| 1. |
- Pagidipati, Neha J., et al.
(författare)
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An examination of the relationship between serum uric acid level, a clinical history of gout, and cardiovascular outcomes among patients with acute coronary syndrome
- 2017
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Ingår i: American Heart Journal. - : MOSBY-ELSEVIER. - 0002-8703 .- 1097-6744. ; 187, s. 53-61
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Tidskriftsartikel (refereegranskat)abstract
- Background Studies have suggested a relationship between higher baseline serum uric acid (sUA) levels and an elevated risk of subsequent ischemic cardiovascular outcomes among acute coronary syndrome (ACS) patients; this relationship may be modified by a clinical history of gout and has not been studied in large patient cohorts. We sought to understand the effect of sUA and gout on ACS outcomes. Methods Using PLATO and TRACER data on 27,959 ACS patients, we evaluated baseline sUA levels in relation to a composite of cardiovascular death, myocardial infarction (MI), or stroke. We assessed interaction terms to determine if a baseline clinical diagnosis of gout modified this putative relationship; 46% (n = 12,882) had sUA levels elevated >6.0 mg/dL. Results Patients with elevated levels were more often male with a history of prior MI, diabetes, and heart failure compared with those with sUA <6.0 mg/dL. The unadjusted risk of the composite endpoint increased with corresponding elevations in sUA levels (per 1 mg/dL increase) (HR = 1.23 [95% CI: 1.20-1.26]) above the statistical inflection point of 5.0 mg/dL. After adjustment, the association between sUA level and the composite outcome remained significant (HR = 1.07 [95% CI: 1.04-1.10]), and baseline gout did not modify this relationship. ' Conclusions In patients with ACS, increasing levels of sUA are associated with an elevated risk of cardiovascular events, regardless of a clinical diagnosis of gout. Further investigation is warranted to determine the mechanism behind this relationship and to delineate whether sUA is an appropriate therapeutic target to reduce cardiovascular risk.
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| 2. |
- Fanaroff, Alexander C., et al.
(författare)
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Frequency, Regional Variation, and Predictors of Undetermined Cause of Death in Cardiometabolic Clinical Trials : A Pooled Analysis of 9259 Deaths in 9 Trials
- 2019
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Ingår i: Circulation. - 0009-7322 .- 1524-4539. ; 139:7, s. 863-873
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Modern cardiometabolic clinical trials often include cardiovascular death as a component of a composite primary outcome, requiring central adjudication by a clinical events committee to classify cause of death. However, sometimes the cause of death cannot be determined from available data. The US Food and Drug Administration has indicated that this circumstance should occur only rarely, but its prevalence has not been formally assessed. METHODS: Data from 9 global clinical trials (2009-2017) with long-term follow-up and blinded, centrally adjudicated cause of death were used to calculate the proportion of deaths attributed to cardiovascular, noncardiovascular, or undetermined causes by therapeutic area (diabetes mellitus/pre-diabetes mellitus, stable atherosclerosis, atrial fibrillation, and acute coronary syndrome), region of patient enrollment, and year of trial manuscript publication. Patient-and trial-level variables associated with undetermined cause of death were identified using a logistic model. RESULTS: Across 127 049 enrolled participants from 9 trials, there were 9259 centrally adjudicated deaths: 5012 (54.1%) attributable to cardiovascular causes, 2800 (30.2%) attributable to noncardiovascular causes, and 1447 (15.6%) attributable to undetermined causes. There was variability in the proportion of deaths ascribed to undetermined causes by trial therapeutic area, region of enrollment, and year of trial manuscript publication. On multivariable analysis, acute coronary syndrome or atrial fibrillation trial (versus atherosclerotic vascular disease or diabetes mellitus/pre-diabetes mellitus), longer time from enrollment to death, more recent trial manuscript publication year, enrollment in North America (versus Western Europe), female sex, and older age were associated with greater likelihood of death of undetermined cause. CONCLUSIONS: In 9 cardiometabolic clinical trials with long-term followup, approximately 16% of deaths had undetermined causes. This provides a baseline for quality assessment of clinical trials and informs operational efforts to potentially reduce the frequency of undetermined deaths in future clinical research.
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| 3. |
- Hess, Connie N., et al.
(författare)
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Differential occurrence, profile, and impact of first recurrent cardiovascular events after an acute coronary syndrome
- 2017
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Ingår i: American Heart Journal. - : MOSBY-ELSEVIER. - 0002-8703 .- 1097-6744. ; 187, s. 194-203
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Tidskriftsartikel (refereegranskat)abstract
- Objective Acute coronary syndrome (ACS) trials typically use a composite primary outcome (myocardial infarction [MI], stroke, or cardiovascular death), but differential patient characteristics, timing, and consequences associated with individual component end points as first events have not been well studied. We compared patient characteristics and prognostic significance associated with first cardiovascular events in the post-ACS setting for initially stabilized patients. Methods We combined patient-level data from 4 trials of post-ACS antithrombotic therapies (PLATO, APPRAISE-2, TRACER, and TRILOGY ACS) to characterize the timing of and characteristics associated with first cardiovascular events (MI, stroke, or cardiovascular death). Landmark analysis at 7 days after index ACS presentation was used to focus on spontaneous, postdischarge events that were not confounded by in-hospital procedural complications. Using a competing risk framework, we tested for differential associations between prespecified covariates and the occurrence of nonfatal stroke vs MI as the first event, and we examined subsequent events after the first nonfatal event. Results Among 46,694 patients with a median follow-up of 358 (25th, 75th percentiles 262, 486) days, a first ischemic event occurred in 4,307 patients (9.2%) as follows: MI in 5.8% (n = 2,690), stroke in 1.0% (n = 477), and cardiovascular death in 2.4% (n = 1,140). Older age, prior stroke/transient ischemic attack, prior atrial fibrillation, and higher diastolic blood pressure were associated with a significantly greater risk of stroke vs MI, whereas prior percutaneous coronary intervention was associated with a greater risk of MI vs stroke. Second events occurred in 32% of those with a first nonfatal stroke at a median of 13 (3, 59) days after the first event and in 32% of those with a first nonfatal MI at a median of 35 (5, 137) days after the first event. The most common second event was a recurrent MI among those with MI as the first event and cardiovascular death among those with stroke as the first event. Conclusions Approximately 9% of patients experienced a first cardiovascular event in the post-ACS setting during a median follow-up of 1 year. Although the profile and prognostic implications of stroke vs MI as the first nonfatal event differ substantially, approximately one-third of these patients experienced a second event, typically soon after the first event. These findings have implications for improving post-ACS care and influencing the design of future cardiovascular trials.
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| 4. |
- Hess, Paul L., et al.
(författare)
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Sudden Cardiac Death After Non-ST-Segment Elevation Acute Coronary Syndrome
- 2016
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Ingår i: JAMA cardiology. - : American Medical Association (AMA). - 2380-6583 .- 2380-6591. ; 1:1, s. 73-79
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE In the current therapeutic era, the risk for sudden cardiac death (SCD) after non-ST-segment elevation acute coronary syndrome (NSTE ACS) has not been characterized completely. OBJECTIVE To determine the cumulative incidence of SCD during long-term follow-up after NSTE ACS, to develop a risk model and risk score for SCD after NSTE ACS, and to assess the association between recurrent events after the initial ACS presentation and the risk for SCD. DESIGN, SETTING, AND PARTICIPANTS This pooled cohort analysis merged individual data from 48 286 participants in 4 trials: the Apixaban for Prevention of Acute Ischemic Events 2 (APPRAISE-2), Study of Platelet Inhibition and Patient Outcomes (PLATO), Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRACER), and Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage Acute Coronary Syndromes (TRILOGY ACS) trials. The cumulative incidence of SCD and cardiovascular death was examined according to time after NSTE ACS. Using competing risk and Cox proportional hazards models, clinical factors at baseline and after the index event that were associated with SCD after NSTE ACS were identified. Baseline factors were used to develop a risk model. Data were analyzed from January 2, 2014, to December 11, 2015. MAIN OUTCOMES AND MEASURES Sudden cardiac death. RESULTS Of the initial 48 286 patients, 37 555 patients were enrolled after NSTE ACS (67.4% men; 32.6% women; median [interquartile range] age, 65 [57-72] years). Among these, 2109 deaths occurred after a median follow-up of 12.1 months. Of 1640 cardiovascular deaths, 513 (31.3%) were SCD. At 6, 18, and 30 months, the cumulative incidence estimates of SCD were 0.79%, 1.65%, and 2.37%, respectively. Reduced left ventricular ejection fraction, older age, diabetes mellitus, lower estimated glomerular filtration rate, higher heart rate, prior myocardial infarction, peripheral artery disease, Asian race, male sex, and high Killip class were significantly associated with SCD. A model developed to calculate the risk for SCD in trials with systematic collection of left ventricular ejection fraction had a C index of 0.77. An integer-based score was developed from this model and yielded a calculated SCD probability ranging from 0.1% to 56.7%(C statistic, 0.75). In a multivariable model that included time-dependent clinical events occurring after the index hospitalization for ACS, SCD was associated with recurrentmyocardial infarction (hazard ratio [HR], 2.95; 95% CI, 2.29-3.80; P <.001) and any hospitalization (HR, 2.45; 95% CI, 1.98-3.03; P <.001), whereas coronary revascularization had a negative relationship with SCD (HR, 0.75; 95% CI, 0.58-0.98; P =.03). CONCLUSIONS AND RELEVANCE In the current therapeutic era, SCD accounts for about one-third of cardiovascular deaths after NSTE ACS. Risk stratification can be performed with good accuracy using commonly collected clinical variables. Clinical events occurring after the index hospitalization are underappreciated but important risk factors.
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