Comparison of the population of Polish patients participating in the TRANSITION study with the international population: a post hoc analysis.

INTRODUCTION: Heart failure (HF) patients discharged from a hospital are at a high risk of death and rehospitalization. Scarce data are available on the use of sacubitril / valsartan in this population in Poland. OBJECTIVE: The aim of this study was to compare the efficacy and tolerability of sacubitril / valsartan in the group of Polish patients who participated in the TRANSITION study with the patients recruited at other sites. PATIENTS AND METHODS: This is a post hoc secondary analysis of the TRANSITION study comparing sacubitril / valsartan initiation pre- vs postdischarge in 991 patients hospitalized for acute decompensated HF with reduced ejection fraction (HFrEF). The Polish subgroup consisted of 104 patients. RESULTS: Significant differences were identified in the characteristics of Polish vs non­Polish populations. At baseline, the Polish population showed higher proportion of men, higher body mass index, lower heart rate, N­terminal pro-B­type natriuretic peptide and high­sensitivity troponin T levels, and significantly lower New York Heart Association class. The Polish patients were better managed in terms of implanted electrotherapy devices, percutaneous coronary interventions, and drug therapy, and were more often hospitalized. The primary end point of achieving the target dose of sacubitril / valsartan at treatment week 10 was met by 45.6% of the Polish patients and 48.4% of the non­Polish population (P = 0.61). Approximately 90% of the Polish patients received and maintained any sacubitril / valsartan dose for 2 weeks over 10­week treatment vs 87.5% of the non­Polish patients (P = 0.36). The rate of permanent sacubitril / valsartan treatment discontinuation was low in both Polish (3.9%) and non­Polish populations (6.4%) (P = 0.33). CONCLUSIONS: Sacubitril / valsartan can be used safely in the early period after an episode of acute HF both in the Polish and non­Polish patients with HFrEF, and the likelihood to achieve the maximum dose is the same despite significant differences between the studied populations.

Reduced thrombin formation and altered fibrin clot properties induced by polyunsaturated omega-3 fatty acids on top of dual antiplatelet therapy in patients undergoing percutaneous coronary intervention (OMEGA-PCI clot).

OBJECTIVE: The goal of this study was to investigate whether omega-3 polyunsaturated fatty acids (n-3 PUFA) are able to alter plasma fibrin clot properties and reduce thrombin formation in stable coronary artery disease patients undergoing percutaneous coronary intervention (PCI). METHODS AND RESULTS: In an investigator-initiated, prospective, double-blind, placebo-controlled, randomized study, patients undergoing PCI who received standard pharmacotherapy were assigned to the treatment with 1 g/day n-3 PUFA (n = 30) or placebo (n = 24) for 1 month. Plasma fibrin clot permeability (K(s)); lysis time (t(50%)); prothrombin fragment 1.2; and peak thrombin generation from automated thrombogram, 8-isoprostaglandin F(2α) (8-iso-PGF(2α), an oxidative stress marker), and C-reactive protein were determined at baseline, 3 to 5 days after randomization, and 30 days after randomization. At baseline, both treatment groups did not differ significantly. A 1-month treatment with n-3 PUFA compared with placebo was associated with 15.3% higher K(s), indicating larger pores in the fibrin network (P = 0.0005); 14.3% shorter t(50%), indicating increased susceptibility to fibrinolysis (P<0.0001); 33.8% lower prothrombin fragment 1.2 (P = 0.0013); 13.4% lower peak thrombin generation (P = 0.04); and 13.1% lower 8-iso-PGF(2α) (P = 0.009). Treatment with n-3 PUFA had no effect on fibrinogen and C-reactive protein. After 1 month of treatment, fibrinogen (r = -0.53, P<0.0001), treatment assignment (r = 0.29, P = 0.006) and 8-iso-PGF(2α) (r = -0.27, P = 0.015) were independently associated with clot permeability (P<0.0001, R(2) = 0.66). CONCLUSIONS: Adding n-3 PUFA to standard therapy in stable patients undergoing PCI significantly decreases thrombin formation and oxidative stress and favorably alters fibrin clot properties. These findings indicate novel antithrombotic effects induced by n-3 PUFA in humans.

Effects of polyunsaturated omega-3 fatty acids on responsiveness to dual antiplatelet therapy in patients undergoing percutaneous coronary intervention: the OMEGA-PCI (OMEGA-3 fatty acids after pci to modify responsiveness to dual antiplatelet therapy) study.

OBJECTIVES: The purpose of this study was to investigate whether omega-3 polyunsaturated fatty acids (PUFAs) are able to modify platelet responsiveness to dual antiplatelet therapy in stable coronary artery disease patients undergoing percutaneous coronary intervention (PCI). BACKGROUND: Although previous studies have suggested antiplatelet properties of omega-3 polyunsaturated fatty acids, it is unknown whether they can enhance platelet inhibition on standard aspirin and clopidogrel treatment. METHODS: The OMEGA-PCI (OMEGA-3 Fatty Acids After PCI to Modify Responsiveness to Dual Antiplatelet Therapy) study was an investigator-initiated, prospective, single-center, double-blind, placebo-controlled, randomized study. Patients receiving standard dual antiplatelet therapy (aspirin 75 mg/day and clopidogrel 600 mg loading dose followed by 75 mg/day) were randomly assigned to receive the addition of 1 g of omega-3 ethyl esters (n = 33) or placebo (n = 30) for 1 month. Platelet function was measured serially by light transmission aggregometry (adenosine diphosphate and arachidonic acid [AA] were used as agonists) and assessment of the phosphorylation status of the vasodilator-stimulated phosphoprotein at baseline, 12 h, 3 to 5 days, and 30 days after randomization. RESULTS: The P2Y(12) reactivity index was significantly lower, by 22.2%, after 1 month of treatment with omega-3 polyunsaturated fatty acids compared with placebo when used in addition to dual antiplatelet therapy (p = 0.020). Maximal platelet aggregation induced by 5 and 20 micromol/l adenosine diphosphate was lower by 13.3% (p = 0.026) and 9.8% (p = 0.029), respectively, after 1 month of treatment with omega-3 polyunsaturated fatty acids compared with placebo. Platelet aggregation after AA stimulation was low and did not change significantly throughout the study. There were no cases of aspirin resistance during follow-up that was suggestive of good compliance with the medication. CONCLUSIONS: The addition of omega-3 ethyl esters to the combination of aspirin and clopidogrel significantly potentiates platelet response to clopidogrel after percutaneous coronary intervention.