Risk Factors, Therapeutic Approaches, and In-Hospital Outcomes in Mexicans With ST-Elevation Acute Myocardial Infarction: The RENASICA II Multicenter Registry

Authors

  • Úrsulo Juárez-Herrera MD, FACC,

    Corresponding author
    • Coronary Unit (Juárez-Herrera), National Institute of Cardiology “Ignacio Chávez,” Mexico City, Mexico; Institute of Cardiology and Vascular Medicine (Jerjes-Sánchez), Tec-Salud. Monterrey Institute of Technology and Higher Education. Nuevo León, Mexico
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  • Carlos Jerjes-Sánchez MD, FACC,

    1. Coronary Unit (Juárez-Herrera), National Institute of Cardiology “Ignacio Chávez,” Mexico City, Mexico; Institute of Cardiology and Vascular Medicine (Jerjes-Sánchez), Tec-Salud. Monterrey Institute of Technology and Higher Education. Nuevo León, Mexico
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  • and The RENASICA II Investigators

    1. Coronary Unit (Juárez-Herrera), National Institute of Cardiology “Ignacio Chávez,” Mexico City, Mexico; Institute of Cardiology and Vascular Medicine (Jerjes-Sánchez), Tec-Salud. Monterrey Institute of Technology and Higher Education. Nuevo León, Mexico
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  • The authors have no funding, financial relationships, or conflicts of interest to disclose.

Address for correspondence:

úrsulo Juárez Herrera, MD, FACC

Coronary Unit, National Institute of Cardiology “Ignacio Chávez”

Juan Badiano No. 1, Col. Secc. XVI

Mexico City, 14080 Mexico

ujuarez@webmedica.com.mx

Abstract

Background

Ischemic heart disease is a growing health problem in Latin America. We aimed to analyze risk factors, acute management, and short-term outcome of Mexicans with ST-elevation myocardial infarction (STEMI).

Hypothesis

Modifiable risk factors are associated with the occurrence of STEMI in Mexicans, and potentially preventable acute complications are responsible for most short-term deaths.

Methods

Among 8600 patients enrolled in Registro Nacional de los Síndromes Coronarios Agudos II (RENASICA II) with a suspected acute coronary syndrome, we analyzed 4555 patients (56%; age 21–100 y) with confirmed STEMI who presented within 24 hours from symptoms' onset.

Results

Smoking (66%), hypertension (50%), and diabetes (43%) were the main risk factors. Most patients (74%) presented with Killip class I (class IV in 4%). Anterior-located STEMI occurred in 56% of cases, and posterior-inferior in 40% of cases. Significant Q waves were present in 43%, right bundle branch block in 7%, left bundle branch block in 5%, first-degree atrioventricular block in 2%, and high-degree atrioventricular block in 2%. A total of 1685 (37%) patients received fibrinolytic therapy (streptokinase, 82%; alteplase, 17%; tenecteplase, 1%), with 31% of patients receiving therapy in <2 hours, 36% in 2–4 hours, 19% in 4–6 hours, and 15% in >6 hours. Thirty percent of patients received either percutaneous coronary intervention or coronary artery bypass grafting during hospitalization. Major adverse cardiovascular events were recurrent ischemia (12%), reinfarction (4%), cardiogenic shock (4%), and stroke (1%). The main predictors of 30-day mortality (10%) in multivariate analysis were age ≥65 years (odds ratio [OR]: 2.47, 95% confidence interval [CI]: 1.94-3.13), Killip class IV (OR: 10.60, 95% CI: 6.09-18.40), and cardiogenic shock (OR: 18.76, 95% CI: 10.60-33.20).

Conclusions

Largely modifiable risk factors and preventable short-term complications are responsible for most STEMI cases and outcomes in this Mexican population.

Introduction

Cardiovascular diseases are the leading cause of death worldwide, with disproportionate representation in low- and middle-income countries (LMICs).[1-3] In Mexico, ischemic heart disease is emerging as the No. 1 cause of death in the elderly and the No. 2 cause in the general population. In 2008, ischemic heart disease was responsible for 59 801 deaths, accounting for approximately 11% of all deaths in Mexico.[4-6]

Recent case–control studies investigating risk factors for myocardial infarction (MI) in Latin America have highlighted the relevance of this rapidly growing health problem.[4-9] High-quality observational studies have provided important insights into the characteristics, treatments, and outcomes for patients with acute coronary syndromes (ACS) treated in everyday clinical practice.[10-12] However, these data may not be generalizable to LMICs.[5, 6] Although observational studies complement information from randomized controlled trials, historically they have been restricted largely to Western populations.[13] Only very recently have observational studies on ACS been conducted in Mexico.[14-16] The largest ACS registry in Mexico and Latin America is the Registro Nacional de Síndromes Coronarios Agudos II (RENASICA II).[14-16] This study has provided important and reliable information on risk factors for ST-elevation myocardial infarction (STEMI) in the Mexican population. The purpose of the present analysis of the RENASICA II registry is to describe the procedures of acute hospital management that reflect everyday clinical practice in Mexico and to identify risk factors associated with in-hospital outcome. A further objective of this article is to compare the epidemiological characteristics between RENASICA II and other recent registries across different populations.

Methods

RENASICA II is a prospective observational registry designed and conducted by the Mexican Cardiology Society. The main objective is to provide insights into risk factors and clinical characteristics, use of diagnostic resources, risk stratification, acute treatments, and hospital outcomes in patients hospitalized with ACS. Seventy-six investigators in 60 hospitals enrolled ACS patients in this registry. Investigators were emergency-department physicians (mainly cardiologists, internal-medicine physicians and emergency-medicine professionals) who evaluated patients with acute chest pain and who were responsible for patient diagnosis, risk stratification, and treatment. Both primary-care and referral hospitals participated in this study. With the aim of studying a nonselected population, the medical centers involved varied in terms of access to on-site cardiac-catheterization facilities, number of acute-care beds, and type of practice. Investigator meetings were held for standardization of diagnostic criteria, data capture, and patient follow-up, but all treatment decisions were the responsibility of the managing physicians. The protocol was submitted to the institutional review boards of the participating centers. Informed consent was obtained from every patient or the legal proxy.

Patients with characteristics of STEMI on electrocardiogram (ECG) and who presented within 24 hours from symptoms' onset were eligible for enrollment. We performed systematic registering of consecutive subjects presenting with ACS symptoms and persistent significant ST-segment elevation on the ECG, defined as positive ST in 2 adjacent leads (≥0.1 mV for leads I through III, aVF, aVL, and V4 through V6; and ≥0.2 mV for leads V1 through V3), as recorded in the first ECG at hospital arrival. The diagnosis of STEMI was confirmed by the presence of biomarkers of myocardial necrosis and characteristic evolving changes on the ECG (mostly the appearance of Q waves). The presence of ischemic heart disease was confirmed on invasive or noninvasive tests. Patients were excluded if they had symptoms precipitated by anemia, hypertension, or heart failure. All treatment decisions were made at the discretion of the treating physicians. To ensure the collection of high-quality data, criteria proposed by Alpert were followed in designing the study. They are, in brief: (1) use of standardized definitions; (2) careful hospital selection; (3) adherence by participating hospitals to local policies in the collection of data; (4) reporting of all collected data; (5) centralization of completed electronic case-report forms; (6) involvement of a professional statistician to monitor data collection and analyses; (7) careful examination of all case-report forms by a central data center; and (8) involvement of a principal investigator and a steering committee to maintain administrative order, adjudicate inconsistencies, and encourage timely submission of documents and performance of data analyses.[13] All investigators underwent a training program for data collection and entry and were provided with a standardized manual that included the study protocol and operational definitions. In addition, clinical monitoring visits were scheduled and sites selected for audit following a randomized approach.[16] Electronic and paper case-report forms, developed by CyberWorks Inc. (Green Bay, WI, USA), were submitted to the central data center (Hospital of Chest and Cardiovascular Disease, Number 34, Mexican Institute of Social Security [IMSS], Monterrey, Nuevo León, Mexico) through a secure Web site by e-mail, compact disc, or another portable electronic file by ordinary mail.

Data were collected on patient demographics (age, sex, height, weight, socioeconomic status, smoking habit, physical activity, dietary patterns, psychosocial factors), personal and family medical history of cardiovascular disease, and traditional risk factors (eg, hypertension, diabetes mellitus (DM), hypercholesterolemia, and history of vascular disease, among other risk factors). Current smokers were defined as those who had smoked tobacco in the previous 12 months and former smokers as those who had stopped smoking >12 months earlier. Patients were considered physically active if they were involved in moderate or intense levels of systematic activity for at least 5 hours per week. Habitual alcohol intake was defined as the consumption of >2 alcoholic beverages ≥3 days per week. We recorded data on the patient clinical status, vital signs at admission, laboratory data, inflammation markers, ECG findings, use of antithrombotic and fibrinolytic therapy, additional cardiovascular disease treatments, risk stratification, invasive and noninvasive procedures, adverse events, and in-hospital outcomes. In-hospital outcome was analyzed through major adverse cardiovascular events, including death, recurrent ischemia, acute MI, reinfarction, shock, and stroke. These events were assessed within 30 days after ACS onset through active rounds and medical-records review during hospitalization, as well as scheduled telephone calls and follow-up visits with survivors within days 30 and 35 after ACS if the hospital discharge occurred before that time. Any readmission was systematically registered in the case-report form and major events consigned, including fatalities. In case of discharge and latter readmission due to a study's cardiovascular event, the patient's RENASICA code was used to retrieve the study records for describing events in detail in open format and focused investigational questions (eg, length of stay [LOS], final in-hospital outcome, treatments used, and further complications). Cases of death at home or during transition toward the managing centers were investigated for related causes based on review of symptoms, sequence of events, and autopsy (if available). Blood samples, physiological tests, and imaging studies were processed and interpreted in the local hospitals and recorded in case-report forms. Any discrepancy between paraclinical records and the rest of the clinical information was discussed directly with the local investigator by members of the Steering Committee.

Statistical Analysis

Continuous parametric variables are reported as means and standard deviations (SDs), and nonparametric variables as medians and interquartile ranges. Relative frequencies were used for categorical data. A binary forward stepwise logistic regression model was constructed to identify independent variables associated with in-hospital mortality. All variables associated with mortality in univariate analysis with a significance cutoff of P < 0.10 were selected for adjustment in the multivariate analysis. After the final step of the model, P < 0.05 was considered to be significant. Adjusted odds ratios (ORs) with 95% confidence intervals (CIs) are provided. All statistical analyses were 2-tailed and performed using GB STAT version 6.5 (Dynamic Microsystems, Inc., Silver Spring, Maryland).

Results

From December 2002 to November 2003, 8600 patients with suspected ACS were enrolled in the RENASICA II study. Of these, 502 patients were excluded due to unspecified chest pain. Of the remaining 8098 patients, 3543 (43.7%) were diagnosed with non–ST-elevation ACS (NSTE-ACS) and 4555 (56.3%) with STEMI (age range, 21–100 y), herein described. Comparing the initial clinical suspicion with study criteria, the diagnostic accuracy for NSTE-ACS and STEMI was 82% and 89%, respectively. On the contrary, in patients who presented with initial diagnosis of unspecified chest pain, 16% had a final diagnosis of ACS. Patients were enrolled at 60 (90%) hospitals (48% public-health-system hospitals, 39% private hospitals, and 12% teaching hospitals from other health systems). Almost half (48%) of the patients were enrolled in Mexico City. Tertiary-care hospitals (35%) with access to coronary angiography, percutaneous transluminal coronary angioplasty, and coronary artery bypass grafting (CABG) enrolled 90% of the patients.

Risk Factors and Clinical Presentation

Table 1 shows the main population descriptive data of this STEMI RENASICA II analysis (n =  4555). The most prevalent risk factors were smoking (66%), hypertension (50%), DM (43%), and hypercholesterolemia (26%). A history of previous MI was present in 23%. On admission, most patients (85%) had typical ischemic chest pain with clinical stability (Table 1). Atypical chest pain was observed in 9% of the patients. Only 1% of patients with STEMI presented without chest pain. Seventy-four percent of patients presented with Killip class I (class II, 17%; class III, 5%; and class IV, 4%).

Table 1. Baseline Characteristics of STEMI Patients From the RENASICA II Study (N =  4555)
VariableValue
  1. Abbreviations: ACE, angiotensin-converting enzyme; ASA, aspirin; BP, blood pressure; CABG, coronary artery bypass grafting; CCB, calcium channel blockers; DM, diabetes mellitus; HTN, hypertension; LMWH, low-molecular-weight heparin; MI, myocardial infarction; PAD, peripheral artery disease; PCI, percutaneous coronary intervention; PTCA, percutaneous transluminal coronary angioplasty; RENASICA II, Registro Nacional de Síndromes Coronarios Agudos II; SD, standard deviation; STEMI, ST-elevation myocardial infarction; UFH, unfractionated heparin.

  2. a

    High-risk STEMI was considered as a large ischemic area at risk for cardiogenic shock.

Age, mean ± SD, y62 ± 12
Male sex77
Medical history, % 
        Angina pectoris33
        DM43
        Smoking66
        Heart failure3
        Hypercholesterolemia26
        HTN50
        MI23
        PAD2
        Renal failure2
        Stroke2
        PTCA6
        CABG2
Chest pain on admission, % 
        Typical85
        Atypical9
Systolic BP, mean ± SD, mm Hg125 ± 27
High-risk STEMI, %a 
        Anterior56
        Inferior/posterior40
        Other4
In-hospital treatment, % 
        ASA88
        ACE inhibitors64
        Angiotensin II inhibitors7
        Beta-Blockers (oral)51
        CCB12
        Glycoprotein IIb/IIIa inhibitors16
        UFH54
        LMWH44
        Nitrates66
        Oral anticoagulation0.4
        Statins14
        Thienopyridines41

Electrocardiogram Findings

The first ECG demonstrating acute ischemia was recorded in this registry obtained either before arrival or at hospital presentation. The anterior-location ischemia occurred in 56% of patients, and in 40% of patients the location was inferior-posterior. A significant Q wave was present on first ECG in 43%. Conduction-system abnormalities were present in 21% of patients: right bundle branch block in 7%, left bundle branch block in 5%, high-degree atrioventricular block in 2%, and first-degree atrioventricular block in 2% (Table 2).

Table 2. ECG Findings and Further Invasive and Noninvasive Diagnostic and Therapeutic Procedures in STEMI Patients From the RENASICA II Study (N =  4555)
VariableRelative Frequency (%)
  1. Abbreviations: AF, atrial fibrillation; AV, atrioventricular; CABG, coronary artery bypass grafting; CT, computed tomography; ECG, electrocardiogram/graphic; IABP, intra-aortic balloon counterpulsation; LBBB, left bundle branch block; RBBB, right bundle branch block; RENASICA II, Registro Nacional de Síndromes Coronarios Agudos II; STEMI, ST-elevation myocardial infarction; SVT, supraventricular tachycardia; TEE, transesophageal echocardiogram; TTE, transthoracic echocardiogram; VAD, ventricular assist device.

ECG findings 
        RBBB7
        LBBB5
        First-degree AV block2
        Second-degree AV block2
        AF3
        SVT1
        Ventricular extrasystoles3
        Ventricular tachycardia1
        Ventricular fibrillation1
Invasive procedures 
        Coronary angiography44
        Angioplasty27
        CABG4
        Transitory pacemaker9
        Permanent cardiac pacing0.4
        Mechanical ventilation7
        Swan-Ganz monitoring5
        IABP3
        VAD0.2
Noninvasive procedures 
        TTE47
        Stress test8
        Cardiac CT scan6
        Noninvasive ventilation2
        TEE2
        Stress ECG1

Biochemical Markers

Total creatine kinase (T-CK) and specific myocardial CK (MB-CK) measurements were obtained in 4512 (99%) and 3,681 (81%) patients, respectively. The T-CK and MB-CK were >3× the normal range in 57% and 55% of patients, respectively; between 1.5 and 3.0× the normal range in 19% and 20%, respectively; and <1.5× the normal range in 24% and 25%, respectively. A rapid qualitative troponin (Tn) I assay was obtained in 15.6% (n =  712) and was positive in all cases.

Pharmacological Treatment

The most frequently used drugs during acute hospitalization were aspirin (88%), nitrates (66%), angiotensin-converting enzyme inhibitors (64%), unfractionated heparin (54%), oral β-blockers (51%), and low-molecular-weight heparin (44%) (Table 1). Among patients under low-molecular-weight heparin treatment, enoxaparin was the most frequently used. Ticlopidine and oral anticoagulation were infrequent.

Reperfusion Therapy

A total of 1685 (37%) patients received fibrinolytic therapy. The elapsed time from symptoms'onset to lytic administration (ie, total ischemia time) was <2 hours in 31% of cases, 2–4 hours in 36%, 4–6 hours in 19%, and >6 hours in 15%. Streptokinase was the most frequent fibrinolytic regimen used (82%), followed by alteplase (17%). Tenecteplase were used only in 1% of patients. In the acute period, 34% of patients did not receive any reperfusion therapy, 10% received deferred percutaneous coronary intervention (PCI), and 4% received CABG (Table 2). Primary PCI was performed in 15% of cases. The overall rate of revascularization during index hospitalization by either PCI or CABG was 30% (n =  1366). Invasive and noninvasive procedures performed during hospitalization are shown in Table 2. Among 1234 patients who received angioplasty and stenting, a successful procedure was observed in 1049 cases (85%), failure was observed in 99 (8%), and a suboptimal outcome was observed in 74 (6%); this information was missing in 22 cases. In 3416 coronary angiograms of STEMI patients, the findings were occlusion of the left anterior descending artery in 65%, the right coronary artery in 53%, the circumflex artery in 37%, the left main coronary artery in 5%, and bypass occlusion in 1%. Transthoracic echocardiograms were performed in 47% of patients.

Major Adverse Cardiovascular Events and In-Hospital Outcome

Among 4555 STEMI patients, the global 30-day case fatality rate was 10% (Table 3). Hospital LOS had a median of 8.1 days. Major adverse cardiovascular events in the STEMI group occurred as follows: recurrent ischemia in 12%, acute MI/reinfarction in 4%, cardiogenic shock in 4%, and stroke in 1%. Other in-hospital cardiovascular outcome measures are shown in Table 3. A logistic regression analysis performed to identify independent variables associated with 30-day case fatality is shown in Table 4. The strongest predictors were cardiogenic shock, Killip class, stroke, and age.

Table 3. MACE and In-Hospital Outcome in STEMI Patients From the RENASICA II Study (N =  4555)
OutcomeRelative Frequency (%)
  1. Abbreviations: CV, cardiovascular; MACE, major adverse cardiac events; RENASICA II, Registro Nacional de Síndromes Coronarios Agudos II; STEMI, ST-elevation myocardial infarction; VF, ventricular fibrillation; VT, ventricular tachycardia.

MACE 
        Case fatality rate10
        Recurrent ischemia12
        Reinfarction4
        Cardiogenic shock4
        Stroke1
In-hospital CV outcome 
        Heart failure8
        Acute pulmonary edema5
        VT5
        Mitral regurgitation2
        Interventricular septal rupture0.3
        Pericarditis2
        Cardiac arrest6
            VF4
            Sustained VT1
            Other nonspecified1
In-hospital bleeding complications 
        Major1
        Minor2
Other 
        Hypotension secondary to fibrinolytic therapy6
        Acute renal failure5
        Sepsis1
Table 4. Multivariate Analysis on Predictors of 30-Day Mortality in STEMI Patients From the RENASICA II Study (N =  4555)a
VariableAdjusted OR (95% CI)P Value
  1. Abbreviations: AV, atrioventricular; CI, confidence interval; CV, cardiovascular; DM, diabetes mellitus; HTN, hypertension; LBBB, left bundle branch block; OR, odds ratio; RENASICA II, Registro Nacional de Síndromes Coronarios Agudos II; STEMI, ST-elevation myocardial infarction. aModel adjusted for sex, CV risk factors (obesity, DM, HTN, and hypercholesterolemia), in-hospital events (infections, bleeding, heart rupture, and arrest), and reperfusion strategies.

Age ≥65 years2.47 (1.94-3.13)<0.001
Variables at hospital presentation  
Killip-Kimball class IV10.60 (6.09-18.40)<0.0001
      High-degree AV block2.99 (2.00-4.46)<0.0001
      Inferior ST elevation1.95 (1.04-3.92)0.02
      LBBB1.72 (1.16-2.56)0.007
Major in-hospital CV events  
      Cardiogenic shock18.76 (10.60-33.20)<0.0001
      Stroke7.38 (2.06-26.37)0.002
      Reinfarction3.48 (1.80-6.70)0.0002

Discussion

The RENASICA II is the largest registry of ACS in Latin America and provides important insights on risk factors and quality of care in this part of the world.[15-17] Here we found that STEMI is the most important cause of hospitalization in ACS patients and lytic therapy is the most frequent reperfusion strategy, with a revascularization rate of 30%. Our data are comparable with those of the Acute Coronary Events—a Multinational Survey of Current Management Strategies (ACCESS) registry (Tables 1 and 5),[11] a multinational observational study on ACS in LMICs, which included Mexican patients. The most important risk factors were smoking, hypertension, DM, and hypercholesterolemia. However, the influence of other growing risk factors such as abdominal obesity, stress, lack of regular exercise, depression, consumption of vegetables and caffeine, economics, and education were not assessed in this registry. For comparison, the most important risk factors in the INTERHEART study (Effect of Potentially Modifiable Risk Factors Associated With Myocardial Infarction in 52 Countries),[7] a Latin American case–control registry (n =  3125) with a small participation of Mexican subjects (n =  25), were abdominal obesity, dyslipidemia, and smoking. A Costa Rican study[8] identified other risk factors as caffeine intake and abdominal obesity, as well as the protective effect of a healthy diet and increased physical activity. In Mexico, the prevalence of these risk factors in STEMI patients is yet unknown but will be addressed in RENASICA III. Another important difference with these studies was the higher prevalence of DM in RENASICA II (43%) as compared with the ACCESS[11] (33%) and INTERHEART[9] (7.2%) studies. Nevertheless, this prevalence of DM in Mexicans with atherothrombotic disease is consistent with that previously observed in other registries.[5, 6]

Table 5. Comparative Data on the Largest ACS Registries, in Alphabetical Order
RegistryMain Characteristics
STEMI (%)NSTEMI (%)Mean Age (y)Men (%)Smoking (%)DM (%)HTN (%)DLP (%)ITD (min)Lytics (%)tPA (%)SK (%)PPCI (%)30-Day Mortality, STEMI (%)30-Day Mortality, NSTEMI (%)
  1. Abbreviations: ACCESS, Acute Coronary Events—a Multinational Survey of Current Management Strategies; ACS, acute coronary syndrome; CREATE, treatment and outcomes of acute coronary syndromes in India; DLP, dyslipidemia; DM, diabetes mellitus; EHS, Euro Heart Survey; GRACE, Global Registry of Acute Cardiac Events; HTN, hypertension; ITD, ischemia time delay; NA, not available; NRMI, National Registry of Myocardial Infarction; NSTEMI, non–ST-elevation myocardial infarction; PPCI, primary percutaneous coronary intervention; RENASICA II, Registro Nacional de Síndromes Coronarios Agudos II; SK, streptokinase; STEMI, ST-elevation myocardial infarction; tPA, tissue plasminogen activator.

ACCESS (N =  12 068)114654597441355641300397.0724052.4
CREATE (N =  20 468)2561395776283037NA3005850597.594
EHS 1 (N =  9798)1842516367342257501706340374071
EHS 2 (N =  6067)1947486364412457471454137375963
GRACE (N =  92 106)23407066705825604614040NA474083
NRMI (N =  1 514 262)225763687126295651602038NA2885–6
RENASICA II (N =  8600)534062776643502636037178215104

Of note, in this Mexican registry the proportion of STEMI cases among ACS patients is comparable with that of registries from high-income countries, such as the Global Registry of Acute Cardiac Events (GRACE), the National Registry of Myocardial Infarction (NRMI), and Euro Heart Survey (EHS) 1 and 2 (Table 5). The frequencies of hypertension and male sex and the 30-day case fatality rate are also comparable; however, the distribution of other traditional risk factors shows important differences between Mexico and high-income populations. Diabetes and smoking are particularly overrepresented in Mexicans, whereas high total blood cholesterol and triglycerides had a lower frequency when compared with high-income populations. However, it should be acknowledged that a low concentration of high-density lipoprotein is the main dyslipidemia among Mexicans, and this variable could be underrepresented in the present study. Unfortunately, the ischemia time delay among patients who received reperfusion strategies in RENASICA II doubled the time consistently observed in developed nations (Table 5). The RENASICA II median hospital LOS (8.1 d) closely relates with that of the GRACE (8 d) and European Network for Acute Coronary Treatment (ENACT) (unstable angina, 8.5 days) studies, but it is different with respect to European registries.[18, 19] Moreover, we are far from the impressive decline in hospital LOS observed in NRMI (4.3 d).[20] Here we observed no difference with respect to in-hospital stay between both invasive and noninvasive reperfusion modalities, which may indicate that lytic therapy is still the best action when the currently preferred modality, PCI, is not available.[21] Therefore, the RENASICA II database can be used to establish treatment priorities and standards of care to reduce hospital LOS in Mexico and Latin America.

Ischemia time delay was similar in the RENASICA II, CREATE (treatment and outcomes of acute coronary syndromes in India), and ACCESS registries (Table 5), which reflects the limitations and barriers that exist in LMICs for a timely first medical contact and decreasing the door-to-reperfusion period. This finding contrasts with North America and Europe.[18, 19, 22, 23] We know that the optimal risk stratification based on biomarkers such as Tns is of crucial importance for improvement of outcome. Observations from RENASICA I (12%),[14] RENASICA II (15.6%), and ENACT (36%)[16] indicate that the availability of the measurement of Tn levels is still very limited. This highlights the need to establish an appropriate risk model tailored particularly to middle-income countries.

Lytic therapy is still the most frequently used approach worldwide in restoring flow in the infarct-related artery.[21] Even after 6 years of difference between the ACCESS and RENASICA II registries, the use of lytic therapy was quite comparable (39% and 37%, respectively; Table 5), which reflects the importance of this reperfusion strategy in developing countries. However, a significant proportion of patients did not receive any reperfusion therapy in both the RENASICA II and ACCESS registries (34% and 39%, respectively), even when they arrived at the hospital during the appropriate time window, an issue that should be addressed by the local authorities and academic institutions. The majority of our patients (82%) were treated with the non–fibrin-specific lytic streptokinase, due to its wider availability and lower cost than fibrin-specific lytics. It is possible that in current times the use of fibrin-specific lytic therapy is increasing in Mexico, an issue being evaluated in the new registry RENASICA III.

This study has several limitations that should be acknowledged. First, RENASICA II data may be old and not representative of the current problems faced in Mexico; to address this topic, the RENASICA III study is ongoing. Because this was not a population-based study, some biases may have been introduced with respect to selection of participating centers, limited monitoring visits, and short-term follow-up. Anthropometric information was not registered, so several adiposity indicators could not be evaluated. Biochemical markers were not measured in a central laboratory, and most patients were recruited in hospitals with coronary units from the Mexico City, so a suboptimal representation of different subpopulations is still possible. Despite these limitations, RENASICA II represents an important step toward identifying evidence that permits recognition of sensitive limitations of the Mexican health system in a more realistic view. This is emphasized by the fact that morbidity and case fatality rates have notable similarity with previous registries (Table 5).[7-11, 17-20, 22-25] We have learned important lessons to improve future registries.

Clinical Implications

Given the impact of ACS in Mexico, RENASICA II represents a link between randomized clinical trials, guidelines, and real clinical practice in a middle-income country. This project has generated important epidemiological information with the potential to change current recommendations and prevention strategies in Latin America. Given that largely modifiable risk factors are associated with STEMI in this population, a revision of the primary prevention practices at the single-patient level should be performed to establish appropriate and timely measures to limit effectively the burden of ACS in developing countries.[26, 27]

Conclusion

The prevalence of smoking and DM in Mexican patients with STEMI is higher than in patients in other series. Most patients arrive at hospital within the first 4 hours and with Killip class I. The most frequent reperfusion strategy is lytic therapy. The mortality predictors are in line with previous studies and reflect most of the real clinical practice in Latin American countries. RENASICA II is the largest ACS registry for a single country in Latin America, which provides important insights into deficiencies that should be addressed in the near future to limit the catastrophic rise in cardiovascular morbidity and mortality of populations living the so-called epidemiological transition.

Acknowledgments

The authors thank Erwin Chiquete, MD, PhD, and Sanofi Mexico for editorial assistance and final drafting. Sanofi, however, did not participate either directly or indirectly in the study design, patient selection, data capture, data analysis, manuscript drafting, or the decision to submit the article for publication.

RENASICA II is a nonfunded multicenter collaborative study performed by the following local investigators and sites. (Numbers in parentheses represent the number of patients enrolled at each site.) Alonso Autrey Caballero and Gabriela Borrayo, Hospital de Cardiología Centro Médico Nacional Siglo XXI, IMSS, Mexico City (1354); Armando García-Castillo, Carlos Jerjes Sánchez-Díaz, Beatriz Maldonado, Armando Astorga, and Jorge García, Hospital of Chest and Cardiovascule Disease, No. 34, IMSS, Monterrey, Nuevo León (1269); Carlos Martínez Sánchez, Úrsulo Juárez, and Héctor González, Instituto Nacional de Cardiología, Mexico City (890); Guillermo Llamas Esperón, Hospital Cardiológica Aguascalientes (519); Marco A. Ramos Corrales, Centro Médico “La Raza,” Mexico City (455); Jesús Martínez Sánchez, Hospital ABC, Mexico City (353); Octavio González Chon, Hospital Médica Sur, Mexico City (305); Jorge Cortez Lawrenz, Hospital CIMA Hermosillo, Sonora (228); Miguel ángel Luna Calvo, Hospital General de Durango (218); Eduardo Salazar Weill, Hospital No. 1, IMSS, Tepic, Nayarit (207); Carlos Martínez Hernández, Hospital Regional “Adolfo López Mateos,” ISSSTE, Mexico City (192); Julio López Cuéllar, Hospital Español, Mexico City (156); Berenice López Cuéllar, Hospital del Carmen, Guadalajara, Jalisco (135); Bernardo R. Encarnación, Centro Médico Nacional “Ruiz Cortines,” Veracruz (125); Marco A. Zúñiga, Centro Médico Nacional Occidente, Guadalajara, Jalisco (117); Ramiro Flores Ramírez, Hospital Universitario, Monterrey, Nuevo León (113); Jorge Carrillo and José Luis Arenas, Hospital Central “Morones Prieto,” San Luis Potosí (112); Alejandro García Reyes, Hospital Especialidades No. 71, IMSS, Torreón, Coahuila (102); Marco A. Alcocer, Hospital Ángeles, Querétaro (99); Ismael Hernández Santa María, Hospital Juárez, Mexico City (94); Carlos Urbano Castillo, Hospital ISSSTE, Guadalajara, Jalisco (87); Federico Rodríguez Wever, Hospital Ángeles del Pedregal, Mexico City (80); Germán A. Gómez Briceño, Hospital General “Manuel Gea González,” Mexico City (76); José Luis Leyva, Centro Médico del Potosí, San Luis Potosí (74); Juan Parcero, Mario Zúñiga, Hospital Excel, Tijuana, Baja California Norte (72); José Ramón Azpiri, Hospital Christus-Muguerza, Monterrey, Nuevo León (71); Amanda Castelán, Centro Médico Nacional Obregón, Sonora (70); Manuel Odín de los Ríos, Hospital General Culiacán, Sinaloa (69); Enrique López Rosas, Centro de Especialidades Médicas, Jalapa, Veracruz (68); Guillermo Ficker, Sanatorio Español, Torreón, Coahuila (64); José R. Ocampo, Hospital Santelena, Mexico City (59); Samuel Guízar, Raúl Rivas, Hospital PEMEX Picacho, Mexico City (59); Sergio Luna, Centro Médico Nacional, IMSS, León, Guanajuato (55); Darío Lemarroy, Hospital PEMEX Villahermosa, Tabasco (51); Alfredo Felipe Hoyos, Hospital Regional, IMSS, Cuernavaca, Morelos (50); Juan Carlos Núñez Fragoso, Hospital General No. 1, IMSS, Durango (49); Marco A. Alcocer, Hospital General, Querétaro (46); Sergio Najar, Efraín Gaxiola, Hospital “Fray Bernardete,” Guadalajara, Jalisco (43); Enrique Gómez Álvarez, Hospital ISSSTE 20 de Noviembre, Mexico City (43); Carmen Aurora Limón, Centro Médico Nacional IMSS, Puebla (41); Julio González Jaramillo, Centro Médico Nacional “El Fénix,” IMSS, Mérida, Yucatán (41); Ambrosio Cruz, PEMEX Hospital Central Norte, Mexico City (39); Alfredo Pérez Gea, Centro Español, Tampico, Tamaulipas (34); Hernán Navarrete Alarcón, ISSSTE Zaragoza, Mexico City (34); Jorge Durón, HGZ No. 2, IMSS, Saltillo, Coahuila (30); Miguel Beltrán, Hospital ISSSTECALLI, Tijuana, Baja California Norte (32); Jesús Manuel Canale, Hospital General del Estado, Hermosillo, Sonora (28); Luis Mario Fuentes, Hospital Star Médica, Morelia, Michoacán (26); Marcos Ibarra Flores, Hospital “San José” Tecnológico de Monterrey (21); José Luis Rodríguez, Hospital General de Zona No. 6, Ciudad Madero, Tamaulipas (16); Norberto Matadamas, Hospital General, Acapulco, Guerrero (15); Héctor Barragán Mar, Hospital Metropolitano, Mexico City (13); Carlos Hernández Herrera, Hospital Especialidades, Monclova, Coahuila (9); Hugo Aguilar Castillo, Hospital “Darío Fernández” ISSSTE, Mexico City (9); Marco Antonio Susarrey, Hospital Cardiomed, Ensenada, Baja California Norte (9); Abel Pavia, Hospital General SSA, Mexico City (8); Miguel A. Romo, Hospital “San José,” Zacatecas (8); Demetrio Kosturakis and Arturo Monroy, Hospital CIMA, Chihuahua (7); José Luis álvarez Cabrera, Centro Médico Naval, Mexico City (7); and Adrián Medina Amarilla, Hospital ALMATER, Mexicali, Baja California Norte (5). Coordinators for RENASICA II nonmedical personnel: Mely Colomer, Cristina Gaytán, Cristina Guerrero, Alfredo Gutiérrez, Xenia Cruz, Lorena Vasto, Miguel Wilson, and Leonor Gómez.

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