Effects Of Large Dosage Of Spironolactone On Left Ventricular Remodeling After Acute Myocardial Infarction

Background: Left ventricular remodeling (LVRM) after acute myocardial infarction (AMI) are the changes in the size, shape and function of the left ventricle. LVRM not only affects the function of the left ventricle in acute period, but also is the important factor of cardiac morbidity and mortality in patients. with acute myocardial infarction. Recently, the affects of the RAAS to LVRM after acute myocardial infarction has come to coincidence. Recent studys indicated that aldosterone in myocardium come from two oringins. One is that the myocardium gets from the serum, and the other is oringins in the myocardium.Objective: to compare the effects of large and lower dosage of spironolactone on ventricular remodeling after acute myocardial infarction and to investigate the efficacy of larger dosage of spironolactone on LVRM compared with lower dosage.Methods: the study population consisted of 48 consecutive acute anterior myocardial infarction patients visiting to our department in time. Selection criteria: patients according with the diagnostic criteria of acute anterior myocardial infarction made by WHO. The criteria include (1) the patient have typical symptom of AMI, with change of the ECG and heightening of cardiac zymogram and cardiac troponin. (2) The ECG consistent with the changes of anterior myocardial infarction. Exclusion criteria: (1)the patients taking non-steroid anti-inflammatory drugs(NSAIDs) and steroid hormone(STH); (2) patients with hyperkalemia(K≥5.5mmol/L); (3) patients suffering form renal inadequacy: blood urea nitrogen (BUN)≥10.71mmol/L(30mg/dL)or serum creatinine (Cr)≥176μmol/L(2.0mg/dL);(4)patients with hypertension or liver cirrhosis or pulmonary fibrosis; (5) patients suffering form other life-threatening diseases(as malignant tumor and so on); (6) patients who are supersensitive to spironolactone. The study contents 42 patients aged 45 to 78 years (28 male and 14 female).Average age is (58.0±10.1).The patients were randomized into two groups: the first group(in all 21 patients,13 male and 8 female, average age(56.8±15.7) accept convetional therapy(including reperfusion, angiotensin converting enzyme inhibitor or angiotensin receptor antagonist, Beta-blocker, antiplatelet and statins).At the same time we add smaller dosage of spironolactone(≤40mg/d). the other group(in all 21 patients,15 male and 6 female, average age(59.3±13.4) accept larger dosage of spironolactone(≥60mg/d) and convetional therapy. During the therapy every patient's keep their unadomed eating habit .we check out the electrolytes twice every week (early morning, empty stomach , median antebrachial vein).If serum potassium steps up, we should decrement or stop using spironolactone. Our experience:(1)do not use larger dosage of ACEI at the same time;(2)confine supplying potassium when using ACEI;(3)adds other uretics to exclude serum potassium;(4)monitor the electrolytes ,liver and renal function intimately. when the serum potassium≥5.0mmol/L,we decrement the dosage of spironolactone or adjust the dosage of other uretics.The cardiac function parameter was measured by SEQUOIA S-512 type ultrasonic diagnostic apparatus (Siemens company, Germany) using a 2.5MHZ frequency linear arrey transducer, including Left Ventricular end-systolic diameter (LVESD), Left Ventricular end-diastolic diameter (LVEDD), Left Ventricular fraction (LVEF), Left Ventricular posterior wall thickness (LVPWT), and Intraventricular Septal thickness (IVST) .Body surface area {BSA(m2) =[0.0061×high(cm)+0.0128×weight(kg)] - 0.01529,} was calculated according to their body length and weight, and Left Ventricular mass index (LVMI) was calculated according to Devereux Formula: LVMI(g/m2)={1.04×[(LVEDD + LVPWT + IVST)3- LVEDD3] - 13.6}÷BSA, at the same time, to calculate Left Ventricular end-systolic volume index (LVESVI) and Left Ventricular end-diastolic volume index(LVEDVI).Cardiothoracic ratio was measured by Kodak Direct View CR 850 type x-ray machine. The patients stood when they were take a photograph of orthotropia chest x-ray. CTR was a ratio of the widest transverse diameter and bony thorax transverse diameter.SAS V8 software pack was used for all the data to make statistical-analysis. Initially the homogeneity of variance among all the groups was analyzed. All the measurement data was denoted by mean±standard deviation and students t test was used to establish significance. Chi-square test was used for analysis of categorical data. We took P<0.05 was as statistic significant level.Results:1. The average dosage of spironolactone was 60.1±12.6 mg/d in larger dosage group and 25.5±2.8 mg/d in smaller dosage group, respectively. The smaller dosage of spironolactone we used in the study is similar to the dosage used in RALES, thus it can be used as a standard contrast in the latter.2. No body died or lost in both larger dosage group and smaller dosage group during the study period.3. The clinical characteristics between two groups including age, CT ratio, NYHA class, LVEF,LVEDVI,LVESVI were well matched (table 1).4. Serum Creatine , Serum Potassium and Serum Magnesium significantly increased compared with baseline(larger dosage group:K+3.92±0.30 mmol/L vs 4.39±0.38 mmol/L , Cr85.96±15.76 mmol/L vs 98.03±20.17 mmol/L,Mg2+0.86±0.19 mmol/L vs 0.98±0.12 mmol/L;smaller dosage group:K+4.02±0.67 mmol/L vs 4.17±0.67 mmol/L,Cr 86.61±13.81 mmol/L vs 86.69±14.57 mmol/L,Mg²⁺0.89±0.13 mmol/L vs 0.88±0.14 mmol/L ;P <0.05). The patients in large dosage of spironolactone had a slightly, but nevertheless statistically significant increase in Serum Creatine,Serum Potassium and Serum Magnesium than those in the smaller dosage group at 3 months follow-up (P<0.05). However, they are all in normal limits. There was no significant difference between two groups in the occurrence of hyperkalemia and renal impairment during the study period. (table2)5. During 3months follow-up, CT ratio,LVEF,LVEDVI,LVESVI were all improved in both groups compared with baseline (larger dosage group:CT ratio 0.50±0.08 vs 0.59±0.09,LVEF 0.44±0.06 vs 0.25±0,LVEDVI 26.55±5.36 vs 32.02±6.35,LVESVI 21.73±4.07 vs 28.57±5.55;smaller dosage group:CT ratio 0.56±0.09 vs 0.61±0.14,LVEF 0.37±0.09 vs 0.29±0.07,LVEDVI 30.31±3.69 vs 28.47±5.99,LVESVI 23.80±4.81 vs 30.31±3.70), whereas, the patients in larger dosage of spironolactone group had a greater improvement than did the patients in the smaller dosage group (P<0.05, Fig1-6 table 3) .Conclusion: Severe complications such as severe hyperkaliemia, renal impairment did not increase in larger dosage group after adjusting dosage of spironolactone and/or adding other diuretics.It is safe to use larger dosage of spironolactone after acute myocardial infarction as long as we monitor the Serum Potassium and renal function.Larger dosage of spironolactone was superior over lower dosage of spironolactone in reversing the ventricular remodeling and improving cardiac systolic function.