Systematic review of efficacy of direct oral anticoagulants and vitamin K antagonists in left ventricular thrombus

Abstract

Aims Left ventricular thrombus (LVT) increases the risk of thrombotic events and mortality. Vitamin K antagonists (VKAs) used to treat LVT have several known risks, as a result of which direct oral anticoagulant (DOAC) use has recently increased. We aimed to evaluate the safety and efficacy of DOACs and VKAs in treating LVT. Methods and results We searched PubMed, Embase, Cochrane Library trials, and Web of Science databases for studies published before 19 April 2022, involving DOAC versus VKA treatment for patients with LVT. This meta‐analysis comprised 21 studies (total patients, n = 3172; DOAC group, n = 888; VKA group, n = 2284). A statistically significant reduction in bleeding events was observed in patients on DOACs vs. those on VKAs (risk ratio (RR) = 0.73, P = 0.004). Patients on DOACs residing in North American and European regions and those with ischaemic heart disease (IHD) had a significantly lower risk of bleeding events than patients residing in other regions or those with a different LVT aetiology, respectively (RR = 0.78, P = 0.04; RR = 0.38, P = 0.02; and RR = 0.63, P = 0.009). A statistically significant reduction in stroke in patients on DOACs versus VKAs (RR = 0.72, P = 0.03) was observed, and patients on DOACs residing in North America and those with IHD had a significantly lower risk of stroke (RR = 0.73, P = 0.04, and RR = 0.61, P = 0.03, respectively). Compared with VKAs, DOACs are statistically associated with an increase in LVT resolution at 1 month (RR = 1.96, P = 0.008). No statistical between‐group difference in all‐cause mortality (RR = 0.72, P = 0.05), systemic embolism (RR = 0.87, P = 0.74), stroke or systemic embolism (RR = 0.90, P = 0.50), and LVT resolution at the end of follow‐up (RR = 1.06, P = 0.13) was observed. Conclusions Compared with VKAs, DOACs significantly reduce the risk of bleeding events and stroke in LVT patients, but mortality was similar in both groups. The advantages are apparent not only in patients belonging to the predominantly white residential areas such as North American and European regions but also in patients with LVT due to IHD. DOACs show promising effects in treating LVT compared with VKAs.

An exploratory study of effectiveness and safety of rivaroxaban in patients with left ventricular thrombus (R-DISSOLVE)

“…Likewise, as evidenced by the HRs of anti-Xa (C-peak) level and platelet count being close to 1.00, there was no association between the two factors and thrombus resolution. In addition, we spilt variables of interest into subgroups based on the LV thrombus resolution of 65.8% in patients with NOACs [ 8 ]. Details were shown in the Supplementary material, Fig.…”

“…As non-vitamin K antagonist oral anticoagulants (NOACs) come with potentially practical advantages over warfarin, NOACs are increasingly used as off-label anticoagulant therapy in patients with intracardiac thrombi without the necessity for frequent laboratory monitoring. Compared with vitamin K antagonists (VKAs), NOACs were non-inferior in the efficacy and safety for the treatment of LV thrombus in two small randomized clinical trials (RCTs) [6,7] and several meta-analyses [8][9][10][11]. In decades of research, earlier guidelines on anticoagulation for LV thrombus primarily recommended the use of VKAs therapy for 3 months [5,12], while the latest American Heart Association scientific statement (2022) recommended that NOACs could be a reasonable alternative to warfarin in patients with LV thrombus, based on supportive though insufficiently powered randomized data [13].…”

Another meta-analysis on novel oral anticoagulants for left ventricular thrombus: when enough is enough?

“…1 Although many systematic reviews have already appraised in detail the risk-benefit balance of NOAC in various clinical setting, left ventricular thrombus represents a relatively orphan topic, wherein vitamin-K antagonists (VKA) are still considered the default treatment strategy. 2,3 Indeed, NOAC appear promising in several settings, but their role, whenever anatomic conditions represent a key pathophysiologic underpinning of thrombosis, is less established, as highlighted by the recent disappointing results of the INVICTUS trial comparing rivaroxaban versus VKA in patients with atrial fibrillation and rheumatic heart disease. 4 Although endothelial damage and inflammation-related hypercoagulability due to subendocardial or transmural necrosis together with local or global systolic dysfunction represent the common premises of LVT, the precise pathophysiology of this condition remains poorly defined.…”

“…Furthermore, currently available evidence suggests there might be a difference not only among safety and efficacy outcomes accomplishments of specific NOAC, for example with apixaban better at preventing major bleeding, [12][13][14][15] but also in NOAC effectiveness depending on the followup duration. 3,14 In this regard, interesting differences in NOAC and VKA clinical outcomes, for example thrombus resolution and death, appear to emerge in a strict follow-up time-dependent fashion only, as displayed in the study by Huang et al, 3 and in the study by Camaj et al 5 Outcome exploratory analysis based on individual anticoagulants or varying follow-up, carried out by Serenelli et al, 6 impacts, albeit mildly, on effects, and these findings might warrant further research on these potentially relevant features.…”

“…Nonvitamin K oral anticoagulants (NOAC) were firstly introduced in 2008, and interest in their possible role in treating multiple thrombotic illnesses has been growing ever since 1 . Although many systematic reviews have already appraised in detail the risk--benefit balance of NOAC in various clinical setting, left ventricular thrombus represents a relatively orphan topic, wherein vitamin-K antagonists (VKA) are still considered the default treatment strategy 2,3 . Indeed, NOAC appear promising in several settings, but their role, whenever anatomic conditions represent a key pathophysiologic underpinning of thrombosis, is less established, as highlighted by the recent disappointing results of the INVICTUS trial comparing rivaroxaban versus VKA in patients with atrial fibrillation and rheumatic heart disease 4 …”