Search

The appropriate use of dual antiplatelet therapy (DAPT) in elderly patients with acute coronary syndrome (ACS) is largely debated. Due to the "demographic transition" in western countries, the elderly represent a growing percentage of patients admitted to hospitals for ACS, and among this high risk setting population most of early and late adverse outcomes occur. The presence of several concomitant "comorbidities" complicate the management strategy of both medical or invasive treatment and the clinical decision making process is challenging. Moreover, elderly people are constantly underrepresented in clinical trials and studies. As a result, there is no specific evidence about the optimal antithrombotic therapy in elderly and no specific recommendations are mentioned in the current ACS guidelines. Currently, the best practice for old people is still rudimentary and principally extrapolated from general cardiovascular guidelines. The management of elderly patients should be based on the evaluation of ischemic and hemorrhagic risk, life expectancy, comorbidities and parameters that are not included in the scores recommended by the current guidelines such as frailty and disability. In the era of "precision medicine", the evaluation of bleeding and ischaemic risk in elderly patients must be a dynamic process because of the risk changing over time. A"tailored therapy by individualized medicine" is the key of management strategy.

Background Coronary artery disease (CAD) has been recognized as a serious and potentially life-threatening complication of Hepatitis C Virus (HCV) infection. High on-treatment platelet reactivity has been associated with high risk of ischemic events in patients with CAD, but data regarding the association with HCV infection are still lacking. This post hoc analysis aims to assess high on-treatment platelet reactivity, severity of CAD, and long-term outcomes of patients with acute coronary syndrome (ACS) who were infected with HCV. Methods and Results Patients with ACS who were infected with HCV (n=47) were matched to patients with ACS and without HCV (n=137) for age, sex, diabetes mellitus, hypertension, and renal function. HCV-infected patients with ACS had higher levels of platelet reactivity (ADP 10 -light transmittance aggregometry, 56±18% versus 44±22% [ P =0.002]; arachidonic acid-light transmittance aggregometry, 25±21% versus 16±15% [ P =0.011]) and higher rates of high on-treatment platelet reactivity on clopidogrel and aspirin compared with patients without HCV. Moreover, HCV-infected patients with ACS had higher rates of multivessel disease (53% versus 30%; P =0.004) and 3-vessel disease (32% versus 7%; P <0.001) compared with patients without HCV. At long-term follow-up, estimated rates of major adverse cardiovascular events (cardiac death, nonfatal myocardial infarction, and ischemia-driven revascularization) were 57% versus 34% ( P =0.005) in HCV- and non-HCV-infected patients with ACS, respectively. In addition, thrombolysis In Myocardial Infarction (TIMI) major bleeding rates were higher in HCV-infected patients (11% versus 3%; P =0.043) compared with noninfected patients. Multivariable analysis demonstrated that HCV infection was an independent predictor of high on-treatment platelet reactivity, severity of CAD, and long-term outcome. Conclusions In this hypothesis-generating study, patients with ACS and HCV infection showed increased on-treatment platelet reactivity, more severe CAD, and worse prognosis compared with patients without HCV.

Background: The relative merits of ticagrelor as compared with prasugrel in patients with acute coronary syndromes for whom invasive evaluation is planned are uncertain., Methods: In this multicenter, randomized, open-label trial, we randomly assigned patients who presented with acute coronary syndromes and for whom invasive evaluation was planned to receive either ticagrelor or prasugrel. The primary end point was the composite of death, myocardial infarction, or stroke at 1 year. A major secondary end point (the safety end point) was bleeding., Results: A total of 4018 patients underwent randomization. A primary end-point event occurred in 184 of 2012 patients (9.3%) in the ticagrelor group and in 137 of 2006 patients (6.9%) in the prasugrel group (hazard ratio, 1.36; 95% confidence interval [CI], 1.09 to 1.70; P = 0.006). The respective incidences of the individual components of the primary end point in the ticagrelor group and the prasugrel group were as follows: death, 4.5% and 3.7%; myocardial infarction, 4.8% and 3.0%; and stroke, 1.1% and 1.0%. Definite or probable stent thrombosis occurred in 1.3% of patients assigned to ticagrelor and 1.0% of patients assigned to prasugrel, and definite stent thrombosis occurred in 1.1% and 0.6%, respectively. Major bleeding (as defined by the Bleeding Academic Research Consortium scale) was observed in 5.4% of patients in the ticagrelor group and in 4.8% of patients in the prasugrel group (hazard ratio, 1.12; 95% CI, 0.83 to 1.51; P = 0.46)., Conclusions: Among patients who presented with acute coronary syndromes with or without ST-segment elevation, the incidence of death, myocardial infarction, or stroke was significantly lower among those who received prasugrel than among those who received ticagrelor, and the incidence of major bleeding was not significantly different between the two groups. (Funded by the German Center for Cardiovascular Research and Deutsches Herzzentrum München; ISAR-REACT 5 ClinicalTrials.gov number, NCT01944800.)., (Copyright © 2019 Massachusetts Medical Society.)

Background: The CHA 2 DS 2 -VASc score predicts stroke risk in patients with atrial fibrillation, but recently has been reported to have a prognostic role even in patients with ACS. We sought to assess the ability of the CHA 2 DS 2 -VASc score to predict the severity of coronary artery disease, high residual platelet reactivity and long-term outcomes in patients with acute coronary syndrome (ACS)., Methods: Overall, 1729 consecutive patients with ACS undergoing invasive management were included in this prospective registry. We assessed platelet reactivity via light transmittance aggregometry after clopidogrel loading. Patients were divided according to the CHA 2 DS 2 -VASc score: group A = 0, B = 1, C = 2, D = 3, E = 4 and F ≥ 5., Results: Patients with higher CHA 2 DS 2 -VASc score were more likely to have a higher rate of multivessel CAD (37%, 47%, 55%, 62%, 67 and 75% in Group A, B, C, D, E and F; p < 0.001); moreover, CHA 2 DS 2 -VASc score correlated linearly with residual platelet reactivity (R = 0.77; p < 0.001). At long-term follow-up, estimated adverse event rates (MACCE: cardiac death, MI, stroke or any urgent coronary revascularization) were 3%, 8%, 10%, 14%, 19% and 24% in group A, B, C, D, E and F; p < 0.001. Multivariable analysis demonstrated CHA 2 DS 2 -VASc to be an independent predictor of severity of coronary artery disease, of high residual platelet reactivity and of MACCE., Conclusions: In a cohort of patients with ACS, CHA 2 DS 2 -VASc score correlated with coronary disease severity and residual platelet reactivity, and therefore it predicted the risk of long-term adverse events., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Aims: The optimal duration of dual antiplatelet therapy after an acute coronary syndrome (ACS) is still unknown and debated. We sought to assess the incidence of adverse clinical events beyond 12 months after an ACS in patients treated by percutaneous coronary intervention (PCI) and clopidogrel., Methods and Results: Among 1,592 consecutive ACS patients treated by PCI enrolled in the RECLOSE 2-ACS study and without event within one year, 1,310 (82%) patients presented at least one risk factor such as age ≥65 years, diabetes, prior myocardial infarction (MI), chronic kidney disease and multivessel coronary disease. The primary endpoint rate (the composite of cardiac death, MI, stroke and any urgent coronary revascularisation) was 3.7% per year after the first 12 months. The adverse event rate beyond 12 months was higher in patients with at least one risk factor as compared with patients without (8.1% vs. 1.8%, p<0.001). Each additional risk factor was associated with a relative risk for long-term adverse events of 1.66 (95% CI: 1.41-1.96; p=0.0001). Independent predictors of late events were age ≥65 years (OR 2.11, 95% CI: 1.38-3.37, p=0.002), insulin-treated diabetes mellitus (OR 2.29, 95% CI: 1.41-3.71, p=0.001), chronic kidney disease (OR 1.93, 95% CI: 1.21-3.09, p=0.006), prior MI (OR 2.71, 95% CI: 1.85-3.97, p=0.0001), and multivessel coronary disease (OR 1.53, 95% CI: 1.18-1.97, p=0.01)., Conclusions: Patients at risk of adverse events beyond 12 months after an ACS may be identified by simple clinical and angiographic characteristics such as age, diabetes, chronic kidney disease, prior MI and multivessel CAD. The risk of adverse events progressively increases with the number of these high-risk features.

The aim of this study was the identification of the optimal cutoff value of high residual platelet reactivity (HRPR) assessed by light transmission aggregometry (LTA) in the responsiveness to clopidogrel and stent thrombosis 2-acute coronary syndrome (RECLOSE 2-ACS) patient cohort to discriminate patients with and without major adverse cardiac events (MACE) and cardiac death at 2 years. The RECLOSE 2-ACS study included 1,789 patients with ACS who underwent LTA after clopidogrel loading. A post hoc cutoff value for HRPR was defined with the ROC curve and the Youden index and compared with the protocol-defined cutoff of 70 %. By ROC analysis, 63 % resulted the optimal cutoff value to predict both MACE and cardiac death at 2 years follow-up. A significant sensitivity improvement for the ROC-based cutoff value was noted (p < 0.001), at the price of lower specificity and predictive accuracy. The latter were 81 % for MACE and 85 % for cardiac death with the 70 % cutoff, while the respective figures were 73 and 75 % with the 63 % cutoff. The areas under the curve were virtually identical with the 70 and 63 % cutoffs both for MACE (0.71) and cardiac death (0.79). A residual platelet reactivity cutoff of 70 % by LTA, compared to the ROC-based cutoff of 63 %, allows for the identification of a subset of patients at very high risk of adverse ischemic events, making LTA-ADP test more acceptable in clinical practice for the identification of subjects at risk than other platelet function assays with broader definitions of HRPR.

Aims: To our knowledge, no randomised study has compared rates of uncovered stent struts in everolimus (EES) vs. new-generation zotarolimus-eluting (ZES-R) stents in acute coronary syndrome (ACS). The aim of our study was to evaluate the completeness of neointimal coverage with optical coherence tomography (OCT) in ACS patients treated with drug-eluting stents (DES) comparing EES versus new-generation ZES-R., Methods and Results: All eligible ACS patients admitted to four Italian centres with a clinical indication for culprit lesion intervention were randomised 1:1 to EES or ZES-R. The primary study endpoint was the percentage of uncovered stent struts evaluated by optical coherence tomography (OCT) at six months. Secondary endpoints were the percentage of malapposed stent struts, percent neointimal hyperplasia cross-sectional area (CSA) and major adverse cardiac events (MACE) at six months. A total of 60 patients were randomised to EES (n=29) or ZES-R (n=31). No differences were observed in baseline characteristics between the two groups. Overall, 31.7% presented with STEMI, of which 68.4% were anterior. The other patients comprised 41.7% NSTEMI and 26.7% troponin-negative ACS. A mean of 1.3±0.6 lesions were treated per patient, with a mean of 1.3±0.5 stents per lesion. At 30 days there was one sudden death. Six-month OCT analysis was performed in 25 lesions in the EES group and in 24 lesions in the ZES-R group. There was no difference in the primary endpoint of uncovered stent struts between groups (EES 6.42% [3.27, 9.57] vs. ZES-R 7.07% [3.22, 10.92]; p=0.80). Furthermore, there were no differences between groups in the percentage of malapposed stent struts, either with (EES 1.19% [0.34, 2.04] vs. ZES-R 0.85% [0.40, 1.30]; p=0.49) or without coverage (EES 1.06% [0.12, 2.01] vs. ZES-R 0.24% [0.05, 0.44]; p=0.09). Percent neointima CSA was similar in both groups (EES 37.0% [18.6, 55.3] vs. ZES-R 26.6% [18.4, 34.8]; p=0.31). At six-month clinical follow-up, no additional patients died or suffered MI. There were four MACE in the EES group and one in the ZES-R group., Conclusions: In our study, in patients presenting with ACS, both EES and ZES-R had low percentages of malapposed and uncovered stent struts at six-month OCT analysis.

Background: In acute coronary syndrome (ACS) patients older than 75 years old, prasugrel 10 mg maintenance therapy has shown less clinical efficacy and higher risk of bleeding. In patients older than 75 years, a prasugrel dose of 5 mg should be used if treatment is deemed necessary., Objective: The aim of this study was to compare platelet reactivity and outcomes in elderly patients receiving prasugrel 5mg therapy with non-elderly patients receiving prasugrel 10 mg therapy., Methods and Results: Consecutive ACS patients undergoing percutaneous coronary intervention (PCI) treated with prasugrel were included. Of 718 patients, 228 (32%) had ≥75 years and received prasugrel 5 mg/day. Residual platelet reactivity (RPR) was 47±18% and 36±16% in the elderly and non-elderly group, respectively (p=0.001). High RPR (≥70%) was found in 9% and 2% (p=0.0001) in elderly and non-elderly patients, respectively. In the 6-month follow-up, there was no difference in mortality, stent thrombosis, and reinfarction rates between the 2 groups but a higher rate of TIMI minor bleeding (7.9% vs 2.4%; p=0.001) in elderly as compared with younger patients. Age≥75 years was independently associated with bleeding events (HR 2.162 [1.105-4.229]; p=0.024)., Conclusions: Elderly patients receiving prasugrel 5mg are more likely to experience high RPR than younger patients treated by prasugrel 10 mg. Despite the use of a reduced prasugrel maintenance dose and a higher level of RPR, elderly patients show increased risk of bleeding during prasugrel therapy as compared to younger patients., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Context: High residual platelet reactivity (HRPR) in patients receiving clopidogrel has been associated with high risk of ischemic events after percutaneous coronary intervention (PCI)., Objective: To test the hypothesis that HRPR after clopidogrel loading is an independent prognostic marker of risk of long-term thrombotic events in patients with acute coronary syndromes (ACS) undergoing an invasive procedure and antithrombotic treatment adjusted according to the results of platelet function tests., Design, Setting, and Patients: Prospective, observational, referral center cohort study of 1789 consecutive patients with ACS undergoing PCI from April 2005 to April 2009 at the Division of Cardiology of Careggi Hospital, Florence, Italy, in whom platelet reactivity was prospectively assessed by light transmittance aggregometry., Interventions: All patients received 325 mg of aspirin and a loading dose of 600 mg of clopidogrel followed by a maintenance dosage of 325 mg/d of aspirin and 75 mg/d of clopidogrel for at least 6 months. Patients with HRPR as assessed by adenosine diphosphate test (≥70% platelet aggregation) received an increased dose of clopidogrel (150-300 mg/d) or switched to ticlopidine (500-1000 mg/d) under adenosine diphosphate test guidance., Main Outcome Measures: The primary end point was a composite of cardiac death, myocardial infarction, any urgent coronary revascularization, and stroke at 2-year follow-up. Secondary end points were stent thrombosis and each component of the primary end point., Results: The primary end point event rate was 14.6% (36/247) in patients with HRPR and 8.7% (132/1525) in patients with low residual platelet reactivity (absolute risk increase, 5.9%; 95% CI, 1.6%-11.1%; P = .003). Stent thrombosis was higher in the HRPR group compared with the low residual platelet reactivity group (6.1% [15/247] vs 2.9% [44/1525]; absolute risk increase, 3.2%; 95% CI, 0.4%-6.7%; P = .01). By multivariable analysis, HRPR was independently associated with the primary end point (hazard ratio, 1.49; 95% CI, 1.08-2.05; P = .02) and with cardiac mortality (hazard ratio, 1.81; 95% CI, 1.18-2.76; P = .006)., Conclusion: Among patients receiving platelet reactivity-guided antithrombotic medication after PCI, HRPR status was significantly associated with increased risk of ischemic events at short- and long-term follow-up., Trial Registration: clinicaltrials.gov Identifier: NCT01231035.

Background: This study is aimed at comparing the clinical outcomes of unprotected left main coronary artery disease (ULMCAD) treatment with contemporary percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) in a "real-world" population.Methods and Results: Overall, 558 consecutive patients with ULMCAD (mean age 71 ± 9 years, male gender 81%) undergoing PCI or CABG were compared. The primary endpoint was the composite of death, nonfatal myocardial infarction, or stroke. Diabetes was present in 29% and acute coronary syndrome in 56%; mean EuroSCORE was 11 ± 8. High coronary complexity (SYNTAX score >32) was present in 50% of patients. The primary composite endpoint was similar after PCI and CABG up to 4 years (15.5 ± 3.1% vs. 17.1 ± 2.6%; p=0.585). The primary end point was also comparable in a two propensity score matched cohorts. Ischemia-driven revascularization was more frequently needed in PCI than in CABG (5.5% vs. 1.5%; p=0.010). By multivariate analysis, diabetes mellitus (HR 2.00; p=0.003) and EuroSCORE (HR 3.71; p < 0.001) were the only independent predictors associated with long-term outcome.Conclusions: In a "real-world" population with ULMCAD, a contemporary revascularization strategy by PCI or CABG showed similar long-term clinical outcome regardless of the coronary complexity. [ABSTRACT FROM AUTHOR]

Background In clinical practice there is a gap between guidelines recommendation and antiplatelet strategies used for acute coronary syndrome (ACS). We sought to evaluate appropriateness of antiplatelet strategies employed in a tertiary center. Methods and results From January to June 2014, 430 ACS were treated with percutaneous coronary intervention by 3 groups of interventional cardiologists. Aspirin and clopidogrel (52%) were the most commonly used antiplatelet therapies, being prasugrel associated with aspirin in 110 (25.5%) and ticagrelor in 97 (22.5%) ACS. Inappropriate use of prasugrel (Tia/Ictus) was found in 2 (1.8%) patients and not recommended use (> 75 years, without diabetes or previous myocardial infarction) in 11 (10%). Not recommended use of ticagrelor (plus warfarin) was found in 4 (4.4%). Switching from clopidogrel to prasugrel occurred in 29% [28 showing high residual platelet reactivity (HRPR: ADP 10 μmol > 70%), and 4 left main stenting], while from clopidogrel to ticagrelor occurred in 13.4% (all showing HRPR, but 1). The most powerful predictor for prescription of 3rd generation P2Y12 inhibitors was the HRPR (OR 5.473, 95%CI 2.41–12.43, p < 0.0001), whereas the behavior of attending cardiologist (HR 0.674, 95%CI 0.573–0.847, p = 0.001) and the older age reduced the probability of receiving it (OR0.963, 95%CI 0.943–0.984, p = 0.001). Conclusions Clopidogrel remained the most common P2Y12 inhibitor employed for ACS. Third generation P2Y12 inhibitor prescription was lower than the one expected by guidelines recommendations, and the switching was largely based on clopidogrel HRPR. These findings suggest the need for a greater effort to improve adherence of cardiology community to current guidelines. [ABSTRACT FROM AUTHOR]

Background Morphine is frequently used in ST-segment elevation myocardial infarction (STEMI) patients, even if recently it has been associated with a delayed onset of action of the oral antiplatelet agents. There are no data regarding the impact of morphine on myocardial reperfusion after primary percutaneous coronary intervention (PPCI). Objective This study sought to assess myocardial reperfusion by early ST-segment resolution (≥ 50% at 30 minutes) according to morphine use in STEMI patients undergoing PPCI. Methods 182 STEMI patients undergoing PPCI and receiving either prasugrel (n = 51) or ticagrelor (n = 131), who were antiplatelet and anticoagulant therapies naïve, were included in the study. All patients had serial ST-segment elevation evaluations by ECG and residual platelet reactivity assessments by VerifyNow P2Y12 Reactivity Units (PRU). Results Overall, 74 (41%) patients received morphine according to the attending physician's preference and showed lower ST-segment resolution rate as compared with patients without morphine (76% vs 87%, p = 0.047). Higher baseline TIMI flow < 2 rate (79% vs 64%, p = 0.036) and peak CPK values (1821 [924–3283] U/L vs 1483 [718–2327] U/L, p = 0.034) were observed in morphine patients. Moreover, a delayed response to oral antiplatelet (PRU area under the curve [AOU0–8]: 1448 ± 448 vs 686 ± 292, p = 0.001) was documented in patients with morphine as compared with those without. The independent predictors of early ST-segment elevation resolution failure were PRU ≥ 208 after antiplatelet loading (OR 2.78, 95% CI 1.08–7.14; p = 0.034) and TIMI flow grade < 3 after PPCI (OR 5.89, 95% CI 1.64–21.12; p = 0.009), but not morphine use. Conclusions In STEMI patients undergoing PPCI, morphine use is associated with a higher residual platelet reactivity and a poorer myocardial reperfusion. Independent predictors of impaired myocardial reperfusion were high residual platelet reactivity and TIMI flow grade after PPCI but not morphine use, questioning the direct relationship between morphine and worse myocardial reperfusion. [ABSTRACT FROM AUTHOR]

Recent guidelines have recommended the use of aspirin and prasugrel in patients with acute coronary syndromes undergoing percutaneous coronary intervention. However, prasugrel use has been evaluated only in randomized trials. This study sought to evaluate bleeding rates and adherence to treatment in “real-world” patients treated with prasugrel. In total 298 consecutive patients 68 ± 10 years old (31% >75 years old) underwent stent implantation and received prasugrel therapy. Indications to prasugrel therapy were (1) ST-elevation acute myocardial infarction (41%), (2) drug-eluting stent implantation in diabetics (24%), (3) stent thrombosis (3%), (4) left main coronary artery drug-eluting stent implantation (6%), and (5) percutaneous coronary intervention in patients with high residual platelet reactivity on clopidogrel therapy (26%). All patients received a loading of prasugrel 60 mg. Patients ≥75 years old and with body weight ≤60 kg received a maintenance dose of 5 mg/day (10 mg/day for all the other patients). Follow-up data including adherence to prasugrel therapy were collected by telephone interviews or outpatient visits. Minimal follow-up length was 6 months (mean 9 ± 3). Major, minor, and minimal bleedings (Thrombolysis In Myocardial Infarction criteria) occurred in 2.7%, 4.7%, and 15.1% of enrolled patients. Low residual platelet reactivity (p = 0.001) and female gender (p = 0.29) were independent predictors of bleeding events. The most frequent minimal bleeding event was epistaxis. Only 8 patients (2.7%) permanently discontinued prasugrel therapy because of bleeding events (n = 4), possible side effects (n = 2), or medical decisions not associated with bleeding or side effects (n = 2). Fourteen patients (4.7%) temporarily discontinued prasugrel (average 6.5 days) mainly because of surgical procedures. No definite or probable stent thrombosis occurred, although 3 patients develop de novo myocardial infarction and 1 an ischemic stroke. There were 11 deaths because of heart failure or refractory cardiogenic shock in 9, pulmonary embolism in 1, and cancer in 1. In conclusion, in clinical practice, major and minor bleeding event rates associated with prasugrel therapy are comparable to those reported in controlled randomized trials. The minimal bleeding event rate is higher than reported but does not seem to affect adherence to treatment. [ABSTRACT FROM AUTHOR]