Marc S Sabatine

Brigham and Women's Hospital, Boston, Massachusetts, United States

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Publications (290)3999.35 Total impact

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    ABSTRACT: Aims: We evaluated the relationship of renal function and ischaemic and bleeding risk as well as the efficacy and safety of ticagrelor in stable patients with prior myocardial infarction (MI). Methods and results: Patients with a history of MI 1-3 years prior from PEGASUS-TIMI 54 were stratified based on estimated glomerular filtration rate (eGFR), with <60 mL/min/1.73 m(2) pre-specified for analysis of the effect of ticagrelor on the primary efficacy composite of cardiovascular death, MI, or stroke (major adverse cardiovascular events, MACE) and the primary safety endpoint of TIMI major bleeding. Of 20 898 patients, those with eGFR <60 (N = 4849, 23.2%) had a greater risk of MACE at 3 years relative to those without, which remained significant after multivariable adjustment (hazard ratio, HRadj 1.54, 95% confidence interval, CI 1.27-1.85, P < 0.001). The relative risk reduction in MACE with ticagrelor was similar in those with eGFR <60 (ticagrelor pooled vs. placebo: HR 0.81; 95% CI 0.68-0.96) vs. ≥60 (HR 0.88; 95% CI 0.77-1.00, Pinteraction = 0.44). However, due to the greater absolute risk in the former group, the absolute risk reduction with ticagrelor was higher: 2.7 vs. 0.63%. Bleeding tended to occur more frequently in patients with renal dysfunction. The absolute increase in TIMI major bleeding with ticagrelor was similar in those with and without eGFR <60 (1.19 vs. 1.43%), whereas the excess of minor bleeding tended to be more pronounced (1.93 vs. 0.69%). Conclusion: In patients with a history of MI, patients with renal dysfunction are at increased risk of MACE and consequently experience a particularly robust absolute risk reduction with long-term treatment with ticagrelor.
    European Heart Journal 10/2015; DOI:10.1093/eurheartj/ehv482 · 15.20 Impact Factor
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    ABSTRACT: Aims: Recent trials have examined the effect of prolonged dual antiplatelet therapy (DAPT) in a variety of patient populations,with heterogeneous results regarding benefit and safety, specifically with regard to cardiovascular and non-cardiovascularmortality. We performed a meta-analysis of randomized trials comparing more than a year of DAPT with aspirinalone in high-risk patients with a history of prior myocardial infarction (MI). Methods and results: A total of 33 435 patients were followed over a mean 31 months among one trial of patients with prior MI (63.3% of total) and five trials with a subgroup of patients that presented with, or had a history of, a prior MI (36.7% of total). Extended DAPT decreased the risk of major adverse cardiovascular events compared with aspirin alone (6.4 vs. 7.5%; risk ratio, RR 0.78, 95% confidence intervals, CI, 0.67–0.90; P ¼ 0.001) and reduced cardiovascular death (2.3 vs. 2.6%; RR 0.85, 95% CI 0.74–0.98; P ¼ 0.03), with no increase in non-cardiovascular death (RR 1.03, 95% CI 0.86–1.23; P ¼ 0.76). The resultant effect on all-cause mortality was an RR of 0.92 (95% CI 0.83–1.03; P ¼ 0.13). Extended DAPT also reduced MI (RR 0.70, 95% CI 0.55–0.88; P ¼ 0.003), stroke (RR 0.81, 95% CI 0.68–0.97; P ¼ 0.02), and stent thrombosis (RR 0.50, 95% CI 0.28–0.89; P ¼ 0.02). There was an increased risk of major bleeding (1.85 vs. 1.09%; RR 1.73, 95% CI 1.19–2.50; P ¼ 0.004) but not fatal bleeding (0.14 vs. 0.17%; RR 0.91, 95% CI 0.53–1.58; P ¼ 0.75). Conclusion: Compared with aspirin alone, DAPT beyond 1 year among stabilized high-risk patients with prior MI decreases ischaemic events, including significant reductions in the individual endpoints of cardiovascular death, recurrent MI, and stroke. Dual antiplatelet therapy beyond 1 year increases major bleeding, but not fatal bleeding or non-cardiovascular death
    European Heart Journal 08/2015; DOI:10.1093/eurheartj/ehv443 · 15.20 Impact Factor
  • Marc S Sabatine · Scott M Wasserman · Evan A Stein
    New England Journal of Medicine 08/2015; 373(8):774-5. · 55.87 Impact Factor
  • Gilles Montalescot · Marc S Sabatine
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    ABSTRACT: International guidelines recommend the use of aspirin treatment immediately and indefinitely in coronary patients. The optimal time to start and the duration of dual antiplatelet therapy (DAPT; aspirin plus a P2Y12 inhibitor) have not been clearly established. Recent clinical trials have provided important new information allowing for evidence-based decisions regarding timing of initiation and duration of DAPT. The benefit-to-risk ratio of DAPT pre-treatment appears to depend on the type of acute coronary syndrome, the time until angiography, and the onset of action of the drug. In stable patients undergoing percutaneous coronary intervention with the latest generation drug-eluting stents, patients should be treated for at least ∼6 months. Shorter courses of therapy may be necessary when special conditions occur (e.g. surgery; oral anticoagulation). Longer courses of therapy may be reasonable in patients at low bleeding risk who are tolerating DAPT well. For patients with ACS, prolonged DAPT is beneficial and therefore reasonable as long as the patient is tolerating the therapy. Individualized management of DAPT must be seen as a dynamic prescription with regular re-evaluations of the risk-benefit to the patient according to changes in his/her clinical profile. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email:
    European Heart Journal 08/2015; DOI:10.1093/eurheartj/ehv377 · 15.20 Impact Factor
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    ABSTRACT: Patients with stable coronary heart disease (CHD) have widely varying prognoses and treatment options. Validated models for risk stratification of patients with CHD are needed. We sought to evaluate traditional and novel risk factors as predictors of secondary cardiovascular (CV) events, and to develop a prediction model that could be used to risk stratify patients with stable CHD. We used independent derivation (912 participants in the Heart and Soul Study) and validation (2876 participants in the PEACE trial) cohorts of patients with stable CHD to develop a risk prediction model using Cox proportional hazards models. The outcome was CV events, defined as myocardial infarction, stroke, or CV death. The annual rate of CV events was 3.4% in the derivation cohort and 2.2% in the validation cohort. With the exception of smoking, traditional risk factors (including age, sex, body mass index, hypertension, dyslipidemia, and diabetes) did not emerge as the top predictors of secondary CV events. The top 4 predictors of secondary events were the following: N-terminal pro-type brain natriuretic peptide, high-sensitivity cardiac troponin T, urinary albumin:creatinine ratio, and current smoking. The 5-year C-index for this 4-predictor model was 0.73 in the derivation cohort and 0.65 in the validation cohort. As compared with variables in the Framingham secondary events model, the Heart and Soul risk model resulted in net reclassification improvement of 0.47 (95% CI 0.25 to 0.73) in the derivation cohort and 0.18 (95% CI 0.01 to 0.40) in the validation cohort. Novel risk factors are superior to traditional risk factors for predicting 5-year risk of secondary events in patients with stable CHD. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.
    Journal of the American Heart Association 07/2015; 4(7). DOI:10.1161/JAHA.114.001646 · 4.31 Impact Factor
  • Giulia Magnani · Marc P. Bonaca · Marc S. Sabatine
    06/2015; DOI:10.1093/ehjcvp/pvv030
  • Robert P Giugliano · Marc S Sabatine
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    ABSTRACT: Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to the low-density lipoprotein receptor, escorting it to its destruction in the lysosome and thereby preventing the recirculation of the low-density lipoprotein receptor to the hepatocyte cell surface. Both gain-of-function mutations in PCSK9 (causing marked increases in low-density lipoprotein cholesterol [LDL-C] concentration and premature atherosclerosis) and loss-of-function mutations (causing modest LDL-C reduction with low rates of coronary heart disease) have been described. Several monoclonal antibodies to PCSK9 have achieved LDL-C reductions of 50% to 70% across various patient populations and background lipid therapies. Phase 2/3 trials have demonstrated good tolerability without clear drug-related toxicity, although the number and duration of patients treated to date is modest. Currently, 4 phase 3 trials involving >70,000 patients are testing whether these drugs reduce cardiovascular events. The U.S. Food and Drug Administration is currently reviewing the existing data to determine whether these agents could be made available prior to the completion of these cardiovascular endpoint trials expected in 2018. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
    Journal of the American College of Cardiology 06/2015; 65(24):2638-51. DOI:10.1016/j.jacc.2015.05.001 · 16.50 Impact Factor
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    ABSTRACT: Resistin is an adipokine secreted by macrophages and inflammatory cells linked to insulin resistance and inflammation. Leptin is an adipokine regulator of appetite and obesity. Although circulating levels of both have been associated with atherosclerosis, few data have reported their relation to coronary events in the context of statin therapy. This study measured on-statin levels of both resistin and leptin through enzyme-linked immunosorbent assay in a nested case-control cohort (n = 176 cases with coronary death, myocardial infarction, or unstable angina pectoris observed in follow-up matched 1:1 to 176 controls) derived from the Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 study, a randomized controlled trial of atorvastatin 80 mg/day versus pravastatin 40 mg/day in patients with a recent acute coronary syndrome. Resistin demonstrated a moderate association with high-sensitivity C-reactive protein (hsCRP; Spearman rho = 0.25, p <0.0001). On-statin resistin levels were linked to recurrent coronary events in conditional logistic regression analysis adjusted for additional risk factors including hsCRP and history of diabetes (tertile 3 vs 1 adjusted odds ratio 2.08; 95% confidence interval [CI] 1.04 to 4.19). An additive risk was noted when patients were stratified by resistin and glycated hemoglobin levels. In contrast, leptin levels were associated with obesity, diabetes, triglycerides, and hsCRP (p <0.001 for each) but demonstrated no association with recurrent coronary events (tertile 3 vs 1 adjusted odds ratio 0.72; 95% CI 0.28 to 1.83). In conclusion, on-statin resistin, but not leptin, is an independent marker of residual risk for recurrent coronary events in patients after hospitalization for an acute coronary syndrome. Copyright © 2015 Elsevier Inc. All rights reserved.
    The American Journal of Cardiology 06/2015; 116(5). DOI:10.1016/j.amjcard.2015.05.038 · 3.28 Impact Factor
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    ABSTRACT: Acute myocardial infarction (AMI) has become a major cause of hospitalization and mortality in China. There has been limited data to date available to characterize AMI presentation, contemporary patterns of medical care, and outcomes in China.
    American Heart Journal 04/2015; 156. DOI:10.1016/j.ahj.2015.04.014 · 4.46 Impact Factor
  • Journal of the American College of Cardiology 03/2015; 65(10). DOI:10.1016/S0735-1097(15)60011-0 · 16.50 Impact Factor
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    ABSTRACT: Background: Evolocumab, a monoclonal antibody that inhibits proprotein convertase subtilisin-kexin type 9 (PCSK9), significantly reduced low-density lipoprotein (LDL) cholesterol levels in short-term studies. We conducted two extension studies to obtain longer-term data. Methods: In two open-label, randomized trials, we enrolled 4465 patients who had completed 1 of 12 phase 2 or 3 studies ("parent trials") of evolocumab. Regardless of study-group assignments in the parent trials, eligible patients were randomly assigned in a 2:1 ratio to receive either evolocumab (140 mg every 2 weeks or 420 mg monthly) plus standard therapy or standard therapy alone. Patients were followed for a median of 11.1 months with assessment of lipid levels, safety, and (as a prespecified exploratory analysis) adjudicated cardiovascular events including death, myocardial infarction, unstable angina, coronary revascularization, stroke, transient ischemic attack, and heart failure. Data from the two trials were combined. Results: As compared with standard therapy alone, evolocumab reduced the level of LDL cholesterol by 61%, from a median of 120 mg per deciliter to 48 mg per deciliter (P<0.001). Most adverse events occurred with similar frequency in the two groups, although neurocognitive events were reported more frequently in the evolocumab group. The risk of adverse events, including neurocognitive events, did not vary significantly according to the achieved level of LDL cholesterol. The rate of cardiovascular events at 1 year was reduced from 2.18% in the standard-therapy group to 0.95% in the evolocumab group (hazard ratio in the evolocumab group, 0.47; 95% confidence interval, 0.28 to 0.78; P=0.003). Conclusions: During approximately 1 year of therapy, the use of evolocumab plus standard therapy, as compared with standard therapy alone, significantly reduced LDL cholesterol levels and reduced the incidence of cardiovascular events in a prespecified but exploratory analysis. (Funded by Amgen; OSLER-1 and OSLER-2 numbers, NCT01439880 and NCT01854918.).
    New England Journal of Medicine 03/2015; 372(16). DOI:10.1056/NEJMoa1500858 · 55.87 Impact Factor
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    ABSTRACT: Background: The potential benefit of dual antiplatelet therapy beyond 1 year after a myocardial infarction has not been established. We investigated the efficacy and safety of ticagrelor, a P2Y12 receptor antagonist with established efficacy after an acute coronary syndrome, in this context. Methods: We randomly assigned, in a double-blind 1:1:1 fashion, 21,162 patients who had had a myocardial infarction 1 to 3 years earlier to ticagrelor at a dose of 90 mg twice daily, ticagrelor at a dose of 60 mg twice daily, or placebo. All the patients were to receive low-dose aspirin and were followed for a median of 33 months. The primary efficacy end point was the composite of cardiovascular death, myocardial infarction, or stroke. The primary safety end point was Thrombolysis in Myocardial Infarction (TIMI) major bleeding. Results: The two ticagrelor doses each reduced, as compared with placebo, the rate of the primary efficacy end point, with Kaplan-Meier rates at 3 years of 7.85% in the group that received 90 mg of ticagrelor twice daily, 7.77% in the group that received 60 mg of ticagrelor twice daily, and 9.04% in the placebo group (hazard ratio for 90 mg of ticagrelor vs. placebo, 0.85; 95% confidence interval [CI], 0.75 to 0.96; P=0.008; hazard ratio for 60 mg of ticagrelor vs. placebo, 0.84; 95% CI, 0.74 to 0.95; P=0.004). Rates of TIMI major bleeding were higher with ticagrelor (2.60% with 90 mg and 2.30% with 60 mg) than with placebo (1.06%) (P<0.001 for each dose vs. placebo); the rates of intracranial hemorrhage or fatal bleeding in the three groups were 0.63%, 0.71%, and 0.60%, respectively. Conclusions: In patients with a myocardial infarction more than 1 year previously, treatment with ticagrelor significantly reduced the risk of cardiovascular death, myocardial infarction, or stroke and increased the risk of major bleeding. (Funded by AstraZeneca; PEGASUS-TIMI 54 number, NCT01225562.).
    New England Journal of Medicine 03/2015; 372(19). DOI:10.1056/NEJMoa1500857 · 55.87 Impact Factor
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    ABSTRACT: Warfarin is the most widely used oral anticoagulant worldwide, but serious bleeding complications are common. We tested whether genetic variants can identify patients who are at increased risk of bleeding with warfarin and, consequently, those who would derive a greater safety benefit with a direct oral anticoagulant rather than warfarin. ENGAGE AF-TIMI 48 was a randomised, double-blind trial in which patients with atrial fibrillation were assigned to warfarin to achieve a target international normalised ratio of 2·0-3·0, or to higher-dose (60 mg) or lower-dose (30 mg) edoxaban once daily. A subgroup of patients was included in a prespecified genetic analysis and genotyped for variants in CYP2C9 and VKORC1. The results were used to create three genotype functional bins (normal, sensitive, and highly sensitive responders to warfarin). This trial is registered with, number NCT00781391. 14 348 patients were included in the genetic analysis. Of 4833 taking warfarin, 2982 (61·7%) were classified as normal responders, 1711 (35·4%) as sensitive responders, and 140 (2·9%) as highly sensitive responders. Compared with normal responders, sensitive and highly sensitive responders spent greater proportions of time over-anticoagulated in the first 90 days of treatment (median 2·2%, IQR 0-20·2; 8·4%, 0-25·8; and 18·3%, 0-32·6; ptrend<0·0001) and had increased risks of bleeding with warfarin (sensitive responders hazard ratio 1·31, 95% CI 1·05-1·64, p=0·0179; highly sensitive responders 2·66, 1·69-4·19, p<0·0001). Genotype added independent information beyond clinical risk scoring. During the first 90 days, when compared with warfarin, treatment with edoxaban reduced bleeding more so in sensitive and highly sensitive responders than in normal responders (higher-dose edoxaban pinteraction=0·0066; lower-dose edoxaban pinteraction=0·0036). After 90 days, the reduction in bleeding risk with edoxaban versus warfarin was similarly beneficial across genotypes. CYP2C9 and VKORC1 genotypes identify patients who are more likely to experience early bleeding with warfarin and who derive a greater early safety benefit from edoxaban compared with warfarin. Daiichi Sankyo. Copyright © 2015 Elsevier Ltd. All rights reserved.
    The Lancet 03/2015; 385(9984). DOI:10.1016/S0140-6736(14)61994-2 · 45.22 Impact Factor
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    ABSTRACT: Genetic variants have been associated with the risk of coronary heart disease. In this study, we tested whether or not a composite of these variants could ascertain the risk of both incident and recurrent coronary heart disease events and identify those individuals who derive greater clinical benefit from statin therapy. A community-based cohort study (the Malmo Diet and Cancer Study) and four randomised controlled trials of both primary prevention (JUPITER and ASCOT) and secondary prevention (CARE and PROVE IT-TIMI 22) with statin therapy, comprising a total of 48 421 individuals and 3477 events, were included in these analyses. We studied the association of a genetic risk score based on 27 genetic variants with incident or recurrent coronary heart disease, adjusting for traditional clinical risk factors. We then investigated the relative and absolute risk reductions in coronary heart disease events with statin therapy stratified by genetic risk. We combined data from the different studies using a meta-analysis. When individuals were divided into low (quintile 1), intermediate (quintiles 2-4), and high (quintile 5) genetic risk categories, a significant gradient in risk for incident or recurrent coronary heart disease was shown. Compared with the low genetic risk category, the multivariable-adjusted hazard ratio for coronary heart disease for the intermediate genetic risk category was 1·34 (95% CI 1·22-1·47, p<0·0001) and that for the high genetic risk category was 1·72 (1·55-1·92, p<0·0001). In terms of the benefit of statin therapy in the four randomised trials, we noted a significant gradient (p=0·0277) of increasing relative risk reductions across the low (13%), intermediate (29%), and high (48%) genetic risk categories. Similarly, we noted greater absolute risk reductions in those individuals in higher genetic risk categories (p=0·0101), resulting in a roughly threefold decrease in the number needed to treat to prevent one coronary heart disease event in the primary prevention trials. Specifically, in the primary prevention trials, the number needed to treat to prevent one such event in 10 years was 66 in people at low genetic risk, 42 in those at intermediate genetic risk, and 25 in those at high genetic risk in JUPITER, and 57, 47, and 20, respectively, in ASCOT. A genetic risk score identified individuals at increased risk for both incident and recurrent coronary heart disease events. People with the highest burden of genetic risk derived the largest relative and absolute clinical benefit from statin therapy. National Institutes of Health. Copyright © 2015 Elsevier Ltd. All rights reserved.
    The Lancet 03/2015; 385(9984). DOI:10.1016/S0140-6736(14)61730-X · 45.22 Impact Factor
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    ABSTRACT: High-sensitivity cardiac troponin T (hsTnT) is used in many countries, but is not available in the United States. Prior evidence has been viewed as inconclusive as to whether low cardiac troponin T (cTnT) concentrations detected with hsTnT are prognostically meaningful compared with fourth-generation cTnT. The aim of this study was to assess the prognostic performance of low-level cTnT elevations using the hsTnT assay compared with the assay (fourth-generation) currently available in the United States. We measured serum cTnT in 4160 patients with non-ST-elevation acute coronary syndrome using both the hsTnT and fourth-generation assays. Patients were stratified at the 99th percentile cut point for each assay. Patients with baseline hsTnT ≥14 ng/L (n = 3697) vs <14 ng/L were at higher 30-day risk of cardiovascular death (CVD) or myocardial infarction (MI) (9.1% vs 1.9%, P < 0.0001). After adjusting for all other elements of the Thrombolysis In Myocardial Infarction risk score, hsTnT ≥14 carried a 5.2-fold higher risk of CVD/MI (95% confidence interval [CI]: 2.6-10.1, P < 0.0001). Low levels of hsTnT (14-50 ng/L) also revealed increased risk (CVD/MI: 6.4%, P = 0.002). Importantly, patients with negative fourth-generation cTnT but positive hsTnT were at 4.5-times higher risk of CVD/MI (95% CI: 1.9-11.0, P = 0.0008) than patients with negative hsTnT. In contrast, patients with a negative hsTnT but positive fourth-generation cTnT result had a lower rate of CVD/MI than with a positive hsTnT (1.3% vs 8.2%, P = 0.0005). Low-level increases in cTnT detected using the hsTnT assay identified patients at a meaningfully higher risk and who might otherwise be missed, and improves upon risk stratification using the cTnT assay currently available in the United States. © 2015 Wiley Periodicals, Inc.
    Clinical Cardiology 03/2015; 38(4). DOI:10.1002/clc.22379 · 2.59 Impact Factor
  • Haiyan Xu · YueJin Yang · Xinran Tang · Marc Sabatine · Stephen Wiviott
    Journal of the American College of Cardiology 03/2015; 65(10):A137. DOI:10.1016/S0735-1097(15)60137-1 · 16.50 Impact Factor
  • Journal of the American College of Cardiology 03/2015; 65(10):A1364. DOI:10.1016/S0735-1097(15)61364-X · 16.50 Impact Factor
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    ABSTRACT: p38 mitogen-activated protein kinase (MAPK) mediates cytokine production and amplification of the inflammatory cascade. Through inhibition of p38 MAPK, losmapimod appears to attenuate the inflammatory response in the vascular wall and thus may help stabilize plaques. The LATITUDE-TIMI 60 trial is a randomized, double-blind, placebo-controlled, parallel-group, multicenter study planned to be conducted in a 3-stage design. Overall, the trial is designed to include 25,500 patients hospitalized with non-ST-elevation or ST-elevation myocardial infarction (MI) randomized to oral losmapimod (7.5 mg twice daily) versus matching placebo. Part A consists of a leading cohort (n = 3,500) that will provide an initial assessment of safety and exploratory efficacy before progressing to part B. Part B (n = ~22,000) of the study is event driven and will provide the primary assessment of efficacy. An independent safety review will be conducted after 3,500 patients in part B1 to determine whether a more focused schedule of clinic visits and laboratory assessments can be implemented (part B2). All patients are to be treated with study drug until week 12 and followed up until week 24. The primary end point is the composite of cardiovascular death, MI, or severe recurrent ischemia requiring urgent coronary revascularization. The key secondary end point is the composite of cardiovascular death or MI. The trial is designed to provide ≥90% power for the primary end point. The LATITUDE-TIMI 60 trial will determine the efficacy and safety of short-term p38 MAPK inhibition with losmapimod in acute MI. The trial design adopts a stepwise approach to decision making and collection of data. Copyright © 2015 Elsevier Inc. All rights reserved.
    American heart journal 02/2015; 169(5). DOI:10.1016/j.ahj.2015.02.012 · 4.46 Impact Factor
  • Nihar R Desai · Marc S Sabatine
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    ABSTRACT: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a serine protease that plays an important role in modulating low-density lipoprotein cholesterol (LDL-C) levels by targeting LDL-C receptors for lysosomal degradation. Genetic association studies have demonstrated that loss-of-function mutations in PCSK9 are associated with low plasma LDL-C levels and a reduction in the incidence of adverse cardiovascular events. Monoclonal antibodies directed against PCSK9 have been developed and have been shown in phase 1, 2, and 3 trials to dramatically reduce LDL-C regardless of background lipid-lowering therapy, including in clinically challenging populations such as patients intolerant to statin therapy and those with familial hypercholesterolemia. To date, the clinical trials have not raised any significant safety concerns, with no appreciable excess of myalgias, elevation in aminotransferases, or other adverse events. Large, cardiovascular outcomes trials are underway to assess definitively the efficacy and safety of 3 monoclonal antibodies (evolocumab, alirocumab, and bococizumab), while additional non-monoclonal antibody approaches to inhibit PCSK9 continue in the early-phase development. Copyright © 2015 Elsevier Inc. All rights reserved.
    Trends in Cardiovascular Medicine 02/2015; DOI:10.1016/j.tcm.2015.01.009 · 2.91 Impact Factor
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    ABSTRACT: Newer troponin assays offer the ability to quantify circulating troponin levels at an order of magnitude lower than contemporary assays, fueling continued debate over the prognostic implications of very low-level increases in concentration. We evaluated the prognostic implications of low-level increases in cardiac troponin I (cTnI) using an investigational single-molecule high-sensitivity assay in patients with acute coronary syndrome (ACS). We measured cTnI using both a high-sensitivity troponin I (hsTnI) assay (Erenna, Singulex, 99(th) percentile 9 pg/ml) and a current generation sensitive assay (TnI-Ultra, Siemens, 99(th) percentile 40 pg/ml) at baseline in 1807 patients with non-ST elevation ACS and compared their prognostic ability for adverse cardiovascular events at 30 days and one year. Among patients with TnI-Ultra<99(th) percentile, patients with elevated hsTnI (≥9 pg/ml) had a significantly higher risk than patients with hsTnI<9 pg/ml: cardiovascular death (CVD) or myocardial infarction (MI) at one year (7.0% vs 3.8%; p<0.001, hazard ratio (HR) 2.05, confidence interval (CI) 1.23-3.41); including a higher risk of CVD (3.5% vs 1.5%, p<0.001) and MI (5.0% vs 2.8%, p<0.001) individually. This higher risk of CVD/MI was independent of clinical risk stratification using the TIMI Risk Score (adj. HR 1.76, CI 1.05-2.90). Moreover, hsTnI showed a trend toward a gradient of risk even below the cTnI 99 percentile. Low-level cardiac troponin detected using a single-molecule technique, below the cutpoint of a contemporary sensitive assay, identified a significant gradient of risk. These findings support the prognostic relevance of low-level cardiac troponin elevation with increasingly sensitive assays in patients with ACS. © The European Society of Cardiology 2014.
    European Heart Journal: Acute Cardiovascular Care 12/2014; 59(13). DOI:10.1177/2048872614564081

Publication Stats

16k Citations
3,999.35 Total Impact Points


  • 2002–2015
    • Brigham and Women's Hospital
      • • TIMI Study Group
      • • Department of Medicine
      Boston, Massachusetts, United States
  • 2001–2015
    • Harvard Medical School
      • Department of Medicine
      Boston, Massachusetts, United States
    • University of Oslo
      Kristiania (historical), Oslo, Norway
  • 2002–2014
    • Harvard University
      Cambridge, Massachusetts, United States
  • 2009–2013
    • University of Massachusetts Boston
      Boston, Massachusetts, United States
    • Massachusetts Institute of Technology
      Cambridge, Massachusetts, United States
  • 2008–2009
    • Broad Institute of MIT and Harvard
      Cambridge, Massachusetts, United States
    • Beth Israel Deaconess Medical Center
      • Department of Medicine
      Boston, Massachusetts, United States
  • 2007
    • University of Cambridge
      • Department of Public Health and Primary Care
      Cambridge, ENG, United Kingdom
  • 2006–2007
    • George Washington University
      Washington, Washington, D.C., United States
  • 2004–2007
    • Emory University
      Atlanta, Georgia, United States
  • 2005–2006
    • Duke University
      Durham, North Carolina, United States
  • 2003–2006
    • University of Texas at Dallas
      Richardson, Texas, United States
    • Washington Hospital Center
      Washington, Washington, D.C., United States
  • 2000–2006
    • Massachusetts General Hospital
      • • Department of Medicine
      • • Division of Cardiology
      • • Thoracic Aortic Center
      Boston, MA, United States
  • 2002–2005
    • Partners HealthCare
      Boston, Massachusetts, United States