Anticoagulation can provide benefit to patients with atrial fibrillation, hypertension, diabetes, angina, acute coronary syndrome, and postoperative heart valve replacement, especially those with risk factors for stroke, and the absolute benefit of anticoagulation far outweighs absolute risk factors such as bleeding. For those at high risk of vascular obstruction, several clinical trials have shown a moderate risk of complications, but the benefit/risk ratio of this prophylactic treatment strategy for patients at low risk of vascular obstruction, is uncertain. And there is no unified international case selection criteria and dosing principles, so the guidelines for antiplatelet therapy especially emphasize individualization of treatment.
1. Which patients should receive anticoagulation therapy
In general, anticoagulation is not required for patients younger than 60 years without a history of stroke, hypertension, diabetes mellitus, coronary artery disease, transient ischemia (TIA) or congestive heart failure.
Those aged 60-75 years with risk factors such as atrial fibrillation, hypertensive disease, diabetes mellitus, coronary artery disease, TIA, stroke, acute coronary syndrome, or heart valve replacement should receive appropriate anticoagulation measures.
In patients over 75 years of age with these risk factors, aggressive anticoagulation measures should be taken, but the administration of warfarin is controversial, but there is agreement on the administration of aspirin.
The prevalence of paroxysmal AF is high, accounting for approximately 40% of all AF patients, and approximately 25% of paroxysmal patients develop persistent AF, and research data suggest that patients with paroxysmal AF should also be treated with aggressive anticoagulation.
In patients with a history of infarction, antiplatelet therapy for 2 years can absolutely reduce reinfarction-like vascular events by 3.6%; reduce stroke and TIA by 3.6%; and reduce acute ischemic stroke by 0.9% with 1 month of antiplatelet therapy. In patients with chronic stable angina, aspirin 75 mg/d significantly reduced the incidence of primary endpoint events, including infarction and sudden death, by 34%.
2. Which patients should not receive anticoagulation therapy
Patients receiving anticoagulation therapy should first be identified as having contraindications to anticoagulation, such as: dementia, chronic renal failure, anemia, prolonged basal prothrombin time measurement compared to control, post-treatment systolic blood pressure >160 mmHg and/or diastolic blood pressure >100 mmHg, severe chronic alcohol dependence with transaminases 3 times above the upper limit of normal, fecal occult blood Positive occult bleeding, history of intracranial hemorrhage, gastrointestinal and genitourinary bleeding within 6 months, severe bleeding in previous warfarin therapy, after head trauma and long-term use of non-steroidal anti-inflammatory drugs.
3.The choice of anticoagulant drugs
3.1 Antithrombotic pioneer – heparin and low molecular heparin
Heparin may be used more for the acute treatment of important thrombotic diseases and is used for thromboprophylaxis in a very urgent situation. Its advantage is that it has a more definite efficacy and a more rapid onset of action. The disadvantage is that it needs to be tested and needs to be monitored regularly with APTT. This requirement for regular monitoring may cause some clinical inconvenience. This inconvenience may lead to an increase in clinical bleeding complications. The second type of low molecular heparin, although it is not required to be monitored according to the drug description, in fact, all heparins are theoretically required to be monitored. And this monitoring is not easy. The advantage of low-molecular heparin is that it is easier to use and has fewer bleeding complications than regular heparin.
3.2 Safe and commonly used – warfarin
Warfarin is the most commonly used drug in anticoagulation therapy for atrial fibrillation and heart valve replacement surgery, and is an oral vitamin K antagonist. Currently, the International normalized Rater (INR) is generally used as the dose standard for warfarin. In recent years, the warfarin doses in several large-scale clinical studies have shown a decreasing trend. The current recommendation of 2.0-3.0 INR is a reference indicator for a lower dose, which can be equally effective in anticoagulation and can lead to a significant reduction in the risk of bleeding.
One study confirmed that the optimal anticoagulation intensity in elderly patients with atrial fibrillation with risk factors for stroke should be 2.0-3.9 INR, and that anticoagulation therapy at intensities below 2.0 INR is not preventive. Other trials have confirmed that stroke in patients with non-valvular atrial fibrillation on warfarin doses below 2.0 INR has a significantly higher incidence of thrombosis. Others have suggested that an anticoagulation intensity of 1.5-2.5 INR in patients over 75 years of age may also prevent thrombosis, so the dose of warfarin is not uniform. Nevertheless, 2.0-3.0 INR is still a widely used reference indicator for regular clinical monitoring of warfarin application.
3.3 Both prevention and treatment – aspirin
The prophylactic effect of aspirin is closely related to the dose, and 100 mg/day is recommended. Warfarin is generally considered to be more ideal than aspirin for anticoagulation therapy, but aspirin is safer, easier to take, and less expensive, and can be considered for patients over 75 years of age who are not suitable for warfarin therapy.
3.4 Stent partner – clopidogrel
Clopidogrel is one of the cardiovascular medications that must be taken after drug-coated vascular stenting. It is a platelet aggregation inhibitor that acts by irreversibly modifying platelet adenosine diphosphate (ADP) receptors, causing activation of the glycoprotein GPIIb/IIIa complex; blocking the expansion of activated platelets and inhibiting platelet aggregation induced by other agonists, thus providing a comprehensive inhibition of platelet aggregation. It is indicated for patients after vascular stenting, who have had recent episodes of stroke, myocardial infarction, and diagnosed peripheral arterial disease, where the drug may reduce the incidence of atherosclerotic events (e.g., myocardial infarction, stroke, and vascular death).
The recommended dose of clopidogrel is 75 mg per day and is not affected when taken with food. No dose adjustment is required in elderly patients or in patients with renal disease. Clopidogrel prolongs bleeding and should be used with caution in patients with wounds (especially in the gastrointestinal tract and inside the eye) that are prone to bleeding. Patients should be aware that it may take longer than usual to stop bleeding on Bolivar, and patients should report abnormal bleeding to their physicians. Patients should inform their physicians that they are taking clopidogrel before surgery and before taking other new medications.
3.5 Star of Hope-Rivaroxaban
Rivaroxaban (trade name Xarelto) is the world’s first oral direct inhibitor of factor Xa. Factor Xa plays a key role in the coagulation cascade, both in the endogenous and exogenous pathways. Rivaroxaban terminates the burst of thrombin production by directly inhibiting factor Xa in a highly selective manner.
Rivaroxaban is rapidly absorbed when administered orally, reaching peak blood levels 2-4 hours after administration, and is not affected by coadministration with food; the absolute bioavailability of 10 mg of rivaroxaban is close to 100%; pharmacokinetic studies indicate that rivaroxaban can be administered once daily; the therapeutic window is wide, and routine coagulation monitoring is not required; no age, sex, weight, or race adjustment is required. Dose adjustment is not required based on age, gender, weight and race.
Currently, rivaroxaban has received marketing approval in Canada, the European Union, South America, Singapore, Australia and other countries and regions. The currently approved indications are for the prevention of VTE in adult patients undergoing major orthopedic surgery (total hip or total knee arthroplasty) of the lower extremities. Currently, rivaroxaban is in the new drug marketing approval stage in China. If rivaroxaban can successfully pass the clinical trial and be applied to the majority of patients, we will no longer need to establish anticoagulation clinics. Patients will be able to make anticoagulation therapy a routine treatment, just as they do with antiplatelet drugs such as aspirin.
Rivaroxaban has made anticoagulation easier and safer to use, increasing the operability of anticoagulation therapy. In the past, we required hospitals to establish anticoagulation clinics when applying anticoagulants and monitor patients with medication. Rivaroxaban has a definite anticoagulant effect, does not require constant monitoring, and is theoretically safer than all previous anticoagulants. However, the final safety assessment will not be known until all trials are completed.
4. Complications of anticoagulation therapy and their prevention
As the number of elderly patients with atrial fibrillation receiving anticoagulation therapy increases, the number of bleeding complications associated with anticoagulation is also increasing. Bleeding complications occurring during anticoagulation therapy are usually categorized into three types: minor, severe and fatal bleeding. Minor bleeding is mainly manifested as epistaxis, hematuria and bleeding spots on the skin. It does not affect the determination of the effect of anticoagulation therapy. Severe bleeding is most common with gastrointestinal bleeding, which usually requires treatment, including hospitalization and blood transfusion, or surgical treatment; fatal bleeding is most commonly intracranial bleeding, whose incidence is low but can directly threaten the patient’s life and is a serious problem faced by anticoagulation therapy.
Advanced age is an important factor in bleeding complications. The increase of bleeding complications in anticoagulation therapy in the elderly may be related to the following factors: increased sensitivity to warfarin in the elderly; increased likelihood of comorbidities with other serious diseases and increased likelihood of reactions between drugs due to the sharing of multiple drugs; decreased patient compliance; and the vulnerability of the elderly to falls and related trauma. Older adults tend to have a history of hypertension or stroke, which are both high-risk factors for stroke in elderly patients with atrial fibrillation and important causes of increased bleeding with anticoagulation therapy. Therefore, anticoagulation therapy in the elderly should be performed with an appropriate reduction in anticoagulation intensity, and aspirin can be switched to aspirin if necessary.
Anticoagulation intensity is another important factor for bleeding complications, and anticoagulation intensity is a stronger predictor of bleeding than age. In the last decade, the intensity of anticoagulation therapy has been reduced from 3.0-4.5 INR in the past to 2.0-3.0 INR at present. numerous clinical trials have demonstrated that elderly patients with atrial fibrillation who have an anticoagulation intensity below 3.0 INR and whose blood pressure is well controlled do not have an increased risk of intracranial hemorrhage.
The duration of anticoagulation therapy can also influence the incidence of bleeding. The risk of bleeding increases 5-10-fold during the first months of warfarin therapy, with a relatively flat incidence of bleeding after 3-6 months. This condition may be associated with over-anticoagulation or the presence of undiagnosed gastrointestinal disease or genitourinary bleeding disorders. The elderly are more sensitive to warfarin and may overreact to warfarin, and loading doses should not be used.
5.Pay attention to the interaction between drugs
Drug interactions can also increase the risk of bleeding. Common drugs that can enhance the potency of anticoagulant drugs include amiodarone, androgens, cimetidine, sulphur withdrawal, erythromycin, thyroxine, metronidazole; drugs that reduce the potency of anticoagulant drugs include antimitotic drugs, barbiturates, phenylephrine, rifampin, etc. Concomitant use with these drugs should be avoided as much as possible during anticoagulation therapy. Appropriate dose adjustments must be used and drug reactions must be observed. In addition, experience with clopidogrel in patients with severe hepatic and renal impairment is extremely limited, so it should be used with caution in these patients who may have a bleeding tendency. Concomitant use of Warfarin is not recommended because of the bleeding tendency associated with its use. Clopidogrel should be used with caution in patients taking concomitant medications that are prone to gastrointestinal wounding (e.g., NSAIDs). This medication is not recommended for pregnant and lactating women.