Switching of oral anticoagulation therapy after PCI in patients with atrial fibrillation: The RE-DUAL PCI trial subanalysis
Selected in JACC: Cardiovascular Interventions by M. Alasnag
The objective of this substudy was to examine the safety of switching patients with atrial fibrillation (AF) who were previously on warfarin or a direct oral anticoagulant (DOAC) to dabigatran dual therapy.
References
Authors
Ten Berg JM, de Veer A, Oldgren J, Steg PG, Zateyshchikov DA, Jansky P, Seung KB, Hohnloser SH, Lip GYH, Nordaby M, Kleine E, Bhatt DL, Cannon CP; RE-DUAL PCI Steering Committee and Investigators.
Reference
JACC Cardiovasc Interv. 2019 Dec 9
Published
December 2019
Link
Read the abstractReviewer
My Comment
Why this study – the rationale/objective?
Previously published data have demonstrated a higher risk of both thromboembolic and bleeding events at the time of switching oral anticoagulation (OAC) regimens. The RE-DUAL PCI study unequivocally concluded that dabigatran dual therapy was safer than warfarin triple therapy after percutaneous coronary revascularization (PCI). The objective of this substudy was to examine the safety of switching patients with atrial fibrillation (AF) who were previously on warfarin or a direct oral anticoagulant (DOAC) to dabigatran dual therapy. In particular, the investigators evaluated two points:
- Whether dabigatran dual-therapy still maintained a lower bleeding risk in those with prior use of OAC requiring a switch in their regimen.
- Whether outcomes differed with respect to previous warfarin versus DOAC use.
How was it executed – the methodology?
A total of 2,725 patients with AF and underwent PCI were randomized to dual therapy with dabigatran (110 or 150 mg twice daily) plus clopidogrel or ticagrelor or triple therapy with warfarin plus aspirin and clopidogrel or ticagrelor (adjusted to achieve an international normalized ratio [INR] of 2.0 to 3.0). Patients were switched to either dabigatran dual therapy or warfarin triple therapy from a vitamin K . antagonist (VKA ) or DOAC (other than dabigatran), be maintained on a VKA or dabigatran, or be started newly on anticoagulation. During the randomization, the switch followed current standard switch protocols. Men and women over the age of 18 years with AF who underwent PCI with bare-metal stents or drug eluting stents both in the setting of an acute coronary syndrome or stable coronary artery disease were included. Prosthetic valves, severe renal insufficiency, and other major coexisting conditions, eg gastrointestinal bleeding or stroke were excluded.
Interestingly, outside the United States, patients >80 years of age (>70 years in Japan) were only randomized to dabigatran 110 mg dual therapy or warfarin triple therapy.
The primary endpoint was the first major bleeding event (MBE) or clinically relevant nonmajor bleeding event (CRNMBE). The main secondary outcome was a composite efficacy outcome of thromboembolic events (myocardial infarction, stroke, or systemic embolism), death, or unplanned PCI or coronary artery bypass grafting. A composite of thromboembolic events or death, individual thromboembolic events and definite stent thrombosis. were other secondary endpoints. Median follow-up was 13 months.
What is the main result?
At baseline, 34.1% of patients were previously taking OAC. Of these, 61.2% were on warfarin and 38.8% were on a DOAC. Alt modified HAS-BLED scores were similar in the 2 groups.
A comparison of the primary and secondary outcomes between the dabigatran dual therapy and warfaring triple therapy was performed with respect to those who were prior OAC users versus who were not. In the dabigatran dual therapy group (both doses), the primary outcome of MBEs or CRNMBEs was consistently lower than those on warfarin triple therapy in both prior OAC users and OAC-naive patients. The primary event rate in prior OAC users was 17% for dabigatran 110 mg dual therapy and 27.2% for warfarin triple therapy. The primary event rate was 15.4% for dabigatran 150 mg dual therapy and 23.4% for warfarin triple therapy. In OAC naive patients, the primary event rate was 14.5% vs 26.8% and 22.5% vs26.7% respectively. The secondary endpoints including a composite of death, thromboembolic events and unplanned PCI were similar for both doses and both categories of OAC users vs OAC naive.
Critical reading and relevance for clinical practice
The decision to switch anticoagulation regimens is always difficult for clinicians. Results of the RE-DUAL PC I trial are reassuring and are consistent with those unveiled in both the ROCKET and ARISTOTLE subanalyses. However, at the conclusion of these pivotal trials, there was a four-fold increase in thromboembolic events during the open label switch. This warrants strict monitoring of INR during the transition in real world practice.
Important limitations of this trial is that it was not powered for the secondary endpoints. Additionally, the majority of those enrolled were not previously on OAC. The trial included patients with both acute coronary syndromes and stable disease allowing a wide application of the results. By enrolling those receiving both bare metal (although rarely used in contemporary practice) and drug eluting stents, the investigators tried to also capture a wider range of PCIs. In 2019, PCI is not only about the stent type, rather, there is emphasis on the complexity of the procedure eg atherectomy use, left main interventions and bifurcations and the size, length and number of stents used. The trialists did not furnish us with a detailed description of the PCIs. Reducing anti-platelet therapy to a single agent is often difficult with complex interventions especially in the setting of an ACS. A global dilemma is addressing dual and triple therapy in elderly patients; as noted in the methods, a higher dose of dabigatran (150 mg) in those over 8o years was not studied (nor was advanced renal insufficiency). These subgroups should be a focus of future studies as they constitute a large number of patients encountered in clinical practice. Finally, these trials primarily targeted patients requiring OAC for non-valvular atrial fibrillation. Whether these results can be extended to other indications such as left ventricular thrombus or deep venous thrombosis remains unknown.
In spite of the limitations, the totality of evidence does suggest that DOAC dual therapy is safer than warfarin triple therapy, regardless of whether patients were previously anticoagulated or not.
No comments yet!