ATLANTA—In high-risk patients with atrial fibrillation who can’t tolerate standard blood thinners, such as warfarin, a combination treatment of aspirin and the more expensive clopidogrel (Plavix, Bristol-Myers Squibb/Sanofi-Aventis) is clinically effective for preventing stroke as well as being cost-effective, according to an ACTIVE-A economic substudy presented Sunday at the American College of Cardiology’s (ACC) 59th annual scientific session.

An economic analysis of the ACTIVE-A (Atrial Fibrillation Clopidogrel Trial with Irbesartan [Avapro; Bristol-Myers Squibb/Sanofi-Aventis] for Prevention of Vascular Events-Aspirin) found that the cost-savings associated with preventing strokes balanced the increased costs associated with adding clopidogrel to daily treatment with aspirin.

Slideshow | The Cost of Clopidogrel Use in Atrial Fibrillation: A Health Economic Analysis of ACTIVE-A

Andre Lamy, Wesley Tong, Peggy Gao, Susan Chrolavicius, Salim Yusuf, Stuart J Connolly

The original ACTIVE-A trial compared clopidogrel with aspirin with aspirin alone for patients with atrial fibrillation at high risk of stroke, who are unsuitable for vitamin K antagonist in 7,554 patients in 33 countries (N Eng J Med 2009; 360:2066-78).

Andre Lamy, MD, an associate professor in the departments of surgery and clinical epidemiology and biostatistics at McMaster University in Hamilton, Ontario, told Cardiovascular Business that about 8-10 percent of the atrial fibrillation patient population cannot tolerate vitamin K antagonists.

Lamy explained that the researchers mainly examined “direct hospitalization and healthcare costs, or costs to the provider, and beyond the hospital. Strokes, which are very expensive due to the long rehabilitation time, do not require patients to spend very long in the hospital.”

For the ACTIVE-A economic substudy, researchers analyzed the average health system costs associated with clinical illnesses requiring hospitalization over the study period of 3.6 years, comparing patients who were randomized to aspirin plus clopidogrel or aspirin plus placebo in the main ACTIVE-A study. They found that although medications cost an average of $2,114 more in clopidogrel-treated patients, the costs associated with clinical illness such as stroke or bleeding came to an average of $1,625 less; procedures, $86 less; and non-study medications, $28 less.

“In short, adding clopidogrel prevents strokes and does not increase healthcare costs,” said Lamy. “We now have an affordable alternative for patients intolerant to warfarin and similar blood thinners. These findings will impact practice not only in the U.S. but also worldwide.”

Overall, costs were $376 higher on average among clopidogrel-treated patients. When total costs were adjusted to account for differences in the year of treatment, they averaged $347 higher among clopidogrel-treated patients, but ranged from $613 lower to $1,307 higher, a cost-neutral result.

The analysis was based on the Canadian health system, but Canadian costs and those associated with the U.S. Medicare system and health maintenance organizations (HMOs) are similar, according to Lamy.

“All costs are somewhat higher in the U.S., but the relationship between strokes prevented and the cost of clopidogrel is likely to yield similar conclusions to the Canadian results, especially given that clopidogrel will soon be available as a generic drug in the U.S.,” he said.

The researchers acknowledged that they could only assess direct healthcare costs—mostly hospitalizations. Indirect costs for clopidogrel plus aspirin versus aspirin alone were presumably lower due to fewer strokes.

“New devices, such as Watchman [Atritech], and medications, such as expensive direct thrombin inhibitors, will all need to undergo economic analysis to see which therapy is appropriate within a healthcare system,” Lamy said.

These findings support the use of clopidogrel plus aspirin in patients unsuitable for vitamin K antagonist therapy in the ACTIVE-A trial, according to Lamy and his colleagues.

Sanofi-Aventis and Bristol-Myers Squibb funded the ACTIVE A trial and this economic analysis.