kinase-MB Elevation Research Articles

The clinical significance of smaller increases in cardiac enzymes following elective percutaneous coronary intervention

In their recently published well designed article Yonetsu and coworkers used optical coherence tomography (OCT) to study the relationship between pre-percutaneous coronary intervention (PCI) plaque morphology and post-PCI creatine kinase-MB (CK-MB) elevation [1]. Elevated CK-MB levels were observed in 28% of patients. The CK-MB elevation was associated with elevated white blood cell count, type B2/C lesions, the presence of thin cap fibroatheroma (TCFA), plaque rupture, and lipid quadrants. In the multivariate analysis, the presence of TCFA (OR 4.68) and type B2/C lesions (OR 4.20) were independent predictors of post-PCI CK-MB elevation.

The assessment of Shin’s method for the prediction of creatinine kinase-MB elevation after percutaneous coronary intervention: an intravascular ultrasound study

Cardiac enzyme release is common after percutaneous coronary intervention (PCI). At present there is no established relationship between the quantity of necrotic core and dense calcium, as assessed by Shin's method using intravascular ultrasound virtual histology (VH-IVUS), and post-PCI creatinine kinase-MB (CK-MB) elevation. A total of 112 consecutive patients with unstable angina and a normal pre-PCI CK-MB level were imaged using VH-IVUS. Patients were divided into 2 groups according to the presence (CK-MB group, n=22) or absence (non CK-MB group, n=90) of a post-PCI CK-MB elevation>1.0 the upper limit of normal (3.6ng/ml). Using Shin's method contours were drawn around the IVUS catheter (instead of the lumen), and the vessel. Mean area and volume of necrotic core and dense calcium were significantly greater in CK-MB group than in non CK-MB group (1.7±0.9mm(2) vs. 0.9±0.6mm(2), P<0.001; 17.2±8.8mm(3) vs. 8.8±5.8mm(3), P<0.001, and 0.9±0.6mm(2) vs. 0.4±0.4mm(2), P=0.001; 9.1±5.8mm(3) vs. 3.9±3.7mm(3), P<0.001, respectively). Percent necrotic core and dense calcium areas calculated by external elastic membrane (EEM) area were significantly greater in CK-MB group than in non CK-MB group (11.9±5.1 vs. 6.6±4.0%, P<0.001 and 6.5±4.0 vs. 3.0±2.9%, P<0.001, respectively). In the multivariate analysis, dense calcium volume and percent necrotic core to EEM at the most diseased segment were the only independent predictors of post-PCI CK-MB elevation (odds ratio: 1.22; 95% confidence interval: 1.09-1.37, P<0.001 and odds ratio: 1.26; 95% confidence interval: 1.12-1.43, P<0.001). Lesions with a greater amount of dense calcium volume and percent necrotic core to EEM, which can be easily identified and quantified on VH-IVUS analyzed using Shin's method, are responsible for post-PCI CK-MB elevation. With a rapid analyzing time, Shin's method may increase the identification of high risk lesions likely to induce a post-procedural myocardial injury in the catheterization laboratory facilitating on-line clinical decision making.

Impact of plaque morphology on creatine kinase-MB elevation in patients with elective stent implantation

The association between percutaneous coronary intervention (PCI) and subsequent myonecrosis has been widely recognized, and worse prognosis has been reported among patients with elevated post-PCI biomarkers. We used optical coherence tomography (OCT) to study the relationship between pre-PCI plaque morphology and post-PCI creatine kinase-MB (CK-MB) elevation. One hundred and twenty-five patients with normal pre-PCI CK-MB levels underwent OCT examination before nonemergency stent implantation. Patients were divided into two groups according to the presence (Group CK, n=35) or absence (Group NCK, n=90) of post-PCI CK-MB elevation ≥ upper limit of the normal range. Clinical and the OCT findings were compared between the two groups. Elevated CK-MB levels was observed in 35 patients (28%). The CK-MB elevation was associated with elevated white blood cell count, type B2/C lesions, the presence of thin cap fibroatheroma (TCFA), plaque rupture, and lipid quadrants. In the multivariate analysis, the presence of TCFA (OR 4.68, 95% CI 1.88-11.64, p=0.001) and type B2/C lesions (OR 4.20, 95% CI 1.30-13.59, p=0.02) were independent predictors of post-PCI CK-MB elevation. TCFA and angiographically complex lesion morphology can predict post-PCI CK-MB elevation in patients treated with elective stent implantation. OCT may be useful in stratifying the risk for nonemergency stent implantation.

Virtual Histology Intravascular Ultrasound Analysis of Non-Culprit Attenuated Plaques Detected by Grayscale Intravascular Ultrasound in Patients With Acute Coronary Syndromes

Noncalcific attenuated plaques identified by grayscale intravascular ultrasound (IVUS) are often seen in patients with acute coronary syndromes and have been associated with no reflow and creatine kinase-MB elevation after percutaneous coronary intervention. Histopathology has shown cholesterol clefts, microcalcification, or organized thrombus. One hundred twenty-four vessels in 64 patients with acute coronary syndromes from the PROSPECT trial were identified for inclusion in the present analysis. After excluding 4 vessels with severe calcification, 9 vessels with <40% plaque burden, and 3 vessels with too few (<3) virtual histology (VH)-IVUS frames for analysis, complete grayscale IVUS and VH-IVUS was available for 108 vessels in 64 patients that contained 39 VH-IVUS thin-capped fibroatheromas (VH-TCFA), 40 thick-capped fibroatheromas (VH-ThFA), and 33 pathologic intimal thickening but no fibrotic or fibrocalcific plaques. Overall, there were 47 grayscale IVUS attenuated plaques in 43 vessels. Compared to the minimum luminal sites of the remaining 65 vessels (controls), attenuated plaques contained larger necrotic core areas (1.5 +/- 0.9 vs 0.9 +/- 0.8 mm(2) in controls, p = 0.001). Fibroatheromas (VH-TCFA or VH-ThFA) were more common at the sites of attenuated plaques than at control sites (VH-TCFA 42.5% vs 29.2%, VH-ThFA 53.2% vs 23.1%, pathologic intimal thickening 4.3% vs 47.7%, p <0.0001). In conclusion, grayscale IVUS attenuated plaques are associated with a large amount of VH-IVUS necrotic core and are markers of the presence of fibroatheromas (VH-TCFA or VH-ThFA). This may explain the biologic instability of these lesions.

Outcome of Undersized Drug-Eluting Stents for Percutaneous Coronary Intervention of Saphenous Vein Graft Lesions

We sought to determine the outcome with undersized drug-eluting stents for percutaneous coronary intervention of saphenous vein graft lesions. Using intravascular ultrasound guidance, 209 saphenous vein graft lesions were treated with drug-eluting stents (153 sirolimus-eluting and 56 paclitaxel-eluting stents). The lesions were divided into 3 groups according to the ratio of the stent diameter to the average intravascular ultrasound reference lumen diameter: group I, <0.89; group II, 0.9 to 1.0; and group III, >1.0. Angiographic no-reflow was defined as a Thrombolysis In Myocardial Infarction flow grade of 0, 1, and 2 after percutaneous coronary intervention. Plaque intrusion was defined as tissue extrusion through the stent struts. Stent malapposition was defined as one or more stent struts that had clearly separated from the vessel wall with evidence of blood speckles behind the strut. No significant differences were found in the use of distal protection devices (group I, 44%; group II, 35%; and group III, 36%; p = 0.5); and no significant differences were found in the incidence of stent malapposition among the 3 groups (group I, 21%; group II, 42%; and group III, 52%; p = 0.001). The plaque intrusion area (group I, 0.13 +/- 0.30 mm(2); group II, 0.25 +/- 0.42 mm(2); and group III, 0.31 +/- 0.40 mm(2); p = 0.018) and plaque intrusion volume (group I, 0.25 +/- 0.68 mm(3); group II, 0.40 +/- 0.68 mm(3); and group III, 0.75 +/- 1.34 mm(3); p = 0.007) were smallest in group I. The plaque intrusion area and plaque intrusion volume correlated with the ratio of the stent diameter to the average intravascular ultrasound reference lumen diameter (r = 0.278, p <0.001 and r = 0.283, p <0.001, respectively). The incidence of a creatine kinase-MB elevation >3 times normal was 6% in group I, 9% in group II, and 19% in group III (p = 0.025). No significant differences were found in the incidence of 1-year target lesion revascularization (group I, 13%; group II, 9%; and group III, 15%; p = 0.5) or target vessel revascularization (group I, 13%; group II, 13%; and group III, 15%; p = 0.9) among the 3 groups. In conclusion, the use of undersized drug-eluting stents to treat patients with saphenous vein graft lesions is associated with a reduction in the frequency of post-percutaneous coronary intervention creatine kinase-MB elevation without an increase in 1-year events.

Timing of clopidogrel loading before percutaneous coronary intervention in clopidogrel-naive patients with stable or unstable angina: A comparison of two strategies

Clopidogrel-naive patients subjected to coronary angiography may be candidates for percutaneous coronary intervention (PCI). Clopidogrel loading with 600 mg at least 2 hours before the procedure is advised for such patients. However, there is no direct evidence that delaying PCI for 2 hours after clopidogrel loading is superior to ad hoc PCI. After coronary angiography, clopidogrel-naive patients (N = 199) with stable or unstable angina, candidates for PCI, were loaded with 900 mg of clopidogrel and then randomized to ad hoc PCI (ad hoc group, n = 103) or delayed PCI 2 hours after loading (delayed group, n = 96). Combined primary end point was death/periprocedural myocardial infarction (MI)/stroke/reintervention within 30 days post-PCI. Secondary end points were periprocedural MI; periprocedural creatine kinase-MB elevation >3 x upper limit of normal; any periprocedural increase of creatine kinase-MB, troponin-I, or myoglobin above upper limit of normal; Thrombolysis in Myocardial Infarction flow <3 after PCI; thrombocytopenia with platelet count of <70,000/mL; major bleeding defined according to the Thrombolysis in Myocardial Infarction criteria; and elevation of high-sensitivity C-reactive protein and soluble P selectin. Primary end point occurred in 12.6% ad hoc group versus 15.6% delayed group patients (P = .34). High-sensitivity C-reactive protein increased in both groups post-PCI (analysis of variance P < .0001) without difference between groups (P = .5). Major bleeding occurred in 2.9% ad hoc group versus 3.1% delayed group patients (P = .9). No significant difference was observed in any other secondary end point. In clopidogrel-naive patients, a strategy of delaying PCI for 2 hours after high-dose clopidogrel loading does not seem to confer any benefit compared to ad hoc PCI.

TCT-90: What is the Optimal Threshold for Defining a Periprocedural Myocardial Infarction? Prognostic Implications Of Creatine Kinase-MB Elevation After Percutaneous Coronary Intervention

TCT-90: What is the Optimal Threshold for Defining a Periprocedural Myocardial Infarction? Prognostic Implications Of Creatine Kinase-MB Elevation After Percutaneous Coronary Intervention

Identifying and classifying myocardial infarctions

In this issue of the Journal , Drs. Shaun Senter and Gary Francis discuss the power of electrocardiographic changes and creatine kinase-MB and troponin elevations in diagnosing acute myocardial infarction. These are not perfect tests.

Post-procedural Troponin T and Creatine kinase-MB elevations influence late outcomes predominantly in patients with stable coronary heart disease

Results:Patientswith PPRFhad a lower ejection fraction (43.2% vs. 52.6%), were more likely to have STEMI as the indication for the PCI (56.0% vs. 18.3%), and cardiogenic shock (29.8% vs. 3.7%) (all p< 0.0001). Baseline creatinine was comparable (156mmol/L vs. 178mmol/L, p= 0.31). The presence of multivessel disease (66.5%) and peripheral vascular disease (PVD; 16.4%) was similar in both groups. Thirty-day mortality (33.9% vs. 4.6%, p< 0.0001), stroke (4.6% vs. 0%, p= 0.02), and overall MACE (39.4% vs. 6.4%, p< 0.0001) were higher in patients with PPRF. Twelve-monthmortality (45.0%vs. 8.3%, p< 0.0001), stroke (5.5% vs. 0%, p= 0.01), and overall MACE (55.0% vs. 19.3%, p< 0.0001) were also higher in patients with PPRF. Multivariate adverse predictors of MACE were cardiogenic shock (4.7; CI 1.7–13.0; p= 0.003), PPRF (OR 3.4; 95% CI 1.6–7.3; p= 0.002), and PVD (3.3; 1.2–9.0; p= 0.02). Conclusion:Development of post-procedural renal failure following PCI portends a poor prognosis. Whether prevention of renal failurewill improve outcomes can only be determined by randomised trials. doi:10.1016/j.hlc.2009.05.555

Biomarker Release After Percutaneous Coronary Intervention

Cardiac biomarkers of necrosis provide clinicians with important “messages” from the heart. They are released into the interstitium of the myocardium after loss of the integrity of cardiac myocyte membranes. The pattern of the rise and fall of an individual biomarker (ie, its release kinetics) depends on its intracellular location in the myocyte, molecular weight, and clearance from the interstitium of the myocardium and ultimately the circulation.1 Cardiac biomarkers play an integral role in the clinical diagnosis of myocardial infarction (MI). Referring to the spontaneous occurrence of MI in patients, the World Health Organization required that at least 2 of the following be present to fulfill the criteria for MI: a history of ischemia-type chest discomfort, evolutionary changes on serially obtained ECG tracings, and a rise and fall in serum cardiac markers.2 Article see p 10 See Editorial Circulation . 2008;118:609–611 See Article Circulation . 2008;118:632–638 Several dramatic advances have occurred in the biomarker component of the diagnosis of MI. Analytes with greater specificity for the myocardium were introduced into clinical medicine, with creatine kinase-MB replacing total creatine kinase and subsequently cardiac-specific troponins replacing creatine kinase-MB as the biomarker of choice for diagnosing MI.3 Assay technology improved as clinical chemists moved from enzymatic activity assays for CK to highly specific immunoassays that can detect progressively smaller concentrations of cardiac troponins in the peripheral circulation.4 Although ST-elevation MI (STEMI) is easily identified on the 12-lead ECG, we now recognize that many patients previously diagnosed with unstable angina are more properly diagnosed as having non–ST-elevation MI (NSTEMI) on the basis of the detection of elevated levels of cardiac troponins in their blood.5 Cardiac biomarkers are used as a rough guide to the extent of myocardial necrosis. The higher the peak biomarker level after STEMI, the larger the …

The effect of mannitol on oxygenation and creatine kinase MB release in patients undergoing multivessel off-pump coronary artery bypass surgery

Despite avoiding cardiopulmonary bypass, off-pump coronary artery bypass surgery is associated with reduction in PaO2 and postoperative respiratory compliance. Also, transient interruption of coronary flow is necessary during distal anastomoses and may impose ischemia-reperfusion myocardial injury. Mannitol is an osmotic diuretic with free radical scavenging properties, and we have evaluated the effects of mannitol on oxygenation and cardiac enzyme release in patients undergoing multivessel off-pump bypass surgery in a prospective, randomized, controlled, double-blind trial. Fifty patients were randomly allocated to receive either 20% mannitol 0.5 g/kg (n = 25) or normal saline 2.5 mL/kg (n = 25) during Y-graft construction. Pulmonary variables and serum sodium concentrations were measured 15 minutes after induction of anesthesia and sternum closure. Creatine kinase MB was measured before and after the operation. Intraoperative and postoperative fluid input and output, time to extubation, and intraoperative hemodynamic variables were also recorded. PaO2 after sternum closure was significantly higher in the mannitol group, with faster time to extubation and shorter length of stay in the intensive care unit. Intraoperative urine output was significantly greater in the mannitol group, without significant differences in fluid input, serum sodium concentration, and hemodynamic variables. Number of patients with a creatine kinase MB level more than 3 times the upper limit of normal was significantly higher in the control group. Mannitol could be safely used without adverse side effects in patients undergoing multivessel off-pump bypass surgery with beneficial effects in terms of preserving oxygenation, earlier extubation, and fewer patients with significant creatine kinase MB elevation.

Creatine kinase-MB elevation after coronary artery bypass grafting surgery in patients with non-ST-segment elevation acute coronary syndromes predict worse outcomes: results from four large clinical trials

To assess the significance of creatine kinase (CK)-MB elevations in outcomes of patients with non-ST-segment elevation acute coronary syndromes (NSTE ACS) who have undergone coronary artery bypass grafting (CABG) surgery. This analysis includes data from 26 465 patients with NSTE ACS enrolled in four major trials. In total, 4626 (17.5%) of patients had CABG within 30 days. Patients were excluded if CK-MB was elevated within 24 h before surgery and there was no CK-MB measured after surgery. Overall, 4401 patients were included in these analyses. The incidence of mortality increased with peak CK-MB ratios of 0-1, >1-3, >3-5, >5-10, and>10x the upper limit of normal measured at the local lab (P<0.001 across categories): 1.1, 2.8, 2.4, 3.1, and 10.8% in hospital; 1.1, 3.0, 2.9, 3.5, and 10.2% at 30 days; and 1.6, 4.4, 4.7, 6.0, and 10.9% at 180 days. Multivariable predictors of 6-month mortality included age, heart rate and randomization, peak CK-MB ratio, time to CABG, prior angina, signs of congestive heart failure and randomization, three- and two-vessel coronary disease, enrolment infarction, ST-segment depression at enrolment, female sex, experimental treatment, and systolic blood pressure. CK-MB elevations after CABG are independently associated with increased risk of mortality in patients with NSTE ACS.

Isolated cTnT Elevation After PCI

A large creatine kinase-MB (CK-MB) elevation after percutaneous coronary intervention (PCI) predicts a reduced chance of survival. Now, researchers

Frequency and Severity of Plaque Prolapse Within Cypher and Taxus Stents as Determined by Sequential Intravascular Ultrasound Analysis

We used intravascular ultrasound to evaluate the incidence, characteristics, and clinical sequel of plaque prolapse within drug-eluting stents. The influence of stent design on plaque prolapse has not been studied. Drug-eluting stents were serially expanded, first at 14 atm and then at 20 atm, with intravascular ultrasound imaging after each inflation. The stent, lumen, and maximum plaque prolapse areas were measured. The residual lumen area and percentage of plaque prolapse burden (maximum plaque prolapse area/stent area) were calculated. Plaque prolapse was divided into grades 1 (<5%), 2 (5% to 10%), and 3 (10% to 20%). Eighty patients (83 lesions, 41 Cypher and 42 Taxus Express stents) were studied. The incidence of plaque prolapse was 41% (17 of 41 lesions) with the Cypher stents versus 24% (10 of 41 lesions) with the Taxus stents after 14 atm (p = 0.096) and 35% (14 of 40) in Cypher stents versus 17.8% (5 of 28) in Taxus stents after 20 atm (p = 0.17). However, the maximum plaque prolapse area was never >20% of the stent area. The frequency and amount of plaque prolapse neither increased nor decreased at higher (20 atm) inflation pressures. Lesions with prolapse were longer (p = 0.004), with a larger external elastic membrane area and greater plaque burden (each p <0.0001) and a larger remodeling index (p = 0.013). Conversely, nonprolapsed plaques had a higher incidence of superficial calcium (p = 0.001). Creatinine kinase-MB elevation was higher with plaque prolapse, and the magnitude of creatinine kinase-MB elevation correlated with the extent of plaque prolapse (r = 0.664, p = 0.002). Multiple logistic regression analysis indicated that a longer lesion length (p = 0.012), and smaller minimal luminal area (p = 0.031) had higher risks of plaque prolapse. In conclusion, plaque prolapse was frequently observed in Cypher and Taxus stents. However, sequential intravascular ultrasound imaging showed that the frequency and amount of plaque prolapse were neither increased nor decreased by additional higher pressure inflations.

Below Radar

Below Radar

Protective role of chronic statin therapy in reducing myocardial damage during percutaneous coronary intervention

Percutaneous coronary intervention (PCI) is frequently associated with troponin I (TnI) elevation. Experimental studies suggest that statins may reduce ischaemia-reperfusion myocardial injury. The study objective was to verify whether chronic treatment with statins might reduce the occurrence and the extent of periprocedural myocardial damage in patients undergoing PCI. Five hundred and fifty-two consecutive patients undergoing PCI were included: 279 were not on statins before PCI, 273 were on statins. TnI levels >or= 0.3 ng/ml were considered indicative of myocardial injury. Statin-treated patients had a higher prevalence of hyperlipidaemia, previous myocardial infarction, and revascularization procedures. Coronary angiography also documented a higher prevalence of multivessel disease. No difference between the two groups was observed regarding the PCI-treated vessel, type of lesions, use of stents and of anti-IIb/IIIa inhibitors. Patients on statins showed the lowest incidence of TnI >or= 0.3 ng/ml (29 vs. 48%, P = 0.00001) and of creatine kinase-MB elevation (7 vs. 12%, P = 0.04). The mean peak TnI levels were significantly lower in patients on statins (1.07 +/- 3.8 vs. 2.73 +/- 12.3, P = 0.00006). Multivariate analysis identified preprocedural statin therapy as the only independent negative predictor of postprocedural abnormal TnI levels (odds ratio = 0.52; 95% confidence intervals 0.34-0.79; P = 0.003). This study shows that chronic therapy with statins reduces the incidence of periprocedural myocardial damage after PCI. The beneficial effect of statins was independent of either the most important clinical and angiographic characteristics or the use of other cardiovascular drugs including beta-blockers. These data support the specific cardioprotective role of statins.

Left Main Coronary Revascularization at the Crossroads

Percutaneous revascularization of left main coronary artery (LMCA) disease has remained controversial for more than 25 years, since LMCA balloon angioplasty was first performed by Andreas Gruentzig in 1978. Summarizing his experience, Gruentzig concluded, “We have not been too successful with dilating left main stems…although the procedure is relatively simple, the potential complications are both sudden and serious.”1 Following the evolution of percutaneous catheter-based therapies to include both bare metal stent and, more recently, drug-eluting stent (DES) platforms in conjunction with advances in periprocedural and postprocedural adjunctive pharmacotherapies, interest in percutaneous LMCA revascularization, particularly unprotected left main, has been renewed. Although studies performed with bare metal stents demonstrated a low rate of in-hospital mortality, the incidence of late coronary restenosis remained high.2–6 In the Unprotected Left Main Trunk Intervention Multi-Center Assessment (ULTIMA) registry, which enrolled 279 patients with unprotected LMCA disease who had percutaneous coronary revascularization (69% bare metal stent), mortality at a 1-year follow-up was proportional to clinical risk stratification (40% in high-risk versus 3.5% in low-risk patient cohorts), and repeated revascularization was required in 34% of cases.6 The experience gleaned from these studies continued to support the American College of Cardiology/American Heart Association (ACC/AHA) guideline recommendations that in reasonable surgical candidates with LMCA disease, coronary bypass surgery is the preferred therapeutic option.7 After the introduction of DES, several small clinical series demonstrated the feasibility and short-term safety of LMCA stenting, while late clinical/angiographic outcomes appeared favorable as compared with historical (nonrandomized) patient cohorts treated with bare metal stents.3,8–11 The cumulative experience with DES treatment for LMCA demonstrated an apparent marked reduction in major adverse cardiovascular events, including target vessel revascularization, during 6 to 12 months of follow-up as compared with the precedent experience after bare metal stent deployment. Article p 2542 The clinical …

Angiographic Adverse Events, Creatine Kinase-MB Elevation, and Ischemic End Points Complicating Percutaneous Coronary Intervention (a REPLACE-2 Substudy)

Several angiographic adverse events during coronary balloon angioplasty have been associated with increased creatine kinase-MB (CK-MB) enzymes and adverse clinical outcomes. The significance of angiographic adverse events in the stent era has not been widely studied. We analyzed 10 types of angiographic adverse events that were reported in the 6,010-patient Second Randomized Evaluation in PCI Linking Angiomax to Reduced Clinical Events (REPLACE-2) trial to determine their relation to CK-MB elevation and clinical ischemic end points after percutaneous coronary intervention (PCI). Angiographic adverse events occurred in 9.1% of REPLACE-2 patients. Most (8 of 10) types of angiographic adverse events were associated with an increased risk of increased CK-MB (p <0.001 for each), and 47% of all patients with an angiographic adverse event developed increased CK-MB. Logistic regression analysis showed that the strongest predictor of death, myocardial infarction, or revascularization at 6 months was the occurrence of an angiographic adverse event during PCI (odds ratio 1.9, 95% confidence interval 1.6 to 2.4, p <0.001). Side branch closure, abrupt closure, any decreased flow during the procedure, angiographic distal embolization, and perforation or tamponade were individual predictors of the occurrence of the combined clinical ischemic end point at 6-month follow-up (p <0.005 for each). In conclusion, most angiographic adverse events during PCI are associated with increased CK-MB and are powerful predictors of adverse clinical events within 6 months.

Aspirin and Clopidogrel Drug Response in Patients Undergoing Percutaneous Coronary Intervention: The Role of Dual Drug Resistance

Aspirin and Clopidogrel Drug Response in Patients Undergoing Percutaneous Coronary Intervention: The Role of Dual Drug Resistance Eli I. Lev, Rajnikant T. Patel, Kelly J. Maresh, Sasidhar Guthikonda, Juan Granada, Timothy DeLao, Paul F. Bray, Neal S. Kleiman We evaluated the response to clopidogrel among aspirin-resistant versus aspirin-sensitive patients undergoing elective coronary stenting. Patients (n = 150) treated with aspirin but not clopidogrel had blood samples drawn at baseline and 24 h after clopidogrel loading. Depending on the definition used, 9% to 15% were resistant to aspirin and 24% to clopidogrel. About half of the aspirin-resistant patients were also resistant to clopidogrel. As a group, aspirin-resistant patients had lower response to clopidogrel (assessed by platelet aggregation and activation markers) than aspirin-sensitive patients. Both aspirin- and clopidogrel-resistant patients had higher incidence of creatine kinase-MB elevation than the respective sensitive patients. We sought to evaluate the response to clopidogrel among aspirin-resistant versus aspirin-sensitive patients undergoing percutaneous coronary intervention (PCI). Wide variability has been reported in response to aspirin and clopidogrel. There are limited data on the simultaneous responses to both drugs. Elective PCI patients (n = 150) who received aspirin for ≥1 week but not clopidogrel were included. All patients received bivalirudin during PCI. Blood samples were drawn at baseline and 20 to 24 h after a 300-mg clopidogrel dose. Aspirin resistance was defined by ≥2 of 3 criteria: rapid platelet function analyzer-ASA score ≥550, 5 μmol/l adenosine diphosphate (ADP)-induced aggregation ≥70%, and 0.5 mg/ml arachidonic acid-induced aggregation ≥20%. Clopidogrel resistance was defined as baseline minus post-treatment aggregation ≤10% in response to 5 and 20 μmol/l ADP. Nineteen (12.7%) patients were resistant to aspirin and 36 (24%) to clopidogrel. Nine (47.4%) of the aspirin-resistant patients were also clopidogrel resistant. Aspirin-resistant patients were more likely to be women and have diabetes than were aspirin-sensitive patients. They also had lower response to clopidogrel, assessed by platelet aggregation and activation markers (flow cytometry-determined PAC-1 binding and P-selectin expression). Elevation of creatine kinase-myocardial band after stenting occurred more frequently in aspirin-resistant versus aspirin-sensitive patients (38.9% vs. 18.3%; p = 0.04) and in clopidogrel-resistant versus clopidogrel-sensitive patients (32.4% vs. 17.3%; p = 0.06). Aspirin-resistant patients as a group have reduced response to clopidogrel. Furthermore, we have identified a unique group of dual drug-resistant patients who may be at increased risk for thrombotic complications after PCI.

Plasma interleukin-18 concentration: a novel marker of myocardial ischemia rather than necrosis in humans

Myocardial ischemia contributes to cytokine expression in the myocardium in animals; therefore, plasma interleukin-18 concentration may be a good marker of myocardial ischemia/injury in patients with possible acute coronary syndrome. We sought to determine whether increases in plasma interleukin-18 concentrations might be indicative of myocardial ischemia in patients with acute coronary syndrome. Plasma interleukin-18 concentrations were assessed in 27 acute coronary syndrome patients in whom creatine kinase activity was within normal range on admission, in addition to 10 controls. Myocardial infarction was retrospectively evidenced in 15 of the 27 patients. All patients with acute coronary syndrome were treated by emergent coronary interventions just after admission. Blood sampling was done immediately after admission to determine plasma IL-18 concentration and biochemical markers of myocardial infarction. An increase in plasma interleukin-18 concentration was observed in acute coronary syndrome patients on admission, regardless of the retrospective evidence of myocardial necrosis. Plasma interleukin-18 elevation preceded creatine kinase-MB elevation in myocardial infarction patients. Plasma interleukin-18 concentrations on admission did not correlate with peak creatine kinase-MB (r=0.38, P=n.s.) or with left ventricular ejection fraction (r=-0.14, P=n.s.). Plasma interleukin-18 concentration elevates quickly after severe myocardial ischemic event regardless of evolving myocardial necrosis. Thus, plasma interleukin-18 concentration may be a good and early marker to identify whether the symptom is due to myocardial ischemia, and therefore, may be used in deciding the therapeutic strategy in individual patients with possible acute coronary syndrome.