POPular TAVI - Antithrombotic Therapy After Transcatheter Aortic Valve Implantation in Patients With a Long-Term Indication for Oral Anticoagulation

ACC 2020 Scientific Sessions Virtual Event - read this report by Mirvat Alasnag

The POPular TAVI trial is an open label randomized study designed to evaluate oral anticoagulation (OAC) alone compared with OAC plus clopidogrel for 3 months in patients undergoing transcatheter aortic valve replacement (TAVR) with a long-term indication for oral anticoagulation. Those who had undergone percutaneous revascularization with a drug eluting stent in the past 3 months or bare metal stent in the last month, allergy or contraindication to OAC were excluded.

A significantly lower bleeding rate in the OAC alone arm

A total of 326 patients were enrolled OAC alone 164 and OAC plus clopidogrel 162. The mean age was 81 years with 44% females. The mean left ventricular EF was 50%. Coronary artery disease was found in 65% of the cohort and only 12% had a previous myocardial infarction. The follow-up was for 3 months. Atrial fibrillation was the most common indication for OAC accounting for 96% of those enrolled. OAC was primarily with a vitamin K antagonist (VKA), 75% and direct oral anticoagulant 24%. Transfemoral TAVR was performed in 87%. Various types of valves were used; Edwards Sapien 3 41%, Medtronic Evolut R 29% and other valves 30%. Embolic protection was employed in 2.5% only.

The co-primary outcomes at 12 months demonstrated a significantly lower bleeding rate in the OAC alone arm.

Outcome

OAC Alone

OAC + Clopidogrel

All bleeding (Valve Academic Research Consortium-2 (VARC2))

(p < 0.01)

21.7%

34.6%

Nonprocedural bleeding (Bleeding Academic Research Consortium (BARC) )

(p = 0.02)

21.7%

34%

OAC alone did not increase ischemic events

It is notable that for those treated with a VKA, the relative risk (95% confidence interval) for all bleeding with OAC alone versus OAC plus clopidogrel was 0.75 (0.5-1.14) and for those treated with a direct oral anticoagulant, the relative risk (95% confidence interval) was 0.28 (0.1-0.75).

The secondary endpoints at 12 months indicate that OAC alone did not increase ischemic events meeting the trial’s pre-specified non-inferiority threshold.

Outcome

OAC Alone

OAC + Clopidogrel

Cardiovascular death, nonprocedural bleeding, myocardial infarction, or stroke

(criteria for non-inferiority met, p for superiority < 0.05)

31.2%

45.5%

Cardiovascular death, myocardial infarction, or stroke

(criteria for non-inferiority met, p for superiority = not significant)

13.4%

17.3%

Only 24% of this cohort were treated with a direct oral anticoagulant; therefore, no conclusive comparisons can be made with VKA. Larger randomized datasets from the ATLANTIS study, which is evaluating direct anticoagulants and powered for ischemic endpoints, remain anticipated.

OAC alone associated with a reduction in bleeding in patients who undergo TAVR and have an indication for LT anticoagulation

This trial clearly indicates that in patients who undergo TAVR and have an indication for long-term anticoagulation, OAC alone is associated with a reduction in all bleeding and procedural bleeding compared with OAC plus clopidogrel with no penalty in terms of major adverse ischemic endpoints. In fact, it appears safer not to administer clopidogrel after TAVR in such a cohort. An important limitation of this study was the use of the BARC definition for procedural bleeding which does not capture access site bleeding. Another limitation is that it is an open-label design and only applicable to atrial fibrillation. No inferences can be made with respect to those requiring OAC for other indications, such as prosthetic valves or left ventricular thrombus. Additionally, it doesn’t address those with prior coronary artery disease and in need of anti-platelet therapy. The trial is only powered for the primary endpoints and not the hazards at 12 months for other endpoints. However, it is worth noting that in the OAC plus clopidogrel arm there was a numerical increase in ischemic events which is difficult to explain but indicates an overall higher risk population. Finally, the role of aspirin and how it modifies ischemic or bleeding events was not addressed in this trial.

A remaining question is: what is the optimal type and duration of OAC/anti-platelet agents in patients without an indication for long-term OAC?