Prasugrel vs. clopidogrel: Making the decision

While further study is clearly needed, some general guidelines can be offered based on what's currently known.

Best candidates.  Prasugrel plus aspirin may be a sensible choice for coronary syndrome patients who are undergoing PCI, have no risk factors for bleeding, and get to the hospital early enough for doctors to determine whether they might need bypass surgery instead.

In contrast, patients with a history of strokes or transient ischemic attacks should avoid prasugrel. (Studies so far have not linked clopidogrel, at least at the approved dose, with increased risks for those patients.) People age 75 or older should probably stick with clopidogrel in most cases, particularly since prasugrel is not recommended for use among this population. For patients who weigh less than about 130 pounds, the package insert says that doctors could consider halving the maintenance dose of prasugrel; although, there is no direct evidence that this smaller dose is actually safer or as effective.

People with active bleeding should avoid both drugs. Those who need bypass surgery should not take prasugrel or, if they've already started, should stop taking it at least a week before their operation. (Clopidogrel should generally be stopped five to seven days before surgery.)

Individualizing the choice.  Despite those general guidelines, doctors should choose the drug regimen based on each patient's particular risk of hemorrhages and blood clots. An increased hemorrhage risk from prasugrel seems to make clopidogrel more desirable, while the high risk of clotting favors prasugrel or the doubled dose of clopidogrel. Some factors that may increase the likelihood or consequences of bleeding, in addition to those listed above, include a history of excessive bleeding (for example, from dental procedures or other minor trauma), stomach ulcers, colon abnormalities, anemia, severe liver disease, and the use of other blood thinners, including nonsteroidal anti-inflammatory drugs such as aspirin, ibuprofen (Advil, Motrin and generics), and naproxen (Aleve and generics). Factors that may make clots more likely include previous clotting problems, heart disease, diabetes, small blood vessels, and the placement of multiple stents, the tiny metallic mesh tubes that prop open PCI-treated vessels.

In general, Consumer Reports medical consultants recommend against using prasugrel for unapproved uses, such as for the prevention of a second heart attack. But they say that off-label use of the drug might be considered for patients who experience a serious blood clot, heart attack, or stroke despite taking clopidogrel. That would be particularly reasonable if doctors can test for platelet responsiveness to clopidogrel.