Clot Busters

What Are Clot Busters?

Clot busting medications break up blood clots. During a heart attack, clot busters also called thrombolytics dissolve the blood clot that is blocking the artery and help restore blood flow to the heart. These medications are injected into the arm through an intravenous (IV) line. They are usually given to heart attack patients in the emergency department; however, they may sometimes be given in the ambulance en route to the hospital.

Benefits of Clot Busters

Women treated with clot busting drugs during a heart attack fare better than women who do not receive these medications. In an overview of nine research studies, clot busting medications reduced the risk of a woman dying within 35 days after a heart attack by 12%.

The benefits are even greater if nonfatal complications are counted. An analysis of the national registry of heart attack patients (called the National Registry of Myocardial Infarction, or NRMI for short) found that 13% of women treated with the clot buster tissue plasminogen activator (tPA or Activase), died or had a stroke while in-hospital compared with nearly 21% of women who did not receive clot busting drugs.

Even so, women did not benefit from clot busting drugs as much as men. Significantly more women treated with clot busters died or had a stroke compared with men treated with clot busters. This is partly because clot busters may be more likely to trigger a stroke in women than in men.

In terms of restoring blood flow to blocked arteries, clot busters work equally well in men and women. Why this does not translate into a similar reduction in death rates is unclear. Some researchers suggest that factors other than clogged arteries may play more of a role in women and elderly patients.

Reasons You May Not Be Able To Take Clot Busters
You SHOULD NOT be treated with clot busters if you:
  • Have ever experienced hemorrhagic stroke (bleeding in the brain)
  • Had a stroke in the last 3 months
  • Have a terminal illness
  • Are bleeding internally
  • Have a bleeding disorder
  • Experienced a serious head or facial injury in the last 3 months
You MIGHT NOT be treated with clot busters if:
  • Your systolic blood pressure (top number) is more than 180 mm Hg
  • Your diastolic blood pressure (bottom number) is more than 100 mm Hg
  • You have ever had a stroke, or are suffering form dementia
  • You have a head injury, trauma, surgery, or prolonged CPR (more than 10 minutes) in the last 2 to 4 weeks
  • You’ve had internal bleeding within the last 2 to 4 weeks
  • You have a peptic ulcer
  • You’ve had an allergic reaction to a clot busting drug before
  • You’ve been treated with streptokinase or anistreplase in the last 2 years
  • You are pregnant, or you recently miscarried or gave birth
  • You are currently taking anticoagulants such as Coumadin ( warfarin)

Risks of Clot Busters

There are different types of stroke; the most common type is due to blockages in the arteries supplying blood to the brain. Clot busters are more often associated with hemorrhagic stroke, which occurs when these arteries rupture and there is bleeding in the brain. Women treated with clot busters are 2 to 3 times more likely to suffer such a stroke than men treated with the same drugs. African Americans are more likely to suffer a stroke after treatment with clot busting drugs than white patients. Some research suggests that the increased risk of stroke in women is because women who have heart attacks are generally older and sicker than men. But other studies have found that even when you take this into account, women are still more likely to suffer a stroke than men.

Because clot busters increase bleeding, there were initial concerns that they may be unsafe for women during menstruation; however, there is now evidence to show that clot busters are safe for women during their menstrual period.

Stroke Risk in Women Treated With Clot Busters*

Study Name

International tPA/SK Mortality Study9

GUSTO-I4, 5

NRMI-26

CCP7

Year published

1993

1995

1998

2000

Number of patients

8261

41,021

71,073

31,732

% women

23

25

30

43

Most common age (yr)

62

61

73

Did women have an increased risk compared with men?

Yes – More than double

Yes – More
than double

Did women have increased risk after accounting for age and other factors?

Yes –
Nearly 3 times the risk

No

Yes –
More than 1.5 times the risk

Yes –
Nearly 1.5 times the risk

*This refers to hemorrhagic stroke or bleeding in the brain
CCP = Cooperative Cardiovascular Project; GUSTO = Global Use of Strategies To Open Occluded Coronary Arteries; NRMI = National Registry of Myocardial Infarction; SK = streptokinase; tPA = tissue plasminogen activator.

Dosing of Clot Busters in Low-weight Patients

The risks of stroke and bleeding complications after treatment with clot busting medications are higher in patients who weigh less than 155 lbs. It is thought that smaller patients, who are more likely to be women, might benefit if drug doses were lowered. A study comparing the standard clot buster, tPA (Activase), with tenecteplase (TNKase), a newer clot buster given in different doses depending on the patient’s weight, found little overall difference between the two. Patients weighing less than 155 lbs were more likely to die or suffer a stroke than heavier patients regardless of the clot buster they received. However, bleeding complications were lower with TNKase and there was suggestive but not conclusive evidence that this clot buster was less likely than Activase to trigger a stroke among women older than 75 years weighing less than 148 lbs.

Choice of Clot Buster

Examples of Approved Clot Busting Medications

Generic:

Alteplase (tPA)

Anistreplase

Streptokinase

Reteplase
(a type of tPA)

Tenecteplase

Common Brand:

Activase

Eminase

Streptase

Retavase

TNKase

How is it given?

IV line

IV line

IV line

IV line

IV line

Can it trigger allergic reactions?

No

Yes

Yes

No

No

Each clot buster has advantages and disadvantages and no one drug is clearly better than any other. For example, studies suggest that alteplase and reteplase are best for quickly restoring blood flow to the heart, but these clot busters have a higher risk of stroke than others. There is some evidence suggesting that tissue plasminogen activator (Activase) is associated with more bleeding in African American patients than streptokinase but more research is needed. Physicians choose which drug to use based on their assessment of each patient’s particular risks.

Clot Busters – Are Women Missing Out?

Are Women Missing Out on Clot Busting Drugs?

Clot busting drugs are not recommended for everyone who has a heart attack. When patients arrive at the emergency department they are assessed to see whether they should be treated with clot busters. Even when women are deemed candidates for clot busting medications, they are less likely to receive them than men. Some researchers suggest that there is no gender bias and that the difference is because women are more likely to be borderline candidates for clot busters than men. In some studies, when factors such as older age and other medical conditions were considered, there was little difference between men and women. However, an analysis of nine large studies on clot busting drugs found that many older, sicker patients benefit from these medications.1 Black women are significantly less likely to be treated with clot busting drugs than white men, even after accounting for factors such as age and other medical problems.

Treatment Delays in the Hospital

Clot busters work best when given within the first 3 hours of a heart attack and continue to be effective up to 12 hours after symptoms begin. They are particularly effective at reducing the risk of dying when given within an hour of when the heart attack begins. Women having a heart attack wait longer to be treated with clot busting drugs compared with men. An analysis of the National Registry of MyocardialInfarction (NRMI-1) found that hospital staff took longer to give clot busting drugs to women compared with men. In a survey of 138,956 Medicare beneficiaries (nearly half were women), women arriving at the hospital during a heart attack who were ideal candidates for clot busting drugs were less likely to receive them within 1 hour than men who were ideal candidates. The NRMI-1 study found that when hospital staff contacted the patient’s primary care physician, it took 20 minutes longer for the patient to receive clot busting drugs. This may be because internists and family physicians are less aware of the benefits of clot busting drugs than cardiologists.18

Delays Getting to the Hospital

Taking longer to get to the hospital during a heart attack often means having to wait longer at the hospital before being treated with clot busting drugs. A study conducted in 14 countries around the world (including the US) found that patients who got to the hospital within 2 hours of the start of their symptoms waited an average of 49 minutes for clot busting drugs, whereas patients who took 6 hours or longer to get to the hospital had to wait an average of 89 minutes before receiving clot busting drugs. Women having heart attacks tend to wait longer than men before going to the hospital. This is probably because women are less likely to realize that they are having a heart attack.

This global study, conducted between 1999 and 2001, found that almost one third of the people experiencing heart attack symptoms waited longer than 6 hours before seeking medical help.

Other Medications Used with Clot Busters

Overview

Heart attack patients treated with clot busters are also given anticoagulants ( blood thinners) and antiplatelets (drugs that make the blood less sticky) to help prevent further clots from developing, and to help prevent clots that have developed from getting bigger.

Heparin

Heparin is an anticoagulant that is given through an intravenous (IV) line in the arm during treatment with some clot busters (alteplase and reteplase). Because heparin affects the blood’s ability to clot, it can lead to bleeding problems. In early studies that combined clot busters and heparin, there were high rates of bleeding problems and stroke. Physicians now use lower doses of heparin to reduce this risk.

Low Molecular Weight Heparin

Finding the right dose of heparin for each patient is tricky; hospital staff must run blood tests and make dose adjustments if necessary. A newer type of heparin calledlow molecular weight heparin (LMWH) does not require such close monitoring. It is also easier to administer: LMWH is injected under the skin twice a day whereas regular heparin is given through an IV line in the arm. LMWH may be substituted for regular heparin in some heart attack patients treated with clot busters. One study showed that patients treated with LMWH and clot busters were less likely to die, suffer a heart attack or angina than those treated with regular heparin. However, there was no significant difference between the two treatments in women. There was also a tendency for people treated with LMWH to have more bleeding problems than those treated with regular heparin. This was especially true for patients older than 75 years.

Aspirin & Antiplatelets

Antiplatelet medications make the blood less sticky, which helps prevent blood clots from forming. Aspirin is the most common antiplatelet. Studies show that the benefits of aspirin and clot busters appear to be additive. Combining the two medications reduces the chances of dying from a heart attack more than either aspirin or clot busters alone.

Super Aspirins

Other antiplatelets include glycoprotein (GP) IIb/IIIa inhibitors. These medications are the so-called “super aspirins” because they work in a similar way to aspirin but have a much stronger effect. Abciximab (pronounced ab-six-i-mab) is one example of a super aspirin.

The combination of clot busters and super aspirins may be used in certain heart attack patients. Research studies suggest that while this combination is faster at restoring blood flow to the heart, this does not seem to lower the risk of dying after a heart attack. This combined therapy also seems to be riskier than clot busters alone. Patients treated with both drugs have a higher risk of bleeding complications and they are more likely to develop a dangerously low blood cell count than patients treated with clot busters alone.  The increased bleeding risk seems to be confined to patients older than 75 years so combined therapy is usually avoided in older patients.

Direct Antithrombins

Direct antithrombins are a type of anticoagulant. They may be substituted for regular heparin in heart attack patients who experience an allergic reaction to heparin. Otherwise, direct thrombin inhibitors are not generally given to heart attack patients. Studies show that combining bivalirudin with clot busters reduces the risk of subsequent heart attack compared with regular heparin. However, this benefit is outweighed by a significant increase in bleeding problems.

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