| BackgroundAspirin has been recognized as an effective antiplatelet agent in the treatment of carotid atherosclerosis and prevention of cerebrovascular events.However,due to the high risk of bleeding events of aspirin,it is necessary to seek a safe,effective and compliant alternative medicine.The Dengzhan Shengmai（DZSM）capsule has been widely used in carotid atherosclerotic diseases.If proven to be non-inferior to aspirin,DZSM might be preferable.ObjectiveWe conducted a randomized trial to test non-inferiority of DZSM to aspirin in the treatment of carotid atherosclerotic plaque.To find new ideas for prevention and treatment of carotid atherosclerotic plaque.MethodsWe did a single-center,prospective,open-label,randomized,non-inferiority trial.Patients with carotid atherosclerotic plaque were enrolled and randomly assigned（1:1）to receive DZSM capsule（0.36 g,3 times a day,orally half an hour after meal）and aspirin（100 mg,once every morning,orally on an empty stomach）,respectively,from 1 Apr.2019 to 30 Sept.2019 in our hospital.Patients in the two groups were given the best medical treatment（BMT）according to relevant guidelines.All patients received atorvastatin calcium tablet（20mg）orally at the same time and were advised to improve their lifestyle and control risk factors.We recorded primary outcome（carotid intima-media thickness（IMT））,secondary outcomes（ischemic events,plaque scores,plaque counts,plaque vulnerability,rate of lumen stenosis,lipid level,fibrinogen）and safety outcomes（adverse events and laboratory tests）by face-to-face follow-up every 3 months.The follow-up period was 12 months.Non-inferiority of DZSM would be shown if the lower limit of the one-sided 97.5%CI of the difference of mean change of IMT between groups was more than-0.06 mm（margin of non-inferiority）.Primary outcome was analyzed in Intention-to-treat（ITT）analysis and Per-Protocol（PP）analysis.This trial was registered with Clinical Trials.gov,CHi CTR1900021365.ResultsFrom Apr.1,2019 to Sept.30,2019,150 patients were enrolled and there was no statistical difference in demographics between groups.ITT analysis showed that the decrease in maximum IMT（（?）IMT）was 0.216±0.160 mm in the DZSM group and0.225±0.149 mm in the control group.The one-sided 97.5%CI for the difference between the two（?）IMTs was more than-0.0593(P non-inferiority=0.0234).Thus,non-inferiority of DZSM was shown in ITT analysis（P<0.025）.There was no significant difference in incidence of ischemic events between groups（P=0.650）.DZSM group significantly reduced plaque scores（P=0.043）and plaque length（P=0.005）,improved plaque vulnerability（P=0.007）,reduced low-density-lipoprotein cholesterol（LDL-C）（P<0.0001）and triglyceride（TG）（P<0.0001）,and improved high-density-lipoprotein cholesterol（HDL-C）（P<0.0001）.There was no significant difference compared with aspirin group（P>0.05）.DZSM group could significantly reduce the total cholesterol（TC）level（P<0.0001）,but the reduction of TC was significantly greater in the aspirin group（P<0.0001）.The fibrinogen level in DZSM group was significantly decreased（P=0.042）,but the decrease in aspirin group was greater,and the difference was statistically significant（P=0.022）.There was significant difference between groups in incidence of total adverse events（14.7%VS.28%,P=0.046）,especially gastrointestinal discomfort（5.3%VS.16%,P=0.034）.Though there was no significant difference in incidence of bleeding events（0 VS.5.3%,P=0.128）,the DZSM group had a tendency of lower incidence.There was no significant difference in laboratory test between groups.ConclusionThis trial demonstrated that DZSM is non-inferior to aspirin in the treatment of carotid atherosclerotic plaque considering efficacy.Meanwhile,DZSM is superior to aspirin in terms of safety.It will provide a new idea and approach for the treatment of carotid plaque,especially for those who are aspirin intolerant. |
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