Meta-analysis Of Efficacy Of Isosorbide Mononitrate And Monitoring The Occurrence Of Adverse Reactions

ObjectiveTo systematically review the efficacy of isosorbide mononitrate(ISMN) for patients with angina pectoris、 heart failure and hypertention, monitoring the occurrence of adverse reactionsMethodsWe electronically searched PubMed, EMbase, Medline, Cochrane, CNKI, WanFang Data and VIP databases from the date of establishment to September 2013 for all randomized controlled trials (RCTs) on the use of ISMN in patients with angina pectoris、heart failure and hypertention. The data extraction and quality assessment of included RCTs were conducted by two reviewers independently. Then, meta-analysis was conducted using RevMan 5.3.5 software. Statistical the incidence of adverse reactions of ISMN in literature and our hospital and collect the case reports of it.ResultsIn the literature of ISMN for patients with angina pectoris, a total of 42 RCTs involving 4228 patients were included.3 of the RCTs only can be used qualitative analysis while 39 of them can be used quantitative analysis. The results of qualitative analysis indicated that ISMN tablets or controlled release tablets can significantly improve total exercise time、the exercise time to 1 mm ST depression time to onset of chest pain and maximal ST depression of AP patients. But the efficacy of ISMN in lowing anginal attacks and nitrogtycerin consumption is unclear. And the efficacy between ISMN and ISDN is also unclear. The results of meta-analysis indicated that ISMN injection was better than the control group in clinical effectiveness (RR=1.19,95%CI 1.09 to 1.29, P<0.05), in improving ischemic ECG (RR=1.20,95%CI 1.06 to 1.36, P<0.05), and also in improving both clinical effectiveness and ischemic ECG (RR=1.15,95%CI 1.10 to 1.21, P<0.05); ISMN tablets was better than the control group in clinical effectiveness (RR=1.19,95%CI 1.10 to 1.28, P<0.05), and in improving ischemic ECG (RR=1.27,95%CI 1.11 to 1.44, P<0.05); However, no significant difference was found between groups in improving the exercise time to 1mm ST segment depression (MD=-4.76,95%CI-25.83 to 16.32, P>0.05), despite prolonged the treatment time (MD=-10.81,95%CI-31.37 to 9.75, P>0.05).In the literature of ISMN for patients with chronic congestive heart failure, a total of 6 RCTs involving 478 patients were included. Studies are all about ISMN injection. The results of meta-analysis indicated that ISMN injection was better than the control group in heart function improved rate (RR=1.19,95%CI 1.05 to 1.35, P<0.05), in improving LVEF (MD=0.09,95%CI 0.04 to 0.15, P<0.05)> FS (MD=0.03,95%CI 0.01 to 0.06, P<0.05) and E/A (MD=0.22,95%CI 0.02 to 0.42, P<0.05).In the literature of ISMN for patients with hypertension, a total of 9 RCTs were included.4 RCTs were ISMN for patients with hypertensive emergency involving 258 patients,5 RCTs were ISMN for patients with ISH involving 396 patients.The results of meta-analysis indicated that ISMN injection was not lower than other antihypertensive drugs (RR=0.93,95%CI 0.84 to 1.03, P>0.05). Subgroup analyzes indicated that ISMN injection was not as good as nitroglycerin injection (RR=0.89,95%CI 0.81 to 0.99, P<0.05). ISMN tablets is not lower than the control group in lowering SBP in patients with ISH (MD=-1.12,95%CI-4.51 to 2.27, P>0.05). Not significantly lower DBP in patients with ISH (MD=12.52,95%CI 8.59 to 16.46, P<0.05).Hence, significantly reduced PP (MD=-14.84,95%CI -19.96 to -9.72, P<0.05).The incidence of adverse reactions of ISMN maily caused by headache, half of the patients can tolerate, but also may caused by dizziness, facial flushing, palpitation, bradycardia, tinnitus, fatigue, nausea, vomiting, hypotension, orth ostatic hypotension, syncope, somnolence, peripheral edema, angina pectoris aggravated, thirst, dreams, fever, skin rash. There are heart nitrate-induced sphincter relaxation induced heartburn reported.ConelusionThe current evidence suggests that ISMN injection is better than nitroglycerin in improving clinical conditions and ischemic ECG of AP patients. But the efficacy among ISMN tablets、sustained release tablets or controlled release tablets in isosorbide dinitrate and nifedipine to the AP patiences is unclear. However, when compared isosorbide mononitrate with isosorbide dinitrate, isosorbide mononitrate tend to be more effective, when compared isosorbide mononitrate with with nifedipine, effectiveness tends to nifedipine. ISMN injection is better than nitroglycerin in improving heart function、LVEF、FS and E/A of heart failure patients. ISMN injection was not lower than nitroglycerin injection and diltiazem injection for patients with hypertensive emergency, but not as good as nitroglycerin injection. ISMN tablets is not lower than other antihypertensive drugs in lowering SBP in patients with ISH, not lower DBP at the same time. Hence, significantly reduced PP. The clinical use of isosorbide mononitrate is safe and effective. Further randomized trials with high-quality and low-risked bias is needed because most trials have been included are medium-quality and unconfirmed low-risk bias RCTs.