risk reduction of the composite outcome measure, including stroke, systemic embolism, and intracranial bleeding.43 In a sub‐analysis from PREFER in AF (PREvention oF Thromboembolic Events‐European Registry in Atrial Fibrillation), data from 505 patients over 85 years old were analysed. It was found that the incidence of thromboembolic events was 2.8% per year without oral anticoagulant treatment versus 2.3% per year with OAC, which is equal to a 0.5% absolute risk reduction. Moreover, in very old patients, the risk of major bleeding was similar in patients on OAC and those on antiplatelet therapy or without antithrombotic treatment.15
Current evidence shows that DOAC efficacy in elderly patients was similar or superior to VKAs, as a result of summarized data from a meta‐analysis of 11 randomised trials comparing DOACs with VKAs in older patients (≥75) treated for acute venous thromboembolism or stroke prevention in AF.44 In the past decade, the four drugs were evaluated in large Phase III trials as alternatives to VKAs in patients with AF at risk of stroke, proving that DOACs are non‐inferior, if not superior, to warfarin for the prevention of stroke/systemic embolic events and for reducing bleeding.12 However, the results in elderly patients varied according to which drug was used, so different meta‐analyses have evaluated results in patients over 75. All DOACs demonstrated a similar‐to‐lower risk of stroke compared to the warfarin, while only apixaban and edoxaban significantly reduced major haemorrhagic events.2,45‐47
Optimizing the risk‐benefit equation in the elderly
When facing anticoagulation in an older patient, the high risk of bleeding may outweigh the benefit of preventing stroke. More than 50% of patients over 65 with atrial fibrillation do not receive anticoagulant treatment, when the guidelines recommend almost systematic anticoagulation of patients in this age group.48
As mentioned earlier, the risk of bleeding increases with age. Physicians must minimize it by controlling the degree of anticoagulation, its duration, and factors that may predispose to bleeding (falls, digestive tract injury, skin hematomas).
Intensity of anticoagulation
A high INR is one of the most critical factors related to the risk of bleeding – hence the importance of maintaining the lowest effective intensity of anticoagulation in the elderly. Several studies have reported a curvilinear relationship between the degree of anticoagulation and the risk of bleeding (Figure 25.1).49
Currently, a target INR of 2.5 (2 to 3) is recommended for treatment of VTE and primary and secondary stroke prevention in individuals with non‐valvular AF. Higher‐intensity anticoagulation may be needed under specific circumstances, such as preventing thromboembolism in those with prosthetic heart valves (2.5–3.5) or recurrent thromboembolism.50
Figure 25.1 Relationship between the intensity of anticoagulation and the risk of thromboembolism (TE) and bleeding in 1865 patients receiving oral anticoagulants after insertion of St Jude prosthetic heart valves. The single open circle represents 12 patients who received only antiplatelet agents because of contraindications to warfarin therapy. INR = international normalization ratio.
Source: Horstkotte et al.,49 ©1993, ICR Publishers.
There is no biomarker that reflects direct anticoagulant biological activity. Fixed doses are given, although, based on studies conducted so far, it is advisable to adjust the dose in different situations, as mentioned above.
Age‐related factors that predispose to bleeding
Tissue modifications
Any bleeding, even if it seems spontaneous, has an anatomical explanation: sometimes as the result of atrophy that occurs with age (which favours skin hematomas), but other times due to injuries (including malignant) in the bladder or bowel that appear earlier than in patients not receiving anticoagulation therapy. All patients who bleed should be investigated for underlying pathology, even if the bleeding episode occurred when the INR was excessive. Clinicians should also consider the possibility of occult bleeding in any patient with unexplained symptoms or signs while receiving anticoagulation.
Falls
One of the most frequently cited reasons for nontreatment is the perception of a high risk of falls and associated concerns about bleeding, especially intracranial haemorrhage.51 The study of Man‐Son‐Hing, et al. estimated that an individual would have to fall 295 times in one year for the risk of fall‐related major bleeding to outweigh the benefit of warfarin in reducing the risk of stroke.52 So, based on available evidence, perception of a high risk of falling should not be taken as justification not to initiate or to withhold anticoagulation in older patients who are otherwise suitable candidates for such therapy.48
Concomitant use of antiplatelets
30% of patients with NVAF who receive treatment with anticoagulants as primary stroke prevention receive antiplatelet agents concomitantly, with the risk of bleeding that this implies. The concomitant use of DOACs with antiplatelet agents has shown a decrease in the incidence of intracranial bleeding and other major bleeds but similar incidence of gastrointestinal bleeding when compared with VKAs and antiplatelets.53
Duration of anticoagulant therapy
Stroke prevention in NVAF or prevention of thromboembolism from a prosthetic heart valve requires long‐term anticoagulation, and many elderly patients are prescribed anticoagulants for these reasons. Although data on the risk of VTE recurrence in elderly subjects are controversial, the risk could be considered no higher – and perhaps even lower – than in younger subjects. Because the risk of bleeding during anticoagulation treatment is higher in elderly subjects, three to six months of anticoagulant treatment in elderly patients with acute VTE is recommended. Extended anticoagulant treatment is not indicated in elderly patients, and any other decision should be carefully evaluated.54
Start‐stop‐start anticoagulation
Starting anticoagulation in elderly patients
Sometimes, starting long‐term anticoagulation in an elderly patient is a complicated decision. In major functional impairment or when life expectancy is short, the benefit that anticoagulation could offer as primary prevention is questionable.
On the other hand, acetylsalicylic acid has been classically considered an alternative to anticoagulation, especially in older patients (regardless of function), in hopes of minimizing the risk of bleeding. There is no current evidence to recommend using salicylic acetic acid in the primary prevention of patients with AF or as a prescription after initial anticoagulation in patients with VTE, and its use is associated with an increased risk of bleeding.15,54
Older patients need closer monitoring during the first month of anticoagulation because the risk of bleeding is higher in this period.55‐57 The elderly are at high risk of over‐anticoagulation at this time, particularly if standard rather than tailored induction doses are used. Siguret et al.
