Efficacy And Safety Of Half-dose Ticagrelor In Elderly Patients With Acute Coronary Syndrome Combined With Chronic Renal Insufficiency

Background:Acute coronary syndrome(ACS)is a severe disease of cardiovascular disease.With the develpment of aging society,aging and chronic renal insufficiency(CRI)have become the recognized risk factors of ACS,and seriously affect the prognosis of patients with ACS.Dual antiplatelet therapy has become the standard drug treatment in patients with ACS,but the patients with CRI and ACS have abnormal clotting mechanism,at the same time the risk of ischemic and bleeding risk.Age is considered to be the most possible factor to increase the risk of bleeding for CRI patients.Therefore,the choice of the class types and dose of antiplatelet drugs in patients is facing great difficulties.Ticagrelor is a new type of oral cyclopentyl triazole pyrimidine(CPTP)class ADP P2Y12 receptor inhibitor,it has a more powerful,faster,and the characteristics of the reversible inhibition of platelets.Ticagrelor itself is active,do not need transform through the metabolism of liver enzyme CYP2C19 gene,and its metabolites AR-C124910 XX also has inhibiting effect on P2Y12 receptor,therefore is not subject to the influence of gene polymorphism.The subgroup analysis of 3237 cases of chronic kidney disease in the study of PLATO has confirmed that Ticagrelor can be significantly reduced major adverse cerebrovascular composite events(MACCE)compared with clopidogrel.Because of the gene,body weight and the body mass index(BMI)have distinct difference between the Asian people and Euramerican population,caucasians has the 30%~70% drug metabolites higher than Asian people.The PHILO study from Japan in patients with ACS for Ticagrelor and clopidogrel had demonstrated that Ticagrelor group and clopidogrel group had similar incidence of the primary cardiovascular endpoint events,but the serious bleeding events was more commonly in the Ticagrelor group.From South Korea study found the clinical endpoint event risk for Ticagrelor group and clopidogrel group was similar for the AMI patients during the period of in hospital,but the TIMI bleeding events was significantly increase in the Ticagrelor group.A study from South Korea found that pharmacokinetic data of 90 mg bid dose exists larger variation reaction in the day,and suggests that in the peak inhibition may appear bleeding risk,so the 45 mg,bid may be more suitable for east Asian populations.Objectives:So the purpose of this study is to explore the long-term efficacy and safety of half dose Ticagrelor in elderly(?75 years)coronary syndrome(ACS)complicated with renal insufficiency(CRI)patients,and provide new evidence for antiplatelet therapy of these patients.Methods:We have selected 93 patients with ACS patients complicated with CRI from January 2015 to July2015 in xijing hospital cardiovascular medicine in hospital,they were divided into full dose of Ticagrelor group(full dose group,n = 48 cases)and half dose group(n = 45).Two groups of patients were given Aspirin enteric-coated,Low molecular heparin,Nitrate drugs,Statins,ACEI and ARB,?-blockers and other conventional treatment.Full dose for Ticagrelor group was given the standard care,namely the first agent loading dose of 180 mg,90 mg,bid.Half dose group was given for first agent loading dose of 90 mg,after 45 mg bid(break in two pieces by nurses during the hospital and oneself after hospital),two groups patients continue aspirin and maintaining dose Ticagrelor to 1 year.The clinical baseline data of two groups were analyzed,and test the ADP mediated platelet inhibition ratio when the patients take medicine for 1 week.Follow up to12 months,recored the main adverse cardiovascular events including unstable angina and stent thrombosis,recurrence of myocardial infarction,heart failure,stroke,and all-cause mortality,recorded all kinds of bleeding events and difficulty breathing during the follow-up period.Results:1.The baseline information,such as age,sex,smoking history,hyperlipidemia,hypertension,liver function,left ventricular ejection fraction(LVEF),medicine conservative treatment patients and eGFR between two groups were no significant difference,but diabetes prevalence and ST elevation acute coronary syndrome(STEACS)in half dose group were lower than that in full dose group(P<0.05).2.After 1 week,the platelet aggregation inhibition rate of patients was 78.1%,and a half dose group was 69.4%,there was statistically difference between two groups(p = 0.04).However,platelet aggregation inhibition rate less than 50% of the patients in full dose groups was 3 cases(6.25%),half dose group was 3 cases(6.67%)there was no significant statistical difference between the two groups(p = 1.00).3.Testing their cardiac function with cardiac ultrasound examination after 12 months,the LVEF of full dose groups of patients was50%±2%,half dose group was 49%±2%,no significant statistical differences between two groups.4.Follow up to 12 mouths,neither signal nor the total major adverse cardiac events(MACCE)between the two groups was not significance(p>0.05).The MACCE of full doses group were 9 cases(19%),2 cases unstable angina,0 cases stent thrombosis,1 case myocardial infarction,3 cases heart failure,1 case cerebral apoplexy,and 2 cases death.Half dose group were 6 cases(13%),2 cases unstable angina,0 cases stent thrombosis,1 case myocardial infarction,1case heart failure,1 case cerebral apoplexy,and 1 case death.5.The total bleeding events of Full dose groupwere 16 cases(33%),(9 cases nasal bleeding,3 cases subcutaneous haemorrhage,3 cases gingival bleeding,1 case conjunctival hemorrhage),half dose group were 6 cases(13%),(4 cases nasal bleeding,2 cases subcutaneous haemorrhage,there was no gingival bleeding and eye conjunctival hemorrhage).there were not fatal bleeding events such as cerebral hemorrhage,gastrointestinal bleeding between two groups.The incidence of bleeding events in half dose group was obviously lower than the full doses group(P<0.05).6.12 cases(25%)dyspnea were observed in full dose group,and 9 cases(20%)in half dose group,there was no statistical significance between two groups(p = 0.63).1 patient in full dose group changed to clopidogrel due to can't tolerate breathing difficulties,and not after.Conclusions:In our country,there was no significant difference between half dose Ticagrelor and full dose Ticagrelor in respect of reducing MACCE in the elderly(?75 years)patients with ACS conbined with CRI,the incidence of bleeding events is lower in half dose,half dose of Ticagrelor have the same effect and better security.