Because of its high prevalence, chronic kidney disease (CKD) remains a major health hazard throughout the world. Patients with CKD have a high prevalence and incidence of acute coronary syndromes (ACS). Despite decades of improved care, their higher risk profile persists and cardiovascular diseases remain their leading cause of death. Along with the reduction of glomerular filtration rate, several physiological processes are impacted and participate in the pathophysiology of ischemic and bleeding events. CKD is associated with an accelerated and severe course of atherothrombotic disease, and this relates to a modified vascular milieu with alterations on the level of the coagulation cascade and platelet aggregation. In addition, pharmacokinetics of several drugs, in particular antithrombotics, are altered and differ from that of non-CKD patients. Patients with CKD therefore represent a challenging population for both physicians and researchers. In addition to these perturbations of physiological processes, CKD patients face 2 major issues. First, there is a clear gap in scientific research as they are commonly underrepresented or excluded from major clinical trials. This is particularly true regarding antithrombotic treatment during ACS. Second, there is a gap in offering evidence-based treatment for these patients including state-of-the art options for revascularization and modern antiplatelet treatment, both of which are commonly underused. During the last decade, new potent oral P2Y ₁₂ -ADP receptor antagonists, prasugrel and ticagrelor, which are more potent antiplatelet agents compared with clopidogrel, were introduced for ACS treatment. However, despite the fact that CKD patients represent a large proportion of those experiencing an ACS and are considered at high risk, there is a lack of dedicated trials and we are left with subgroup analysis of large randomized clinical trials were stage 4 and dialysis patients were rare. In the present review we summarize the mechanisms involved in the high ischemic and bleeding risk of CKD patients and the risk–benefit ratio of potent antiplatelet drugs during ACS.

Clopidogrel low response as assessed by several different biological tests correlates with poor prognosis after percutaneous coronary intervention (PCI). However, recent randomized clinical trials (RCT) testing the strategy of individual antiplatelet therapy tailoring based on one sole test have all shown negative results. Poor correlation between the different tests may explain the difficulties of patient selection and identification of “true poor responders” to clopidogrel. In this prospective study, clopidogrel response was assessed in 100 consecutive patients between 18 and 24 hours after a 600 mg clopidogrel loading dose using three different tests: light transmission aggregometry with 10 μmol ADP (LTA, results expressed as platelet aggregation percentage: PAP), Verify Now P2Y₁₂ (VN, results expressed as P2Y₁₂ reaction unit: PRU) and vasodilatator-stimulated phosphoprotein (VASP, results expressed as platelet reactivity index: PRI). Patients under chronic clopidogrel therapy were excluded. The mean PAP, PRU and PRI values were 38.6%, 176.1 PRU and 52.4%, respectively. When clopidogrel response was analyzed as continuous variable, there was a good correlation between the different tests: LTA/VN (R²= 0.642, p < 0.001), LTA/VASP (R²= 0.409, p < 0.001) and VN/VASP (R²= 0.616, p < 0.001). However, when clopidogrel response was analyzed as pre-specified cut-off points to define patients as “poor or good responders” (according to the literature: 50% PAP for LTA, 235 PRU for VN and 50% PRI for VASP), only 47% of the patients were defined as “good” or “poor responders” by the three tests. Altogether, 33% of the patients were defined as “poor responders” by only one test, 20% by two tests and only 16% by the three tests. The correlation between the different tests is good when clopidogrel response is analyzed as continuous variable. Each individual is however rarely (less than 50%) defined as “poor or good responder” by all the three tests when pre-specified cut-off values are used. A sole test might not be sufficient to manage antiplatelet therapy in an individual patient and these results may explain the results of recent RCT showing the lack of benefit of systematic antiplatelet therapy monitoring strategy.

Background: Atypical clinical presentation in acute myocardial infarction (AMI) patients is not uncommon; most studies suggest that it is associated with unfavorable prognosis.Hypothesis: Long‐term clinical impact differs according to predominant symptom presentation (typical chest pain, atypical chest pain, syncope, cardiac arrest, or dyspnea) in AMI patients.Methods: FAST‐MI 2010, a nationwide French registry, included 4169 patients with AMI in 213 centers at the end of 2010 (76% of active centers). Demographics, medical history, hospital management, and outcomes were compared according to predominant symptom presentation.Results: Typical chest pain with no other symptom was reported in 3020 patients (68% in STEMI patients, 76% in NSTEMI patients). Atypical chest pain, dyspnea, syncope, and cardiac arrest were reported in 11%, 11%, 5%, and 1%, respectively. Patients with atypical clinical presentation had a higher cardiovascular risk profile and received fewer medications and a less invasive strategy. Using Cox multivariate analysis, atypical chest pain was not associated with higher death rate at 3 years (HR: 0.96, 95% CI: 0.69‐1.33, P = 0.78), whereas cardiac arrest (HR: 2.44, 95% CI: 1.00‐5.97, P = 0.05), syncope (HR: 1.70, 95% CI: 1.18‐2.46, P = 0.005), and dyspnea (HR: 1.66, 95% CI: 1.31‐2.10, P < 0.001) were associated with higher long‐term mortality compared with patients with typical isolated chest pain. Similar trends were observed in STEMI and NSTEMI populations.Conclusions: Atypical clinical presentation is observed in about 20% of AMI patients. Cardiac arrest, dyspnea, and syncope represent independent predictors of long‐term mortality in STEMI and NSTEMI populations.

Background Guidelines recommend using risk stratification tools in acute myocardial infarction (AMI) to assist decision making. The TIMI Risk Score for Secondary Prevention (TRS‐2P) has been recently developed to characterize long term risk in patients with MI. Hypothesis We aimed to assess the TRS‐2P in the FAST‐MI registries. Methods We used data from 3 one‐month French registries, conducted 5 years apart, from 2005 to 2015, including 13,130 patients with AMI (52% ST‐elevation myocardial infarction (STEMI)). Atherothrombotic risk stratification was performed using the TRS‐2P score. Patients were divided in 3 categories: G1 (Low‐risk; TRS‐2P=0/1); G2 (Intermediate‐risk; TRS‐2P=2); and, G3 (High‐risk; TRS‐2P≥3). Baseline characteristics and outcomes were analyzed according to TRS‐2P categories. Results A total of 12,715 patients (in whom TRS‐2P was available) were included. Prevalence of G1, G2, and G3 was 43%, 24% and 33% respectively. Clinical characteristics and management significantly differed according to TRS‐2P categories. TRS‐2P successfully defined residual risk of death at one‐year (C‐statistic 0.78): 1‐year survival was 98% in G1, 94% in G2, and 78.5% in G3 (P<0.001). Using Cox multivariate analysis, G3 was independently associated with higher risk of death at 1‐year (Hazard ratio (HR) 4.61; 95% confidence interval (CI): 3.61‐5.89), as G2 (HR 2.08; 95%CI: 1.62‐2.65) compared to G1. The score appeared robust and correlated well with mortality in STEMI and NSTEMI populations, as well as in each cohort separately. Conclusions The TRS‐2P appears to be a robust risk score, identifying patients at high‐risk after AMI irrespective of the type of MI and historical period.

Mechanical circulatory support (MCS) devices are effective tools in managing refractory cardiogenic shock (CS). Data comparing veno-arterial extracorporeal membrane oxygenation (VA-ECMO) and IMPELLA^® are however scarce. We aimed to assess outcomes of patients implanted with these two devices and eligible to both systems. From 2004 to 2020, we retrospectively analyzed 128 patients who underwent VA-ECMO or IMPELLA^® in our institution for refractory left ventricle (LV) dominant CS. All patients were eligible to both systems: 97 patients were first implanted with VA-ECMO and 31 with IMPELLA^®. The primary endpoint was 30-day all-cause death. VA-ECMO patients were younger (52 vs. 59.4, p = 0.006) and had a higher lactate level at baseline than those in the IMPELLA^® group (6.84 vs. 3.03 mmol/L, p < 0.001). Duration of MCS was similar between groups (9.4 days vs. 6 days in the VA-ECMO and IMPELLA^® groups respectively, p = 0.077). In unadjusted analysis, no significant difference was observed between groups in 30-day mortality: 43.3% vs. 58.1% in the VA-ECMO and IMPELLA^® groups, respectively (p = 0.152). After adjustment, VA-ECMO was associated with a significant reduction in 30-day mortality (HR = 0.25, p = 0.004). A higher rate of MCS escalation was observed in the IMPELLA^® group: 32.3% vs. 10.3% (p = 0.003). In patients eligible to either VA-ECMO or IMPELLA^® for LV dominant refractory CS, VA-ECMO was associated with improved survival rate and a lower need for escalation.