Oral Anticoagulation in HF Patients With Atrial Fibrillation
Oral Anticoagulation in HF Patients With Atrial Fibrillation
The ESC AF guidelines, the Asian Pacific Society of Cardiology, and the Latin American Society of Cerebrovascular Diseases recommend that patients with a moderate-to-high risk of stroke be started on a VKA. Despite these recommendations, the risk-adjusted use of warfarin in the 10 countries included in our observations ranged from 25.1% to 65.5%, with most of the countries having <50% rate of use. The 2 countries with the lowest adjusted rates of anticoagulation were Taiwan and the Philippines with rates of 25.1% and 25.5%, respectively. The country with the highest adjusted rate was Australia with 65.2% VKA use at discharge. These vast differences may reflect disparities in resources or access to care within these regions.
In the past 30 years, Latin America has experienced significant demographic, epidemiologic, nutritional, and socioeconomic changes leading to an escalation in the prevalence of cardiovascular disease. In addition, most South American countries have a hybrid health care system of public and private medical coverage, which makes the level of coverage and access to medical resources obstacles for physicians who are managing chronic diseases. Likewise, cardiovascular disease mortality in the Asia Pacific region is on the rise because of poor adherence to recommended guidelines. This pattern is especially prominent in most migrant and mobile populations who have limited access to adequate health care. Therefore, the lack of access to medical resources and poor surveillance systems present obstacles to physicians prescribing and monitoring the use of VKAs. These disparities in the use of anticoagulation present an opportunity for improving quality of care.
Increasing the use of prophylactic anticoagulation in patients with HF and AF is essential to reducing the incidence and burden of stroke. The number of patients surviving a stroke is estimated to be 4.4 million in Southeast Asia and 9.1 million in the western Asia Pacific region. Likewise, the prevalence of stroke has been found to be between 6% and 9% in Latin American patients older than 65 years. Because most of the AF-related morbidity and mortality may be caused by stroke, it is important that all patients who meet the criteria be started on an effective anticoagulant. However, when deciding to initiate anticoagulation therapy, the risk of stroke must be carefully weighed against the risk of bleeding.
Interestingly, our findings indicated that patients with higher CHADS2 scores were less likely to be discharged with a VKA. We hypothesize that the paradoxical underuse of anticoagulation in patients with high CHADS2 scores might be explained by increased clinical concerns for bleeding, especially in older individuals. Moreover, worsening kidney function is a risk factor for not receiving a VKA at discharge. One possible explanation for this observation is that renal function is a surrogate for overall patient health. Consequently, physicians are less likely to prescribe anticoagulants for sicker patients (those with worsening renal function) for fear of bleeding. A survey study conducted in 2001 showed that when using VKAs, many physicians overestimate the risk of bleeding and underestimate the benefit from stroke prevention. Furthermore, many physicians also overestimated the benefit of aspirin in stroke prevention.
In our study, we observed higher aspirin use in the higher-risk (CHADS2 score ≥2) patients compared with the low-risk (CHADS2 score = 1) patients; this indicates that, in higher-risk patients, physicians favored antiplatelet therapy. In fact, the effect of aspirin in preventing stroke in higher-risk patients is very modest when compared with the benefit of VKAs. Furthermore, the increased risk of bleeding associated with VKAs when compared with aspirin is offset by the stroke-reducing benefits of VKAs.
A new bleeding risk score, HAS-BLED (Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or anemia, Labile INR, Elderly, and Drugs/alcohol), was developed using risk factors from a cohort study as well as bleeding risk factors from systematic reviews. In our cohort, VKA use was decreased in older individuals with higher creatinine levels (2 components of the HAS-BLED model). Consequently, the patients at higher risk for bleeding are less likely to receive a VKA at discharge. Because age also contributes to the CHADS2 score, patients with higher risk of bleeding also have a higher risk of stroke. Therefore, the decrease in anticoagulation in patients with higher risk of stroke may be explained by increased physician concern for bleeding, especially in older individuals.
In addition, a physician managing a patient who experiences a major bleeding event is less likely to prescribe VKAs, whereas managing a patient who experiences a stroke event does not increase the use of VKAs. This phenomenon can be further complicated by the difficulty of maintaining a therapeutic international normalized ratio with VKAs. The use of VKAs requires frequent monitoring, drug adjustments, and significant diet changes. These challenges might help to explain why VKAs are underused by physicians who treat patients with limited access to health care resources in the developing world.
Novel oral anticoagulation agents that do not require strict monitoring, have better safety profiles, and have more predictable effects may dramatically change the approach to managing patients with AF. These novel agents, such as dabigatran, apixaban, and rivaroxaban, are more convenient to use than VKAs, are associated with lower rates of intracerebral hemorrhage, and have the potential to increase adherence to therapy in regions where access to care and resources are limited. Although these agents will have higher initial acquisition costs, their net economic impact on health care costs will require further analysis.
First, the data for this registry were collected retrospectively from medical chart review and are dependent on the accuracy of medical personnel and completeness of the medical records from the individual hospitals. Although contraindications and intolerances were recorded in the registry, a proportion of untreated patients classified as eligible for treatment may have had contraindications that were not documented. Second, the type and duration of AF was not documented in the registry. Third, for the purposes of our analysis, we combined new-onset AF and history of AF, which can be a problem because they have different prognostic values, characteristics, outcomes, and indications for VKAs. Fourth, clinical outcomes, including stroke, mortality, and rehospitalization, were not included in the registry. Therefore, we were not able to explore the consequences of lack of anticoagulation in this patient population. Finally, the ADHERE-International registry may include hospitals with a higher likelihood of following evidence-based recommendations. Therefore, the true rates of anticoagulation use in these regions might be lower.
Discussion
The ESC AF guidelines, the Asian Pacific Society of Cardiology, and the Latin American Society of Cerebrovascular Diseases recommend that patients with a moderate-to-high risk of stroke be started on a VKA. Despite these recommendations, the risk-adjusted use of warfarin in the 10 countries included in our observations ranged from 25.1% to 65.5%, with most of the countries having <50% rate of use. The 2 countries with the lowest adjusted rates of anticoagulation were Taiwan and the Philippines with rates of 25.1% and 25.5%, respectively. The country with the highest adjusted rate was Australia with 65.2% VKA use at discharge. These vast differences may reflect disparities in resources or access to care within these regions.
In the past 30 years, Latin America has experienced significant demographic, epidemiologic, nutritional, and socioeconomic changes leading to an escalation in the prevalence of cardiovascular disease. In addition, most South American countries have a hybrid health care system of public and private medical coverage, which makes the level of coverage and access to medical resources obstacles for physicians who are managing chronic diseases. Likewise, cardiovascular disease mortality in the Asia Pacific region is on the rise because of poor adherence to recommended guidelines. This pattern is especially prominent in most migrant and mobile populations who have limited access to adequate health care. Therefore, the lack of access to medical resources and poor surveillance systems present obstacles to physicians prescribing and monitoring the use of VKAs. These disparities in the use of anticoagulation present an opportunity for improving quality of care.
Increasing the use of prophylactic anticoagulation in patients with HF and AF is essential to reducing the incidence and burden of stroke. The number of patients surviving a stroke is estimated to be 4.4 million in Southeast Asia and 9.1 million in the western Asia Pacific region. Likewise, the prevalence of stroke has been found to be between 6% and 9% in Latin American patients older than 65 years. Because most of the AF-related morbidity and mortality may be caused by stroke, it is important that all patients who meet the criteria be started on an effective anticoagulant. However, when deciding to initiate anticoagulation therapy, the risk of stroke must be carefully weighed against the risk of bleeding.
Interestingly, our findings indicated that patients with higher CHADS2 scores were less likely to be discharged with a VKA. We hypothesize that the paradoxical underuse of anticoagulation in patients with high CHADS2 scores might be explained by increased clinical concerns for bleeding, especially in older individuals. Moreover, worsening kidney function is a risk factor for not receiving a VKA at discharge. One possible explanation for this observation is that renal function is a surrogate for overall patient health. Consequently, physicians are less likely to prescribe anticoagulants for sicker patients (those with worsening renal function) for fear of bleeding. A survey study conducted in 2001 showed that when using VKAs, many physicians overestimate the risk of bleeding and underestimate the benefit from stroke prevention. Furthermore, many physicians also overestimated the benefit of aspirin in stroke prevention.
In our study, we observed higher aspirin use in the higher-risk (CHADS2 score ≥2) patients compared with the low-risk (CHADS2 score = 1) patients; this indicates that, in higher-risk patients, physicians favored antiplatelet therapy. In fact, the effect of aspirin in preventing stroke in higher-risk patients is very modest when compared with the benefit of VKAs. Furthermore, the increased risk of bleeding associated with VKAs when compared with aspirin is offset by the stroke-reducing benefits of VKAs.
A new bleeding risk score, HAS-BLED (Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or anemia, Labile INR, Elderly, and Drugs/alcohol), was developed using risk factors from a cohort study as well as bleeding risk factors from systematic reviews. In our cohort, VKA use was decreased in older individuals with higher creatinine levels (2 components of the HAS-BLED model). Consequently, the patients at higher risk for bleeding are less likely to receive a VKA at discharge. Because age also contributes to the CHADS2 score, patients with higher risk of bleeding also have a higher risk of stroke. Therefore, the decrease in anticoagulation in patients with higher risk of stroke may be explained by increased physician concern for bleeding, especially in older individuals.
In addition, a physician managing a patient who experiences a major bleeding event is less likely to prescribe VKAs, whereas managing a patient who experiences a stroke event does not increase the use of VKAs. This phenomenon can be further complicated by the difficulty of maintaining a therapeutic international normalized ratio with VKAs. The use of VKAs requires frequent monitoring, drug adjustments, and significant diet changes. These challenges might help to explain why VKAs are underused by physicians who treat patients with limited access to health care resources in the developing world.
Novel oral anticoagulation agents that do not require strict monitoring, have better safety profiles, and have more predictable effects may dramatically change the approach to managing patients with AF. These novel agents, such as dabigatran, apixaban, and rivaroxaban, are more convenient to use than VKAs, are associated with lower rates of intracerebral hemorrhage, and have the potential to increase adherence to therapy in regions where access to care and resources are limited. Although these agents will have higher initial acquisition costs, their net economic impact on health care costs will require further analysis.
Study Limitations
First, the data for this registry were collected retrospectively from medical chart review and are dependent on the accuracy of medical personnel and completeness of the medical records from the individual hospitals. Although contraindications and intolerances were recorded in the registry, a proportion of untreated patients classified as eligible for treatment may have had contraindications that were not documented. Second, the type and duration of AF was not documented in the registry. Third, for the purposes of our analysis, we combined new-onset AF and history of AF, which can be a problem because they have different prognostic values, characteristics, outcomes, and indications for VKAs. Fourth, clinical outcomes, including stroke, mortality, and rehospitalization, were not included in the registry. Therefore, we were not able to explore the consequences of lack of anticoagulation in this patient population. Finally, the ADHERE-International registry may include hospitals with a higher likelihood of following evidence-based recommendations. Therefore, the true rates of anticoagulation use in these regions might be lower.
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