Aspirin deep vein thrombosis: Does aspirin prevent venous thromboembolism? | Hematology, ASH Education Program
An Aspirin a Day May Not Keep DVT Away
Aspirin has been used for decades to treat health problems ranging from the common headache and arthritis to fever and toothaches, and for the prevention of heart attacks. Aspirin therapy works by helping the body reduce pain, fever, swelling, and to prevent the formation of specific types of blood clots. In fact, it can be used to prevent blood clots that flow to the brain and cause certain types of stroke.
The American Heart Association recommends aspirin therapy to prevent a recurrence of heart attacks, recurring angina, and second strokes. But when it comes to deep vein thrombosis (DVT), a condition in which a clot forms in a deep vein, typically in your leg or pelvic area, there is controversy about the usefulness of aspirin therapy.
Aspirin Therapy and DVT
“Aspirin therapy has virtually no role to play in the treatment of deep vein thrombosis or the prevention,” says Jack Ansell, MD, chairman of the department of medicine at Lenox Hill Hospital in New York City. “Aspirin interferes with arterial platelet aggregation [sticking to other platelets as a clump], which has major important effects in cardiovascular circulation. But for DVT, there is no case in which it is appropriate.”
DVT Prevention: Aspirin Therapy During Surgery
Dr. Ansell says that a number of orthopedic surgeons believe that, during surgery for hip or knee replacements, aspirin therapy can prevent dangerous blood clots that cause DVT. “A good number of surgeons still use aspirin, even when there is a major debate among physicians as to how effective it is. But most experts will not agree that it’s effective or appropriate.”
The American Academy of Orthopaedic Surgeons (AAOS) has pre- and post-surgical guidelines that are designed to prevent pulmonary embolism, a sometimes fatal condition in which a blood clot caused by DVT breaks free and travels to the lungs.
The AAOS guidelines say that in the case of a total joint arthroplasty, in which a joint is replaced, an orthopedic surgeon may use three treatment options to help prevent a pulmonary embolism:
- The blood thinner warfarin (Coumadin and others)
- A mechanized treatment for blood clots in which a sleeve-like device regularly compresses the legs during and after surgery to keep the blood flowing
Aspirin Therapy and DVT: The Debate
A recent study on this topic was presented at an AAOS meeting in which researchers examined data from more than 93,840 patients who had undergone knee replacement surgery. They compared the risk of pulmonary embolism, death, surgical site bleeding, and infections in patients who received aspirin and with patients who were given other therapies.
The number of blood clots that developed in the lungs of patients who took aspirin was the same as for those who took warfarin, which is injected. However, patients who took aspirin may have been less at risk for blood clots in the first place.
Is this enough evidence to use aspirin as a DVT treatment? Not according to Ansell, the AAOS, and the American College of Chest Physicians, who believe that heparin, low-molecular-weight heparin (LMWH), or warfarin should be used before joint replacement surgery to prevent both DVT and pulmonary embolism. There is no clear evidence that aspirin can help to prevent most cases of blood clots, says Ansell.
Aspirin is also not a means for preventing DVT in people who sit motionless while traveling long distances. The best way to prevent DVT when sitting for long periods is to get up and walk around as much as possible when on an airplane and to stop every few hours and stretch your legs when driving long distances.
Aspirin Therapy: What It Helps
Since aspirin reduces the ability of bloods platelets to stick to each other, it’s often prescribed to those not only at risk of a clot-related stroke, but also for those who have certain blood vessel diseases.
But you need to avoid aspirin if you have the following conditions:
- Pregnancy, unless prescribed by your doctor
- High blood pressure
- Bleeding disorders
- Asthma, in some cases
- Aspirin allergy or sensitivity
Side effects of aspirin therapy include increased risk of stomach bleeding and kidney failure.
If you’re worried about DVT, talk to your doctor about your individual risk factors and the things you can do to minimize those risks.
Can Aspirin Prevent a DVT?
You’ve heard of people with prior heart attack history being on low-dose aspirin therapy to prevent another heart attack, so doesn’t the same apply to blood clots? Aspirin therapy is designed to thin the blood, right?
Not necessarily, at least not with any guarantee. It is true that aspirin therapy can be an effective blood thinning or anticoagulation therapy for some, but not in all situations. It may be considered in scenarios where the development of a deep vein thrombosis (DVT) or blood clot in a deep vein is not the result of immobility, post-surgical recovery, or other obvious cause.
A couple of studies have shown the aspirin therapy can reduce the risk of recurrent DVTs or pulmonary embolisms (PE) by “more than a third without significantly increasing the risk of bleeding. However, a 2016 study found no difference in the rate of development of venous thrombo-embolism (VTE) following orthopedic procedure such as a total hip or knee arthroplasty procedures.
Both a DVT and VTE are, essentially, venous blood clots. The “embolism” defines the status of the clot after it is broken free and travels through the bloodstream. One of the dangers of a blood clot on the move is the potential to block blood flow in the lungs, known as a pulmonary embolism or PE.
What exactly does aspirin do?
Aspirin components also act as an anticoagulant of sorts, but self-diagnosis and taking aspirin on a daily basis to thin the blood is not recommended without the supervision of a physician.
Some medical experts believe that aspirin therapy can be just as effective as more potent (and expensive) blood thinning medications available on the market today for the preventions of certain blood clots, such as those that may develop following an orthopedic procedure such as joint replacement.
Most of the studies in this area focus on patients who have undergone joint replacement therapies, as artificial joints do provoke a higher risk of blood clot development following surgery. Common anticoagulant or blood thinning medications giving to post-surgical patients include Xarelto or heparin. However, aspirin is also an option.
Studies have emphasized that the aspirin therapy is given following initial treatment with an anticoagulant medication immediately post-surgery. In the studies, over 700 orthopedic joint replacement patients were placed on a 10-day therapy of heparin, followed by four weeks of low-dose aspirin (81 mg) daily.
In this particular study, a couple of individuals on the aspirin therapy did end up developing a blood clot. Even so, the aspirin therapy has been deemed as a safe alternative for some. Studies continue regarding the potential of aspirin to reduce bleeding.
At this point, aspirin therapy as an anticoagulant or preventive for development of a DVT post-surgery is not a recognized standard of care, but it is something that patients can discuss with their physicians.
Treating Deep Vein Thrombosis with Aspirin
What is Deep Vein Thrombosis?
Deep vein (venous) thrombosis (DVT) is a condition where a thrombus, a blood clot, develops in the deep vein(s) of the body. While these blood clots can technically develop in just about any deep vein of the body, they generally tend to occur in the deep veins of the leg. This can lead to swelling and pain of the leg but sometimes may result in no signs or symptoms at all. The swelling and pain of the leg(s) as a result of DVT is the least of your worries, however.
There is a possibility that a little piece of the thrombus may break off. Once broken off, this little piece is now called an embolus. This embolus can travel to, and lodge itself within, the lungs. A blood clot in the lungs is called a pulmonary embolism because pulmon- means lungs. In some cases, a pulmonary embolism can lead to death. That’s why DVT should not be taken lightly.
DVT can be caused by many things, including clotting disorders of the body where the blood clots too easily; injury to the deep veins of the body, such as from an accident or surgery; or even general lack of mobility, such as when a person sits for too long during an airplane ride.
What is Aspirin?
Briefly, let’s turn our attention to acetylsalicylic acid, otherwise just called aspirin. This is a kind of NSAID, or non-steroidal anti-inflammatory drug. Aspirin is used to relieve pain and to reduce a fever. So, people who have headaches, muscle pain, or even arthritis may take an aspirin. Other people may have been told to take an aspirin to reduce the risk of a stroke or a heart attack.
The reason some doctors tell their patients to take aspirin to help prevent a stroke or heart attack is because both may be caused by a blood clot (thrombus). Aspirin helps prevent the formation of blood clots. It does so by stopping blood components called platelets from sticking to one another, so it’s also classified as an antiplatelet drug. Platelets are important for the formation of blood clots. If platelets can’t stick together, blood clots are less likely to form.
Is Aspirin Useful For DVT?
So is aspirin useful for treating or preventing DVT? Well, aspirin helps prevent blood clot formation but it doesn’t break up the blood clot. This means if DVT has already occurred, it won’t dissolve a blood clot that’s already there. However, there is some evidence that aspirin is helpful in preventing DVT.
Some doctors recommend that aspirin be given to patients who cannot tolerate more serious anticoagulants (blood thinners), like warfarin (Coumadin), in order to prevent DVT. However, it must be noted that aspirin is not as effective in preventing blood clots from forming as blood thinners are. All in all, if a patient cannot take an anticoagulant and has no other options, aspirin is better than nothing for the prevention of DVT.
Deep vein (venous) thrombosis (DVT) is a condition where a thrombus, a blood clot, develops in the deep vein(s) of the body. A piece of this thrombus may break off. At that point, that little piece is called an embolus. The embolus can travel to the lungs and cause a pulmonary embolism, a blood clot in the lungs. This is a potentially fatal condition.
There is evidence that a drug called acetylsalicylic acid, otherwise just called aspirin, can help prevent DVT. Aspirin is a kind of NSAID, or non-steroidal anti-inflammatory drug, which also prevents the aggregation of platelets, important components of blood clots. While not as effective as anticoagulants (blood thinners) like warfarin, aspirin can provide some preventive protection from DVT in patients who cannot tolerate stronger anticoagulants.
Medical Disclaimer: The information on this site is for your information only and is not a substitute for professional medical advice.
More Risk with the Same Reward
More blood thinners aren’t automatically better, another study confirms.
A new publication in JAMA Internal Medicine focuses on the minimal pros and the concerning cons of combining a daily aspirin with a drug from the newer class of anticoagulants that include apixaban, dabigatran, edoxaban and rivaroxaban.
Patients were taking one of these direct oral anticoagulants known as DOACs to prevent strokes from non-valvular atrial fibrillation or for the treatment of venous thromboembolic disease (deep vein thrombosis or pulmonary embolism). The included patients did not have another reason to take aspirin such as a recent history of a heart attack or a history of a heart valve replacement.
The researchers discovered that almost one-third of the people who were prescribed a DOAC were also taking aspirin without a clear reason for the aspirin.
“The patients on combination therapy were more likely to have bleeding events but they weren’t less likely to have a blood clot,” says lead author Jordan Schaefer, M.D., an assistant professor of internal medicine and a hematologist at Michigan Medicine. “Therefore, it’s important that patients ask their doctors if they should be taking aspirin when they are prescribed a direct oral anticoagulant.”
The combination of an anticoagulant and an antiplatelet may be appropriate for people who have had a recent heart attack, recent coronary stent placement or bypass surgery, prior mechanical valve surgery or known peripheral artery disease, among other conditions says co-author Geoffrey Barnes, M. D., M.Sc., an assistant professor of internal medicine and a vascular cardiologist at the Michigan Medicine Frankel Cardiovascular Center.
For the others, “combination therapy may not be happening intentionally; rather, the addition of aspirin might get overlooked because it’s not in any one specialist or general care provider’s territory,” Barnes says.
The authors note that there are many medical conditions and situations where adding aspirin with a direct oral anticoagulant has not been adequately studied. Schaefer adds that they plan to confirm their study findings in a larger, longer study because there were not many blood clots that occurred during the timeframe of this study, potentially limiting their ability to assess if aspirin could be beneficial.
Previously, Schaefer and Barnes also reported a significant increase in adverse outcomes for people taking both aspirin and warfarin, a different kind of anticoagulant.
SEE ALSO: More Than One-Third of Patients Risk Major Bleeding By Doubling Up on Blood Thinners
Schaefer originally presented these registry-based cohort study results at the 2019 annual meeting of the American Society of Hematology.
Paper cited: “Adverse Events Associated with the Addition of Aspirin to DOAC Therapy Without a Clear Indication,” JAMA Internal Medicine. DOI: 10.1001/jamainternmed.2021.1197
Prevent DVT (deep vein thrombosis) when you travel
Travel-related DVT is rare in healthy people. But if you’re travelling long distance, there are several ways you can reduce your risk.
DVT (deep vein thrombosis) is when a blood clot forms in a deep vein, usually in the leg, and blocks blood flow. It can happen after sitting still during long journeys by bus, train, or air.
Read more about the symptoms and treatment of DVT.
General advice to reduce your risk of travel-related DVT
If you’re travelling for 3 hours of more by plane, train or car, take these steps during the journey to reduce your risk of DVT:
- wear loose, comfortable clothes
- do calf exercises at least every half hour – raise your heels, keeping your toes on the floor, then bring them down 10 times. Then raise and lower your toes 10 times
- walk around whenever you can
- drink plenty of water
- do not drink alcohol or take sleeping pills
Who’s at extra risk of travel-related DVT?
Some health conditions and other things may increase your risk of DVT on long journeys. You’re at higher than average risk of DVT if you:
- have a history of DVT or pulmonary embolism
- have cancer
- have had a stroke
- have heart disease
- have an inherited tendency to get blood clots
- have had recent surgery – especially in the tummy, pelvic region or legs
- are very overweight
- are pregnant or you’ve had a baby in the previous 6 weeks
- take oestrogen-containing medicines such as HRT (hormone replacement therapy) or the combined contraceptive pill
If you think you’re at extra risk of DVT, see your GP before you travel. You might have to take extra precautions such as wearing flight socks or compression stockings during the journey.
Flight socks and compression stockings
Wearing compression stockings or flight socks during journeys of 3 hours or more can help prevent DVT if you’re at an increased risk.
The stockings or socks are usually knee length; compression stockings can also be thigh high.
They work by putting gentle pressure on your leg and ankle to help blood flow.
Compression stockings and flight socks come in different sizes with different levels of compression. Class 1 stockings have the lowest compression (with a pressure of 14-17 mmHg at the ankle) and are generally sufficient to prevent DVT.
It’s important that compression stockings are worn correctly. Ill-fitting stockings could further increase the risk of DVT.
You can buy compression stockings and flight socks from pharmacies, airports and many high-street shops and pharmacies. They can also be prescribed by a GP.
Get advice on size and proper fitting from a pharmacist or another health professional.
Travelling while recovering from a previous DVT
If you had DVT recently, you’re probably taking medicine, such as apixaban or warfarin, to prevent new blood clots.
If that’s the case, your medicine will protect you from getting another DVT while you’re taking it. So, your risk of getting a DVT from travelling is low and there should be no reason why you cannot travel, including long haul. Speak to your doctor if you have any concerns before you travel.
If you had a DVT within the last 2 weeks, get the all-clear from your doctor before travelling.
Read a traveller’s experience of getting DVT from flying.
Page last reviewed: 18 April 2019
Next review due: 18 April 2022
Aspirin Dose and Venous Thromboembolism Prevention after Total Hip and Knee Arthroplasty – Consult QD
By Carlos Higuera-Rueda, MD
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Patients undergoing total joint arthroplasty (TJA) are at risk of developing venous thromboembolism (VTE), which includes deep venous thrombosis (DVT) and pulmonary embolism (PE). Historically, without prophylaxis the rate of DVT in patients undergoing TJA was between 35 percent and 85 percent. Over time, surgical approaches and operative times improved dramatically; epidural and spinal anesthesia were chosen preferentially; pneumatic compression pumps were also introduced; and most importantly, patients were encouraged to mobilize earlier. Almost all physical therapy protocols today recommend same-day out-of-bed activities after surgery. With the introduction of these perioperative modifications, the incidence of VTE events underwent a dramatic reduction in clinically symptomatic DVTs and fatal PEs.
Recently, the incidence of VTE is reported to be less than 1 percent to 2 percent. With such a low incidence and the standardization of multimodal prophylaxis practices, it became difficult to distinguish differences in efficacy of different chemoprophylactic modalities.
Chemoprophylactic modalities abound, so is aspirin appropriate?
There is a wide and expanding array of VTE chemoprophylactic agents for patients undergoing TJA. Potent agents, such as low-molecular-weight heparin (LMWH), warfarin or the newer anticoagulation agents have been the accepted practice. Many well-known challenges associated with these agents, such as the risk of bleeding and wound-related infections and difficulties with administration, titration and monitoring, were brought into scrutiny in the search for an ideal chemoprophylaxis.
Aspirin has long been established as an effective drug for preventing arterial thromboembolic events in cardiovascular and cerebrovascular diseases (low-dose 81mg). The role of aspirin as an effective modality for the prevention of VTE following TJA has been described in the medical literature for many decades. Aspirin is well tolerated, inexpensive and easy to administer with no need for routine blood monitoring.
Determining optimal dose
With the endorsement of aspirin in many published guidelines (American Academy of Orthopaedic Surgeons 2009, 2011 and American College of Clinical Pharmacy 2012) and the additional emerging evidence demonstrating its efficacy, aspirin gained popularity in the orthopaedic community as an effective VTE prophylactic agent following TJA.
The only remaining question was about the optimal dose, and we endeavored to answer this question. If a regimen of 325 mg twice a day was efficacious (the current recommended regimen), would a smaller dose (81 mg twice a day) be equivalently efficacious given its pharmacodynamics and also have less risk of complications?
We retrospectively reviewed 16,000 medical records for primary TJA patients between 2012 and 2016. We identified 9,602 patients who received enteric-coated aspirin twice daily after surgery for four to six weeks depending on surgeons’ preference. A total of 2,360 patients received 81 mg (low-dose group) and 7,242 patients received 325 mg aspirin (high-dose group). Complications collected within 90 days after surgery were VTEs (DVT and PE), bleeding (gastrointestinal and wound bleeding) and mortality.
For patients who underwent total hip arthroplasty (THA), no statistical significant difference was observed between the aspirin groups in terms of VTE, DVT, PE, bleeding risk or mortality (Figures 1, 2). After adjusting for confounders, low-dose versus high-dose aspirin was not associated with increased risk for VTE, DVT, PE, bleeding or mortality after THA.
Figure 1: Incidence of venous thromboembolism (VTE), deep venous thrombosis (DVT) and pulmonary embolism (PE) within 90 days after total hip arthroplasty (THA).
Figure 2: Incidence of bleeding (gastrointestinal and wound) and mortality within 90 days after total hip arthroplasty (THA).
For patients who underwent total knee arthroplasty (TKA), there were no statistically significant differences between the groups in term of VTE, PE, bleeding or mortality after surgery (Figure 3, 4). However, the incidence of DVT was lower in the low-dose aspirin group compared to high-dose group (0.53 percent versus 1.41 percent, respectively. p=0.01). Interestingly, low-dose aspirin was associated with reduced risk of DVT compared to high-dose aspirin in the regression model after accounting for confounders (OR=0.38, 95 percent CI [0.17 – 0.84], p=0.006). In addition, low-dose versus high-dose aspirin was not associated with increased risk of VTEs (p=0.10), PE (p=0.17), bleeding (p=0.79) or mortality (p=0.78) within 90 days after TKA.
Figure 3: Incidence of venous thromboembolism (VTE), deep venous thrombosis (DVT) and pulmonary embolism (PE) within 90 days after total knee arthroplasty (TKA).
Figure 4: Incidence of bleeding (gastrointestinal and wound) and mortality within 90 days after total knee arthroplasty (TKA).
Physician takeaways from this study
Overall, there was no difference in VTE incidence following TKAs/THAs in low-dose versus high-dose aspirin groups. Both aspirin regimens showed similar results in terms of risk of bleeding (GI and wound) and mortality after TJA.
We concluded that low dose of aspirin (81 mg twice a day) is not inferior to a higher dose of aspirin (325 mg twice a day) in the prevention of VTE following total hip and knee arthroplasty. We currently use ASA 81 mg PO BID for four weeks in primary arthroplasty procedures in low-risk patients.
Journal of Trauma and Acute Care Surgery
Current prophylaxis does not completely prevent deep vein thrombosis (DVT) in trauma patients. Recent data suggest that platelets may be a major contributor to hypercoagulability after trauma, indicating a potential role for antiplatelet medications in prophylaxis for DVT. We sought to determine if preinjury aspirin use was associated with a reduced incidence of lower extremity DVT in trauma patients.
Using a retrospective case-control design, we matched 110 cases of posttrauma lower extremity DVT one-to-one with controls using seven covariates: age, admission date, probability of death, number of DVT risk factors, sex, mechanism of injury, and presence of head injury. Data collected included 26 risk factors for DVT, prehospital medications, and in-hospital prophylaxis. Logistic regression models were created to examine the relationship between prehospital aspirin use and posttrauma DVT.
Preinjury aspirin was used by 7.3% of cases (patients diagnosed with in-hospital DVT) compared with 13.6% of controls (p = 0.1). Aspirin was associated with a significant protective effect in multivariate analysis, with an odds ratio of 0.17 (95% confidence interval, 0.04–0.68; p = 0.012) in the most complete model. When stratified by other antithrombotic use, aspirin showed a significant effect only when used in combination with heparinoid prophylaxis (odds ratio, 0.35; 95% confidence interval, 0.13–0.93; p = 0.036).
Preinjury aspirin use seems to significantly lower DVT rate following injury. This association is strongest when heparinoid prophylaxis is prescribed after patients on preinjury aspirin therapy are admitted. Aspirin as added prophylaxis for DVT in trauma patients needs to be further evaluated.
LEVEL OF EVIDENCE
Prognostic and epidemiologic study, level III.
Combined intermittent pneumatic leg compression and pharmacological prophylaxis to prevent deep vein thrombosis and pulmonary embolism
Deep vein thrombosis (DVT) and pulmonary embolism (PE), collectively known as venous thromboembolism (VTE), occurs when a blood clot develops inside the veins of the lower extremities (DVT) and travels to the lungs (PE). All of this can be a complication of surgery or injury.These complications prolong hospital stay and are associated with long-term disability and death. Patients undergoing total hip or knee arthroplasty, or surgery for colorectal cancer are at high risk for venous thromboembolism. Obstruction of venous blood flow, increased blood clotting, and damage to blood vessel walls all contribute. Addressing several of these causes can help prevent complications.Mechanical intermittent pneumatic compression of the legs (intermittent pneumatic compression, AUC) removes obstructions to blood flow (venous congestion), while medications such as aspirin and anticoagulants (low molecular weight heparin) reduce blood clotting. These drugs are used for pharmacological prophylaxis (drugs that prevent blood clots). However, these medications can also increase the risk of bleeding. This review is an update to a review first published in 2008.
Research characteristics and main results
We identified 22 studies with 9137 participants to be included in this review (current as of May 2016). The average age of the participants was reported to be 65.2 years. Most of the participants either underwent a high-risk procedure or had a high-risk condition. Predisposing conditions were orthopedic surgery in 12 studies; urological, cardiothoracic, neurosurgical, traumatological, general surgical, gynecological or other conditions in other studies.
Compared to AUC alone, AUC in combination with drugs did not show any difference in the incidence (number of new cases) of PE (12 studies with 3017 participants). The incidence of DVT was reduced with AUC plus drugs compared with AUC alone (11 studies with 2934 participants). Adding the drug to the AUC, however, increased the risk of any bleeding compared to AUC alone by 0.66-4.0%. Major bleeding was characterized in the same way, the increase ranged from 0.1 to 1.5%. Further analysis of different subgroups of participants (orthopedic versus non-orthopedic patients) showed no difference for DVT, while there was no way to assess differences between subgroups for PE.
Compared with drug treatment alone, the combination of AUC and drugs reduced the incidence of PE (10 studies with 3544 participants). The incidence of DVT did not differ between the drug treatment groups and the combination of AUC with drugs (11 studies with 2866 participants). No differences were observed in the incidence of bleeding (3 studies with 244 participants). Further analysis of different subgroups of participants (orthopedic and non-orthopedic patients) did not show any difference in the frequency of PE and DVT between the two.
Quality of evidence
From this review, we obtain moderate-quality evidence consistent with current recommendations to support the combination of AUC and pharmacological prophylaxis to reduce DVT and PE in hospitalized patients (versus AUC or pharmacological prophylaxis alone). Moderate-quality evidence suggests that the addition of pharmacological prophylaxis to AUC increased the risk of bleeding compared to AUC alone (a side effect not expectedly seen with the addition of a physical modality, AUC, to pharmacological prophylaxis (very low quality evidence).The quality of the evidence was rated as moderate or very low, rather than high, due to the risk of bias, imprecision and inconsistency in the studies.
90,000 Interventions for the prevention of venous thromboembolic complications in adults undergoing arthroscopic knee surgery
Arthroscopy is used to treat various types of damage to the structures of the knee joint. Patients may benefit from this intervention, but there is a small risk of developing venous thromboembolism.Venous thromboembolism occurs when blood clots (blood clots) form in the deep veins of the lower extremities. Patients may experience pain in the calf muscles and edema of the lower extremities (called symptomatic deep vein thrombosis or DVT), in which case there is a risk that the blood clot can travel to the vessels of the lungs (pulmonary embolism or PE).
This systematic review included clinical trials evaluating drug use in patients undergoing knee arthroscopy.These medicines thin the blood and can therefore help prevent blood clots.
This review is an update to a review first published in 2007. A search for a review update was conducted on August 14, 2019.
Characteristics of studies and main results
Pooled data from five clinical trials show that the use of low molecular weight heparin (LMWH), a drug given daily under the skin of the abdomen, does not reduce the risk of PE or symptomatic DVT. Using LMWH can reduce the risk of asymptomatic DVT. The use of LMWH did not have a clear effect on the development of edema or bleeding.
In one study, the use of oral rivaroxaban did not reduce the risk of PE and DVT, and did not lead to an increase in the frequency of bleeding compared with placebo. Another study comparing aspirin versus control reported no cases of PE or DVT. The use of LMWH compared with the use of compression stockings did not decrease the incidence of PE, but decreased the incidence of DVT.In the group of patients wearing compression stockings, the incidence of DVT was higher than expected.
There is a small risk of developing venous thromboembolic complications (PE or DVT) in healthy adults after arthroscopic knee surgery. There is vague evidence that the use of LMWH, aspirin, or rivaroxaban may be beneficial in reducing the small risk of PE and symptomatic DVT.
Certainty of evidence
The certainty of the evidence varied among the interventions used and the outcomes assessed. We lowered the certainty of the evidence for PE and symptomatic DVT from high to moderate due to inaccurate results and a small number of cases. We lowered the level of certainty of the evidence for asymptomatic blood clots to very low due to the risk of bias in clinical trials because the participants knew what treatment they were receiving. This could have affected the medical staff who performed the screening for blood clots without symptoms. We also lowered the level of certainty of the evidence due to indirection, as there is uncertainty about the relevance of asymptomatic DVT in the context of knee arthroscopy.
Medic warned Russians about the risk of thrombosis after coronavirus
In order to avoid thrombosis after suffering COVID-19, doctors prescribe anticoagulant therapy to patients. The chief physician of the Filatov Moscow Clinical Hospital Valery Vechorko told about this on his Telegram channel.
“One of the formidable complications after the disease, which I would like to pay special attention to, are thrombosis – they occur in 20-30% of cases and can lead to strokes and heart attacks, the cases of which after the transferred COVID-19 are now accumulating, but there is a direct connection between two diseases have yet to be studied, ”he wrote.
Vechorko attached to his post, link to the memo of the Russian Ministry of Health. It says that the most common complication after an infection is shortness of breath. It occurs in 31.7% of people.
Thrombosis is in second place – 20-30%, in third – cough (13.5%). 12.7% of Russians who have undergone coronavirus complain of chest pain and tachycardia.
According to Vechorko, heparin drugs or new oral coagulants are needed to avoid thrombosis.“This group of drugs allows for the prevention of thrombosis, especially of the pulmonary arteries, and death from their formation. It should be noted that aspirin and other drugs were less effective, ”he added.
The head physician of a Moscow hospital noted with regret that thrombosis can appear in a patient within a month after the first symptoms of the disease appear. This often happens if there are prerequisites in the anamnesis: atrial fibrillation, varicose veins, thrombophlebitis and other diseases of the cardiovascular system.
“Some time after discharge, it is advisable to make a coagulogram. This test allows you to assess blood clotting. In a negative scenario, it is necessary to continue taking anticoagulant therapy until the condition returns to normal, ”wrote Vechorko. At the same time, he recalled that a specialist should monitor the treatment and prescription of drugs.
At the same time, to avoid blood thickening, the doctor advised to drink plenty of fluids, especially in hot weather.
At the end of July, infectious disease doctor Andrei Pozdnyakov said in a commentary to RIA Novosti that thrombosis carries additional risks for patients’ lives.
“First of all, these are people with a genetic predisposition. It should be noted that this is quite common in the population, so there are a lot of people who need to closely monitor the state of blood vessels, ”the specialist emphasized.
The medic explained that the endothelium – the layer of cells that line the inner surface of the vessels – is favorable for the reproduction of the coronavirus. When an infection affects the endothelium, the lining of the vessels loses its elasticity.
“Since the endothelium is restored rather slowly, thrombosis may occur if the inner lining of the vessels is disturbed by the SARS-COV-2 virus.At the same time, a person may not even suspect that he is developing a blood clot, ”the doctor warned.
Pozdnyakov noted that women who take oral contraceptives are most prone to thrombosis. Diseases of the endocrine system, which are associated, including with excess weight, can also affect the tendency to increased thrombus formation.
“That is why COVID-19 is extremely unpleasant for people with cardiovascular and endocrine pathology, their blood clotting changes greatly and they die most often from thrombotic complications,” the specialist added.
According to the latest data, 22,010 new cases of coronavirus were recorded in Russia per day. In total, more than 6.3 million cases have been identified in the country. More than 5.6 million Russians have recovered, almost 161 thousand people have died.
SIMPLE, FAST, EFFECTIVE Three principles of endovascular intervention – “InfoMedPharmDialogue”
Carotid stent thrombosis is a rarer complication. In the GKB them. I.V. Davydovsky, according to A.Yu. Bocina, double antiplatelet therapy (aspirin 250 mg + clopidogrel 300 mg) is started in the operating room.From the second day, the dose of clopidogrel is reduced (aspirin 250 mg + clopidogrel 75 mg), and after discharge, the combination of aspirin 100/125 mg + clopidogrel 75 mg is left for 6 months. In addition, in the hospital, stent patency is monitored (duplex scanning).
Often, patients develop nonspecific complications – aspiration pneumonia and deep vein thrombosis of the lower extremities. For the prevention of aspiration pneumonia, swallowing assessment and, if necessary, gastric tube placement is necessary.It is very important to carry out hygienic preparation of the oral cavity. In addition, the head end of the bed can be raised 30–45 °. In the absence of prospects for a quick restoration of swallowing, a tracheostomy is installed in the patient. Intermittent compression is recommended for the prevention of deep vein thrombosis. Do not use compression with elastic bandages! In the absence of intracranial hemorrhagic complications based on CT results, the patient is prescribed anticoagulants (preferably
low molecular weight heparins) in prophylactic dosages.
Recurrent ischemic stroke is a fairly frequent complication, the prevention of which should be started already in the hospital. For this, in the first 24–48 hours after the onset of a stroke, it is recommended to prescribe aspirin at a dosage of 150–300 mg, regardless of the pathogenetic variant of the disease. Patients with noncardioembolic stroke and NIHSS ≤3 are advised to prescribe DAPT within the first 24 hours after the onset of stroke.
When prescribing preventive treatment for ischemic stroke, it is very important to understand what it may be associated with. If the pathogenetic variant of stroke is atherothrombotic or lacunar, then an antiplatelet agent is prescribed. In the event of a cardioembolic stroke, the patient should receive an oral anticoagulant.
However, the main conclusion made by A.Yu. Bocin, concerns the terms of rehabilitation. It should be started as early as possible – even in the intensive care unit. The rehabilitation program is developed with the participation of a multidisciplinary team and is checked every day.
An operation to remove varicose veins of the legs is called phlebectomy.It is aimed at restoring normal blood flow through the deep veins of the extremities.
The following types of interventions are used:
- Combined operation.
- Laser coagulation.
- Radiofrequency obliteration.
This operation is performed by a vascular surgeon or, in other words, a phlebologist. The doctor of this particular specialty will prescribe the necessary examination and determine whether there are indications for surgical treatment. In the initial stages of the disease, our specialist will perform the intervention under local anesthesia.In severe cases, hospitalization will be recommended.
Laser coagulation – one of the types of phlebectomy, in which a laser light-emitting diode is inserted into a vein
The classic method of intervention, which includes 4 stages:
- Crossectomy – ligation and transection of the great or small saphenous vein in the area where it flows into the deep vein. This leads to a stop of blood flow in them.
- Stripping – removal of the diseased vein trunk.
- Perforating vein ligation is the ligation of the vessels that connect the deep and superficial veins. The dressing is needed to prevent the discharge of blood into the superficial system.
- Miniflebectomy – direct removal of varicose nodes and veins through small single skin punctures.
At the initial stages of the disease, some stages can be used as independent methods of treatment, and some stages can be replaced by minimally invasive interventions using a laser or radiofrequency ablation – sealing the lumen of a vein by heating its wall and creating a microburn. These two methods are minimally invasive, since a small incision is made on the skin to insert the electrode into the vessel, and the veins themselves are not removed from the legs.
Under local anesthesia, a laser light guide is passed into the desired vessel, which produces controlled burns of the vein wall. This causes them to overgrow. After the operation, the legs remain beautiful (without scars and scars), the postoperative recovery period is short.
The method is based on the precise effect of thermal energy on the walls of the veins. A disposable catheter is inserted into the vessel, its heating temperature and extraction rate are constantly monitored. Under its influence, the lumen of the altered vein sticks together, while pain is minimal. In one step, it is possible to perform the full scope of the operation on two legs.
Indications and contraindications for surgical treatment
Visually protruding saphenous veins
Pregnancy and breastfeeding
Stagnation of blood in the lower extremities
Severe chronic diseases (high-risk arterial hypertension, ischemic disease, diabetes mellitus)
Distribution of varicose veins above the knee
Atherosclerosis of the lower extremities
Chronic edema and fatigue in the legs, regular pain
Acute deep vein thrombosis
Frequent transferred thrombosis
Infectious and inflammatory diseases of the skin in the operation area (boils, erysipelas, eczema)
Impossibility of long-term compression after surgery
Limited active movements
Preparing for operation
Phlebectomy is performed after a special duplex ultrasound scan of the veins (it allows you to see and examine blood circulation) to determine the scope of the intervention and the likelihood of using minimally invasive methods. The standard preoperative examination includes:
- Analyzes – total blood and urine tests, biochemical, hemostasiogram, research for HIV, hepatitis and syphilis.
- Consultation of therapist and ECG to determine contraindications to treatment.
Compression underwear is selected in advance, which is preferable to elastic bandages, since it creates uniform pressure of the required force.
Immediately before the operation, the patient needs to shave his legs.If anesthesia is planned, then a cleansing enema is performed. The intervention is performed strictly on an empty stomach, in front of it, in a standing position, the patient is marked with the places of the changed veins.
Classic phlebectomy progress
The operation can be performed under general or spinal anesthesia (when an anesthetic is injected into the spinal canal and the patient loses sensitivity to pain below the lumbar level, but remains conscious). In any case, the patient’s body is fixed so that he does not harm himself with a sharp movement during the intervention: he is tied to the table with ribbons through the body.
- Crossectomy is performed. The use of crossectomy as an independent operation is possible in emergency cases, for example, with thrombosis of superficial veins, in order to prevent deep thrombosis.
- Stripping is done in several ways:
- With a Babcock probe, when a metal tourniquet is inserted into the vein through the incision left over from the previous stage to the end of the vein to be removed. A second incision is also made to guide the end of the probe outside the pathological vein.At the end of the probe there is an olive with a cutting surface. The doctor slowly pulls on the handle, the vein is cut off from the surrounding tissue and stretched. This is the most traumatic method.
- An invagination probe also pulls out a vein, but it seems to be turned inside out. A probe is inserted into the upper incision, and through the lower one it is fixed to the vein. Then the tissue of the vessel is separated under the action of a pulling movement, and the vein is gradually turned inside out, like a stocking.
- PIN stripping is similar to the previous method, but it only requires one cut from the first step.
- Cryostripping is performed using a special cryoprobe, which causes the end of the vein to freeze to it and it is turned inside out and pulled out of the leg, as in the invagination method. An alternative to this stripping is radiofrequency and laser vein removal.
- Ligation of perforating veins. It is necessary to prevent the discharge of blood from deep veins into superficial ones and as preparation for the next stage. It is performed subfascial or suprafascial (that is, the fascial sheath covering the muscles – it is dissected (if subfascial) or not (if suprafascial).
- Miniflebectomy can be used at the initial stage of the disease as an independent operation when there is a single altered vein. For her, punctures are made in the areas marked before the operation, the varicose vein or the knot is hooked and crossed, after which they are removed.
Classical phlebectomy is performed upon admission to the hospital. If the stages of intervention are replaced by minimally invasive ones – radiofrequency or laser treatment – then they are performed on an outpatient basis under local anesthesia.
Immediately after the operation, you can move your legs and bend them. The next day, it is recommended to wear compression stockings or tights. You need to wear them around the clock throughout the month. After that – wear only during the day, the term is prescribed by the specialist individually.
During the first two days, anesthesia is performed with non-narcotic analgesics, phlebotonics are prescribed (Phlebodia). Prevention of thrombosis is carried out with antiplatelet agents – drugs that reduce blood clotting, for example, Aspirin in a low dosage.Antibiotics are prescribed according to indications.
No highly specialized diet required.
Dressings are performed on the 1st, 3rd and 6th days after the operation. After the operation, the patient stays in the hospital for up to 7 days; before discharge, the stitches are removed on the 6-7th day. In the popliteal region, this is done later – on the 10-12th day. After returning home, it is forbidden to take hot baths and go to the bathhouse, it is recommended to quit smoking, control your weight. You need to eat right, dose physical activity, wear comfortable shoes.Swimming and cycling are very useful.
After the signs of venous insufficiency have disappeared, you can consult a doctor to decide whether to reduce the compression class of the garment or refuse to wear it.
Possible complications and causes of relapse
Injury of the operation or violation of the technique can lead to the following complications:
- Hematomas – accumulation of blood in cavities in place of large trunks or nodes. Prevention of this complication – good hemostasis – vascular ligation to exclude bleeding during surgery and compression with linen or bandages after it.
- Bleeding is possible on the first day from small subcutaneous vessels.
- Infection of wounds.
- Lymphorrhea and lymphocele (formation of lymph-filled cavities).
- Disruption of skin sensitivity due to nerve damage.
Deep vein thrombosis or thromboembolism at the present stage of the development of surgery is extremely rare.
Most of the postoperative complications go away on their own. If an infection develops, it is necessary to remove the stitches and use topically antibacterial agents. Patients from risk groups are prescribed antibiotics already during and after surgery: these are elderly people with concomitant pathology, diabetes mellitus and immunodeficiency.
Damage to the lymphatic vessels causes lymphorrhea – lymph leakage. Such a complication is possible with rough handling of tissues during crossectomy in the groin area. Treatment is carried out conservatively in the case of lymphorrhea, emptying through a puncture or an open wound with lymphocele – the accumulation of lymph in the cavity.
Decreased sensitivity on the inner side of the leg and foot, the appearance of paresthesia – a feeling of “creeping creeps”, is associated with trauma to the nerves in the immediate vicinity of the saphenous veins. This condition develops in 25% of cases when stripping is performed.
The development of relapse is possible, despite the use of high-tech methods of intervention. The reasons for this are as follows:
- violation of the technique of the operation or structural features did not lead to blockage of the veins;
- in veins with normal results of the operation, recanalization occurred – restoration of the vessel lumen;
- Inguinal reflux, when good obliteration (closure of the lumen) of the main vein resulted in a discharge of blood at the level of tributaries in the groin.
In the long term, phlebectomy can be complicated by recurrence in 10–20% of cases.
Rivaroxaban and Aspirin®: Trends and Strategies
Symposium was opened by Dr. Martin Bechem is the head of the Cardiology and Hematology Research Group at Bayer Schering Pharma . He spoke about the main achievements of the company in the development of drugs for the treatment and prevention of cardiac and vascular pathology. New therapeutic strategies were presented, which are the focus of the company’s current efforts.This is a study of the effectiveness of rivaroxaban in the prevention of strokes in patients with atrial fibrillation, in the secondary prevention of acute coronary syndrome, in the treatment and prevention of deep vein thrombosis; studying the efficacy of riociguat (a soluble guanylate cyclase stimulator) in the treatment of chronic thromboembolic pulmonary hypertension and pulmonary arterial hypertension; creation and study of molecules of new drugs for use in the early stages of heart failure, anemia in patients with chronic kidney disease and various forms of pulmonary hypertension.
Atherothrombosis is the leading cause of acute myocardial infarction, ischemic stroke, sudden cardiac death and acute peripheral vascular disease.
Venous thromboembolism (VTE) refers to deep vein thrombosis (DVT) and pulmonary embolism (PE). In this regard, there is a constant search for effective anticoagulants with a good safety profile.
More recently, Bayer HealthCare has introduced a new generation oral anticoagulant rivaroxaban to the global pharmaceutical market.Despite the fact that only a few years have passed since the creation of the drug, it has demonstrated its effectiveness and safety in large studies and has established itself as a first-line agent for the treatment and prevention of a wide range of acute and chronic diseases resulting from atherothrombosis and venous thromboembolism. As noted head of the Department of Cardiology University G. d’Annunzio (Italy) Professor Raffaele De Caterina , according to statistics, 640,000 cases of deep vein thrombosis and 383,000 cases of pulmonary embolism have been registered in the countries of the European Union.At the same time, VTE in these countries causes more than half a million deaths per year, which is twice the number of deaths from AIDS, breast cancer, prostate cancer and deaths due to road traffic accidents.
The incidence of post-thrombotic syndrome is also high: it develops in one third of patients who underwent DVT. In the European Union, post-thrombotic syndrome is reported annually in 600,000 patients. In severe cases, it causes incurable ulcers in the lower extremities, which can lead to amputation.
The pathophysiology of atherothrombosis, PE and DVT is based on common pathogenetic factors that cause increased blood clotting and blood clots. Thus, for all of the above forms of vascular pathology, anticoagulant therapy should be prescribed. Currently, new drugs are being developed in this direction. While the classic anticoagulants (heparin and vitamin K antagonists) are nonspecific, affecting several coagulation factors, the newer anticoagulants are more specific.In addition, newer anticoagulants have been shown to be more effective and safer in recent studies.
Professor of Internal Medicine, Director of the Clinic for Vascular Medicine, Head of the Vascular Center in Darmstadt (Germany) Rupert Bauersachs spoke about the possibility of changing the paradigm in the treatment of venous thromboembolism due to the emergence of a new generation of anticoagulants. Currently, the standard treatment for VTE is parenteral administration of heparin, low molecular weight heparins, or fondaparinux in the acute period followed by a switch to oral vitamin K antagonists.However, this scheme has a number of negative aspects: the need for individual dose selection with regular monitoring of INR and platelets, the presence of undesirable pharmacological effects of vitamin K antagonists, including a high probability of their negative interaction with food and other drugs. In addition, it is rather difficult to determine the optimal timing of anticoagulant treatment. Guidelines for the treatment of VTE indicate that the duration of anticoagulant therapy should be 3 months in patients with a low risk of recurrent thrombosis, while in patients with idiopathic VTE, an indefinite long-term use of anticoagulants is assumed.At the same time, in the course of treatment, it is constantly necessary to assess the “risk: benefit” ratio, and the results of such an assessment do not always confirm the prevalence of the latter.
Every year, 1–2% of patients on long-term anticoagulant therapy have severe or fatal bleeding. Risk factors for the development of such bleeding are the patient’s age over 65, a history of gastrointestinal bleeding or stroke, comorbid factors (a history of myocardial infarction, hematocrit <30%, creatinine> 1.5 mg / dL, diabetes mellitus).In patients without risk factors, the likelihood of developing severe or fatal bleeding over 4 years is 3%, in patients with 1 or 2 of the above risk factors, 12%, and in patients with 3 or 4 risk factors, the likelihood is 53%.
Based on the above situation, many patients and doctors prefer to avoid long-term use of anticoagulants in the development of idiopathic thromboembolism for the first time, despite the high risk of recurrent VTE, therefore, the possibility of using a new generation of anticoagulants that do not have the side effects characteristic of classical heparins or vitamin K antagonists should be considered.
Rivaroxaban is a novel oral coagulation factor Xa inhibitor with a bioavailability of more than 80%, a rapid onset of action, and a half-life of 7-11 hours. The drug has a fixed dose for taking once a day, and it does not require monitoring of the INR.
The data from the phase III clinical trial EINSTEIN-DVT, conducted in patients with acute symptomatic deep vein thrombosis, demonstrated the same efficacy of rivaroxaban monotherapy in the prevention of recurrent VTE as with standard therapy (enoxaparin, vitamin K antagonists), with a comparable safety profile.Thus, it was found that oral administration of rivaroxaban 15 mg twice a day for 3 weeks followed by switching to a dose of 20 mg once a day can be recommended for urgent and long-term treatment of VTE.
A follow-up study, EINSTEIN-Extension, evaluated the efficacy and safety of rivaroxaban versus placebo for the secondary prevention of VTE in patients who had previously received anticoagulant therapy for 6 or 12 months. It was found that rivaroxaban, when taken orally at a dose of 20 mg per day for 6 or 12 months, significantly reduced the risk of VTE recurrence by 82% compared with placebo with a low frequency of bleeding.
Thus, the results of these studies are the basis of a new paradigm in the treatment of VTE. Ease of administration, a favorable “risk: benefit” ratio, no need for dose selection and monitoring of INR give rivaroxaban the opportunity to become a new standard of VTE therapy, displacing heparin and vitamin K antagonists.
The role of new anticoagulants in the prevention of stroke in patients with atrial fibrillation was presented in a report by Professor Roland Veltkamp (University of Heidelberg, Germany) .Atrial fibrillation is the most common form of persistent arrhythmias in adults. In people aged 60 and over, the prevalence is 4% and increases to 9% in patients over the age of 80. Atrial fibrillation is the cause of at least 15–20% of ischemic stroke cases. It is often asymptomatic, and asymptomatic atrial fibrillation has been found to be responsible for most cases of cryptogenic strokes.
Oral anticoagulants are currently used to prevent stroke in patients with atrial fibrillation. Large studies (AFASAK, SPAF, BAATAF, CAFA, SPINAF) have shown a reliably high efficacy of warfarin in the primary prevention of strokes in patients with atrial fibrillation compared with Aspirin® and placebo. The ACTIVE-W (Atrial fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events) study shows that warfarin is more effective than the combination of clopidogrel and Aspirin®, and remains the first-line drug for the prevention of stroke and other thromboembolic complications in patients with atrial fibrillation.However, as the previous speaker mentioned, unfortunately, classical anticoagulants are characterized by the need for dose selection, INR control and a number of undesirable side effects, which reduces compliance and leads to the fact that only 60% of patients with atrial fibrillation who have indications for long-term use of anticoagulants are taking these drugs.
The appearance on the pharmaceutical market of new oral anticoagulants, in particular rivaroxaban, makes it possible to carry out anticoagulant therapy without constant monitoring of INR. In four large, randomized phase III trials in patients with atrial fibrillation, stroke and systemic thromboembolism are the primary endpoints.
In the ROCKET AF study, the largest double-blind trial of stroke prevention in patients with atrial fibrillation, rivaroxaban 20 mg daily was more effective than adjusted dose warfarin and reduced the relative risk of stroke and systemic thromboembolism without CNS involvement.
Thus, the new anticoagulants are more effective in preventing stroke in patients with atrial fibrillation than standard oral anticoagulants, and can successfully replace them. Rivaroxaban is registered in Ukraine under the brand name Ksarelto. It is used at a dose of 10 mg once a day for the prevention of thrombosis in patients after extensive orthopedic interventions on the lower extremities.
During the symposium, another topical topic was discussed – primary and secondary prevention of acute cardiovascular events and the place of Aspirin® in it.
The first randomized study of the efficacy of Aspirin® in the prevention of vascular mortality was conducted in 1974. The research team was led by Professor Peter Elwood (Cardiff University School of Medicine, Wales, UK) . Since then, he has led many studies on the use, efficacy and safety of this drug. At this symposium, Professor R. Elwood talked about how to properly evaluate and interpret research results.He built his report on examples from clinical studies of Aspirin®. Thus, the participants of the symposium had the opportunity not only to understand the terminology for describing clinical trials, but also to familiarize themselves with the data obtained in them, which are useful in clinical practice. For example, the use of low-dose Aspirin® has been found to reduce the risk of death from a cardiovascular event by 33%. This indicator is interpreted as a relative risk.
In a group of patients who have recently undergone a cardiovascular event, in order to save one life, 25 people must be treated with Aspirin® for a year. At the same time, in the group of patients who had a cardiovascular event several years ago, in order to save one life, 200 people need to be treated with Aspirin®, and among healthy people without a history of cardiovascular events, this figure will be 1000 people.
Director of the Department of Cardiology, Vascular Medicine and Emergency Conservative Care, Professor Harald Darius (Berlin, Germany) presented statistics on mortality from acute coronary syndrome in Western Europe.In the UK, between 1990 and 2004, the death rate fell from 210 to 170 per 100,000 people per year; in Germany – from 225 to 140 cases per 100,000 people per year; in the Netherlands – from 190 to 70 cases per year, in France – from 100 to 80 cases. Thus, from year to year, there is a decrease in this indicator, mainly due to the optimization of clinical diagnostics and treatment with the use of mechanical reperfusion of the coronary artery in combination with antithrombotic therapy.
Combined antiplatelet therapy is the standard treatment for patients with acute coronary syndrome: the antiplatelet effect of Aspirin® is potentiated by the inhibitor of ADP-induced platelet aggregation, clopidogrel.
The recently completed Phase II ATLAS ACS-TIMI 46 (Anti-Xa Therapy to Lower cardiovascular events in addition to Aspirin with or without thienopyridine therapy in Subjects with Acute Coronary Syndrome – Thrombolysis In Myocardial Infarction 46) evaluated the efficacy and safety of a highly specific inhibitor Ha-factor rivaroxaban in patients with acute coronary syndrome who took only Aspirin® or Aspirin® in combination with clopidogrel.The primary efficacy endpoint was a combination of death, myocardial infarction, stroke, and severe recurrence of ischemia requiring myocardial revascularization for 6 months. The combination of death, myocardial infarction and stroke within 6 months was chosen as the main secondary endpoint.
It was found that the use of rivaroxaban for 6 months reduced the risk of major ischemic events (mortality, myocardial infarction, stroke, and recurrent ischemia requiring myocardial revascularization) and significantly reduced the frequency of the secondary endpoint (mortality, MI, and stroke) (Fig. one).
Research is ongoing on the ability of rivaroxaban in combination with standard therapy (Aspirin® + clopidogrel) to reduce the risk of cardiovascular events in patients with acute coronary syndrome (ATLAS-II (phase III)). Two dosage regimens of rivaroxaban are evaluated – 2.5 and 5 mg 2 times a day.
Professor J.M. Gaziano (Harvard Medical School, USA) was devoted to the effectiveness of Aspirin® in the presence of risk factors for cardiovascular events.The hypothesis that antiplatelet therapy reduces cardiovascular risk has been tested in over 400 clinical studies. It has been demonstrated that Aspirin®, as a secondary prophylaxis agent, reduces the risk of developing nonfatal myocardial infarction by 34%, the risk of developing nonfatal stroke by 25%, the risk of death from vascular events by 15%, and the overall risk by 22%. Thus, Aspirin® is one of the most effective agents for the secondary prevention of acute cardiovascular events. The effectiveness of Aspirin® in primary prevention is also shown. Before we prescribe Aspirin® for each patient as primary or secondary prophylaxis, it is necessary to determine the degree of cardiovascular risk and assess the “risk: benefit” ratio of Aspirin®, which is strongly recommended in most modern guidelines. Methodology for assessing the degree of risk of cardiovascular events and the need to prescribe Aspirin® as primary prevention professor J.M. Gaziano demonstrated on the example of a clinical case.The patient is a 56-year-old man, does not smoke, without a history of cardiovascular diseases and diabetes mellitus. From family history it is known that the father died at the age of 45 from myocardial infarction. A clinical examination of the patient revealed controlled arterial hypertension (BP 144/89 mm Hg). Body mass index (BMI) is 28. Lipid profile: total cholesterol – 243 mg / dl, LDL – 172 mg / dl, HDL – 39 mg / dl, triglycerides – 158 mg / dl. It is necessary to assess the presence of cardiovascular risk and its degree in this patient and decide on the appointment of Aspirin® as the primary prevention of cardiovascular events.
The assessment of cardiovascular risk is carried out using scales (Framingham, SCORE, Reynolds risk scale, Gaziano scale). In this case, according to the Framingham scale (taking into account such parameters as age, levels of cholesterol, lipoproteins and blood pressure, nicotine status), the patient scored 16 points, which indicates a 25% cardiovascular risk. The patient is shown the appointment of Aspirin® and the elimination of his existing risk factors – hypertension (antihypertensive therapy), hyperlipidemia (statins), lifestyle changes aimed at reducing BMI.
Professor Carlo Patrono, Head of the Department of Pharmacology at the School of Medicine at the Catholic University (Rome, Italy) , spoke about what’s new in the field of Aspirin® research. He emphasized that the absolute benefit of Aspirin® (shows how many cases of vascular events can be prevented by prescribing the drug to 1000 patients) as a means of prevention directly depends on the severity of cardiovascular risk in each patient. Four large studies are currently underway on the efficacy of Aspirin® as a prophylactic agent in 50,000 patients at intermediate risk for cardiovascular events. The risk in these patients is due to the presence of diabetes mellitus (ASCEND ACCEPT-D), old age (ASPREE), or a group of factors not including diabetes mellitus (ARRIVE).
Another area of research for Aspirin® is currently studying it as a chemopreventive agent.The UK-TIA and BDAT studies show that Aspirin® at a daily dose of 300 mg reduces the incidence of sporadic colorectal cancer by up to 75% over a 10-year follow-up period.
An analysis of the results of all randomized clinical trials, which compared groups of patients who took and did not take Aspirin® for more than four years, showed that Aspirin® reduced the risk of bowel cancer by 20%, and in patients who took the drug for more than 5 years, – by 34%.Long-term follow-up of these patients showed that the 20-year risk of dying from colorectal cancer remained 20% lower in patients taking Aspirin®. At the same time, the indicators of the benefits of Aspirin® directly depended on the duration of its use.
Thus, at present, a paradigm for the successful use of low-dose Aspirin® as an antiplatelet agent has been formulated. Further joint efforts of Bayer HealthCare pharmaceutical company and clinical research specialists should be directed towards understanding the mechanism of action of Aspirin® as a chemopreventive agent, determining its optimal dose and dosage regimen to achieve this effect.
Prepared by Natalia Kuprinenko
90,000 Surgeons urge to abandon powerful anticoagulants in favor of aspirin
After hip or knee arthroplasty, strong drugs are usually used to prevent thromboembolism. Surgeons explain that in modern operations such drugs are not needed, ordinary aspirin
After knee or hip replacement surgery, a dangerous complication often occurs – deep vein thrombosis. Less often, but also sometimes an even more life-threatening condition occurs – pulmonary embolism. Surgeons are well aware of this and prophylactically prescribe anticoagulant drugs to their patients. Some doctors recommend powerful and expensive anticoagulants such as enoxaparin sodium (Lovenox) and rivaroxaban (Xarelto). However, experts from the Department of Orthopedic Surgery at the University of Michigan argue that regular aspirin can easily cope with the same role.These words are supported by scientific research. The first was conducted over two years, from 2013 to 2015, when aspirin use increased from 10 to 50% among patients operated on for hip or knee replacement. At the same time, the incidence of blood clots, pulmonary embolism and deaths did not increase at all. Inspired by this result, surgeons further increased the proportion of patients on aspirin to 70%. And even then, the indicators listed did not change.But then how did the practice of prescribing powerful anticoagulants come about? The fact is that earlier endoprosthetics took place somewhat differently: the operations lasted longer, were more invasive and were performed under general anesthesia. All of this increased the risk of blood clots. Modern minimally invasive surgeries are performed under local anesthesia. Most often, the patient can go home on the day of the operation. The new conditions simply do not require as impressive thrombosis prophylaxis as they once did. By the way, surgeons say that the best prevention is not drugs at all, but the most common walking – you need to move as much as possible.By the way, taking stronger remedies just in case is also not a good idea. Strong anticoagulants require constant monitoring of the patient’s blood clotting, frequent dose adjustments and, of course, they are more expensive. Based on the postoperative experience of 41,537 Michigan patients, the researchers are ready to bring up the routine use of aspirin to prevent blood clots. Experts are calling for aspirin to become a routine practice in the prevention of thromboembolism after arthroplasty.