Thrombotic events and rebleeding after hemorrhage in patients taking direct oral anticoagulants for non-valvular atrial fibrillation.

Several direct oral anticoagulants have been developed to prevent cardiogenic thrombosis in patients with atrial fibrillation, on the other hand, have the complication of bleeding. Since clinical course after bleeding with direct oral anticoagulant remains unclear, the present retrospective cohort study was to clarify the course after hemorrhage among patients receiving direct oral anticoagulants. Among all 2005 patients prescribed dabigatran, rivaroxaban, apixaban, or edoxaban between April 2011 and June 2017, subjects comprised 96 patients with non-valvular atrial fibrillation who experienced relevant bleeding during direct oral anticoagulant therapy (Bleeding Academic Research Consortium type 2 or above). The clinical course after hemorrhage was reviewed to examine whether rebleeding or thrombotic events occurred up to the end of December 2019. Gastrointestinal bleeding was the most frequent cause of initial bleeding (57 patients, 59%). Rebleeding occurred in 11 patients (4.5%/year), with gastrointestinal bleeding in 10 and subarachnoid hemorrhage in 1. All rebleeding occurred in patients who resumed anticoagulation therapy. Another significant factor related with rebleeding included past history of gastrointestinal bleeding. On the other hand, major adverse cardiac and cerebrovascular events occurred in 6 patients older than 75 years old or more (2.5%/year), with systemic thrombosis in 4 and cardiac death in 2. All 4 patients with systemic thrombosis withheld anticoagulants after index bleeding, although only 10 patients withheld anticoagulation therapy. Rebleeding should be taken care of when anticoagulants are resumed after bleeding, particularly among patients who initially experienced gastrointestinal bleeding. Systemic thrombosis occurred at a high rate when anticoagulant therapy was withheld after bleeding.

Blood Coagulation Changes With or Without Direct Oral Anticoagulant Therapy Following Transcatheter Aortic Valve Implantation.

Thromboembolic events remain clinically unresolved after transcatheter aortic valve implantation (TAVI). The use of direct oral anticoagulant (DOAC) to reduce thrombosis associated with TAVI remains controversial. This study aimed at investigating the periprocedural change in blood coagulation and thrombolysis parameters in 199 patients undergoing transfemoral TAVI. Prothrombin activation fragment 1 + 2 (F1 + 2), thrombin-antithrombin complex (TAT), soluble fibrin monomer complex (SFMC), and fibrin/fibrinogen degradation product (FDP) levels were measured before and 1 hour after TAVI and 1, 2, and 7 days postoperatively. Of the 199 patients, 49 were treated with DOAC (apixaban in 32, edoxaban in 10, and rivaroxaban in 7). The F1 + 2 and TAT levels immediately increased 1 hour after TAVI and then gradually decreased in both groups. The SFMC level also significantly increased with a peak on day 1. The FDP level gradually increased, peaking on day 2. The values of F1 + 2, TAT, SFMC, and FDP in patients who used DOAC were significantly lower than those who did not use DOAC at 1 hour after TAVI in F1 + 2 (600 [452 to 765] vs 1055 [812 to 1340] pmol/L; p < 0.001), TAT (21.4 [16.2 to 37.0] vs 38.7 [26.4 to 58.7] µg/mL; p < 0.001) and on day 1 in SFMC (18.2 [9.4 to 57.9] vs 113.4 [70.9 to 157.3] µg/mL; p < 0.001) and day 2 in FDP (6.0 [4.7 to 10.0] vs 12.6 [8.2 to 17.4] µg/mL; p < 0.001). Ischemic stroke within 30 days after TAVI occurred in 3 patients (1.5%), who were not treated with DOAC. Coagulation cascade activation was observed after TAVI. DOAC could reduce transient hypercoagulation following TAVI.

Long-Term Clinical and Angiographic Outcomes After Implantation of New-Generation Drug-Eluting Stents for Patients on Maintenance Hemodialysis.

Prior research has revealed poorer clinical outcomes after drug-eluting stent (DES) implantation for hemodialysis patients. This study aims to investigate the long-term clinical and angiographic outcomes after new-generation DES implantation for hemodialysis patients.We retrospectively enrolled 91 consecutive patients (118 lesions) who underwent successful new-generation DES (everolimus-, zotarolimus-, and biolimus-eluting stents) implantation for the first time. We measured the serum calcium and phosphorus levels in the blood samples obtained just before hemodialysis. The follow-up period of clinical events was, at least, 1.5 years. In this study, major adverse cardiac and cerebrovascular events (MACCE) and clinically driven target lesion revascularization were reported in 36 (39.6%) and 11 (12.1%) patients, respectively. The prevalence of peripheral artery disease was significantly higher in the MACCE group (41.7% versus 14.5%, P = 0.006). The serum calcium level was significantly higher in the MACCE group (9.34 ± 0.92 mg/dL versus 8.77 ± 0.88 mg/dL; P = 0.004). The multivariate Cox proportional hazards model revealed that the serum calcium level (hazard ratio, 1.86; 95% confidence interval [CI]: 1.26-2.77; P = 0.002), suboptimal (over 55 mg2/dL2) calcium-phosphorus product (hazard ratio, 3.27; 95% CI: 1.41-7.61; P = 0.006) and the coexistence of peripheral artery disease (hazard ratio, 3.15; 95% CI: 1.49-6.65; P = 0.003) were independent predictors of MACCE.For hemodialysis patients, MACCE remains a frequent occurrence after new-generation DES implantation and is associated with calcium-phosphate metabolism and peripheral artery disease.

Impact of Serum Phosphorus Levels on Outcomes After Implantation of Drug-Eluting Stents in Patients on Hemodialysis.

BACKGROUND: Elevated serum phosphorus level is an important risk factor for cardiovascular death in general patients on hemodialysis (HD). However, the effect of serum phosphorus levels on outcomes after drug-eluting stent (DES) implantation in HD patients is unknown.Methods and Results:This was a post-hoc study of the OUCH study series, a series of prospective multicenter registries of HD patients who underwent DES implantation comprising 359 patients from 31 centers in Japan. Patients were categorized into 3 groups according to their preprocedural serum phosphorus levels. The 1-year clinical outcomes of the 336 patients treated for de novo lesions were evaluated. Compared with patients with high (>5.5 mg/dL; n=65) or normal (3.5-5.5 mg/dL; n=219) serum phosphorus levels, those with low serum phosphorus levels (<3.5 mg/dL; n=52) had significantly fewer target lesion revascularization events (13.9% vs. 16.9% vs. 1.9%; P=0.0090) and major adverse cardiac and cerebrovascular events (29.2% vs. 31.1% vs. 13.5%; P=0.032). Multivariate logistic regression analysis revealed that low serum phosphorus level was an independent negative predictor for major adverse cardiac and cerebrovascular events (adjusted odds ratio, 0.31; 95% confidence interval, 0.12-0.70; P=0.0036). CONCLUSIONS: Lowering of serum phosphorus levels beyond the current recommended range may be considered in HD patients who undergo DES implantation.

Add-on Antiplatelet Effects of Eicosapentaenoic Acid With Tailored Dose Setting in Patients on Dual Antiplatelet Therapy.

The aim of this study was to investigate the antiplatelet effects of eicosapentaenoic acid (EPA) at a sufficient dose following coronary stent implantation. Thirty-one patients on dual antiplatelet therapy with aspirin and clopidogrel were treated with highly purified EPA-E (Epadel®) for 12 weeks. Based on our previous study, patients with a high baseline EPA/arachidonic acid (AA) ratio (≥ 0.37; n = 11) were given a standard dose (1800 mg daily) of EPA-E, whereas those with a low EPA/AA ratio (< 0.37; n = 20) were given a high dose (2700 mg daily) to reach the target value of > 0.92. Platelet function was then evaluated with agonist-induced aggregation using light transmittance aggregometry and VerifyNow®. After EPA-E treatment, the EPA/AA ratio significantly increased from 0.28 to 1.31 (P < 0.001). Collagen (1, 2, and 4 µg/mL)-induced maximal platelet aggregation (MPA) was significantly suppressed after EPA-E administration (from 28.0 to 24.0, P = 0.033; from 44.0 to 40.0, P = 0.016; from 60.0 to 56.0, P = 0.010; respectively). However, there were no changes in MPA induced by adenosine diphosphate and AA and in P2Y12 reaction units (PRU) and aspirin reaction units. After EPA-E treatment, PRU was significantly suppressed in 8 patients showing high on-treatment platelet reactivity (HTPR) (baseline 305; 266-321 versus on-treatment 256; 233-261, P = 0.012), but not in those without HTPR (201; 156-220 versus 183; 159-233, P = 0.212). In conclusion, EPA treatment at a sufficient dose suppressed platelet aggregation and showed possible add-on effects in patients with clopidogrel hyporesponsiveness.