New and noteworthy research from the medical literature landscape

The “ triple-therapy ” anticoagulation regimen ( consisting of a vitamin K antagonist [ VKA ] plus dual antiplatelet therapy [ DAPT ] with a P2Y 12 inhibitor and aspirin ) has been shown to reduce thrombotic and stroke risk in patients with atrial fibrillation ( AF ) undergoing percutaneous intervention ( PCI ) with stent placement . However , this regimen does increase bleeding risk .

According to results from the PIONEER AF-PCI trial published in the New England Journal of Medicine , the oral factor Xa inhibitor rivaroxaban , when added to a

P2Y 12 inhibitor or DAPT , leads to similar efficacy , but a lower risk of bleeding , compared with standard VKA-based triple therapy .

C . Michael Gibson , MD , of the Department of Medicine at Beth Israel Deaconess Medical Center and Harvard Medical School , in Boston , Massachusetts , and authors enrolled 2,124 adult patients between May 2013 and July 2015 to this international , multicenter , randomized , controlled , open-label trial .

Patients with paroxysmal , persistent , or permanent nonvalvular AF ( defined as AF not considered

TABLE 1 . Safety Outcomes Associated With Each Treatment Cohort ( Primary Endpoint )

to be caused by a primary valve stenosis ) who had undergone PCI with stent placement were eligible for inclusion . Patients were excluded if they had any condition known to increase the risk of bleeding ( including a history of stroke or transient ischemic attack or anemia of an unknown cause with a hemoglobin concentration < 10 g / dL ).

Patients were randomized 1:1:1 to the following three groups :

• group 1 : low-dose rivaroxaban ( 15 mg once daily )

TABLE 2 . Efficacy Outcomes Associated With Each Treatment Cohort ( Secondary Endpoint )

Death from cardiovascular causes

15 ( 2.4 %)

Myocardial infarction 19 ( 3 %)

Stroke 8 ( 1.3 %)

Stent thrombosis 5 ( 0.8 %)

Major adverse cardiovascular event or stent thrombosis

HR = hazard ratio

Group 1 Group 2

41 ( 6.5 %)

Groups 1 and 2

14 ( 2.2 %)

17 ( 2.7 %)

10 ( 1.5 %)

6 ( 0.9 %)

36 ( 5.6 %)

Groups 1 and 2 vs . Group 3 Group 1 vs . Group 3 Group 2 vs . Group 3

Group 3 HR p value HR p value HR p value

Major bleeding 14 ( 2.1 %)

Minor bleeding 7 ( 1.1 %)

Bleeding that requires medical attention

93 ( 14.6 %)

12 ( 1.9 %)

7 ( 1.1 %)

102 ( 15.8 %)

26 ( 2 %)

14 ( 1.1 %)

195 ( 15.2 %)

20 ( 3.3 %)

13 ( 2.2 %)

139 ( 22.6 )

11 ( 1.9 %)

21 ( 3.5 %)

7 ( 1.2 %)

4 ( 0.7 %)

36 ( 6 %)

0.59 ( 95 % CI 0.47-0.76 )

0.66 ( 95 % CI 0.33-1.31 )

0.51 ( 95 % CI 0.20-1.28 )

0.61 ( 95 % CI 0.47-0.80 )

1.29 ( 95 % CI 0.59-2.80 )

0.86 ( 95 % CI 0.46-1.59 )

1.07 ( 95 % CI 0.39-2.96 )

1.20 ( 95 % CI 0.32-4.45 )

1.08 ( 95 % CI 0.69-1.68 )

< 0.001 0.63 ( 95 % CI 0.50-0.80 )

0.23 0.57 ( 95 % CI 0.28-1.16 )

0.14 0.50 ( 95 % CI 0.20-1.26 )

< 0.001 0.67 ( 95 % CI 0.52-0.86 )

* Data are for all participants who underwent randomization and received at least one dose of the trial regimen during the treatment period . HR = hazard ratio

< 0.001 0.61 ( 95 % CI 0.50-0.75 )

0.11 0.61 ( 95 % CI 0.34-1.09 )

0.13 0.51 ( 95 % CI 0.24-1.08 )

0.002 0.64 ( 95 % CI 0.51-0.80 )

0.52 1.19 ( 95 % CI 0.54-2.62 )

0.62 0.75 ( 95 % CI 0.40-1.42 )

0.89 1.36 ( 95 % CI 0.52-3.58 )

0.79 1.44 ( 95 % CI 0.40-5.09 )

0.75 0.93 ( 95 % CI 0.59-1.48 )

0.09

0.07

< 0.001

0.66

0.37

0.53

0.57

0.76 plus a P2Y 12 inhibitor for 12 months ( n = 709 ; mean age = 70.4 years )

• group 2 : very – low-dose rivaroxaban ( 2.5 mg twice daily ) plus DAPT for 1 , 6 , or 12 months ( n = 709 ; mean age = 70.0 years )

• group 3 : standard therapy with a dose-adjusted VKA ( once daily ) plus DAPT for 1 , 6 , or 12 months ( n = 706 ; mean age = 69.9 years )

Randomization occurred within 72 hours after stent sheath removal , once the international normalized ratio was ≤2.5 . Investigators selected the duration of DAPT ( 1 , 6 , or 12 months ) and intended

P2Y 12 inhibitor ( clopidogrel , prasugrel , or ticagrelor ) for each patient .

At 12 months of follow-up , Dr . Gibson and authors found that “ treatment that included either low-dose or very – low-dose rivaroxaban was associated with a lower risk of clinically significant bleeding – the study ’ s primary endpoint – compared with standard triple therapy that included a [ VKA ].”

Clinically significant bleeding ( defined as a composite of major bleeding or minor bleeding per Thrombolysis in Myocardial Infarction criteria or bleeding requiring medical attention ) occurred in 16.8 percent of patients in group 1 , 18 percent in group 2 , and 26.7 percent in group 3 .

Hazard ratios for clinically significant bleeding between the rivaroxaban-based regimens and the VKA-based regimens were :

• 0.59 for group 1 vs . group 3 ( 95 % CI 0.47-0.76 ; p < 0.001 )

• 0.63 for group 2 vs . group 3 ( 95 % CI 0.50-0.80 ; p < 0.001 )

16 ASH Clinical News January 2017 Annual Meeting Edition