Blood Thinners Post-PCI Show Possible Mortality Reduction, Increased Bleeding Risk

Patients with a history of stable angina or another acute coronary syndrome who have undergone percutaneous coronary intervention (PCI) may have a reduced risk of all-cause in-hospital mortality but an increased risk of bleeding when given heparin combined with glycoprotein 2b/3a inhibitors (GPI), potent antiplatelet agents, after the procedure, according to a recent study published in JACC: Cardiovascular Interventions.

Using data from ACC’s CathPCI Registry®, researchers assessed records from 970,865 patients between July 2009, and September 2011. Almost one third of cases were treated with GPI. After adjusting for many factors, relative risk reductions in mortality ranged from 10% to 28%. The risk reduction in mortality was enhanced in patients with myocardial infarction (MI). However, after risk adjustments, GPI use was found to be associated with an increased risk of major bleeding.

“These findings suggest that, in the modern era of PCI, there may still be a role for the judicious use of GPI in high-risk patients, particularly if heparin is used for anticoagulation, as it was in over one half of patients included in this study,” said David M. Safley, MD, FACC, the study’s lead author. Safley noted the findings “also serve to highlight the relatively low usage of bivalirudin.”

In an accompanying editorial, A. Michael Lincoff, MD, FACC, noted the limitations due to the observational nature of the analysis. “Without randomization, any observed associations between the treatment variable (GPI) and outcome cannot be proven to be causative,” Lincoff wrote.

While acknowledging the robustness of the statistical methods used, Lincoff added, “There is no advantage of GPI over bivalirudin, and the latter strategy reduces bleeding.”

Safley DM, Venkitachalam L, Kennedy KF, et al. J Am Coll Cardiol Intv. 2015;8(12):1574-82.

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Gone but Not Forgotten: Very Late Scaffold Thrombosis with Bioresorbable Scaffolds

Very late scaffold thrombosis may occur at advanced stages of scaffold resorption, according to a study recently published in JACC.

Between March 2014, and February 2015, 171 patients underwent revascularization using the bioreosorbable vascular scaffold (BVS) and 4 patients experienced very late (>1 year) scaffold thrombosis at 44 (case 1), 19 (cases 2 and 4) and 21 (case 3) months after implantation. All patients underwent quantitative coronary angioplasty analysis and optical coherence tomography (OCT), while cases 1 through 3 also underwent histopathological assessment of the thrombus aspirate and case 1 underwent spectroscopic assessment.

The OCT showed malapposed scaffold struts surrounded by thrombus in 7.1% of struts in case 1, 9.0% in case 2, and 8.9% in case 4. In cases 2 and 4, scaffold discontinuity was struts in the lumen center and was the cause of malapposition. In case 3, the researchers found uncovered scaffold struts with superimposed thrombus. OCT percent area stenosis during very late scaffold thrombosis was high in case 1 (74.8%) and case 2 (70.9%), and there was no evidence of excessive neointimal hyperplasia. In case 1, the spectroscopic thrombus aspirate analysis showed persistence of intracoronary polymer fragments.

The authors summarized the principle findings that (1) very late scaffold thrombosis may occur despite antiplatelet therapy after implantation when scaffold resorption would be expected to be at advanced stages or near completion; (2) polymer resorption may not be complete as late at 4 years after implantation; (3) the presence of malapposed and uncovered scaffold struts in direct contact with thrombus suggests a potential triggering role, which was seen in all cases; and (4) scaffold discontinuity (seen in cases 2 and 4) and restenosis (seen in cases 1 and 2) related to the resorption process may be potential triggers for very late scaffold thrombosis.

The authors also noted an observed high frequency of malapposed struts surrounded by thrombus in 3 of the 4 cases, writing that “OCT failed to show evidence of coronary evaginations, a finding correlated with positive remodeling.” In two cases, the researchers observed a high frequency of uncovered scaffold struts in addition to the main finding of late strut discontinuity. “Only uncovered struts not immobilized by neointima can protrude into the lumen when structural integrity is lost and subsequently cause late scaffold strut discontinuity, a finding suggesting that neointimal coverage may be particularly important after implantation of BVSs,” the authors wrote.

They also added that, “although the number of cases is too small to allow for meaningful quantification of cellular thrombus components, it is notable that none of the aspirates showed eosinophilic cells.”

In an accompanying editorial comment, Gregg W. Stone, MD, FACC, and Juan F. Granada, MD, FACC, wrote that, while this study was small, it “provides useful insight into the possible causes of very late device failures among patients receiving first-generation BVS technology,” and that, while physicians should not yet be worried about very late scaffold thrombosis after BVS, they should be aware.

Räber L, Brugaletta S, Yamaji K, et al. J Am Coll Cardiol. 2015;66(17):1901-14.

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Nonobstructive Coronary Artery Disease in Women

Ischemic heart disease (IHD) in women often goes unnoticed. However, new findings are leading to the recognition of nonobstructive coronary artery disease (CAD) as a cause of IHD among women. In a state-of-the-art review published in JACC, members of the ACC’s Cardiovascular Disease in Women Committee examined the current information and knowledge gaps and gave their recommendations for management of this condition.

The authors wrote that nonobstructive CAD is very common in women, including those with the typical symptoms of IHD. It was long thought that, although conditions other than obstructive CAD may cause ischemia and related conditions, these occurrences were infrequent and lacked clinical implications beyond the condition. Recent findings, however, have caused a change in this opinion. There is currently no guideline-recommended therapy available for patients with symptoms of IHD and nonobstructive CAD. Care for these patients was not included in the recent IHD guideline that focused on obstructive CAD. The authors wrote that their recommendations can inform the clinical community as well as future guidelines.

The authors added that these issues raise questions about the presence of coronary atherosclerosis, myocardial ischemia and coronary microvascular dysfunction (CMD). Looking at previous evidence, they stated that atherosclerosis is present in most cases, but there may be a referral bias in play. There have been data showing that in women with nonobstructive CAD, as the extent and severity of inducible ischemia increases, so do IHD-related event rates. Finally, studies have linked CMD to atherosclerosis risk factors with adverse outcomes, providing support for its link with several risk factors. There are also findings that women have greater arteriolar wall thickness and diffusion radius relative to body surface area and cardiomyocyte width, which may cause them to be predisposed to ischemia. The authors also added that studies with larger numbers of women with CAD are required to confirm findings and clarify mechanisms of underlying CMD.

Syndromes associated with nonobstructive CAD and adverse outcomes include chronic stable angina, acute coronary syndromes (ACS) and sudden cardiac death. Predictors of adverse outcomes in patients with nonobstructive CAD are similar to those with obstructive CAD, with a few exceptions. The association of left ventricular systolic function seen in those with obstructive CAD is not present. Hypertension has been found to be present in patients with both obstructive and nonobstructive CAD. Effective control of hypertension in women is proven to reduce the risk of cardiovascular disease (CVD), but whether the benefit is the same for women with nonobstructive versus obstructive CAD is not clear. Type 2 diabetes and prediabetes are prevalent among women and nonobstructive CAD is more common in patients with diabetes. There is a worsening of CMD seen with increasing insulin resistance. CMD is an independent predictor of mortality in patients with diabetes. Patients with diabetes and impaired coronary flow reserve have similar CVD mortality compared to patients with obstructive CAD but without diabetes.

Regarding knowledge gaps in the treatment of women with IHD and nonobstructive CAD, the authors pointed out that, while there has been a push for cardiovascular research focusing on women, none have specifically addressed this issue. They added that information on three points is essential—identifying specific mechanisms, defining optimal diagnostic approaches, and discovering novel treatment strategies and their follow-up. Finally, clinical trials are needed to provide for the development of evidence-based guidelines.

“Even without definitive information about mechanisms, it may be possible to use the limited information currently available to test new strategies to improve outcomes,” the authors wrote. “To accelerate development of new diagnostic and therapeutic regimens, an integrated approach to phase II and III clinical trials that incorporates multiple efficacy variables, including angiography, biomarkers of microvascular dysfunction, and other factors should be considered.”

The authors wrote that information should foster: (1) development of more precise tools to better risk stratify patients with nonobstructive CAD; (2) prospective trials to assess benefits of intensive medical therapy directed at ischemia and atherosclerosis progression in these patients; and (3) discovery of novel management strategies for these patients, most of whom are women. “In the future, if we aim at preventing these events, the paradigm of risk stratification for prevention must move from identification of obstructive atherosclerosis to an earlier stage that includes nonobstructive [CAD]”

Pepine CJ, Ferdinand KC, Shaw LJ, et al. J Am Coll Cardiol. 2015;66(17):1918-33.

Keywords: Acute Coronary Syndrome, Angina, Stable, Angioplasty, Balloon, Coronary, Coronary Artery Disease, Coronary Disease, Heparin, Hospital Mortality, Percutaneous Coronary Intervention, Platelet Aggregation Inhibitors, Thrombosis, Tomography, Optical Coherence, CardioSource WorldNews Interventions

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