456 Monotherapy with a P2Y12 inhibitor or aspirin for patients with established atherosclerosis: an updated meta-analysis

Un uomo di 39 anni giungeva in Pronto Soccorso per dolore toracico oppressivo. In anamnesi riferiva pregressa tubercolosi, familiarità per cardiopatia ischemica, pregresso tabagismo ed iperomocisteinemia. Decorso clinico acuto I parametri vitali erano nella norma; all’ECG presentava sopraslivellamento del tratto ST nelle derivazioni laterali e sottoslivellamento nelle inferiori. Veniva posta diagnosi di STEMI laterale ed eseguita coronarografia d’urgenza risultata negativa. L’ecocardiogramma evidenziava lieve dilatazione del ventricolo destro (Vdx) con funzione conservata ed ipocinesia sottotricuspidalica. Agli esami ematochimici gli indici di flogosi risultavano lievemente aumentati; il picco di Troponina I è risultato 177600 ng/L. Veniva sottoposto a risonanza magnetica cardiaca (RMC) che concludeva per cardiomiopatia infiammatoria in fase acuta con riscontro di funzione sistolica del ventricolo sinistro (Vsn) ai limiti inferiori con focale ipocinesia della parete laterale media, funzione destra lievemente ridotta con ipocinesia in sede sottotricuspidalica e bulging sisto-diastolici in corrispondenza del tratto di efflusso e dell’angolo costofrenico del Vdx, oedema e late gadolinium enhancement (LGE) a distribuzione subepicardica (pattern non-ischemico) del Vsn coinvolgente anche il Vdx. Si concludeva per miocardite acuta. Indagando più a fondo si scopriva che: una zia paterna era morta improvvisamente a 50 anni; per cardiopalmo il paziente si era sottoposto ad ECG Holter delle 24 h con riscontro di frequenti BEV tipo BBdx/asse superiore. Veniva eseguita la biopsia endomiocardica: dei cinque frammenti prelevati due erano suggestivi di miocardite, tre mostravano fibroadiposi sostitutiva. Si concludeva per miocardite attiva negativa per virus cardiotropi. Dato il riscontro bioptico ed il coinvolgimento biventricolare veniva sospettata una hot-phase di cardiomiopatia aritmogena. Follow-up Dopo 6 mesi all’ECG erano presenti bassi voltaggi nelle derivazioni periferiche ed onde T piatte in sede infero-laterale (Figure 1A). Alla successiva RMC persistevano le alterazioni di funzione e cinetica biventricolare, erano presenti sfumati spot di oedema, segni di infiltrazione adiposa della parete laterale media del Vsn e della parete libera del Vdx; inoltre venivano descritti estesi segni di LGE a distribuzione subepicardica circonferenziale del Vsn con coinvolgimento esteso del Vdx (Figure 2B). L’analisi genetica ha individuato la presenza di una variante nucleotidica rara c.c. 1652-1G>T nell’introne 11 del Gene DSC2 (desmocollina). Veniva posta diagnosi di Cardiomiopatia Aritmogena Biventricolare secondo i Criteri di Padova. Discussione La Cardiomiopatia Aritmogena è una malattia ereditaria del miocardio che raramente può manifestarsi con episodi simil-miocardite (hot-phase). In questi casi una corretta anamnesi personale e familiare, la caratterizzazione tissutale e la genetica rappresentano mezzi fondamentali per un corretto inquadramento diagnostico.

Disparities by sex in P2Y12 inhibitor therapy duration, or differences in the balance of ischaemic-benefit and bleeding-risk clinical outcomes in older women versus comparable men following acute myocardial infarction? A P2Y12 inhibitor new user retrospective cohort analysis of US Medicare claims data

ObjectivesTo determine if comparable older women and men received different durations of P2Y12 inhibitor therapy following acute myocardial infarction (AMI) and if therapy duration differences were justified by differences in ischaemic benefits and/or bleeding risks.DesignRetrospective cohort.Setting20% sample of 2007–2015 US Medicare fee-for-service administrative claims data.Participants≥66-year-old P2Y12 inhibitor new users following 2008–2013 AMI hospitalisation (N=30 613). Older women compared to older men with similar predicted risks of study outcomes.Primary and secondary outcome measuresPrimary outcome: P2Y12 inhibitor duration (modelled as risk of therapy discontinuation). Secondary outcomes: clinical events while on P2Y12 inhibitor therapy, including (1) death/hospice admission, (2) composite of ischaemic events (AMI/stroke/revascularisation) and (3) hospitalised bleeds. Cause-specific risks and relative risks (RRs) estimated using Aalen-Johansen cumulative incidence curves and bootstrapped 95% CIs.Results10 486 women matched to 10 486 men with comparable predicted risks of all 4 study outcomes. No difference in treatment discontinuation was observed at 12 months (women 31.2% risk; men 30.9% risk; RR 1.01; 95% CI 0.97 to 1.05), but women were more likely than men to discontinue therapy at 24 months (54.4% and 52.9% risk, respectively; RR 1.03; 95% CI 1.00 to 1.05). Among patients who did not discontinue P2Y12 inhibitor therapy, women had lower 24-month risks of ischaemic outcomes than men (13.1% and 14.7%, respectively; RR 0.90; 95% CI 0.84 to 0.96), potentially lower 24-month risks of death/hospice admission (5.0% and 5.5%, respectively; RR 0.91; 95% CI 0.82 to 1.02), but women and men both had 2.5% 24-month bleeding risks (RR 0.98; 95% CI 0.82 to 1.14).ConclusionsRisks for death/hospice and ischaemic events were lower among women still taking a P2Y12 inhibitor than comparable men, with no difference in bleeding risks. Shorter P2Y12 inhibitor durations in older women than comparable men observed between 12 and 24 months post-AMI may reflect a disparity that is not justified by differences in clinical need.

211 Impact of smoking habits on baseline and on-treatment platelet reactivity in STEMI patients treated with third generation P2Y12

Aims Smoking habit is a well-known risk factor for cardiovascular disease. High on-treatment platelet reactivity has been associated with high risk of ischaemic events in STEMI patients. The relationship between platelet reactivity and smoking habit was investigated only in few studies, and the impact of smoke on platelet reactivity in STEMI patients treated with 3rd generation P2Y12 inhibitor is still lacking. This study aim to assess the impact of smoking habits on baseline and on-treatment platelet reactivity in STEMI patients treated with 3rd generation P2Y12 inhibitor. Methods Overall, 429 STEMI patients were enrolled in this study. Patients were divided into two groups according to smoking habit. Platelet reactivity was assessed by VerifyNow at baseline and after 3rd generation P2Y12 inhibitor (ticagrelor or prasugrel) loading dose (LD). Blood samples were obtained at baseline (T0), and after 1 h (T1), 2 h (T2), 4w6 h (T3) and 8–12 h (T4) after LD. Results The mean age of the enrolled population was 62 ± 12 and male rate was 75%. Patients with smoking habit were younger (75.8% vs. 38.9%, P < 0.001 for age <65 years), with higher prevalence of family history of CAD, while with a lower rate hypertension (43.4% vs. 65.9%, P < 0.001) and previous myocardial infarction (5.3% vs. 11.4%, P = 0.022). Smoker patients had lower platelet reactivity either at baseline [T0: 249 (205–285) vs. 284 (230–324), P < 0.001] or at 2 h after the LD [T2: 107 (18–279) vs. 136 (51–260), P = 0.003]. Similarly, Smoker patients experienced a lower rate of in-hospital composite adverse event of death, Re-infarction, stroke or acute kidney injury (1.6% vs. 12.4%; P≤0.001). Multivariate analysis demonstrated that left ventricular ejection fraction at admission (OR = 0.916, 95% CI 0.865–0.969; P = 0.002), and platelet reactivity at baseline (OR = 1.013, 95% CI 1.002–1.024; P = 0.024) were independent predictors of in-hospital composite adverse event. Conclusions Smoker status is associated with lower platelet reactivity either at baseline or after LD and with a better short-term prognosis in STEMI patients treated by dual antiplatelet therapy with ticagrelor or prasugrel.

Reversible P2Y12 inhibitor versus irreversible P2Y12 inhibitor in ACS patients undergoing PCI (the acute coronary syndrome israeli survey (ACSIS)

Introduction Based on data from randomized controlled trials, both American and European guidelines recommend treating acute coronary syndrome (ACS) patients with second generation P2Y12 inhibitors.1,2 Direct head-to-head comparison of these agents was scarce until the recent publication of the ISAR-REACT-5 study which demonstrated the superiority of the Irreversible thienopyridine type P2Y12 inhibitor (prodrug) over the reversible P2Y12 inhibitor in terms of 1-year composite of death, myocardial infarction (MI), and stroke.3,4,5 Given the unexpected outcomes of this trial, we sought to perform a comparison of ticagrelor and prasugrel in real-life ACS patients. Purpose To compare the outcomes of ACS (acute coronary syndrome) patients undergoing in-hospital PCI (percutaneous coronary intervention) treated with the Irreversible thienopyridine type P2Y12 inhibitor (prodrug) versus the reversible P2Y12 inhibitor. Methods ACSIS (Acute Coronary Syndrome in Israel) is a national ACS snapshot survey conducted in all 25 cardiology departments in Israel since 2000 over a two-month period, every two to three years. Both the Irreversible thienopyridine type P2Y12 inhibitor (prodrug) and the reversible P2Y12 inhibitor were commercially introduced in Israel in 2010. We therefore considered patients enrolled in ACSIS surveys 2010–2018 for the present analysis. Results Among 7,233 patients enrolled to the ACSIS (Acute Coronary Syndrome in Israel) registry between 2010 and 2018, we identified 1133 eligible patients treated with the Irreversible thienopyridine type P2Y12 inhibitor (prodrug) and 825 with the reversible P2Y12 inhibitor. In hospital complication rates, including rates of stent thrombosis, were roughly similar between groups. Compared to the reversible P2Y12 inhibitor, the Irreversible thienopyridine type P2Y12 inhibitor (prodrug) was associated with lower 1-year death in ST-elevation myocardial infarction (STEMI) patient compared to non-ST-elevation ACS (NSTE-ACS) patients (p for interaction 0.03). In propensity score matched STEMI patients (502 receiving the Irreversible thienopyridine type P2Y12 inhibitor (prodrug), 251 the reversible P2Y12 inhibitor) 30-day re-hospitalization rate (p<0.05), 30-day MACE (the composite of death, MI, stroke, urgent revascularization; p=0.006), and 1-year mortality rates (p=0.08) were higher in the the reversible P2Y12 inhibitor group compared to the the Irreversible thienopyridine type P2Y12 inhibitor (prodrug) group; In NSTE-ACS patients, outcomes were not impacted by drug choice. Conclusion The Irreversible thienopyridine type P2Y12 inhibitor (prodrug) was more effective than the reversible P2Y12 inhibitor in STEMI patients, but not in NSTE-ACS patients. FUNDunding Acknowledgement Type of funding sources: Foundation. Main funding source(s): the Israeli working group on acute cardiac care of the Israel heart society

Not-high before-treatment platelet reactivity in patients with STEMI:prevalence, clinical characteristics, response to therapy and outcomes

Background Platelet reactivity (PR) has been indicated as a pathophysiological key element for ST-Elevation Myocardial Infarction (STEMI) development. In STEMI patients, PR following pharmacological treatment has been extensively studied with focus on patients with on-treatment high platelet reactivity (HPR). Patients with before-treatment not-high platelet reactivity (NHPR) have been poorly studied so far. Purpose Aim of the study is to investigate the prevalence, clinical characteristics, response to therapy and outcomes of baseline prior to treatment NHPR among patients with STEMI undergoing primary PCI. Methods We analysed the data from 358 STEMI patients with assessment of PR by VerifyNowbefore P2Y12 inhibitor loading dose (LD). All patients received a P2Y12 inhibitor (ticagrelor or prasugrel) LDafter baseline PR assessment. Blood samples were obtained at baseline (T0), and after 1 hour (T1), 2 hours (T2), 4–6 hours (T3) and 8–12 hours (T4) after LD. HPR was defined as Platelet Reactivity Unit values ≥208, while patients with values <208 at baseline were defined as having NHPR. Results Overall, 20% patients had NHPR. Patients with before-treatment NHPR values were more frequently young, of male gender and more frequently smokers (p=0.005), overweight or obese (p=0.009), affected by dyslipidemia (p=0.03) and with a family history of coronary artery disease (p=0.04). Age and male gender resulted both independent predictors of NHPR, even after propensity score adjustment. The percentage of inhibition of PR after ticagrelor or prasugrel LD was similar between HPR and NHPR patients at each time point (figure 1) and residual PR was constantly lower in patients with before-treatment PRU <208 from baseline to 8–12 hours from LD (figure 2). However, patients with HPR showed worse in-hospital clinical outcomes, and the composite adverse outcome endpoint of death, reinfarction, stroke, acute kidney injury or heart failure was significantly higher (10.0% vs 1.4%; p=0.017) as compared with the NHPR group. Conclusions A significant proportion of patients presenting with STEMI has a baseline NHPR; they are predominantly young males with a high-risk cardiovascular profile. NHPR is associated with better in-hospital outcomes as compare with patients with HPR. Further studies are needed to better understand the underlying pathophysiology in order to find out potential personalized treatments in this setting. FUNDunding Acknowledgement Type of funding sources: None.