Registry: DAPT Discontinuation Less Associated With Second-Gen DES Thrombosis Compared to First-Gen DES

Download this article's Factoid (PDF & PPT for Gold Subscribers)

 

Patients who discontinue dual antiplatelet therapy (DAPT) in the first year after percutaneous coronary intervention (PCI) face less risk of stent thrombosis if they received second-generation rather than first-generation drug-eluting stents (DESs), according to a retrospective analysis from a single-center registry published online April 3, 2014, ahead of print in the American Journal of Cardiology. However, regardless of stent model, discontinuation led to higher MACE, including mortality.

Ron Waksman, MD, of Medstar Washington Hospital Center (Washington, DC), and colleagues analyzed 1-year rates of Academic Research Consortium (ARC)-defined stent thrombosis in 6,236 patients who received DESs from 2003 to 2012 at their institution.   

Patients were divided into first- (n = 4,217) and second-generation (n = 2,019) DES cohorts.

 First-generation DESs consisted of sirolimus-eluting (Cypher; Cordis/Johnson & Johnson; Warren, NJ) and paclitaxel-eluting devices (Taxus; Boston Scientific; Natick, MA). Second-generation consisted of everolimus-eluting stents (Xience V; Abbott Vascular; Santa Clara, CA; or Promus; Boston Scientific; Natick, MA). 

Additionally, within each DES-generation cohort, patients were categorized by the timing of clopidogrel discontinuation in the year after their procedure:

  •  Early (< 3 months)
  • Late (3-12 months) 
  • Continued (on DAPT for full 12 months) 

Discontinuation Rates Relatively Low

Overall, 341 patients (8.1%) in the first-generation DES cohort discontinued clopidogrel within 12 months with 2.5% discontinuing early (median 34 days) and 5.6% late (median 181 days). In the second-generation DES cohort, 126 patients (6.2%) discontinued clopidogrel within 12 months with 2.8% discontinuing early (median 22 days) and 3.4% late (median 184 days).

In the first-generation cohort, both early and late discontinuation were associated with higher incidence of ARC-defined definite and definite/probable ST compared with those who did not discontinue the therapy (table 1).

Table 1. Stent Thrombosis at 1 Year: First-Generation Cohort by Discontinuation Timing

 

Early
(n = 104)

Late
(n = 237)

Continued
(n = 3,874)

P Valuea

Definite ST

3.8%

1.3%

0.5%

0.001

Definite/Probable ST

3.8%

2.5%

0.9%

0.002

aAcross groups.

Numerically, there were more stent thrombosis events in first-generation patients who discontinued therapy early vs late, but the difference was not statistically significant.

In contrast, only one case of stent thrombosis was seen in the second-generation DES cohort, and it occurred in a patient who did not discontinue clopidogrel.

Regardless of stent type, mortality and MACE (all-cause death, MI, and definite/probable stent thrombosis) were higher with early and late DAPT discontinuation compared with continuation of therapy up to 1 year (P < 0.001 across groups for all comparisons).

In the first-generation DES cohort, the reason for early discontinuation was linked to allergy (18.8%), bleeding (24.6%), physician decision (18.8%), and end of prescription (24.6%); late discontinuation was driven by physician decision (28.1%) and end of prescription (41%). While allergy and physician decision also drove early discontinuation in the second-generation cohort (38.5% and 34.6%, respectively), physician decision was the predominant reason for late discontinuation (47.1%). Lack of compliance as a reason for discontinuing therapy decreased markedly from first-generation to second-generation DES patients (from 8.7% to 0 in early discontinuers and 4.5% to 2.9% in late discontinuers).

Did DES Make the Difference?

Dr. Waksman and colleagues say thinner stent struts, a reduced and more biocompatible polymer

layer, early and complete drug elution, and the use of newer rapamycin analogues in second-generation DESs result in more complete endothelial healing vs first-generation DESs. This, in turn, translates to a reduction in stent thrombosis without compromising efficacy, they add.

The investigators observe, however, it is “highly possible” that DAPT discontinuation contributed to the overall increase in MACE in the first-generation cohort, and similar increases, primarily driven by death, were seen in the second-generation cohort as well.

It is also possible that patients who discontinued DAPT prematurely were sicker, Dr. Waksman and colleagues note, adding, “This is suggested by the fact that the majority of the deaths occurring were non-cardiac related deaths…. Thus the patient-related risks and circumstances leading to [DAPT withdrawal were] perhaps the dominant factor accounting for increased mortality rather than the withdrawal of [DAPT] itself.”

A second possibility, they say, is that the protective effect of prolonged clopidogrel applies not only to stent thrombosis but also to other ischemic events that contribute to overall MACE incidence.

Finally, the authors note that they “cannot rule out potential benefit for longer duration of dual antiplatelet therapy even when second-generation DES[s] are used.”

Dr. Waksman and colleagues cite some study limitations including that the DES cohorts were treated at different time periods and results may be confounded by other changes in clinical practice and adjuvant therapies. Additionally, results were not adjusted for baseline differences among the groups, and the study was underpowered to detect true differences in ST among the groups.

Less Need for Protracted DAPT?

 “This is an interesting study that supports converging lines of evidence that second-generation [DESs] appear less dependent on protracted DAPT than do first-generation [DESs],” Deepak L. Bhatt, MD, MPH, of Brigham and Women’s Hospital (Boston, MA), wrote in an email with TCTMD.

“While we still don’t really know the optimal duration of DAPT for either generation of DES, if the physician decides to discontinue DAPT within the first year, the risks seem much lower with second- than with first-generation [DESs],” he added.


Source:
Loh JP, Torguson R, Pendyala LK, et al. Impact of early versus late clopidogrel discontinuation on stent thrombosis following percutaneous coronary intervention with first- and second-generation drug-eluting stents. Am J Cardiol. 2014;Epub ahead of print.  

 

Related Stories:

Disclosures
  •  Dr. Waksman reports no relevant conflicts of interest. 
  •  Dr. Bhatt reports receiving research grants from Amarin, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Medtronic, Roche, Sanofi Aventis, and The Medicines Company. 

We Recommend

Comments