Christopher P Cannon

Boston Biomedical Research Institute, Boston, Massachusetts, United States

Are you Christopher P Cannon?

Claim your profile

Publications (829)6221.24 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Quality improvement is central to improving the care of patients with cardiovascular disease; however, the optimum type of data feedback to support such efforts is unknown. Over 26 months, 149 eligible Acute Coronary Treatment and Intervention Outcomes Network Registry-Get With The Guidelines hospitals were randomized to receive either standard (n = 76 control) or targeted (n = 73 intervention) performance feedback reports for acute myocardial infarction patient care. Each report summarized performance on identified metrics (providing hospitals with detailed data on their 3 lowest-performing quality metrics, relative to their peers). Intervention sites received 5 targeted feedback reports. Overall composite performance was compared between cohorts at end of study and as a change from baseline. Intervention (n = 60) and control (n = 64) hospitals that completed the study had similar baseline performance (median score 83.7% vs 84.2%). Over 26 months of follow-up, the change in overall composite score across hospitals was neutral (median 0.1% [interquartile range {IQR} -2.4% to 3.3%]). There was no difference in observed improvement in either the intervention (median -0.2% [IQR-2.6% to 3.3%]) or control (median 0.1% [IQR -2.2% to 3.4%]) hospitals. We were unable to demonstrate that targeted performance feedback reports lead to more rapid care improvements than standard reports. Future directions should explore the relationship between hospital self-selection of targeted metrics and the identification and promulgation of less common metrics-particularly those that reflect processes of care. Copyright © 2014 Elsevier Inc. All rights reserved.
    American heart journal. 01/2015; 169(1):132-141.e2.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Prior studies have noted that in-hospital adherence to secondary prevention measures varied among patients undergoing coronary artery bypass grafting, percutaneous coronary revascularization or no-intervention. We sought to study contemporary temporal trends in the in-hospital management of patients with coronary artery disease. Using data from the national GWTG-CAD registry, we sought to compare adherence with 6 performance measures (aspirin within 24 hours, discharge on aspirin, discharge on beta-blockers, patients with low ejection fraction discharged on angiotensin converting enzyme inhibitor /angiotensin receptor blocker, smoking cessation counseling, use of lipid lowering medications) in eligible coronary artery disease patients who underwent coronary artery bypass graft surgery, percutaneous coronary intervention or no-intervention between 2003 and 2008. A total of 113,971 patients with coronary artery disease were treated at 193 hospitals Overall adherence with all 6 quality of care measures improved over time in all 3 treatment groups, but was highest at all time periods in percutaneous coronary intervention patients compared with coronary artery bypass graft surgery patients; whereas no-intervention patients had the lowest use of prevention measures at all time points (p<0.0001) Similarly, 100% adherence to all 6 measures was superior in percutaneous coronary intervention patients at all time points (p<0.0001). On multivariable adjustment for case-mix of patients, the majority of these differences persisted. Over the last decade, overall adherence with secondary prevention measures improved significantly in patients hospitalized with coronary artery disease regardless of revascularization strategy. However, there still exist select opportunities for improving adherence, particularly among patients undergoing coronary artery bypass graft surgery or no-intervention. Copyright © 2014 Elsevier Inc. All rights reserved.
    The American journal of medicine. 11/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: Aims: We sought to describe the differential effect of bleeding events in acute coronary syndromes (ACS) on short- and long-term mortality according to their type and severity. Methods and results: The PLATO trial randomised 18,624 ACS patients to clopidogrel or ticagrelor. Post-randomisation bleeding events were captured according to bleeding type (spontaneous or procedure-related), with PLATO, TIMI, and GUSTO definitions. The association of bleeding events with subsequent short-term (<30 days) and long-term (>30 days) all-cause mortality was assessed using time-dependent Cox proportional hazard models. A model was fitted to compare major and minor bleeding for mortality prediction. Of 18,624 patients, 2,189 (11.8%) had at least one PLATO major bleed (mean follow-up 272.2±123.5 days). Major bleeding was associated with higher short-term mortality (adjusted hazard ratio [HR] 9.28; 95% confidence interval [CI]: 7.50-11.48) but not with long-term mortality (adjusted HR 1.28; 95% CI: 0.93-1.75). Spontaneous bleeding was associated with short-term (adjusted HR 14.59; 95% CI: 11.14-19.11) and long-term (adjusted HR 3.38; 95% CI: 2.26-5.05) mortality. Procedure-related bleeding was associated with short-term mortality (adjusted HR 5.29; 95% CI: 4.06-6.87): CABG-related and non-coronary-procedure-related bleeding were associated with a higher short-term mortality, whereas PCI or angiography-related bleeding was not associated with either short- or long-term mortality. Similar results were obtained using the GUSTO and TIMI bleeding definitions. Conclusions: Major bleeding is associated with high subsequent mortality in ACS. However, this association is much stronger in the first 30 days and is strongest for spontaneous (vs. procedure-related) bleeding.
  • [Show abstract] [Hide abstract]
    ABSTRACT: To investigate the cost effectiveness of ticagrelor versus clopidogrel in patients with acute coronary syndromes (ACS) in the Platelet Inhibition and Patient Outcomes (PLATO) study who were scheduled for non-invasive management.
    Heart (British Cardiac Society) 09/2014; · 5.01 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Lipoprotein-associated phospholipase A2 (Lp-PLA2) has been hypothesized to be involved in atherogenesis through pathways related to inflammation. Darapladib is an oral, selective inhibitor of the Lp-PLA2 enzyme.
    JAMA The Journal of the American Medical Association 08/2014; · 29.98 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Bone metastasis is a poor prognostic indicator in melanoma. Some authors have advocated only palliative treatment for patients with osseous disease.
    Clinical Orthopaedics and Related Research 07/2014; · 2.79 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To describe specific causes of death and evaluate whether bleeding events and infection contributed to mortality in all ticagrelor-treated and clopidogrel-treated patients with acute coronary syndromes.
    Heart (British Cardiac Society) 06/2014; · 5.01 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    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 05/2014; · 1.83 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Anacetrapib is a cholesteryl ester transfer protein (CETP) inhibitor that has previously been shown to reduce low-density lipoprotein cholesterol (LDL-C) and raise high-density lipoprotein cholesterol (HDL-C) in patients with or at high risk of coronary heart disease in the 76-week, placebo-controlled, Determining the Efficacy and Tolerability of CETP Inhibition with Anacetrapib (DEFINE) trial. Here, we report the results of the 2-year extension to the DEFINE study where patients (n = 803) continued on the same assigned treatment as in the original 76-week study. Treatment with anacetrapib during the 2-year extension was well tolerated with a safety profile similar to patients on placebo. No clinically important abnormalities in liver enzymes, blood pressure, electrolytes, or adverse experiences were observed during the extension. At the end of the extension study, relative to the original baseline value, anacetrapib reduced Friedewald-calculated LDL-C by 39.9% and increased HDL-C by 153.3%, compared to placebo. The apparent steady state mean plasma trough concentration of anacetrapib was ∼640 nmol/L. Geometric mean plasma concentrations of anacetrapib did not appear to increase beyond week 40 of the 2-year extension of the 76-week DEFINE base study. In conclusion, an additional 2 years of treatment with anacetrapib were well tolerated with durable lipid-modifying effects on LDL-C and HDL-C.
    Journal of Cardiovascular Pharmacology and Therapeutics 04/2014; · 3.07 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    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; · 14.72 Impact Factor
  • [Show abstract] [Hide abstract]
    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
  • Clinical Cardiology 03/2014; · 1.83 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Due to a high burden of systemic cardiovascular events, current guidelines recommend the use of statins in all patients with peripheral artery disease (PAD). We sought to study the impact of statin use on limb prognosis in patients with symptomatic PAD enrolled in the international REACH registry. Statin use was assessed at study enrolment, as well as a time-varying covariate. Rates of the primary adverse limb outcome (worsening claudication/new episode of critical limb ischaemia, new percutaneous/surgical revascularization, or amputation) at 4 years and the composite of cardiovascular death/myocardial infarction/stroke were compared among statin users vs. non-users. A total of 5861 patients with symptomatic PAD were included. Statin use at baseline was 62.2%. Patients who were on statins had a significantly lower risk of the primary adverse limb outcome at 4 years when compared with those who were not taking statins [22.0 vs. 26.2%; hazard ratio (HR), 0.82; 95% confidence interval (CI), 0.72-0.92; P = 0.0013]. Results were similar when statin use was considered as a time-dependent variable (P = 0.018) and on propensity analysis (P < 0.0001). The composite of cardiovascular death/myocardial infarction/stroke was similarly reduced (HR, 0.83; 95% CI, 0.73-0.96; P = 0.01). Among patients with PAD in the REACH registry, statin use was associated with an ∼18% lower rate of adverse limb outcomes, including worsening symptoms, peripheral revascularization, and ischaemic amputations. These findings suggest that statin therapy not only reduces the risk of adverse cardiovascular events, but also favourably affects limb prognosis in patients with PAD.
    European Heart Journal 02/2014; · 14.72 Impact Factor
  • [Show abstract] [Hide abstract]
    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
  • Source
    [Show abstract] [Hide abstract]
    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 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
  • Source
    [Show abstract] [Hide abstract]
    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
  • [Show abstract] [Hide abstract]
    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
  • [Show abstract] [Hide abstract]
    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;
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Observational studies have raised concerns that high-potency statins increase the risk of acute kidney injury. We therefore examined the incidence of kidney injury across 2 randomized trials of statin therapy. PROVE IT-TIMI 22 enrolled 4162 subjects after an acute coronary syndrome (ACS) and randomized them to atorvastatin 80 mg/day versus pravastatin 40 mg/day. A-to-Z enrolled 4497 subjects after ACS and randomized them to a high-potency (simvastatin 40 mg/day×1 months, then simvastatin 80 mg/day) versus a delayed moderate-potency statin strategy (placebo×4 months, then simvastatin 20 mg/day). Serum creatinine was assessed centrally at serial time points. Adverse events (AEs) relating to kidney injury were identified through database review. Across both trials, mean serum creatinine was similar between treatment arms at baseline and throughout follow-up. In A-to-Z, the incidence of a 1.5-fold or ≥0.3 mg/dL rise in serum creatinine was 11.4% for subjects randomized to a high-potency statin regimen versus 12.4% for those on a delayed moderate-potency regimen (odds ratio [OR], 0.91; 95% confidence interval [CI], 0.76 to 1.10; P=0.33). In PROVE IT-TIMI 22, the incidence was 9.4% for subjects randomized to atorvastatin 80 mg/day and 10.6% for subjects randomized to pravastatin 40 mg/day (OR, 0.88; 95% CI, 0.71 to 1.09; P=0.25). Consistent results were observed for different kidney injury thresholds and in individuals with diabetes mellitus or with moderate renal dysfunction. The incidence of kidney injury-related adverse events (AEs) was not statistically different for patients on a high-potency versus moderate-potency statin regimen (OR, 1.06; 95% CI, 0.68 to 1.67; P=0.78). For patients enrolled in 2 large randomized trials of statin therapy after ACS, the use of a high-potency statin regimen did not increase the risk of kidney injury.
    Journal of the American Heart Association. 01/2014; 3(3):e000784.
  • [Show abstract] [Hide abstract]
    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. · 3.21 Impact Factor

Publication Stats

30k Citations
6,221.24 Total Impact Points


  • 2001–2014
    • Boston Biomedical Research Institute
      Boston, Massachusetts, United States
    • University of Texas Health Science Center at San Antonio
      • Division of Hospital Medicine
      San Antonio, TX, United States
  • 1999–2014
    • University of California, San Francisco
      • • Division of Cardiology
      • • Division of Hospital Medicine
      San Francisco, California, United States
    • Allegheny General Hospital
      Pittsburgh, Pennsylvania, United States
    • Maine Medical Center
      Portland, Maine, United States
    • Universitair Ziekenhuis Leuven
      • Department of Cardiology
      Leuven, VLG, Belgium
  • 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
    • University of Maryland, Baltimore
      • Division of Cardiology
      Baltimore, MD, United States
    • Danbury Hospital
      Danbury, Connecticut, United States
    • Case Western Reserve University
      • MetroHealth Heart and Vascular Center
      Cleveland, OH, 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
  • 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
  • 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
    • Concordia University–Ann Arbor
      Ann Arbor, Michigan, United States
    • North Carolina Clinical Research
      Raleigh, North Carolina, United States
    • Singapore-MIT Alliance
      Cambridge, Massachusetts, United States
    • Uppsala Monitoring Centre
      Uppsala, Uppsala, Sweden
    • Cleveland Clinic
      Cleveland, Ohio, United States
    • California State University, Sacramento
      Sacramento, California, United States
    • University of Michigan
      Ann Arbor, Michigan, 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
    • 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
  • 1998–2008
    • University of Southern California
      • Division of Gastrointestinal and Liver Diseases
      Los Angeles, CA, United States
  • 1998–2006
    • Henry Ford Hospital
      Detroit, Michigan, United States
  • 2002–2004
    • Madigan Army Medical Center
      Tacoma, Washington, United States
  • 2001–2004
    • Beverly Hospital, Boston MA
      Beverly, Massachusetts, 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
    • University of Oslo
      Kristiania (historical), Oslo County, Norway
    • New York Presbyterian Hospital
      New York City, New York, United States
  • 1999–2002
    • Emory University
      • Division of Cardiology
      Atlanta, GA, United States
  • 1998–2002
    • Good Samaritan Hospital
      Suffern, New York, 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