested in the preteear= ment setting against in-aboratory clopidogrel. The CHAMPION-PHOENIX trial (included stable and unstable patients) found cangrelor to significantly decrease the combined primary etficacy endpoint and stent thrombosis within 48hours compared swith clopidogeel in P2Y12 inhibitor naive patients undergoing PCI’ without increase in severe bleeding. Its use shotild be limited to. high-risk patients unable to take oral medication.® 3 for stable angina when coronary anatomy isnot known, the evidence does not support pretreatment over in-laboratory loading with elopido- ‘gel Itcoronary anatomy isknown (or high probability ff PCI) then pretreatment with clopidogrel (600mg) at least 2hours before procedure is recommended ‘There ino role for preprocedral anticoagulants, In sa Non ST elevation acute coronary syndrome (NSTE-ACS) Data from PCI-CURE showed benefit of pretreat- rent with clopidogrel and aspirin in NSTE-ACS both betore and after PCI, even though the median time trom randomisation to PCI was 10 days—in contrast to contemporary recommendation for early referral and invasive management (within AShours). Subsequent studies in NSTE-ACS were equivocal’ '” showing no benelit of clopidogrel pretreatment, A non-randomised study of clopido- tgrel pretreatment (300mg loading =12hours oF 1 600mg loading 22hours before angiography) was associated with similar adjusted short-term ischaemic and bleeding outcomes compared with inlaboratory 600g, clopidogrel loading (=2hours before or alter PCI). Overall, in the setting ot early invasive therapy, the evidence supporting pretreat ment with clopidogeel in NSTE-ACS is limited. Pretreatment with ticagrelor against in-laboratory treatment has not been tested. In PLATO," treat- ment before coronary angiography was permitted and did not exclude patients pretreated with clopidogrel before randomisation. Study analysis showed pretreat iment to be safe but without ischaemia reduction. BM) “aan AG, Nem Q Hear 2027107 585-592, 60:10, 1 3Bhear-2018-315050 385 ‘YBLAdoD Aq payDa}oie SANBAG }ZOZ "4 JOqUAAONY Uo jiU0D Tula HeAUy/dhjy WOY PaPEOIUMEG “9ZOZ JOqWAAON ¥ UO O6OSLE-61OZ-1UEDUIEL LO} Se PausHNd ys1y 3HeOHEtec ers Table 1 _ Summary of pivotal trials for antithrombotic agents sty Tmber of paints Agent used Tndation —__Teatment ration Primary endpoint Safty end pont Pao 9828 spin Tear ‘AS wih or witout 2 months Dea Mischa Mier tein 203 * Steen SeeTeageer 116 Teal rine ploy! Ti 7Waspdogel — 125Cophogel evan rae rion 12608 spins Pa! as E15 monte Deanna Maj edag 20? Tessas 5% pats ad fd stoke 2a ‘spins Copley ra 8% rege 1 8%cpagel Pega Le testenng bed 1st Os clogged cone 56 spline Coplagel scswahousT 3-12 mas Deane stole Maj edng nor * ‘tention am 37s Chpdoge Depcins Pat 82% Chpdoge! ——-274Pasnel ‘iaPouge P0001 Peon cuRVTvn2e 3191 Fieri soioogant corel STEMI ‘meth Composite of clon TM major Boe es Geldoge * inact anayideaty 15chpdagel * Fcotrctdopdoget acto w israel Posto Ssictphoged P06 2 rePeugel consis 20078 Fondiprn, oes as Destnteacony Majer beng or ‘hema 2he—Fondapacin ropa Serdar 154 Exoapan 57% —trorapin P0001 ots aruwic 8 revetment agers inabostoy STEM: Fndot STOR ST segment No iterence a stom oye rekon opin endoins TA 3 ow int tet ary before 7S a array ons cr wn PL pereaanos cornu avert STEM, ST Eon NocedaT aon The only randomised smdy of pretreatment in second in-laboratory 30mg dase compared with this population was the ACCOAST study which 60mg before PCI, after coronary anatomy had tested halt-dose prasugrel (30mg) followed by a been defined.” The results showed no benefit Table 2 Tals of prolonged duration of antthrombotics Fellow up study Novo patents Agent used uation cacy endpoints Safety endpoint recast ane “pos eaglar cong wo etd 33 emt ean "Wa major beg ams ‘spins eager S0mg we mes a) Tage sng: 785% 50mg. 26% AG previous 1-3 yeas with ws fom 777 ag 23% igh haem ik spine cto: 804% Flcrbo 06% Pea ws i920 Teele (0 wo tines 3 doysAspiin 38.8 moths Friary endpoint TM mar ewig ama * Cacahasocke Teale = 22% Stable 0 and ype ites, pineplacbo spring = 108, histo of revs MSs eos ‘Heuspe ast Teal 160 40 ies a dain Pinay endpant Tl mao bldg am * CVéeabanicke ——TeaplrsAspiin=20% Saba of THEME patents who spn TeagelersAspin73% Ayprnsplcedo=1 1% dewet FC Zepeineplceho-hcie Peaaoh reaor Nena eet 15% recon in Tear sm oart et Aspiinchenapyidne for 12 montts 30 months Stem trontess, _aerate-svertedng a ‘ OAs 20monhe Omens 25% CS wih igh chon vk in thinapyiin for 30 moths 112m det) 12 mente) 6% stoke reat 12530 mene 59% 12 mone counass 205 ‘ovraaban 251mg wo tiesa yin 23 Dest Majer eng a7 s ns am a ‘Sle aro scar ora ing tos a cy (Guaroatane gin) fsoabans Aspen) ene « A9GRoaaber Ltn spin Sess reaooi FeO Fr READ WA DAFT aa apie erp TM Tenshi n Nol TR 586 ‘Zaman AG, lee Q Heat 207,107 385-59, do 10.1136 2019-315090 ‘YBLAdoD Aq payDa}oie SANBAG }ZOZ "4 JOqUAAONY Uo jiU0D Tula HeAUy/dhjy WOY PaPEOIUMEG “9ZOZ JOqWAAON ¥ UO O6OSLE-61OZ-1UEDUIEL LO} Se PausHNd ys1y 3HeOHTable 3 Tals of short duration DAPT LEADERS FREE 2015 [acSastable angina onvcone 200 [AcSstable angina ‘enon ania AcSstable angina TMUGHT 209 cSastable angina 2866 HBR patents ‘I monthafDAPTfelowedby_12-nth olow-up Biofeedom (DE) vs asprin alone ams 1956 HBR patents mom DAP (aspinrmosty12-momt follow-up Resolute Ory (DE9) vs coir) Boreedom DES) After 2 mnths 52% on single ar spin: 55.9% Pavia: ati%s 1200 paens>75 yeas month DAPT for state angina 12-onth follow-up Synergy (ES) Smonts DAPT or cs aus 7118 patents at HER or Tagelor+Aspin for 3 mons. 12nonth follow-up ighiscacmicrik then “eager Asin ws “eagelersplacbo Target son revsclarsatien: Death, A stent hromboss 5.1% Blfresdom 98% Bofeedom vs, 98% BMS a9 Ms Poon! Peo. Primary safety endpoint: Stent thrombosis Caric deatiMistent thrombosis 09% a 12 months for bth ATVs 169% ae P0011 fornonineay P0393 Bling, BARC2-5 P=0A Primary endpoint louse mortality, Stn romboss My sucker chaemi-civen target 18 forboh arms ein evasion Bleeding: 54 in bth ams ES 11.6% 95 BMS 16.4% P02 Primary endpoint: BARC2,3,5 Death om ay case ron Z fat Mor non tl stoke 3.9% imboth arms 0.01 farroinfeorsy "as BARC eng Sada reszrch allaboration BM, are meta sient DART, dl anata era DES dug ing it HBR, ih bled kT agrlr ff pretreatment in the ischaemic endpoint but a 90% increased risk of major and life-threatenin bleeding, In the PCI subgroup, there was also no evidence of ischaemic benelit.” The ACTION group meta-analysis also failed t0 show a signi cant mortality reduction with pretreatment with increased major bleeding.” The failure of pretreatment with oral P2YI2 inhibitors in NSTEACS was surprising given the central role of platelets in atherothcombotic disease and rises questions about whether the mode of delivery—oral versus patenteral—could be important. The evidence for GPI’s pre-dates use of routine oral dual antiplatelet therapy (DAPT) and early invasive treatment. While eacly trials demonstrated reduction in ischaemic events (largely reduction in myocardial infarction (MI) in favour of GP] in combination with unfrac- tionated heparin (UFH) compared with UFH alone," a consistent major bleeding risk was seen. Overall, there is no evidence for beneiit Of routine upstreain GDI in paticnts scheduled for PCI and receiving DAPT treatment." With ticagrelor or prasugrel, randomised data with GPT use are limited; therctore, use of these agents for pretreatment is not recommended. Cangrelor alsa lacks evidence in the preseice of prasugeel or ticagrelor.” Jn summary, aspirin (loading and! maintenance) carries a IA recommendation for pretreatment in NSTE-ACS with teragelor (I80me) added as soon. a the coronary anatomy is established (IDC). It tieagrelor is unavailable, then clopidogrel 600m can be given but prasugeel is not recommended (ila). The use of cingrelor in P2Y12-natve patients tunable to take oral medication caries aIbA recor aendation. If the wait for coronary angiography js longer (>24hours), antiplatelet pretreatment should be considered With respect to anticoagulants, the OASIS-5 trial showed equivalence of fondaparinus. 25mg od subcutaneously) to heparin in reducing composite events but with a reduced risk of bleeding.”* As a result, fondaparinus carries a class IA recommendation for pretreat- ment of NSTE-ACS but patients should receive UFH during PCL Where foudaparinux is not available, then enoxaparin (1 mg/kg two times a day, subcutaneously) is preferred (class IB).* ST elevation myocardial infarction (STEM!) The only pretreatment study was ATLANTIC? which showed no benefit in the composite primary end-points of infarct artery TIMI 3 flow and 709 ST segment resolution, One reason ‘may have been the short median time berween the loading doses in the pretreatment and no pretreatment groups (about 30min) which was likely insufficient to allow for significant sepa- ation in platelet inbibition between the two groups ar the time of PCL Although TRITON-IMI 38° did not allow pretreatment with prasugrel, the consensus has been to accept administration of prasugrel in patients with STEMI undergoing primary PCI within |2hours from symptoms, Cangrelor lacks evidence inthis setting with CHAMPION-PHOENIX including only 1896 STEMI patients ‘The European Society of Cardiology, European Association of Cardiothoracie Surgeons ESC-EACTS) guidelines (aspirin IA) recommend ticagrelor of pras- ‘ugtel betore PCI (LA). Cangrelor (lb) or GPI (IbC) ‘may be considered in P2Y12 inhibitor naive patients ‘unable to rake oral medication.? PHARMACOLOGY DURING INTERVENTION Stable angina The use of parenteral anticoagulants is standard of care dusing elective PCI to inhibit thrombin gener- ation with UEH and bivalirudin being the most widely studied.”*~* Low molecular weight heparin nay be considered especially if the patient was on this preprocedure. The recommendation is to use Zaman AG, Aleem Q Heart 2021107, 585-9, do 10.1136heryn-2019315090 387 ‘YBLAdoD Aq payDa}oie SANBAG }ZOZ "4 JOqUAAONY Uo jiU0D Tula HeAUy/dhjy WOY PaPEOIUMEG “9ZOZ JOqWAAON ¥ UO O6OSLE-61OZ-1UEDUIEL LO} Se PausHNd ys1y 3HeOHEtec 70-100U/kg. of UFH. Anticoagulant teeatment should be stopped once PCI is completed, Non-ST elevation acute coronary syndrome and ST elevation Mil LUFH is cost effective and trials in the contemporary era of radial access show equivalence” oF supeti- ority to bivalirudin.”* Overall, there is no compel- Ting evidence for the benetic of routine use of GPL in NSTE-ACS or STE-MI patients undergoing PCI with P2Y'12 antiplateler treatment with use limited to bail cut situations, The evidence on cangrelor suggests thar the potential benetie (rapid platelet inhibition) is independent of the clinical presentation. Thus, cangrelor may be considered in specific setings in ZY 12-nave patients undergoing high risk PCL PHARMACOLOGY AFTER INTERVENTION The duration of DAPT after PCI should consider patient-specitic risk, clinical presentation, and procedural actors, Prolonged DAPT for all patents reduces stent thrombosis and MI at the expense of increased bleeding. In certain clinical scenarios, there is evidence for both shortening t Lmonth or extending beyond 12 months", There are also data showing safety and efficacy of stopping aspirin at 3 months and continuing with a single P2Y12 anti- platelet agent. Stable angina For all stents, the recommended duration of DAPT (aspirin and clopidogrel) is 6 months and aspirin continued thereafter for lite, The COMPASS trial”? demonstrated the value of Tow (vascular?) dose rivaroxaban (2.5 mg two times a day) in combina- ‘ion with aspirin, However, this trial was nor inked 0 myocardial revascularisation procedures. ‘The GLOBAL-LEADERS trial in patients under- going PCI tor both stable and unstable disease, eval= tated I month of aspirin plus ticagrelor followed by 23 months of ticagrelor monotherapy compared with Lyear of DAPT (aspirin plus clopidogrel in stable of ticagrelor in unstable) followed by l year cf aspirin monotherapy:"* The primary outcome showed no significant reduction but safety was confirmed. The findings were similar in multiple rested subgroups In THEMIS” patients with stable disease and diabetes without history of MI or stroke, tieageelor plus aspirin had a lower incidence of ischaemic events but a higher incidence of major bleeding, Importantly, in a prespecified PCI patient populae tion, ricageelor plus aspirin provided a favourable niet clinical benetit.” ‘The GLOBAL-LEADERS and THEMIS studies ‘underscore the point that in an unselected patient population undergoing PCL for stable angina, there is no benefit of extending DAPT or substituting aspirin with a more potent P2Y12 agent. However, based on THEMIS-PCI, long-term therapy with ticagrelor in addition to aspirin should be consid- cred in patients with diabetes and a history of PCL who have tolerated antiplatelet therapy, have high ischaemic risk and low bleeding tisk. Non-ST elevation ACS and ST elevation MI ‘The guidelines recommend 12 months of DAPT (aspirin with either ticagrelor oF prastigrel) post- procedure, However, it sin this subset of high patients after ACS where evidence is growing for extending duration beyond Lyear. The PEGASUS: ‘TIMI 54" study randomised patients with a history: fof AMI (most underwent PCI) to aspirin and tica- agrelor (60mg, two times a day or 90mg two times a day) versus aspirin and placebo. Alter a median follow-up of 33 months, the ticagrelor groups had mniticantly lower rates of major adverse cardiovas- cular and Cerebrovascular Events (MACCE) with higher rates ot TIMI major bleeding (with higher rates of bleeding with 90mg ewo times a day vs 60mg two times a day) with similar rates of intra- cranial haemorthage or taral bleeding among the three groups. The study is important in demon- strating the efficacy of prolonged DAPT in high= ris patients and supports the safety of this strategy in selected patients. A substudy analysis in patients swith diabetes “with prior MI demonstrated a reduc- tion in ischaemic events with ticagrelor and aspirin. Taken together with the THEMIS-PCI study, there is growing evidence for extending ticagtelor for secondary prevention in high-risk subgroups, The ESC guidelines recommend extending tiea- agrelor 60mg two times a day beyond 12 months with aspisin in patients with previous MI and high ischaemic tisk who have tolerated DAPT without bleeding complications (ULB) PHARMACOLOGY IN PATIENTS IN ATRIAL FIBRILLATION ON EXISTING ANTICOAGULANTS UNDERGOING Pct ‘The main focus in patients sith atrial fibrillation (AF) is stroke prevention. Several tials” guide therapy in this population with all powered for bleeding endpoints compared with vitamin K antagonist (VKA) and not for ischaemic oF stroke prevention The WOEST study. demonsteated safery of sing a combination of clopidogrel and wartarin alone in terms of thrombotic events with reduced overall bleeding risk, The PIONEER RE-DUAL,” AUGUSTUS “and ENTRUST” trials farther reinforced the concept of redundancy of aspirin dite to increased bleeding in patients with AF treated with anticoagalant and P2V12 inbib- itor. The AUGUSTUS trial used a factorial design to specifically evaluate a single P2Y12 inhibitor with an anticoagulant versus triple therapy. with aspirin. This tal confirmed first, superiority of apixaban over VKA in reducing bleeding and second, similae efficacy but less bleeding, with dual therapy (apixaban and P2Y12 with >9200 of patients on clopidogee), Pretreatment Direct oral anticoagulants (DOAC) should be with- held for 24hours (48hours for those with renal impairment on dabigatean ~ creatinine clearance <50ml_/min).”" For patients on VKA, this does not ‘Zaman AG, lee Q Heat 207,107 385-59, do 10.1136 2019-315090 ‘YBLAdoD Aq payDa}oie SANBAG }ZOZ "4 JOqUAAONY Uo jiU0D Tula HeAUy/dhjy WOY PaPEOIUMEG “9ZOZ JOqWAAON ¥ UO O6OSLE-61OZ-1UEDUIEL LO} Se PausHNd ys1y 3HeOH[ra ® A & @ oe Renal Lverdsease Active cancer Low platelet (275 years) disease a ‘Sroke, Beedag _—r Desig NSAIDs, Planned surgery on DAPT, ch Dav ortanstusion stores rocont tauma or surgery ex) (=o Figure 1 Markers of high bleeding risk. BAVM, brain arteriovenous malformation; ICH, intracranial haemorrhage; NSAID, nonsteroidal anti inflammatory drugs; OAC, oral anticoagulant. need ro be interrupted" bur US guidelines recom: ‘mend a washout period betore PCI using preferably, radial access when international normalised ratio (INR) ©2 (or if femoral when INRS1.5)~” As there is scant evidence for preloading with P2Y12 antiplatelet agents, patients on oral anticoag tlants should only receive treatment once coronary anatomy is known and decision made to proceed to PCI. The overwhelming trial evidence is to give clopidagrel (300mg) in-laborstory Patients presenting with NSTE-ACS on DOAC should stop treatment for 24 hous before PCI. It the clinical situation demands urgent revasculatisa- ‘ion (eg, STEMI), then studies suggest tha an unin. certupted steategy is not associated with increased bleeding or major cardiovascular events compared with bridging therapy. Treatment during PCI There ate limited data to guide parenteral anti: coagulants during PCI. For patiemts on VKA additional parenteral anticoagulants may not be needed it INR is >2.5 at the time of elective PCI." However, for preservat 1 of radial artery patency, mended and it may be prudent to give this at the time of radial sheath removal rather than at br a dosing level of 30-SOUk, is recom- cedure start ‘With patients on DOAG, use of parenteral hepatin (70-100 U/kg) during PCT is recommended regard- less of the timing of the last DOAC dose." The use of parenteral antiplatelet agents (cangrelor or GPI) hhas no evidence base and should be restricted to bail out siruations. Cangrelor may be pretersed on account ofits shorter half-life. Treatment after PCL The dose of DOAC should reflect the regimen tested in arials of patients with AF undergoing PCL For patients who prefer VKA, the INR should be targeted tothe lower end of the therapeutic range (2.02.5), In a meta-analysis of four randomised trial patients on dual antithrombotic therapy (DAT) showed a 4796 reduction in TIMI major of minor bleeding compared with triple antithrombotic therapy (TAT) with no difference in major adverse cardiac events or stroke." Trials of DOAC in patients undergoing PCI build fon data from WOEST to add clarity and guide antiplatelet therapy. The consistency of signiti- cantly lower bleeding with DAT (clopidogrel has most evidence) across all trials supports its use cover TAT and represents the default steategy: In selected patients at high ischaemicithzombotic and low bleeding risks, low-dose aspirin therapy (pe therapy) may be extended tor limited period of time (month) alter PCL Thhete are some data with tcagelog, parcculaely in combination with dabigatan, wich showed ster and elficacy consistent with those of dopidogeel but ‘with numerically higher Uceding.” Asa result, the US thidelines include eagrelor as sn option in patents at high ischaemiclthromboric and low bleeding risk with omission of aspisin in keeping with the RE-DUAL PCL rial Indirect suppor for tcagrlorasantiplaelet monotherapy somes from the TWILIGHT sudy which reported teduced bleeding without an increase in ischaemic events aspsinteatment was stopped 3 months afte PCL and patents continued on tcagelor monotherapy alone. Dataon prasugel witha DOSC ae limited toa small soudy reporting a near fourfold increase in bleeding, with TAT and thus its use isnot recommended.” Trials of ew generation dg lacing stent (DES) in high bleding sak patints demonstrating safety snd eftcacy of shore duration dil antiplatelet therapy (6ce below) have led to gnidelines recommending their use in patients with AF undergoing PCL ‘Zaman 6, lee Q Heart 2021-107 385-59, do: 10.11 36herin- 2019315090 388 3 2 3 g g i 8 2 z 3 2 gEtec ers > Theres no mortality benefit of pretreatment with P2¥12 inhibitors in patients undergoing percutaneous coronary intervention (PCI. > The recommended duration of DAPT after PCI for stable ang months. “ial data with specific drug eluting stents (LEADERS-FREE, ONYX-ONE) show safety of t-month duration in high bleeding risk. >> For certain high ischaemic risk patents, trial (THEMIS-PCL, PEGASUS) data show ischaemic benefit wth extended duration DAPT (ticagrelor plus ‘xpi. > Unfractionated heparin remains the anticoagulant of choice during PCL >> There is no role for routine use of intravenous glycoprotein inhibitors in PCI and their use i reserved only for bailout scenarios. angrelor may be considered in specific settings in P2¥12-naive patients undergoing high-tisk Pcl > Patients on warfarin for atrial fibrillation do not need to stop therapy before PCI. fon direct oral anticoagulants this should be withheld 24 hours prior to ‘Procedure (or 48hours if on dabigatran and creatine clearance <50 mUmin) fr for Educ In summary, after PCI in patients on anticoagu- lants, a bleedinglischaemic/stroke isle assessment should be pettormed. European guidelines recom send dual therapy with clopidogrel and am OAC in high bleeding risk (IlaA). For all others, triple therapy is recommenced with aspirin, clopidogrel, and ain OAC for up to Lmonth (UaB) after which time aspitin is stopped. In patients a high ischaemic risk, or other anatomical/procedural characteristics and low bleeding, risk triple therapy for up to 6 ‘months can be considered (Ila). Alter 12 months, antiplatelets should be stopped and oral anticoag~ tlacion continued at the dose effective for stroke HIGH BLEEDING RISK PATIENTS The treatment options for patients at high bleeding risk (gue 1) have become more focused with rials showing elficacy and safety of DES with short dica- tions of dual antiplatelet therapy.***" In LEADERS- FREE, the polymer free, BioFreedom stent showed superiority to its bare metal counterpart for safety and efficacy. The ONYX-ONE trial compared a polymer based zotarolimus eluting stent to the BioFreedom in high bleeding risk and was non inferior with regard to safety and efficacy at Lyeat In SENIOR, patients>75 years (eather than specitic high bleeding risk) were allocated 1month DAPT for stable angina or 6 months if presenting, with ACS. The results confirmed that DES (Synergy) find short DAPT duration was superior to BMS Heart Education in Heart articles are accredited for CME by various providers. To answer the accompanying multiple choice questions (MCQs) and obtain your credits, click onthe "Take the Test’ lnk onthe online version of the atic. ‘The MCQS are hosted on BMJ Learning All users must complete a one-time registration on BMJ Learning and subsequently og in on every visit using their ‘username and password to access modules and their CME record Accreditation is only valid for2 years from the date of publication. Printable CME certificates are available to users that achieve the minimum pass mark with respect co all-cause mortality, MI, stroke and ischaemiz-dlriven target lesion revascularisation. These tials, by contirming satety and eticacy of DES with short duration DAPT, have changed prac- tice with patients at high risk of bleeding under ‘going PCI now receiving DES, Nevertheless, it must the remembered thar the trade-off between bleeding events and ischaemic protection of prolonging DAPT beyond Imonth in this patient subse has not been tested All patients should undergo radial access, where possible and receive a proton punip inhibitor (LB), Stable angina There is no evidence for pretreatment with P2Y12 agent which shouldbe started in the laboratory (clo dogrel 300mg) once coronary anatomy is known. After PCI, clopidogrel. should be continued for Imonth (IIbC). The ESC guidelines give 3 months uration (laB) as an option if the balance of bleeding and ischaemic isk favours the latte. The choice of anticoagulation dosing the procedure is heparin and the lower dose of the recommenced 70-100U/ keg should be used with addtional doses up to the rmiaximum 100Uikg if procedure is prolonged, Non ST elevation ACS and ST elevation MI Pretreatment and peritreatmentare asforstable angina The choice of P2Y12 agent can be extended t0 use of tiengrelor both in-aborstory and postprocedure. The only randomised trial of shortened DAPT (6 months) alter ACS in the high bleeding risk group (based only on age >75 years) is SENIOR, A meca- analysis of six teals” comparing 3-month and S-month DAPT against 12 months identtied those with ACS and reported a sion-signiticant increase in the risk of MI or stent thrombosis in the 6 months arm but importantly no signal with respect to cardiac ot allecanse death, With 3-month duration, ischaemic complications increased substantially leading the ESC to recommend Gemonth duration of DAPT tellowing [ACS for high bleeding risk (PRECISE-DAPT =25 (2B). However, the TWILIGHT study of contempo- rary practice provides evidence for saety and eflicacy for ticagrelor monotherapy beyond 3 months, In summary, stable angina patients at high bleeding risk undergoing PCI can receive DES and be sately treated with Imouth of clopido- gel. Following ACS, patients should have 6 months of clopidogrel or in high-ischaemic risk, ticagrelor. In selected cases of acute coronary ic risk is judged to be greater than bleeding risk, dual therapy with syndrome where ischa ticagrelor may be considered and aspirin stopped after 3 months, SUMMARY ‘The comerstone of pharmacology for patients tundergoing PCI remains oral dual antiplatelet therapy. There is scant evidence for pretreatment before coronary anatomy is known, After PCI, advances in stent technology have rediced DAPT uration from 12 to 6 months in stable patients and a0 ‘Zaman AG, lee Q Heat 207,107 385-59, do 10.1136 2019-315090 {UBUAdOD Aq payoajaid YSaN6 AG }ZOZ "1Z JOQUIAAON Uo /1N0D Tula HeALY/ch|Y WON PAPEOIUMOG “OO JAQWAAON y UO O6OSLE-6102-IUMMEDUIGEL LOL Se PausHNd yS1y UEAH_‘1month in high bleeding tsk, In high ischaemic, low bleeding risk patients, tial evidence has led to recommendations to extend antiplatelet of low dose anticoagulant (svazosaban) therapy beyond 12 months, Although randomised trial evidence of optimal dose is lacking, periproceural use of anti coagulant therapy with UFH has extensive clinical experience and safety profil ‘Aclvances in. antithrombotic medications. and carefully conducted clinical trials have improved cutcomes in paticnts undergoing coronary inter- vention. Nevertheless, zeal world evidence” showing recurrent ischaemic events in nearly a fith of patients with ACS gives impetus to search for even mote effective pharmacological agents Contributors AGZ and OA contibuted equal to this manus Funding The authors have not dedaed speci gantfr this researc fom any funding agency inthe publ, comme or rotor prof sector. Competing interests AG2 as rected consulting and ature fees om asta ZenecsSanoibyerDaich Sankyo. Patient consent for publication Not reed Provenance and peer review tet conmislones:eealy res revened Data availability statement Al data relevant to he study re Ince nthe arte ‘Author note References which ice a * are considered to be ey eer. Supplemental material Ths content hasbeen supplied by the autor) ths not bee veted by BM Publishing Grow Lied (2) 2nd may at hae been pes evened. Ay ions recommendations dscussed are soley those ofthe autos) and ae not endorsed by BRL BML sda al aby and responsi axing fom ay elance placed on the content Wher the content ince ay translated materi BMI dos not warant th accra andelabiy ofthe tarstons ting but ot ied to cal regulators, inca quienes terminology, eg ram and ug dosage) ane nl espn er any ear or omisions asing fom ratslaton and adaptation o: oer (Open access This san open access tice distrib in ‘zoréance uth the Crete Commons atrbuton Non Commer (CC BNC 40) ese which permits tes to distribute, rem, adapt, bull yon this wok non-commeraly ‘and cense the devatve works on deen ems, provided the origina work s pope cited, propriate ced hen, any changes made dates, an the use pon comet Se: Np? ‘teabvecommens.cxgikenses!- 08. orciD i at G Zaman tps o10000-0003-4891 8682 REFERENCES 1 Yano, Omo Hoe 5, er Detemlants of homb a genetaton feo aciy and endothe dsurcticnn Fates on a ample tag vohenent aces tes than etary in Wows ad owt $008.29:1729-38. 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