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DAPT score can identify patients who may benefit from shorter DAPT
In patients undergoing PCI, prolonged dual antiplatelet therapy may reduce ischemic events in patients with high DAPT scores but may be harmful for those with low scores, according to published findings.
To assess the safety and efficacy of DAPT duration according to DAPT score, the researchers applied the DAPT score to patients who underwent PCI in the PRODIGY trial. Patients randomly received one of four stent types and were randomly assigned to 6 or 24 months of DAPT at 30 days. Treatment included a maintenance dose of clopidogrel of 75 mg daily for up to 6 or 24 months as well as a low dose of aspirin, which was prescribed indefinitely in all patients.
The primary efficacy endpoint was a composite of death, MI or cerebrovascular accident, and the primary safety endpoint was a composite of type 3 or 5 bleeding according to the Bleeding Academic Research Consortium (BARC) definitions.
Efficacy affected
Of the 1,970 patients included in the study, 44.9% had a DAPT score of 2 or higher and 55.1% had a score less than 2. The reduction in the primary efficacy endpoint with prolonged vs. shorter DAPT was greater among patients with DAPT scores of at least 2 (risk difference, –2.05 percentage points; 95% CI, –5.04 to 0.95), compared with those with DAPT scores less than 2 (risk difference, 2.91 percentage points; 95% CI, –0.43 to 6.25), according to the data.
The researchers noted, however, that the reduction in the primary efficacy endpoint with prolonged DAPT among patients with high DAPT scores varied by stent type (P for interaction = .005), with patients who received paclitaxel-eluting stents having a lower risk for events with prolonged vs. shorter DAPT. After excluding patients who received PES, the risk difference with prolonged vs. shorter DAPT was similar for those with high (risk difference, 1.23 percentage points; 95% CI, –2.41 to 4.86) and low DAPT scores (risk difference, 2.38 percentage points; 95% CI, –1.12 to 5.87; P for interaction = .65).
Results also indicated an increase in BARC type 3 or 5 bleeding with prolonged DAPT among patients with DAPT scores less than 2 (risk difference, 2.58 percentage points; 95% CI, 0.71-4.46), compared with those with DAPT scores of 2 or greater (risk difference, 0.2 percentage points; 95% CI, –1.2 to 1.6; P = .046).
“[The] study suggests that the DAPT score can be used to identify patients who should be treated with short-term DAPT, but it is not useful for determining which patients treated with current-generation drug-eluting stents derive a net benefit from extending therapy beyond 1 year,” J. Dawn Abbott, MD, from the Warren Alpert School of Medicine at Brown University in Providence, Rhode Island, wrote in an accompanying editorial.
Abbott noted other DAPT duration scores also have shortcomings.
“Although risk scores can assist with decision-making, clinical judgment remains essential. There may be PCI patients with current-generation [DES] for whom DAPT duration as short as 1 month or as long as a lifetime is reasonable,” she wrote.
Additionally, Abbott noted genetic determinants of responsiveness to antiplatelet therapy are not yet accounted for in the current DAPT scores.
“The future may bring point-of-care genetic tests or imaging methods that better identify patients who are vulnerable to recurrent ischemic events. Patient preferences also matter. We should strive to practice shared decision-making that factors in evidence and patient values,” she wrote. – by Melissa Foster
Disclosure: Please the full study for a list of the researchers’ relevant financial disclosures. Abbott reports receiving grants from Abbott Cardiovascular Systems, AstraZeneca, Bristol-Myers Squibb and Medinol, and having financial ties with Pfizer and Recor.
Perspective
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It is reassuring to see that the DAPT risk score does separate ischemic benefit and bleeding risk for a broad-spectrum cohort of patients beginning at 30 days post-PCI. These data provide external validation of the DAPT risk score in the context of three major and obvious caveats.
No. 1, the primary efficacy and safety endpoints analyzed in the current study from PRODIGY are significantly different from the ischemic risk endpoint and bleeding risk endpoint used in the derivation of the DAPT risk score. The present analysis uses the composite of death, MI and cerebrovascular accident as a primary efficacy endpoint and BARC 3 or 5 bleeding as the primary safety endpoint. Conversely, in the DAPT trial, we used the composite of MI and stent thrombosis to reflect ischemic event risk and GUSTO moderate/severe bleeding to reflect bleeding event risk. Further, the period for analysis in the PRODIGY study is for all patients beyond 30 days post-PCI and in the DAPT trial was for patients who were free from MACCE and major bleeding as well as compliant with DAPT therapy beyond 1 year following randomization.
No. 2, the current subgroup analysis by stent type is severely underpowered, with 500 patients or fewer in each stent group. This stands as an objective comparison to the stent subtypes analyzed in the DAPT trial, which included 4,703 everolimus-eluting stents, 2,666 PES, 1,264 zotarolimus-eluting stents and 1,118 sirolimus-eluting stents. Thus, subgroup analyses made from the DAPT trial include many more patients: The DAPT PES subgroup is more than five times greater and the DAPT EES subgroup is more than nine times greater than the corresponding subgroups in the current analysis.
No. 3, the conclusions that “extended DAPT provides ischemic benefit only with PES” and that “whether prolonged DAPT benefits patients with high scores treated with contemporary DES requires further study” ignores the important observations from the DAPT trial in 4,703 EES (contemporary DES) patients, which observed a 60% reduction in stent thrombosis and a 40% reduction in MI with prolonged (30 months) vs. shorter duration (12 months) of DAPT (Mauri L, et al. N Engl J Med. 2014;doi: 10.1056/NEJMoa1409312; Yeh RW, et al. JAMA. 2016;doi:10.1001/jama.2016.3775). Data from that analysis show that the DAPT risk score effectively stratified risk-benefit among patients treated only with EES (contemporary DES). Furthermore, the DAPT trial analysis showed no statistically significant interaction by stent type for the important endpoints of MI and stent thrombosis. Thus, based on a quantum greater number of patients analyzed, the DAPT trial analysis would suggest that patients treated with contemporary DES do derive ischemic event benefit from longer duration of DAPT. To the point made in the present analysis, whether or not this level of ischemic event benefit derived in contemporary DES patients effectively counterbalances the bleeding risk entailed by longer-duration DAPT is still a point of debate.
Overall, the PRODIGY analysis appears to be an external validation that the DAPT risk score was effective and may well be the gold standard decision tool to individualize DAPT duration among patients who reach 6 to 12 months without a major bleeding or ischemic event. These are positive findings and further support the use of the DAPT risk score.
Interestingly, the researchers did not use the recently developed PRECISE-DAPT score, as described by Valgimigli et al in a separate study. These investigators will likely assess the relative sensitivity and specificity of that tool compared with the DAPT risk score in a future publication. I personally think that the PRECISE-DAPT score is very useful and complementary to the DAPT risk score, but in the future, I would hope to see more data comparing the predictive accuracy of the two scores early following PCI.