Anticoagulants are still the first-line prevention for most blood clots. The use of clot busters is reserved for acute cases in which a clot is seriously obstructing blood flow to an area of the body. The most common examples of this are during a heart attack and ischemic stroke, which are caused by a blockage in the flow of oxygen-rich blood to the heart or brain. Administering clot busters within four hours, particularly in the first 70 minutes, or three hours for a stroke, following the onset of symptoms, can greatly decrease the amount of tissue damage to the heart or brain caused by a lack of oxygen (hypoxia). The benefits of clot busters decrease over time. After 24 hours, they offer no advantage over anticoagulants for treatment of these conditions.

Clot-busting therapy remains an important rapid treatment method for people who have an ischemic stroke, in which the blood supply to the brain is disrupted by a blood clot. However, it is considered controversial by some because of the relatively high risk of bleeding in the body. It is also for this reason that people who suffer from hemorrhagic strokes, caused by excess bleeding in the brain, should not be given clot busters. These drugs may increase the bleeding and worsen the stroke. 

Before administering a clot buster to a stroke patient, the physician will always order a computed tomography (CT scan, which is a painless x-ray procedure that can determine whether the stroke is due to obstruction by a blood clot (ischemic) or by bleeding into the brain (hemorrhagic). Besides late arrival at the hospital, this need for a CT scan is the principle delay in administering clot busters. 

Despite the effectiveness of clot-busting medications for treating ischemic stroke, many patients are not able to benefit from their use. Researchers have found that as few as 22 percent of patients suffering a stroke arrive at the hospital within three hours of the onset of symptoms. Of these, only about 8 percent are candidates for clot-buster therapy.  Better recognition of the signs and symptoms of stroke could increase the number of patients who benefit from the use of clot-busting drugs.

With heart attack patients, clot–busting therapy is generally considered slightly less effective than rapid access to balloon angioplasty (within two hours of onset of symptoms), which also helps reestablish blood flow to the heart. However, clot-busting therapy remains a very important part of heart attack treatment because of the limited access to angioplasty treatment for many heart attack patients.

In addition to treating heart attack and stroke, other conditions that may be treated by clot busters include:

• Deep vein thrombosis. The formation of a blood clot in the deep veins of the legs. Clot busters are somewhat controversial in this area because of the risk of serious bleeding complications.
  
  
• Pulmonary embolism. A clump of material (e.g., a blood clot) that has traveled through the bloodstream and lodged within a blood vessel in the lungs, blocking blood flow. Clot-busting drugs may be used when the clot is large and is associated with low blood pressure and/or dysfunction of the right side of the heart.
  
  
• Thrombosis of an artificial heart valve. This is especially common in patients with artificial hearts valves who stop using necessary anticoagulants or receive an inefficient dose. The condition may result in severe obstruction of the heart valve resulting in pulmonary edema or collapse. Clot-busting drugs may dissolve the valve clot and allow normal flow through these valves.
  
  
• Occlusive peripheral artery disease (PAD). An advanced form of PAD in which the plaque that has formed within a peripheral artery accumulates to the point where blood flow within the artery is blocked (occluded).

Clot busters can also be rinsed through a catheter to clear any obstructing blood clots during a catheter-based procedure. While such procedures (e.g., balloon angioplasty) are generally scheduled to prevent the risk of a coronary event, they can also be used to reduce the damage caused by such events as they are occurring. In fact, research has suggested that women, people with diabetes and older stroke patients may benefit more from angioplasty than clot-busting medications.

However, the benefit of clot-busting medications is that they can be given "in the field," whereas angioplasty procedures must take place in a medical setting. Under a physician’s direction, first-responders, such as paramedics, can administer these medications for heart attack patients. This can shave valuable minutes off the time it takes to begin treatment. Research has shown that “the earlier, the better” applies to both clot-busting medication and angioplasty.