Major bleeding in acute coronary syndromes

Treatment of acute coronary syndrome has been based on the prevention of ischemic complications by means of antithrombotic therapy and invasive strategies. The desired reduction reached in the recurrence of ischemic events reveals its price, an increase in the occurrence of major bleeding. Initially tolerated as a benign complication, it is now shown to be an important predictor of mortality. Greater attention dedicated to the prognostic impact of bleeding is recent, motivated by the development of new antithrombotic agents. Detailed analysis of the risk factors for myocardial infarction or bleeding is an important issue and allows institution of individualized approach.     

Renal insufficiency increases mortality in acute coronary syndromes regardless of TIMI risk score

BACKGROUND: Non ST-segment elevation acute coronary syndromes (NSTE ACS) are the most frequent cause of admission to intensive care units. Early risk assessment and implementation of optimal treatment are of special importance in these patients. Previous studies have demonstrated that renal insufficiency is an independent risk factor in patients with cardiovascular disease. AIM: To assess the effects of renal function on the course of treatment and prognosis in patients with NSTE ACS admitted to hospitals without on-site invasive facilities but with a possibility of immediate transfer to a reference centre with a catheterisation laboratory. METHODS: Twenty-nine community hospitals without on-site invasive facilities participated in the Krakow Registry of Acute Coronary Syndromes - a prospective, multicentre, web-based, observational registry. Renal insufficiency (RI) was defined as creatinine clearance (CrCl) <60 ml/min. RESULTS: NSTE ACS was diagnosed in 1396 patients. Renal insufficiency was diagnosed in 34% of all patients. Only 17% of them had been diagnosed with RI prior to admission. Transfer for invasive treatment was undertaken in 10% of RI patients as compared to 16% of patients with CrCl >60 ml/min (NS). In-hospital mortality among patients remaining on conservative treatment in community hospitals was significantly higher among RI patients (4.0 vs. 0.6%; p <0.001). Thienopyridines were less frequently used in RI patients (46 vs. 54%; p <0.05). In-hospital mortality among RI patients remaining in community hospitals and treated conservatively was higher than among non-RI patients in each TIMI risk score group: 7.3 vs. 2.4% (p <0.05) in the high risk group, 4.1 vs. 1.4% (NS) in the moderate and 3.6 vs. 0% (p <0.001) in the low risk group. Multivariate logistic regression analysis identified reduced creatinine clearance and a history of heart failure as independent factors influencing mortality. CONCLUSIONS: Renal insufficiency was present in one-third of NSTE ACS patients. Patients with renal insufficiency had worse clinical risk profile and received less aggressive treatment. Patients with NSTE ACS and renal insufficiency treated conservatively had higher in-hospital mortality. Renal insufficiency modifies mortality irrespective of the TIMI risk score. Creatinine clearance should be considered in modification of the TIMI risk score scale.     

Renal insufficiency and mortality from acute coronary syndromes

Background

Although there is accumulating evidence that renal insufficiency is an independent risk factor for mortality after acute myocardial infarction (AMI), it is not known whether renal dysfunction is associated with an increased mortality rate after a broad range of acute coronary syndromes, including unstable angina.

Methods

We examined consecutive patients from 24 Veterans Affairs hospitals with confirmed AMI or unstable angina between March 1998 and February 1999, who were categorized into groups according to estimated glomerular filtration rate (GFR). Multivariable regression was used to assess the independent association between GFR and the 7-month mortality rate, adjusting for differences in patient characteristics and treatment.

Results

Of the 2706 patients, 436 (16%) had normal renal function (GFR >90 mL/min/1.73 m²), 1169 (43%) had mild renal insufficiency (GFR 60-89 mL/min/1.73 m²), 864 (32%) had moderate renal insufficiency (GFR 30-59 mL/min/1.73 m²), and 237 (9%) had severe renal insufficiency (GFR <30 mL/min/1.73 m²). Patients with renal insufficiency were less likely to undergo coronary angiography or to receive aspirin or β-blockers at discharge. In multivariable models, renal insufficiency was associated with a higher odds of death (mild renal insufficiency: odds ratio [OR] = 1.76; 95% CI, 0.93-3.33; moderate renal insufficiency: OR = 2.72; 95% CI, 1.43-5.15; and severe renal insufficiency: OR = 6.18; 95% CI, 3.09-12.36; all compared with normal renal function). The associations between renal insufficiency and mortality rate were similar in both the AMI and unstable angina subgroups (P value for interaction = .45).

Conclusions

Renal insufficiency is common and is associated with higher risks for death in patients with a broad range of ACS at presentation. Future efforts should be dedicated to determining whether more aggressive treatment will optimize outcomes in this patient population.     

Coagulation activation and long-term outcome in acute coronary syndromes

After an episode of unstable angina or myocardial infarction, a high proportion of patients show biochemical signs of coagulation activation, expressed as persistently elevated thrombin generation, in their blood. It is not known whether this has any influence on long-term outcome. In this prospective multicenter cohort study, we assessed the relation of persistently elevated thrombin generation to outcome in 319 consecutive patients with acute coronary syndromes enrolled in the Global Use of Strategies To Open occluded coronary arteries (GUSTO) IIb trial. Plasma prothrombin fragment 1 + 2 levels, an index of "in vivo" thrombin generation, was measured during the acute phase and after 1, 6, and 12 months, and its relation to outcome was assessed during a median 29-month follow-up period. The primary end point of cardiac death or myocardial (re)infarction occurred in 61 patients (19%). There was a U-shaped relationship between plasma prothrombin fragment 1 + 2 levels and the risk of developing the primary end point; intermediate levels (1.5-1.9 nM) were associated with the lowest risk, whereas both higher (> 1.9 nM) and lower (< 1.5 nM) values were associated with an increased risk (relative risk [RR] 1.56 and 95% confidence interval [CI], 1.25-2.28; RR, 1.35 and 95% CI, 1.11-1.86, respectively). After an episode of acute coronary syndrome, both high and low levels of thrombin generation are predictors of an increased risk of an unfavorable outcome.     

Influence of gender on long-term mortality in patients presenting with non-ST-elevation acute coronary syndromes undergoing percutaneous coronary intervention

Although an invasive strategy has predominately been studied in men with non-ST-segment elevation acute coronary syndromes (NSTE-ACSs), its role in low-risk women is unclear. We sought to examine gender differences in a real-world registry of patients with NSTE-ACS who underwent percutaneous coronary intervention (PCI). Patients with NSTE-ACS undergoing PCI at the Cleveland Clinic, Cleveland, Ohio from 2003 through 2007 (n = 1,874) were included. In-hospital and long-term mortalities were assessed. Cox proportional hazards models were constructed to study the influence of gender on mortality. Interactions with age and biomarker status were examined. Women were older and had a higher incidence of co-morbid conditions compared to men. They had a smaller reference vessel diameter compared to men. Despite these characteristics there was no overall difference in in-hospital (1.4% vs 1.6%) or long-term (14.6% vs 15.8%) mortality between men and women. However, there was evidence of a significant effect modification by age (p = 0.012) and troponin status (p = 0.0073) for long-term mortality such that women <60 years of age, especially those who were troponin negative, had more than a twofold increase in long-term mortality compared to men (p = 0.007). In conclusion, although overall mortality rates are similar between men and women undergoing PCI for NSTE-ACS, women <60 years old with negative biomarkers have a higher mortality than their men peers.     

Medication performance measures and mortality following acute coronary syndromes

PURPOSE: To identify patient and health care factors which are related to the use of medical treatments that comprise quality measures and to assess the relation of these measures with mortality. METHODS: The study sample consisted of 20 140 patients with acute coronary syndromes from the international GRACE registry. Multivariable logistic regression modeling was used to determine predictors of quality performance. Quality indicators were use of aspirin and beta-blockers within 24 hours and at hospital discharge, use of angiotensin-converting enzyme (ACE) inhibitors at discharge, and in-hospital mortality. RESULTS: Use of medications in eligible patients at discharge ranged from 73% for ACE inhibitors to 93% for aspirin. High-risk features (eg, heart failure, older age) were related to failure to use aspirin and beta-blockers. Being at a teaching hospital and care by a cardiologist were associated with better use of aspirin and beta-blockers. Coronary artery bypass surgery was associated with failure to use ACE inhibitors and aspirin. When hospitals were divided into quartiles of quality performance, adjusted in-hospital mortality was 4.1% in the top versus 5.6% in the bottom quartile, representing a 27% (95% confidence interval: 11% to 42%) lower relative mortality. CONCLUSION: Identification of factors associated with failure to use proven treatments, including high-risk groups that would derive particular benefit from effective therapies, provides an opportunity to focus quality improvement interventions. The association of lower hospital mortality with better use of selected medical treatments supports their measurement to improve quality of care.     

Performance of stent thrombosis and bleeding risk scores in out-of-hospital cardiac arrest due to acute coronary syndromes

BackgroundPatients with out-of-hospital cardiac arrest (OHCA) due to acute coronary syndromes (ACS) who undergo percutaneous coronary intervention (PCI) are at high risk of bleeding and thrombosis. While predictive bleeding and stent thrombosis risk scores have been established, their performance in patients with OHCA has not been evaluated.MethodsAll consecutive patients admitted for OHCA due to ACS who underwent PCI between January 2007 and December 2019 were included. The ACTION and CRUSADE bleeding risk scores and the Dangas score for early stent thrombosis risk were calculated for each patient. A C-statistic analysis was performed to assess the performance of these scores.ResultsAmong 386 included patients, 82 patients (21.2%) experienced severe bleeding and 30 patients (7.8%) experienced stent thrombosis. The predictive performance of the ACTION and CRUSADE bleeding risk scores for major bleeding was poor, with areas under the curve (AUCs) of 0.596 and 0.548, respectively. Likewise, the predictive performance of the Dangas stent thrombosis risk score was poor (AUC 0.513). Using multivariable analysis, prolonged low-flow (odds ratio [OR] 1.03, 95% confidence interval [CI] 1.00–1.05; P = 0.025), reduced haematocrit or fibrinogen at admission (OR 0.93, 95% CI 0.88–0.98; P = 0.010 and OR 0.61; 95% CI 0.41–0.89; P = 0.012, respectively) and the use of glycoprotein IIb/IIIa inhibitors (OR 2.10, 95% CI 1.18–3.73; P = 0.011) were independent risk factors for major bleeding.ConclusionThe classic bleeding and stent thrombosis risk scores have poor performance in a population of patients with ACS complicated by OHCA. Other predictive factors might be more pertinent to determine major bleeding and stent thrombosis risks in this specific population.     

Usefulness of the TIMI Risk Index in predicting short- and long-term mortality in patients with acute coronary syndromes

In a cohort of 710 patients with acute coronary syndromes (ACSs), we demonstrated that the Thrombolysis In Myocardial Infarction Risk Index--a predictor of 30-day mortality in clinical trial patients with ST-elevation myocardial infarction (STEMI)--is a strong predictor of short- and long-term mortality with good discrimination ability (c statistics 0.77 to 0.79) among all subtypes of ACSs (STEMI, non-STEMI, and unstable angina pectoris). These results verify the utility of the Risk Index in unselected patients with STEMI, broaden its application to other types of ACSs, and extend its utility to stratification of long-term mortality risk.     

Renal function and risk stratification in acute coronary syndromes

In this prospective cohort study we analyzed the impact of admission renal function on the hospital course of 2,503 patients with unstable angina pectoris (UAP) and acute myocardial infarction (AMI). The patients were stratified into quartile groups (Q1 to Q4) defined by baseline corrected creatinine clearance (cCrCl) values of 51.4, 63.8, and 76.8 mg/min/72 kg. The proportions of patients with a discharge diagnosis of AMI increased with declining cCrCl, from 35.5% in Q4 to 46.0% in Q1 (p <0.0001). The frequency of left ventricular (LV) failure (Q4 4.5%, Q1 31.0%, p <0.0001) and cardiac death (Q4 0.5%, Q1 9.5%, p <0.0001) also increased linearly with decreasing cCrCl, with no evidence that the prognostic impact of renal dysfunction was different in AMI or UAP (p for interaction 0.15). Logistic regression analysis confirmed the independent effects of cCrCl on outcome, with odds of LV failure and cardiac death for patients in Q4 being 0.34 (95% confidence intervals 0.16 to 0.72) and 0.14 (95% confidence intervals 0.03 to 0.74), respectively, relative to patients in Q1. No threshold was detected for the adverse effects of renal dysfunction on outcomes; the log odds of LV failure and cardiac death against quartiles of cCrCl both showed significant linear trends (p <0.0001) with each change in quartile, resulting in risk reductions of 55% (odds [SE] 0.45 [0.03]) and 65% (odds [SE]: 0.35 [0.05]), respectively. In conclusion, renal function showed a graded association with LV failure and hospital death that was independent of diagnosis (UAP or AMI) and other baseline variables. There was no detectable threshold of renal dysfunction for these adverse prognostic effects.     

Troponin as a risk factor for mortality in critically ill patients without acute coronary syndromes

OBJECTIVES: We sought to assess the mechanism and prognostic value of elevated troponins in patients without acute coronary syndromes (ACS). BACKGROUND: Cardiac troponins are used as specific markers for the diagnosis of ACS. Recent studies reported a considerable number of critically ill patients without ACS as being troponin-positive, especially patients with sepsis, pulmonary embolism, renal failure, and stroke. METHODS: We analyzed 58 consecutive, critically ill patients admitted for reasons other than ACS, according to their troponin status. Thirty-day mortality, left ventricular ejection fraction (LVEF), and a panel of inflammatory cytokines were compared between troponin-positive and troponin-negative patients. Relevant coronary artery disease was excluded either by stress echocardiography or autopsy. RESULTS: Of the 58 critically ill patients, 32 (55%) without evidence of ACS were troponin-positive. Positive troponin levels were associated with higher mortality (22.4% vs. 5.2%, p < 0.018) and a lower LVEF (p = 0.0006). Troponin-positive patients had significantly higher median levels of tumor necrosis factor (TNF)-alpha, its soluble receptor, and interleukin (IL)-6. A subgroup of 10 aplastic patients was troponin-negative at study entry. Three became troponin-positive during leukocyte recovery and subsequently died, whereas all the others stayed troponin-negative and survived. Flow-limiting coronary artery disease was not demonstrable at autopsy or stress echocardiography in 72% of troponin-positive patients. CONCLUSIONS: Elevated troponin is a mortality risk factor for medical intensive care patients admitted for reasons other than ACS. It is associated with decreased left ventricular function and higher levels of TNF-alpha and IL-6.     

Composite risk scores for acute coronary syndromes

There have been considerable advances in the management of acute coronary syndromes in the recent past. There are three risk scoring systems used for prognosticating these patients. An attempt is made in this article to discuss the pros and cons of the different risk scoring systems and their clinical utility.     

Role of coronary risk factors in blood thrombogenicity and acute coronary syndromes

Recent advances in basic science have linked some systemic risk factors to endothelial dysfunction which gives rise to atherosclerotic disease and triggers the progression of thrombotic complications. Superficial erosion of the stenotic plaque can be observed in one-third of acute coronary syndromes (ACS). In these cases the presence of classic risk factors such as diabetes mellitus, hypercholesterolemia and smoking favor a state of "vulnerable blood" or high risk. Increased thrombogenicity can exacerbate thrombus formation and is able to trigger an ACS. The vessel endothelium regulates contractile, mitogenic and thrombotic activities of the vessel wall. Risk factors impair both homeostasis and hemostasis of the vessel wall and promote inflammatory signals. Platelet and monocyte activation favors the expression of tissue factor (TF), thus triggering the coagulation cascade with thrombin generation and clot formation. Increased blood thrombogenicity linked to classic risk factors may be associated with circulating TF levels which are much higher than those observed in healthy subjects without risk factors. These observations not only emphasize the usefulness of aggressive management of risk factors but open a new avenue for future studies to devise therapeutic strategies to treat ACS by inhibiting TF expression.