ABSTRACT
Objective: To observe the efficacy of ticagrelor for treating elderly acute coronary syndrome (ACS) patients with elective PCI and having low response to clopidogrel; to explore the bleeding risks induced by ticagrelor replacement. Methods: A total of 945 ACS patients ≥ 65 years treated in our hospital from 2014-01 to 2017-01 were enrolled. All patients received aspirin and clopidogrel dual antiplatelet therapy (DAPT), thrombelastography (TEG) was used to detect platelet inhibition rate when DAPT ≥ 5 days. Based on platelet inhibition rate, the patients were divided into 2 groups:Ticagrelor replacement group, n=293 patients with low response to clopidogrel and switched to ticagrelor treatment, when adjusted DAPT ≥ 5 days, platelet inhibition rate was rechecked to compare the changes; Clopidogrel group, the patients were continuously treated by the same medication, n=652. The patients were followed-up for 3 months, bleeding events were evaluated by TIMI criteria and compared between 2 groups. Risk factors of ticagrelor induced bleeding were assessed by multivariate Logistic regression analysis. Results: Platelet inhibition rates in Ticagrelor replacement group were (51.70±42.90) %, (48.99±41.85) % and (55.08±25.70) % at (5-7) d, (8-14) d and (15-90) d ticagrelor treatment, which were higher than previous clopidogrel treatment (14.50±24.15) %, all P<0.05. The incidences of severe bleeding events were similar between 2 groups, P=0.96. Multivariate Logistic regression analysis presented that female (OR=4.329, P=0.000), low body weight (OR=0.817, P=0.039) and elevated fasting blood glucose (OR=1.251, P=0.028) were the independent risk factors for bleeding complication in ticagrelor treated elderly ACS patients. Conclusion: Compared with clopidogrel, ticagrelor may faster and more effectively inhibit platelet aggregation without increasing severe bleeding; female, low body weight and elevated fasting blood glucose were the independent risk factors for bleeding complication in ticagrelor treated elderly ACS patients with elective PCI.
ABSTRACT
Objective:To synthesize analogues of 6-[4-(4-substituted acyl piperazinyl)phenyl]-4, 5-dihydro-3(2H)pyri-dazinones and 6-[4-(4-substituted acyl piperazinyl)phenyl]-5-methyl-4,5-dihydro-3(2H)pyridazinones in search for more potent and selective antithrombotic drugs. Methods:Many reactions such as Friedel-Crafts reaction,hydrolysis,cyclation, acyla-tion,substitution were used to synthesize the title compounds. Born method was applied for preliminary pharmacological test in vitro. Results : Twelve title compounds were synthesized, in which 10 compounds were firstly reported. Their structures were identified by element analysis and 1H-NMR. Conclusion:Results of preliminary pharmacological test show that all synthesized compounds are effective against platelet aggregation induced by ADP in vitro. The activity of compound (9) is the most potent. The activity of compound (6), (7), (10), (11), (12) are also better than that of CCI-17810.