Switching of Oral P2Y12 Inhibitor Treatment in Patients with Acute Coronary Syndrome: Prevalence, Predictors, and Prognosis.

BACKGROUND AND OBJECTIVE: Dual antiplatelet therapy is one of the main treatments in acute coronary syndrome (ACS). Switching antiplatelet agents may be necessary in some patients to improve efficacy or safety. The objective of this study was to determine the prevalence, predictors, and implications of clinical switching in patients during hospital admission and 1-year follow-up at discharge. METHODS: Observational, prospective, multicenter registry study in patients discharged following an admission for ACS and followed up for 1 year. We analyzed ischemic and bleeding events as well as treatment changes. RESULTS: We recruited 1717 patients; in-hospital switching occurred in 425 (24.8%): 15.1% to clopidogrel and 84.9% to newer antiplatelet drugs (prasugrel or ticagrelor). Those switched to newer antiplatelets were younger, with lower scores on the GRACE and CRUSADE scales, admitted more frequently for ST-elevation myocardial infarction and underwent more invasive management and percutaneous revascularization. The clinical cardiologist was responsible for most in-hospital switching to newer antiplatelets (79.6%). The loading dose of the second antiplatelet did not affect incidence of bleeding events. Post-discharge switching was infrequent (2%) and depended mainly on clinical indications; only 30% was related to a new ACS. CONCLUSIONS: In a contemporary registry with ACS, in-hospital switching of antiplatelet drugs was frequent. Those switched to newer antiplatelets were younger and admitted more frequently for ST-elevation myocardial infarction. Post-discharge switching was infrequent.

Chronic Kidney Disease and Third-Generation P2Y12 Inhibitors Use in Patients With Acute Coronary Syndrome: Impact on the Prognosis at 1 Year.

Chronic kidney disease (CKD) is associated with worse clinical outcomes in patients with acute coronary syndrome. However, they are underrepresented in clinical trials. We aimed to investigate differences in prognosis of acute coronary syndrome patients with and without CKD, focusing on the use of novel P2Y12 receptor inhibitors. This multicenter registry involved patients with acute coronary syndrome from 3 tertiary institutions. After excluding anticoagulated patients and patients on antiplatelet monotherapy, 1280 patients remained. During 1 year of follow-up, we recorded all major adverse cardiovascular events (composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal ischemic stroke), bleeds (Bleeding Academic Research Consortium classification) and deaths. Of 1280 patients, 325 (25.4%) had CKD; 55.5% of non-CKD patients and 22.7% of CKD patients were prescribed novel P2Y12 inhibitors. During follow-up, CKD patients under novel P2Y12 inhibitors showed a not statistically significant lower mortality and incidence of thrombotic events than clopidogrel-treated ones. In contrast, non-CKD patients taking novel P2Y12 inhibitors had better outcomes in terms of major adverse cardiovascular events (4.72 vs 9.41; P = .006), all-cause mortality (1.32 vs 4.24; P = .006), and severe bleeding events (Bleeding Academic Research Consortium 3-5) (0.94 vs 2.82; P = .030), without differences for any bleeding (8.11 vs 8.47; P = .849). Bleeding risk was not increased by using third-generation P2Y12 inhibitors in either group of patients. In conclusion, the use of third-generation P2Y12 inhibitors among non-CKD patients was associated with better outcomes. CKD patients receiving third-generation P2Y12 inhibitors treatment showed no statistically significant lower mortality and thrombotic events. Bleeding risk was not increased with the use of third-generation P2Y12 inhibitors in either group of patients.

Under-prescription of novel antiplatelet drugs in patients with acute coronary syndrome and previous cardiovascular disease.

BACKGROUND: Patients with acute coronary syndrome (ACS) and previous cardiovascular disease (CVD) (stroke, peripheral arterial disease [PAD] or coronary artery disease [CAD]) are at high risk of serious events and mortality. Current clinical guidelines recommend new antiplatelet drugs (NADs) for high cardiovascular risk patients with ACS; however, these drugs are underused in different scenarios. METHODS: This study included 1717 ACS patients from 3 tertiary hospitals. Of them, 641 (37.33%) suffered from previous CVD: 149 patients with stroke, 154 patients with PAD and 541 patients with CAD. Bleeding, mortality and major adverse cardiac events (MACE) at 1 year of follow-up after hospital discharge were analyzed. RESULTS: NADs administration during hospital stay and at discharge was less frequent in patients with previous CVDs (P<0.001, for both). Cox analysis in this cohort of patients showed that clopidogrel prescription at discharge was independently associated with MACEs (HR: 1.59 [95% CI: 1.03-2.45]; P=0.036) and with death (HR: 1.99 [95% CI: 1.00-3.98]; P=0.049) in multivariate analysis. More specifically, when ticagrelor prescription at discharge was compared with clopidogrel, a significant death reduction was found in both, the univariate and the multivariate Cox analysis (HR: 4.54 [95% CI: 2.26-9.13]; P<0.001 and HR: 2.61 [95% CI: 1.16-5.90]; P=0.021, respectively). CONCLUSIONS: New antiplatelet drugs, especially ticagrelor, showed lower rates of mortality in patients with CVD without differences for bleeding. Despite the recommendations of current clinical guidelines for high risk patients with ACS, the use of NADs is very low in "real-life" patients with previous CVD.

Impact of anemia as risk factor for major bleeding and mortality in patients with acute coronary syndrome.

BACKGROUND: Anemia is frequent in acute coronary syndrome (ACS) patients and is associated with worse clinical outcomes. We aimed to investigate the therapeutic strategies, the use of novel P2Y12 inhibitors, and the prognostic implication of anemia in a "real world" cohort of ACS patients. METHODS: This is an observational and prospective registry including 1717 ACS patients from three tertiary hospitals. During hospitalization we recorded the clinical management and the antiplatelet therapy at discharge. Patients were divided into 2 groups according to the baseline hemoglobin level, i.e. anemic (hemoglobin < 13 g/dL in men and <12 g/dL in women) and non-anemic patients. Bleeding events, mortality and major adverse cardiovascular events (MACEs) were recorded during 1-year of follow-up. RESULTS: Anemia was present in 445 (25.9%) patients. Cardiac catheterization (83.8% vs. 94.5%, p < .001), and revascularization by percutaneous coronary intervention (53.5% vs. 70.5%, p < .001) were less frequent in these patients. Excluding anticoagulated patients, novel P2Y12 inhibitors were less prescribed in anemic patients (OR 2.80 [95% CI 2.13-3.67], p < .001). Anemia was independently associated with major bleeding (HR 2.26 [95% CI 1.07-4.78], p = .033) and all-cause mortality (HR 1.62 [95% CI 1.03-2.56], p = .038), but not with MACE. At 1-year of follow-up, the risk of mortality in anemic patients taking clopidogrel was higher (HR 2.38 [95% CI 1.01-5.67]; p = .049). CONCLUSIONS: In this registry involving ACS patients, anemia had influence on clinical management and antiplatelet therapy. Patients suffering from anemia had higher risk for major bleeding and mortality. In particular, anemic patients treated with clopidogrel had even more mortality events.

Disparities in the Estimation of Glomerular Filtration Rate According to Cockcroft-Gault, Modification of Diet in Renal Disease-4, and Chronic Kidney Disease Epidemiology Collaboration Equations and Relation With Outcomes in Patients With Acute Coronary Syndrome.

BACKGROUND: A simple method to assess renal function is the estimated glomerular filtration rate, and it shows prognostic implications. However, it remains unknown which equation should be used in patients with acute coronary syndrome. We compared the ability and correlation of the Cockcroft-Gault, Modification of Diet in Renal Disease-4 (MDRD-4), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations and their predictive performance for major adverse cardiovascular events, all-cause mortality, and major bleeding in a cohort of patients with acute coronary syndrome. METHODS AND RESULTS: Multicenter prospective registry involving 1699 consecutive patients with acute coronary syndrome from 3 tertiary institutions. At entry, renal function was assessed using the Cockcroft-Gault, MDRD-4, and CKD-EPI-creatinine equations. During 12 months of follow-up, we recorded all major adverse cardiovascular events (composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal ischemic stroke), bleeding events (Bleeding Academic Research Consortium classification), and all-cause mortality. Receiver operating characteristic curve comparisons demonstrated that Cockcroft-Gault equation had higher predictive ability compared with MDRD-4 equation for major adverse cardiovascular events (0.651 versus 0.616; P=0.023), major bleeding (0.600 versus 0.551; P=0.005), and all-cause mortality (0.754 versus 0.717; P=0.033), as well as higher predictive ability compared with CKD-EPI equation for major bleeding (0.600 versus 0.564; P=0.018). Integrated discrimination improvement and net reclassification improvement analyses showed superior discrimination and reclassification of Cockcroft-Gault equation. Decision curve analyses graphically demonstrated higher net benefit and clinical usefulness of the Cockcroft-Gault equation in comparison with MDRD-4 and CKD-EPI equations. CONCLUSIONS: In patients with acute coronary syndrome, the Cockcroft-Gault equation presented superior predictive ability for major adverse cardiovascular events, major bleeding, and all-cause mortality compared with MDRD-4 equation, and superior predictive ability for major bleeding compared with CKD-EPI equation. The Cockcroft-Gault equation also showed higher net benefit and clinical usefulness.

Low body weight and clinical outcomes in acute coronary syndrome patients: results of the ACHILLES Registry.

BACKGROUND: Being overweight increases the risk of cardiovascular diseases and mortality. However, among high-body-weight patients with established acute coronary syndrome (ACS) this evidence is not clear. In this scenario, a low body weight (LBW) has been proposed to confer higher prognostic risk and higher bleeding risk with new P2Y12 inhibitors. AIMS: We aimed to examine differences in mortality, catheterizations/revascularizations, antiplatelet therapy and ischemic/bleeding adverse events between ACS patients with LBW. METHODS: This is a multicenter registry involving 1576 consecutive ACS patients (ST-elevation myocardial infarction (STEMI), non-STEMI, or unstable angina) from three tertiary institutions. Patients were divided into two groups: LBW (weight < 60 kg, n = 176) and non-LBW (weight ⩾ 60 kg, n = 1400). During 12 months follow-up, we recorded management (catheterizations/revascularizations), antiplatelet therapy, major adverse cardiovascular events (MACEs), bleeding events (BARC classification), and mortality. RESULTS: Catheterizations (86.4% vs. 93.4%; p = 0.001) and revascularizations (64.8% vs. 76.1%; p = 0.001) were significantly lower in the LBW group. At discharge, prescription of new P2Y12 inhibitors was also lower in LBW patients (24.4% vs. 37.8%; p = 0.001). After 12-month follow-up, the incidence of MACE (HR 1.61 (95% CI 1.03-2.50]; p = 0.038) and mortality (HR 2.18 (95% CI 1.33-3.58); p = 0.002) was higher in LBW patients compared with non-LBW. In contrast, there were no significant differences for bleeding events. CONCLUSIONS: LBW in ACS patients was associated with higher incidence of MACE and mortality. In this group of patients less catheterizations and coronary revascularizations were performed. Despite there being no differences in bleeding rates, new P2Y12 inhibitors were less prescribed in LBW patients.

Therapeutic management and one-year outcomes in elderly patients with acute coronary syndrome.

BACKGROUND: Elderly represents a subgroup of high-risk ACS patients due to their advanced age and other comorbidities. Unfortunately, they are also often under-represented in many studies and clinical trials. Furthermore, cardiologists commonly find difficulties in the choice of the antiplatelet treatment and even on whether invasive revascularization should be used. In this study, the management of elderly ACS patients regarding antiplatelet therapy and revascularization procedures will be analyzed. METHODS: 1717 ACS patients were consecutively included in this study from 3 tertiary Hospitals in the Southeast of Spain. Of them, 529 (30.8%) were ≥ 75 years. They were mainly male (60.7%) with a mean age of 81.4±4.7 years. Clinical characteristics, treatment received (antiaplatelet therapy, revascularization) and outcome were analyzed. RESULTS: Regression analysis showed that being ≥ 75 years is independently associated with neither performing catheterization (79.6% vs 97.1%), nor revascularization (51.8% vs 72.5%), being the medical conservative treatment the election in these elderly patients (40.6% vs 18.9%) (p < 0.001 for all). Furthermore, ticagrelor prescription were significantly decreased in older patients (11.5% vs 19.6%; p < 0.001). Regarding patients outcome after one-year of follow-up, being ≥ 75 years was associated with death, major adverse cardiac events (MACE) and major bleeding (all of them p < 0.001). Importantly, nor performing catheterization was independently associated with MACE and death in Cox multivariate analysis in elderly patients. CONCLUSIONS: Elderly patients with ACS are undertreated both invasively and pharmacologically, and this fact might be associated with the observed worse outcomes.