Prevention of Bleeding in Patients with Atrial Fibrillation Undergoing PCI with Stenting

PIONEER AF AF
Atrial fibrillation (= AF). A heart rhythm disorder where chambers in the upper heart (atria) beat more rapidly than those in the lower section of the heart. Blood is not pumped out of the upper chambers completely during beating, and may pool and form a clot. A stroke results if a section of clot dislodges from the upper chambers and becomes lodged in the brain.
-PCI: An Open-Label, Randomised, Controlled, Multicentre Study Exploring Two Treatment Strategies of Rivaroxaban and a Dose-Adjusted Oral VKA VKA
Vitamin K antagonist (= VKA). An anticoagulant that inhibits multiple steps in the blood clotting process. Administered orally, the dose varies by patient, and regular monitoring and dose adjustment are required. Vitamin K antagonists have interactions with food and other drugs. Due to the many limitations of this drug, many of those who are treated are outside of the required target INR range, which can be the cause for increased bleeding or a greater risk of stroke.
Treatment Strategy in Subjects with AF who Undergo PCI

Objective

  • To compare the safety of the following three treatment strategies after PCI with stent placement in patients with paroxysmal, persistent, or permanent non-valvular atrial fibrillation1

Study Design1, 2

PIONEER study design

aDose of rivaroxaban is reduced to 10 mg OD in subjects with CrCl 30⎼50 ml/min. bFirst dose 72 to 96 hours after sheath removal. cClopidogrel daily maintenance dose is 75 mg OD; alternate P2Y12 inhibitors: prasugrel 10 mg OD or ticagrelor 90 mg BID allowed (≤15% of participants). dNVAF NVAF
Non-valvular atrial fibrillation (= NVAF). The term NVAF is restricted to cases in which atrial fibrillation occurs in the absence of rheumatic mitral stenosis or a prosthetic heart valve.
is defined as AF not considered to be caused by a primary valve stenosis. eSubjects with history of previous stroke or TIA TIA
Transient ischaemic attack (= TIA). Also known as a ‘mini stroke’. This is caused by a temporary disruption in the blood supply to part of the brain.
were excluded. fFirst dose 12 to 96 hours after sheath removal. gDAPT consisted of low-dose ASA (75 to 100 mg OD) and P2Y12 inhibitor. hASA 75 to 100 mg OD. iAt the investigators discretion, an INR INR
International normalised ratio (= INR). A system for assessing the clotting tendency of blood in patients receiving anticoagulant therapy. For patients with atrial fibrillation, the recommended target INR range is between 2 and 3. If the INR is higher than 3, patients are at risk of serious bleeding. If the INR is less than 2, patients are at risk of a blood clotting event.
target of 2.0 to 2.5 may be used as some guidelines recommend.

Clinical End Points1

  • Primary end point:
    • The occurrence of clinically significant bleeding (a composite of major bleeding or minor bleeding according to TIMI TIMI
      Thrombolysis in Myocardial Infarction (= TIMI) bleeding criteria. This is a score used to determine the likelihood of ischaemic events or mortality in patients with unstable angina or non-ST segment elevation myocardial infarction (NSTEMI). There is also a separate TIMI risk score for patients with ST segment elevation myocardial infarction (STEMI).
      criteria or bleeding requiring medical attention)
  • Secondary end points:
    • Incidence of each component of the primary safety end point
    • Occurrence of a major adverse cardiovascular event (a composite of death from cardiovascular causes, MI MI
      Myocardial infarction (= MI). This is commonly known as a heart attack. This is usually caused by a blood clot that stops the blood flowing to part of the heart muscle. As a result, the heart muscle becomes damaged.
      or stroke)
    • Each component of the major adverse cardiovascular event end point
    • Rates of stent thrombosis thrombosis
      Formation of a clot inside a blood vessel.

Key Findings

  • Administration of either low-dose rivaroxaban (15 mg OD) plus a P2Y12 inhibitor for 12 months or very-low-dose rivaroxaban (2.5 mg BID) plus DAPT for 1, 6 or 12 months was associated with a lower rate of clinically significant bleeding vs standard therapy with a VKA plus DAPT for 1, 6 or 12 months1
  • The rates for each component of the cardiovascular efficacy end point did not differ significantly among the three treatment groups1

AF AF
Atrial fibrillation (= AF). A heart rhythm disorder where chambers in the upper heart (atria) beat more rapidly than those in the lower section of the heart. Blood is not pumped out of the upper chambers completely during beating, and may pool and form a clot. A stroke results if a section of clot dislodges from the upper chambers and becomes lodged in the brain.
, atrial fibrillation; PCI, percutaneous coronary intervention; VKA VKA
Vitamin K antagonist (= VKA). An anticoagulant that inhibits multiple steps in the blood clotting process. Administered orally, the dose varies by patient, and regular monitoring and dose adjustment are required. Vitamin K antagonists have interactions with food and other drugs. Due to the many limitations of this drug, many of those who are treated are outside of the required target INR range, which can be the cause for increased bleeding or a greater risk of stroke.
, vitamin K antagonist; NVAF NVAF
Non-valvular atrial fibrillation (= NVAF). The term NVAF is restricted to cases in which atrial fibrillation occurs in the absence of rheumatic mitral stenosis or a prosthetic heart valve.
, non-valvular atrial fibrillation; OD, once daily; BID, twice daily; DAPT, dual antiplatelet therapy; ASA, acetylsalicylic acid; INR INR
International normalised ratio (= INR). A system for assessing the clotting tendency of blood in patients receiving anticoagulant therapy. For patients with atrial fibrillation, the recommended target INR range is between 2 and 3. If the INR is higher than 3, patients are at risk of serious bleeding. If the INR is less than 2, patients are at risk of a blood clotting event.
, international normalised ratio; TIMI TIMI
Thrombolysis in Myocardial Infarction (= TIMI) bleeding criteria. This is a score used to determine the likelihood of ischaemic events or mortality in patients with unstable angina or non-ST segment elevation myocardial infarction (NSTEMI). There is also a separate TIMI risk score for patients with ST segment elevation myocardial infarction (STEMI).
, thrombolysis in myocardial infarction; MI MI
Myocardial infarction (= MI). This is commonly known as a heart attack. This is usually caused by a blood clot that stops the blood flowing to part of the heart muscle. As a result, the heart muscle becomes damaged.
, myocardial infarction; CrCl, creatinine clearance; TIA TIA
Transient ischaemic attack (= TIA). Also known as a ‘mini stroke’. This is caused by a temporary disruption in the blood supply to part of the brain.
, transient ischaemic attack.