In patients with diabetes and long coronary lesions who receive drug-eluting stents (DES), short-term reductions in target lesion revascularization (TLR) and adverse events are sustained out to 2 years when cilostazol is added to standard dual antiplatelet therapy, according to pooled results from 2 studies reported online December 7, 2009, ahead of print in the American Journal of Cardiology.
In the DECLARE-DIABETES and DECLARE-LONG trials, patients with diabetes and long lesions, respectively, were first randomized to sirolimus-eluting or paclitaxel-eluting stents, and then randomized to dual antiplatelet therapy (aspirin plus clopidogrel) with or without cilostazol. Both trials showed that triple therapy decreased TLR, TVR, and MACE at 9 months.
In the new report, researchers led by Seung-Jung Park, MD, PhD, of Asan Medical Center (Seoul, South Korea), pooled the results of both studies, finding that these reductions were maintained at 2 years (table 1).
Table 1. Two-Year Outcomes
|
Triple Therapy
(n = 450)
|
Dual Therapy
(n = 450)
|
P Value
|
TLR
|
4.2%
|
9.1%
|
0.003
|
TVR
|
6.2%
|
10.0%
|
0.038
|
MACEa
|
5.6%
|
10.4%
|
0.007
|
a Composite of death, MI, and TLR.
Rates of death, MI, and stent thrombosis were equivalent between the 2 groups. Interestingly, at 9 months, the composite of death, MI, and TVR was lower in the triple therapy group (3.8% vs. 8.0%; P = 0.007), but this difference just missed statistical significance at 2 years (7.6% with triple therapy vs. 11.3% with dual therapy; P = 0.053). This was mainly due to an additional 2 MIs that occurred in the triple therapy arm between 9 months and 2 years; no additional MIs occurred in the dual therapy arm over this time period.
In terms of adverse drug effects, there was more discontinuation in triple-therapy patients due to rashes and gastrointestinal problems, but bleeding rates were low and equivalent between the triple- and dual-therapy groups (table 2).
Table 2. Adverse Drug Affects at Least 6 Months Post-Index Procedure
|
Triple Therapy
(n = 450)
|
Dual Therapy
(n = 450)
|
P Value
|
Minor Bleedinga
|
1.1%
|
1.6%
|
0.561
|
Skin Rash
|
6.0%
|
1.8%
|
< 0.001
|
GI Problem
|
4.7%
|
1.6%
|
< 0.001
|
Drug Discontinuation
|
14.9%
|
1.8%
|
< 0.001
|
a There were no occurrences of major bleeding.
Most adverse drug effects resolved after stopping cilostazol. On multivariable analysis, independent predictors of 2-year TLR were cilostazol (HR 0.44; 95% CI 0.25-0.78; P = 0.005), sirolimus-eluting stents (HR 0.27; 95% CI 0.14-0.52; P = 0.0001), postprocedural minimal lumen diameter (HR 0.43; 95% CI 0.25-0.76; P = 0.003), and lesion length (HR 1.03; 95% CI 1.01-1.05; P = 0.022).
In subgroup analysis, Dr. Park and colleagues found that cilostazol helped lower 2-year TLR rates in men as well as patients with paclitaxel-eluting stents, diabetes, small vessels, long lesions, and LAD lesions. The researchers note that, to their knowledge, the study represents the first time investigators have attempted to compare long-term safety and efficacy of triple antiplatelet therapy with standard dual therapy after DES implantation.
Tailored Therapy Proposed
Based on the results, the researchers suggest that “tailored application of triple antiplatelet therapy in patients or lesions at high risk of clinical restenosis or cardiac events after DES implantation may be justified.”
The researchers were quick to point out that the study had a few limitations. In particular, stress tests to detect myocardial ischemia were not routinely performed, which might have led to bias regarding clinical decisions related to TLR. In addition, the number of patients in the study was too small to evaluate differences in cardiac events, and the DECLARE trials were both originally designed to determine the superiority of triple vs. dual antiplatelet therapy for in-stent late loss.
Study Details
Dual therapy consisted of aspirin (200 mg/day ≥ 24 hours before the procedure and from then on) and clopidogrel (loading dose of 300 mg, followed by 75 mg/day for at least 6 months). Patients receiving cilostazol were given a 200-mg loading dose of the drug immediately after the procedure and 100 mg twice daily for 6 months.
Source:
Lee SW, Chun KJ, Park SW, et al. Comparison of triple antiplatelet therapy and dual antiplatelet therapy in patients at high risk of restenosis after drug-eluting stent implantation (from the DECLARE-DIABETES and -LONG trials).
Am J Cardiol. 2010:Epub ahead of print.
Disclosures:
- The study was supported by the CardioVascular Research Foundation (Seoul, South Korea) and a grant from the Korean Ministry of Health and Welfare.
- The study contained no statement regarding physician conflicts of interest.
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Please click here for the Chinese translation.