Studies Suggest Less Stringent Dual Antiplatelet Use After DES

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Two important areas of clinical uncertainty regarding dual antiplatelet therapy after drug-eluting stent (DES) implantation—how long it should last and whether it can be interrupted—have been addressed by a pair of studies. One suggests that just 3 months of therapy may be enough in select patients receiving a particular second-generation DES, while the other observed that briefly stopping the drugs after the first month has negligible impact on ischemic risk. 

Findings from both studies were published online September 19, 2012, ahead of print in the Journal of the American College of Cardiology.

Three Months of DAPT as Safe as 12

The RESET study, originally presented at the annual American College of Cardiology/i2 Scientific Session in March 2012 in Chicago, IL, tested a strategy of shorter-term dual antiplatelet therapy in patients receiving DES A team led by Myeong-Ki Hong, MD, of Yonsei University College of Medicine (Seoul, South Korea), randomized 2,117 patients with angina or AMI scheduled for elective PCI at 26 South Korean centers to 1 of 2 strategies:

  • Endeavor zotarolimus-eluting stents (ZES; Medtronic, Santa Rosa, CA) plus 3 months of dual antiplatelet therapy (n = 1,059)
  • Other DES, including Resolute ZES (Medtronic), SES, or EES, plus 12 months of dual therapy (n = 1,058)

Baseline characteristics were similar between the 2 groups.

At 1 year, the group receiving Endeavor plus 3 months of dual therapy experienced the same rate of the primary endpoint (cardiovascular death, MI, stent thrombosis, ischemia-driven TVR, or bleeding) as those receiving other DES plus 1 year of dual therapy, thereby meeting the criteria for noninferiority. Individual endpoints also were similar between the groups (table 1).

Table 1. Clinical Outcomes at 1 Year


Endeavor + 3 Months of Dual Therapy
(n = 1,059)

Other DES + 12 Months of Dual Therapy
(n = 1,058)

P Value

Primary Endpoint



< 0.01a

CV Death












Definite/Probable Stent Thrombosis




Major or Minor Bleeding




a P value for noninferiority.

Between 3 and 12 months after the index PCI, no patient in the Endeavor group suffered stent thrombosis despite the absence of protection, while 3 patients in the other DES group who were still on dual therapy had such an event.

On subgroup analysis, results for the primary endpoint were unaffected by age (threshold of 65 years), diabetes status, congestive heart failure, multivessel disease, reference vessel diameter (threshold of 3 mm), lesion length (threshold of 20 mm), or ACS. In addition, when the 63 patients (5.9%) in the Endeavor group who interrupted dual therapy during the 3- month regimen were excluded from analysis, again no differences in 1-year clinical outcomes were seen between the groups.

“[B]alanced DES that can offer both safety and efficacy are desirable, especially for those who may need to stop [dual antiplatelet therapy] early after DES implantation,” Dr. Hong and colleagues conclude.

Study Limitations Argue for Caution

In an editorial accompanying the paper, Bernhard Witzenbichler, MD, of Charité-Campus Benjamin Franklin (Berlin, Germany), advises caution in interpreting the data.

First, the authors based the sample size on an anticipated primary endpoint rate of 10%, he writes; since the actual rate was only 4.7%, the study’s finding of noninferiority may be unreliable. Furthermore, the low event rate may be explained in part by the generally low anatomic risk profile of the study cohort. Dr. Witzenbichler also points out that 1-year follow-up may be insufficient to detect potential late safety problems, especially in a higher-risk population.

Complicating interpretation, Dr. Witzenbichler observes, is the fact that the Endeavor ZES has largely been replaced by the Resolute ZES, which has a different, slow-release polymer and greater antiproliferative punch. In addition, Endeavor was compared with a mix of first- and second-generation DES. Finally, only 14% of patients in the study presented with NSTEMI, which is the patient group likely to reap the greatest benefit from prolonged antiplatelet therapy, regardless of the type of stent implanted.

When DAPT Is Interrupted

To parse the effect of interrupting antiplatelet drugs during the first year after DES implantation, investigators led by Ignacio Ferreira-González, MD, PhD, of Vall d’Hebron Hospital (Barcelona, Spain), looked at 1,622 patients from the ACDC cohort study who received at least 1 DES at 29 Spanish centers during a 3-month period in 2008.

Patients were followed up at 3, 6, 9, and 12 months to ascertain current medication use, medications temporarily or permanently interrupted since the previous inquiry, the reasons for such interruption, and any hospital readmissions. Those who died, experienced ACS, underwent bypass surgery, or were lost to follow-up before 1 year were excluded from analysis.

Over the first year, 172 patients (10.6%) interrupted at least 1 antiplatelet drug, almost two-thirds of them (64.5%) only temporarily. The drug stopped was clopidogrel in 79 patients and aspirin in 38; both drugs were interrupted in 55 patients. The median number of days without dual therapy in those who resumed the regimen was 7 (interquartile range, 5-8.5 days). The incidence of discontinuation varied slightly across the 3-month intervals (2.16%, 1.7%, 3.6%, and 3.6% at 3, 6, 9, and 12 months, respectively), but only 1 patient interrupted therapy during the first month.

With Brief Gap, No Harm Done

Overall, 87 patients (5.4%) experienced a major cardiac event during the first year. Only 7 of these patients (8%)—all of whom had ACS—reported some interruption of dual therapy, a rate that was similar to the 10.7% of 1,535 patients without events (or who had been censored before the end of follow-up) reporting discontinuation (P = 0.23).

After adjustment for differences related to the patients’ overall risk, the severity and natural history of their disease, and the hospital where they were treated, major cardiac events were not associated with discontinuation regardless of whether patients interrupted aspirin, clopidogrel, or both drugs.

The authors conclude that although discontinuation of dual therapy during the first year after DES implantation is not uncommon, it is usually temporary and unlikely to be followed by major cardiovascular events, at least if it occurs after the first month. This information “could be helpful in situations with conflicting risks, such as the unexpected need for major noncardiac surgery in patients with DES, but [this] needs further confirmation because stent thrombosis, even if rare, may have dire consequences,” they add. 

Interpretation May Be Difficult 

In his editorial, Dr. Witzenbichler lauds the ACDC researchers for probing the timing and length of therapy interruptions rather than simply categorizing patients as being “on” or “off” therapy, as others have done.

However, he raises several issues that make interpretation of the data problematic:

  • During the first 6 months, the median interval from initial discontinuation of a thienopyridine to stent thrombosis has been shown to be 13.5 days, whereas here the median discontinuation lasted only 7 days
  • The temporal connection between discontinuation and subsequent events beyond 6 months is relatively loose, and in the current study twice as many patients interrupted therapy in the last 6 months of the prescribed regimen as in the first 6 months, suggesting that delayed consequences may not have been captured.
  • Because event rates were low, the study may be underpowered 


1. Kim B-K, Hong M-K, Shin D-H, et al. A new strategy for discontinuation of dual antiplatelet therapy: The RESET trial (REal Safety and Efficacy of 3-month dual antiplatelet Therapy following Endeavor zotarolimus-eluting stent implantation). J Am Coll Cardiol. 2012;Epub ahead of print.

2. Ferreira-González I, Marsal JR, Ribera A, et al. Double antiplatelet therapy after drug-eluting stent implantation: Risk associated with discontinuation within the first year. J Am Coll Cardiol. 2012;Epub ahead of print.

3. Witzenbichler B. Dual antiplatelet therapy after drug-eluting stent implantation: Is it time to slacken the reins? J Am Coll Cardiol. 2012;Epub ahead of print.



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  • The RESET trial was supported by the Cardiovascular Research Center (Seoul, South Korea), Medtronic, and grants from various South Korean governmental agencies.
  • Dr. Hong reports receiving research grants from the Cardiovascular Research Center and Medtronic.
  • The ACDC study was supported by grants from Bristol-Myers-Squibb and the Fondo de Investigación Sanitaria.
  • Dr. Ferreira-González reports no relevant conflicts of interest.
  • Dr. Witzenbichler reports receiving lecture fees from Abbott Vascular, Biotronik, Boston Scientific, and Medtronic.

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