All NSTE-ACS patients aged between 18 and 90 years from October 2016 to June 2017 admitted to Huashan Hospital (Shanghai, China) were screened for this study. All patients enrolled have received elective PCI and had normal cardiac troponin T (cTnT) or elevated cTnT with stable or declining tendency prior to PCI. Written informed consent for PCI and this clinical study was obtained by all participants. Exclusion criteria were the followings: (1) increased pre-PCI cTnT values (rising above 20% of the previous value) or undetermined tendency; (2) severe liver dysfunction (ALT/AST >3 times of normal value, but only AST elevation is not excluded); (3) severe renal dysfunction (creatinine clearance rate <30 ml/min); (4) no informed consent; (5) patients with coronary artery bypass grafting history.
Eligible patients were randomized as the salvianolate group or the control group via simple random classification. Patients in the salvianolate group received intravenous salvianolate solution 200mg/100ml 2h before PCI, 22h and 46h after PCI with a rate of 60 ml/h. Patients in the control group received intravenous saline with the same volume and rate. All enrolled patients received standard medical care in accordance with the guidelines for the management of patients with NSTE-ACS, such as anti-platelet, anticoagulation therapy, lipid-lowering therapy, angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB), or other antihypertensive therapy if clinically indicated. PCI was performed according to the current guidelines for the management of acute coronary syndromes . The specific intervention strategies were dependent on cardiologists' discretion. All patients were followed up in outpatient service or telephone interview at one month and one year after PCI. Our study adheres to CONSORT guidelines.
PCI related myocardial injury or myocardial infarction was diagnosed according to the third universal definition of myocardial infarction . PCI related myocardial infarction (PMI) meets the criteria including: (1) cTnT values >5 times of upper reference limit (URL) after PCI if patients with normal baseline cTnT values; (2) post-PCI cTnT values rising >20% of pre-PCI value if patients with elevated pre-PCI cTnT values but cTnT levels are stable or falling. In addition, at least one of the following criteria must be present: (1) evidence of prolonged ischemia (>20 min) as demonstrated by prolonged chest pain; (2) ischemic ST changes or new pathological Q waves; (3) angiographic evidence of a flow limiting complication including loss of patency of a side branch, persistent slow-flow, no-reflow, or embolization; (4) imaging evidence with lack of viable myocardium or new regional wall motion abnormality. For patients who have isolated cTnT elevation after PCI, they can only be diagnosed as PCI related myocardial injury.
We further categorized all PCI-related myocardial injury into mild myocardial injury or severe myocardial injury. Mild myocardial injury was defined as increase of post-PCI cTnT values <5 times URL with normal baseline values or a rise of post-PCI cTnT values <20% of the baseline value with elevated pre-PCI cTnT; Severe myocardial injury was an elevation of cTnT values >5 times with normal baseline values or a rise of post-PCI cTnT values >20% of the baseline value with elevated pre-PCI cTnT in the absence of ischemic, angiographic or imaging findings. Major coronary artery with stenosis more than 50% is defined as impaired vessel.
Blood samples were collected in all enrolled patients before and at 8, 24 and 48h after PCI to measure cTnT to diagnose PCI related myocardial injury or myocardial infarction. Other baseline biochemical markers were also obtained.
Baseline characteristics including age, body mass index (BMI), past medical history were collected. Angiographic features and procedural characteristics were recorded. Data of patients were collected under anonymous conditions at Huashan Hospital.
The primary endpoint of this study is the incidence of severe myocardial injury or myocardial infarction after PCI. Secondary endpoints are all-cause death and incidence of major adverse cardiac events (MACEs), such as cardiovascular death, hospitalization for heart failure, myocardial infarction, stent thrombosis, or target vessel revascularization within one year after PCI.
Data from all participants were analyzed based on per-protocol (PP) analysis. Baseline clinical and demographic characteristics in addition to angiographic and intervention features were expressed as mean ± SD or median according to their distribution. Normally distributed values were compared by Student t-test. Otherwise, Mann–Whitney U test was used. The differences of proportions were analyzed using the Chi-square test. Multivariate logistic regression was used to find independent protective factors for PCI related severe myocardial injury or myocardial infarction. The difference of prognosis between control group and salvianolate group was analyzed using Logrank test. Two-sided tests were used and values of p < 0.05 were considered to be significant. All analysis was conducted using SAS 9.4 software (SAS institute Inc., Cary, USA).