Research On The Effect Of Drug Resistance Of Atorvastatin To Nitroglycer

Objective: Nitroglycerin is one kind of nitrate medications. Nitroglycerin plays a pharmacological role of expanding peripheral arteriovenous vessels, improving myocardial hemodynamics and ischemic myocardial blood supply. Currently nitroglycerin is still quite important in the treatment of heart disease caused by cardiac insufficiency and coronary atherosclerosis. The continuous use of nitroglycerin lasting 48-72 hours can led to the decrease of the curative effect(drug-resistance) and limit its clinical effect, which has become one of the focuses of the clinical problems and been widely studied. The study found that the causes of nitroglycerin resistance are more, but the vascular endothelium, neuroendocrine and the complex interaction between oxygen free radicals can cause nitroglycerin resistance.3-hydroxy-3-methyl glutaric acyl coenzyme A reductase inhibitors initial was firstly used as lipid-lowering drug, but it is research that the drug can improve vascular endothelial function. The mix use of nitroglycerin and 3-hydroxy-3-methyl glutaric acyl coenzyme A reductase inhibitors whether can improve nitroglycerin resistance is uncertain. Some domestic researchers have done vitro experiment, making nitroglycerin resistance animal model in rats, which proves that atorvastatin can improve the resistance of nitroglycerin.The researchers abroad have observed the effect on atorvastatin in maintaining nitroglycerin used in the treatment of healthy people, to prevent the development of drug resistance and endothelial function disorder, but it has not been done further research on clinical experiment. This topic aims to the mixture use of atorvastatin and maintain nitroglycerin on clinical patients, evaluating the clinical efficacy and safety of the resistance of atorvastatin on nitroglycerin, which provides a choice for the resistance of nitroglycerin.Methods: The research is to choose 60 patients of our hospital whose hospitalization time is between January and August of 2014,with 1-10 years medical history, of which 24 cases are men, 36 cases are women. The average age ranges from 62.5 to 71.5. The requirements are as follows:(1) sign informed consent and cooperate with the test;(2) diagnosed with high heart cardiac insufficiency, expanding heart cardiac insufficiency, senile heart valve disease cardiac insufficiency, cor pulmonale, cardiac insufficiency, coronary heart disease and cardiac insufficiency;(3) meet HYNA heart function class of 3-4; all patients with left ventricular ejection fraction(LVEF) <50%;(4) liver function, creatine kinase live up to atorvastatin standard;(5) blood test elevated b-type brain natriuretic peptide(BNP). The followings should be ruled out:(1) hypertrophy obstruction type cardiomyopathy patients with cardiac insufficiency, rheumatic cardiac insufficiency(for both in the treatment is not suitable for the use of nitroglycerin);(2)with nitroglycerin used contraindications: blood pressure is lower than 90/60 MMHG, heart rate < 60 times/min, the heart rate > 100 times/min, severe anemia, Hb < 30 g/L, glaucoma, nitroglycerin allergies, cranial pressure higher.(3)with atorvastatin contraindication, creatine kinase(CK) 5 times more than normal and liver function abnormal 3 times more than normal.The study adopts the method of randomization,all the chosen patients should go on basic treatment.Basic treatment includes:(1) the limit of sodium、water and oxygen;(2) nutrition and diet;(3) rest;(4) remove the incentive for treatment;(5) giving diuretic therapy. At the same time with basic treatment, the selected patients were randomly divided into group A and group B, with group A servering as nitroglycerin and atorvastatin joint application, group B for separate using of nitroglycerin. Initial nitroglycerin for group A and B is 5 ug/min, every 3-5 minutes with 5ug/min, if it is invalid up to 20 ug/min, the amount can be gradually added by 10 ug/min, and the maximum amount can be up to 100 ug/min. Nitroglycerin is controlled with speed by infusion pump all the way, dynamic ecg, blood pressure monitoring, the adjustable point is as following: systolic blood pressure,100 MMHG or A 20%drop in blood pressure, keeping nitroglycerin is constant at this time. On the basis group A takes atorvastatin 20 mg/day. The clinical outcome, hemodynamic parameters,left ventricular ejection fraction, the BNP, CK, liver function, and adverse reactions are monitored.All the data is analysized by software SPSS17.0, and measured with x ?s. Diversity of the mean in the group adopts the comparison between mean adopts, if P≤0.05, the difference is statistically significant. Count data is measured with frequency and percentage, the group comparison using Х 2 test.Results: 60 patients are successfully completed on schedule, except 1 case cardiac sudden death, 1 case affected by blood pressure using amiodarone treatment because of quickness arrhythmia.1 hemodynamic comparisonGroup A: blood pressure(128.70±9.97)before the experiment, experiment 1 d(124.23±10.34), 2d(118.33±11.37), 3 d(113.99±8.59), 4d(108.97± 7.43), and 5 d(106.27 ± 4.59), 6 d(102.47 ± 4.08), 7 d(98.78±4.31)Group B: blood pressure(127.12±11.28) before the experiment, experiment 1 d(125.54±13.44)(121.97±10.63), 2 d, 3 d(118.21 ±7.47), 4 d(113.46 ±8.03) and 5 d(109.33±6.60), 6 d(105.56 ± 7.02), 7 d(101.20 ±4.47).The hemodynamic change in both groups is statistically different(P< 0.05)2 comparion of patients clinical outcomeGroup A of 21 patients were markedly effective, 8 cases effective and 1 cases ineffective, the total effective rate was 96.67%.Group B of 11 patients were markedly effective, 16 patients effective, 3 cases ineffective, the total effective rate was 90.00%The clinical outcome in both groups was statistically different(P<0.05) 3 the comparion of left ventricular ejection fractionGroup A: the heart ejection fraction before treatment is: 37.50±9.16, the heart ejection fraction after 1 week treatment was 50.34 ± 7.96Group B: the heart ejection fraction before treatment is: 35.92± 7.21, the heart ejection fraction after 1 week treatment was 45.25±9.22The left ventricular ejection fraction in group A and B before and after treatment in patients was statistically different(P<0.05)4 the comparison of test projects:The BNP comparison(see Table 4)Group A: plasma BNP level before treatment is: 342.57±84.55 pg/ml, plasma BNP after 1 week treatment is pg/ml(64.22±30.03).Group B: plasma BNP level before treatment is: 348.25 ± 81.66 pg/ml, plasma BNP after 1 week treatment is pg/ml(89.96±45.88).BNP test project in both groups was statistically different(P<0.05)5 adverse reactions:CK of 1 patient from group A is mildly elevated(<1.5 times of the upper limit of normal), no discomfort symptoms, 1 week after discontinuation CK back to normal.1 case from group A with muscle pain, nausea, mild, no effect on daily work and life, no treatment, no patients stops drug due to adverse reaction.Conclusion: Clinical combination of 20 mg china-arab simvastatin statin and nitroglycerin is used in the treatment of heart failure, which can effectively prevent the nitroglycerin continuous static point caused by the development of drug resistance, and it can effectively improve cardiac insufficiency outcome, with rare adverse reactions. It is worthy of clinical promotion.