Effect Of Nicorandil On Index Of Microcirculatory Resistance In Patients With Ischemic Heart Disease:A Meta-analysis

BackgroundCoronary microcirculation is mainly composed of anterior arterioles and arterioles with coronary artery diameter less than 0.5mm,It is the main source of blood flow resistance and the main place for coronary blood perfusion,providing oxygen and nutrition for tissues,removing metabolic wastes,controlling inflammation,injury repair,and performing fluid exchange with tissues.Abnormalities in the structure and function of coronary microcirculation can lead to CMVD(coronary microvascular disease),CMVD is defined as a clinical syndrome with objective evidence of exertional angina pectoris or myocardial ischemia caused by the abnormal structure and(or)function of the anterior arterioles and arterioles in response to a variety of pathogenic factors.Studies have shown that about 40%of patients with coronary heart disease have symptoms of ischemic angina but the results of coronary angiography are generally normal,the main reason is the existence of CMVD.With the development of imaging technology,there are currently a variety of invasive and non-invasive imaging techniques used to assess the coronary microcirculatory function.IMR(index of microcirculatory resistance)is an indicator proposed in recent years for the invasive assessment of coronary microcirculatory function,it is not affected by epicardial vascular stenosis and hemodynamics,which is considered to be one of the best indicators for accuracy,sensitivity and repeatability of evaluating the degree of coronary microcirculation damage.Nicorandil is the first adenosine triphosphate(ATP)-sensitive potassium channel opener with nitrate vasodilator effect.Studies have shown that nicorandil may improve coronary microcirculatory function by dilating resistance vessels,protecting vascular endothelium,resisting oxidative stress and other mechanisms There are currently no large randomized controlled trials or meta-analyses assessing the effect of nicorandil on microcirculatory function in patients with ischemic heart disease(IHD).Purpose(1)To evaluate the effect of nicorandil on the IMR through a meta-analysis,and explore the protective effect of nicorandil on coronary microcirculation in patients with IHD.(2)To investigate the effect of nicorandil on IMR in patient with percutaneous coronary intervention(PCI)treatment.MethodsCochrane Central Register of Controlled Trials(CENTRAL),PUBMED,EMBASE,CNKI,and Wanfang electronic databases were searched for eligible studies published until March 2021.Two reviewers independently extracted and recorded the following data:(1)Characteristics of all included studies(the authors of the literature,year of publication,design of the study);(2)Characteristics of included patients(number of patients,mean age,sex);(3)treatments(therapeutic indication,type of drug,dose,follow-up duration,etc);(4)clinical outcomes(IMR values before and after treatment).Two reviewers independently assessed study quality by using the Cochrane’Risk of bias’ tool.The Q test and I2 statistic were used to evaluate heterogeneity between studies.A fixed-effects model was used for analysis in the case of low heterogeneity among trials,a random-effect model was used for analysis in the case of moderate or high heterogeneity among trials.A subgroup analysis was conducted based on the type of literature(whether it is an RCT study)and intervention measures(whether PCI treatment is performed),potential sources of heterogeneity were identified by sensitivity analyses.ResultsSix trials including a total number of 382 participants were identified.Nicorandil could significantly reduce IMR values in patients with IHD compared with the control group(MD=-4.94,95%confidence interval-7.49 to-2.39,I2=72%,P=0.0001).The reduction of IMR value in nicorandil group is also much more pronounced(MD=6.64,95%confidence interval 4.56 to 8.72,I2=0%,P<0.00001).In the PCI-treated subgroup,nicorandil could significantly reduce the IMR value(MD=-7.51,9%confidence interval-10.29 to-4.01,I2=51%,P<0.00001).In the non-PCI treated subgroup,nicorandil could also reduce the IMR values,but to a lesser extent(MD=-1.92,95%confidence interval-3.59 to-0.26,I2=0%,P=0.02).Conclusions(1)Nicorandil could significantly ameliorate coronary microcirculatory function in patients with IHD(2)The protective effect of nicorandil on coronary microcirculation is more remarkable in PCI subgroup compared with non-PCI subgroup.