Original Research

Anticoagulation Therapy by Age and Embolic Risk for Nonvalvular Atrial Fibrillation in Mexico an UpperMiddleIncome Country: The CARMENAF Registry

Authors: {'first_name': 'Manlio F.', 'last_name': 'M\xc3\xa1rquez'},{'first_name': 'Manuel A.', 'last_name': 'Ba\xc3\xb1os-Gonz\xc3\xa1lez'},{'first_name': 'Milton E.', 'last_name': 'Guevara-Valdivia'},{'first_name': 'Jorge', 'last_name': 'V\xc3\xa1zquez-Acosta'},{'first_name': 'Manuel O.', 'last_name': 'de los R\xc3\xados Ibarra'},{'first_name': 'Julio A.', 'last_name': 'Aguilar-Linares'},{'first_name': 'Marcelo', 'last_name': 'Jim\xc3\xa9nez-Cruz'},{'first_name': 'Norberto', 'last_name': 'Matadamas-Hern\xc3\xa1ndez'},{'first_name': 'Roc\xc3\xado', 'last_name': 'Camacho-Casillas'},{'first_name': 'Reynaldo', 'last_name': 'Maga\xc3\xb1a-Maga\xc3\xb1a'},{'first_name': 'Ulises', 'last_name': 'Rojel-Mart\xc3\xadnez'},{'first_name': 'Marco A.', 'last_name': 'Alcocer-Gamba'},{'first_name': 'Susano', 'last_name': 'Lara-Vaca'},{'first_name': 'Humberto', 'last_name': 'Rodr\xc3\xadguez-Reyes'},{'first_name': 'Marco A.', 'last_name': 'Islava-G\xc3\xa1lvez'},{'first_name': 'Lidia E.', 'last_name': 'Betancourt-Hern\xc3\xa1ndez'},{'first_name': 'Nicol\xc3\xa1s', 'last_name': 'Reyes-Reyes'},{'first_name': 'Miguel E.', 'last_name': 'Beltr\xc3\xa1n-G\xc3\xa1mez'},{'first_name': 'Carlos', 'last_name': 'Cant\xc3\xba-Brito'},{'first_name': 'Alberto Z.', 'last_name': 'Ba\xc3\xb1os-Velasco'},{'first_name': 'Pedro J.', 'last_name': 'del Rivero Morfin'},{'first_name': 'J. Antonio', 'last_name': 'Gonz\xc3\xa1lez-Hermosillo'}


Background: Documenting the patterns of oral anticoagulation therapy (OAT) is essential to prevent thromboembolic complications of nonvalvular atrial fibrillation (NVAF).

Objective: To report the patterns of OAT according to age and thromboembolic risk in patients included in CARMEN-AF, a nationwide registry of NVAF in Mexico, an upper middle-income country.

Material and methods: There were 1,423 consecutive patients =18 years old and with at least one thromboembolic risk factor enrolled in the CARMEN-AF Registry at their regular clinical visit during a three-year period. They were analyzed according to 1) age, 2) AF type, and 3) CHA2DS2-VASc score.

Results: Overall, 16.4% of patients did not receive antithrombotic treatment, 19.4% received antiplatelet drugs (APD), 29.2% vitamin K antagonists (VKA), and 34.6% direct oral anticoagulants (DOAC). With increasing age, the proportion of subjects treated with VKA decreased significantly from 36.2% in subjects 2DS2-VASc =2) compared with the moderate risk group (41% in CHA2DS2-VASc = 1).

Conclusions: VKA use for NVAF in Mexico decreased in relation to increasing age. The proportion of DOAC therapy was the same in all age groups. Nevertheless, elderly patients with high thromboembolic risk received a suboptimal thromboprophylaxis. These data could help to improve gaps in the implementation of global guidelines.

Clinical trial registration: http://www.clinicaltrials.gov. Unique identifier: NCT02334852.


Keywords: Atrial fibrillationembolic riskanticoagulation therapyantithrombotic treatmentvitamin K antagonistdirect oral anticoagulantMexico 
DOI: http://doi.org/10.5334/gh.767
 Accepted on 23 Jan 2020            Submitted on 14 Jan 2019


Oral anticoagulation therapy (OAT) is the cornerstone of stroke prevention in nonvalvular atrial fibrillation (NVAF) [1]. Current registries of anticoagulation therapy (ACT) for NVAF are a priority in high-income countries [2, 3]. However, in upper middle-income countries like Mexico, there is scarce epidemiological data about OAT for NVAF [4, 5].

CARMEN-AF (Registry of Atrial Fibrillation and Embolic Risk in Mexico) is a nationwide, industry-independent registry, developed as a means to bridge the information gap about OAT for NVAF in Mexico [6]. Herein, we report the results of the CARMEN-AF Registry, analyzed by age, AF type, and thromboembolic risk.

Material and Methods

CARMEN-AF is an ongoing, observational, longitudinal, multi-center, nationwide registry of OAT in NVAF in Mexico. A full list of the investigators of the Registry could be consulted in the Appendix A of this article. The protocol has already been published [6]. An English version of the Registry of Atrial Fibrillation and Embolic Risk in Mexico (CARMEN-AF) could be consulted in Supplementary Material. Mexico’s economic status as an upper-middle income country is based on the 2013 World Bank Classification according to gross national income per capita [7]. A total of 1,423 consecutive patients were enrolled in a three-year period (September 19, 2014 – December 18, 2017).

Study population

Eligible patients were at least 18 years old, with one or more risk factors for thromboembolism evaluated by CHA2DS2-VASc score and diagnosed with NVAF at least 6 months prior to their inclusion. Patients were included independent of anti-thrombotic therapy (ATT) (antiplatelet drugs [APD], vitamin K antagonists [VKA] or direct oral anticoagulants [DOAC] available in Mexico [dabigatran, rivaroxaban, and apixaban]). We used cross-sectional data obtained at patient recruitment. Physicians performed data collection at regular clinic visits using a paper-based case report form, with subsequent capture in an electronic case report form for data storage.

A table specifying the centers that participated, grouped by state (geographical distribution), and details about the type of clinic (public/private, second/third level), and the type of practice (the specialty of the center coordinator) can be consulted in the supplementary material. It also includes the type of residence of the patients (urban or rural). All patients were treated in urban centers (mostly by cardiologists), representing 29 states of the Mexican Republic. All patients were assessed at an initial clinical visit with a complete medical history and physical examination (Table 1).

Table 1

Geographical distribution (Mexican states) of subjects included in CARMEN-AF and other related variables.

Center State Level of care Type Specialty of the coordinator Type of residency of the patients (Urban, rural, both)

Sociedad Cardiovascular de Aguascalientes Aguascalientes Third Private Electrophysiologist Urban
Hospital Hidalgo Aguascalientes Third Public Cardiologist Both
Hospital Regional No1 IMSS, Tijuana Baja California Second Public Cardiologist Both
Hospital Angeles Tijuana Baja California Third Private Cardiologist/Internist Urban
Plaza Medical Baja California Third Private Cardiologist Urban
Hospital General ISSSTE, La Paz Baja California sur Third Public Cardiologist/Internist Urban
Hospital GE ‘Dr Javier Buenfil Osorio’ INDESALUD Campeche Third Public Cardiologist Both
Instituto Nacional de Cardiologist ‘Ignacio Chavez’ Mexico City Third Public Electrophysiologist Both
Hospital de Especialidades, Centro Medico Nacional ‘La Raza’ IMSS Mexico City Third Public Electrophysiologist Both
Hospital de Cardiologist del Centro Medico Nacional ‘Siglo XXI’ IMSS Mexico City Third Public Electrophysiologist Both
Hospital General de Mexico Mexico City Third Public Electrophysiologist Urban
Instituto Nacional de Ciencias Medicas y Nutricion ‘Salvador Zubiran’ Mexico City Third Public Neurologist Urban
CIMA Chihuahua Chihuahua Third Private Cardiologist Urban
Unidad Medica de Alta Especialidad No71 IMSS, Coahuila Coahuila Third Public Cardiologist Urban
Hospital General de Zona No 10, Manzanillo Colima Second Public Cardiologist/Internist Urban
Hospital General de Zona No 1 IMSS, Durango Durango Second Public Cardiologist/Internist Both
ISSEMYM Toluca Estado de Mexico Third Public Electrophysiologist Urban
Hospital Angeles Leon Guanajuato Third Private Electrophysiologist Both
Hospital General de Acapulco Guerrero Third Public Cardiologist/Internist Both
Hospital General de Pachuca Hidalgo Third Public Cardiologist/Internist Both
Hospital Civil de Guadalajara Jalisco Third Public Cardiologist/Internist Urban
Hospital General de Uruapan Michoacan Second Public Cardiologist Both
Instituto Nacional de Trasplantes Morelos Second Private Cardiologist/Internist Urban
Instituto de Cardiologist y Medicina Vascular Hospital Zambrano, Tec Salud Nuevo Leon Third Private Electrophysiologist Urban
Hospital Regional de Alta Especialidad de Oaxaca Oaxaca Third Public Cardiologist. Internist Urban
Clinica Molina Oaxaca Segunda Public Cardiologist Urban
Hospital General del Sur de Puebla Puebla Third Private Electrophysiologist Urban
Hospital Angeles de Puebla Puebla Third Private Electrophysiologist Urban
Instituto del Corazon Queretaro Queretaro Third Private Internist Both
Hospital General de Zona No3 IMSS Quintana Roo Second Public Cardiologist Both
Hospital Central ‘Dr Ignacio Morones Prieto’ San Luis Potosi Third Public Cardiologist Both
Torre Medica Olivos San Luis Potosi Primer Private Cardiologist Urban
Hospital Civil de Culiacan Sinaloa Public Cardiologist Both
Angeles Culiacan Sinaloa Third Private Cardiologist/Internist Urban
Hospital General de Culiacan Sinaloa Second Public Cardiologist/Internist Both
Centro Medico Nacional del Noroeste IMSS Sonora Third Public Cardiologist Both
Hospital Regional de Alta Especialidad ‘Juan Graham Casasus’ Tabasco Third Public Cardiologist/Internist Both
Hospital Regional de PEMEX Ciudad Madero Tamaulipas Third Public Cardiologist Both
Unidad Medica de Alta Especialidad No 14 IMSS Veracruz Third Public Cardiologist Both
Star Medica Merida Yucatan Third Private Cardiologist Urban
Hospital ‘San Agustin’ Zacatecas Third Private Cardiologist Both

Statistical methodology

Data was analyzed using SPSS v. 22.0. Demographic differences among continuous variables with normal distribution were examined using Student’s t-test; Wilcoxon signed-rank test was used when variables failed normality test. Categorical variables were analyzed using Chi-square test, either Fisher’s exact test or Yates’s correction for continuity. A 2-tail test with a P value <0.05 was considered statistically significant.

Informed consent

Informed consent was obtained from each patient and the study protocol conforms to the ethical guidelines of the 1975 Declaration of Helsinki as reflected in a priori approval by the institution’s human research committee.


A total of 1,423 consecutive patients were enrolled in a three-year period (September 19, 2014–December 18, 2017). Mean age of participants was 69 ± 13 years old. 731 (51.4%) were male. Complete demographic characteristics are shown in Table 2.

Table 2

Demographic characteristics.

Demographic characteristics

All(n = 1,423) Male(n = 731) Female(n = 692) P*

Gender (%) 51.4 48.6 ns
Age, years ± SD 69 ± 13 68 ± 13 70 ± 12 =0.002
Weight, kg ± SD 75 ± 16 80 ± 15 69 ± 14 <0.0001
Body Mass Index, kg/m2 ± SD 28.5 ± 5.0 28.4 ± 4.6 28.7 ± 5.4 ns

* P value was obtained comparing Gender groups using Chi-square test and Student’s t-test.

NVAF was paroxysmal in 37.3% of the cases, persistent in 22.1%, permanent in 40.6%; AF was asymptomatic in 59.4% of patients. The most prevalent comorbidities (Table 3) in patients with NVAF were hypertension (72.5%), diabetes (28.4%), heart failure (23.6%) and smoking (16.4%).

Table 3

Comorbidities of total population.


(%) All (n = 1,423) Male (n = 731) Female (n = 692) P*

Hypertension 72.5 71.3 73.8 ns
Diabetes 28.4 31.3 25.3 =0.007
Heart failure 23.6 25.3 21.8 ns
Smoking 16.4 23.9 8.5 <0.0001
Alcoholism 9.2 17.1 0.9 <0.0001
Nonischemic cardiomyopathy** 8.9 10.3 7.5 =0.042
Coronary Artery Disease 7.1 9.7 4.3 <0.0001
Obstructive sleep apnea 3.9 5.2 2.6 =0.008
Peripheral artery disease 1.8 1.0 2.7 =0.010

* P value was obtained comparing Gender groups using Chi-square test and Student’s t-test.

** Hipertensive, Idiopathic, and restrictive.

Related to ATT, 16.6% of patients were not receiving any; 19.4% were receiving APD, and 63.9% of the patients were receiving oral anticoagulants (VKA = 416, 29.2%; DOAC = 493, 34.6%). OAT was either monotherapy (56.9%) or combined with one or two APD (7.2%) (Table 4).

Table 4

Antithrombotic therapy according to AF type.

Antithrombotic therapy according to AF type

(%) P = 0.037* All (n = 1,423) Paroxysmal (n = 531) Persistent (n = 314) Permanent (n = 578)

Without treatment 16.6 17.5 15.9 16.1
Antiplatelet 19.4 22.4 19.7 16.4
Anticoagulant 56.8 53.7 54.1 61.1
Anticoagulant + Antiplatelet 5.7 4.9 8.9 4.7
Triple therapy 1.5 1.5 1.3 1.7

* P value was obtained comparing Gender groups using Chi-square test and Student’s t-test.

Antithrombotic therapy by AF type

In accordance to AF type (paroxysmal, persistent, and permanent), suboptimal ATT (no ATT or just APD treatment) was observed in 40.3% of patients in the paroxysmal group, 35.7% in the persistent group, and 32.5% in the permanent group. There was a statistically significant difference between treatments when the groups were compared. (P = 0. 026) (Figure 1).

Figure 1 

Antithrombotic therapy by AF type (%).

* P value was obtained comparing AF type groups vs Treatment groups using Chi-square test.

Antithrombotic therapy by thromboembolic risk

The thromboembolic risk was assessed using CHA2DS2-VASc score (moderate risk = 1 point; high risk ≥2 points). No significant difference was observed on ATT between moderate and high thromboembolic risk subjects. Interestingly, inadequate ATT was observed in 36.4% of high thromboembolic risk patients: 20.1% were treated with APD and 16.3% did not receive any treatment (Figure 2).

Figure 2 

Antithrombotic therapy according to CHA2DS2-VASc risk (%).

* P value was obtained comparing Treatment groups vs CHA2DS2-VASc groups using Chi-square test.

Antithrombotic therapy by age

As the CHA2DS2-VASc score classifies thromboembolic risk according to age, patients were divided into three groups (Figure 3). In the group of patients younger than 65 years old, 70.4% received OAT (DOAC 34.2%, VKA 36.2%), 15.2% received APD and 14.3% did not receive ATT. In the 65–74 years old group, 66.4% of patients received OAT (DOAC 36.0%, AVKs 30.4%), 17.8% received APD, and 15.9% did not receive ATT. In the group of patients’ ≥75 years old, 56.4% received OAT (DOAC 33.9.0%, VKA 22.5%), 24.5% were on APD, and 19.0% received no treatment.

Figure 3 

Antithrombotic therapy according to age (%).

* P value was obtained comparing Treatment groups vs Age groups using Chi-square test.

Bleeding risk

There was a significant difference in HAS-BLED score between men and women; it was higher in men (1.82 ± 1.0 vs 1.71 ± 0.9; P = 0.032). According to bleeding risk, more women had a low risk of bleeding than men (9.7% vs 6.3%, P = 0.012), while more men had a high risk (20.8% vs 16.8%, P = 0.030) [19].

Of the studied population, 9.5% of women and 19.2% men at high risk of bleeding (HAS-BLED score = ≥3) did not receive any antithrombotic therapy (P = 0.021).


Patients with AF have 5 times greater risk of stroke than the general population [8]. There is significant evidence that the use of oral anticoagulants, both VKA and DOAC, reduce the risk of stroke in patients with NVAF [9, 10, 11, 12]. Thromboembolic risk assessment should be performed at diagnosis using CHA2DS2-VASc score, and OAT should be started in patients with moderate and high risk of thrombosis (score ≥ 2) [1].

Clinical registries are proven to evaluate the correct application of treatment guidelines.

CARMEN-AF was designed to find out current information about the status of OAT for NVAF in Mexico. The main finding of this registry was that despite most of the patients in our cohort (85.6%) were classified as high thromboembolic risk according to CHA2DS2-VASc score (≥2), 35.8% of the total population diagnosed with NVAF were not receiving OAT or only received APD, a suboptimal therapy.

It was also found a trend in the use of OAT according to age. In Mexico, OAT is less commonly prescribed for elderly patients, despite that age is a well-known risk factor for thromboembolism; this conduct may be related to the fear of hemorrhagic complications in this group of patients according to HAS-BLED score [13]. Elderly patients who did receive OAT were more likely to be prescribed with a DOAC instead of VKA, probably due to better adherence and ease of use of DOAC [14].

Data collected by CARMEN-AF shows similarities with other large-scale NVAF registries. In Mexico, an upper middle-income country, hypertension remains the main comorbidity, just as in GLORIA-AF and GARFIELD registries. Also, the proportion of participants with high thromboembolic risk as assessed by CHA2DS2-VASc scores was very similar among the three registries (GLORIA-AF 86.1%; GARFIELD 84.3%; CARMEN-AF 85.6%). Finally, in Mexico DOAC are preferred as OAT in contrast with some other countries in Latin America, in which VKA remains the therapy of choice for prevention of thromboembolic complications in NVAF [15, 16, 17].

In order to understand differences among registries, we must remember that CARMEN-AF had a greater proportion of permanent NVAF (40.6%), while GLORIA-AF reported only 11.1% and GARFIELD 13.1% (P < 0.0001). Also, the amount of patients left untreated in CARMEN-AF (16.6%) is greater than GARFIELD (12.3%) and GLORIA-AF (7.8%) global cohorts, as well as GLORIA-AF Latin America cohort (4.2%) [15, 16, 18]. Significant differences in treatment were observed between the three registries (P < 0.0001).


CARMEN-AF was based on the prescription of antithrombotic therapy by different specialists; therefore, our data may not apply to other healthcare givers.

According to protocol, this survey recruited only patients with CHA2DS2-VASc≥ 1. Thus, no data on patients with score zero (low risk of stroke) were available.

Both patients and physicians knew they were participants of a registry; this might have led to higher overall anticoagulation rates compared with general population.

Unfortunately, the socioeconomic status as a variable is not available for the entire study.


CARMEN-AF demonstrated a suboptimal thromboprophylaxis in NVAF in Mexico, an upper-middle income country, accounting for relevant differences with respect to high-income countries. Identification of gaps in the implementation of global guidelines between countries is the first step towards the objectives of the World Heart Federation Roadmap for NVAF.

Additional File

The additional files for this article can be found as follows:

Appendix A

Full list of the investigators and their participating centers of the Registry of Atrial Fibrillation and Embolic Risk in Mexico (CARMEN-AF). DOI: https://doi.org/10.5334/gh.767.s1

Supplementary material

A full English version of the design of the Registry of Atrial Fibrillation and Embolic Risk in Mexico (CARMEN-AF), to assist our global audience to a better approaching to the original article published in Spanish in 2016 in Archivos de Cardiología de México. DOI: https://doi.org/10.5334/gh.767.s2


AF = Atrial fibrillation

APD = Antiplatelet drugs

ATT = Antithrombotic therapy

DOAC = Direct oral anticoagulants

NVAF = Nonvalvular atrial fibrillation

OAT = Oral anticoagulation therapy

VKA = Vitamin K antagonists


The authors would like to thank MedicaWeb for the technical support provided in the development of the CARMEN-AF Registry, as well as the Mexican Society of Cardiology for their endorsement.

Funding Information

Bayer, Boehringer-Ingelheim, and Pfizer unrestrictedly support the CARMEN-AF Registry, only for academic purposes. They did not intervene in the design of the CARMEN-AF Registry or in the elaboration of this material.

Clinical Trial Registration

http://www.clinicaltrials.gov. Unique identifier: NCT02334852.

Competing Interests

Doctors González-Hermosillo and Manlio F. Márquez have participated in other industry-sponsored registries and have been speakers for some companies that supported the CARMEN-AF Registry.


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