Our aim was to evaluate the effectiveness of oral anticoagulation (OAC) in patients aged ≥80 years with nonvalvular atrial fibrillation in daily clinical practice. From February 1, 2000 to June 30, 2009, we enrolled all patients aged ≥80 years with nonvalvular atrial fibrillation attended at 2 outpatient cardiology clinics of a tertiary care university hospital. The patients received antithrombotic treatment according to the recommendations from scientific societies and were prospectively followed, with major events (i.e., all-cause death, stroke, transient ischemic attack, peripheral embolism, severe bleeding) analyzed according to the treatment group (OAC vs no OAC). Of 269 patients included in the present study (87 men, mean age 83 ± 3 years), 164 received OAC (61%). After 2.8 ± 1.9 years of follow-up, the raw rates (per 100 patient-years) of embolic events (1.52% vs 8.30%, p <0.0001) and mortality (6.67% vs 10.94%, p = 0.04) were lower for patients receiving OAC, with a nonsignificant greater rate of severe bleeding (3.03% vs 1.25%, p = 0.14). The probability of survival free of major embolic or hemorrhagic events at the mean follow-up was greater for patients receiving OAC (82.27% vs 66.10%, p = 0.004). After adjustment for age, gender, coronary heart disease, and embolic risk, evaluated using the CHADS 2 score (congestive heart failure, 1 point; hypertension [blood pressure consistently >140/90 mm Hg or hypertension medication], 1 point; age ≥75 years, 1 point; diabetes mellitus, 1 point; previous stroke or transient ischemic attack, 2 points), only OAC was an independent predictor of embolic events (hazard ratio 0.17, 95% confidence interval 0.07 to 0.41, p <0.001). The CHADS 2 score (hazard ratio 1.32, 95% confidence interval 1.01 to 1.73, p = 0.04) and OAC (hazard ratio 0.52, 95% confidence interval 0.31 to 0.88, p = 0.01) were independent predictors of mortality. In conclusion, OAC according to the scientific societies’ recommendations is effective and safe in daily clinical practice, even in patients aged ≥80 years.
The aim of the present study was to evaluate the effectiveness and safety of oral anticoagulation (OAC) as thromboembolic prophylaxis for patients aged ≥80 years with nonvalvular atrial fibrillation (NVAF) in daily clinical practice.
Methods
We included in the present study all consecutive patients with permanent NVAF attended from February 1, 2000 to June 30, 2009 at a general outpatient cardiology clinic of a university hospital. The cardiology clinics receive patients from primary care physicians, from the emergency department, and from hospitalization for cardiology and internal medicine. In every patient, cardioversion was considered, with those who finally achieved sinus rhythm excluded. The present analysis included all patients aged ≥80 years who were included in the study.
Our thromboembolic prophylaxis protocol has been described in previous publications and was established by consensus among investigators, after reviewing the guidelines of the Spanish Society of Cardiology for antithrombotic treatment in cardiology that had been published before the design of our study and the scientific evidence available at that time. During the course of the study, the guidelines from the Spanish Society of Cardiology on cardiac arrhythmias and the American College of Cardiology/American Heart Association/European Society of Cardiology guidelines for atrial fibrillation became available. After reviewing these documents, the protocol was not changed, because it was consistent with the basic principles of the 3 guidelines. In brief, each patient was examined for cardioembolic risk factors (CERFs) and contraindications for anticoagulation. The following CERFs were identified and prospectively included in the database: age ≥75 years (all patients in the present study because of the inclusion criteria), hypertension, diabetes mellitus, previous cardioembolic event (e.g., stroke, transient ischemic attack, peripheral embolism), coronary disease, congestive heart failure, atrial enlargement (anteroposterior diameter ≥50 mm), and left ventricular dysfunction (ejection fraction ≤0.45). Patients with an absolute anticoagulation contraindication were treated with aspirin, other platelet aggregation inhibitors, or no antithrombotic treatment, at the discretion of the responsible physician. Patients with no contraindication for anticoagulation and with ≥1 additional CERFs (other than age ≥75 years) were offered OAC. Sufficient time was spent explaining the benefits and risks of OAC to the patients and their families to avoid treatment refusal because of incomplete or inadequate information. The decision to administer OAC was left to the cardiologist for patients with advanced age as the only CERF and no contraindications. The treatment of every patient was prospectively registered, and 2 study groups were considered: those who received OAC and those who did not, irrespective of the use of platelet aggregation inhibitors. We also considered 3 subgroup analyses: men versus women, patients aged 80 to 84 years versus those aged ≥85 years, and those with a CHADS 2 score of 1 (only advanced age as the CERF) versus those with a CHADS 2 score of ≥2 (CHADS 2 : congestive heart failure, 1 point; hypertension [blood pressure consistently >140/90 mm Hg or hypertension medication], 1 point; age ≥75 years, 1 point; diabetes mellitus, 1 point; previous stroke or transient ischemic attack, 2 points). We did not perform a more detailed analysis of the results for all CHADS 2 scores because of the small number of patients and events in each subgroup. The coagulation controls and therapeutic plan were established by expert hematologists who set a target international normalized ratio (INR) of 2 to 3 and who were unaware of the study parameters. Most patients received acenocumarol; only a minority received warfarin. Patients gave their informed consent, and the local ethics committee approved the study.
The patients were followed up annually in the clinic, and the occurrence of embolic events (e.g., stroke, transient ischemic attack, peripheral embolism), severe bleeding (bleeding that caused death or required a blood transfusion or hospital admission), and death was recorded. After every admission because of an event, the clinical history was examined for confirmation. If the patient presented with a possible cardioembolic event that had not been studied (e.g., symptoms suggestive of a transient ischemic attack), consultation with the appropriate specialist was requested. The cause of death (cardiovascular vs noncardiovascular) was established after reviewing the medical history of the patients who had died in hospital or the information given by their physicians or relatives.
All basal and follow-up data were included in a database created using the Statistical Package for Social Sciences software (SPSS, Chicago, Illinois). Quantitative data are presented as the mean ± SD, and qualitative data as proportions. The raw rates of events were calculated for 100 patient-years of follow-up. Subgroup comparisons were performed using Student’s t test for parametric data, the Mann-Whitney U test for nonparametric data, and the chi-square or Fisher exact test for qualitative data. The probability of survival free of events at the mean follow-up was estimated using the Kaplan-Meier method, and the results were compared using the log-rank test. CHADS 2 scores were obtained retrospectively using the data from the first visit of each patient. Multivariate analyses were performed using the Cox proportional hazards method, with cardioembolic and hemorrhagic events and all-cause mortality as dependent variables and OAC as the independent variable. The models were adjusted by all covariates that showed differences (p <0.20) between patients receiving OAC and the rest of the series. p values <0.05 were considered significant. The Statistical Package for Social Sciences software (SPSS) was used for statistical analysis.
Results
From February 1, 2000 to June 30, 2009, 269 patients were included in the present study. The mean age was 83 ± 3 years, and 32% were men. Of the 269 patients, 73% were aged 80 to 84 years, 21% 85 and 89 years, and only 6% ≥90 years old. The symptoms were as follows: 78% were asymptomatic, 18% presented with dyspnea, 2% had palpitations, and 2% had chronic stable angina.
A total of 164 patients received anticoagulants (61%). This proportion was greater among the patients aged 80 to 84 years than among those aged ≥85 years (66% vs 47%, p <0.01) and among those with a CHADS 2 score of ≥2 than among those with a CHADS 2 score of 1 (64% vs 47%, p = 0.03). The reasons for not prescribing anticoagulants were a high perceived risk of therapeutic noncompliance (n = 44), decision by the responsible physician (n = 26), patient refusal (n = 14), severe anemia (n = 5), gastrointestinal disease with a high risk of severe bleeding (n = 4), severe recent bleeding (n = 4), a high risk of severe or frequent trauma (n = 3), severe uncontrolled hypertension (n = 3), and other reasons (n = 2).
The patients prescribed OAC were younger than the other patients and had presented with a greater frequency of hypertension and coronary heart disease and a greater CHADS 2 score than the nonanticoagulated patients ( Table 1 ). No significant differences were found between the 2 groups with respect to the frequency of the other risk factors. Most nonanticoagulated patients received antiplatelets (95%), mainly aspirin (87% of all nonanticoagulated patients).
| Variable | Anticoagulation | p Value | |
|---|---|---|---|
| Yes (n = 164) | No (n = 105) | ||
| Age (years) | 83 ± 3 | 84 ± 4 | <0.01 |
| Men | 58 (35%) | 29 (28%) | 0.19 |
| Hypertension | 126 (77%) | 69 (66%) | 0.04 |
| Diabetes mellitus | 46 (28%) | 20 (19%) | 0.09 |
| Heart failure | 28 (17%) | 17 (16%) | 0.85 |
| Previous embolic event | 30 (18%) | 12 (11%) | 0.13 |
| Ischemic heart disease | 21 (13%) | 3 (3%) | <0.01 |
| Atrial enlargement | 23 (14%) | 8 (8%) | 0.13 |
| left ventricle systolic dysfunction | 8 (5%) | 4 (4%) | 0.46 |
| CHADS 2 score | 2.59 ± 1.15 | 2.24 ± 1.05 | 0.01 |
| 1 | 23 (14%) | 26 (25%) | |
| 2 | 71 (43%) | 46 (44%) | |
| 3 | 35 (21%) | 18 (17%) | |
| ≥4 | 35 (21%) | 15 (14%) | 0.09 |
After 2.8 ± 1.9 years of follow-up, 1 patient was lost to follow-up (0.37%) and 736 patient-years of observation had been accumulated. A total of 27 embolic events (13 transient ischemic attacks, 11 strokes, and 3 cases of peripheral embolism), 17 cases of severe bleeding, and 60 deaths had occurred. The raw rates of events are listed in Tables 2 and 3 . The raw embolic event rate was significantly lower in the patients who had received OAC, with a nonsignificantly greater rate of bleeding events. The combined embolic and hemorrhagic event rate and all-cause mortality was also lower in this subgroup. We found lower raw rates of nonfatal stroke, fatal stroke, and cardiovascular death among the OAC group, with nonsignificant trends toward lower rates of transient ischemic attacks and peripheral embolism and toward greater rates of nonfatal and fatal severe bleeding. The probability of survival free of major embolic or hemorrhagic events at the mean follow-up point was greater for patients in the OAC group (82.27% vs 66.10%, p = 0.004).
| Variable | Anticoagulation | p Value | |
|---|---|---|---|
| Yes (n = 164) | No (n = 105) | ||
| Transient ischemic attack | 5 (1.08) | 8 (3.32) | 0.07 |
| Nonfatal stroke | 1 (0.22) | 4 (1.66) | 0.05 |
| Fatal stroke | 0 (0) | 6 (2.49) | <0.01 |
| Peripheral embolism | 1 (0.22) | 2 (0.83) | 0.27 |
| All embolic events | 7 (1.52) | 20 (8.30) | <0.01 |
| Nonfatal bleeding | 9 (1.95) | 3 (1.25) | 0.76 |
| Fatal bleeding | 5 (1.08) | 0 (0) | 0.17 |
| All severe bleeding | 14 (3.03) | 3 (1.25) | 0.14 |
| All embolic and hemorrhagic events | 21 (4.55) | 23 (9.55) | <0.01 |
| Cardiovascular death | 8 (1.67) | 15 (5.86) | <0.01 |
| Other causes of death | 24 (5) | 13 (5.08) | 0.99 |
| All-cause death | 32 (6.67) | 28 (10.94) | 0.04 |
| Variable | Anticoagulation | No Anticoagulation | p Value | HR ⁎ (95% CI) | p Value |
|---|---|---|---|---|---|
| Embolic events | |||||
| Men | 2/58 (1.20) | 4/29 (6.06) | 0.06 | 0.21 (0.04–1.17) | 0.08 |
| Women | 5/105 (1.70) | 16/76 (9.14) | <0.001 | 0.18 (0.06–0.49) | 0.001 |
| Age 80–84 years | 6/129 (1.56) | 14/66 (9.59) | <0.01 | 0.14 (0.05–0.37) | <0.001 |
| Age ≥85 years | 1/35 (1.29) | 6/39 (6.32) | 0.13 | 0.29 (0.03–2.69) | 0.27 |
| CHADS 2 score | |||||
| 1 | 0/23 (0) | 7/26 (10.47) | 0.01 | 0.02 (0.00–6.55) | 0.18 |
| ≥2 | 7/141 (1.77) | 13/79 (7.47) | <0.01 | 0.22 (0.09–0.57) | 0.002 |
| All patients | 7/164 (1.52) | 20/105 (8.30) | <0.01 | 0.17 (0.07–0.41) | <0.001 |
| Severe bleeding | |||||
| Men | 4/58 (2.40) | 2/29 (3.03) | 0.68 | 0.82 (0.15–4.66) | 0.83 |
| Women | 10/105 (3.40) | 1/76 (0.57) | 0.06 | 09 (0.78–47.75) | 0.09 |
| Age 80–84 years | 11/129 (2.87) | 3/66 (2.06) | 0.76 | 1.47 (0.40–5.41) | 0.57 |
| Age ≥85 years | 3/35 (3.86) | 0/39 (0) | 0.09 | 103.40 (0.01–1.5 × 10 6 ) | 0.34 |
| CHADS 2 score | |||||
| 1 | 0/23 (0) | 0/26 (0) | 0.99 | ||
| ≥2 | 14/141 (3.55) | 3/79 (1.7) | 0.24 | 2.23 (0.63–7.82) | 0.21 |
| All patients | 14/164 (3.03) | 3/105 (1.25) | 0.14 | 2.66 (0.76–9.32) | 0.13 |
| All embolic and hemorrhagic events | |||||
| Men | 6/58 (3.59) | 6/29 (9.09) | 0.10 | 0.41 (0.13–1.30) | 0.13 |
| Women | 15/105 (5.10) | 17/76 (9.71) | 0.08 | 0.51 (0.26–1.03) | 0.06 |
| Age 80–84 years | 17/129 (4.43) | 17/66 (11.65) | <0.01 | 0.35 (0.18–0.70) | 0.003 |
| Age ≥85 years | 4/35 (5.15) | 6/39 (6.32) | 0.99 | 1.62 (0.37–7.20) | 0.52 |
| CHADS 2 score | |||||
| 1 | 0/23 (0) | 7/26 (10.47) | 0.01 | 0.02 (0.00–6.55) | 0.18 |
| ≥2 | 21/141 (5.32) | 16/79 (6.90) | 0.08 | 0.56 (0.29–1.08) | 0.09 |
| All patients | 21/164 (4.55) | 23/105 (9.55) | <0.01 | 0.46 (0.25–0.83) | 0.01 |
| All-cause death | |||||
| Men | 14/58 (7.87) | 4/29 (5.48) | 0.51 | 2.50 (0.66–9.51) | 0.18 |
| Women | 18/105 (5.94) | 24/76 (13.11) | 0.006 | 0.38 (0.20–0.72) | 0.003 |
| Age 80–84 years | 24/129 (5.98) | 18/66 (11.39) | 0.03 | 0.42 (0.22–0.79) | 0.007 |
| Age ≥85 years | 8/35 (10.20) | 10/39 (10.23) | 0.99 | 1.49 (0.53–4.17) | 0.45. |
| CHADS 2 score | |||||
| 1 | 2/23 (3.00) | 6/26 (8.73) | 0.27 | 0.25 (0.04–1.63) | 0.15 |
| ≥2 | 30/141 (7.26) | 22/79 (11.76) | 0.07 | 0.60 (0.34–1.85) | 0.08 |
| All patients | 32/164 (6.67) | 28/105 (10.94) | 0.04 | 0.52 (0.31–0.88) | 0.01 |
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