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Akshay Bagai,
Warren J Cantor,
Mary Tan,
Wesley Tong,
Andre Lamy,
David Fitchett,
Eric A Cohen,
Shamir R Mehta,
Bjug Borgundvaag,
John Ducas,
Michael Heffernan,
Vladimír Džavík,
Laurie Morrison,
Brian Schwartz,
Charles Lazzam,
Anatoly Langer, Shaun G Goodman
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ABSTRACT: In patients with ST-elevation myocardial infarction treated with fibrinolysis, routine early percutaneous coronary intervention (r-PCI) improves clinical outcomes at 30 days compared with a more standard approach of performing early PCI only for failed fibrinolysis (s-PCI).
We report prespecified secondary clinical outcomes and cost implications of r-PCI compared with s-PCI from the Canadian TRANSFER-AMI trial. Average cost per patient in each arm was calculated based on a microcosting approach. Bootstrap method (5,000 samples) was used to calculate standard errors and 95% CI.
At 1 year, rates of death or reinfarction (10.3% vs 11.6%, P = .50), hospital readmission (15.4% vs 16.5%, P = .64) and subsequent revascularization after index hospitalization (6.9% vs 8.7%, P = .30) were similar between the r-PCI and s-PCI arms. The difference in cost per patient between r-PCI and s-PCI was CAD $1,003 (95% CI, -$247 to $2,211). Since a greater proportion of patients were transported by air (vs land) in the r-PCI arm (9.4% vs 3%), and the ratio of abciximab to eptifibatide use was higher in the r-PCI arm compared with s-PCI (2:1 vs 4:5), we undertook additional post hoc cost scenario analyses. In a scenario where patients are transported by land only and eptifibatide is used as the sole GPIIb/IIIa inhibitor, the difference in cost per patient between r-PCI and s-PCI was estimated to be CAD $108 (95% CI, -$1,114 to $1,344).
At 1 year, there is no difference in the clinical composite outcome of death or reinfarction between r-PCI and s-PCI strategies. Greater cost with r-PCI, although statistically insignificant, is economically important.
American heart journal 04/2013; 165(4):630-637.e2. · 4.65 Impact Factor
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Jason J Rose,
L Kristin Newby,
Samuel Broderick,
Karen Chiswell,
Frans Van de Werf,
Paul W Armstrong,
Kenneth W Mahaffey,
Robert A Harrington,
E Magnus Ohman,
Robert P Giugliano, Shaun G Goodman,
Harvey D White,
Robert M Califf,
Christopher B Granger,
Renato D Lopes
Journal of the American College of Cardiology 03/2013; · 14.16 Impact Factor
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Sergio Leonardi,
Amanda Stebbins,
Renato D Lopes,
Yuliya Lokhnygina,
Meredith Todd,
Deepak L Bhatt,
Gregg W Stone,
A Michael Lincoff,
Harold L Dauerman,
C Michael Gibson,
Harvey D White,
Keyur H Parikh,
Luis Gruberg,
Howard C Herrmann,
Brent T McLaurin, Shaun G Goodman,
Kenneth W Mahaffey
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ABSTRACT: OBJECTIVES: Using data from the CHAMPION percutaneous coronary intervention (PCI), we determined the relationship between clopidogrel started at least 5 days before PCI (maintenance of clopidogrel) and PCI-related enzymatic infarct size. BACKGROUND: Clopidogrel is recommended in patients with acute coronary syndrome (ACS) managed with PCI, but its effect on PCI-related myonecrosis in contemporary patients has not been quantified. PATIENTS AND METHODS: Patients with ACS (with or without ST-segment elevation) who underwent PCI and had at least three creatine kinase-MB (CK-MB) samples after PCI were included. Enzymatic infarct size was defined as the peak CK-MB concentration indexed by its upper limit of normal. Associations between maintenance clopidogrel and enzymatic infarct size were explored using multivariable linear regression (with and without missing data imputation) and propensity score analysis using inverse probability weighting. RESULTS: Of 8877 patients randomized, 6327 (71.3%) were included (median age 61 years, 73% male, 13% ACS with ST-segment elevation). Of these 6327 patients, 2015 (31.8%) were on maintenance clopidogrel. After multivariable adjustment, maintenance clopidogrel was associated with a reduction in enzymatic infarct size {β=-0.63; 47% decrease in peak CK-MB [95% confidence interval (CI) 35, 56%]}. Multivariable linear regression with multiple imputations and inverse probability weighting propensity score analysis yielded similar results, with maintenance clopidogrel associated with 44% (95% CI 33, 53%) and 29% (95% CI 24, 33%) infarct size reductions. CONCLUSION: In this subgroup analysis of modern ACS patients, clopidogrel maintenance was independently associated with smaller enzymatic infarct size after PCI. These results are consistent with previous observations suggesting a benefit of clopidogrel on the procedural outcome and quantify this benefit.
Coronary artery disease 02/2013; · 1.56 Impact Factor
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Hwee Teoh,
Jean-Pierre Després,
Robert Dufour,
David H Fitchett,
Lianne Goldin, Shaun G Goodman,
Stewart B Harris,
Anatoly Langer,
David C W Lau,
Eva M Lonn,
G B John Mancini,
Philip A McFarlane,
Paul Poirier,
Rémi Rabasa-Lhoret,
Mary K Tan,
Lawrence A Leiter
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ABSTRACT: BACKGROUND: We evaluated the risk assessment and management patterns employed by primary care physicians in patients at elevated cardiometabolic risk. METHODS: Between April 2011 and March 2012, multiple physicians from 9 Primary Care Teams (PCTs) and 88 physicians from traditional nonteam (Solo) practices completed a practice assessment on the management of 2461 patients > 40 years old with no clinical evidence of cardiovascular disease and diagnosed with at least 1 of the following: dyslipidemia, type 2 diabetes mellitus (T2DM), or hypertension. RESULTS: Individuals with dyslipidemia, T2DM, or hypertension tended to have a body mass index ≥ 25 kg/m2. Waist circumference measurements, obtained for only 392/829 (47.0%) Solo patients, revealed that 88.9% of these individuals were abdominally obese and that at least 52.2% of Solo patients had metabolic syndrome. Cardiovascular risk, determined by the physicians for 83.5% of all patients without T2DM and typically performed using traditional risk engines, was often miscalculated (43.2% PCTs, 58.8% Solo; P = 0.0007). Healthy behavioural modifications were infrequently recommended (< 50%). Pharmacotherapy was widely used (> 70%) but treatment targets were infrequently met. The composite outcome of guideline-recommended low-density lipoprotein cholesterol, glycemic, and blood pressure targets was met by 9.0% and 8.1% of patients managed by PCT and Solo physicians respectively. CONCLUSIONS: Obesity and cardiovascular risk were underassessed and the latter often underestimated. Patients were infrequently counselled on the benefits of healthy behavioural changes. A paradigm change in assessing and managing obesity and cardiovascular risk via aggressive lifestyle interventions is warranted in individuals at elevated cardiometabolic risk.
The Canadian journal of cardiology 02/2013; · 3.36 Impact Factor
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ABSTRACT: AimsThe selection of optimal endpoints for cardiovascular clinical trials continues to be challenging. We examined an alternative interpretation of a series of trials when the individual event severity is considered.Methods and resultsWe analysed three contemporary myocardial infarction (MI) trials of early percutaneous coronary intervention after fibrinolysis, using a weighted composite method. This method allows the examination of the heterogeneity in the direction and magnitude of component endpoints, and multiple events (vs. first event). We incorporated a physician-assessed severity of each component endpoint in all patients for the five-item composite in the largest study, Trial of Routine Angioplasty and Stenting after Fibrinolysis to Enhance Reperfusion in Acute Myocardial Infarction (TRANSFER-AMI), which enrolled 1059 ST-elevation MI patients. The traditional approach yielded event-free survival probabilities of 0.89 [95% confidence interval (CI) 0.86-0.91] for the early invasive arm and 0.83 (95% CI 0.79-0.86) for the standard care arm (P = 0.004). After accounting for the clinician-investigator-determined weights, the effective survival probabilities were 0.93 (95% CI 0.91-0.95) for the early invasive arm and 0.93 (95% CI 0.90-0.95) with no significant difference (P = 0.54). The same pattern was observed in the three-trial cohort using a four-item composite with an observed improvement in event-free survival outcomes (P = 0.01), which was no longer apparent after the severity weights were considered (P = 0.44).Conclusion
This analysis highlights the importance of considering the relative severity and multiple events in the evaluation of a clinical trial.
European Heart Journal 12/2012; · 10.48 Impact Factor
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Paul A Gurbel,
David Erlinge,
E Magnus Ohman,
Benjamin Neely,
Megan Neely, Shaun G Goodman,
Kurt Huber,
Mark Y Chan,
Jan H Cornel,
Eileen Brown,
Chunmei Zhou,
Joseph A Jakubowski,
Harvey D White,
Keith A A Fox,
Dorairaj Prabhakaran,
Paul W Armstrong,
Udaya S Tantry,
Matthew T Roe
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ABSTRACT: CONTEXT The relationship of platelet function testing measurements with outcomes in patients with acute coronary syndromes (ACS) initially managed medically without revascularization is unknown. OBJECTIVE To characterize the differences and evaluate clinical outcomes associated with platelet reactivity among patients with ACS treated with clopidogrel or prasugrel. DESIGN, SETTING, AND PATIENTS Patients with medically managed unstable angina or non-ST-segment elevation myocardial infarction were enrolled in the TRILOGY ACS trial (2008 to 2011) comparing clopidogrel vs prasugrel. Of 9326 participants, 27.5% were included in a platelet function substudy: 1286 treated with prasugrel and 1278 treated with clopidogrel. INTERVENTIONS Aspirin with either prasugrel (10 or 5 mg/d) or clopidogrel (75 mg/d); those 75 years or older and younger than 75 years but who weighed less than 60 kg received a 5-mg prasugrel maintenance dose. MAIN OUTCOME MEASURES Platelet reactivity, measured in P2Y12 reaction units (PRUs), was performed at baseline, at 2 hours, and at 1, 3, 6, 12, 18, 24, and 30 months after randomization. The primary efficacy end point was a composite of cardiovascular death, myocardial infarction, or stroke through 30 months. RESULTS Among participants younger than 75 years and weighing 60 kg or more, the median PRU values at 30 days were 64 (interquartile range [IQR], 33-128) in the prasugrel group vs 200 (IQR, 141-260) in the clopidogrel group (P < .001), a difference that persisted through all subsequent time points. For participants younger than 75 years and weighing less than 60 kg, the median 30-day PRU values were 139 (IQR, 86-203) for the prasugrel group vs 209 (IQR, 148-283) for the clopidogrel group (P < .001), and for participants 75 years or older, the median PRU values were 164 (IQR, 105-216) for the prasugrel group vs 222 (IQR, 148-268) for the clopidogrel group (P < .001). At 30 months the rate of the primary efficacy end point was 17.2% (160 events) in the prasugrel group vs 18.9% (180 events) in the clopidogrel group (P = .29). There were no significant differences in the continuous distributions of 30-day PRU values for participants with a primary efficacy end point event after 30 days (n = 214) compared with participants without an event (n = 1794; P = .07) and no significant relationship between the occurence of the primary efficacy end point and continuous PRU values (adjusted hazard ratio [HR] for increase of 60 PRUs, 1.03; 95% CI, 0.96-1.11; P = .44). Similar findings were observed with 30-day PRU cut points used to define high on-treatment platelet reactivity-PRU more than 208 (adjusted HR, 1.16; 95% CI, 0.89-1.52, P = .28) and PRU more than 230 (adjusted HR, 1.20; 95% CI, 0.90-1.61; P = .21). CONCLUSIONS Among patients with ACS without ST-segment elevation and initially managed without revascularization, prasugrel was associated with lower platelet reactivity than clopidogrel, irrespective of age, weight, and dose. Among those in the platelet substudy, no significant differences existed between prasugrel vs clopidogrel in the occurence of the primary efficacy end point through 30 months and no significant association existed between platelet reactivity and occurrence of ischemic outcomes. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00699998.
JAMA The Journal of the American Medical Association 11/2012; 308(17):1785-1794. · 30.03 Impact Factor
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Ravi R Bajaj, Shaun G Goodman,
Raymond T Yan,
Alan J Bagnall,
Gabor Gyenes,
Robert C Welsh,
Kim A Eagle,
David Brieger,
Krishnan Ramanathan,
Francois R Grondin,
Andrew T Yan
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ABSTRACT: The early diagnosis of acute coronary syndrome (ACS) remains challenging, and a considerable proportion of patients are diagnosed with "possible" ACS on admission. The Global Registry of Acute Coronary Events (GRACE/GRACE(2)) and Canadian Registry of Acute Coronary Events (CANRACE) enrolled 16,618 Canadian patients with suspected ACS in 1999 to 2008. We compared the demographic and clinical characteristics, use of cardiac procedures, prognostic accuracy of the GRACE risk score, and in-hospital outcomes between patients given an admission diagnosis of "definite" versus "possible" ACS by the treating physician. Overall, 11,152 and 5,466 patients were given an initial diagnosis of "definite" ACS and "possible" ACS, respectively. Patients with a "possible" ACS had higher GRACE risk score (median 130 vs 125) and less frequently received aspirin, clopidogrel, heparin, or β blockers within the first 24 hours of presentation and assessment of left ventricular function, stress testing, cardiac catheterization, and percutaneous coronary intervention (all p <0.05). Patients with "possible" ACS had greater rates of in-hospital myocardial infarction (9.0% vs 2.0%, p <0.05) and heart failure (12% vs 8.9%, p <0.05). The GRACE risk score demonstrated excellent discrimination for in-hospital mortality in both groups and for the entire study population. In conclusion, compared to patients with "definite" ACS on presentation, those with "possible" ACS had higher baseline GRACE risk scores but less frequently received evidence-based medical therapies within 24 hours of admission or underwent cardiac procedures during hospitalization. The GRACE risk score provided accurate risk assessment, regardless of the initial diagnostic impression.
The American journal of cardiology 11/2012; · 3.58 Impact Factor
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Jan H Cornel,
Richard C Becker, Shaun G Goodman,
Steen Husted,
Hugo Katus,
Anwar Santoso,
Gabriel Steg,
Robert F Storey,
Marius Vintila,
Jie L Sun,
Jay Horrow,
Lars Wallentin,
Robert Harrington,
Stefan James
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ABSTRACT: Habitual smoking has been associated with increased platelet reactivity, increased risk of thrombotic complications and greater efficacy of clopidogrel therapy over placebo. In the PLATO trial, ticagrelor compared to clopidogrel in patients with acute coronary syndromes (ACS) reduced the primary composite end point of vascular death, myocardial infarction and stroke, without increasing overall rates of major bleeding. We evaluated the results in relation to smoking habits.
Interactions between habitual smokers (n = 6678) and in ex/nonsmokers (n = 11,932) and the effects of randomized treatments on ischemic and bleeding outcomes were evaluated by Cox regression analyses.
Habitual smokers had an overall lower risk profile and more often ST-elevation ACS. After adjustment for baseline imbalances, habitual smoking was associated with a higher incidence of definite stent thrombosis (adjusted HR, 1.44 [95% CI, 1.07-1.94]); there were no significant associations with other ischemic or bleeding end points. The effects of ticagrelor compared to clopidogrel were consistent for all outcomes regardless of smoking status. Thus, there was a similar reduction in the primary composite end point for habitual smokers (adjusted HR, 0.83 [95% CI, 0.68-1.00]) and ex/nonsmokers (adjusted HR, 0.89 [95% CI, 0.79-1.00]) (interaction P = .50), and in definite stent thrombosis for habitual smokers (adjusted HR, 0.59 [0.39-0.91]) and ex/nonsmokers (adjusted HR, 0.69 [95% CI, 0.45-1.07]) (interaction P = .61).
In patients hospitalized with ACS, habitual smoking is associated with a greater risk of subsequent stent thrombosis. The reduction of vascular death, myocardial infarction, stroke, and stent thrombosis by ticagrelor compared to clopidogrel is consistent regardless of smoking habits.
American heart journal 09/2012; 164(3):334-342.e1. · 4.65 Impact Factor
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Vineet Bhan,
Warren J Cantor,
Raymond T Yan,
Shamir R Mehta,
Laurie J Morrison,
Michael Heffernan,
David Fitchett,
Vladimir Džavík,
John Ducas,
Bjug Borgundvaag,
Eric A Cohen, Shaun G Goodman,
Andrew T Yan
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ABSTRACT: The TRANSFER-AMI study demonstrated that early routine percutaneous coronary intervention post-fibrinolysis (pharmacoinvasive strategy) is superior to conservative management for ST-elevation myocardial infarction. However, it is not clear whether treatment efficacy differs between men and women.
In this pre-specified subgroup analysis, we compared the efficacy of a pharmacoinvasive strategy in men versus women with acute ST-elevation myocardial infarction who were randomized to a pharmacoinvasive versus standard management following fibrinolysis. The primary end point was a composite of death, recurrent myocardial infarction, recurrent ischemia, heart failure and shock at 30 days. We tested for treatment heterogeneity between men and women using the Breslow-Day test. We also performed multivariable analysis adjusting for GRACE risk score and its interaction with treatment assignment, and evaluated for death/recurrent myocardial reinfarction as a secondary outcome.
Of the 1059 patients, 843 were men and 216 were women. Compared to men, women were older, had worse Killip class, higher GRACE risk score, and higher rates of death and death/myocardial reinfarction at 30 days. The primary end point did not differ significantly between men and women (13.4% vs 16.7%, P = .22). Compared to standard treatment, a pharmacoinvasive strategy was associated with a lower rate of the primary end point in men (17.5% vs 9.4%, respectively, P < .001), but not in women (16.2% vs 17.1%, P = .86). There was a trend toward an interaction between treatment assignment and sex for the composite primary end point (P = .06). After adjustment for the significant interaction between GRACE risk score and treatment (P < .001), there was no significant interaction between sex and treatment for all the end points (all P > .40).
The borderline heterogeneity in treatment efficacy of a pharmacoinvasive strategy in men versus women was no longer evident after adjustment for the difference in baseline risk. This suggests that sex per se was not an important determinant of the efficacy of a pharmacoinvasive strategy. Owing to the small number of women in this trial, further study in this area is needed.
American heart journal 09/2012; 164(3):343-50. · 4.65 Impact Factor
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Matthew T Roe,
Paul W Armstrong,
Keith A A Fox,
Harvey D White,
Dorairaj Prabhakaran, Shaun G Goodman,
Jan H Cornel,
Deepak L Bhatt,
Peter Clemmensen,
Felipe Martinez, [......],
Ramon Corbalan,
Mircea Cinteză,
R Craig McLendon,
Kenneth J Winters,
Eileen B Brown,
Yuliya Lokhnygina,
Philip E Aylward,
Kurt Huber,
Judith S Hochman,
E Magnus Ohman
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ABSTRACT: The effect of intensified platelet inhibition for patients with unstable angina or myocardial infarction without ST-segment elevation who do not undergo revascularization has not been delineated.
In this double-blind, randomized trial, in a primary analysis involving 7243 patients under the age of 75 years receiving aspirin, we evaluated up to 30 months of treatment with prasugrel (10 mg daily) versus clopidogrel (75 mg daily). In a secondary analysis involving 2083 patients 75 years of age or older, we evaluated 5 mg of prasugrel versus 75 mg of clopidogrel.
At a median follow-up of 17 months, the primary end point of death from cardiovascular causes, myocardial infarction, or stroke among patients under the age of 75 years occurred in 13.9% of the prasugrel group and 16.0% of the clopidogrel group (hazard ratio in the prasugrel group, 0.91; 95% confidence interval [CI], 0.79 to 1.05; P=0.21). Similar results were observed in the overall population. The prespecified analysis of multiple recurrent ischemic events (all components of the primary end point) suggested a lower risk for prasugrel among patients under the age of 75 years (hazard ratio, 0.85; 95% CI, 0.72 to 1.00; P=0.04). Rates of severe and intracranial bleeding were similar in the two groups in all age groups. There was no significant between-group difference in the frequency of nonhemorrhagic serious adverse events, except for a higher frequency of heart failure in the clopidogrel group.
Among patients with unstable angina or myocardial infarction without ST-segment elevation, prasugrel did not significantly reduce the frequency of the primary end point, as compared with clopidogrel, and similar risks of bleeding were observed. (Funded by Eli Lilly and Daiichi Sankyo; TRILOGY ACS ClinicalTrials.gov number, NCT00699998.).
New England Journal of Medicine 08/2012; 367(14):1297-309. · 53.30 Impact Factor
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ABSTRACT: Despite advances in the management of patients with an acute coronary syndrome (ACS), cardiogenic shock (CS) remains the leading cause of death in these patients. The objective of this observational study was to describe the characteristics, management, and hospital outcomes of patients with an ACS complicated by CS. Our secondary study objective was to describe trends in the incidence and hospital case-fatality rates (CFRs) of CS and predictors of increased hospital mortality in these high-risk patients.
The population consisted of patients enrolled in the GRACE study between 1999 and 2007 who were hospitalized with an ACS.
During the years under study, 2,992 patients (4.6%) developed CS. Patients with CS were more likely to be older, have a history of diabetes or atrial fibrillation, and present with a higher pulse rate or cardiac arrest. Cardiac catheterization was performed on 1,706 (57%) and in-hospital revascularization on 1,408 patients (47%) with CS. Patients with CS were less likely to receive evidence-based cardiac medications compared with patients who did not develop CS. The in-hospital CFR of patients with CS was 59.4%, compared with 2.3% in those who did not develop CS. Factors associated with an increased risk of dying in patients with CS included advanced age, diabetes mellitus, angina, and stroke. Adjusted incidence rates and hospital CFRs of CS showed modest declines over time.
Continued efforts are needed to reduce the incidence and CFRs of CS complicating ACS.
American heart journal 06/2012; 163(6):963-71. · 4.65 Impact Factor
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Michelle L O'Donoghue,
Deepak L Bhatt,
Marcus D Flather,
Shinya Goto,
Dominick J Angiolillo, Shaun G Goodman,
Uwe Zeymer,
Philip E Aylward,
Gilles Montalescot,
Rafal Ziecina,
Hiroyuki Kobayashi,
Fang Ren,
Stephen D Wiviott
[show abstract]
[hide abstract]
ABSTRACT: Atopaxar is a reversible protease activated receptor (PAR)-1 thrombin receptor antagonist that interferes with platelet signaling. The effects of PAR-1 antagonists on biomarkers remain unknown. The primary objective was to assess the effects of atopaxar on biomarkers of inflammation and platelet activation. The LANCELOT-CAD trial randomized 720 subjects to atopaxar (50, 100, or 200 mg daily) or matching placebo for 24 weeks. Biomarkers were assessed at serial time points. A linear mixed model to account for repeated measures was used to evaluate the change in biomarker concentration from randomization across time to week 24. Least square means were determined from the linear mixed models. The concentration of sCD40L decreased on average over time by -553 (95 % CI -677, -429) ng/L in the combined atopaxar group versus -30.3 (-249 to 189) ng/L fall in the placebo arm (P < 0.001) and a dose-dependent trend was seen across treatment groups (P < 0.001 for trend). In contrast, Lp-PLA(2) mass rose on average over time by 12.6 (95 % CI 10.0, 15.3) ng/ml in the combined atopaxar group as compared with 2.6 (95 % CI -2.1, 7.3) ng/ml in the placebo arm (P < 0.001). Similarly, the concentration of IL-18 rose by 17.5 (95 % CI 12.4, 22.6) pg/ml in the atopaxar group versus a -1.2 (95 % CI -10.2, 7.8) pg/ml fall in the placebo group (P < 0.001). The effects of atopaxar on Lp-PLA(2) and IL-18 appeared to be dose-dependent (P < 0.001 for trend) and were observed in J-LANCELOT. Atopaxar did not have a significant effect on other inflammatory markers. In conclusion, atopaxar appeared to decrease sCD40L, but did not demonstrate an anti-inflammatory effect in patients with stable CAD. Although atopaxar increased the concentration of Lp-PLA(2) and IL-18, the clinical relevance of these findings remains unknown and warrants further investigation and validation.
Journal of Thrombosis and Thrombolysis 06/2012; 34(1):36-43. · 1.48 Impact Factor
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ABSTRACT: BackgroundThe prognostic value of perfusion imaging was assessed in low- risk patients after myocardial infarction (MI) and compared
with clinical and angiographic variables. Methods and Results. Rest thallium and dipyridamole technetium 99m sestamibi single
photon emission computed tomography imaging was performed in 203 (91%) low- risk patients 3 to 21 days after MI who were enrolled
in a trial of low- dose warfarin sodium and aspirin. Patients were considered low risk with planned nonintervention, on the
basis of an uncomplicated course after MI, negative submaximal stress electrocardiography, and the absence of significant
angiographic disease requiring revascularization. During a minimum follow- up of 12 months, 69 patients (34%) had clinical
events: 1 cardiac death, 7 MIs, 26 admissions for unstable angina, 18 coronary bypass grafting, and 17 angioplasty. Univariate
analysis identified the extent of significant angiographic stenoses ( ≥70% ) and the extent of scintigraphic defect as predictive
of future events. On multivariate analysis, the presence of any scintigraphic reversibility had the strongest correlation
with clinical events, with better predictive value than angiographic multivessel stenoses (P =.0006 vs P =.003).
ConclusionsIn the low- risk population after MI, scintigraphic reversibility remains a strong predictor of cardiac events, with greater
prognostic value than angiographic data. The extent of scintigraphic reversibility was directly correlated with clinical events.
Therefore scintigraphic imaging remains clinically relevant for risk stratification in the current low- risk population after
MI.
Journal of Nuclear Cardiology 04/2012; 8(2):136-143. · 2.67 Impact Factor
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Darar Al Khdair,
Lamia Alshengeiti,
Basem Elbarouni,
Raymond T Yan,
Francois R Grondin,
Frederick A Spencer,
Sven Pallie,
David Brieger,
Kim A Eagle,
Iqwal Mangat,
Sheldon Singh, Shaun G Goodman,
Andrew T Yan
[show abstract]
[hide abstract]
ABSTRACT: The prognostic impact of atrial fibrillation (AF) in the setting of acute coronary syndrome (ACS) is controversial. Furthermore, there are limited real-world data on the management of ACS patients with history of AF.
The Global Registry of Acute Coronary Events (GRACE/GRACE2) and Canadian Registry of Acute Coronary Events (CANRACE) enrolled 14,285 patients across Canada between 1999 and 2008. Patients were stratified by the presence of history of AF. We compared clinical characteristics, medical therapies, cardiac procedures, and clinical outcomes between the 2 groups.
Overall, 1333 of the enrolled patients (9.3%) had history of AF, of whom 51.5% presented with non-ST-segment elevation myocardial infarction, 29.5% with unstable angina, and 19.1% with ST-segment elevation myocardial infarction. Compared with the group without, patients with a history of AF less frequently received evidence-based antiplatelet and antithrombin therapies, left ventricle ejection fraction assessment, and coronary angiography (all P < 0.001); they also had higher unadjusted rates of in-hospital death, myocardial (re)infarction, and heart failure. However, in multivariable analysis, history of AF was not found to be independently associated with in-hospital mortality (adjusted odds ratio [OR] = 1.12; 95% confidence interval (CI), 0.73-1.73; P = 0.61) or death and/or myocardial reinfarction (adjusted OR = 1.15; 95% CI, 0.87-1.5; P = 0.34).
History of AF is common among ACS patients. They received less evidence-based medical and invasive therapies than ACS patients without history of AF. History of AF is a negative independent predictor of in-hospital coronary angiography but was not found to be independently associated with adverse outcomes.
The Canadian journal of cardiology 03/2012; 28(4):443-9. · 3.36 Impact Factor
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Shaun G Goodman,
Robert Clare,
Karen S Pieper,
José C Nicolau,
Robert F Storey,
Warren J Cantor,
Kenneth W Mahaffey,
Dominick J Angiolillo,
Steen Husted,
Christopher P Cannon,
Stefan K James,
Jan Kilhamn,
P Gabriel Steg,
Robert A Harrington,
Lars Wallentin
[show abstract]
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ABSTRACT: The clinical significance of the interaction between clopidogrel and proton pump inhibitors (PPIs) remains unclear.
We examined the relationship between PPI use and 1-year cardiovascular events (cardiovascular death, myocardial infarction, or stroke) in patients with acute coronary syndrome randomized to clopidogrel or ticagrelor in a prespecified, nonrandomized subgroup analysis of the Platelet Inhibition and Patient Outcomes (PLATO) trial. The primary end point rates were higher for individuals on a PPI (n=6539) compared with those not on a PPI (n=12 060) at randomization in both the clopidogrel (13.0% versus 10.9%; adjusted hazard ratio [HR], 1.20; 95% confidence interval [CI], 1.04-1.38) and ticagrelor (11.0% versus 9.2%; HR, 1.24; 95% CI, 1.07-1.45) groups. Patients on non-PPI gastrointestinal drugs had similar primary end point rates compared with those on a PPI (PPI versus non-PPI gastrointestinal treatment: clopidogrel, HR, 0.98; 95% CI, 0.79-1.23; ticagrelor, HR, 0.89; 95% CI, 0.73-1.10). In contrast, patients on no gastric therapy had a significantly lower primary end point rate (PPI versus no gastrointestinal treatment: clopidogrel, HR, 1.29; 95% CI, 1.12-1.49; ticagrelor, HR, 1.30; 95% CI, 1.14-1.49).
The use of a PPI was independently associated with a higher rate of cardiovascular events in patients with acute coronary syndrome receiving clopidogrel. However, a similar association was observed between cardiovascular events and PPI use during ticagrelor treatment and with other non-PPI gastrointestinal treatment. Therefore, in the PLATO trial, the association between PPI use and adverse events may be due to confounding, with PPI use more of a marker for, than a cause of, higher rates of cardiovascular events.
http://www.clinicaltrials.gov. Unique identifier: NCT00391872.
Circulation 02/2012; 125(8):978-86. · 14.74 Impact Factor
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Basem Elbarouni,
S Behnam Banihashemi,
Raymond T Yan,
Robert C Welsh,
Jan M Kornder,
Graham C Wong,
Frederick A Anderson,
Frederick A Spencer,
François R Grondin, Shaun G Goodman,
Andrew T Yan
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ABSTRACT: Current guidelines recommend the measurement of fasting lipid profile and use of statins in all patients with acute coronary syndrome (ACS). However, the temporal trends of lipid testing and statin therapy in "real-world" patients with ACS are unclear. From January 1999 through December 2008, the prospective, multicenter, Global Registry of Acute Coronary Events (GRACE/GRACE(2)/CANRACE) enrolled 13,947 patients with ACS in Canada. We stratified the study population based on year of presentation into 3 groups (1999 to 2004, 2005 to 2006, and 2007 to 2008) and compared the use of lipid testing and use of statin therapy in hospital. Overall, 70.8% of patients underwent lipid testing and 79.4% received in-hospital statin therapy; these patients were younger and had lower GRACE risk scores (p <0.001 for the 2 comparisons) compared to those who did not. Over time there was a significant increase in rates of in-hospital statin therapy (70% in 1999 to 2004 to 84.5% in 2007 to 2008, p for trend < 0.001) but only a minor increase in rates of lipid testing (69.4% in 1999 to 2004 to 72.4% in 2007 to 2008, p for trend = 0.003). After adjusting for confounders, this increasing temporal trend remained statistically significant for statin therapy (p <0.001) but not for lipid testing. Lipid testing was independently associated with in-hospital statin use (adjusted odds ratio 1.62, 95% confidence interval 1.27 to 2.08, p <0.001). In patients who did have lipid testing, those with low-density lipoprotein cholesterol level >130 mg/dl (3.4 mmol/L) were more likely to be treated with in-hospital statins. In conclusion, there has been a significant temporal increase in the use of in-hospital statin therapy but only a minor increase in lipid testing. Lipid testing was strongly associated with in-hospital statin use. A substantial proportion of patients with ACS, especially those at higher risk, still do not receive these guideline-recommended interventions in contemporary practice.
The American journal of cardiology 02/2012; 109(10):1418-24. · 3.58 Impact Factor
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ABSTRACT: Our objective was to determine the association of activated partial thromboplastin time (aPTT) with recurrent ischemic events and non-coronary artery bypass surgery-related thrombolysis in myocardial infarction major bleeding. We studied 4,985 patients with high-risk non-ST-segment elevation acute coronary syndromes (NSTE ACS) participating in SYNERGY, a prospective, randomized, international trial designed to emulate contemporary practice wherein unfractionated heparin (UFH) is given intravenously and titrated according to a weight-adjusted dosing nomogram to a target aPTT of 1.5-2 times the upper limit of normal (approximately 50-70 s). Aspirin was administered to 95% of patients, clopidogrel to 63%, and glycoprotein IIb/IIIa receptor inhibitors to 58%. More than 90% of patients underwent early coronary angiography, and 69% were revascularized. Used as a time-dependent covariate, aPTT was evaluated as a predictor of time to ischemic or major hemorrhagic events in proportional hazards regression models. Using discrete variable analysis, aPTT was categorized as persistently below a lower threshold of anticoagulation (<50 vs. ≥50 s) for recurrent ischemic events and above an upper threshold (>70 vs. ≤70 s) for major hemorrhagic events. UFH treatment lasted a median of 42 (30, 78) h. At >6-12 (n = 3,021), >12-24 (n = 3,406), and >24-48 (n = 2,497) h, 34, 41, and 46% of patients achieved the target aPTT range, respectively. Both before and after adjusting for baseline predictors of anticoagulant response and risk score (age, hypertension, diabetes, smoking, ST depression, and renal function), no significant relationship between aPTT values and recurrent ischemic events or major bleeding was found. No relationship was observed between clinical outcomes and aPTT values persistently above or below the designated thresholds. Measurements of aPTT were not associated with clinical outcomes among patients with NSTE ACS treated with UFH. The required intensity of anticoagulation for benefit may be relatively modest when UFH is administered concomitantly with dual or triple platelet-directed therapy, particularly in patients undergoing early coronary revascularization.
Journal of Thrombosis and Thrombolysis 02/2012; 34(1):114-9. · 1.48 Impact Factor
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Shahar Lavi,
Warren J Cantor,
Amparo Casanova,
Mary K Tan,
Andrew T Yan,
Vladimír Džavík,
David Fitchett,
Eric A Cohen,
Bjug Borgundvaag,
Michael Heffernan,
John Ducas, Shaun G Goodman
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ABSTRACT: An early invasive strategy after fibrinolysis for ST-elevation myocardial infarction (STEMI) improves outcomes, but the relative efficacy and safety of enoxaparin compared with unfractionated heparin (UFH) as part of this approach are unknown.
In the TRANSFER-AMI trial, patients with high-risk STEMI received fibrinolysis and were then randomized to either standard treatment or to immediate transfer for coronary angiography. In this substudy, the outcome of patients aged <75 years treated with enoxaparin is compared with that of patients who received UFH. Logistic regression and propensity score models were used to evaluate the efficacy and safety of these anticoagulants. Enoxaparin was administered to 498 patients, and UFH, to 448 patients, at the time of fibrinolysis. Approximately 50% in each group were randomized to the early invasive strategy. The primary composite end point of death, reinfarction, recurrent ischemia, new or worsening heart failure, or cardiogenic shock at 30 days occurred in 11.9% and 11.6% of the patients who received enoxaparin and UFH, respectively (adjusted odds ratio 0.95 [95% CI 0.60-1.51], P = .84). Enoxaparin use was associated with more access site bleeding (5.0% vs 2.9%, P = .04) and mild bleeding (12.1% vs 7.8%, P = .03).
Among high-risk patients with STEMI undergoing early or late transfer for cardiac catheterization after fibrinolysis, enoxaparin was associated with similar efficacy compared with UFH, but there was more minor bleeding with enoxaparin (ClinicalTrials.gov no. NCT00164190).
American heart journal 02/2012; 163(2):176-81.e2. · 4.65 Impact Factor
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Stephanie Poon, Shaun G Goodman,
Raymond T Yan,
Raffaele Bugiardini,
Arlene S Bierman,
Kim A Eagle,
Nina Johnston,
Thao Huynh,
Francois R Grondin,
Karin Schenck-Gustafsson,
Andrew T Yan
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ABSTRACT: The question of whether gender-related disparities still exist in the treatment and outcomes of patients presenting with acute coronary syndromes (ACS) remains controversial. Using data from 4 registries spanning a decade, we sought to determine whether sex-related differences have persisted over time and to examine the treating physician's rationale for adopting a conservative management strategy in women compared with men.
From 1999 to 2008, 14,196 Canadian patients with non-ST-segment elevation ACS were recruited into the Acute Coronary Syndrome I (ACSI), ACSII, Global Registry of Acute Coronary Events (GRACE/GRACE(2)), and Canadian Registry of Acute Coronary Events (CANRACE) prospective multicenter registries.
Women in the study population were found to be significantly older than men and were more likely to have a history of heart failure, diabetes, or hypertension. Fewer women were treated with thienopyridines, heparin, and glycoprotein IIb/IIIa inhibitors compared with men in GRACE and CANRACE. Female gender was independently associated with a lower in-hospital use of coronary angiography (adjusted odds ratio 0.76, 95% CI 0.69-0.84, P < .001) and higher in-hospital mortality (adjusted odds ratio 1.26, 95% CI 1.02-1.56, P = .036), irrespective of age (P for interaction =.76). Underestimation of patient risk was the most common reason for not pursuing an invasive strategy in both men and women.
Despite temporal increases in the use of invasive cardiac procedures, women with ACS are still more likely to be treated conservatively, which may be due to underestimation of patient risk. Furthermore, they have worse in-hospital outcomes. Greater awareness of this paradox may assist in bridging the gap between current guidelines and management practices.
American heart journal 01/2012; 163(1):66-73. · 4.65 Impact Factor
