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Calculating Who Will (and Won’t) Benefit from DAPT
R
ecently, we have seen a new systematic review of the use of dual antiplatelet therapy
(DAPT)1 and the recent update of the ACC/
American Heart Association (AHA) guidelines on
duration of DAPT in patients with coronary artery
disease (CAD).2
The DAPT study demonstrated that the risks
of MI and stent thrombosis (ST) beyond 1 year
after PCI were reduced by continued thienopyridine therapy (clopidogrel or prasugrel) plus aspirin
compared to placebo plus aspirin at 12 months.
That’s the good news; as you can imagine, the beneficial effects of being randomized to 18 months of
continued DAPT after 12 months of such therapy
came at the cost of higher moderate and severe
bleeding than being rerandomized to placebo and
aspirin for the same period of time. Moreover,
there was a nominal signal suggesting increased
all-cause mortality with continued DAPT. (See the
May issue of ACCEL for more details.)
All of this was important to know, of course,
but the relative benefit and risk was not well-defined. Specifically, in trying to balance risk versus
benefit from continued DAPT, how did a history
of MI prior to stent treatment affect this risk/benefit analysis? And was there any additional utility
to using a decision tool (DAPT Score) to better
gauge benefit versus risk? Those issues were at the
heart of a new analysis of the DAPT study.
treatment period (12–30 months) for ischemic
(MI and/or ST) and bleeding (GUSTO moderate/
severe) events were compared according to DAPT
score. Rates of MI were 3.8% vs. 2.4% (p = 0.01)
for patients with any MI versus no MI.
Continued thienopyridine reduced late MI
compared with placebo regardless of MI history
TABLE
DAPT Score
Variable
Points
Age ≥ 75 yrs
-2
Age 65 to < 75 yrs
-1
Age < 65 yrs
0
Current cigarette smoker
1
Diabetes mellitus
1
MI at presentation
1
Prior PCI or prior MI
1
Stent diameter < 3 mm
1
Paclitaxel-eluting stent
1
CHF or LVEF < 30%
2
Saphenous vein graft PCI
2
A score of ≥ 2 is associated with a favorable benefit/risk ratio for
prolonged DAPT while a score of < 2 is associated with an unfavorable benefit/risk ratio.
CHF = congestive heart failure; DAPT = dual antiplatelet therapy;
A TOOL TO INDIVIDUALIZE THERAPY
LVEF = left ventricular ejection fraction; MI = myocardial infarction;
Recently, Robert W. Yeh, MD, and colleagues
published a paper in JACC presenting a clinical decision tool to identify patients expected
to derive benefit versus harm from continuing
thienopyridine (clopidogrel or prasugrel) therapy
beyond 1 year post-PCI.3 Dr. Yeh is an interventional cardiologist and director of the new Center
for Outcomes Research in Cardiology at Beth Israel
Deaconess Medical Center, Boston, MA.
The tool was based on stratification of patients participating in the DAPT study and was
validated on patients in the PROTECT (PatientRelated Outcomes with Endeavor versus Cypher
Stenting) trial.
You can see the DAPT Score detailed in the
TABLE. Overall, lower DAPT scores were associated
with higher bleeding risk (with or without continued thienopyridine therapy) and less ischemic
benefit from treatment while higher DAPT scores
were associated with lower bleeding risk and
larger absolute ischemic benefit.
The 25,682 patients enrolled in the DAPT
study were categorized according to any history
of MI prior to the index procedure or no history
of MI. Risk differences during the randomized
PCI = percutaneous coronary intervention.
18
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(HR: 0.46; p < 0.001 any MI; HR: 0.60; p = 0.003
no MI) and increased bleeding (HR: 1.86; p = 0.01
any MI; 1.58; p = 0.01 no MI). DAPT scores ≥ 2
were associated with reductions in MI/ST with
continued thienopyridine versus placebo (2.7% vs.
6.0%; p < 0.001 any MI; 2.6% vs. 5.2%; p = 0.002
no MI), with bleeding rates of 1.5% vs. 1.1%
(p = 0.24) and 2.2% vs. 2.0% (p = 0.68), respectively.
Among patients with DAPT scores < 2, in both
groups, continued thienopyridine was associated
with increased bleeding (3.2% vs. 1.2%, p = 0.01
any MI; 2.9% vs. 1.6%, p = 0.004 no MI), and ischemic rates of 2.1% vs. 3.2% (p = 0.17) for patients
with previous MI and 1.5% vs. 2.0% (p = 0.21) for
those without.
NOT EASY (BUT CLEARER)
Yeh and colleagues, although patients with any MI
(versus no MI) derived greater absolute reductions
in risk for MI/ST, the relative hazards for major
bleeding events were similar (HR: 1.86; p = 0.01
any MI; HR: 1.58; p = 0.01 no MI).
Of note, the DAPT score included a history of
MI; by definition, patients with any MI would be
expected to have higher scores. Nonetheless, the
score still differentiated between those who would
benefit from or be harmed by continuation of thienopyridines among patients within each of these
groups. Note that 35% of the no MI cohort had
high DAPT scores, which would predict ischemic
benefit exceeding bleeding risk; on the other hand,
30% of the any MI cohort had low DAPT scores
which would predict bleeding risk exceeding ischemic benefit.
Thus, almost one-third of the patients in either
MI subgroup (any or no) might have been more
accurately prescribed risk appropriate duration
of dual antiplatelet therapy based on DAPT score
compared with MI status alone.
Based on this study, here’s
what you need to know:
among patients with MI eligible for prolonged thienopyridine therapy at 1-year postPCI, the DAPT Score appears
to provide a more accurate
benefit versus risk assessment
To listen to an
interview with
upon which individualized
Robert W. Yeh, MD,
thienopyridine therapy may
talking about the
be appropriately prescribed.
DAPT Study, scan the
code. The interview
A high DAPT score (≥ 2)
was conducted by
predicts ischemic benefit
E. Magnus Ohman,
without incremental bleeding
MD.
risk with extended thienopyridine therapy beyond 1 year.
(Keep a copy of the TABLE
handy so you can calculate the
DAPT score. Or you can use
an online calculator, available
at the DAPT study website:
daptstudy.org/
for-clinicians/score_calculator.htm).
REFERENCES:
1. Bittl JA, Baber U, Bradley SM, et al. J Am Coll Cardiol.
2016;doi:10.1016/j.jacc.2016.03.512
2. Levine GN, Bates ER, Bittl JA, et al. J Am Coll Cardiol.
2016; doi:10.1016/j.jacc.2016.03.513
3. Kereiakes DJ, Yeh RW, Massaro JM, et al. J Am Coll Cardiol.
2016 doi:10.1016/j.jacc.2016.03.485
Where are we then? Optimizing therapy for
individual patients in order to minimize these
counterbalancing risks is complex and not simply
determined by MI status. Indeed, in the study by
July 2016