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Archive for the ‘endovascular thrombectomy’ Category


UPDATED on 2/25/2019

https://www.medpagetoday.com/cardiology/prevention/78202?xid=nl_mpt_SRCardiology_2019-02 25&eun=g99985d0r&utm_source=Sailthru&utm_medium=email&utm_campaign=CardioUpdate_022519&utm_term=NL_Spec_Cardiology_Update_Active

 

ICER announced plans to look at icosapent ethyl (Vascepa) and rivaroxaban (Xarelto) as add-on therapies in cardiovascular disease.

Heart attack risk is rising among young women. But NHANES data show women are still ahead of men on control of hypertension, diabetes, and cholesterol. (Circulation)

Two Classes of Antithrombotic Drugs: Anticoagulants and Antiplatelet drugs

Reporter: Aviva Lev-Ari, PhD, RN
These drugs are used to treat
  • strokes,
  • myocardial infarctions,
  • pulmonary embolisms,
  • disseminated intravascular coagulation (DIC) and
  • deep vein thrombosis (DVT)
— all potentially life-threatening conditions.
THERAPEUTIC STRATEGIES
• Degrade fibrinogen/fibrin (fibrinolytic agents)
GOAL: eliminate formed clots
• Inhibit clotting mechanism (anticoagulants)
GOAL: prevent progression of thrombosis
• Interfere either with platelet adhesion and/or aggregation (antiplatelet drugs)
GOAL: prevent initial clot formation
Antithrombotic therapy has had an enormous impact in several significant ways.
  • Heparin has made bypass surgery and dialysis possible by blocking clotting in external tubing.
  • Antithrombotic therapy has reduced the risk of blood clots in leg veins (also known as deep-vein thrombosis or DVT), a condition that can lead to death from pulmonary embolism (a clot that blocks an artery to the lungs) by more than 70 percent. And most importantly,
  • it has markedly reduced death from heart attacks, the risk of stroke in people with heart irregularities (atrial fibrillation), and the risk of major stroke in patients with mini-strokes.

Antithrombotic Therapy

This article was published in December 2008 as part of the special ASH anniversary brochure, 50 Years in Hematology: Research That Revolutionized Patient Care.

Normally, blood flows through our arteries and veins smoothly and efficiently, but if a clot, or thrombus, blocks the smooth flow of blood, the result – called thrombosis – can be serious and even cause death. Diseases arising from clots in blood vessels include heart attack and stroke, among others. These disorders collectively are the most common cause of death and disability in the developed world. We now have an array of drugs that can be used to prevent and treat thrombosis – and there are more on the way – but this was not always the case.

Classes of Antithrombotic Drugs

Image Source: http://www.hematology.org/About/History/50-Years/1523.aspx

The most important components of a thrombus are fibrin and platelets. Fibrin is a protein that forms a mesh that traps red blood cells, while platelets, a type of blood cell, form clumps that add to the mass of the thrombus. Both fibrin and platelets stabilize the thrombus and prevent it from falling apart. Fibrin is the more important component of clots that form in veins, and platelets are the more important component of clots that form in arteries where they can cause heart attacks and strokes by blocking the flow of blood in the heart and brain, respectively, although fibrin plays an important role in arterial thrombosis as well.

There are two classes of antithrombotic drugs: anticoagulants and antiplatelet drugs. Anticoagulants slow down clotting, thereby reducing fibrin formation and preventing clots from forming and growing. Antiplatelet agents prevent platelets from clumping and also prevent clots from forming and growing.

Anticoagulant Drugs

The anticoagulants heparin and dicumarol were discovered by chance, long before we understood how they worked. Heparin was first discovered in 1916 by a medical student at The Johns Hopkins University who was investigating a clotting product from extracts of dog liver and heart. In 1939, dicumarol (the precursor to warfarin) was extracted by a biochemist at the University of Wisconsin from moldy clover brought to him by a farmer whose prize bull had bled to death after eating the clover.

Both of these anticoagulants have been used effectively to prevent clots since 1940. These drugs produce a highly variable anticoagulant effect in patients, requiring their effect to be measured by special blood tests and their dose adjusted according to the results. Heparin acts immediately and is given intravenously (through the veins). Warfarin is swallowed in tablet form, but its anticoagulant effect is delayed for days. Therefore, until recently, patients requiring anticoagulants who were admitted to a hospital were started on a heparin infusion and were then discharged from the hospital after five to seven days on warfarin.

In the 1970s, three different groups of researchers in Stockholm, London, and Hamilton, Ontario, began work on low-molecular-weight heparin (LMWH). LMWH is produced by chemically splitting heparin into one-third of its original size. It has fewer side effects than heparin and produces a more predictable anticoagulant response. By the mid 1980s, LMWH preparations were being tested in clinical trials, and they have now replaced heparin for most indications. Because LMWH is injected subcutaneously (under the skin) in a fixed dose without the need for anticoagulant monitoring, patients can now be treated at home instead of at the hospital.

With the biotechnology revolution has come genetically engineered “designer” anticoagulant molecules that target specific clotting enzymes. Anti-clotting substances and their DNA were also extracted from an array of exotic creatures (ticks, leeches, snakes, and vampire bats) and converted into drugs by chemical synthesis or genetic engineering. Structural chemists next began to fabricate small molecules designed to fit into the active component of clotting enzymes, like a key into a lock.

The first successful synthetic anticoagulants were fondaparinux and bivalirudin. Bivalirudin, a synthetic molecule based on the structure of hirudin (the anti-clotting substance found in leeches), is an effective treatment for patients with heart attacks. Fondaparinux is a small molecule whose structure is based on the active component of the much larger LMWH and heparin molecules. It has advantages over LMWH and heparin and has recently been approved by the FDA. Newer designer drugs that target single clotting factors and that can be taken by mouth are undergoing clinical testing. If successful, we will have safer and more convenient replacements for warfarin, the only oral anticoagulant available for more than 60 years.

Antiplatelet Drugs

Blood platelets are inactive until damage to blood vessels or blood coagulation causes them to explode into sticky irregular cells that clump together and form a thrombus. The first antiplatelet drug was aspirin, which has been used to relieve pain for more than 100 years. In the mid-1960s, scientists showed that aspirin prevented platelets from clumping, and subsequent clinical trials showed that it reduces the risk of stroke and heart attack. In 1980, researchers showed that aspirin in very low doses (much lower than that required to relieve a headache) blocked the production of a chemical in platelets that is required for platelet clumping. During that time, better understanding of the process of platelet clumping allowed the development of designer antiplatelet drugs directed at specific targets. We now have more potent drugs, such as clopidogrel, dipyridamole, and abciximab. These drugs are used with aspirin and effectively prevent heart attack and stroke; they also prolong the lives of patients who have already had a heart attack.

SOURCE 
Anticoagulation Drugs:
  • heparin (FONDAPARINUX HEPARIN (Calciparine, Hepathrom, Lipo-Hepin, Liquaemin, Panheprin)
  • warfarin – 4-HYDROXYCOUMARIN (Coumadin) WARFARIN (Athrombin-K, Panwarfin)
  • rivaroxaban (Xarelto)
  • dabigatran (Pradaxa)
  • apixaban (Eliquis)
  • edoxaban (Savaysa)
  • enoxaparin (Lovenox)
  • fondaparinux (Arixtra)
  • ARGATROBAN BIVALIRUDIN (Angiomax)
  • DALTEPARIN (Fragmin)
  • DROTRECOGIN ALFA (ACTIVATED PROTEIN C) (Xigris)
  • HIRUDIN (Desirudin)
  • LEPIRUDIN (Refludan)
  • XIMELAGATRAN (Exanta)

ANTIDOTES

  • PHYTONADIONE (Vitamin K1)
  • PROTAMINE SULFATE AMINOCAPROIC ACID (EACA) (generic, Amicar) (in bleeding disorders)
Antiplatelet Drugs
  • ACETYL SALICYLIC ACID (aspirin) 
  • clopidogrel (Plavix)
  • dipyridamole (Persantine)
  • abciximab (Centocor)
  • EPTIFIBATIDE (Integrilin)
  • TICLOPIDINE (Ticlid)
  • TIROFIBAN (Aggrastat)

THROMBOLYTICS

  1. ANISTREPLASE (APSAC; Eminase)
  2. STREPTOKINASE (Streptase, Kabikinase)
  3. TISSUE PLASMINOGEN ACTIVATORS (tPAs):
  • ALTEPLASE (Activase),
  • RETEPLASE (Retavase),
  • TENECTEPLASE (TNKase)
  • UROKINASE (Abbokinase)

Fibrinolytic Drugs

Fibrinolytic therapy is used in selected patients with venous thromboembolism. For example, patients with massive or submassive PE can benefit from systemic or catheter-directed fibrinolytic therapy. The latter can also be used as an adjunct to anticoagulants for treatment of patients with extensive iliofemoral-vein thrombosis.

Arterial and venous thrombi are composed of platelets and fibrin, but the proportions differ.

  • Arterial thrombi are rich in platelets because of the high shear in the injured arteries. In contrast,
  • venous thrombi, which form under low shear conditions, contain relatively few platelets and are predominantly composed of fibrin and trapped red cells.
  • Because of the predominance of platelets, arterial thrombi appear white, whereas venous thrombi are red in color, reflecting the trapped red cells.

SOURCE

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Expanded Stroke Thrombectomy Guidelines: FDA expands treatment window for use (Up to 24 Hours Post-Stroke) of clot retrieval devices (Stryker’s Trevo Stent) in certain stroke patients

Reporter: Aviva Lev-Ari, PhD, RN

 

The stent retriever from Stryker was cleared for thrombectomy-eligible patients as initial therapy to reduce paralysis and other stroke disability only as an addition to tissue plasminogen activator (tPA). Previously, the device was approved only for use within 6 hours of ischemic stroke onset.

 

FDA Clears Trevo Stent Retriever for Up to 24 Hours Post-Stroke

FDA move follows expanded stroke thrombectomy guidelines

by Nicole Lou, Reporter, MedPage Today/CRTonline.org

“Time is critical following the onset of stroke symptoms. Expanding the treatment window from 6 to 24 hours will significantly increase the number of stroke patients who may benefit from treatment,” said Carlos Peña, PhD, director of the division of neurological and physical medicine devices at the FDA’s Center for Devices and Radiological Health, in a statement. “Healthcare providers and their patients now have better tools for treating stroke and potentially preventing long-term disability.”

The American Heart Association and American Stroke Association recently revised their guidelines to recommend stent retriever use up to 24 hours after symptom onset. This was announced at the International Stroke Conference in January, where the DEFUSE 3 trial added to the evidence from DAWN in demonstrating benefits to relatively late endovascular thrombectomy.

In particular, DAWN data were used to support the FDA’s latest decision. Trial investigators had reported more functional independence when patients were randomized to Trevo thrombectomy over medical management alone.

SOURCE

https://www.medpagetoday.com/cardiology/strokes/71183

 

FDA expands treatment window for use of clot retrieval devices in certain stroke patients

For Immediate Release

February 15, 2018

Summary

FDA expands treatment window for use of clot retrieval devices in certain stroke patients

Release

The U.S. Food and Drug Administration today cleared the use of the Trevo clot retrieval device to treat certain stroke patients up to 24 hours after symptom onset, expanding the device’s indication to a broader group of patients. This device is cleared for use as an initial therapy for strokes due to blood clots (also known as an acute ischemic stroke) to reduce paralysis, speech difficulties and other stroke disabilities and only as an addition to treatment with a medication that dissolves blood blots called tissue plasminogen activator (t-PA). The device was previously cleared for use in patients six hours after symptom onset.

“Time is critical following the onset of stroke symptoms. Expanding the treatment window from 6 to 24 hours will significantly increase the number of stroke patients who may benefit from treatment,” said Carlos Peña, Ph.D., director of the division of neurological and physical medicine devices at the FDA’s Center for Devices and Radiological Health. “Health care providers and their patients now have better tools for treating stroke and potentially preventing long-term disability.”

A stroke is a serious medical condition that requires emergency care and can cause lasting brain damage, long-term disability or even death. According to the Centers for Disease Control and Prevention, stroke is the fifth leading cause of death in the U.S. and is a major cause of serious disability for adults. About 795,000 people in the U.S. have a stroke each year. Ischemic strokes represent about 87 percent of all strokes.

The Trevo device was first cleared by the FDA in 2012 to remove a blood clot and restore blood flow in stroke patients who could not receive t-PA or for those patients who did not respond to t-PA therapy. In 2016, the FDA allowed expanded marketing of the device for certain patients in addition to treatment with t-PA if used within six hours of the onset of symptoms. Today’s expanded indication increases the amount of time that the device can be used once the symptoms are present.

Trevo is a clot removal device that is inserted through a catheter up into the blood vessel to the site of the blood clot. When the shaped section at the end of the device is fully expanded (up to three to six millimeters in diameter), it grips the clot, allowing the physician to retrieve the clot by pulling it back through the blood vessel along with the device for removal through a catheter or sheath.

The FDA evaluated data from a clinical trial comparing 107 patients treated with the Trevo device and medical management to 99 patients who had only medical management. About 48 percent of patients treated with the Trevo device were functionally independent (ranging from no symptoms to slight disability) three months after their stroke compared to 13 percent of patients who were not treated with the Trevo device.

Risks associated with using the Trevo device include a failure to retrieve the blood clot, embolization (blockage) to new territories in the brain, arterial dissections and vascular perforations, and access site complications at the femoral (thigh) artery entry point.

Trevo was reviewed through the premarket notification (510(k)) pathway. A 510(k) is a premarket submission made by device manufacturers to the FDA to demonstrate that the new device is substantially equivalent to a legally marketed predicate device. The FDA granted premarket clearance of the Trevo device to Concentric Medical Inc.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.

SOURCE

https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm596983.htm

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