Browsing by Author "Scirica, Benjamin M"

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    ItemOpen Access
    Angina and Future Cardiovascular Events in Stable Patients With Coronary Artery Disease: Insights From the Reduction of Atherothrombosis for Continued Health (REACH) Registry.
    (Journal of the American Heart Association, 2016-09-28) Eisen, Alon; Bhatt, Deepak L; Steg, P Gabriel; Eagle, Kim A; Goto, Shinya; Guo, Jianping; Smith, Sidney C; Ohman, E Magnus; Scirica, Benjamin M; REACH Registry Investigators
    The extent to which angina is associated with future cardiovascular events in patients with coronary artery disease has long been debated.Included were outpatients with established coronary artery disease who were enrolled in the REACH registry and were followed for 4 years. Angina at baseline was defined as necessitating episodic or permanent antianginal treatment. The primary end point was the composite of cardiovascular death, myocardial infarction, or stroke. Secondary end points included heart failure, cardiovascular hospitalizations, and coronary revascularization. The independent association between angina and first/total events was examined using Cox and logistic regression models. Out of 26 159 patients with established coronary artery disease, 13 619 (52%) had angina at baseline. Compared with patients without angina, patients with angina were more likely to be older, female, and had more heart failure and polyvascular disease (P<0.001 for each). Compared with patients without angina, patients with angina had higher rates of first primary end-point event (14.2% versus 16.3%, unadjusted hazard ratio 1.19, CI 1.11-1.27, P<0.001; adjusted hazard ratio 1.06, CI 0.99-1.14, P=0.11), and total primary end-point events (adjusted risk ratio 1.08, CI 1.01-1.16, P=0.03). Patients with angina were at increased risk for heart failure (adjusted odds ratio 1.17, CI 1.06-1.28, P=0.002), cardiovascular hospitalizations (adjusted odds ratio 1.29, CI 1.21-1.38, P<0.001), and coronary revascularization (adjusted odds ratio 1.23, CI 1.13-1.34, P<0.001).Patients with stable coronary artery disease and angina have higher rates of future cardiovascular events compared with patients without angina. After adjustment, angina was only weakly associated with cardiovascular death, myocardial infarction, or stroke, but significantly associated with heart failure, cardiovascular hospitalization, and coronary revascularization.
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    Outcomes According to Cardiac Catheterization Referral and Clopidogrel Use Among Medicare Patients With Non-ST-Segment Elevation Myocardial Infarction Discharged Without In-hospital Revascularization.
    (J Am Heart Assoc, 2016-03-14) Hess, Connie N; Hellkamp, Anne S; Roe, Matthew T; Thomas, Laine; Scirica, Benjamin M; Peng, S Andrew; Peterson, Eric D; Wang, Tracy Y
    BACKGROUND: While use of P2Y12 receptor inhibitor is recommended by guidelines, few studies have examined its effectiveness among older non-ST-segment elevation myocardial infarction patients who did not undergo coronary revascularization. METHODS AND RESULTS: We included unrevascularized non-ST-segment elevation myocardial infarction patients ≥65 years discharged home from 463 ACTION Registry-GWTG hospitals from 2007 to 2010. Rates of discharge clopidogrel use were described for patients with no angiography, angiography without obstructive coronary artery disease (CAD; ≥50% stenosis in ≥1 vessel), and angiography with obstructive CAD. Two-year outcomes were ascertained from linked Medicare data and included composite major adverse cardiac events (defined as all-cause death, myocardial infarction readmission, or revascularization), and individual components. Outcomes associated with clopidogrel use were adjusted using inverse probability-weighted propensity modeling. Of 14 154 unrevascularized patients, 54.7% (n=7745) did not undergo angiography, 10.6% (n=1494) had angiography without CAD, and 34.7% (n=4915) had angiography with CAD. Discharge clopidogrel was prescribed for 42.2% of all unrevascularized patients: 37.8% without angiography, 34.1% without obstructive CAD at angiography, and 51.6% with obstructive CAD at angiography. Discharge clopidogrel use was not associated with major adverse cardiac events in any group: without angiography (adjusted hazard ratio [95% CI]: 0.99 [0.93-1.06]), angiography without CAD (1.04 [0.74-1.47]), and angiography with CAD (1.12 [1.00-1.25], Pinteraction=0.20). CONCLUSIONS: We found no association between discharge clopidogrel use and long-term risk of major adverse cardiac events among older, unrevascularized non-ST-segment elevation myocardial infarction patients. Clopidogrel use in this population requires further prospective evaluation.
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    Role of ST2 in non-ST-elevation acute coronary syndrome in the MERLIN-TIMI 36 trial.
    (Clinical chemistry, 2012-01) Kohli, Payal; Bonaca, Marc P; Kakkar, Rahul; Kudinova, Anastacia Y; Scirica, Benjamin M; Sabatine, Marc S; Murphy, Sabina A; Braunwald, Eugene; Lee, Richard T; Morrow, David A

    Objective

    We investigated the prognostic performance of ST2 with respect to cardiovascular death (CVD) and heart failure (HF) in patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) in a large multinational trial.

    Background

    Myocytes that are subjected to mechanical stress secrete ST2, a soluble interleukin-1 receptor family member that is associated with HF after STE-ACS.

    Methods

    We measured ST2 with a high-sensitivity assay in all available baseline samples (N=4426) in patients enrolled in the Metabolic Efficiency With Ranolazine for Less Ischemia in the Non-ST-Elevation Acute Coronary Syndrome Thrombolysis in Myocardial Infarction 36 (MERLIN-TIMI 36), a placebo-controlled trial of ranolazine in NSTE-ACS. All events, including cardiovascular death and new or worsening HF, were adjudicated by an independent events committee.

    Results

    Patients with ST2 concentrations in the top quartile (>35 μg/L) were more likely to be older and male and have diabetes and renal dysfunction. ST2 was only weakly correlated with troponin and B-type natriuretic peptide. High ST2 was associated with increased risk for CVD/HF at 30 days (6.6% vs 1.6%, P<0.0001) and 1 year (12.2% vs 5.2%, P<0.0001). The risk associated with ST2 was significant after adjustment for clinical covariates and biomarkers (adjusted hazard ratio CVD/HF 1.90, 95% CI 1.15-3.13 at 30 days, P=0.012; 1.51, 95% CI 1.15-1.98 at 1 year, P=0.003), with a significant integrated discrimination improvement (P<0.0001). No significant interaction was found between ST2 and ranolazine (Pinteraction=0.15).

    Conclusions

    ST2 correlates weakly with biomarkers of acute injury and hemodynamic stress but is strongly associated with the risk of HF after NSTE-ACS. This biomarker and related pathway merit further investigation as potential therapeutic targets for patients with ACS at risk for cardiac remodeling.
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    Semaglutide and cardiovascular outcomes in patients with obesity and prevalent heart failure: a prespecified analysis of the SELECT trial.
    (Lancet, 2024-08-24) Deanfield, John; Verma, Subodh; Scirica, Benjamin M; Kahn, Steven E; Emerson, Scott S; Ryan, Donna; Lingvay, Ildiko; Colhoun, Helen M; Plutzky, Jorge; Kosiborod, Mikhail N; Hovingh, G Kees; Hardt-Lindberg, Søren; Frenkel, Ofir; Weeke, Peter E; Rasmussen, Søren; Goudev, Assen; Lang, Chim C; Urina-Triana, Miguel; Pietilä, Mikko; Lincoff, A Michael; SELECT Trial Investigators
    BACKGROUND: Semaglutide, a GLP-1 receptor agonist, reduces the risk of major adverse cardiovascular events (MACE) in people with overweight or obesity, but the effects of this drug on outcomes in patients with atherosclerotic cardiovascular disease and heart failure are unknown. We report a prespecified analysis of the effect of once-weekly subcutaneous semaglutide 2·4 mg on ischaemic and heart failure cardiovascular outcomes. We aimed to investigate if semaglutide was beneficial in patients with atherosclerotic cardiovascular disease with a history of heart failure compared with placebo; if there was a difference in outcome in patients designated as having heart failure with preserved ejection fraction compared with heart failure with reduced ejection fraction; and if the efficacy and safety of semaglutide in patients with heart failure was related to baseline characteristics or subtype of heart failure. METHODS: The SELECT trial was a randomised, double-blind, multicentre, placebo-controlled, event-driven phase 3 trial in 41 countries. Adults aged 45 years and older, with a BMI of 27 kg/m2 or greater and established cardiovascular disease were eligible for the study. Patients were randomly assigned (1:1) with a block size of four using an interactive web response system in a double-blind manner to escalating doses of once-weekly subcutaneous semaglutide over 16 weeks to a target dose of 2·4 mg, or placebo. In a prespecified analysis, we examined the effect of semaglutide compared with placebo in patients with and without a history of heart failure at enrolment, subclassified as heart failure with preserved ejection fraction, heart failure with reduced ejection fraction, or unclassified heart failure. Endpoints comprised MACE (a composite of non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death); a composite heart failure outcome (cardiovascular death or hospitalisation or urgent hospital visit for heart failure); cardiovascular death; and all-cause death. The study is registered with ClinicalTrials.gov, NCT03574597. FINDINGS: Between Oct 31, 2018, and March 31, 2021, 17 604 patients with a mean age of 61·6 years (SD 8·9) and a mean BMI of 33·4 kg/m2 (5·0) were randomly assigned to receive semaglutide (8803 [50·0%] patients) or placebo (8801 [50·0%] patients). 4286 (24·3%) of 17 604 patients had a history of investigator-defined heart failure at enrolment: 2273 (53·0%) of 4286 patients had heart failure with preserved ejection fraction, 1347 (31·4%) had heart failure with reduced ejection fraction, and 666 (15·5%) had unclassified heart failure. Baseline characteristics were similar between patients with and without heart failure. Patients with heart failure had a higher incidence of clinical events. Semaglutide improved all outcome measures in patients with heart failure at random assignment compared with those without heart failure (hazard ratio [HR] 0·72, 95% CI 0·60-0·87 for MACE; 0·79, 0·64-0·98 for the heart failure composite endpoint; 0·76, 0·59-0·97 for cardiovascular death; and 0·81, 0·66-1·00 for all-cause death; all pinteraction>0·19). Treatment with semaglutide resulted in improved outcomes in both the heart failure with reduced ejection fraction (HR 0·65, 95% CI 0·49-0·87 for MACE; 0·79, 0·58-1·08 for the composite heart failure endpoint) and heart failure with preserved ejection fraction groups (0·69, 0·51-0·91 for MACE; 0·75, 0·52-1·07 for the composite heart failure endpoint), although patients with heart failure with reduced ejection fraction had higher absolute event rates than those with heart failure with preserved ejection fraction. For MACE and the heart failure composite, there were no significant differences in benefits across baseline age, sex, BMI, New York Heart Association status, and diuretic use. Serious adverse events were less frequent with semaglutide versus placebo, regardless of heart failure subtype. INTERPRETATION: In patients with atherosclerotic cardiovascular diease and overweight or obesity, treatment with semaglutide 2·4 mg reduced MACE and composite heart failure endpoints compared with placebo in those with and without clinical heart failure, regardless of heart failure subtype. Our findings could facilitate prescribing and result in improved clinical outcomes for this patient group. FUNDING: Novo Nordisk.