Practice Update: Cardiology

Full-dose oral triple therapy with DAPT

and full-dose anticoagulation should be

avoided in patients with atrial fibrillation

Results of PIONEER to date lead to the conclusion that abandoning full-dose triple therapy is

warranted in patients with atrial fibrillation. This conclusion was explained in a discussion of

PIONEER at AHA 2016.

eepak L. Bhatt, MD, MPH, of Brigham and Women’s

Hospital, Boston, Massachusetts, explained that one of the

most common conundrums in all of cardiovascular medicine

pertains to the care of patients with atrial fibrillation who need

percutaneous coronary intervention. Both dual antiplatelet therapy

and oral anticoagulant therapy seem necessary to reduce risks of stent

thrombosis and thromboembolism, respectively.

Intensifying the antithrombotic regimen, however, leads to more

bleeding. A greater appreciation of bleeding has emerged in recent

years. Fatal or intracranial bleeding would provide a direct causal

pathway for the now well-known association between bleeding and

death.

Bleeding may be associated with partial or complete interruption or

cessation of the various components of the antithrombotic regimen.

Other medications, such as statins and beta blockers, are sometimes

also stopped and may or may not be resumed. Transfusions, either

appropriately or inappropriately, may be administered.

Hospitalisations frequently occur around major bleeding episodes,

and these can lead to a series of tests and procedures, may increase

the risk of nosocomial infections, or lead to other adverse sequelae

from hospitalisation. Thus, through direct and indirect pathways,

bleeding requiring hospitalisation can cause major morbidity, including

cardiovascular morbidity.

Another development concomitant with advances in our understanding

of anticoagulation and the introduction of

novel oral anticoagulants into widespread

clinical practice has been the evolution in

stenting.

Second-generation drug-eluting stents

constitute a major advance. In addition to

offering low restenosis rates, they appear

to lead to lower stent thrombosis rates than

first-generation drug-eluting stents or even

older bare metal stents. This reduction in

stent thrombosis is apparent in late and very

late stent thrombosis, but also has been

demonstrated with respect to early stent

thrombosis, at least with certain second-

generation drug-eluting stents.

Two modest-size randomised trials, the What

is the Optimal antiplatElet and anticoagulant

therapy in patients with oral anticoagulation

and coronary StenTing? (WOEST) and Triple

Therapy in Patients on Oral Anticoagulation

After Drug Eluting Stent Implantation

(ISAR-TRIPLE), have shown that double

therapy (single antiplatelet therapy plus

full-dose vitamin K antagonists) appeared to

provide similar efficacy and reduced bleeding versus triple therapy

(dual antiplatelet therapy plus full-dose vitamin K antagonism).

Curiously, a signal of less ischaemic/thrombotic complications was

suggested with double therapy, though these two trials were not

powered for efficacy endpoints. It remained possible, however, that

excess bleeding with triple therapy overwhelmed any potential gain in

efficacy. Furthermore, the role, if any, of the novel oral anticoagulants

in place of vitamin K antagonists such as warfarin remained poorly

characterised.

Interestingly, even when the duration of full dose triple therapy was 6

weeks in ISAR-TRIPLE, a large percentage of the bleeding had already

occurred. Thus, abbreviating the course of full-dose triple therapy does

not diminish the risks of bleeding as much as we would like to believe.

If a patient passes this early potent bleeding stress test, the subsequent

risk of bleeding is lower, but may still be substantial in terms of

cumulative risk over time. These early and late bleeding risks seem

to be particularly high in older patients.

In the PIONEER Atrial Fibrillation – Percutaneous Coronary

Intervention trial, 2124 stented patients with atrial fibrillation were

randomised to one of three groups:

•

Group 1:

reduced-dose rivaroxaban 15 mg daily plus a P2Y12 for

12 months.

•

Group 2:

rivaroxaban 2.5 mg BID with stratification to a

prespecified duration of dual antiplatelet therapy of 1, 6, or

12 months.

•

Group 3:

the control arm of dose-adjusted vitamin K antagonism

daily with a similar dual antiplatelet therapy stratification as

above.

The primary endpoint of the post hoc analysis, all-cause mortality or

recurrent hospitalisation due to an adverse event, was significantly

lower in both experimental arms than in the control arm: 34.9% in

Group 1 and 31.9% in Group 2 vs 41.9% in Group 3. Mortality rates

were similar in the three arms.

The salutary effects seen in Group 1 and Group 2 were due to

reductions in hospitalisations for both bleeding and cardiovascular

causes, with no significant effect on other types of hospitalisations. No

significant differences were observed between the two experimental

arms.

Some have speculated that in the patient in whom conventional

full-dose triple therapy is contemplated, such as the patient with

atrial fibrillation who harbours an acute coronary syndrome and/

or is undergoing a percutaneous coronary intervention, that left

atrial appendage closure may provide the best option to address

thromboembolic risk and bleeding simultaneously. Large randomised

trials are necessary to compare these closure devices against novel

oral anticoagulants. These include the novel dosing regimens studied

in PIONEER.

DECEMBER 2016

AHA 2016