Michel R. Le May

A Citywide Protocol for Primary PCI in ST-Segment Elevation Myocardial Infarction

BACKGROUND If primary percutaneous coronary intervention (PCI) is performed promptly, the procedure is superior to fibrinolysis in restoring flow to the infarct-related artery in patients with ST-segment elevation myocardial infarction. The benchmark for a timely PCI intervention has become a door-to-balloon time of less than 90 minutes. Whether regional strategies can be developed to achieve this goal is uncertain. METHODS We developed an integrated-metropolitan-area approach in which all patients with ST-segment elevation myocardial infarction were referred to a specialized center for primary PCI. We sought to determine whether there was a difference in door-to-balloon times between patients who were referred directly from the field by paramedics trained in the interpretation of electrocardiograms and patients who were referred by emergency department physicians. RESULTS Between May 1, 2005, and April 30, 2006, a total of 344 consecutive patients with ST-segment elevation myocardial infarction were referred for primary PCI: 135 directly from the field and 209 from emergency departments. Primary PCI was performed in 93.6% of patients. The median door-to-balloon time was shorter in patients referred from the field (69 minutes; interquartile range, 43 to 87) than in patients needing interhospital transfer (123 minutes; interquartile range, 101 to 153; P<0.001). Door-to-balloon times of less than 90 minutes were achieved in 79.7% of patients who were transferred from the field and in 11.9% of those transferred from emergency departments (P<0.001). CONCLUSIONS Guideline door-to-balloon-times were more often achieved when trained paramedics independently triaged and transported patients directly to a designated primary PCI center than when patients were referred from emergency departments.

Point-of-care genetic testing for personalisation of antiplatelet treatment (RAPID GENE): a prospective, randomised, proof-of-concept trial

BACKGROUND Prospective assessment of pharmacogenetic strategies has been limited by an inability to undertake bedside genetic testing. The CYP2C19*2 allele is a common genetic variant associated with increased rates of major adverse events in individuals given clopidogrel after percutaneous coronary intervention (PCI). We used a novel point-of-care genetic test to identify carriers of the CYP2C19*2 allele and aimed to assess a pharmacogenetic approach to dual antiplatelet treatment after PCI. METHODS Between Aug 26, 2010, and July 7, 2011, 200 patients were enrolled into our prospective, randomised, proof-of-concept study. Patients undergoing PCI for acute coronary syndrome or stable angina were randomly assigned to rapid point-of-care genotyping or to standard treatment. Individuals in the rapid genotyping group were screened for the CYP2C19*2 allele. Carriers were given 10 mg prasugrel daily, and non-carriers and patients in the standard treatment group were given 75 mg clopidogrel daily. The primary endpoint was the proportion of CYP2C19*2 carriers with high on-treatment platelet reactivity (P2Y12 reactivity unit [PRU] value of more than 234) after 1 week of dual antiplatelet treatment, which is a marker associated with increased adverse cardiovascular events. Interventional cardiologists and data analysts were masked to genetic status and treatment. Patients were not masked to treatment allocation. All analyses were by intention to treat. This study is registered with ClinicalTrials.gov, NCT01184300. FINDINGS After randomisation, 187 patients completed follow-up (91 rapid genotyping group, 96 standard treatment). 23 individuals in each group carried at least one CYP2C19*2 allele. None of the 23 carriers in the rapid genotyping group had a PRU value of more than 234 at day 7, compared with seven (30%) given standard treatment (p=0·0092). The point-of-care genetic test had a sensitivity of 100% (95% CI 92·3-100) and a specificity of 99·3% (96·3-100). INTERPRETATION Point-of-care genetic testing after PCI can be done effectively at the bedside and treatment of identified CYP2C19*2 carriers with prasugrel can reduce high on-treatment platelet reactivity. FUNDING Spartan Biosciences.

Aspirin Plus Clopidogrel Versus Aspirin Alone After Coronary Artery Bypass Grafting The Clopidogrel After Surgery for Coronary Artery Disease (CASCADE) Trial

Background— Clopidogrel inhibits intimal hyperplasia in animal studies and therefore may reduce saphenous vein graft (SVG) intimal hyperplasia after coronary artery bypass grafting. The Clopidogrel After Surgery for Coronary Artery DiseasE (CASCADE) study was undertaken to evaluate whether the addition of clopidogrel to aspirin inhibits SVG disease after coronary artery bypass grafting, as assessed at 1 year by intravascular ultrasound. Methods and Results— In this double-blind phase II trial, 113 patients undergoing coronary artery bypass grafting with SVGs were randomized to receive aspirin 162 mg plus clopidogrel 75 mg daily or aspirin 162 mg plus placebo daily for 1 year. The primary outcome was SVG intimal hyperplasia (mean intimal area) as determined by intravascular ultrasound at 1 year. Secondary outcomes were graft patency, major adverse cardiovascular events, and major bleeding. One-year intravascular ultrasound and coronary angiography were performed in 92 patients (81.4%). At 1 year, SVG intimal area did not differ significantly between the 2 groups (4.1±2.0 versus 4.5±2.1 mm2, aspirin-clopidogrel versus aspirin-placebo, P=0.44). Overall 1-year graft patency was 95.2% in the aspirin-clopidogrel group compared with 95.5% in the aspirin-placebo group (P=0.90), and SVG patency was 94.3% in the aspirin-clopidogrel group versus 93.2% in the aspirin-placebo group (P=0.69). Freedom from major adverse cardiovascular events at 1 year was 92.9±3.4% in the aspirin-clopidogrel group and 91.1±3.8% in the aspirin-placebo group (P=0.76). The incidence of major bleeding at 1 year was similar for the 2 groups (1.8% versus 0%, aspirin-clopidogrel versus aspirin-placebo, P=0.50). Conclusions— Compared with aspirin monotherapy, the combination of aspirin plus clopidogrel did not significantly reduce the process of SVG intimal hyperplasia 1 year after coronary artery bypass grafting. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00228423.Background— Clopidogrel inhibits intimal hyperplasia in animal studies and therefore may reduce saphenous vein graft (SVG) intimal hyperplasia after coronary artery bypass grafting. The Clopidogrel After Surgery for Coronary Artery DiseasE (CASCADE) study was undertaken to evaluate whether the addition of clopidogrel to aspirin inhibits SVG disease after coronary artery bypass grafting, as assessed at 1 year by intravascular ultrasound. Methods and Results— In this double-blind phase II trial, 113 patients undergoing coronary artery bypass grafting with SVGs were randomized to receive aspirin 162 mg plus clopidogrel 75 mg daily or aspirin 162 mg plus placebo daily for 1 year. The primary outcome was SVG intimal hyperplasia (mean intimal area) as determined by intravascular ultrasound at 1 year. Secondary outcomes were graft patency, major adverse cardiovascular events, and major bleeding. One-year intravascular ultrasound and coronary angiography were performed in 92 patients (81.4%). At 1 year, SVG intimal area did not differ significantly between the 2 groups (4.1±2.0 versus 4.5±2.1 mm2, aspirin-clopidogrel versus aspirin-placebo, P =0.44). Overall 1-year graft patency was 95.2% in the aspirin-clopidogrel group compared with 95.5% in the aspirin-placebo group ( P =0.90), and SVG patency was 94.3% in the aspirin-clopidogrel group versus 93.2% in the aspirin-placebo group ( P =0.69). Freedom from major adverse cardiovascular events at 1 year was 92.9±3.4% in the aspirin-clopidogrel group and 91.1±3.8% in the aspirin-placebo group ( P =0.76). The incidence of major bleeding at 1 year was similar for the 2 groups (1.8% versus 0%, aspirin-clopidogrel versus aspirin-placebo, P =0.50). Conclusions— Compared with aspirin monotherapy, the combination of aspirin plus clopidogrel did not significantly reduce the process of SVG intimal hyperplasia 1 year after coronary artery bypass grafting. Clinical Trial Registration— URL: . Unique identifier: [NCT00228423][1]. # Clinical Perspective {#article-title-35} [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00228423&atom=%2Fcirculationaha%2F122%2F25%2F2680.atom

Stenting versus thrombolysis in acute myocardial infarction trial (STAT)

OBJECTIVES We sought to directly compare primary stenting with accelerated tissue plasminogen activator (t-PA) in patients presenting with acute ST-elevation myocardial infarction (AMI). BACKGROUND Thrombolysis remains the standard therapy for AMI. However, at some institutions primary angioplasty is favored. Randomized trials have shown that primary angioplasty is equal or superior to thrombolysis, while recent studies demonstrate that stent implantation improves the results of primary angioplasty. METHODS Patients presenting with AMI were randomly assigned to primary stenting (n = 62) or accelerated t-PA (n = 61). The primary end point was the composite of death, reinfarction, stroke or repeat target vessel revascularization (TVR) for ischemia at six months. RESULTS The primary end point was significantly reduced in the stent group compared with the accelerated t-PA group, 24.2% versus 55.7% (p < 0.001). The event rates for other outcomes in the stent group versus the t-PA group were as follows: mortality: 4.8% versus 3.3% (p = 1.00); reinfarction: 6.5% versus 16.4% (p = 0.096); stroke: 1.6% versus 4.9% (p = 0.36); recurrent unstable ischemia: 9.7% versus 26.2% (p = 0.03) and repeat TVR for ischemia: 14.5% versus 49.2% (p < 0.001). The median length of the initial hospitalization was four days in the stent group and seven days in the t-PA group (p < 0.001). CONCLUSIONS Compared with accelerated t-PA, primary stenting reduces death, reinfarction, stroke or repeat TVR for ischemia. In centers where facilities and experienced interventionists are available, primary stenting offers an attractive alternative to thrombolysis.

Usefulness of mean platelet volume as a biomarker for long-term outcomes after percutaneous coronary intervention.

Larger size platelets have enhanced reactivity. The mean platelet volume (MPV) is a marker of platelet activation and is usually measured as part of blood testing. The aim of the present study was to investigate the utility of the MPV as a biomarker in prognosticating the long-term outcomes after percutaneous coronary intervention (PCI). The baseline MPV values from consecutive patients undergoing PCI were screened. Of the 1,432 patients, the composite primary end point of mortality or myocardial infarction at 1 year occurred in 80 (5.6%). The patients in the highest tertile (MPV >9.1 fL) had an increased frequency of the primary end point compared to those in the mid (8.1 to 9.1 fL) and lowest (<8.1 fL) tertiles (9.0%, 4.5%, and 3.5%, respectively; p <0.01). Logistic regression analysis demonstrated diabetes (odds ratio 2.44, 95% confidence interval 1.48 to 4.00) and highest tertile of MPV (odds ratio 2.42, 95% confidence interval 1.47 to 3.99) as the best predictors of adverse outcomes. In patients with acute coronary syndrome, the preprocedural MPV and troponin levels demonstrated a comparable predictive relation to the primary end point (receiver operator characteristics curve analysis, area under the curve 0.64, p = 0.01; and 0.63, p = 0.01, respectively). In conclusion, an elevated MPV was a strong independent predictor of long-term outcomes after PCI. The preprocedural MPV had prognostic value similar to that of troponin in patients with acute coronary syndrome. These findings could be of importance in the clinical evaluation of patients before PCI and the design of future studies assessing antiplatelet therapies.

Reduction in Mortality as a Result of Direct Transport From the Field to a Receiving Center for Primary Percutaneous Coronary Intervention

OBJECTIVES This study sought to determine whether mortality complicating ST-segment elevation myocardial infarction (STEMI) was impacted by the design of transport systems. BACKGROUND It is recommended that regions develop systems to facilitate rapid transfer of STEMI patients to centers equipped to perform primary percutaneous coronary intervention (PCI), yet the impact on mortality from the design of such systems remains unknown. METHODS Within the framework of a citywide system where all STEMI patients are referred for primary PCI, we compared patients referred directly from the field to a PCI center to patients transported beforehand from the field to a non-PCI-capable hospital. The primary outcome was all-cause mortality at 180 days. RESULTS A total of 1,389 consecutive patients with STEMI were assessed by the emergency medical services (EMS) and referred for primary PCI: 822 (59.2%) were referred directly from the field to a PCI center, and 567 (40.8%) were transported to a non-PCI-capable hospital first. Death at 180 days occurred in 5.0% of patients transferred directly from the field, and in 11.5% of patients transported from the field to a non-PCI-capable hospital (p < 0.0001. After adjusting for baseline characteristics in a multivariable logistic regression model, mortality remained lower among patients referred directly from the field to the PCI center (odds ratio: 0.52, 95% confidence interval: 0.31 to 0.88, p = 0.01). Similar results were obtained by using propensity score methods for adjustment. CONCLUSIONS A STEMI system allowing EMS to transport patients directly to a primary PCI center was associated with a significant reduction in mortality. Our results support the concept of STEMI systems that include pre-hospital referral by EMS.

Statin Therapy and Saphenous Vein Graft Disease After Coronary Bypass Surgery: Analysis From the CASCADE Randomized Trial

BACKGROUND Current guidelines recommend statin therapy after coronary artery bypass grafting (CABG) to attain low-density lipoprotein (LDL) levels less than 100 mg/dL. Whether achieving LDL levels less than 70 mg/dL improves postoperative graft patency remains unknown. METHODS The CASCADE (Clopidogrel after Surgery for Coronary Artery Disease) trial was a randomized study that evaluated the addition of clopidogrel to aspirin on the development of saphenous vein graft disease after CABG. Patients received the standard of care regarding postoperative statin therapy with targeted LDL levels less than 100 mg/dL. Twelve months postoperatively, patients returned for a coronary angiogram and saphenous vein graft (SVG) intravascular ultrasonogram. In this post hoc analysis, the impact of statin therapy on graft patency and vein graft intimal hyperplasia was assessed. RESULTS LDL levels significantly declined over the period of the trial (p = 0.002). Twelve months postoperatively, 58.4% patients achieved LDL levels less than 70 mg/dL. Twelve-month graft patency was higher for patients with LDL levels less than 100 mg/dL (96.5%) compared with patients with LDL levels >100 mg/dL (83.3%, p = 0.03), even after adjustment in multivariate analysis (odds ratio [OR], 5.2; 95% confidence interval [CI], 1.3-21.6; p = 0.02). However, no improvement in graft patency was noted with further LDL reduction to less than 70 mg/dL (p = 1.00). Consistent statin use throughout the trial period was independently associated with less vein graft intimal hyperplasia documented by intravascular ultrasound at 12 months (p = 0.04). CONCLUSIONS Statin therapy to achieve LDL levels less than 100 mg/dL was independently associated with improved graft patency in the CASCADE trial. Randomized clinical trials are warranted to prospectively evaluate postoperative LDL reduction to less than 70 mg/dL and its impact on graft patency after CABG.

Diagnostic performance and potential clinical impact of advanced care paramedic interpretation of ST-segment elevation myocardial infarction in the field.

OBJECTIVES Most studies of pre-hospital management of ST-elevation myocardial infarction (STEMI) have involved physicians accompanying the ambulance crew, or electrocardiogram (ECG) transmission to a physician at the base hospital. We sought to determine if Advanced Care Paramedics (ACPs) could accurately identify STEMI on the pre-hospital ECG and contribute to strategies that shorten time to reperfusion. METHODS A STEMI tool was developed to: 1) measure the accuracy of the ACPs at diagnosing STEMI; and 2) determine the potential time saved if ACPs were to independently administer thrombolytic therapy. Using registry data, we subsequently estimated the time saved by initiating thrombolytic therapy in the field compared with in-hospital administration by a physician. RESULTS Between August 2003 and July 2004, a correct diagnosis of STEMI on the pre-hospital ECG was confirmed in 63 patients. The performance of the ACPs in identifying STEMI on the ECG resulted in a sensitivity of 95% (95% confidence interval [CI] 86%-99%), a specificity of 96% (95% CI 94%-98%), a positive predictive value (PPV) of 82% (95% CI 71%-90%), and a negative predictive value (NPV) of 99% (95% CI 97%-100%). ACP performance for appropriately using thrombolytic therapy resulted in a sensitivity of 92% (95% CI 78%-98%), a specificity of 97% (95% CI 94%-98%), a PPV of 73% (95% CI 59%-85%) and an NPV of 99% (95% CI 97%-100%). We estimated that the median time saved by ACP administration of thrombolytic therapy would have been 44 minutes. CONCLUSIONS ACPs can be trained to accurately interpret the pre-hospital ECG for the diagnosis of STEMI. These results are important for the design of regional integrated programs aimed at reducing delays to reperfusion.

Hospitalization Costs of Primary Stenting Versus Thrombolysis in Acute Myocardial Infarction Cost Analysis of the Canadian STAT Study

Background—We previously showed that primary stenting was more effective than accelerated tPA in reducing the 6-month composite of death, reinfarction, stroke, or repeat revascularization for ischemia. This study looks at the hospitalization costs of primary stenting compared with accelerated tPA. Methods and Results—Initial and 6-month hospitalization costs were computed for all patients randomly assigned to primary stenting (n=62) or accelerated tPA (n=61) in the Stenting versus Thrombolysis in Acute myocardial infarction Trial (STAT). Costs and resource usage were collected in detail for each patient. Physician fees were obtained directly from billings to the Ontario Health Insurance Plan. The length of initial hospitalization was 6.7±11.3 days in the stent group and 8.7±6.7 days in the tPA group (P <0.001). Total hospitalization days at 6 months were 8.3±13 days in the stent group and 12.1±14.0 days in the tPA group (P =0.001). Hospitalization costs were less in the stent group for the initial hospitalization,

Transradial Versus Transfemoral Artery Approach for Coronary Angiography and Percutaneous Coronary Intervention in the Extremely Obese

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