HOST-ASSURE Supports Three-Drug Anticlotting Regimen After Angioplasty

March 25, 2012—The American College of Cardiology (ACC) announced that findings from the HOST-ASSURE trial demonstrated that cilostazol (Pletal [Otsuka Pharmaceutical Co., Ltd., Tokyo, Japan]) added to dual-antiplatelet therapy (100 mg of aspirin and 75 mg of clopidogrel) for a regimen of triple-antiplatelet therapy (TAT) in high-risk patients undergoing angioplasty is as safe and effective as a double-dose dual-antiplatelet therapy (DDAT) using aspirin and double-dose clopidogrel (150 mg). Principal Investigator Hyo-Soo Kim, MD, presented the findings at the ACC's annual scientific sessions in Chicago.

According to the ACC, several studies have demonstrated that cilostazol not only prevents platelet clumping, but also aids in preventing restenosis, encouraging vasodilation, protecting kidneys, and improving blood levels of lipids. Previous studies supported the addition of cilostazol to conventional dual-antiplatelet therapy, but the drug is unfamiliar to many Western physicians. Under the brand name Pletal, cilostazol was developed by Otsuka, a Japanese company that has not widely marketed the drug outside of Asia and has not sponsored a large clinical trial for it.

Dr. Kim commented, “TAT is widely used in Korea and Japan because we experienced the benefit of cilostazol in terms of major adverse cardiovascular events (MACE) after angioplasty. In the numerous clinical studies about angioplasty, we have an impression that the MACE rate is lower in Korean studies than in Western ones.”

“Most clinical evidence supporting cilostazol's benefit comes from investigator-initiated trials like ours,” added Dr. Kim. “HOST-ASSURE is the first large-scale randomized trial to directly compare the two treatment strategies and confirm the noninferiority of TAT compared with DDAT.”

HOST-ASSURE, which will follow patients for 3 years, is a 2 X 2 factorial trial designed to compare the two antiplatelet regimens and two types of drug-releasing stents (data to be reported in the future). Patients were randomly assigned to TAT (1,879 patients) or to DDAT (1,876 patients). All patients received 300 to 600 mg of clopidogrel plus 300 mg of aspirin before angioplasty with (TAT) or without (DDAT) a loading dose of 200 mg of cilostazol. In the TAT group, 100 mg of cilostazol twice daily was added to DAT for 1 month after the procedure; in the DDAT group, the maintenance regimen was 150 mg of clopidogrel with aspirin.

The primary endpoint was the occurrence of events including cardiovascular-related death, nonfatal heart attack, stroke, and major bleeding at 1 month after angioplasty, which amounted to 23 patients (1.2%) in the TAT group and 27 patients (1.4%) in the DDAT group. These findings demonstrated noninferiority of the three-drug regimen compared with the double-dose two-drug treatment. The TAT group had fewer heart attacks (one patient vs five patients). The DDAT group had fewer side effects (eight patients), but none of the 34 patients in the TAT group who had side effects developed life-threatening or severe adverse reactions. The most frequent side effects of cilostazol are headache and gastrointestinal trouble, and most of the side effects are reversible, Dr. Kim noted.

“This study provides evidence for the already popular adjunctive use of cilostazol in clinical practice in Asia—in particular in Korea and Japan,” concluded Dr. Kim. “If TAT is equivalent to a potent regimen such as DDAT that is used for high-risk patients, TAT would be preferred because it has additional vascular biologic benefit on top of its antiplatelet effect.”