Observational Study Supports Continuing Oral Anticoagulation During PCI

For patients sent for an unplanned PCI, a strategy of maintaining oral anticoagulation is not associated with a higher risk of ischemic complications or bleeding when compared with a strategy of interrupting the direct oral anticoagulant (DOAC) or vitamin K antagonist (VKA) a day or two before the procedure, a new observational analysis confirms.

Published in the April 12, 2021, issue of JACC: Cardiovascular Interventions, the study, drawing on the large SWEDEHEART registry, supports the current recommendations from the European Society of Cardiology (ESC) for uninterrupted oral anticoagulation (U-OAC) in patients with atrial fibrillation, venous thromboembolism, or a mechanical heart valve undergoing unplanned, nonemergent PCI, investigators say.

“Undoubtedly, U-OAC is a simpler strategy and was associated with shorter duration of hospital stay, which is in line with previous studies,” writes lead investigator Dimitrios Venetsanos, MD, PhD (Karolinska Institute/Karolinska University Hospital, Stockholm, Sweden), and colleagues. “Thus, it may be assumed that U-OAC is a more cost-effective strategy, which has previously been shown in the setting of other cardiovascular interventions in OAC-treated patients.

The procedural management of patients on OAC undergoing nonemergent PCI is not without controversy, and there is currently disagreement between the European and North American guidelines. In the 2020 ESC guidelines for NSTE ACS, the uninterrupted strategy is preferred for nonemergent PCI in patients with NSTE ACS and for VKA-treated patients needing elective PCI. In contrast, a 2020 consensus statement from the American College of Cardiology (ACC) recommends an interrupted strategy with warfarin (until the INR is ≤ 2.0) or for 24 to 48 hours if a DOAC is used (depending on the agent, renal function, and radial or femoral access). An interrupted approach is also recommended by North American experts who updated recommendations for antithrombotic therapy in AF patients undergoing PCI.

Dharam Kumbhani, MD (UT Southwestern Medical Center, Dallas, TX), the lead author of the ACC consensus statement, agreed that the optimal treatment approach remains “somewhat controversial,” noting that the present study hints that patients on OAC might continue treatment uninterrupted if undergoing unplanned PCI. Despite equivalent MACCE and bleeding rates with the two approaches, Kumbhani is cautious in his interpretation.

“For an observational study, I always feel like a ‘causal’ conclusion gives me some pause no matter how strong the data are,” he told TCTMD. While the study is interesting and useful, “I’m not sure it has the granularity to change practice one way or the other,” he said. Nonetheless, the present study is one of the largest to date and includes patients treated over a long period of time. That period captured a time when warfarin was used exclusively but also includes the introduction of DOACs in 2012 and their growing use in practice.

To TCTMD, interventional cardiologist Sanjit Jolly, MD (McMaster University/Hamilton Health Sciences, Canada), said routine clinical practice at his center is to hold OAC the day before the procedure, although he said there is little data to support that approach. “However, this analysis is reassuring,” he said in an email. “We have data that it is safe to implant pacemakers on OAC and so this is analogous data, but not randomized.”

In an editorial, Piera Capranzano, MD, PhD (University of Catania, Italy), and Dominick Angiolillo, MD, PhD (University of Florida College of Medicine, Jacksonville), agree that the new study supports the European approach but randomized evidence is really needed before this strategy is adopted in routine clinical practice.

For them, both interrupted (I-OAC) and uninterrupted strategies among patients undergoing PCI can be options in clinical practice, although which approach is best depends on multiple factors, such as bleeding and thrombotic risk profiles and indication for the procedure. For example, U-OAC might be considered in those at high thrombotic risk, especially in those treated with VKAs, or in the setting of PCI for NSTE ACS where stopping anticoagulation would significantly delay the procedure or affect length of stay. They note, as did Kumbhani, that this is less of a factor with DOACs, which don’t require as much time for washout/reversal.

No Bleeding Signal With Uninterrupted OAC

For the study, which spanned 2005 to 2017, the researchers identified all patients treated with oral anticoagulation therapy, including warfarin, dabigatran (Pradaxa; Boehringer Ingelheim), rivaroxaban (Xarelto; Bayer/Janssen), or apixaban (Eliquis; Bristol-Myers Squibb)—admitted acutely to the hospital for PCI or coronary catheterization in the SWEDEHEART registry. In total, they included 6,486 patients who went to the catheterization laboratory, including 3,163 who stayed on the oral anticoagulant and 3,322 patients who had oral anticoagulation stopped for at least 24 hours before the procedure. Patients undergoing PCI for STEMI, aortic dissection, complications after CABG surgery, or cardiac arrest were excluded from the analysis.

The number of patients with a prescription for OAC who required PCI or coronary angiography increased threefold over the study period. Also, the uninterrupted approach to antithrombotic therapy increased 13% each year, as did the use of DOACs. In 2017, 53% of patients were treated with one of the newer anticoagulants. At baseline, 80% of patients in the interrupted and uninterrupted treatment arms had an ACS, but U-OAC patients were less likely to undergo PCI and were more likely to be treated via the radial artery and to receive a DES.

In the propensity-matched analysis, which included 2,108 patients in each treatment arm, the MACCE rate (death, MI, or stroke) at 120 days was 8.2% in both the U-OAC and I-OAC groups. Rates of death and stroke before and after adjustment did not differ between the treatment approaches and while the rate of MI was higher with I-OAC in the unadjusted model, it was not significantly different in the fully adjusted analysis.

The rate of net adverse cardiac and cerebrovascular events (NACCE, which includes any bleeding event plus MACCE) was 12.6% in the I-OAC and 12.9% in the U-OAC treatment arms, a nonsignificant difference before and after adjustment. In terms of major bleeding, the rates were 5.6% and 6.0% in the I-OAC and U-OAC groups, respectively, a nonsignificant difference. Similarly, U-OAC was not associated with any more risk of major in-hospital bleeding (non-CABG) or major/minor bleeding (non-CABG) than I-OAC.

Hospital stays were significantly longer with the I-OAC approach (median 5 vs 4 days; P < 0.01).

In their editorial, Capranzano and Angiolillo note several limitations of the observational analysis, including the absence of INR values among those treated with VKAs, lack of information on the timing of the last DOAC dose in the I-OAC group, and limited information about adjunctive parenteral anticoagulation therapy used during PCI. Additionally, while 34.6% of patients were treated with femoral access, the researchers did not report whether there was an interaction between U-OAC versus I-OAC and the access site.

Indication for OAC Important

When drafting the North American consensus statement, Kumbhani said there was a lot of discussion about the periprocedural management of patients undergoing PCI, adding that laboratory protocols varied considerably among proceduralists. Most preferred radial-access interventions in patients with an indication for oral anticoagulation and emphasized the need to be watchful for bleeding complications, particularly if operators performed the procedure via the femoral artery. 

Overall, Kumbhani said a randomized trial testing the I-OAC versus U-OAC strategy in patients undergoing unplanned PCI would be important, but the underlying indication for anticoagulation is an important factor to consider with such a trial.

“Looking at it from the other side, what do you lose by waiting, other than length of stay?” said Kumbhani. “Potentially, you increase the risk of systemic embolism by stopping the anticoagulants but that’s probably only going to be true for very, very few patients with atrial fibrillation. So the underlying indication for oral anticoagulation is going to be very important. Somebody who has had multiple strokes and has known left atrial appendage thrombus—that patient is very different from the vast majority of patients with atrial fibrillation on oral anticoagulation for stroke prophylaxis with a CHA₂DS₂-VASC score of 2 or 3. Even if you were to stop anticoagulation for 2 or 3 days, I don’t think you’re going to dramatically increase the risk of systemic thromboembolic disease.”

On the other hand, for a patient with a mechanical valve, or one with a high thromboembolic risk, the risks of stopping oral anticoagulant therapy are probably too high, he said. In the present analysis, the researchers did not see a higher risk of stroke among those who had their OAC stopped, he noted.

Interestingly, Kumbhani pointed out that roughly 45% of patients in both the I-OAC and U-OAC treatment arms were discharged on triple therapy, that being an OAC plus dual antiplatelet therapy. Given the recent publication of trials comparing double versus triple antithrombotic therapy, that high percentage of patients discharged on triple therapy likely does not reflect current medical practice, he said. “So, even though the data are contemporary, I think there are a lot of aspects that make it non-contemporaneous, particularly given all the AF-PCI trials,” said Kumbhani.