Short-term efficacy of ticagrelor in acute ST-segment elevation myocardial infarction patients undergoing an emergency percutaneous coronary intervention

Comparison of myocardial infarction-related indexes in the two groups

There were no statistically significant differences in the baseline characteristics of the ticagrelor and clopidogrel groups (Table 1). There were also no significant between-group differences in the infarction site, infarct-related vascular location, coronary artery opening time, maximum balloon expansion pressure, implant stent length and diameter, and TIMI risk score (P > 0.05; Table 2).

Comparison of perfusion indicators of culprit vessels in the two groups

As shown in Table 3, the incidence of TIMI grade III blood flow in the ticagrelor group was significantly higher than that in the clopidogrel group (P < 0.05). There was no statistically significant difference in the incidence of TIMI grades 0–II blood flow in the two groups (P > 0.05). However, the corrected TIMI frame count (CTFC) in the anterior descending, circumflex, and right coronary arteries was statistically significantly lower in the ticagrelor group as compared with that in the clopidogrel group (P < 0.05).

Comparison of the incidence of stent thrombosis after the PCI in the two groups

During the follow-up, there was only one case of definite or probable acute stent thrombosis in the clopidogrel group and no cases in the ticagrelor group. There was also only one case of definite or probable subacute stent thrombosis in the clopidogrel group and no cases in the ticagrelor group. There was no significant between-group difference in the incidence of acute stent thrombosis, subacute stent thrombosis, or total stent thrombosis (P > 0.05; Table 3).

Comparison of the antiplatelet effect of the drug treatment in the two groups

There were no statistically significant differences in the PLT count, MPV, and PDW in the ticagrelor and clopidogrel groups at three different measurements times: immediately after admission and 2 h and 7 d postdrug treatment (P > 0.05; Table 4).

Thromboelastography (TEG) was used to evaluate the antiplatelet effect of the drugs. There were no significant between-group differences in the AA% and MA_AA at the three detection moments (P > 0.05; Table 5). There was no significant between-group difference in the ADP% and MA_ADP immediately after admission (P > 0.05). However, 2 h and 7 d after the drug treatment, the ADP% in the ticagrelor group increased significantly and the MA_ADP decreased significantly as compared with these parameters in the clopidogrel group (P < 0.05).

Comparison of complications and side effects in the two groups

As shown in Table 6, there were no cases of bradycardia in either group and no statistically significant difference in the incidence of hemorrhages in the two groups (P > 0.05). However, the incidences of dyspnea and kidney failure in the clopidogrel group were clearly lower than those in the ticagrelor group (P < 0.05).

Comparison of ischemic endpoint events in the two groups

Follow-up of ischemic endpoints during hospitalization and within 30 d postdischarge in both groups revealed no statistically significant between-group differences in cardiac death, nonfatal myocardial infarction, and emergency coronary revascularization (P > 0.05, Table 7).

Subjects

This study was approved by the ethics committee of Yantai Affiliated Hospital of Binzhou Medical University, China and Xuzhou Central Hospital, China. All patients provided signed informed consent forms.

In total, 97 STEMI patients (males, n = 52; females, n = 45) who were admitted to our hospital between December 2013 and May 2015 were sequentially enrolled. These patients underwent emergency coronary angiography (CAG) and PCI. The age range of the patients was 38–75 y (62.19 ± 11.25 y). The patients were assigned random numbers according to the hospital admission time, and these random numbers were then sorted using a computer-generated random number sequence in a table. Based on the treatment, the patients were divided into two groups: a ticagrelor group (n = 49) and a clopidogrel group (n = 48). The patients were followed up by telephone within 30 d after discharge.

According to a two-sample, two-sided equality test [29], 48 patients in each group will have power of 97.51 in estimating a 20% difference in the incidence of thrombolysis in myocardial infarction (TIMI) grade III blood flow. The inclusion of 48 patients in each group made it possible to detect a significant difference at the levels of α = 0.05 and β = 0.0249.

Inclusion criteria

The inclusion criteria were as follows: i) patients aged 38–75 y, with indications for emergency PCI surgery; ii) patients meeting diagnostic criteria of acute myocardial infarction stipulated by the Chinese Society of Cardiology (2010); iii) patients with STEMI onset of no more than 12 h or with chest tightness and persistent ST-segment elevation after 12-h onset; iv) acute myocardial infarction patients who had not undergone revascularization for nonculprit vascular lesions, including lesions in other parts of culprit vessels and non-culprit vessels within 30 d; and v) patients who agreed to participate in this clinical trial at the time of admission and signed written informed consent before surgery.

Exclusion criteria

The exclusion criteria were as follows: i) patients with severe adverse reactions to ticagrelor or resistance to clopidogrel or allergies to contrast agents; ii) patients who were not suitable for a PCI according to their clinical experience, previous examinations, and CAG diagnosis; iii) patients with left main disease, cardiogenic shock, and an acute STEMI within 24 h of thrombolysis; iv) patients with a history of PCIs or coronary artery bypass grafting; v) patients with a high risk of bleeding or active bleeding or surgery or trauma within 3 mo prior to enrollment; vi) patients who had taken proton pump inhibitors or H₂ antagonists within 1 wk prior to enrollment; vii) patients with abnormal findings on routine blood work (hemoglobin of < 100 g/L and platelet count of < 100 × 10⁹/L); viii) patients with a previous myocardial infarction or other heart disease and/or severe heart failure (New York Heart Association class III–IV); ix) patients with endocrine diseases, such as diabetes, digestive tract ulcers, acute and chronic infections, malignant tumors, blood diseases, and immune system diseases (e.g., rheumatic disease of connective tissues); x) patients with cerebrovascular diseases and peripheral vascular diseases; xi) patients with severely abnormal liver and kidney function (i.e., an increase in alanine aminotransferase and aspartate aminotransferase of more than three times the normal levels due to a non-ST-elevation myocardial infarction; a serum creatinine level of more than180 umol/L); xii) patients with a history of heparin-induced thrombocytopenia; xiii) patients with severely uncontrolled hypertension (systolic blood pressure ≥ 180 mmHg and/or diastolic blood pressure ≥ 110 mmHg); and xiv) patients who had any conditions deemed inappropriate by the investigators for inclusion in the study (e.g., late presenters where the efficacy of antiplatelet therapy was substantially diminished).

Drug treatment

Standardized use of antiplatelet drugs before the PCI

The patients in the ticagrelor group received 300 mg of aspirin (Bayer, Germany) and 180 mg of ticagrelor (AstraZeneca, UK) once daily, and the patients in the clopidogrel group received 300 mg of aspirin and 600 mg of clopidogrel (Sanofi, France) once daily.

Standardized use of antiplatelet drugs after the PCI

The patients in the ticagrelor group took 100 mg of aspirin once daily, in addition to 90 mg of ticagrelor twice daily, for 12 mo after surgery.

The patients in the clopidogrel group took 100 mg of aspirin once daily, in addition to 75 mg of clopidogrel once daily, for 12 mo after surgery.

Related drug treatment

Patients with specific indications were treated with low-molecular-weight heparin, IIb/IIIa glycoprotein inhibitors, β-receptor inhibitors, angiotensin-converting-enzyme inhibitors/angiotensin receptor blockers, statins, calcium channel blockers, nitrates, and proton pump inhibitors/ H₂ antagonists.

Coronary interventional therapy (CAG plus PCI)

The patient’s radial artery was used with the needle inserted at the most obvious pulsation according to the Seldinger method. With the guidance of the puncture needle, the guide wire was set and then fed into the arterial dilatation sheath, followed by an injection of 3,000 U heparin sodium into the outer sheath tube for anticoagulation. Catheters were then delivered along the sheath to the left and right coronary openings under the guidance of J-shaped guide wire. In left coronary artery, contrast agent (iohexol, 350 mg/ml) was administered in five projections (spider, foot, liver, head, and right shoulder) and in the right coronary artery, contrast agent was administered at least in the left anterior oblique and head projections. If necessary, other positions can be added to achieve the full display of the coronary artery segments. The experienced clinical cardiologists performed all the operations. Two experienced cardiac intervention specialists evaluated the following parameters: the degree of coronary artery stenosis, using the internationally accepted visual method, which is calculated as the percentage of reduction in the diameter of stenosis as compared with the diameter of normal coronary vessels at the proximal and distal ends.

The degree of coronary artery stenosis is calculated using the internationally accepted visual method, which is calculated as the percentage of the diameter of the stenosis that is smaller than the decrease in the diameter of the normal coronary artery at the concentric and distal end of the adjacent stenosis. All results were based on consensus. The observation indexes are shown in Supplementary Table 1.

Blood specimen collection

Elbow venous blood (5 ml) was collected immediately after admission prior to any drug treatment and again 2 h after the drug treatment. Another 5 ml of fasting elbow venous blood was collected 7 d after the drug treatment. Following the blood collection, a tourniquet was not applied, and tapping the blood vessels at the puncture site was avoided. The collected blood specimen was not subjected to any violent oscillations to reduce potential damage to platelets and avoid hemolysis of the specimen.

Determination of relevant detection indicators

Platelet determination

Using an XE-2100D blood analyzer (SYSMEX, Japan) and associated reagents, the platelet (PLT) count, mean platelet volume (MPV) [30], and platelet distribution width (PDW) were determined immediately after admission and 2 h and 7 d after the drug treatment.

Thromboelastography determination

Thromboelastography (TEG) was performed using a thromboelastography analyzer (TEG-5000; Haemoscope Corporation, USA) and platelet aggregation detection kit (coagulation method) according to the instructions of the manufacturer. Briefly, immediately after admission and 2 h and 7 d postdrug treatment, 5 ml of elbow venous blood was placed in a citric acid tube. Then, 1 ml of blood was added to the tube containing kaolin and mixed gently. Subsequently, 360 μl of the kaolin-treated blood sample was added to a preheated test cup containing 20 μl of 0.2 M CaCl₂. The total clot strength (MAthrombin) of thrombin-induced platelet activation was measured using the TEG coagulation analyzer. Briefly, the blood sample was placed in a static cylindrical stainless steel cup in which the coagulation analyzer automatically adjusted the temperature to remain at 37° C and then rotated at an angle of 4°45', with each rotation lasting 10 sec. The blood sample was monitored by immersing the small stainless steel cylinder in the blood sample and the sensor that was connected to the cylinder. When the blood sample was in a liquid state, the rotation of the cup did not affect the inner cylinder, and the signal reflected on the tracing paper by the sensor was a straight line. When the blood coagulated, the movement amplitude of the small stainless steel cylinder was affected by the strength of the fibrin-platelet complex. The rotation of the cup drove the cylinder to move at the same time; as the internal resistance continued to increase, the movement of the built-in cylinder driven by the cup gradually weakened. This process was converted and recorded by the sensor. The data were then automatically analyzed and processed using a computer, generating the TEG.

Then, prepared activator F (10 μl) was added to two blank test cups, followed by the addition of 10 μl of arachidonic acid (AA) and adenosine diphosphate (ADP) reagents, respectively. In total, 360 μl of heparinized whole blood was placed in two test cups and mixed to form a whole blood cross-linked clot activated by platelet activator. The AA-induced platelet inhibition rate (AA%), platelet aggregation rate of the AA pathway (MA_AA), ADP-induced platelet inhibition rate (ADP%), and platelet aggregation rate of the ADP pathway (MA_ADP) were then obtained using the TEG analyzer and associated computer software according to the method described above to evaluate the effects of the drug treatments (i.e., aspirin, clopidogrel, and ticagrelor) on platelet function.

Statistical analysis

SPSS version 22.0 statistical software was used for data analysis. The measurement data were expressed as mean ± standard deviation (SD). For data that conformed to a normal distribution, differences between the two groups were analyzed using an independent samples t-test. For data with a non-normal distribution, the Mann–Whitney U test was used for the analysis of between-group differences. The enumeration data are shown as cases/percentage (n/%) and analyzed using a chi-square (χ²) test or Fisher’s exact probability analysis. A value of P < 0.05 was considered statistically significant.