STEMI and NSTEMI: Real-world Study in Mexico (RENASCA)

Archives of Medical Research

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(2019)

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ORIGINAL ARTICLE

STEMI and NSTEMI: Real-world Study in Mexico (RENASCA) Gabriela Borrayo-S
anchez,a Mart
ın Rosas-Peralta,b Erick Ram
ırez-Arias,c Guillermo Saturno-Chiu,c Joel Estrada-Gallegos,c Rodolfo Parra-Michel,d Hugo R. Hernandez-Garc
ıa,d Ernesto A. Ayala-L
opez,e Rafael Barraza-Felix,e Andr
es Garc
ıa-Rinc
on,e D
ebora Adalid-Arellano,e Guillermo Careaga-Reyna,f Jos
e L. L
azaro-Castillo,f Lidia E. Betancourt-Hern
andez,g Roc
ıo Camacho-Casillas,h Martha Hern
andez-Gonzalez,i Germ
an Celis-Quintal,i Beatriz Villegas-Gonz
alez,j Marco Hern
andez-Carrillo,k Zaria M. Benitez Arechiga,k Abelardo Flores-Morales,c Ana C. Sep
ulveda-Vildosola,l RENASCA IMSS Group a

Programa ‘‘A Todo Coraz
on’’, Centro M
edico, Nacional, Siglo XXI, Instituto Mexicano del Seguro Social, Ciudad de M
exico, M
exico Programa ‘‘A Todo Coraz
on’’, Centro M
edico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Ciudad de M
exico, M
exico c Hospital de Cardiolog
ıa, Centro Medico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Ciudad de M
exico, Mexico d Hospital de Especialidades, Centro Medico Nacional de Occidente, Instituto Mexicano del Seguro Social, Guadalajara, Jalisco, Mexico e Hospital de Especialidades, Centro Medico Nacional La Raza, Instituto Mexicano del Seguro Social, Ciudad de M
exico, Mexico f Hospital General, Centro Medico Nacional La Raza, Instituto Mexicano del Seguro Social, Ciudad de M
exico, Mexico g Hospital de Especialidades Veracruz, Instituto Mexicano del Seguro Social, Veracruz, Mexico h Hospital de Especialidades Coahuila, Instituto Mexicano del Seguro Social, Coahuila, Mexico i Hospital de Especialidades Guanajuato, Instituto Mexicano del Seguro Social, Guanajuato, Mexico j Hospital de Especialidades Puebla, Instituto Mexicano del Seguro Social, Puebla, Mexico k Hospital de Especialidades Sonora, Instituto Mexicano del Seguro Social, Sonora, M
exico l Unidad de Investigaci
on y Educaci
on en Salud Pol
ıtica, Centro M
edico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Ciudad de M
exico, M
exico b

Received for publication October 30, 2018; accepted January 18, 2019 (ARCMED_218_483).

Introduction. Mexico is the country with the highest mortality due to acute myocardial infarction in adults older than 45 years old according to the OECD (28 vs. 7.5% of the average). The first real-world study, RENASCA IMSS, showed a high-risk population at 65%, but 50% without reperfusion strategies. The aim was to describe the clinical presentation, treatment, and outcomes of acute coronary syndromes at the IMSS. Methods. RENASCA IMSS is a nation-wide, prospective, longitudinal-cohort study. We include consecutive patients with an Acute Coronary Syndrome diagnosis (ACC/AHA/ ESC) admitted in 177 representative hospitals of the IMSS (166 of second level and 11 of third level of attention). In an electronic database clinical, paraclinical, times, reperfusion treatment, complications, and other variables were assessed. Confidentiality was maintained in data and informed consent was obtained. Registrer calibration was performed with more than 80% of the variables and 80% of the cases. Results. From March 1, 2014 to December 25, 2017; 21,827 patients were enrolled presenting an average age 63.2
11.7, 75% men (16,259) and 25% women (5,568). The most frequent risk factors were: hypertension (60.5%), smoking (46.8%), diabetes (45.5%), dyslipidemia (35.3%) and metabolic syndrome (39.1%). STEMI diagnosis was established in 73.2% of the patients and NSTEMI in 26.8%. The STEMI group within the Code Infarction showed an improvement in the reperfusion therapy (34.9% before vs. 71.4% after, p #0.0001) and reduction of mortality (21.1 vs. 9.4%, p #0.0001); while the NSTEMI group showed high risk set by a GRACE score of 131.5
43.7 vs. 135.9 þ 41.7, p #0.0001. Mortality was more frequent within the STEMI group (14.9 vs. 7.6%, p #0.0001).

Address reprint requests to: Gabriela Borrayo-S
anchez, Commissioned to ‘‘A Todo Corazon’’, Centro M
edico, Nacional, Siglo XXI, Instituto Mexicano del Seguro Social, Av. Cuauht
emoc 330, Col. Doctores, Del.

Cuauht
emoc, 06720, Ciudad de M
exico, M
exico; Phone: (þ52) (55) 1200-4002; E-mail: [email protected] or gabriela.borrayo@ imss.gob

0188-4409/$ - see front matter. Copyright Ó 2019 IMSS. Published by Elsevier Inc. https://doi.org/10.1016/j.arcmed.2019.01.005

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Conclusions. RENASCA IMSS study represents the largest Acute Coronary Syndromes real-world study in Mexico, demonstrating that the Mexican population has a high risk. Patients with a STEMI diagnosis were more frequently enrolled and were associated with higher mortality and complications; however, there is improvement in the reperfusion therapy and in mortality with the Code Infarction strategy. Ó 2019 IMSS. Published by Elsevier Inc. Key Words: Acute coronary syndrome, STEMI, NSTEMI, Code infarction, Risk stratification, National Registry, RENASCA.

Introduction

Methods

Acute Coronary Syndrome (ACS) and stroke remain to be the first cause of death, according to the WHO (World Health Organization) these diseases were responsible for 15 million of deaths in 2015 (1). Mexico is the country with the highest mortality due to acute myocardial infarction in adults older than 45 years since 2013 according to the OECD (Organization for Economic Co-operation and Development) and it incremented in 2017 with 28 vs. 7.5% of the average (2). Reperfusion therapy is the cornerstone in the treatment of acute myocardial infarction and anticoagulation followed by an early invasive strategy in high-risk patients with a NSTEMI diagnosis. The first real-world study RENASCA (National Registry of the Acute Coronary Syndromes) (3) in the IMSS (Mexican Institute of Social Security) showed a highrisk population at 65%, with a high rate in the risk factors, mainly in diabetes mellitus (46% vs. 25% in the European registries), and a poor adherence to the reperfusion strategies (42% Fibrinolytic therapy, 8% with Primary PCI, and 50% did not receive any form of reperfusion). Some other national registries have also shown a high percentage of patients without any form of reperfusion (47.4%) as well as a low PCI (15%) (4). In other countries the average of patients that did not any form of reperfusion is closed to 30% (29.7% Australia/New Zealand/Canada, 33% United States, 28% Argentina/ Brazil, and 29.5% in Europe) (5). Registries are studies with real-world evidence that allow a greater inclusion of patients, complement the knowledge obtained from the clinical trials in less time and with lower costs; they allow the researching in the health systems to evaluate therapeutic strategies, clinical outcomes, and studies of quality improvement (6). The strongest of all is the multinational registry GRACE (7), it identifies 8 determinant variables of mortality/infarction within 5 years in moderate and high risk, compared with low risk (HR 2.1 y 6.3 respectively) (8), as well as the therapeutic approach with early invasive strategy and the use of some anticoagulant drugs such as fondaparinux (9,10). Our aim was to systematically describe the epidemiological presentation of ACS in the national registry of the IMSS, the treatment practices and the impact of the acute coronary syndrome type in cardiovascular complications in-hospital.

Consecutive patients with an ACS diagnosis were enrolled (ACC/AHA/ESC) (11,12) admitted in representative hospitals of the second and third level of attention of the IMSS. Type 1 myocardial infarction was identified in 90% of cases, 8% corresponded to type 2 myocardial infarction and 2% type 4; other types of myocardial infarction were not included. At the same time patients with NSTEMI according with AHA/ACC criteria were included. In a standard database clinical, electrocardiographic, times, reperfusion treatment, complications, and other variables were assessed under the instructions of filling and with a responsible coordinator in each center. Confidentiality in the data was maintained and informed consent was obtained, prior authorization of the National Commission for Scientific Research, and registered at clinicaltrials.gov (NCT02255344). Registrer calibration was performed with more than 80% of the variables and 80% of the cases with random audits performed in the different centers. The median of following up was 10.3 months with interquartile range of 6 to 18 months. Statistical Analysis Measures of central tendency and dispersion were made according to the distribution of the variables. Student’s t-test was performed in normally independent groups or U MannWhitney as corresponding; categorical variables were analyzed using c2 test. The Odds Ratio was calculated with 95% confidence interval comparing ACS types. Logistic regression was used to evaluate the dependent variables with the presence of MACE and mortality in-hospital. The Kaplan Meier survival curve was used to evaluate the one year mortality and long rank test was used. All tests were two-sided and considered statistically significant at alfa level of #0.05. Results Population Results. From March 1, 2014 to December 25, 2017; 21,827 patients were enrolled in representative hospitals of the second and third level of attention of the IMSS, the average age was 63.2
11.7, 75% were men (16,259) and 25% were women (5,568). The most frequent

STEMI and NSTEMI Real-world Study

risk factors were: hypertension (60.5%), smoking (46.8%), diabetes (45.5%), dyslipidemia (35.3%), and metabolic syndrome (39.1%). STEMI diagnosis was established in 73.2% of the patients and NSTEMI in 26.8%. The Metabolic syndrome was more common in the NSTEMI patients according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) classification (38.7 vs. 40.4%, p 5 0.028), the most common risk factor was hypertension, especially in the NSTEMI patients (68.8 vs. 57.4%, p #0.0001); nevertheless, within the female gender, the prevalence was greater (71 vs. 78.5%, p #0.0001, respectively).

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discharge it is reduced by at least 10%. The most used heparin was enoxaparin (68.7 vs. 63.7%) compared to unfractionated heparin (11 vs. 11.5%). The intravenous nitrates were used in a low proportion (12.5 vs. 17.1%), as well as the intravenous diuretics (13.7 vs. 14.8%). Inotropes like Dopamine, Dobutamine, and Levosimendan were more commonly used in the STEMI patients. Treatment with Aspirin, Angiotensin Converting Enzyme Inhibitor, and Statin at admission was 42.2% and 44 % in STEMI and NSTEMI, and at discharge was 42.9 and 43.5% respectively. If a b-blocker is added to these three medications at discharge, 34.6 and 36.8% were observed respectively (Table 3). Oral glucose-lowering treatment was low (1.9 vs. 7.7%) compared to insulin treatment (11.7 vs. 11.2%).

Clinical Features The general characteristics according to ACS type can be observed in the Table 1, emphasizing in the NSTEMI patients an older age, BMI, higher prevalence of the female gender, medical history of prior angina or infarction events, hypertension, dyslipidemia, and metabolic syndrome. The GRACE score was greater in the NSTEMI patients compared with the STEMI group (135.9
41.7 vs. 131.4
43.7, p #0.0001). Patients with a STEMI diagnosis were more common within the IMSS units with the Code Infarction strategy distributed in previously designed attention networks; nevertheless, patients that were admitted spontaneously had more frequently NSTEMI diagnosis (33.3 vs. 14.5%). Typical chest pain remains to be the most common clinical manifestation, followed by neurovegetative symptoms especially within the STEMI group, syncope was the less common manifestation. Hemodynamic assessment with little differences and within normal parameters is presented in Table 1. Biomarkers The size of myocardial necrosis determined by the biomarker levels such as total creatinine phosphokinase (4:1), creatinine kinase MB fraction (3:1), troponin (8:1), and myoglobin (2:1) were significantly higher in the STEMI group (Table 2). Even though the total amount of leucocytes at admission and the levels of C-reactive protein were higher in the STEMI patients, the levels of fibrinogen and uric acid were higher in the NSTEMI patients. Although the lipid profile was within the normal parameters in both types of ACS, both total cholesterol and LDL were higher in patients with a STEMI diagnosis; both groups showed triglyceride levels higher than the normal rate. It also draws attention a high average of glucose in both ACS groups, more important at discharge in patients with STEMI (207
111 mg vs. 184
105 mg, p !0.0001), as well as in glycated haemoglobin (7.39 vs. 7.25%, p 5 0.075). In-hospital Treatment and at Discharge In both SCA groups dual antiplatelet therapy (aspirin and clopidogrel) at admission was higher than 80%; nevertheless, at

In-hospital Complications Within the early in-hospital complications stand out a higher prevalence of right and left bundle branch block in the NSTEMI patients; nevertheless, atrioventricular blocks, as well as the arrythmias (atrial fibrillation, ventricular fibrillation and ventricular tachycardia) were more common in the STEMI group (8.8 vs. 7.4%, p 5 0.001), and so did the acute kidney failure (8.7 vs. 6.7%, p 5 0.008). Cardiovascular death was higher in the STEMI patients group compared with the NSTEMI group (14.9 vs. 7.6%), but the major adverse cardiovascular events were higher in NSTEMI (27.5 vs. 30.9%) by angina and infarction events (Table 4, Figure 1). In the NSTEMI patients, a high risk was observed with a GRACE score of 131.5
43.7 vs. 135.9
41.7, p !0.0001. Nevertheless, in the STEMI patients with the Infarction code strategy as an attention protocol, an improvement in the reperfusion was observed (34.9% before vs. 71.4% after, p #0.0001); mainly, the group that did not receive any form of reperfusion decreased (65.2 vs. 28.6%, p) at the expense of an increase of the fibrinolytic therapy (25.5 vs. 40.1%, p) as well as the PCI (9.4 vs. 31.3%). In-hospital death reduction was significant with this strategy (21.1 vs. 9.4%, p #0.0001). (Table 5).

Discussion Real-world evidence through registries allows identifying the clinical epidemiology of ACS, from the frequency of cardiovascular risk factors in different countries and populations, its affectation by gender and age, as well as the ACS clinical presentation and spectrum. Compared to the GRACE (13) study report, ACS occurred 2e3 years earlier in our population and was associated with a higher frequency of diabetes and hypertension, the first one occurring up to 48% in the Mexican population compared to 24% of the population included in the GRACE study. This is our reality, the number of patients into this age group (mean 63.2
11.7). It was alarming high risk with one of the most

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Table 1. General characteristics of the enrolled patients in the National Registry of Acute Coronary Syndromes at the IMSS (RENASCA IMSS) Total population Variable Gender Male Female Age BMI Risk factors Smoking Hypertension Diabetes Mellitus Dyslipidemia Metabolic Syndrome (NCEP ATPIII) Cardiovascular history Previous myocardial infarction Previous angina Cerebrovascular accident Provenance Transfer to another IMSS hospital Spontaneous Private hospital Same hospital Clinical manifestations Typical chest pain Dyspnea Syncope Neurovegetative symptoms Hemodynamic assessment Heart rate Respiration rate SBP DBP GRACE score

STEMI

NSTEMI/UA

n [ 21,827

n [ 15,981 (73.2%)

n [ 5,846 (26.8%)

16,259 (74.5%) 5,568 (25.5%) 63.3
11.5 27.6
3.9

12,338 (77.2%) 3,643 (22.8%) 62.9
11.7 27.59
3.9

3,921 (67.1%) 1,925 (32.9%) 64.2
11.6 27.75
4.0

10,210 13,203 9,932 7,705 8,535

(46.8%) (60.5%) (45.5%) (35.3%) (39.3%)

4,212 (19.3%) 3,736 (17.1%) 395 (1.8%)

7,821 9,179 7,232 5,471 6,186

(48.9%) (57.4%) (48.9%) (34.2%) (38.7%)

2,250 (14.1%) 1,958 (12.3%) 277 (1.7%)

!0.0001a !0.0001a 0.225a !0.0001a 0.028a

1,962 (33.6%) 1,778 (30.4%) 118 (2%)

!0.0001a !0.0001a 0.168a !0.0001a

(72.2%) (19.6%) (4.0%) (4.1)

12,486 2,323 614 558

(78.1%) (14.5%) (3.8%) (3.5%)

3,271 1,947 281 347

(56.0%) (33.3%) (4.8%) (5.9%)

13,479 8,229 1,013 7,710

(61.7%) (37.7%) (4.6%) (35.3%)

9,527 6,041 818 6,196

(59.6%) (37.8%) (5.1%) (38.8%)

3 952 2,188 195 1,514

(67.6%) (37.4%) (3.3%) (25.9%)

80
18 19
4.5 123
24 75
14 131.4
43.7

!0.0001a !0.0001a 0.007a

(40.9%) (68.8%) (46.2%) (38.2%) (40.4%)

2,389 4,024 2,700 2,234 2,389

15,757 4,270 895 905

79.6
18.5 19
4 124
24 75
14 133.7
42.7

p Value

78
18 19
4.3 126
23 75
13 135.9
41.7

!0.0001a 0.625a !0.0001a !0.0001a 0.001b 0.01b !0.0001b 0.872b !0.0001b

STEMI, ST-elevation myocardial infarction; NSTEMI/UA, Non-ST-elevation myocardial infarction or Unstable angina; BMI, Body mass index; SBP, Systolic blood pressure; DBP, Diastolic blood pressure. a 2 c. b t Student.

huge diabetes rate compared to the rest of the world. Nevertheless, in the presence of high rate of hypertension, overweight and dyslipidemia the expected prevalence of diabetes is high, although it was more than expected. Hypertension was detected in 58% vs. 63%, which represents an average of 5% more in our population. The Metabolic Syndrome was also more frequent in 39.5% according to the NCEP ATP III, compared to the data reported in the United States which is 24%, and in Spain which is 12% (14). The foregoing makes it clear that Mexican population could be considered as the one with the higher risk worldwide. An important topic to mention is to recognize that LDL-cholesterol was not measured in all patients (65%) and it measured was performed during hospitalization. This cant explained the results under register. Early diagnosis is essential in ACS; therefore, clinical, electrocardiographic data, determination of biomarkers, and experience of the trained staff are key (15); despite

the same pathophysiological context, the clinical manifestations are different, in our population typical chest pain was more frequent in the NSTEMI group, while neurovegetative symptoms and syncope were more frequent in the STEMI group. Biomarkers have become very important in the diagnosis and stratification of the ACS patients (16,17), currently its use must be a routine clinical practice in the evaluation of the patients with chest pain (17); nevertheless, its low specificity and its positive predictive value do not allow to differentiate the cause of myocardial damage and in the case of STEMI, it does not allow to differentiate between type 1 and 2, as emphasized in the 4th STEMI Definition (18); and is not possible to differentiate its increase due to other cardiac causes in stable ischemic heart disease. Therefore, in NSTEMI group the complementary use of algorithms, in which the percentage of absolute and relative variation can support the diagnosis, both in the absence of significant changes in the

STEMI and NSTEMI Real-world Study

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Table 2. Differences between STEMI and NSTEMI on biochemistry determinations Total population Variable Hemoglobin (gr) (M
SD) Admission Minimum Hematocrit (%) (M
SD) Admission Minimum Total leucocytes (M
SD) Admission Maximum Platelets (M
SD) thousand Admission Minimum Fibrinogen (mg) (M
SD) Admission Maximum C-reactive protein (ng) Q50 (25,75) Glucose (mg) (M
SD) Admission Maximum Glycated hemoglobin (%) Q50 (25,75) Urea (mg) (M
SD) Admission Maximum Creatinine (mg) Q50 (25,75) Admission Maximum Uric acid (mg) (M
SD) Total cholesterol (mg) (M
SD) HDL (mg) (M
SD) LDL (mg) (M
SD) Triglycerides (mg) (M
SD) Maximum CPK U/L (Q50,25,75) Maximum CK-MB U/L (Q50,25,75) Maximum Troponin (Q50,25,75) Maximum Myoglobin (Q50,25,75)

STEMI

NSTEMI/UA

n [ 15,981 (73.2%)

n [ 5,846 (26.8%)

p Value

14.1
2.4 13.0
2.6

14.3
2.3 13.8
2.4

13.8
2.4 12.7
2.6

!0.0001a !0.0001a

41.6
7.5 38.1
8.3

41.0
7.5 38.3
8.3

40.2
7.4 37.2
8.1

!0.0001a !0.0001a

11,048
4,095 12,108
4,487

11,543
4,060 12,567
4,449

9,651
3,864 10,667
4,298

!0.0001a !0.0001a

234
77 206
73

233,809
76,000 205,603
72,757

237,053
79,981 209,805
75,376

0.005a 0.015a

n [ 21,827

488
175 546
148 3.34 (1.1, 8.7)

482
176 538
192 3.92 (1.13,11.05)

503
168 566
173 3.0 (0.95, 7.91)

!0.0001a !0.0001a 0.273b

184
101 201
110

190
103 207
111

161
90 184
105

!0.0001a !0.0001a

7.3 (6.1,9.3) 43.3
26 51
33 (0.8,1.31) 1.1 (0.9, 1.5) 6.0
1.9 166
50.2 44
30 95
54 167
103 993 (285, 2335) 106 (40, 248) 17.8 (3.2, 132) 267 (116, 500)

7.39 (6.2,9.5) 42.6
25.3 49.8
30.6 1.00 (0.80, 1.31) 1.10 (0.90,1.50) 5.95
1.87 166
51 43.5
30 96.3
56.3 166.3
103.4 1260 (456, 2,705) 136 (54, 282) 27.6 (6.8, 244) 348 (135, 500)

7.25 (6.15, 8.77) 45.2
27.9 54.3
37.1 1.00 (0.80, 1.34) 1.1 (0.90, 1.53) 6.11
2.07 164
51 44.9
31 91.6
46.7 166.8
101.6 297 (108, 870) 45 (22, 103) 3.50 (0.26, 21.7) 169 (53.8, 443)

0.075b !0.0001a !0.0001a 0.629b 0.629b 0.05a 0.245a 0.229a 0.023a 0.884a !0.0001b !0.0001b !0.0001b 0.001b

STEMI, ST-elevation myocardial infarction; NSTEMI/UA, Non-ST-elevation myocardial infarction or Unstable angina; M
SD, mean
Standard deviation; Q, Quartile; HDL, high-density lipoprotein; LDL, high-density lipoprotein; CPK, Total creatinine phosphokinase; CK-MB, Creatinine kinase MB fraction; Q50, Quartile 50, Quartile 25, Quartile 75. a t Student. b U Mann Whitney.

ST segment (rule-out) as well as changes (rule-in), in whom invasive studies should not be delayed, in other words, the diagnostic and therapeutic procedures must be facilited (19). As expected, in our study the STEMI patients showed a higher elevation of high-sensitivity troponin that in our environment is becoming generalized just as is the use of the creatine phosphokinase fraction MB, only 80% of the STEMI group used high sensitivity troponin and there underutilization in the NSTEMI group, this can also explain the underdiagnosed of NSTEMI in medical centers. Although other biomarkers such as copeptin can complement rapid diagnosis, they are not used. High sensitivity C-reactive protein (hsCRP) on the other

hand, is the most commonly used in ACS diagnosis and prognosis as well as high-sensitivity troponin. They are used as a prognostic marker to guide NSTEMI early invasive treatment as well as a predictor of heart failure after an infarction (20). There are new inflammatory markers focused on the monoclonal antibodies treatment against C5 inhibitor of the p38 mitogen-activated protein kinase (21). In our study we found higher elevation of other pro-inflammatory markers such as fibrinogen and uric acid in the NSTEMI patients. In the ETIAM study we identified that fibrinogen levels higher than 500 mg/dl are predictors of MACE in STEMI patients, therefore, independently of ACS, this biomarker with greater accessibility, in addition

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Table 3. Medication at admission and discharge of the enrolled patients in the National Registry of Acute Coronary Syndromes at the IMSS (RENASCA IMSS) Total population Variable Aspirin Admission Discharge Clopidogrel Admission Discharge Enoxaparin Admission Unfractionated heparin Admission Oral nitrates Admission Discharge Intravenous nitrates Admission Statins Admission Discharge Fibrates Admission Discharge Beta-blockers Admission Discharge ACE inhibitors Admission Discharge ARB Admission Discharge ASA þ Statin þ ACEb Admission Discharge ASA þ Statin þ ACE þ BBb Admission Discharge Diuretics Admission Discharge Calcium antagonists Admission Discharge Amiodarone Admission Discharge Digoxin Admission Discharge Intravenous dobutamine Intravenous dopamine Intravenous levosimendan Oral glucose-lowering drugs Admission Discharge Insulin Admission Discharge

STEMI

NSTEMI/UA

n [ 15,981 (73.2%)

n [ 5,846 (26.8%)

p Value

19,344 (88.6%) 15,991 (72.8%)

14,152 (88.6%) 11,408 (71.4%)

5,192 (88.8%) 4,483 (76.7%)

0.306a !0.0001a

17,955 (82.3%) 14,400 (66.0%)

13,221 (82.7%) 10,475 (65.5%)

4,734 (81.0%) 3,925 (67.1%)

0.003a 0.028a

14,695 (67.3%)

10,972 (68.7%)

3,723 (63.7%)

!0.0001a

2,568 (11.8%)

1,896 (11.0%)

672 (11.5%)

3,525 (16.1%) 2,661 (12.2%)

2,404 (15.0%) 1,608 (10.1%)

1,121 (19.2%) 1,053 (18%)

!0.0001a !0.0001a

2,997 (13.7%)

1,995 (12.5%)

1,002 (17.1%)

!0.0001a

10,210 (46.8%) 13,683 (62.7%)

7,821 (48.9%) 9,919 (62.1%)

2,389 (40.9%) 3,764 (64.4%)

!0.0001a 0.002a

297 (1.9%) 258 (1.6%)

136 (2.3%) 191 (3.3%)

0.031a !0.0001a

10,185 (46.6%) 11,102 (50.9%)

6,983 (43.7%) 7,858 (49.2%)

3,202 (54.8%) 3,244 (55.5%)

!0.0001a !0.001a

10,822 (49.6%) 10,797 (49.4%)

7,690 (48.1%) 7,781 (48.7%)

3,132 (53.6%) 3,012 (51.5%)

!0.0001a !0.0001a

1,072 (4.9%) 1,154 (5.3%)

638 (4.0%) 632 (4.0%)

434 (7.4%) 522 (8.9)

!0.0001a !0.0001a

9,310 (42.7%) 9,405 (43.0%)

6,736 (42.2%) 6,862 (42.9%)

2,574 (44.0%) 2,543 (43.5%)

0.013a 0.459a

6,947 (31.8%) 7,680 (35.2%)

4,863 (30.4%) 5,528 (34.6%)

2,084 (35.6%) 2,152 (36.8%)

!0.0001a 0.001a

3,060 (14.0%) 2,803 (12.8%)

2,194 (13.7%) 1,972 (12.3%)

866 (14.8%) 831 (14.2%)

0.042a !0.0001a

916 (4.2%) 1,234 (5.6%)

616 (3.9%) 767 (4.8%)

300 (5.1%) 467 (8.0%)

!0.0001a !0.0001a

952 (4.4%) 544 (2.5%)

727 (4.5%) 376 (2.4%)

225 (3.8%) 168 (2.9%)

0.025a 0.030a

n [ 21,827

433 (1.9%) 449 (2.0%)

686 400 1,439 1,200 513

(3%) (1.8%) (6.6%) (5.5%) (2.3%)

265 271 1,152 951 395

(1.7%) (1.7%) (7.2%) (6.0%) (2.5%)

421 129 287 249 118

0.462a

(7.2%) (2.2%) (4.9%) (4.3%) (2.0%)

!0.0001a 0.013a !0.0001a !0.0001a 0.056a

754 (3.5%) 640 (2.9%)

306 (1.9%) 495 (3.1%)

448 (7.7%) 145 (2.5%)

!0.0001a !0.017a

2,522 (11.6%) 1,970 (9%)

1,865 (11.7%) 1,154 (7.2%)

657 (11.2%) 816 (14.0%)

0.389a !0.0001a

STEMI, ST-elevation myocardial infarction; NSTEMI/UA, Non-ST-elevation myocardial infarction or Unstable angina; ACE, Angiotensin Converting Enzyme; ARB, Angiotensin II receptor blockers; ASA, Acetylsalicylic acid; BB, b-blockers. a 2 c. b Single- components separately.

STEMI and NSTEMI Real-world Study

7

Table 4. Comparing complications in-hospital between the enrolled patients in the National Registry of Acute Coronary Syndromes at the IMSS (RENASCA IMSS)

Variable RBBB LBBB AV block Atrial fibrillation Ventricular fibrillation Ventricular tachycardia Killip Classification $2 Cardiogenic shock Mechanical complications Mitral regurgitation Septal rupture Free wall rupture Pericarditis Acute renal failure Angina Myocardial infarction Cerebrovascular accident Cardiovascular death MACE

STEMI

NSTEMI/UA

n [ 15,981 (73.2%)

n [ 5,846 (26.8%)

782 487 1,504 453 403 554 3,035 1,413 464 374 60 30 212 1,394 2,061 486 120 2,380 4,387

(4.9%) (3%) (9.4%) (2.8%) (2.5%) (3.5%) (19%) (8.8%) (2.9%) (2.3%) (0.37%) (0.18%) (1.3%) (8.7%) (12.9%) (3.0%) (0.8%) (14.9%) (27.5%)

375 342 218 148 90 156 1,249 431 209 201 6 2 33 389 1,271 202 40 442 1,809

(6.4%) (5.9%) (3.7%) (2.5%) (1.5%) (2.7%) (21.4%) (7.4%) (3.6%) (3.4%) (0.10%) (0.03%) (0.6%) (6.7%) (21.7%) (3.5%) (0.7%) (7.6%) (30.9%)

Odds ratio (CI 95%)

p Value

1.33 1.97 2.52 0.89 1.63 1.29 1.15 1.19 1.24

(1.17e1.51) (1.70e2.27) (2.19e2.89) (0.73e1.07) (1.30e2.05) (1.09e1.54) (1.07e1.24) (1.08e1.33) (1.05e1.47)

!0.0001a !0.0001a !0.0001a 0.243a !0.0001a 0.003a !0.0001a 0.001a 0.01a

2.3 1.31 1.87 1.14 0.91 1.97 1.18

(1.60e3.38) (1.17e1.46) (1.73e2.02) (0.96e1.34) (0.63e1.30) (1.78e2.17) (1.10e1.26)

!0.0001a 0.008a !0.0001a 125a 651a !0.0001a !0.0001a

STEMI, ST-elevation myocardial infarction; NSTEMI/UA, Non-ST-elevation myocardial infarction or Unstable angina; CI, confidence Interval; RBBB, Right bundle branch block; LBBB, Left bundle branch block; AV Atrioventricular; MACE, Major adverse cardiovascular events. a 2 c.

to hsCRP and high-sensitivity troponins are essential in the stratification and prognosis of these patients. In this regard, in patients with a NSTEMI diagnosis, since 2014, clinical practice guidelines (12) indicate that risk stratification crucial to the prognosis and allows to approach treatment strategy (invasive vs. symptomguided) and the most opportune time (early vs. late), so that high-risk patients are indicated with early invasive treatment (IA Class). GRACE score in high-risk patients is a highly predictive factor of death to 5 years, in the same way, moderate-risk patients showed a higher mortality compared to low-risk patients (8). In the first RENASCA study (3) in Mexican population, The GRACE score $150 points conferred in-hospital higher mortality and higher complications, being more evident in the STEMI patients. In the same way, the GRACE score was higher compared to other populations, especially in the NSTEMI patients. The immediate early invasive strategy (#2 h) in high-risk NSTEMI patients should follow a similar strategy to STEMI patients, while the early invasive strategy (#24 h) allows anticoagulation and PCI in centers with hemodynamic room or transferring them (12). Secondary prevention after an ACS is considered as a strategy at discharge, from changes in lifestyle, cardiac rehabilitation and adherence to treatment, which can modify the short and long-term outcomes. Compared to GRACE (91%) and EUROASPIRE IV (93%) studies (22), in our study Aspirin was prescribed in a lower proportion

at admission (88.7%) as well as discharge (74%), being even lower in STEMI patients; in the same way, statin was prescribed in a lower proportion (62%) than the observed in the OPERA study (80%) and EUROASPIRE IV (85%). When we evaluated the intensive therapy of secondary prevention with 3 drugs based on aspirin, statin and an ACE inhibitor, the prescription at discharge was reduced to 42.9 and 43.5% in STEMI and NSTEMI respectively without significant difference, being significantly lower when a beta blocker is added (34.6 vs. 36.8%, respectively). Aggressive therapy for secondary prevention has shown benefits mainly in the STEMI patients, although the mono components have reduced a new event between 25% to 30%, and it is attributed a greater adherence (23), to collect the components in a polypill (24) has been proposed and this level has been associated to the level of adherence (25) and studies are still being developed. Care networks in STEMI patients have shown an increase in PCI and an important reduction of mortality in European countries (26). In our country through the Code Infarction strategy as a care network, patients were mostly referred from the care networks, while NSTEMI patients came more often spontaneously. The majority of our registered patients corresponded to STEMI (real word evidence), this can be a consequence of the great attention to STEMI secondary to the recent implementation of Code Infarction. The natural history of ACS has been finaly changed in our country, was the regionalized therapeutic approach with the

8

Borrayo-S
anchez et al./ Archives of Medical Research

-

(2019)

-

Figure 1. One year Kaplan-Meier survival curve in global population according to type of SCA (STEMI versus NSTEMI).

implementation of the institutional strategy Code Infarction. The organization and effective communication through regional attention networks allowed to reduce the target time intervals, both the time of first contact and electrocardiogram, the door-to-needle time, as well as the doorto-balloon time; however, there is still much to be done in the total ischemia time. According to STEMI European guidelines, IA class instructions without discussion stablish to give the patients a reperfusion treatment in less than 12 h, but it is clearly that the quicker the patients is treated the better will be the outcome; PCI is preferred over fibrinolytic therapy when a hemodynamic room is available; nevertheless, fibrinolytic therapy must be performed in those centers far from a hemodynamic room; immediate PCI after fibrinolytic

therapy or pharmaco invasive strategy is recommended. Currently the increase in reperfusion, preferably with PCI has reduced mortality; however there are abysmal differences between low and intermediate income countries to high income countries. The future challenges will be to standardize and improve care times through care protocols applied in care networks; seek a complete revascularization, still controversial treat only the responsible artery or other vessels. The adjunctive therapy for ACS focused on antiplatelet treatment in NSTEMI patients in addition to stratifying the risk of cardiovascular events, is necessary to stratify the risk of bleeding, so that patients at high risk of bleeding and non-valvular atrial fibrillation (27); it is necessary to optimize the doses to achieve the net benefit (28). In our

Table 5. Reperfusion therapy in patients with ST-elevation myocardial infarction Treatment Did not receive any form of reperfusion Fibrinolytic therapy Primary PCI PCI, Percutaneous coronary intervention. a 2 c.

Before ‘‘Infarction Code’’ (n [ 7,466)

After ‘‘Infarction Code’’ (n [ 8,422)

p Value

4,866 (65.2%) 1,901 (25.5%) 699 (9.4%)

2,409 (28.6%) 3,381 (40.1%) 2,632 (31.3%)

!0.0001a

STEMI and NSTEMI Real-world Study

study, only 2.75% presented this type of arrhythmia in both ACS groups (601 patients), without any difference. However, we found a reduction in the prescription between admission and discharge of both aspirin (95 vs. 71.9%) and clopidogrel (89.4 vs. 64.4%) respectively, which allows us to identify an area of opportunity in adherence to the evidence from clinical practice guidelines to patient discharge (29), not only in the antiplatelet treatment but also in the handling of ACE and statins (30). In our real-world registry, cardiovascular death was higher in the STEMI patients group compared with the NSTEMI group, we believe it is secondary to receive more patients in a critical situation that previously (before infarction code). In-hospital major complications were frequent in a significant way in the STEMI patients group including the presence of cardiogenic shock (8.8 vs. 7.4%), severe arrhythmias such as ventricular fibrillation and ventricular tachycardia (2.5 vs. 1.5% and 3.5 vs. 2.7%, respectively), acute renal failure (8.7 vs. 6.7%), the glomerular filtration was not registered, and the calculation with formula was not done. However, the new angina events were more frequent in the NSTEMI group. Limitations of the Study The main limitations of the study are those corresponding to real-world studies.

Conclusions Real-world studies such as RENASCA IMSS, the largest ACS registry in Mexico, have demonstrated that the Mexican population has a high risk. Patients with a STEMI diagnosis were more frequently enrolled and were associated with higher mortality and complications. Despite of important improvements in the reperfusion therapy and into the mortality with the code infarction, this great challenge needs to be continued.

Acknowledgments IMSS Foundation, especially to its director, Patricia Guerra Melendez.

Conflict of Interest The authors declare no conflict of interest.

RENASCA IMSS Group Aguascalientes (Jos
e Luis Cruz-Valenciano), Baja Cali
fornia (Arturo Alvarez-Tostado Verdugo, Allan Guillermo Hern
andez-Aguilar, C
esar Alberto Figueroa-Torres, Jos
e

9

Luis Garc
ıa-Arcadia, Mart
ın Alejandro Dautt-Espinoza, Ram
on Rojo-L
opez, Abraham Mart
ınez, Fernando L
opezOrrantia, Francisco Javier Camacho-Reyes, Fabiola Mac
ıas-Corona), Baja California Sur (Marina FloresL
opez, Claudia Guadalupe Valdivia-Armenta, Jos
e S
anchez, Oscar Daniel Le
on-Beltr
an, Cesar ZamoraGarc
ıa, Karla Mar
ıa Morales-Gonz
alez), Campeche (H
ector Manuel Mena-Miranda, Gerardo G
amez-Almaraz), Coahuila (Ana Isema ramos-S
anchez, Rub
en Valdez-D
ıaz, Mar
ıa Berenice Escobedo-Rosales, Manuel CuerdaMart
ınez, Leticia Isabel Samaniego-R
ıos, Matilde Jim
enez-Bautista, Claudia Catalina Rodr
ıguez-Tenorio, Mar
ıa Carmen Garc
ıa-Garc
ıa), Colima (Luis Cortes-Villa, Jos
e Mart
ın G. Villafa~na-Ledezma, Levi Sem Fern
andezCasillas, Faustino Villalvazo-L
opez), Chiapas (Jorge Manuel Alegr
ıa-S
anchez, Jos
e Marcos-Mart
ınez, Rub
en Hilemo-Armegol, Maria Magdalena Pola-Velazquez, Fernando Dom
ınguez-Salgado, Mart
ın Aquiles L
opez-G
omez, Mar
ıa de la luz Hidalgo-Trinidad, Brenda del Carmen Le
on-Rodr
ıguez, Francisco Ricardo Escobar-Diaz, Gustavo V
azquez-N
u~nez, Efra
ın Le
on-Gamboa, Edgar CarreraCamacho, Francisco Javier Hern
andez-N
u~nez), Chihuahua (Martha Avitia-Talamantes, Jorge Arturo-Torres, Carlos
Carmona-Barr
on, Omar Fierro, Miguel Angel ArredondoVizcarra, C
esar Humberto Neave-Valenzuela, Fabiola Rivera-Rojo, Ra
ul E. Gutierrez-Aguirre, Nohem
ı Romo, Andr
es Ju
arez-A., Jorge Alberto Granados, Claudia RezaRam
ırez, Manuel Ortiz, Bertha Alicia Herrera-Pi~n
on, Luis Arturo Valles-R., C
esar Dionisio-Decanini), D. F. Norte
(Jos
e Angel Baltazar-Torres, Ernesto Garc
ıa-Hern
andez, Miguel Russi-Hern
andez, Germ
an Arias-Rebatet, Lilia
Vega-Cervantes, Angel Miranda-Betancourt, Antonio Gilberto G
omez-Castro, Pedro Jos
e G
omez-Casanova), D. F. Sur (Jose Lu
ıs Aranza-Aguilar, Eduardo Almeida-Guti
errez, Javier Fernando Antezana-Castro, Carlos Ernesto Castillo-Herrera, Arturo Hern
andez-Paniagua, Juan RosasPe~na, Sergio Lozada-Andrade, Sergio Ra
ul GuillenEspinosa, Gildardo Normando Cano-Manzano, Gabriel Ch
avez-Covarrubias, Francisco Javier Padilla-Del Toro, Alberto Rosendo-Ru
ız, Jos
e Luis Montes-Cervantes, Susana Trejo-Ru
ız), Durango (Juan Jos
e Viesca Gaona, Jos
e Valeriano Ib
a~nez-De la Rosa), Estado de M
exico Oriente (Miriam Victoria S
anchez-Castro, Arturo Gonz
alez-Agui~ naga, Pedro Luis Vargas-Guti
errez, Pedro Oscar Rodr
ıguez
Cabrera, Pedro Franco-Segura, Genaro Angel CuazochpaDelgadillo, Rafael Villanueva-Romero, Jos
e C
esar Vel
azquez-Castillo, Mar
ıa Rosalina Madera-Ba~ nuelos, Ram
on Armando S
anchez-Tamayo, Elizabeth Ram
ırezCh
avez), Estado de M
exico Poniente (Javier Ulises Andere-Montes de Oca, C
esar Douglas Pazar
an-Montelongo, Erick Augusto Serrano-S
anchez, Ernesto D
ıaz-G
omez, Rodolfo Hern
andez-Ru
ız), Guanajuato (Karla Janet IslasSoriano, Pedro Gonzalez-Carrillo, Gustavo Enrique Morales-Jacome, Jos
e Manuel Ju
arez, Manuel CaudilloPe~na, Manuel P
erez-Gir
on, Guadalupe Ulises Garc
ıa-

10

Borrayo-S
anchez et al./ Archives of Medical Research

Zavala, Victor Hugo P
erez-Nieto, Medardo Mojica, Tania P
erez-Rend
on, Fernando Couto, Carmen Rodr
ıguez-Denis, Miguel Gonz
alez, Sandra Ivette Miranda-Ochoa, Rigoberto P
erez-Benites), Guerrero (Tom
as Hern
andez-Quijano, Edgar Balbuena-Herrera, Oscar Alfaro-Santos, Rub
en Dar
ıo Meza-Rend
on, David Ruanova-Le
on, Esperanza
Ortigoza-Campos, Evelia Barrera, Mar
ıa de los Angeles Tejeda-Rodr
ıguez, Minerva Gatica-Medina, Maricela Gonz
alez, Mirna Mart
ınez, Mar
ıa del Refugio OteroVargas), Hidalgo (Jesus Angel Quintero-Ram
ırez), Jalisco (Jose de Jesus Gonz
alez-Izquierdo, Roberto RojasCastillo, Ram
on Ivan De Dios-P
erez, Jos
e Fredy RaigosaHern
andez, Mar
ıa Rosalina Orozco-P
erez, Oliver S
anchez-Castellanos, V
ıctor Vicente Gauna-Ru
ız de Le
on, Luis Gonzalo Meines-Orozco, Lilia del Carmen Guti
er
rez-Mora, Guillermo Alvarez-Zambrano, Luis Ricardo
Rea-Asencio, Susana Beas-Roque, Juan Reynaldo AngelZ
u~ niga, Sa
ul Sigala-Jim
enez, Enrique Rubio-Nolasco, Carlos Ernesto Gonz
alez-Enr
ıquez, Wuilberto Guti
errezAstorga, Pedro Carrillo-Mart
ınez, Marco Antonio Rodr
ıguez-Pe~ na, Rommel Andr
es V
azquez-Bernal, Guillermo Velazco-Brise~ no, Claudia Gudelia Cadena-Ortiz, M
onica Maricela Castellanos-Tadeo, Luis Antonio RicoCarrizales, Miguel Calleros-Mariscal), Michoac
an (Rom
an Acosta-Rosales, Mario Alberto Mart
ınez-Lemus, Eber Ram
ırez-Oley, Jos
e Guadalupe Rodr
ıguez-Vargas, Francisco Monsibaiz-Salinas), Morelos (Victor Manuel V
azquez-Z
arate, Filiberto Linaldi-Yep
ez, Jos
e Miguel Montiel-Rojas, Armando Ortiz-Guemes, Raul AguilarLara, Araceli Ruiz-Carballo), Nayarit (Misael Ley-Mej
ıa, Miguel Calleros-Mariscal, Abel Mu~ noz-Arreola, Ma. De
los Angeles Monjaraz-M
endez), Nuevo Le
on (Maria Guadalupe Garza-Sagastegui, Guillermo Sahagun-S
anchez, Jorge Garc
ıa-Aguilar, Juan Francisco Vargas-Ram
ırez, Oddir Jauregui-Ruiz, Mayela Azuara-Castillo, Oscar Omar Barajas-Castillo, Carlos Alejandro Delgado-Cort
es, Gerardo Quintanilla-V
azquez, Graciano de la Fuente-Reta, Francisco Javier L
opez-Tuxpan, Timoteo Coyoc-Vivas, Alejandro L
opez-Villareal, Berna Barrera-Oliveros, Jessica Antonia Aguilar-Hern
andez, Lizbeth Alejandra Dur
an-Cavazos, Gerardo Ram
ırez-Sandoval, Ana Mar
ıa Jim
enezBenavides, Jorge Aguilar- Ponce, Adri
an Francisco Espinosa-Reyna, Cynthia Yosheida C
ardenas-Urquizo, Nora Aid
e Celada-Ram
ırez, Sandra Luz D
ıaz-Rinc
on, Oaxaca (Victor Manuel San Pedro-Suarez, Perla VasquezAltamirano, Edgar Moreno-Rubio de Celis, Edgar Rodr
ıguez-Villanueva, Juan Carlos D
avila-Fern
andez), Puebla (Eduardo Ram
on Morales-Hern
andez, Gonzalo Tolosa-Dzul, Luis Leodegario Peynado-Gooldbowne, Adolfo Carrillo-R
ıos, Marco Antonio Villase~ nor-Villa, Elia Martha Santana-Vergara, Jose David L
opez-Borgolla, Jos
e Dom
ınguez-Naranjo, Guillermo Hern
andez-Guzm
an, Silvia Romero-Cervantes), Quer
etaro (Jesus Javier Magallanes-Camacho, Marycroof Nancy Ortiz-Pereyra, Juana Ang
elica Garc
ıa-Bonilla, Ernesto Pombo-Bartelt),

-

(2019)

-

Quintana Roo (Enrique Leobardo Ure~na-Bogar
ın, Mois
es Alejandro Toledo-Pensamiento, Mar
ıa Margarita ChavezHernandez, Mart
ın S
anchez-Alva, Araceli Gonz
alezFondon, Bardo Javier Velez-Garc
ıa, Crysehelen Jim
enez-Aguilar, Lino A. Guzman-D, Jesus MateosL
opez), San Luis Potos
ı (Jaime Enrique Manzano Lim
on, Beatriz Leonor Fern
andez Ruiz, Lucio Correa Sosa, Francisco Javier Venegas Ledesma, Ver
onica Viveros Vega), Sinaloa (Sergio Oswaldo Pacheco-Calder
on), Sonora (Cruz M
onica L
opez-Morales, Santiago Sandoval-Navarrete, Javier Alejandro Salas-Anaya, Roc
ıo Guadalupe Valadez Zamora, Jos
e Carlos Antonio D
ıaz-Paz, Javier Ignacio Arce-Corral, Jes
us Ram
on Osuna-Casta~neda, Erasmo Melo-L
opez, Jes
us Aar
on L
opez-Boj
orquez, Jos
e Sergio GilSamaniego), Tabasco (Luis Gerardo Ochoa-Jimenez, Jeslia Torres-Morales, Carlos Blaisdell-Vidal, Beatriz Adriana Jim
enez-Velasco, Marcos David Castillo-V
azquez, Eduardo Contreras-P
erez, Irma Dinorah Castillo-Almeida, Adriana Hern
andez-Camas, Oscar Manuel Cort
azar-Calasich, Mar
ıa Magdalena Zenteno-Ram
on, Yunia Mar
ıa RamosQuevedo, Jos
e Francisco Flores-De la Mora), Tamaulipas (Raul De Le
on-Escobedo, Karina Silva Vera, Hugo Palomino-Espinosa, Manuel Vergara-Lozano, Felipe Guarneros-S
anchez), Tlaxcala (Arturo Navarrete-S
anchez, Mar
ıa Luisa Ru
ız-Tirado, Marco Polo-Ballinas), Veracruz Norte (Mario Ram
on Mu~noz-Rodr
ıguez, Vicente Espinosa-Rico, V
ıctor Bernal-Dolores, Elvira Garc
ıaCordero, V
ıctor Manuel Gonz
alez-Arreola, Miguel Quiroga-Herrera, Israel Alejandro Hern
andez-Rivera, Mar
ıa Antonieta Garc
ıa-Tapia, Jos
e Aguilera-Campos, Indi D
ıaz-S
anchez, Alfonso Garc
ıa-Rodr
ıguez, Sergio Adri
an Lima-Ben
ıtez, Alma Delia Ruedas-Zamudio, Margarito Le
on-Caba, Carolina P
erez-G
omez, Alfredo AlmendraMeri~no, Victor Hugo Flores-Marin, Artemio Hern
andezTorres, Claudia Andrea Fern
andez-Acosta), Veracruz Sur (Carlos Alberto Flores-Aguilar, Oscar Enr
ıquez-Palomec, Juan Jes
us Lasserre-Boa, Francisco Castro-Ortiz, Juan Gabriel Pachuque~no-Miranda, Pedro Mart
ınez-Serena), Yucat
an (Luis Fernando Aguilar-Castillejos, Arturo Sebasti
an Jim
enez-Chale, Roberto Betancourt-Ortiz, Jacinto HerreraLe
on, V
ıctor Daniel Aldaco-Garc
ıa, Alberta BautistaBotello), Zacatecas (Gerardo Manuel-Sauceda-Mu~noz).

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