This Study Observes the Usage of Non-vitamin K Antagonist Oral Anticoagulants (NOACs) in Elderly Patients With a Heart Rhythm Disorder in Spain

Serum creatinine concentration from the last available blood sample analysis was retrieved from patients' medical records. Serum creatinine concentration from the last available blood sample analysis according to current NOAC type is reported.

Results from the last available blood sample analysis from patients' medical records were used to retrieve the creatinine clearance (CrCl). These results were directly collected in the Electronic Case Report Form (eCRF).

In cases where CrCl was not available in patients's medical record but serum creatinine was available, CrCl was estimated using Cockcroft-Gault formula:

CrCl = (140 - Age(years)) x Weight (kilogram) x [0.85 if female] / 72 x [Serum Creatinine (milligram/deciliterL)]

Reported are Crcl values which are calculated according to:

• Cockcroft-Gault formula and CrCl values directly collected in the eCRF
• Cockcroft-Gault formula only
• Directly collected in the eCRF

Results from the last available blood sample analysis from patients' medical records were used to retrieve the creatinine clearance (CrCl). These results were directly collected in the Electronic Case Report Form (eCRF).

In cases where CrCl was not available in patients' medical record but serum creatinine was available, CrCl was estimated using Cockcroft-Gault formula:

CrCl = (140 - Age(years)) x Weight (kilogram) x [0.85 if female] / 72 x [Serum Creatinine (milligram/deciliterL)]

The number of participants for each of the following creatinine clearance (CrCl) ranges is reported:

• CrCl ≥90: Kidney damage with normal or increased glomerular filtration rate (GFR)
• CrCl 60-89: Kidney damage with mild decreased GFR
• CrCl 30-59: Moderate decrease in GFR
• CrCl 15-29: Severe decrease in GFR
• CrCl <15: Kidney failure

Results from the last available blood sample analysis from patients' medical records were used to retrieve AST concentration. AST concentration from the last available blood sample according to non-vitamin K antagonist oral anticoagulant (NOAC) type is reported.

Results from the last available blood sample analysis from patients's medical records were used to retrieve ALT concentration. ALT concentration from the last available blood sample according to NOAC type is reported.

Results from the last available blood sample analysis from patients's medical records were used to retrieve bilirubin concentration. Bilirubin concentration from the last available blood sample according to NOAC type is reported.Results from the last available blood sample analysis from patients' medical records were used to retrieve bilirubin concentration. Bilirubin concentration from the last available blood sample according to NOAC type is reported.

Results from the last available blood sample analysis from patients' medical records were used to retrieve haemoglobin concentration. Haemoglobin concentration from the last available blood sample according to NOAC type is reported.

Results from the last available blood sample analysis from patients's medical records were used to retrieve platelet levels. Platelet levels from the last available blood sample according to NOAC type is reported.

Results from the last available blood sample analysis from patients' medical records were used to retrieve serum creatinine, ALT, AST, bilirubin, hemoglobin concentration and platelet levels.

For each reported laboratory parameter the values were categorized in two categories:

Serum creatinine:

• Normal value : 0.6-1.2 mg/dl in males and 0.5-1.1 mg/dl in females
• High/low value

ALT:

• Normal values: 7-55 units per liter (UI/L)
• High/low values

AST:

• Normal values: 8-48 UI/L
• High/low values

Bilirubin:

• Normal values: 0.2-1.2 milligram per deciliter (mg/dl)
• High/low values

Haemoglobin:

• Normal values: 12-18 gram/deciliter (g/dL)
• High/low values

Platelets:

• Normal values: 150-450 x10^3/µL
• High/low values

The number of years since NVAF diagnosis was obtained from number of years between date of NVAF diagnosis and date of study visit.

The date of NVAF diagnosis was retrieved from patient's medical records. The number of years since NVAF diagnosis and date of study visit is reported for:

• All patients;
• Patients treated previously with vitamin K antagonists (VKA);
• Patients treated with NOAC as first anticoagulant .

NVAF was categorized in four categories:

• Persistent;
• Long standing persistent;
• Permanent;
• Paroxysmal.

The European Heart Rhythm Association (EHRA) score of atrial fibrillation is a classification system for the extent of atrial fibrillation. It places patients in one of five categories based on how much they are limited during physical activity; the limitations/symptoms are in regard to normal breathing and varying degrees in shortness of breath and/or angina.

The EHRA categories are the following:

1-no symptoms 2a-mild symptoms; normal daily activity not affected. 2b-moderate symptoms; normal daily activity not affected. 3-severe symptoms; normal daily activity affected. 4-disabling; normal daily activity discontinued.

Number of patients with (category Yes) and without (category No) cardioversion, ablation, coronary interventions and pacemaker carrier according to current NOAC type is reported.

Number of patients in each category of coronary interventions according to current non-vitamin K antagonist oral anticoagulant (NOAC) type is reported.

Coronary interventions were categorized in:

• Percutaneous coronary intervention and
• Coronary artery bypass grafting.

Number of patients in each category of heart failure, coronary artery disease, sleep apnoea-hypopnoea syndrome, hypertension and hyperlipidaemia according to current non-vitamin K antagonist oral anticoagulant (NOAC) type is reported.

Heart failure, coronary artery disease, sleep apnoea-hypopnoea syndrome, hypertension and hyperlipidaemia were categorized in the following two categories:

• No;
• Yes.

The NYHA provides a simple way of classifying the extent of heart failure and it has 4 categories:

• A - No objective evidence of cardiovascular disease
• B - Objective evidence of minimal cardiovascular disease
• C - Objective evidence of moderately severe cardiovascular disease
• D - Objective evidence of severe cardiovascular disease Number of heart failure patients in each category of New York Heart Association (NYHA) classification according to current NOAC type is reported.

Left ventricular ejection fraction (LVEF) according to current non-vitamin K antagonist oral anticoagulant (NOAC) type is reported. LVEF was obtained from the patients' medical records.

The Charlson Comorbidity Index is a method of categorizing comorbidities of patients based on the International Classification of Diseases (ICD) diagnosis. Each comorbidity category has an associated weight (from 1 to 6), based on the adjusted risk of mortality or resource use, and the sum of all the weights results in a single comorbidity score for a patient. A score of zero indicates that no comorbidities were found. The higher the score, the more likely the predicted outcome will result in mortality or higher resource use. Up to 12 comorbidities with various weightings can result in a maximum score of 24. The minimum score is zero.

Number of patients with (Yes) and without (No) the comorbidities which were included in the Charlson Comorbidity Index according to current NOAC type is reported.

The comorbidities which were included in the Charlson Comorbidity Index were the following:

• Myocardial infarction
• Congestive heart failure
• Peripheral vascular disease
• Cerebrovascular disease
• Dementia
• Chronic Obstructive Pulmonary Disease (COPD)
• Connective tissue disease
• Peptic ulcer disease
• Liver disease (No/Mild/Moderate to severe)
• Diabetes mellitus (No/Uncomplicated/End-organ damage)
• Hemiplegia
• Moderate to severe renal disease
• Solid Tumor (No/Localized/Metastatic)
• Leukaemia
• Lymphoma
• Acquired Immune Deficiency Syndrome (AIDS).

Reported is the number of patients in each category of:

• Any history of thromboembolic events
• Transient Ischemic Attack (TIA)
• Ischemic stroke
• Haemorrhagic stroke
• Embolism systemic
• Deep vein thrombosis
• Pulmonary embolism.

Any history of thromboembolic events, Transient Ischemic Attack (TIA), ischemic stroke, haemorrhagic stroke, embolism systemic, deep vein thrombosis and pulmonary embolism were categorized in the following two categories:

• No
• Yes.

Number of patients in each category of stable angina, unstable angina, myocardial infarction with ST segment elevation and myocardial infarction without ST segment elevation according to current non-vitamin K antagonist oral anticoagulant (NOAC) type is reported.

Stable angina, unstable angina, myocardial infarction with ST segment elevation myocardial infarction without ST segment elevation were categorized in the following 2 categories:

• Yes;
• No.

Total number of thromboembolic events, number of each type of thromboembolic events, number of stable and unstable anginas, and number of ST and non-ST myocardial infarction according to current non-vitamin K antagonist oral anticoagulant (NOAC) type is reported.

Number of patients with (category Yes) and without (category No) any history of bleeding events and number of patients in each category of the following bleeding types is reported:

• Intracranial
• Digestive
• Genitourinary
• Gingival
• Nasal
• Pulmonary
• Articular-muscular
• Conjunctival.

Intracranial, digestive, genitourinary, gingival, nasal, pulmonary, articular-muscular, conjunctival were categorized in two categories:

• No
• Yes.

Total number of bleeding events and number of bleeding events for the following bleeding types is reported:

• Intracranial
• Digestive
• Genitourinary
• Gingival
• Nasal
• Pulmonary
• Articular-muscular
• Conjunctival.

The Congestive heart failure, Hypertension, Age (> 75), Diabetes mellitus, Stroke/TIA, Vascular disease, Age 65-74, Sex Category (CHA2DS2-VASc) score is a clinical prediction rule to estimate the risk of stroke in patients with Atrial Fibrillation (AF); it is frequently used to determine the need for an anticoagulation therapy, relating the high scores to a great risk of stroke and a low score corresponds to a lower risk of stroke. CHA2DS2-VASc stroke risk score may range from 0 to 9 with 0 being the best outcome.

The Congestive heart failure, Hypertension, Age (> 75), Diabetes mellitus, Stroke/TIA, Vascular disease, Age 65-74, Sex Category (CHA2DS2-VASc) total score was categorized in three categories, according to the risk of stroke:

• Low risk (score 0 in male; score 1 in female)
• Moderate risk (score 1 in male; score 2 in female)
• High risk (score ≥2 in male; score ≥3 in female)

Hypertension, Abnormal renal and liver function, Stroke (1 point), Bleeding history or predisposition, Labile International Normalized Ratio (INR), Elderly (>65 years), Drugs and Alcohol (HAS-BLED) score may range from 0 to 9 with 0 being the best outcome. The high scores indicate a greater risk of bleeding and a low score corresponds to a lower risk of bleeding.

The Hypertension, Abnormal renal and liver function, Stroke (1 point), Bleeding history or predisposition, Labile INR, Elderly (>65 years), Drugs and Alcohol (HAS-BLED) total score was categorized in three categories according to the bleeding risk:

• Low risk (score 0)
• Intermediate risk (score 1-2)
• High risk (score ≥3)

Number of patients in each category (No;Yes) of any concomitant treatments to NOAC and number of patients in each category (No; Yes) for each concomitant treatment to NOAC at study visit according to current NOAC type is reported.

The concomitant treatment to non-vitamin K antagonist oral anticoagulant (NOAC) were the following:

• Angiotensin-Receptor Blockers (ARB) or Angiotensin Converting Enzyme inhibitors (ACE) inhibitor
• Beta-blocker
• Calcium channel blockers
• Diuretics
• Amiodarone
• Statin
• Proton pump inhibitor
• H2-receptor antagonist
• Digoxin
• NSAIDs (Nonsteroidal Anti-Inflammatory Drugs)
• Dronedarone
• Ketoconazole
• Cyclosporine
• Itraconazole
• Other antiarrhythmics

Number of patients in each category of previous Vitamin K Antagonists (VKA) treatment according to duration since the first non-vitamin K antagonist oral anticoagulant (NOAC) initiation is reported.

Previous VKA treatment was categorized in 2 categories:

• No;
• Yes.

Number of patients treated previously (before they were treated with non-vitamin K antagonist oral anticoagulant (NOAC)) with the Vitamin K Antagonists (VKA) acenocoumarol and number of patients treated previously with the VKA warfarin according to duration since the first NOAC initiation is reported.

Duration of treatment (in years) is reported for:

• All patients treated previously with Vitamin K Antagonists (VKA) (row:All patients treated previously with VKA)
• Patients treated only with the VKA warfarin (row: Warfarin patients)
• Patients treated only with the VKA acenocoumarol (row: Acenocoumarol patients)

Duration (in years) since non-valvular atrial fibrillation (NVAF) diagnosis until first NOAC initiation according to duration since the first NOAC initiation is reported for:

• All patients
• Patients treated previously with VKA
• Patients treated only with NOAC as anticoagulant (AC)

Number of patients who received dabigatran, rivaroxaban, apixaban, edoxaban as first NOAC and number of patients who received dabigatran 110 mg BID (twice daily), dabigatran 150 mg BID, rivaroxaban 15 mg once daily (QD), rivaroxaban 20 mg QD, apixaban 2.5 mg BID, apixaban 5 mg BID, edoxaban 30 mg QD and edoxaban 60 mg QD as first NOAC according to duration since the first NOAC initiation is reported.

Number of patients who changed (increased and decreased) and did not change the first non-vitamin K antagonist oral anticoagulant (NOAC) dose according to duration since the first NOAC initiation is reported.

Treatment duration (in years) is reported for:

• Patients who stopped first NOAC treatment;
• Patients who did not stop the first NOAC treatment.

Reason for first NOAC treatment discontinuation was categorized in four categories:

• Lack of effectiveness
• Investigator's decision
• Patient's decision
• Adverse event

Reason for first NOAC treatment change was categorized in four categories:

• Lack of effectiveness
• Investigator's decision
• Patient's decision
• Adverse event

Number of switches to a new non-vitamin K antagonist oral anticoagulant (NOAC) per patient according to duration since the first NOAC initiation is reported.

Number of patients based on the number of switches to a new NOAC per patient according to duration since the first NOAC initiation is reported.

Number of switches to a new NOAC was categorized in 3 categories:

• 0 switches
• 1 switch
• 2 switches.

Total number of switches according to duration since the first NOAC initiation is reported.

Reason for switch was categorized in four categories:

• Lack of effectiveness
• Investigator's decision
• Patient's decision
• Adverse event

Number of patients who received dabigatran, rivaroxaban, apixaban, edoxaban as second NOAC and number of patients who received dabigatran 110 mg BID (twice daily), dabigatran 150 mg BID, rivaroxaban 15 mg once daily (QD), rivaroxaban 20 mg QD, apixaban 2.5 mg BID, apixaban 5 mg BID, edoxaban 30 mg QD and edoxaban 60 mg QD as second NOAC according to duration since the first NOAC initiation is reported.

Number of patients who changed (increased or decreased) and did not change the second non-vitamin K antagonist oral anticoagulant (NOAC) dose according to duration since the first NOAC initiation is reported.

Second NOAC treatment duration (in years) according to duration since the first NOAC initiation is reported.

Reason for second non-vitamin K antagonist oral anticoagulant (NOAC) treatment discontinuation was categorized in four categories:

• Lack of effectiveness
• Investigator's decision
• Patient's decision
• Adverse event

Reason for second NOAC treatment change was categorized in four categories:

• Lack of effectiveness
• Investigator's decision
• Patient's decision
• Adverse event

Number of patients who received dabigatran, rivaroxaban, apixaban, edoxaban as third NOAC and number of patients who received dabigatran 110 mg BID (twice daily), dabigatran 150 mg BID, rivaroxaban 15 mg once daily (QD), rivaroxaban 20 mg QD, apixaban 2.5 mg BID, apixaban 5 mg BID, edoxaban 30 mg QD and edoxaban 60 mg QD as third NOAC according to duration since the first NOAC initiation is reported.

Number of patients who changed (increased and decreased) and did not change the third non-vitamin K antagonist oral anticoagulant (NOAC) dose according to duration since the first NOAC initiation is reported.

Duration of third NOAC treatment for patients who stopped NOAC treatment.

Reason for Third NOAC treatment discontinuation was categorized in four categories:

• Lack of effectiveness
• Investigator's decision
• Patient's decision
• Adverse event

Reason for Third NOAC treatment change was categorized in four categories:

• Lack of effectiveness
• Investigator's decision
• Patient's decision
• Adverse event

Duration (in years) in NOAC treatment is reported for:

• All patients (patients who received or did not receive VKA)
• Patients treated previously with Vitamin K Antagonists (VKA)
• Patients treated with NOAC as first anticoagulant

Number of patients in each category of total time in non-vitamin K antagonist oral anticoagulant (NOAC) treatment according to duration since the first NOAC initiation is reported.

Total time in NOAC treatment was categorized in 4 categories:

• <1 year;
• 1-2 years;
• 2-3 years;
• >3 years.

Number of patients for each type of following antiplatelet treatment that the patients ever received is reported:

• None (reports the patients who did not receive any antiplatelet treatment)
• Acetyl salicylic acid
• Clopidogrel
• Prasugrel
• Ticlopidine
• Ticagrelor
• Cilostazol
• Triflusal
• Dipyridamole
• Others (other antiplatelet treatment than above mentioned).

Number of patients for each of the following antiplatelet treatment types at the time of study visit according to duration since the first NOAC initiation is reported:

• None (reports the patients who did not receive any antiplatelet treatment)
• Acetyl salicylic acid
• Clopidogrel
• Prasugrel
• Ticlopidine
• Ticagrelor
• Cilostazol
• Triflusal
• Dipyridamole
• Others (other antiplatelet treatment than above mentioned).

Time in treatment with antiplatelet agents (in years) according to duration since the first NOAC initiation is reported.

Clinical Frailty Scale (CFS) is used commonly to assess frailty. It is a 9-point scale from 1 to 9 (1=very fit; 2=well; 3=Managing well; 4=Vulnerable; 5=Mildly frail; 6=Moderately frail; 7=Severely frail; 8=very severely frail; 9=terminally ill) that summarizes the overall level of fitness or frailty of an older adult after they had been evaluated by a health care professional. Applying the CFS to patients is quick and requires data collection by watching the patient (mobilize), inquiring about their habitual physical activity and ability. A person with a score >4 was considered frail.

Clinical Frailty Scale (CFS) is used commonly to assess frailty. It is a 9-point scale from 1 to 9 (1=very fit; 2=well; 3=Managing well; 4=Vulnerable; 5=Mildly frail; 6=Moderately frail; 7=Severely frail; 8=very severely frail; 9=terminally ill) that summarizes the overall level of fitness or frailty of an older adult after they had been evaluated by a health care professional. Applying the CFS to patients is quick and requires data collection by watching the patient (mobilize), inquiring about their habitual physical activity and ability.

CFS was categorized in two categories, according to this ranges:

• Frailty patients - CFS scoring >4
• Non-frailty patients - CFS scoring ≤4

Reason for First NOAC usage was categorized in the following two categories:

• Primary prevention;
• Secondary prevention.