Oral Anticoagulation Alone Best for Stable CAD Patients With AF: Meta-analysis

For patients with stable CAD who require oral anticoagulation (OAC) for atrial fibrillation (AF), there’s no need to add antiplatelet therapy to the mix, according to results of a new meta-analysis.

Taking OAC alone for 6 to 12 months following ACS or PCI was associated with less cardiovascular mortality, major bleeding, and net adverse clinical events (NACE) when compared with combination therapy using OAC and an antiplatelet agent.

The results, published online last week as a brief report in JACC, showed a 31% lower risk of cardiovascular death and a 54% lower risk of major bleeding with OAC alone compared with combination therapy and no differences in MACE for up to 30 months among almost 6,000 patients enrolled in six randomized trials: ADAPT AF-DES, OAC-ALONE, AFIRE, PRAEDO-AF, EPIC-CAD, and AQUATIC.

The findings held true even for patients at high risk for thrombotic events.

In a way, the new data, which represent the largest and most contemporary evidence in the field, give a feeling of “déjà vu,” according to senior author Marco Valgimigli, MD, PhD (Cardiocentro Ticino Institute, Lugano, Switzerland), since previous meta-analyses have shown less bleeding risk with OAC monotherapy compared with combination therapy.

Those studies have not been able to show any difference in ischemic events or mortality, however.

“Many in our cardiovascular community would still prefer to accept a higher bleeding risk if there is uncertainty about the risk of MI and stroke,” he told TCTMD. “The precision of the estimate is so good now that basically [we know] there is only harm in using two [agents] at the same time.” The findings should lead to a change in future guidelines, Valgimigli added.

Meta-analysis Findings

The meta-analysis, which was led by Giuseppe Gargiulo, MD, PhD (University of Naples Federico II, Italy), included 5,924 patients, with 50.1% randomized to OAC alone and 49.9% to OAC plus a single antiplatelet agent. Atrial fibrillation was the most common indication for OAC (98.4%), and 81.6% had a prior PCI.

Over a mean follow-up of 12 to 30 months, the odds of cardiovascular death (HR 0.69; 95% CI 0.51-0.95) and trial-defined major bleeding (HR 0.46; 95% CI 0.32-0.66) were lower among those randomized to OAC monotherapy compared with those who also took an antiplatelet agent.

Similar findings were observed for NACE (HR 0.61; 95% CI 0.47-0.79), major or clinically relevant nonmajor bleeding (HR 0.49; 95% CI 0.39-0.62), and any bleeding (HR 0.54; 95% CI 0.47-0.63).

There were no differences observed for MACE (HR 0.84; 95% CI 0.68-1.04), all-cause death (HR 0.78; 95% CI 0.54-1.13), MI (HR 1.00; 95% CI 0.56-1.76), stroke (HR 0.93; 95% CI 0.64-1.35), or stent thrombosis (HR 1.50; 95% CI 0.40-5.65).

At 1 year, researchers estimated that OAC monotherapy was associated with six fewer cardiovascular deaths, 15 fewer major bleeding events, 65 fewer major or clinically relevant nonmajor bleeding events, seven fewer all-cause deaths, one less stroke, 11 fewer MACE, 24 fewer NACE, and an equal number of MIs per 1,000 patients.

‘Conclusive’ Story

Duk-Woo Park, MD (Asan Medical Center, Seoul, South Korea), one of the study’s co-authors, said the most notable finding was the “clinically relevant” reduction in cardiovascular mortality with OAC monotherapy.

“Bleeding reduction with OAC alone was expected and is consistent with prior studies,” he told TCTMD in an email. “The most striking finding was that this benefit was accompanied by no apparent ischemic penalty, even after inclusion of newer trials enrolling patients at relatively high atherothrombotic risk. . . . That is important because one of the main reasons many clinicians continue single antiplatelet therapy beyond 1 year is concern about late-occurring ischemic events.”

The most striking finding was that this benefit was accompanied by no apparent ischemic penalty. Duk-Woo Park

“This meta-analysis is pretty much making the story conclusive now,” Valgimigli said. “It should be monotherapy as early as possible, and basically patients should be left on oral anticoagulation alone. . . . This should be routine.”

At this point, “at least from 6 months onwards, it’s no longer justified,” he continued, adding that the ongoing MATRIX-2 trial will hopefully give more answers as to whether that time point can be moved even earlier.

Park agreed that several questions remain, including around very high-risk patients with “recurrent coronary events, complex multivessel PCI, or prior stent thrombosis,” he said. Additionally, whether the type of antiplatelet agent used makes a difference is unclear. “As practice increasingly shifts toward [direct oral anticoagulant]-based regimens, it would be valuable to understand whether there are important differences across specific agents (eg, specific NOAC) or doses.”

Park stressed that these findings are only applicable to patients with stable CAD, and not in the early post-PCI or post-ACS periods “where antithrombotic decisions are different and more nuanced.” Rather, he said, “the message here is not that antiplatelet therapy is unnecessary altogether, but rather that once patients are beyond the higher-risk acute phase and remain on long-term OAC, simplification to OAC alone appears both safer and, based on these data, potentially more effective overall.”

Lastly, Park concluded, “I also think the reduction in net adverse clinical events is especially clinically meaningful because it captures what matters most in everyday practice: minimizing bleeding without giving up ischemic protection.”