Patching Up the Differences: Vascular Closure with Topical Hemostasis versus Manual Compression

The very nice study by Narins et al described in this edition of the Journal of Invasive Cardiology compares 75 patients randomized to vascular closure using a topical patch containing a polysaccharide-based procoagulant with 75 patients randomized to manual compression.1 Although the study found that those randomized to the patch had lower time to hemostasis and ambulation, several potentially confounding factors need to be kept in consideration. First, the vascular closure literature is replete with studies that depend on two of the softer endpoints in interventional cardiology: time to hemostasis and time to ambulation.2 Although the authors have taken care to predefine their management parameters carefully, the decision algorithm for these endpoints has typically involved a substantial element of subjectivity. Second, lack of blinding on these soft endpoints has great potential to bias the results, despite the investigators’ best intentions. Third, female gender3 and diabetes4 are two of the strongest determinants of adverse events in vascular closure; for example, the former has been associated with an odds ratio of 7.8:1 for retroperitoneal hemorrhage.5 These demographic features are also associated with small femoral arteries6 and have been reported in both the early7 and more recent8 literature as the strongest or among the strongest correlates of vascular complications (with intra-aortic balloon pumps, devices that have provided particular challenges for femoral access management, and which shed insight into femoral vascular closure problems in general). The substantially higher proportion of women in the current study (greater than twice that of the control group) and a nonsignificantly higher proportion of diabetics would add to a concern regarding the influence of patient selection on outcomes, but is largely addressed by appropriately performed multivariate analysis. Skepticism regarding topical hemostasis centers on some core unanswered questions: How does the active ingredient penetrate to the arterial surface from the skin, and is penetration to the arteriotomy site required for its hemostatic benefits? These questions remain paramount in the minds of most interventionists and cardiac catheterization laboratory staff, unrelated to the potential effectiveness of the myriad agents used in the various topical preparations. The concerns are exacerbated by the requirement for manual compression during topical patch deployment, preventing communication between the skin surface and the arteriotomy during the necessary compression of the tissue track and by inference preventing any active agent from penetrating to the site of bleeding. A secondary question raised is the accelerated coagulation of blood in the tissue track at the skin surface, potentially leading to clot retraction away from the arteriotomy surface. Lack of convincing in vivo data confounds the acceptance of patches by a significant portion of the invasive cardiology community, although some elegant work has been done to assess the effectiveness of these agents in vitro.9 Finally, patches do not actively approximate the arteriotomy itself, unlike vascular closure devices (VCDs) that sandwich, stitch or clip the arteriotomy closed. Despite these reservations, patch users, including this author on occasion, have anecdotally observed what appears to be facilitated hemostasis in a variety of settings, including after failed closure with a number of invasive VCDs (although failed closure, to the best of my knowledge, is not an approved patch indication per se). Patches do have several highly appealing features. First, they leave no foreign body behind, thereby minimizing the risk of infection, a serious drawback of all but one of the invasive VCDs.4 Second, they are truly noninvasive because they are not introduced into the tissue track; the introduction of additional hardware into the tissue track by all of the invasive VCDs adds an additional cause of post-procedure groin infections, an event associated with major morbidity and a mortality in the 6% range.4 Third, they function by accelerating hemostasis. A variety of closure devices actively approximate the vessel edges but have no thrombosing agent. Others passively approximate the vessel edges with a sealing agent; the relative efficacy of thrombosing agents versus sealing agents has not been systematically studied. (Some of the more recent invasive VCDs have partially addressed one disadvantage they have compared to manual compression or patches and are deployed through the sheath used for the catheterization procedure, a modest but potentially important improvement that prevents introduction of a new foreign body directly through the skin into the tissue track, and eliminates the tissue track upsizing that is involved with the most commonly used VCDs). A final but important advantage of the topical patches, if they can be shown to be effective, would be their substantially lower cost than the invasive VCDs. The ultimate answer will lie in randomized and blinded trials, which the current study is not. I am aware of only one such study in the literature,10 and although blinded, it was quite small and with limited endpoints so that it serves more for hypothesis generation than any conclusive demonstration of the efficacy of patches. Although some patches have characteristics that make blinding difficult, others do not. Unlike the invasive closure devices, patches lend themselves well to a double-blind, placebo-controlled trial, and this will be the only way to convince skeptics that this technology is in fact effective. The vascular closure literature remains weak in general, with most studies of the invasive VCDs also lacking compelling data to argue for routine use.11 Meta-analyses have generally suggested vascular complications favoring manual compression rather than VCDs.12 Two recent elegant propensity analyses have shown trends that were either neutral13 or favored VCDs.14 However, these were single-site studies at hospitals with meticulous access and closure techniques and extensive experience with vascular closure. A propensity analysis by one of these groups involved a topical patch and also demonstrated favorable results15 with shortened time to hemostasis and ambulation, although it should be noted that the rates of any vascular complication were decreased in the patch group for diagnostic but not interventional procedures; the latter again raises the issue of whether passive closure devices have inherent limitations in the interventional anticoagulation/antiplatelet milieu. Convincing the skeptics that these devices are in fact effective will require blinded studies. Although the study in this issue of the Journal was elegantly performed, a randomized, blinded, intention-to-treat analysis is needed. The possibility of an “emperor’s clothes” syndrome remains for VCDs in general, and topical patches in particular, and this concern will continue to dominate end-users’ opinions regarding the myriad of available patches until such a study is conducted.

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