Manuel Jesús Macías's research while affiliated with Hospital General Universitario de Alicante and other places

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Publications (6)


Clinical implications of diabetes mellitus in patients with acute coronary syndrome: Prognostic role and use of new P2Y12 receptor inhibitors
  • Article

January 2022

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31 Reads

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1 Citation

Diabetes Research and Clinical Practice

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Juan Miguel Ruiz-Nodar

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Aims We investigated the impact of diabetes mellitus (DM) in acute coronary syndrome (ACS) patients, and the 2-year prognosis based on antiplatelet therapy. Methods This is a prospective and multicenter registry including hospitalized ACS patients. Clinical management and antiplatelet therapy at discharge were recorded. Bleeding events, all-cause mortality and major adverse cardiovascular events (MACEs) were recorded during 2-years and compared according to DM and the P2Y12 receptor inhibitor. Results From 1717 ACS patients, 653 (38%) had DM. Diabetic patients were older, more commonly females, with higher prevalence of comorbidities and more conservative management. After excluding antiplatelet monotherapy or oral anticoagulation, clopidogrel was prescribed in 59.6% of DM patients. Cox regression analysis showed that DM was an independent risk factor for MACE (aHR 1.39, 95% CI 1.05-1.83). The use of clopidogrel instead of ticagrelor/prasugrel was also independently associated with MACE (aHR 1.71, 95% CI 1.11-2.63), and all-cause mortality (aHR 2.47, 95% CI 1.23-4.96) in diabetic patients (log-rank p-values <0.001). Conclusions In ACS patients, DM was associated with higher risk of MACE. In such patients, the use of ticagrelor/prasugrel reduced MACE and mortality compared to clopidogrel. Novel P2Y12 receptor inhibitors might be used as the first therapeutic choice in these high-risk patients.

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Kaplan‐Meier survival curves for different events, comparing clopidogrel versus novel P2Y12 inhibitors. BARC, Bleeding Academic Research Consortium; HR, hazard ratio; MACE, major adverse cardiovascular event; TIMI (Thrombolysis in myocardial infarction).
One‐year efficacy and safety of prasugrel and ticagrelor in patients with acute coronary syndromes: Results from a prospective and multicentre ACHILLES registry
  • Article
  • Full-text available

February 2020

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124 Reads

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6 Citations

British Journal of Clinical Pharmacology

British Journal of Clinical Pharmacology

Background Prasugrel and ticagrelor have demonstrated higher efficacy than clopidogrel in their main clinical trials for patients with acute coronary syndrome (ACS). However, the long‐term prognosis and different clinical characteristics related to the type of antiplatelet prescription in current clinical practice ACS patients have not been analysed in depth. The objective of this study was to analyse the clinical profile of ACS and the efficacy and safety of novel oral P2Y12 inhibitors in current clinical practice patients discharged afterACS. Methods We collected data from the ACHILLES registry, and an observational, prospective and multicentre registry of patients discharged after ACS. We analysed baseline characteristics, clinical profile and therapy during ACS admission and compared with the different treatments at discharge. After 1 year of follow‐up, ischaemic and major bleeding events were analysed. Multivariate Cox regression analysis and Kaplan Meier curves were also plotted. Results Of 1717 consecutive patients, 1294 (75.4%) were discharged with a P2Y12 inhibitor without oral anticoagulation. Novel oral P2Y12 inhibitors were indicated in 47%. Patients treated with clopidogrel were elderly (69.1 ± 13.4 vs 60.4 ± 11.5 years; P < .001) and had a higher prevalence of cardiovascular risk factors. GRACE and CRUSADE scores were higher in the clopidogrel than in novel oral P2Y12 inhibitors group (P < .001). After 1 year of follow‐up, 64(5.0%/year) patients had a new myocardial infarction, 127(10.0%/year) had a major adverse cardiovascular event (MACE) and 78(6.1%/year) died. Patients treated with clopidogrel had a significantly higher annual rate of cardiovascular mortality, MACE and all‐cause mortality (allP < .001) without differences in major bleeding (P = .587) compared with novel oral P2Y12 inhibitors. After multivariate adjustment for the main clinical variables related to adverse prognosis in ACS patients, the discharge with novel oral P2Y12 inhibitors therapy was independently associated with lower risk of all‐cause mortality (HR0.49, 95% CI [0.24‐0.98], P = .044) and lower risk of MACE (HR0.64, 95% CI [0.41‐0.98], P = .044). Conclusions In this prospective, observational and current clinical practice ACS registry, the use of novel oral P2Y12 inhibitors was associated with a reduction in adverse events compared with clopidogrel in patients with ACS. Novel oral P2Y12 inhibitors prescription at discharge was independently associated with lower all‐cause mortality and MACE without differences in bleeding events. However, clopidogrel remained the most common P2Y12 inhibitor employed for ACS, especially in older and high‐risk patients.

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

January 2019

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93 Reads

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2 Citations

Clinical Drug Investigation

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.


Fig 1. Flow chart of patients and analyzed subgroups. STEMI: ST-elevation myocardial infarction; NSTE-ACS: non-ST-elevation ACS; PCI: percutaneous coronary intervention; CABG: coronary artery bypass graft.
Table 1 . Baseline patient characteristics.
Table 2 . Management during admission.
Table 4 . Medium-term events.
Conservatively managed patients with non-ST-segment elevation acute coronary syndrome are undertreated with indicated medicines

November 2018

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113 Reads

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3 Citations

Introduction and aims: Patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) are often managed conservatively. Clinical practice guidelines recommend treating these patients with the same pharmacological drugs as those who receive invasive treatment. We analyze the use of new antiplatelet drugs (NADs) and other recommended treatments in people discharged following an NSTE-ACS according to the treatment strategy used, comparing the medium-term prognosis between groups. Methods: Prospective observational multicenter registry study in 1717 patients discharged from hospital following an ACS; 1143 patients had experienced an NSTE-ACS. We analyzed groups receiving the following treatment: No cardiac catheterization (NO CATH): n = 134; 11.7%; Cardiac catheterization without revascularization (CATH-NO REVASC): n = 256; 22.4%; percutaneous coronary intervention (PCI): n = 629; 55.0%; and coronary artery bypass graft (CABG): n = 124; 10.8%. We assessed major adverse cardiovascular events (MACE), all-cause mortality, and hemorrhagic complications at one year. Results: NO CATH was the oldest, had the most comorbidities, and was at the highest risk for ischemic and hemorrhagic events. Few patients who were not revascularized with PCI received NADs (NO CATH: 3.7%; CATH-NO REVASC: 10.6%; PCI: 43.2%; CABG: 3.2%; p<0.001). Non-revascularized patients also received fewer beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARB), and statins (p<0.001). At one year, MACE incidence in NO CATH group was three times that of the other groups (30.1%, p<0.001), and all-cause mortality was also much higher (26.3%, p<0.001). There were no significant differences in hemorrhagic events. Belonging to NO CATH group was an independent predictor for MACE at one year in the multivariate analysis (HR 2.72, 95% CI 1.29–5.73; p = 0.008). Conclusions: Despite current invasive management of NSTE-ACS, patients not receiving catheterization are at very high risk for under treatment with recommended drugs, including NADs. Their medium-term prognosis is poor, with high mortality. Patients treated with PCI receive better pharmacological management, with high use of NADs.


Figure 1: Patients' outcome depending on their age. Comparison of patients' deaths and MACE after 1-year of follow-up. 
Figure 3: Kaplan-Meier cumulative survival curve showing the effect of being 75 or older on adverse events in ACS patients. A. Effect of age on all cause deaths. B. Effect of age on MACE. C. Effect of age on bleeding events (BARC 3-5, major bleeding). 
Therapeutic management and one-year outcomes in elderly patients with acute coronary syndrome

September 2017

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71 Reads

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12 Citations

Oncotarget

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.


Table 1 . Demographic and Clinical Baseline Characteristics of Both the ECV and FANTASIIA Populations 
Is the ORBIT bleeding risk score superior to the HAS-BLED score in anticoagulated atrial fibrillation patients?

August 2016

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102 Reads

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25 Citations

Circulation Journal

Background: Several bleeding risk scores have been validated in patients with atrial fibrillation (AF). The ORBIT score has been recently proposed as a simple score with the best ability to predict major bleeding. The present study aimed to test the hypothesis that the ORBIT score was superior to the HAS-BLED score for predicting major bleeding and death in "real world" anticoagulated AF patients.Methods and Results:We analyzed the predictive performance for bleeding and death of 406 AF patients who underwent 571 electrical cardioversion procedures and 1,276 patients with permanent/persistent AF from the FANTASIIA registry. In the cardioversion population, 21 patients had major bleeding events and 26 patients died. The predictive performance for major bleeding of HAS-BLED and ORBIT were not significantly different (c-statistics 0.77 (95% CI 0.66-0.88) and 0.82 (95% CI 0.77-0.93), respectively; P=0.080). For the FANTASIIA population, 46 patients had major bleeding events and 50 patients died. The predictive performances for major bleeding of HAS-BLED and ORBIT were not significantly different (c-statistics 0.63 (95% CI 0.56-0.71) and 0.70 (95% CI 0.62-0.77), respectively; P=0.116). For death, the predictive performances of HAS-BLED and ORBIT were not significantly different in both populations. The ORBIT score categorized most patients as "low risk". Conclusions: Despite the original claims in its derivation paper, the ORBIT score was not superior to HAS-BLED for predicting major bleeding and death in a "real world" oral anticoagulated AF population.

Citations (5)


... This is a post-hoc analysis of the ACHILLES registry (AntiagregaCión en HospitaLes del Levante Español), whose design has been described elsewhere [8][9][10]. Briefly, ACHILLES is an observational, prospective, multicenter, consecutive registry, which analyzed therapeutic management and the use of different treatment strategies and antiplatelet drugs in patients discharged following an ACS. ...

Reference:

High medium-term incidence of major cardiovascular events in discharged patients with unstable angina
One‐year efficacy and safety of prasugrel and ticagrelor in patients with acute coronary syndromes: Results from a prospective and multicentre ACHILLES registry
British Journal of Clinical Pharmacology

British Journal of Clinical Pharmacology

... On the other hand, deescalation of the P2Y12 inhibition is defined as a decrease in platelet inhibition and includes switching from potent P2Y12 inhibitor to clopidogrel [9]. Although the literature regarding the appropriateness and safety of this practice is limited, studies reveal that switching to clopidogrel occurs mainly due to adverse effects, bleeding episodes, need for concomitant anticoagulation therapy and physician's discretion without any specific reason [4,10]. ...

Switching of Oral P2Y12 Inhibitor Treatment in Patients with Acute Coronary Syndrome: Prevalence, Predictors, and Prognosis
  • Citing Article
  • January 2019

Clinical Drug Investigation

... This is a post-hoc analysis of the ACHILLES registry (AntiagregaCión en HospitaLes del Levante Español), whose design has been described elsewhere [8][9][10]. Briefly, ACHILLES is an observational, prospective, multicenter, consecutive registry, which analyzed therapeutic management and the use of different treatment strategies and antiplatelet drugs in patients discharged following an ACS. ...

Conservatively managed patients with non-ST-segment elevation acute coronary syndrome are undertreated with indicated medicines
PLOS ONE

PLOS ONE

... In addition, discharge instructions are a solution to their postdischarge worries. In the treatment of ACS combined with diabetes mellitus, there is a certain damage to the body of elderly patients, and with various physical functions declining with age, they are prone to a series of adverse reactions, and most patients experience adverse reactions followed by poor mood, which affects the efficacy and reduces the quality of life [19,20]. Note. ...

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

Oncotarget

... Nevertheless, there are works that prove that the HAS-BLED score performed better than the CHA2DS2-VASc score in anticoagulated patients with AF [50]. While other bleeding scores have been suggested, such as ORBIT or ATRIA, the HAS-BLED score has been proven as superior to both scores in the "real-world" of oral anticoagulated patients with AF [51,52]. ...

Is the ORBIT bleeding risk score superior to the HAS-BLED score in anticoagulated atrial fibrillation patients?

Circulation Journal