Clinical outcomes after detection of elevated cardiac enzymes in patients undergoing percutaneous intervention

AbstractObjectives. We examined the relations of elevated creatine kinase (CK) and its myocardial band isoenzyme (CK-MB) to clinical outcomes after percutaneous coronary intervention (PCI) in patients enrolled in Integrilin (eptifibatide) to Minimize Platelet Aggregation and Coronary Thrombosis-II (trial) (IMPACT-II), a trial of the platelet glycoprotein IIb/IIIa inhibitor eptifibatide.Background. Elevation of cardiac enzymes often occurs after PCI, but its clinical implications are uncertain.Methods. Patients undergoing elective, scheduled PCI for any indication were analyzed. Parallel analyses investigated CK (n = 3,535) and CK-MB (n = 2,341) levels after PCI (within 4 to 20 h). Clinical outcomes at 30 days and 6 months were stratified by postprocedure CK and CK-MB (multiple of the site’s upper normal limit).Results. Overall, 1,779 patients (76%) had no CK-MB elevation; CK-MB levels were elevated to 1 to 3 times the upper normal limit in 323 patients (13.8%), to 3 to 5 times normal in 84 (3.6%), to 5 to 10 times normal in 86 (3.7%), and to >10 times normal in 69 patients (2.9%). Elevated CK-MB was associated with an increased risk of death, reinfarction, or emergency revascularization at 30 days, and of death, reinfarction, or surgical revascularization at 6 months. Elevated total CK to above three times normal was less frequent, but its prognostic significance paralleled that seen for CK-MB. The degree of risk correlated with the rise in CK or CK-MB, even for patients with successful procedures not complicated by abrupt closure.Conclusions. Elevations in cardiac enzymes, including small increases (between one and three times normal) often not considered an infarction, are associated with an increased risk for short-term adverse clinical outcomes after successful or unsuccessful PCI

Mechanism of benefit of combination thrombolytic therapy for acute myocardial infarction: A quantitative angiographic and hematologic study

AbstractObjectives. The goal of this study was to lend insight into the mechanisms responsible for the beneficial effects of combination thrombolytic therapy.Background. Combination thrombolytic therapy for acute myocardial infarction bas been associated with less reocclusion and fewer in-hospital clinical events than has monotherapy.Methods. Infarct-related quantitative coronary dimensions and hemostatic protein levels were evaluated in 287 patients with acute myocardial infarction during the early (90-min) and convalescent (7-day) phases after administration of recombinant tissue-type plasminogen activator (rt-PA), urokinase or combination rt-PA and urokinase.Results. Minimal lumen diameter was similar in the 90-min and 7-day phases after treatment with rt-PA, urokinase and combination rt-PA and urokinase (0.72 ± 0.45 mm, 0.62 ± 0.53 mm and 0.75 ± 0.58 mm, respectively, at 90 min, p = 0.16; and 1.05 ± 0.56 mm, 1.12 ± 0.72 mm and 0.94 ± 0.54 mm, respectively, at 7 days, p = 0.22). In-hospital clinical event and reocclusion rates were less frequent in patients receiving combination therapy than in those receiving monotherapy (25% vs. 38% and 32% for rt-PA and urokinase, respectively, p = 0.084; and 3% vs. 13% and 9% for rt-PA and urokinase, respectively, p = 0.03), but these events were unrelated to early or late coronary dimensions. Patients receiving combination therapy or urokinase monotherapy had significantly higher peak fibrin degradation products (1,307 ± 860 and 1,285 ± 898 μg/ml vs. 435 ± 717 μg/ml, respectively, p < 0.0001) and lower nadir fibrinogen levels (0.85 ± 1.00 and 0.75 ± 0.53 g/liter vs. 1.90 ± 0.86 g/liter, respectively, p < 0.0001) than did those receiving rt-PA monotherapy. Peak fibrinogen degradation products indirectly correlated (p = 0.004) and baseline (p = 0.026) and nadir (p = 0.089) fibrinogen levels directly correlated with reocclusion.Conclusions. Lower in-hospital clinical event and reocclusion rates observed with combination thrombolytic therapy may relate to systemic hematologic factors rather than to the residual lumen obstruction after thrombolysis

Hemorrhagic complications associated with the use of intravenous tissue plasminogen activator in treatment of acute myocardial infarction

: Little attention has been paid to the importance of clinical factors associated with bleeding complications caused by the use of thrombolytic agents. The goal of our study was to examine clinical and hematologic factors associated with an increased risk of bleeding in a prospectively observed population that received intravenous tissue plasminogen activator for acute myocardial infarction.: Bleeding complications were evaluated in 386 consecutive patients treated with 150 mg of tissue plasminogen activator over six to eight hours for acute myocardial infarction. All patients also underwent immediate cardiac catheterization.: Quantitation of blood loss during the patients' hospital stay included a median drop in hematocrit of 11.4 points, a median nadir hematocrit of 31.2, a 14 percent rate of significant clinically evident bleeding, and a 31 percent rate of transfusion of two or more units of blood. All of these parameters were much more severe in patients treated with coronary artery bypass surgery. Access site hematoma was the most common source of bleeding (45 percent of patients), whereas 8 percent had gastrointestinal bleeding, two patients had retroperitoneal bleeding, and two patients had intracranial bleeding. The median nadir fibrinogen was 1.3 g/liter. Multiple linear regression models were used to investigate the relationship between clinical variables, including multiple hematologic measurements, and measures of the amount of blood loss. The use of coronary artery bypass grafting was the variable most closely associated with hemorrhage. Other invasive procedures (angioplasty and intra-aortic balloon pumping) were also associated with increased bleeding. Among the patient descriptors examined, lighter weight, older age, female sex, and history of hypertension were associated with greater blood loss. Of laboratory coagulation parameters, only nadir fibrinogen levels were significantly associated with more bleeding.: Careful clinical evaluation may improve assessment of the risk/benefit ratio of thrombolytic therapy.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27546/1/0000590.pd

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p&lt;0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (&lt;1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (&lt;1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Multivessel coronary artery disease: A key predictor of short-term prognosis after reperfusion therapy for acute myocardial infarction

Results of recent studies have suggested that routine cardiac catheterization may be unnecessary after reperfusion therapy for acute myocardial infarction. Therefore to better define the short-term prognostic value of early coronary angiography, and specifically the prognostic significance of multivessel coronary artery disease, the angiographic findings of 855 patients consecutively enrolled in five phases of the TAMI study were correlated with their in-hospital outcome. All patients received intravenous thrombolytic therapy (tissue plasminogen activator, urokinase, or both agents) and underwent cardiac catheterization within 90 minutes of the initiation of therapy. Multivessel disease, defined as the presence of &gt;= 75% luminal diameter stenosis in two or more major epicardial arteries, was documented in 236 patients. When compared with the group of patients without multivessel disease, this group had a higher prevalence of coronary risk factors and more frequently had a history of antecedent ischemic chest pain. Although the severity of the infarct zone dysfunction was similar in the two groups (-2.77 +/- 1.00 vs -2.50 +/- 1.09 SD/chord, p = NS), global left ventricular ejection fraction was lower in the group with multivessel disease (48.6 +/- 12.4% vs 51.8 +/- 10.6%, p p = 0.0001). The in-hospital mortality rate, predominantly the result of myocardial failure and cardiogenic shock, was also significantly higher in the multivessel group (11.4% vs 4.2%, p p p = 0.01), TIMI grade infarct vessel flow (p = 0.03), and patient age (p = 0.03). According to this model the prognostic significance of one additional year of age was equivalent to a reduction in left ventricular function of 1.1 ejection fraction percentage points; one additional diseased vessel was equivalent to 15 additional years of age or a reduction in ejection fraction of 16 percentage points. These data suggest that more aggressive revascularization procedures should be considered in the early postinfarction period for patients with multivessel disease and noninfarct zone dysfunction. In the absence of reliable noninvasive techniques, coronary angiography remains the procedure of choice for identifying this high-risk subgroup.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29410/1/0000484.pd