Editorial comment
Pretreatment with P2Y12 inhibitors in ST-elevation myocardial infarction: Should we keep doing it?
Dose de carga de inibidor P2Y12 o mais cedo possível no contexto de enfarte agudo do miocárdio com supradesnivelamento do segmento ST: fazer ou não fazer, eis a questão
Gonçalo Proença
Assistente Graduado Cardiologia, Coordenador Unidade de Cardiologia Hospital de Cascais, Portugal
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"tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "563" "paginaFinal" => "564" ] ] "autores" => array:1 [ 0 => array:3 [ "autoresLista" => "Gonçalo Proença" "autores" => array:1 [ 0 => array:3 [ "nombre" => "Gonçalo" "apellidos" => "Proença" "email" => array:1 [ 0 => "gproenca03@gmail.com" ] ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Assistente Graduado Cardiologia, Coordenador Unidade de Cardiologia Hospital de Cascais, Portugal" "identificador" => "aff0005" ] ] ] ] "titulosAlternativos" => array:1 [ "pt" => array:1 [ "titulo" => "Dose de carga de inibidor P2Y12 o mais cedo possível no contexto de enfarte agudo do miocárdio com supradesnivelamento do segmento ST: fazer ou não fazer, eis a questão" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Dual antiplatelet therapy is an established and essential treatment in acute coronary syndrome (ACS) patients, with a class I recommendation in the European and American guidelines. Current practice in many centers still mandates an upfront loading dose with a P2Y<span class="elsevierStyleInf">12</span> inhibitor as soon as possible, before percutaneous coronary intervention (PCI). However, the evidence is scarce and conflicting, and benefits from routine pretreatment before arrival at the cath lab remain uncertain. This is true for non-ST-elevation myocardial infarction and even more so for ST-elevation myocardial infarction (STEMI) patients.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">What is the rationale of pretreatment?</span><p id="par0010" class="elsevierStylePara elsevierViewall">One of the main arguments is biological plausibility.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> Since ACS most frequently results from occlusion of an artery by a platelet-rich thrombus, it is logical to assume that early administration of aspirin and a P2Y<span class="elsevierStyleInf">12</span> inhibitor should provide greater benefit, enabling the highest level of platelet inhibition in the shortest possible time. For clopidogrel, still the most frequently used P2Y<span class="elsevierStyleInf">12</span> inhibitor, its pharmacokinetic characteristics are relevant, given its very slow onset of action. However, various studies and meta-analyses suggest that pretreatment with clopidogrel in patients with STEMI reduces the rate of ischemic events without excess bleeding.<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">2,3</span></a> Regarding ticagrelor, although it does not require metabolic activation to exert its antiplatelet action, it is still extensively metabolized; its only active metabolite, AR-C124910XX, is as potent as ticagrelor itself. In the setting of ACS, intestinal uptake of ticagrelor may be significantly delayed, especially in patients administered morphine and in those with STEMI.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Besides these reasonable arguments, a possible psychological effect should be borne in mind, arising from the comfort some physicians may feel from doing something that is thought of as being biologically important for the patient, especially since the same drug is used in both pretreatment and in cath lab loading. We live in an era of widely used and safer radial access, and the number of patients who require urgent bypass surgery in this context is very small. Add the well-known fact that times from first medical contact to reperfusion are much longer than recommended in many centers and the question “why not do it sooner?” begins to look logical. Unfortunately, as in many other clinical contexts, biological and pathophysiological plausibility does not necessarily mean clinical efficacy. When tested with good methodology, plausible treatments may even prove harmful.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">What does the most robust evidence available tell us?</span><p id="par0020" class="elsevierStylePara elsevierViewall">The Administration of Ticagrelor in the Cath Lab or in the Ambulance for New ST Elevation Myocardial Infarction to Open the Coronary Artery (ATLANTIC) trial,<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a> published in 2014, was an international multicenter double-blind trial that recruited 1862 patients with STEMI (<6 hours duration) and randomized them to ticagrelor given prehospital (in the ambulance) or in the cath lab. The coprimary endpoints were the proportion of patients who did not achieve a 70% or greater resolution of ST-segment elevation before PCI and the proportion of patients who did not have Thrombolysis in Myocardial Infarction flow grade 3 in the infarct-related artery at initial angiography. Secondary end points included the rates of major adverse cardiovascular events and definite stent thrombosis at 30 days. The take-home message of this trial was that compared to in-hospital administration, prehospital administration of ticagrelor appears to be safe and may offer a small benefit in preventing stent thrombosis without any difference in major bleeding, but does not improve pre-PCI coronary reperfusion. The time difference between the two arms was only 31 minutes, a small difference that may have played a role in the end result.</p><p id="par0025" class="elsevierStylePara elsevierViewall">More recently, using data from the Swedish Coronary Angiography and Angioplasty Registry,<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">6,7</span></a> Redfors et al.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">6</span></a> studied 44<span class="elsevierStyleHsp" style=""></span>804 patients admitted with STEMI between 2005 and 2016, investigating the association between pretreatment with P2Y<span class="elsevierStyleInf">12</span> inhibitors (58.3% clopidogrel, 35.3% ticagrelor and 5.3% prasugrel) and the risk of adverse outcomes using a propensity score to account for clustering of patients within hospitals. The primary endpoint was all-cause mortality at 30 days. Secondary endpoints were infarct-related artery occlusion, 30-day stent thrombosis, in-hospital bleeding, neurological complications and cardiogenic shock. The majority of patients (85%) were pretreated. The authors found no statistically significant association between prehospital treatment and lower in-hospital mortality, improved infarct artery patency, lower stent thrombosis, or higher bleeding rates. However, confidence intervals were wide, ranging from real benefit to harm, which make firm conclusions impossible.</p><p id="par0030" class="elsevierStylePara elsevierViewall">In this issue of the <span class="elsevierStyleItalic">Journal</span>, Guedes and coworkers<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">8</span></a> return to this open and still unanswered question. They looked at a series of 4123 STEMI patients admitted between 2010 and 2017 and compared those receiving a P2Y<span class="elsevierStyleInf">12</span> loading dose before or in the cath lab. The main efficacy endpoint was major adverse events (MAE) and the main safety endpoint was a composite of major bleeding, hemoglobin drop >2 g/dl and need for transfusion. As in the Swedish series, most patients received a clopidogrel loading dose prior to arrival at the cath lab. Their conclusion is that this strategy does not appear to provide any benefit regarding mortality or MAE. Furthermore, there was an increased bleeding risk, raising concerns about safety.<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">8</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">The authors deserve commendation for addressing this issue and their work provides yet another piece of evidence that should be taken into account by physicians when deciding the best timing to administer a P2Y<span class="elsevierStyleInf">12</span> loading dose. However, the limitations of this study should be kept in mind: it is retrospective, the two groups were very heterogeneous, and the time difference between the groups in antiplatelet therapy administration, a critical piece of information, is not provided.</p><p id="par0040" class="elsevierStylePara elsevierViewall">There is thus still no definitive answer at this time. Unfortunately, trials testing a strategy of very rapid onset and high level of P2Y<span class="elsevierStyleInf">12</span> receptor inhibition at the time of PCI using intravenous cangrelor did not address this question, providing only indirect evidence suggesting a reduction in ischemic risk.<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">9</span></a></p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">So what should be done?</span><p id="par0045" class="elsevierStylePara elsevierViewall">As stated in the current European Society of Cardiology STEMI guidelines,<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a> earlier administration may be preferable to achieve early efficacy, particularly when there are long delays, which are unfortunately still very common. However, in cases in which a STEMI diagnosis is not clear, the patient has a high bleeding risk or a significant probability of undergoing surgical coronary revascularization or whenever other etiologies that may require urgent surgical treatment cannot be ruled out, delaying P2Y<span class="elsevierStyleInf">12</span> inhibitor loading must be considered.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Conflicts of interest</span><p id="par0050" class="elsevierStylePara elsevierViewall">The author has no conflicts of interest to declare.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:5 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "What is the rationale of pretreatment?" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "What does the most robust evidence available tell us?" ] 2 => array:2 [ "identificador" => "sec0015" "titulo" => "So what should be done?" ] 3 => array:2 [ "identificador" => "sec0020" "titulo" => "Conflicts of interest" ] 4 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:10 [ 0 => array:3 [ "identificador" => "bib0055" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "When is the best time for the second antiplatelet agent in non-ST elevation acute coronary syndrome?" 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 8 | 3 | 11 |
| 2024 October | 31 | 33 | 64 |
| 2024 September | 46 | 30 | 76 |
| 2024 August | 44 | 33 | 77 |
| 2024 July | 58 | 32 | 90 |
| 2024 June | 31 | 30 | 61 |
| 2024 May | 35 | 21 | 56 |
| 2024 April | 43 | 31 | 74 |
| 2024 March | 33 | 18 | 51 |
| 2024 February | 28 | 26 | 54 |
| 2024 January | 27 | 20 | 47 |
| 2023 December | 27 | 25 | 52 |
| 2023 November | 20 | 30 | 50 |
| 2023 October | 17 | 15 | 32 |
| 2023 September | 23 | 20 | 43 |
| 2023 August | 19 | 21 | 40 |
| 2023 July | 22 | 6 | 28 |
| 2023 June | 23 | 17 | 40 |
| 2023 May | 32 | 26 | 58 |
| 2023 April | 16 | 9 | 25 |
| 2023 March | 29 | 25 | 54 |
| 2023 February | 27 | 20 | 47 |
| 2023 January | 22 | 13 | 35 |
| 2022 December | 41 | 19 | 60 |
| 2022 November | 32 | 24 | 56 |
| 2022 October | 27 | 29 | 56 |
| 2022 September | 17 | 42 | 59 |
| 2022 August | 22 | 27 | 49 |
| 2022 July | 23 | 44 | 67 |
| 2022 June | 19 | 29 | 48 |
| 2022 May | 27 | 32 | 59 |
| 2022 April | 24 | 37 | 61 |
| 2022 March | 25 | 43 | 68 |
| 2022 February | 32 | 40 | 72 |
| 2022 January | 18 | 29 | 47 |
| 2021 December | 26 | 36 | 62 |
| 2021 November | 24 | 49 | 73 |
| 2021 October | 29 | 46 | 75 |
| 2021 September | 21 | 35 | 56 |
| 2021 August | 22 | 33 | 55 |
| 2021 July | 12 | 23 | 35 |
| 2021 June | 24 | 20 | 44 |
| 2021 May | 25 | 44 | 69 |
| 2021 April | 77 | 48 | 125 |
| 2021 March | 44 | 20 | 64 |
| 2021 February | 35 | 8 | 43 |
| 2021 January | 29 | 17 | 46 |
| 2020 December | 7 | 5 | 12 |
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