Christopher P Cannon

Boston Biomedical Research Institute, Boston, Massachusetts, United States

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Publications (787)5468.01 Total impact

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    ABSTRACT: The optimal platelet inhibition strategy for ACS patients managed without revascularization is unknown.We aimed to evaluate efficacy and safety of ticagrelor vs. clopidogrel in the non-ST-elevation acute coronary syndrome (NSTE-ACS) subgroup of the PLATO trial, in the total cohort, and in the subgroups managed with and without revascularization within 10 days of randomization. We performed a retrospective analysis of the primary endpoint of cardiovascular death/myocardial infarction/stroke. Among 18 624 PLATO patients, 11 080 (59%) were categorized as NSTE-ACS at randomization. During the initial 10 days, 74% had angiography, 46% PCI, and 5% CABG. In NSTE-ACS patients, the primary endpoint was reduced with ticagrelor vs. clopidogrel [10.0 vs. 12.3%; hazard ratio (HR) 0.83; 95% confidence interval (CI) = 0.74-0.93], as was myocardial infarction (6.6 vs. 7.7%; HR 0.86; 95% CI = 0.74-0.99), cardiovascular death (3.7 vs. 4.9%; HR 0.77; 95% CI = 0.64-0.93), and all-cause death (4.3 vs. 5.8%; HR 0.76; 95% CI = 0.64-0.90). Major bleeding rate was similar between treatment groups (13.4 vs. 12.6%; HR 1.07; 95% CI = 0.95-1.19), but ticagrelor was associated with an increase in non-CABG major bleeding (4.8 vs. 3.8%; HR 1.28; 95% CI = 1.05-1.56). Within the first 10 days, 5366 (48.4%) patients were managed without revascularization. Regardless of revascularization or not, ticagrelor consistently reduced the primary outcome (HR 0.86 vs. 0.85, interaction P = 0.93), and all-cause death (HR 0.75 vs. 0.73, interaction P = 0.89) with no significant increase in overall major bleeding. In patients with NSTE-ACS, benefit of ticagrelor over clopidogrel in reducing ischaemic events and total mortality was consistent with the overall PLATO trial, independent of actually performed revascularization during the initial 10 days.
    European Heart Journal 04/2014; · 14.10 Impact Factor
  • Clinical Cardiology 03/2014; · 1.83 Impact Factor
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    ABSTRACT: Background-Major bleeding has received increasing attention as a target for quality improvement in care of patients with acute myocardial infarction. However, little is known about variation in bleeding across hospitals and whether variation is attributable to quality of hospital care, treatments, or case mix.Methods and Results-We characterized hospital variation in major bleeding events (an absolute hemoglobin drop ≥4 g/dL, intracranial hemorrhage, retroperitoneal bleed, or transfusion) among 99 200 patients with non-ST-segment elevation myocardial infarction in the National Cardiovascular Data Registry (NCDR) Acute Coronary Treatment and Intervention Outcomes Network Registry-Get With the Guidelines (ACTIOM Registry-GWTG) between January 2007 and June 2010. A total of 9566 (9.6%) patients experienced a major bleeding event during hospitalization. The median of the estimated distribution of major bleeding rates across hospitals was 9.4% (interquartile range, 7.5%-11.7%), with some hospitals having bleeding rates >2.3 times higher than others (10th-90th percentile, 6.1%-14.2%). Multivariable hierarchical models revealed that differences in case mix explained 19.2% of the hospital variation in bleeding complications, where anticoagulation and antiplatelet strategies explained an incremental 9.9% and 6.8%, respectively. Together, 32.3% of hospital variation in major bleeding rates was attributable to differences in patient case mix and identifiable differences in treatment strategies in patients with non-ST-segment elevation myocardial infarction.Conclusions-In-hospital major bleeding rates varied widely across hospitals. Although patient factors and treatments explained less than one third of hospital-level variation, ≈70% of bleeding variation remains after adjustment. A better understanding of causes for substantial hospital-level bleeding variations is needed to help target high-risk patients or practices and to optimize care.
    Circulation Cardiovascular Quality and Outcomes 03/2014; · 5.66 Impact Factor
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    ABSTRACT: <0.001, per calendar year). In-hospital coronary artery bypass grafting and renal insufficiency were independently associated with lower use (adjusted odds ratio, 0.55; 95% confidence interval, 0.48-0.63 and adjusted odds ratio, 0.58; 95% confidence interval, 0.52-0.64, respectively).Conclusions-Results from this large US national registry suggest that 1 in 5 eligible patients hospitalized for acute coronary syndrome failed to receive American College of Cardiology/American Heart Association class I guideline-recommended ACEI/ARB therapy, and the use varies by patient factors. In particular, the low likelihood of ACEI/ARB after coronary artery bypass grafting surgery or in patients with renal insufficiency raises concern. These findings highlight an unmet need in this population and provide an incentive for additional quality improvement efforts.
    Circulation Cardiovascular Quality and Outcomes 02/2014; · 5.66 Impact Factor
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    ABSTRACT: Many patients treated with oral anticoagulants for atrial fibrillation undergo percutaneous stent implantation, where dual antiplatelet therapy (DAPT) is also recommended. The current evidence to support triple oral antithrombotic therapy (TOAT) in these patients is limited, and new strategies are being discussed to optimize outcomes. There will be variation in antithrombotic strategies in patients with atrial fibrillation needing stenting. We surveyed US-based cardiologists serving as clinical investigators in academic sites and posted an online "question of the month" on cardiosource.org. Seventy-five (10.7%) responses were received to the email survey and 119 to the online question. Bare-metal stenting (BMS) was a priori preferred over drug-eluting stenting (DES) for 50.6% of patients. Only 8.8% of the responders chose newer anticoagulants in addition to DAPT as the preferred oral anticoagulant. For duration of TOAT, 79.4% of physicians recommended stopping DAPT at 1 month when BMS was used in patients presenting without acute coronary syndrome (ACS) vs 57.4% in patients with ACS. In patients implanted with a DES, 73.5% and 76.5% preferred stopping DAPT at 6 to 12 months (no ACS vs ACS, respectively). When asked which of the 2 antiplatelet agents they would recommend stopping after the above durations, 50% chose to quit aspirin. The survey highlights an interest in the new strategy of dropping aspirin, but the lack of concrete evidence triggers undesired diversity in clinical approaches. High-quality data on the efficacy and safety of such interventions are needed to further consolidate these approaches.
    Clinical Cardiology 02/2014; 37(2):103-7. · 1.83 Impact Factor
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    ABSTRACT: The relationships between Q waves that appear during the acute phase of ST-elevation myocardial infarction (STEMI), clinical characteristics, ST-segment resolution (STRes), and clopidogrel therapy in patients treated with fibrinolysis are not well described. We hypothesized that Q waves would be associated with less successful reperfusion and increased cardiovascular events. In the CLARITY-TIMI 28 trial, 3491 STEMI patients treated with fibrinolysis were randomized to clopidogrel or placebo. Electrocardiograms were evaluated for STRes post-fibrinolysis and the presence of pathologic Q waves during the index hospitalization in 3322 patients. Q waves were identified in 2045 patients (61.6%) prior to discharge and were associated with increased odds of congestive heart failure (CHF) (adjusted odds ratio [ORadj ]: 2.10, P = 0.002) or the composite of cardiovascular death/CHF at 30 days (ORadj : 2.08, P ≤ 0.001). Q waves were associated with lower odds of Thrombolysis in Myocardial Infarction [TIMI] flow grade 2 to 3 (ORadj : 0.78, P = 0.028), TIMI myocardial perfusion grade 3 (ORadj : 0.83, P = 0.029), and complete STRes at 90 minutes (ORadj : 0.80, P = 0.030). Patients with both a Q wave and incomplete STRes 90 minutes after fibrinolysis were at higher risk for cardiovascular death or CHF (11.1%) than patients with no Q wave and at least partial STRes (1.9%). Overall, clopidogrel tended to be equally or more effective in patients without Q waves compared to those with Q waves. Among STEMI patients treated with fibrinolysis, evaluating for Q waves prior to discharge is a simple method of assessing for less successful reperfusion and an increased risk of adverse 30-day cardiovascular outcomes. The combination of Q waves and 90-minute STRes allows additional risk refinement.
    Clinical Cardiology 01/2014; · 1.83 Impact Factor
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    ABSTRACT: The aim of this study was to assess the effects on lipids and safety during a 12-week reversal period after 18 months of treatment with anacetrapib. The cholesteryl ester transfer protein inhibitor anacetrapib was previously shown to reduce low-density lipoprotein cholesterol by 39.8% (estimated using the Friedewald equation) and increase high-density lipoprotein (HDL) cholesterol by 138.1%, with an acceptable side-effect profile, in patients with or at high risk for coronary heart disease in the Determining the Efficacy and Tolerability of CETP Inhibition With Anacetrapib (DEFINE) trial. A total of 1,398 patients entered the 12-week reversal-phase study, either after completion of the active-treatment phase or after early discontinuation of the study medication. In patients allocated to anacetrapib, placebo-adjusted mean percentage decreases from baseline were observed at 12 weeks off the study drug for Friedewald-calculated low-density lipoprotein cholesterol (18.6%), non-HDL cholesterol (17.6%), and apolipoprotein B (10.2%); placebo-adjusted mean percentage increases were observed for HDL cholesterol (73.0%) and apolipoprotein A-I (24.5%). Residual plasma anacetrapib levels (about 40% of on-treatment apparent steady-state trough levels) were also detected 12 weeks after cessation of anacetrapib. No clinically important elevations in liver enzymes, blood pressure, electrolytes, or adverse experiences were observed during the reversal phase. Preliminary data from a small cohort (n = 30) revealed the presence of low concentrations of anacetrapib in plasma 2.5 to 4 years after the last anacetrapib dose. In conclusion, after the cessation of active treatment, anacetrapib plasma lipid changes and drug levels decreased to approximately 40% of on-treatment trough levels at 12 weeks after dosing, but modest HDL cholesterol elevations and low drug concentrations were still detectable 2 to 4 years after the last dosing.
    The American Journal of Cardiology. 01/2014; 113(1):76–83.
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    ABSTRACT: Background Revascularization availability at US hospitals varies and may impact care quality for acute coronary syndrome patients. HypothesisThe hypothesis of this study was that there would be differences in care quality at Get With The Guidelines–Coronary Artery Disease (GWTG-CAD) hospitals based on revascularization capability. Methods For acute coronary syndrome patients admitted to GWTG-CAD hospitals between 2000 and 2010, care quality at hospitals with or without revascularization capability was examined by assessing conformity with performance and quality measures. ResultsThis study included 95 999 acute coronary syndrome patients admitted to 310 GWTG-CAD hospitals. There were 89 000 patients admitted to 226 revascularization-capable hospitals and 6999 patients admitted to 84 hospitals without revascularization capability included. Adjusted multivariate analysis demonstrated that 8 of the 19 measures were more frequently performed in the revascularization cohort: aspirin (odds ratio [OR]: 1.41, 95% confidence interval [CI]: 1.04-1.92), clopidogrel (OR: 2.31, 95% CI: 1.78-3.00), lipid-lowering therapies at discharge (OR: 1.39, 95% CI: 1.04-1.87), lipid-lowering therapies for low-density lipoprotein >100 mg/dL (OR: 1.85, 95% CI: 1.23-2.77), achievement of blood pressure
    Clinical Cardiology 01/2014; · 1.83 Impact Factor
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    ABSTRACT: Objectives The goal of this study was to determine whether there is a relationship between aspirin dose and the potent antiplatelet agent prasugrel in the TRITON–TIMI 38 (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel–Thrombolysis In Myocardial Infarction 38) study. Background Optimal aspirin dosing after acute coronary syndromes remains uncertain. Previous studies have raised questions regarding an interaction between high-dose aspirin and the potent antiplatelet agent ticagrelor. Methods In TRITON–TIMI 38, we classified 12,674 patients into low-dose (<150 mg) or high-dose (≥150 mg) aspirin groups based on discharge dose. We identified independent correlates of dose selection and studied the impact of aspirin dose on the clinical effects of prasugrel. Results There was significant geographical variation in aspirin dosing, with North American patients receiving high-dose aspirin more frequently than other countries (66% vs. 28%; p < 0.001). Clinical factors correlating with high-dose aspirin included previous percutaneous coronary intervention and use of aspirin before randomization. Characteristics associated with the use of low-dose aspirin included age ≥75 years, white race, and use of bivalirudin or a glycoprotein IIb/IIIa inhibitor during coronary intervention. Regardless of low- or high-dose aspirin use, prasugrel had lower rates of the primary efficacy endpoint (cardiovascular death, myocardial infarction, or stroke [CVD/MI/stroke]) (hazard ratio [HR]CVD/MI/stroke = 0.78 [95% confidence interval (CI) 0.64 to 0.95] and HRCVD/MI/stroke = 0.87 [95% CI 0.69 to 1.10], respectively; p value for interaction = 0.48) and higher rates of the primary safety endpoint (HR TIMI major bleeding = 1.40 [95% CI 0.81 to 2.42] and TIMImajor bleeding = 1.30 [95% CI 0.63 to 2.68], respectively; p value for interaction = 0.84) compared with clopidogrel. Conclusions In TRITON–TIMI 38, the safety and efficacy outcomes of prasugrel compared with those of clopidogrel were directionally consistent regardless of aspirin dose, although only the primary efficacy endpoint achieved statistical significance. There was no clinically meaningful interaction of aspirin with prasugrel, suggesting that previous observations with potent antiplatelet agents indicating differential results are not universal. (A Comparison of Prasugrel [CS-747] and Clopidogrel in Acute Coronary Syndrome Subjects Who Are to Undergo Percutaneous Coronary Intervention; NCT00097591)
    Journal of the American College of Cardiology 01/2014; 63(3):225–232. · 14.09 Impact Factor
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    ABSTRACT: Objectives This study reports the treatment effect of ticagrelor on myocardial infarction (MI) and the strategy for and impact of event adjudication in the PLATO (Platelet Inhibition and Patient Outcomes) trial. Background In PLATO, ticagrelor reduced cardiovascular death, MI, or stroke in patients with acute coronary syndromes (ACS). Methods A clinical events committee (CEC) prospectively defined and adjudicated all suspected MI events, based on events reported by investigators and by triggers on biomarkers. Treatment comparisons used CEC-adjudicated data and, per protocol, excluded silent MI. Results Overall, 1,299 (610 ticagrelor, 689 clopidogrel) MIs reported by the CEC occurred during the trial. Of these, 1,097 (504 ticagrelor, 593 clopidogrel) contributed to the primary composite end point. Site investigators reported 1,198 (580 ticagrelor, 618 clopidogrel) MIs. Ticagrelor significantly reduced overall MI rates (12-month CEC-adjudicated Kaplan-Meier rates: 5.8% ticagrelor, 6.9% clopidogrel; hazard ratio [HR]: 0.84; 95% confidence interval [CI]: 0.75–0.95). Non-procedural MI (HR: 0.86; 95% CI: 0.74–1.01) and MI related to percutaneous coronary intervention or stent thrombosis tended to be lower with ticagrelor. MIs related to coronary artery bypass graft surgery were few, but a numerical excess was observed in patients assigned ticagrelor. Analyses of overall MI using investigator-reported data showed similar results but did not reach statistical significance (HR: 0.88; 95% CI: 0.78–1.00). Conclusions In patients with ACS, ticagrelor significantly reduced the incidence of MI compared with clopidogrel, with consistent results across most MI subtypes. CEC procedures identified more MI end points compared with site investigators. Clinical trial NCT00391872
    Journal of the American College of Cardiology 01/2014; 61(10):E2. · 14.09 Impact Factor
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    ABSTRACT: Background Nonsteroidal anti-inflammatory drugs (NSAIDs) other than aspirin have been linked to heart failure, salt retention, adverse ventricular remodeling, and thrombosis. We therefore sought to assess their impact on cardiovascular events in outpatients with stable atherothrombotic disease. Methods We analyzed 44,095 patients in the REduction of Atherothrombosis for Continued Health (REACH) registry with information on NSAID use and 4-year follow-up. Cox proportional hazard models, including NSAID use as a time-dependent covariate, were constructed and adjusted for key baseline characteristics. End points of interest included multivariate adjusted: cardiovascular death/myocardial infarction/stroke/ischemic hospitalizations; cardiovascular death/myocardial infarction/stroke; hospitalization for heart failure; and individual components of the composite end points. Results Compared with NSAID nonusers (n = 39,675), NSAID users (n = 4420) were older (70 vs 68 years), more frequently female and white, and had more baseline heart failure and atherosclerotic risk factors (hypertension, dyslipidemia, diabetes, reduced creatinine clearance) (all P < .001). NSAID use was associated with an increased hazard for cardiovascular death/myocardial infarction/stroke/ischemic hospitalizations (adjusted hazard ratio [adj. HR] 1.12; 95% confidence interval [CI], 1.04-1.21; P = .003) and for cardiovascular death/myocardial infarction/stroke (adj. HR 1.16; 95% CI, 1.03-1.30; P = .02). There also was a higher risk of myocardial infarction (adj. HR 1.37; 95% CI, 1.12-1.68; P = .002), stroke (adj. HR 1.21; 95% CI, 1.00-1.45; P = .048), heart failure hospitalizations (adj. HR 1.18; 95% CI, 1.03-1.34; P = .013), and ischemic hospitalizations (adj. HR 1.17; 95% CI, 1.07-1.27; P = .001). Conclusion Among patients with stable atherothrombosis, NSAID use is associated with a higher risk of myocardial infarction, stroke, and hospitalizations for both ischemia and heart failure.
    The American Journal of Medicine. 01/2014; 127(1):53–60.e1.
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    ABSTRACT: Background Extensive coronary artery disease (CAD) is associated with higher risk. In this substudy of the PLATO trial we examined the effects of randomized treatment on outcome events and safety in relation to the extent of CAD. Methods Patients were classified according to presence of extensive CAD (defined as 3-vessel disease, left main disease or prior coronary artery bypass graft surgery). The trial’s primary and secondary end points were compared using Cox proportional hazards regression. Results Among 15,388 study patients for whom the extent of CAD was known, 4,646 (30%) had extensive CAD. Patients with extensive CAD had more high risk characteristics and experienced more clinical events during follow-up. They were less likely to undergo percutaneous coronary intervention (58% vs. 79%, P < 0.001) but more likely to undergo coronary artery bypass graft surgery (16% vs. 2%, P < 0.001). Ticagrelor, compared to clopidogrel, reduced the composite of cardiovascular death, myocardial infarction, and stroke in patients with extensive CAD [14.9% vs. 17.6%; hazard ratio (HR) 0.85 (0.73, 0.98)] similar to its reduction in those without extensive CAD [6.8% vs. 8.0%; HR 0.85 (0.74, 0.98), Pinteraction = 0.99]. Major bleeding was similar with ticagrelor vs. clopidogrel among patients with [25.7% vs. 25.5%; HR, 1.02 (0.90, 1.15) and without [7.3% vs. 6.4%; HR, 1.14 (0.98, 1.33), Pinteraction = 0.24] extensive CAD.Conclusions Patients with extensive CAD have higher rates of recurrent cardiovascular events and bleeding. Ticagrelor reduced ischemic events to a similar extent both in patients with and without extensive CAD, with bleeding rates similar to clopidogrel.
    American Heart Journal. 01/2014;
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    ABSTRACT: Background Despite overall improvements in cardiovascular-disease therapies and outcomes, medication nonadherence remains an important barrier to effective secondary prevention of atherothrombotic disease. HypothesisLong-term medication adherence in outpatients with stable atherothrombotic disease is impacted by demographic and clinical factors. Methods We examined data from the prospective international Reduction of Atherothrombosis for Continued Health (REACH) Registry. Analyses were derived from 25 737 patients with established atherothrombotic disease with complete adherence data at enrollment and at year 4. Adherence was defined as patients' self-report of taking medications based on class I American College of Cardiology/American Heart Association guidelines for secondary prevention as defined, including antiplatelet agents, statins, and antihypertensive medications. ResultsAmong patients with atherothrombotic disease, 12 500 (48.6%) were deemed adherent to guideline-recommended medications. Adherent patients were younger, white, and had less polyvascular disease. Hispanic and East Asian patients were less likely to be adherent as compared with white patients (odds ratio [OR]: 0.72, 95% confidence interval [CI]: 0.59-0.88; and OR: 0.67, 95% CI: 0.53-0.83, respectively). Patients who had a nonfatal MI or underwent coronary angioplasty/stenting during follow-up were more likely to be adherent compared with patients without these events (OR: 1.73, 95% CI: 1.25-2.38; and OR: 2.15, 95% CI: 1.72-2.67, respectively). On the other hand, nonfatal stroke during follow-up was inversely associated with adherence (OR: 0.77, 95% CI: 0.61-0.97). Conclusions Using a large international registry of outpatients with atherothrombotic disease, we found that age, region, race/ethnicity, and incident cardiovascular events were predictive of long-term guideline adherence for secondary prevention, suggesting that certain patient groups may benefit from targeted interventions to improve adherence.
    Clinical Cardiology 12/2013; 36(12). · 1.83 Impact Factor
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    International journal of cardiology 11/2013; · 7.08 Impact Factor
  • Circulation 10/2013; · 15.20 Impact Factor
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    ABSTRACT: Among nontraditional cardiovascular risk factors, recent influenzalike infection is associated with fatal and nonfatal atherothrombotic events. To determine if influenza vaccination is associated with prevention of cardiovascular events. A systematic review and meta-analysis of MEDLINE (1946-August 2013), EMBASE (1947-August 2013), and the Cochrane Library Central Register of Controlled Trials (inception-August 2013) for randomized clinical trials (RCTs) comparing influenza vaccine vs placebo or control in patients at high risk of cardiovascular disease, reporting cardiovascular outcomes either as efficacy or safety events. Two investigators extracted data independently on trial design, baseline characteristics, outcomes, and safety events from published manuscripts and unpublished supplemental data. High-quality studies were considered those that described an appropriate method of randomization, allocation concealment, blinding, and completeness of follow-up. Random-effects Mantel-Haenszel risk ratios (RRs) and 95% CIs were derived for composite cardiovascular events, cardiovascular mortality, all-cause mortality, and individual cardiovascular events. Analyses were stratified by subgroups of patients with and without a history of acute coronary syndrome (ACS) within 1 year of randomization. Five published and 1 unpublished randomized clinical trials of 6735 patients (mean age, 67 years; 51.3% women; 36.2% with a cardiac history; mean follow-up time, 7.9 months) were included. Influenza vaccine was associated with a lower risk of composite cardiovascular events (2.9% vs 4.7%; RR, 0.64 [95% CI, 0.48-0.86], P = .003) in published trials. A treatment interaction was detected between patients with (RR, 0.45 [95% CI, 0.32-0.63]) and without (RR, 0.94 [95% CI, 0.55-1.61]) recent ACS (P for interaction = .02). Results were similar with the addition of unpublished data. In a meta-analysis of RCTs, the use of influenza vaccine was associated with a lower risk of major adverse cardiovascular events. The greatest treatment effect was seen among the highest-risk patients with more active coronary disease. A large, adequately powered, multicenter trial is warranted to address these findings and assess individual cardiovascular end points.
    JAMA The Journal of the American Medical Association 10/2013; 310(16):1711-20. · 29.98 Impact Factor
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    ABSTRACT: Abstract In the PLATelet inhibition and patient Outcomes (PLATO) study of patients with acute coronary syndromes, ticagrelor reduced mortality compared to clopidogrel but the mechanisms for this mortality reduction remain uncertain. We analysed adverse events (AEs) consistent with either pulmonary infection or sepsis, and subsequent mortality, in 18,421 PLATO patients treated with ticagrelor or clopidogrel. AEs occurring within 7 days of last dose of study medication were defined as "on-treatment". Serial measurements of blood leukocyte counts, C-reactive protein and interleukin-6 were performed. Fewer on-treatment pulmonary AEs occurred in the ticagrelor compared to the clopidogrel group (275 vs. 331 respectively; p = 0.019), with fewer deaths following these AEs (33 vs. 71; p < 0.001), particularly in those who remained on study medication three days after AE onset (10 vs. 43; p < 0.001). There were fewer deaths attributed to sepsis in the ticagrelor group (7 vs. 23; p = 0.003). Leukocyte counts were lower in the clopidogrel group during treatment (p < 0.0001 at 1, 3 and 6 months) but not at 1 month post-discontinuation. C-reactive protein increased more at discharge in the ticagrelor group (28.0 ± 38.0 vs. 26.1 ± 36.6 mg/l; p < 0.001) and interleukin-6 remained higher during the first month of treatment with ticagrelor. We conclude that the mortality risk following pulmonary AEs and sepsis in acute coronary syndrome patients appears to be lower during ticagrelor compared to clopidogrel therapy. Further work should assess whether ticagrelor and clopidogrel have differential effects on immune signalling.
    Platelets 10/2013; · 2.24 Impact Factor
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    ABSTRACT: To assess the prognostic utility of lipoprotein (a) [Lp(a)] in individuals with coronary artery disease (CAD). Data regarding an association between Lp(a) and cardiovascular (CV) risk in secondary prevention populations are sparse. Plasma Lp(a) was measured in 6762 subjects with CAD from three studies; data were then combined with eight previously published studies for a total of 18,979 subjects. Across the three studies, increasing levels of Lp(a) were not associated with the risk of CV events when modeled as a continuous variable (OR 1.03 per log-transformed SD, 95% CI 0.96-1.11) or by quintile (OR Q5:Q1 1.05, 95% CI, 0.83-1.34). When data were combined with previously published studies of Lp(a) in secondary prevention, subjects with Lp(a) levels in the highest quantile were at increased risk of CV events (OR 1.40, 95% CI 1.15-1.71), but with significant between-study heterogeneity (P=0.001). When stratified on the basis of LDL cholesterol, the association between Lp(a) and CV events was significant in studies in which average LDL cholesterol was ≥130 mg/dl (OR 1.46, 95% CI 1.23-1.73, P<0.001), whereas this relationship was not significant for studies with an average LDL cholesterol <130 mg/dl (OR 1.20, 95 CI 0.90-1.60, P=0.21). Lp(a) is significantly associated with the risk of CV events in patients with established CAD; however, there exists marked heterogeneity across trials. In particular, the prognostic value of Lp(a) in patients with low cholesterol levels remains unclear.
    Journal of the American College of Cardiology 10/2013; · 14.09 Impact Factor
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    ABSTRACT: Blood lipids have major cardiovascular and public health implications. Lipid-lowering drugs are prescribed based in part on categorization of patients into normal or abnormal lipid metabolism, yet relatively little emphasis has been placed on: (1) the accuracy of current lipid measures used in clinical practice, (2) the reliability of current categorizations of dyslipidemia states, and (3) the relationship of advanced lipid characterization to other cardiovascular disease biomarkers. To these ends, we developed the Very Large Database of Lipids (NCT01698489), an ongoing database protocol that harnesses deidentified data from the daily operations of a commercial lipid laboratory. The database includes individuals who were referred for clinical purposes for a Vertical Auto Profile (Atherotech Inc., Birmingham, AL), which directly measures cholesterol concentrations of low-density lipoprotein, very low-density lipoprotein, intermediate-density lipoprotein, high-density lipoprotein, their subclasses, and lipoprotein(a). Individual Very Large Database of Lipids studies, ranging from studies of measurement accuracy, to dyslipidemia categorization, to biomarker associations, to characterization of rare lipid disorders, are investigator-initiated and utilize peer-reviewed statistical analysis plans to address a priori hypotheses/aims. In the first database harvest (Very Large Database of Lipids 1.0) from 2009 to 2011, there were 1 340 614 adult and 10 294 pediatric patients; the adult sample had a median age of 59 years (interquartile range, 49-70 years) with even representation by sex. Lipid distributions closely matched those from the population-representative National Health and Nutrition Examination Survey. The second harvest of the database (Very Large Database of Lipids 2.0) is underway. Overall, the Very Large Database of Lipids database provides an opportunity for collaboration and new knowledge generation through careful examination of granular lipid data on a large scale.
    Clinical Cardiology 10/2013; · 1.83 Impact Factor
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    ABSTRACT: We sought to investigate whether there is a relationship between aspirin dose and the potent antiplatelet agent prasugrel in the TRITON-TIMI 38 study. Optimal aspirin dosing following acute coronary syndrome remains uncertain. Previous studies have raised questions regarding an interaction between high-dose aspirin and the potent antiplatelet agent ticagrelor. In TRITON-TIMI 38, we classified 12,860 patients into low-dose (<150 mg) or high-dose (≥150 mg) aspirin groups based on discharge dose. We identified independent correlates of dose selection and studied the impact of aspirin dose on clinical effects of prasugrel. There was significant geographical variation in aspirin dosing, with North American patients receiving high-dose aspirin more frequently than other countries (66% vs. 28%, p<0.001). Clinical factors correlating with high-dose aspirin included prior percutaneous coronary intervention, prior myocardial infarction, and use of aspirin or beta-blockers prior to randomization. Characteristics associated with use of low-dose aspirin included age ≥75 years, white race, and use of bivalirudin or a glycoprotein IIb/IIIa inhibitor during coronary intervention. Regardless of low-dose or high-dose aspirin, prasugrel had lower rates of the primary efficacy endpoint (HRCVdeath/MI/stroke=0.78, 95% CI 0.64-0.95 and HRCVdeath/MI/stroke=0.87, 95% CI 0.69-1.10, respectively; P-int=0.48) and higher rates of the primary safety endpoint (HRTIMI major bleeding=1.40, 95% CI 0.81-2.42 and HRTIMI major bleeding=1.30, 95% CI 0.63-2.68, respectively; P-int=0.84) compared with clopidogrel. In TRITON-TIMI 38, the safety/efficacy of prasugrel compared to clopidogrel was directionally consistent regardless of aspirin dose, though only the primary efficacy endpoint achieved statistical significance. There was no clinically meaningful interaction of aspirin with prasugrel, suggesting that previous observations with potent antiplatelet agents indicating differential results are not universal. http://clinicaltrials.gov/show/NCT00097591; NCT00097591.
    Journal of the American College of Cardiology 10/2013; · 14.09 Impact Factor

Publication Stats

23k Citations
5,468.01 Total Impact Points

Institutions

  • 2001–2014
    • Boston Biomedical Research Institute
      Boston, Massachusetts, United States
  • 1993–2014
    • Brigham and Women's Hospital
      • • TIMI Study Group
      • • Department of Medicine
      • • Division of Cardiovascular Medicine
      Boston, Massachusetts, United States
    • Harvard Medical School
      • • Department of Medicine
      • • Division of Emergency Medicine
      Boston, Massachusetts, United States
  • 2013
    • University of Toronto
      • Department of Medicine
      Toronto, Ontario, Canada
  • 2011–2013
    • Uppsala University
      • Department of Medical Sciences
      Uppsala, Uppsala, Sweden
    • National Heart Centre Singapore
      Tumasik, Singapore
  • 2007–2013
    • The University of Sheffield
      • Department of Cardiovascular Science
      Sheffield, England, United Kingdom
    • Radboud University Medical Centre (Radboudumc)
      Nymegen, Gelderland, Netherlands
    • Cornell University
      • Department of Medicine
      Ithaca, NY, United States
    • Bridgeport Hospital
      Bridgeport, Connecticut, United States
    • Boston College, USA
      Boston, Massachusetts, United States
  • 2002–2013
    • Partners HealthCare
      Boston, Massachusetts, United States
  • 2012
    • University of Rochester
      Rochester, New York, United States
    • Aarhus University Hospital
      • Department of Cardiology
      Århus, Central Jutland, Denmark
  • 2011–2012
    • Albert Einstein College of Medicine
      • Cardiology
      New York City, NY, United States
  • 2010–2012
    • University of New Mexico
      • Division of Cardiology
      Albuquerque, New Mexico, United States
    • National Heart, Lung, and Blood Institute
      Maryland, United States
    • University of Chicago
      • Department of Medicine
      Chicago, IL, United States
    • CSU Mentor
      Long Beach, California, United States
    • University of Illinois at Chicago
      Chicago, Illinois, United States
    • Assistance Publique – Hôpitaux de Paris
      Lutetia Parisorum, Île-de-France, France
    • University Center Rochester
      • Department of Community and Preventive Medicine
      Rochester, Minnesota, United States
    • Uppsala University Hospital
      Uppsala, Uppsala, Sweden
    • Auckland City Hospital
      Окленд, Auckland, New Zealand
    • University at Buffalo, The State University of New York
      • Department of Medicine
      Buffalo, NY, United States
  • 2008–2012
    • St. Michael's Hospital
      Toronto, Ontario, Canada
    • Case Western Reserve University
      • MetroHealth Heart and Vascular Center
      Cleveland, OH, United States
    • Danbury Hospital
      Danbury, Connecticut, United States
    • University of Maryland, Baltimore
      • Division of Cardiology
      Baltimore, MD, United States
    • Celera
      Alameda, California, United States
  • 2001–2012
    • University of Texas Southwestern Medical Center
      • Medical School
      Dallas, Texas, United States
    • Duke University Medical Center
      • • Duke Clinical Research Institute
      • • Division of Cardiology
      Durham, NC, United States
  • 1999–2012
    • University of California, San Francisco
      • • Division of Cardiology
      • • Division of Hospital Medicine
      San Francisco, CA, United States
    • Maine Medical Center
      Portland, Maine, United States
    • Universitair Ziekenhuis Leuven
      • Department of Cardiology
      Leuven, VLG, Belgium
    • Allegheny General Hospital
      Pittsburgh, Pennsylvania, United States
  • 2005–2011
    • Massachusetts General Hospital
      • • Division of Cardiology
      • • Department of Radiology
      Boston, MA, United States
    • Ukranian Research Institute of Aviation Technology
      Kievo, Kyiv City, Ukraine
    • University of Auckland
      • Department of Medicine
      Auckland, Auckland, New Zealand
    • The University of Chicago Medical Center
      Chicago, Illinois, United States
  • 2007–2010
    • Harvard University
      • Department of Economics
      Cambridge, MA, United States
  • 2006–2010
    • University of Cambridge
      • Department of Public Health and Primary Care
      Cambridge, ENG, United Kingdom
    • University of Michigan-Flint
      Flint, Michigan, United States
    • Duke University
      Durham, North Carolina, United States
  • 2002–2010
    • Royal College of Surgeons in Ireland
      • Department of Clinical Pharmacology
      Dublin, Leinster, Ireland
  • 1998–2010
    • University of Southern California
      • Division of Gastrointestinal and Liver Diseases
      Los Angeles, California, United States
  • 2009
    • Centre Hospitalier Universitaire de Montpellier
      Montpelhièr, Languedoc-Roussillon, France
    • Harbor-UCLA Medical Center
      Torrance, California, United States
    • University of Alabama at Birmingham
      Birmingham, Alabama, United States
    • North Carolina Clinical Research
      Raleigh, North Carolina, United States
    • Singapore-MIT Alliance
      Cambridge, Massachusetts, United States
    • Uppsala Monitoring Centre
      Uppsala, Uppsala, Sweden
    • Concordia University–Ann Arbor
      Ann Arbor, Michigan, United States
    • University of Michigan
      Ann Arbor, Michigan, United States
    • California State University, Sacramento
      Sacramento, California, United States
    • Cleveland Clinic
      Cleveland, Ohio, United States
    • Monash University (Australia)
      • Department of Epidemiology and Preventive Medicine
      Melbourne, Victoria, Australia
  • 2002–2009
    • Beth Israel Deaconess Medical Center
      • • Department of Medicine
      • • Division of Cardiovascular Medicine
      Boston, MA, United States
  • 1999–2009
    • Hospital of the University of Pennsylvania
      • • Department of Emergency Medicine
      • • Division of Cardiovascular Medicine
      Philadelphia, Pennsylvania, United States
  • 1994–2009
    • University of Massachusetts Medical School
      • Department of Medicine
      Worcester, MA, United States
    • University of Minnesota Duluth
      Duluth, Minnesota, United States
    • University of Missouri
      • School of Medicine
      Columbia, MO, United States
  • 2007–2008
    • Johns Hopkins Medicine
      • Department of Medicine
      Baltimore, MD, United States
  • 2004–2008
    • University of Texas MD Anderson Cancer Center
      • Department of Orthopaedic Oncology
      Houston, TX, United States
    • William Beaumont Army Medical Center
      El Paso, Texas, United States
    • University of North Carolina at Chapel Hill
      North Carolina, United States
    • Washington University in St. Louis
      • Division of Cardiovascular Division
      Saint Louis, MO, United States
    • Beverly Hospital, Boston MA
      Beverly, Massachusetts, United States
    • University of Oklahoma Health Sciences Center
      Oklahoma City, Oklahoma, United States
  • 2001–2008
    • Baystate Medical Center
      • • Division of Cardiology
      • • Department of Medicine
      Springfield, Massachusetts, United States
  • 1998–2006
    • Henry Ford Hospital
      Detroit, Michigan, United States
  • 2002–2004
    • Madigan Army Medical Center
      Tacoma, Washington, United States
  • 2003
    • Baylor College of Medicine
      • Section of Cardiology
      Houston, TX, United States
    • University of Pennsylvania
      • Department of Medicine
      Philadelphia, PA, United States
    • Assaf Harofeh Medical Center
      Ayun Kara, Central District, Israel
  • 1995–2003
    • University of California, Los Angeles
      • • Department of Orthopaedic Surgery
      • • Division of Cardiology
      Los Angeles, CA, United States
    • New York Presbyterian Hospital
      New York City, New York, United States
    • University of Oslo
      Kristiania (historical), Oslo County, Norway
  • 1999–2002
    • Emory University
      • Division of Cardiology
      Atlanta, GA, United States
  • 1998–2002
    • Good Samaritan Hospital
      Cincinnati, Ohio, United States
  • 1996–2001
    • Good Samaritan Hospital Los Angeles
      Los Angeles, California, United States
  • 1997
    • Columbia University
      • Department of Medicine
      New York City, NY, United States
    • University of Texas Health Science Center at Houston
      Houston, Texas, United States