High Loading Dose Of Clopidogrel Research Articles

Platelet reactivity following high loading doses of clopidogrel in patients undergoing primary percutaneous coronary angioplasty: A pilot study: The CArdiovascular Percutaneous Intervention TriAL Group (CAPITAL) LOAD Study

BackgroundRapid inhibition of platelet function is critical in patients referred for primary percutaneous coronary intervention (PCI) to prevent stent thrombosis. We sought to determine the antiplatelet effects of two clopidogrel high loading dose (LD) strategies on platelet reactivity in patients presenting with ST-elevation myocardial infarction (STEMI). MethodsPatients referred for primary PCI were randomly assigned to one of two clopidogrel LDs initiated before catheterization: 600mg vs. 600/600mg (second dose 3h after first LD). Platelet function testing was performed at baseline, and at 1, 2, 4, 6, 24, and 48h after the initial LD using the VerifyNow device. The primary endpoint was the proportion of patients with high platelet reactivity (HPR) at 24h defined as a P2Y12 reaction unit (PRU) measurement >208. ResultsFifty-four patients were assigned to clopidogrel as a single 600mg LD (n=27) or as a 600/600mg double LD (n=27). The proportion of patients with HPR at 24h was recorded in 44.0% assigned to the 600mg LD and 24.0% of patients assigned to 600/600mg LD, p=0.23. The mean PRU at 24h was 191±102 in the 600mg group and 152±94 in the 600/600mg group, p=0.16. There was no difference at all time points in HPR, and in mean PRUs between the LD regimens. ConclusionsHigh platelet reactivity persisted at 24h in a significant proportion of patients referred for primary PCI regardless of two clopidogrel high LD strategies. These results may have implications regarding the risk of early stent thrombosis in STEMI patients treated with clopidogrel.

Association between peak neutrophil count, clopidogrel loading dose, and left ventricular systolic function in patients with primary percutaneous coronary intervention.

Inflammation plays an important role in plaque development and left ventricular remodeling during acute myocardial infarction (AMI). Clopidogrel may exhibit some anti-inflammatory properties and high loading dose of clopidogrel results in improved clinical outcomes in patients with AMI. 357 patients who received successful primary percutaneous coronary intervention from January 2008 to March 2011 in Peking University Third Hospital were included in this study. Different loading dose of clopidogrel (300 mg, 450 mg, or 600 mg) was given at the discretion of the clinician. Neutrophils reached their peak values on the first day after AMI. Higher levels of peak neutrophil and lower left ventricular ejection fraction (LVEF) were found in patients of low clopidogrel loading dose group (300 mg or 450 mg). After adjusting for the related confounders, a logistic regression model showed that low clopidogrel loading dose remained an independent predictor of low LVEF (LVEF ≤ 50%) [OR: 1.97, 95% CI: 1.03–3.79, P = 0.04]. Low clopidogrel loading dose was associated with higher peak neutrophil count and poor left ventricular systolic function, suggesting an important role of clopidogrel loading dose in the improvement of left ventricular function and high loading dose may exhibit better anti-inflammatory properties.

GW24-e1357 Short-term outcomes of high loading dose clopidogrel pretreatment before emergent percutaneous coronary intervention in patients with acute myocardial infarction

ObjectivesTo compare the short-term efficiency and safety of high loading dose (600 mg) clopidogrel pretreatment with that of routine loading dose (300 mg) before emergent percutaneous coronary intervention (PCI) in...

Abciximab bolus with optional infusion in intervention for ST-elevation myocardial infarction

Objectives. The standard abciximab regimen is a bolus dose followed by a 12-h infusion. Whether the bolus dose alone is sufficient for ST-elevation myocardial infarction patients receiving a high loading dose of clopidogrel is unknown. Design. In an observational study, 693 consecutive patients were treated with abciximab during percutaneous coronary intervention for ST-elevation myocardial infarction. Totally 354 patients received standard strategy of abciximab bolus and infusion followed by 339 patients that recieved abciximab bolus only (271 patients) or bolus and infusion if suboptimal result (68 patients) in combination with a higher loading dose of clopidogrel (600 mg) – the modified strategy. Results. The two groups were similar regarding baseline characteristics and in hospital bleeding events. At 30 days, the composite of death, re-infarction or target vessel revascularization was 9.1% in the standard and 7.5% in the modified strategy (p = 0.45). The rate of stent thrombosis was lower in the modified strategy group with 0% and 2.3% in the standard group (p < 0.001) and the mean total medical cost was lower in the modified strategy group with €8032 and €8665 in the standard group (p < 0.001). Conclusions. In primary percutaneous coronary intervention with a loading dose of 600 mg clopidogrel, it seems safe and cost-saving to give abciximab bolus with optional infusion.

Relation between the vasodilator-stimulated phosphoprotein phosphorylation assay and light transmittance aggregometry in East Asian patients after high-dose clopidogrel loading

We analyzed the relation between platelet aggregation measured by light transmittance aggregometry (LTA) and platelet reactivity index (PRI) measured by vasodilator-stimulated phosphoprotein phosphorylation (VASP-P) assay. It has been suggested that LTA and VASP-P assay correlate differently according to the level of P2Y12 receptor blockade by thienopyridines. We simultaneously measured platelet function by LTA and VASP-P assay in 466 East Asians undergoing elective percutaneous coronary intervention after a 600-mg clopidogrel loading. High on-clopidogrel platelet reactivity (HPR) was defined by published consensus criteria. The degree of correlation between LTA and the VASP-P assay was different according to PRI levels. The correlation was lower in patients with poor responsiveness (PRI >60%) (n = 216) (0.035 ≤ r(2) ≤ 0.047), which was greater in responsive patients (PRI ≤60%) (n = 250) (0.315 ≤ r(2) ≤ 0.526). Despite a 600-mg loading, East Asians had a high prevalence of HPR (40.1%-63.5%), and the prevalence of HPR also differed between LTA and VASP-P assay. A PRI cutoff of >58% (area under curve, 0.829; 95% confidence intervals, 0.792-0.862; P < .001) corresponded to the published HPR cutoff by 5-μM adenosine diphosphate-induced maximal platelet aggregation >46%. This is the largest study correlating platelet reactivity measured by LTA and VASP-P assay in a percutaneous coronary intervention-treated cohort. The correlation is dependent on the level of responsiveness. Future investigations are needed to better define the optimal cutoffs of HPR measured by LTA and VASP-P assay for personalized antiplatelet therapy.

Effects of High Loading Dose of Clopidogrel in ST Elevated Myocardial Infarction Treated with Fibrinolytic Agent

The purpose of the present study was to evaluate the effects of different loading doses of clopidogrel on ST segment resolution on ECG, changes in cardiac enzyme levels and serum levels of high-sensitivity C-reactive protein (Hs-CRP) in patients with ST elevated myocardial infarction (STEMI) treated with fibrinolytic therapy. Patients admitted to our cardiology clinic with a diagnosis of STEMI and treated with fibrinolytic therapy were included: Group 1 (n=58) received a 300 mg loading dose of clopidogrel, Group 2 (n=55) a 450 mg loading dose and Group 3 (n=59) a 600 mg loading dose. A 75 mg/d maintanence dose of clopidogrel was given in all groups. All demographic characteristics and baseline laboratory parameters were statistically similar among three groups (p > 0.05). When ST resolution periods were compared, most patients in Group 3 had ST resolution at 30 minutes; Group 2 at 60 minutes and Group 1 at 90 minutes (p < 0.05). Peak levels of creatine kinase (CK) and CK-MB were as follows: Group 3, 8(th) hour, Group 1 and 2, 12(th) hour. Peak levels of those enzymes were significantly lower in Group 3 than in Group 1 and 2 ( < 0.05). Although basal hs-CRP levels of all groups were similar, the increase in hs-CRP levels at 48 hours was lower with higher clopidogrel loading doses (p < 0.05). In this study comparing three different clopidogrel loading doses, the higher doses provided earlier ECG resolution, earlier and lower peak CK and CK-MB levels and lower levels of hs-CRP.

THE INFLUENCE OF HIGH FIRST DOSE AND STANDARD DOSE OF CLOPIDOGREL ON THE LEVELS OF SCD40L AND HS-CRP IN THE SERUM OF THE PATIENTS WITH ACS AFTER INTERVENTIONAL PROCEDURES

ObjectivesDiscuss the influence of High loading dose and standard dose of clopidogrel on serum sCD40L, hs-CRP levels in acute coronary syndrome patients after intervention operation and postoperative cardiovascular events for...

Impaired bioavailability and antiplatelet effect of high-dose clopidogrel in patients after cardiopulmonary resuscitation (CPR)

Bioavailability of clopidogrel in the form of crushed tablets administered via nasogastric tube (NGT) has not been established in patients after cardiopulmonary resuscitation. Therefore, we performed a study comparing pharmacokinetic and pharmacodynamic response to high loading dose of clopidogrel in critically ill patients after cardiopulmonary resuscitation (CPR) with patients scheduled for elective coronary angiography with stent implantation. In the NGT group (nine patients, after cardiopulmonary resuscitation, mechanically ventilated, therapeutic hypothermia), clopidogrel was administered in the form of crushed tablets via NGT. Ten patients undergoing elective coronary artery stenting took clopidogrel per os (po) in the form of intact tablets. Pharmacokinetics of clopidogrel was measured with high-performance liquid chromatography (HPLC) before and at 0.5, 1, 6, 12, 24 h after administration of a loading dose of 600 mg. In five patients in each group, antiplatelet effect was measured with thrombelastography (TEG; Platelet Mapping) before and 24 h after administration. The carboxylic acid metabolite of clopidogrel was detected in all patients in the po group. In eight patients, the maximum concentration was measured in the range of 0.5-1 h after the initial dose. In four patients in the of NGT group, the carboxylic acid metabolite of clopidogrel was undetectable and in the remaining patients was significantly delayed (peak values at 12 h). All patients in the po group reached clinically relevant (>50 %) inhibition of thrombocyte adenosine diphosphate (ADP) receptor after 24 h compared with only two in the NGT group (p = 0.012). There was a close correlation between peak of inactive clopidogrel metabolite plasmatic concentration and inhibition of the ADP receptor (r = 0.79; p < 0.001). The bioavailability of clopidogrel in critically ill patients after cardiopulmonary resuscitation is significantly impaired compared with stable patients. Therefore, other drugs, preferentially administered intravenously, should be considered.

A high loading dose of clopidogrel reduces myocardial infarct size in patients undergoing primary percutaneous coronary intervention: A magnetic resonance imaging study

We sought to determine whether a 600-mg loading dose of clopidogrel reduces myocardial infarct size compared with a 300-mg dose using contrast-enhanced magnetic resonance imaging in patients undergoing primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI). In 198 patients undergoing primary PCI for STEMI, contrast-enhanced magnetic resonance imaging was performed a median of 7 days after the index event. Infarct size was measured on delayed-enhancement imaging, and area at risk (AAR) was quantified on T2-weighted images. Baseline characteristics were not significantly different between the 600-mg clopidogrel loading group (n = 117) and the 300-mg group (n = 81). The median infarct size was significantly smaller in the 600-mg group than in the 300-mg group (17.3% [8.9%-26.2%] vs 21.7% [12.9%-30.0%], P = .03). Myocardial salvage index ([AAR - infarct size] × 100/AAR) was greater in the 600-mg group than in the 300-mg group (47.7 [33.7-60.9] vs 32.0 [23.6-51.5], P < .01). Patients in the 600-mg group also had a significantly lower extent of microvascular obstruction and smaller number of segments with >75% of infarct transmurality than did those in the 300-mg group. After propensity score matching, the 600-mg group had smaller infarct size and greater myocardial salvage index compared with the 300-mg group. In multivariate analysis, the use of a 600-mg clopidogrel loading dose significantly reduced the risk of a large infarct (odds ratio 0.53, 95% CI 0.29-0.98, P = .04). In patients undergoing primary PCI for STEMI, a 600-mg loading dose of clopidogrel reduced myocardial infarct size and improved myocardial salvage compared with a 300-mg loading dose.

Is a higher loading dose of clopidogrel more effective during primary angioplasty for patients with STEMI?

Evaluation of: Patti G, Barczi G, Orlic D et al. Outcome comparison of 600 and 300 mg loading doses of clopidogrel in patients undergoing primary percutaneous coronary intervention for ST-segment elevation myocardial infarction: Results from the ARMYDA-6 MI randomized study. J. Am. Coll. Cardiol. 58, 1592–1599 (2011). Primary angioplasty remains the mainstay of therapy for patients with ST-elevation myocardial infarction. Given the high prothrombotic state and large thrombotic burden in these patients, there is need for more rapid and potent platelet inhibition. To date, there have been several observational studies and one randomized trial supporting the notion that clopidogrel 600 mg compared with 300 mg improves outcomes. The ARMYDA-6 trial is the first randomized trial comparing clopidogrel 600 mg versus 300 mg specifically in a population with ST-elevation myocardial infarction. The authors found that a 600 mg loading dose of clopidogrel was associated with a significant reduction in the infarct size...

Efficacy and safety of a high loading dose of clopidogrel administered prehospitally to improve primary percutaneous coronary intervention in acute myocardial infarction: the randomized CIPAMI trial

To compare a loading dose of 600mg clopidogrel given in the prehospital phase versus clopidogrel administered only after the diagnostic angiogram in patients with STEMI scheduled for primary PCI. The optimal time and dose for the initiation of clopidogrel therapy in patients with STEMI scheduled for primary PCI has not been studied in prospective randomized trials. The primary efficacy endpoint was the TIMI 2/3 patency of the infarct-related artery in the diagnostic angiography immediately prior to PCI. We randomized 337 patients to prehospital (n=166) loading dose versus standard therapy (n=171). The time interval between initiation of clopidogrel therapy and diagnostic angiography was 47min. TIMI 2/3 patency before PCI was not different between the groups (49.3 vs. 45.1%, P=0.5). We observed a trend towards a reduction of the combined endpoint death, re-infarction, and urgent target vessel revascularization in the prehospital-treated patients (3.0 vs. 7.0%, P=0.09), this difference was significant if patients were classified as treated (4/161 vs. 13/174; 2.5 vs. 7.5%, P<0.05). There was no difference in TIMI major bleeding complications (9.1 vs. 8.2%, P=0.8). Early inhibition of the platelet ADP-receptor with a high loading dose of 600mg clopidogrel given in the prehospital phase in patients with STEMI scheduled for primary PCI is safe, did not increase pre-PCI patency of the infarct vessel, but was associated with a trend towards a reduction in clinical events.

AS-017 A High Loading Dose of Clopidogrel Reduces Myocardial Infarct Size in Patients Undergoing Primary Percutaneous Coronary Intervention: A Magnetic Resonance Imaging Study

AS-017 A High Loading Dose of Clopidogrel Reduces Myocardial Infarct Size in Patients Undergoing Primary Percutaneous Coronary Intervention: A Magnetic Resonance Imaging Study

Temporal trends and practice variations in clopidogrel loading doses in patients with non–ST-segment elevation myocardial infarction, from the National Cardiovascular Data Registry

A higher loading dose of clopidogrel achieves a more rapid and consistent degree of platelet inhibition than standard dosing, although the clinical benefit of higher doses has not been clearly established. The use of the different doses in clinical practice is not known. We evaluated the patient, procedural, and hospital characteristics associated clopidogrel loading doses given to patients with non-ST-segment elevation myocardial infarction (NSTEMI). The National Cardiovascular Data Registry ACTION Get With the Guidelines Registry was queried for patients with NSTEMI admitted from 2007 to 2008. Demographic, clinical, and procedural information were collected on standardized data forms. Patients were categorized according to the clopidogrel loading dose received. Temporal trends in the use of different doses were evaluated in quarterly time intervals. Between January 1, 2007, and December 31, 2008, the use of a 600-mg clopidogrel loading dose increased steadily from 36.4% to 45.5%, whereas the use of 300 mg decreased slightly from 40.1% to 37.1%. Patients loaded with clopidogrel before cardiac catheterization were more likely to receive 300 mg, whereas those receiving a loading dose at the time of catheterization more often received 600 mg. The temporal increase in the use of 600 mg clopidogrel loading doses was not explained by temporal changes in periprocedural loading, use of early invasive management of patients with NSTEMI, or use of antithrombotics or glycoprotein 2b/3a inhibitors. Higher loading dose clopidogrel increased between 2007 and 2008. Higher-dose clopidogrel was more frequently used in lower-risk patients undergoing an early invasive strategy and receiving periprocedural loading.

Standard versus high loading doses of clopidogrel in Asian ST-segment elevation myocardial infarction patients undergoing percutaneous coronary intervention: Insights from the Korea Acute Myocardial Infarction Registry

The optimal loading dose of clopidogrel in Asian patients with ST-segment elevation myocardial infarction (STEMI) has not been fully investigated. We compared bleeding, vascular complications, and midterm outcomes of a 300-mg versus a 600-mg loading dose of clopidogrel in a large series of Korean patients with STEMI undergoing primary percutaneous coronary intervention (PCI). A total of 2,664 STEMI patients (age 61.96 ± 11.91 years, men 70.4%) who underwent primary PCI were enrolled in this study. The patients were divided into a standard loading dose group (300 mg; n = 1,447 patients) and a high loading dose group (600 mg; n = 1,217 patients). Bleeding and vascular complications, and in-hospital and clinical outcomes up to 12 months were compared between the 2 groups. In-hospital bleeding and vascular complications were similar between the 2 groups. There were no differences in bleeding and vascular complications and in 1- and 12-month clinical outcomes, including mortality, myocardial infarction, repeated PCI, and major adverse cardiac events, between the 2 groups. These findings were consistent even after the propensity score-matched analysis. The standard loading dose of clopidogrel may be as safe and similarly effective as the high loading dose in Asian STEMI patients undergoing primary PCI.

Comparison of Adverse Cardiovascular Events and Bleeding Complications of Loading Dose of Clopidogrel 300 mg Versus 600 mg in Stable Patients Undergoing Elective Percutaneous Intervention (from the CADICE Study)

In large clinical trials enrolling patients with acute coronary syndromes, a high loading dose of clopidogrel (600 mg) has been found to be more effective compared to a low loading dose (300 mg). However, the applicability of these data to stable patients who undergo elective percutaneous coronary intervention is still unclear. A total of 400 patients who underwent elective PCI were prospectively randomized to receive either 600 mg (n = 200) or 300 mg (n = 200) of clopidogrel, followed by a daily maintenance dose of 75 mg. The primary end point was the presence of major adverse cardiovascular events (combined death, myocardial infarction, acute neurologic event, stent thrombosis, and need for percutaneous or surgical revascularization of the target vessel) during hospitalization and at 30 days. The secondary end point was periprocedural vascular complications, major bleeding, and cardiac enzyme elevation. There were no differences in the primary end point among the groups immediately after the procedure (3.5% of patients in the 300-mg group vs 4.5% of those in the 600-mg group, p = 0.799) or at 30 days (6% vs 5%, respectively, p = 0.826). The rates of periprocedural vascular complications (2.5% vs 3%, respectively, p = 1.00), bleeding complications (9% vs 8.5%, respectively, p = 1.00), and cardiac enzyme elevation (11% vs 15.5%, respectively, p = 0.317) were similar between the 2 groups. In conclusion, adverse cardiovascular events and bleeding complications during the initial hospitalization and at 30-day follow-up were similar when a 600-mg loading dose of clopidogrel was used compared to the conventional dose of 300 mg.

The safety of clopidogrel

Importance of the field: Clopidogrel is an antiplatelet prodrug widely used in acute coronary syndromes and after intravascular stent placement. Acute or chronic use can cause bleeding, a major adverse effect, which can lead to drug discontinuation or noncompliance with therapy.Areas covered in this review: The mechanism of action of clopidogrel, safety of different loading doses of clopidogrel, its use as a solitary antiplatelet agent and concomitant use with other antiplatelet agents such as aspirin and warfarin are discussed. Thrombotic thrombocytopenic purpura, a rare but important adverse event, has also been reviewed. Literature searches including randomized controlled trials were conducted in Medline.What the reader will gain: Clinicians will be able to understand the safety profile of using different doses of clopidogrel and the incidence of bleeding when used alone or in combination with other antiplatelet agents.Take home message: Compared to aspirin, clopidogrel when taken alone causes less severe bleeding and less intracranial hemorrhage. Higher loading dose of clopidogrel is associated with increased bleeding. When combined with other antiplatelet agents, risk of bleeding increases, but like any other drug, the risks have to be weighed against potential benefits.

Effectiveness of In-Laboratory High-Dose Clopidogrel Loading Versus Routine Pre-Load in Patients Undergoing Percutaneous Coronary Intervention: Results of the ARMYDA-5 PRELOAD (Antiplatelet therapy for Reduction of MYocardial Damage during Angioplasty) Randomized Trial

This study sought to evaluate safety and effectiveness of in-laboratory (in-lab) 600-mg clopidogrel loading pre-percutaneous coronary intervention (PCI) versus routine 6-h pre-load. Clopidogrel pre-treatment significantly improves outcome in patients undergoing PCI; however, efficacy of an in-lab loading strategy before PCI after coronary angiography versus routine pre-load has not been fully characterized. A total of 409 patients (39% with acute coronary syndrome) were randomized to receive a 600-mg clopidogrel loading dose 4 to 8 h before PCI (pre-load group, n = 204) or a 600-mg loading dose given in the catheterization lab after coronary angiography, but prior to PCI (in-lab group, n = 205). Primary end point was 30-day incidence of major adverse cardiac events: cardiac death, myocardial infarction (MI), or unplanned target vessel revascularization. There was no significant difference in primary end point between the 2 randomization arms (8.8% in-lab vs. 10.3% pre-load; p = 0.72); this was mainly driven by periprocedural MI (8.8% vs. 9.3%, p = 0.99). No increased risk of bleeding or vascular complications was observed in the pre-load arm (5.4% vs. 7.8%; p = 0.42). As determined by the VerifyNow assay (Accumetrics, San Diego, California), patients in the in-lab group showed higher platelet reactivity during PCI and 2 h after intervention versus those in the pre-load arm (p < or = 0.043). ARMYDA-5 PRELOAD (Antiplatelet therapy for Reduction of MYocardial Damage during Angioplasty) trial indicates that a strategy of 600-mg in-lab clopidogrel load pre-PCI may have similar clinical outcomes as routine 4- to 8-h pre-load. Thus, when indicated, in-lab clopidogrel administration can be a safe alternative to routine pre-treatment given before knowing patients' coronary anatomy.

AS-78: High-Dose Clopidogrel Loading Is Safe and Effective in Patients with ST-Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention

AS-78: High-Dose Clopidogrel Loading Is Safe and Effective in Patients with ST-Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention

Antiplatelet Therapy After Percutaneous Coronary Intervention

Current guidelines recommend dual antiplatelet therapy (DAPT) that includes aspirin and the platelet P2Y12 ADP receptor antagonist clopidogrel after percutaneous coronary intervention (PCI). These recommendations are based on data that DAPT with the P2Y12 inhibitors clopidogrel reduces major adverse cardiac events after PCI in stable angina and acute coronary syndrome (ACS) patients when compared with aspirin, or aspirin in combination with warfarin.1 Despite treatment with DAPT, patients with ACS undergoing PCI are at elevated risk for recurrent ischemic events compared with stable angina patients in part because of increased platelet thrombotic activity in ACS. In addition, there is considerable interindividual variability in the degree of platelet inhibition achieved by clopidogrel, and high residual platelet activity in the setting of clopidogrel therapy (hyporesponsiveness) is associated with adverse cardiovascular (CV) events after PCI. Clopidogrel hyporesponsiveness is related to a variety of clinical and genetic factors that alter pharmacokinetics, and diabetes, congestive heart failure (CHF), and obesity are associated with reduced efficacy. Clopidogrel is a prodrug that requires conversion by the hepatic cytochrome P450 system (CYP) to an active metabolite, and it can take up to 6 hours for clopidogrel to have maximal effect after the loading dose. Genetic polymorphisms that reduce CYP activity result in decreased hepatic metabolism of clopidogrel. Among persons treated with clopidogrel, carriers of specific reduced function CYP2C19 alleles have impaired clopidogrel conversion, significantly lower levels of active metabolite, diminished platelet inhibition, and higher rates of adverse CV events and stent thrombosis after PCI.2 The prevalence of CYP2C19 polymorphisms ranges from 30% to 60% depending on ethnicity.2,3 Medications that inhibit CYP activity also reduce clopidogrel conversion, and some proton pump inhibitors (PPI) that reduce CYP function (eg, omeprazole) diminish clopidogrel metabolite levels and efficacy measured by platelet function testing. The interaction between clopidogrel and …

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.