Further information: Medical Treatment of Unstable Angina, Acute Non–ST-Elevation Myocardial Infarction, and Coronary Artery Spasm (see p937) and Treatment of Acute ST-Elevation Myocardial Infarction (see p963) from Cardiovascular Medicine, 3rd Edn*

Investigators conducted this observational study [1] to evaluate whether efforts over the past 20 years to improve outcomes for patients hospitalized with acute myocardial infarction (AMI) had also resulted in a reduction in hospitals’ Risk-Standard Mortality Rates (RSMR), thereby showing hospitals’ improvements in short-term mortality rates for AMI and in between-hospital variation in short-term mortality rates. Within the period studied, the emphasis had been on achieving improved outcomes for patients who had been hospitalized for AMI. Clinical practice guidelines emphasizing the importance in the use of evidence-based medicine were published by the American Heart Association and the American College of Cardiology, and as a result of such emphasis, and as determined by evaluating data obtained from Medicare patients discharged from hospitals between January 1995 and December 2006, the number of deaths was shown to decrease in MI patients. However, whether the same favorable results had been achieved by hospitals to improve short-term mortality rates for AMI and in between-hospital variation in short-term mortality rates was not known. The results of examining the data obtained from the Medicare patients showed that the reduction in hospital-specific RSMRs was from 18.8% in 1995 to 15.8% in 2006 (odds ratio, 0.76; 95% confidence interval [CI], 0.75–0.77). Also from 1995–2006, reduction in between-hospital heterogeneity in the RSMRs was apparent. The coefficient of variation decreased in 1995 from 11.2 % to 10.8%, the interquartile range from 2.8% to 2.1%, and the between-hospital variance from 4.4% to 2.9%.

[1] Krumholz, HM, Wang Y, Chen J, et al. Reduction in acute myocardial infarction mortality in the United States. JAMA 2009;302:767-73

Note: You may need subscriptions to access content from links on this page. You are responsible for obtaining these subscriptions.

* To view the online text from the book, please navigate to SpringerLink or use the DVD to access electronic content. SpringerLink is a subscription service. For further information, click here.

Further information: Atrial Fibrillation and Flutter (see p1955) from Cardiovascular Medicine, 3rd Edn*

Investigators conducted the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial to compare two fixed doses of dabigratran with the open-label use of warfarin in patients who had atrial fibrillation (AF) and were at risk for stroke [1]. In the randomized, noninferiority trial, the blinded, fixed doses of dabigatran administered were 110 mg twice daily or 150 mg twice daily and were compared with unblinded, adjusted-dose warfarin. Primary outcome of the trail was stroke or systemic embolism, and secondary outcomes were stroke, systemic embolism, and death. Between December 2005 and December 15, 2007, 18,113 patients from 951 clinical centers in 44 countries were enrolled into the three treatment groups. A patient’s eligibility included documented AF within 6 months prior to recruitment, and at least one additional characteristic, such as previous stroke or transient ischemic attack, left ventricular ejection fraction (LVEF) less than 40%, NYHA class II or higher heart failure symptoms 6 months prior, and at least 75 years of age. Patients who had diabetes, hypertension, or CAD could be age 65–74. Median follow-up was 2.0 years.

Warfarin is a vitamin K antagonist used in patients with AF to reduce their risk of stroke and death, but it has a primary complication of intracranial hemorrhage. Therefore, results showing that the dose of 150 mg of dabigatran was associated with lower rates of stroke and systemic embolism (primary outcome) were of interest (1.69% per year in warfarin group; 1.53% per year in group who received 110 mg of dabigatran; 1.11% per year in group who received 150 mg of dabigatran). Major bleeding rate was 3.36% per year in warfarin group, 2.71% in the 110 mg dabigatran group, and 3.11% per year in the 150 mg of dabigatran group. Hemorrhagic stroke rate was 0.38% per year for warfarin, 0.12% per year for 110 mg of dabigatran 10% per year for 150 mg of dabigatran.

The investigators concluded that from the data that in comparison with warfarin, dabigatran dosed at 150 mg revealed lower stroke and systemic embolism, but had similar rates of major hemorrhage.

In an accompanying editorial [2], Brian Gage emphasized that while warfarin has been a recommended treatment for AF patients at risk for stroke for some time, the complications in administration of the medication have precluded its use for some patients, and he believes it is necessary to develop new oral anticoagulants. He concludes that in regard to the current study of dabigatran, patients who are currently on a well-controlled INR regimen should stay with warfarin, but patients with AF and an additional risk factor for stroke would benefit from the use of dabigatran. He stated that the 110 mg dose appears safer, the 150 mg dose appears more efficacious, and that while additional studies are needed, patients with AF plus additional risk factors could benefit from its use.

[1] Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus warfarin in patients with atrial fibrillation (RE-LY). N Engl J Med 2009;361:1139-1151

[2] Gage BF. Can we rely on RE-LY? N Engl J Med 2009;361:1200-1202

Note: You may need subscriptions to access content from links on this page. You are responsible for obtaining these subscriptions.

* To view the online text from the book, please navigate to SpringerLink or use the DVD to access electronic content. SpringerLink is a subscription service. For further information, click here.

Further information: Peripheral Arterial Diseases (see p1681), Carotid Artery Intervention (see p1741), and Endovascular Procedures for the Treatment of Peripheral Vascular Disease (see p1755) from Cardiovascular Medicine, 3rd Edn*

Investigators conducted the Dutch Echocardiographic III (DECREASE III) trial [1] to determine whether or not statin therapy could reduce the postoperative incidence of adverse cardiac events in patients undergoing noncardiac, elective vascular surgery. Patients were eligible for this randomized, double-blind, placebo-controlled trial if they had not previously taken a statin, were over 40 years of age, and were scheduled for noncardiac vascular surgery at Erasmus Medical Center between June 2004 and April 2008. The types of surgery included abdominal aortic aneurysm repair, distal aortoiliac reconstruction, lower-limb arterial reconstruction, or carotid-artery endarterectomy. From a total of 497 patients enrolled, 250 patients were assigned to fluvastatin and 247 to placebo a median of 37 days before surgery. The primary end point of the study was the development of myocardial ischemia, either as transient ECG signs of ischemia, release of troponin T, or both within 30 days post-surgery. The secondary end point was the composite of death from cardiovascular causes and nonfatal myocardial infarction (MI).

The primary end point of myocardial ischemia within 30 days post-surgery occurred in 27 (10.8%) of 250 patients in the fluvastatin group, and the secondary end point of cardiovascular death occurred in a total of six patients in the fluvastatin group. The primary end point occurred in 47 (19.0%) of the 247 patients who took placebo. There were 12 patient deaths in the placebo group, and eight were cardiovascular deaths. Although the pathophysiology of perioperative cardiac events is not clear, it is thought that a statin worked for these patients by reducing the risk of atherosclerotic plaque rupture-induced MI by stabilizing unstable coronary plaques.

The authors of this paper concluded that the use of fluvastatin therapy in patients having vascular surgery reduced adverse events postoperatively.

[1] Schouten O, Boersma E, Hoeks SE, et al. Fluvastatin and perioperative events in patients undergoing vascular surgery. N Engl J Med 2009;361:980-989.

Note: You may need subscriptions to access content from links on this page. You are responsible for obtaining these subscriptions.

* To view the online text from the book, please navigate to SpringerLink or use the DVD to access electronic content. SpringerLink is a subscription service. For further information, click here.

Further information: Regulation of Cardiac Contraction and Relaxation (see p1189) from Cardiovascular Medicine, 3rd Edn*

In the August 27, 2009 issue of the New England Journal of Medicine, two original articles and an editorial were published regarding the advantages and limitations of the new generation of sensitive troponin assays. The articles by Reichlin et al [1] and Keller et al [2] both concur that with the sensitive assays, the accuracy of troponin for the diagnosis of myocardial infarction (MI) was improved over the older assays. In an editorial, David Morrow [3] stated that differentiation between tissue specificity of troponin for cardiomyocyte injury and myocardial infarction caused by ischemia is diminished with new, more sensitive assays, but the overall diagnostic accuracy is a major step forward in MI detection.

The Advantageous Predictors of Acute Coronary Syndromes Evaluation (APACE) [1] was a prospective, international, multicenter study, and from April 2006 through April 2008, 786 patients were recruited. These patients had presented to the emergency department of a participating hospital with symptoms of myocardial infarction (MI), such as chest pain or angina pectoris. Onset or peak of symptoms had occurred 12 hours before presentation. Four sensitive cardiac troponin assays, Abbott-Architect Troponin I, Roche High-Sensitive Troponin T, Roche Troponin I and Siemens Troponin I Ultra, plus a standard assay, Roche Troponin T, were used to determine cardiac troponin levels at presentation. In patients for whom AMI was the final diagnosis, cardiac troponin levels were significantly higher at presentation in all five assays than in patients who had a different diagnosis. In the case of non-ST-segment elevation MI (NSTEMI) and in the case of ST-segment elevation MI (STEMI), the diagnostic performance of the cardiac troponin levels was similar. However, for patients whose final diagnosis was unstable angina, the cardiac troponin levels were significantly lower than for patients with MI. Patients with chest pain that was from other cardiac causes had similar levels to those with unstable angina, but both were significantly higher than those patients whose chest pain was from noncardiac causes. Results showed that when patients presented with a recent onset of chest pain, the four sensitive cardiac troponin assays used in the study had an early and excellent diagnostic performance. Early diagnosis of MI by the sensitive cardiac troponin assays substantially improves a patient’s prognosis, not only for patients with MI, but also in order to begin proper medical management for patients with unstable angina.

The second paper [2] reports on a study on the use of a newer sensitive troponin assay, the investigators enrolled 1818 consecutive patients from January 2007 to December 2008 who presented with new-onset chest pain at chest-pain units in three German study centers. For this study, one sensitive troponin assay was used. To obtain a primary diagnosis of acute myocardial infarction (AMI), the following conventional assays also used were Roche Troponin T and Seimens Dimension RxL Troponin I. To assess the diagnostic value of the sensitive troponin I assay alone, as well as to determine how soon a diagnosis could be made, two criteria were used to classify patients with AMI, unstable angina, and patients who had an elevated troponin level from causes other than coronary in origin. Investigators concluded that of the two assessments, the diagnostic accuracy was highest with the sensitive troponin I assay (area under the receiver-operating-characteristic curve [AUC], 0.96), as compared with the troponin T assay (AUC, 0.85) and traditional myocardial necrosis markers. Use of the sensitive troponin I assay significantly improved early diagnosis of AMI and could be safely used to rule out or rule in the coronary causes of chest pain.

In an editorial [3] in the same issue of the New England Journal of Medicine on the latest generation of sensitive troponin assays, David Morrow evaluates the advantages and limitations of the assays as reported in two articles. Dr. Morrow agreed that the investigators had shown that the new generation of sensitive troponin assays improved overall diagnostic accuracy and functioned as better tests. However, he warned that the results also showed a trade-off of superior clinical sensitivity for diminished clinical specificity for diagnosis of AMI, and thus, additional and larger studies are warranted.

[1] Reichlin T, Hochholzer W, Bassetti S, et al. Early diagnosis of myocardial infarction with sensitive cardiac troponin assays. N Engl J Med 2009;361:858-67.

[2] Keller T, Zeller T, Peetz D, et al. Sensitive troponin I assay in early diagnosis of acute myocardial infarction. N Engl J Med 2009;361:868-77.

[3] Morrow, D. Clinical application of sensitive troponin assays. N Engl J Med 2009;361:913-15.

Note: You may need subscriptions to access content from links on this page. You are responsible for obtaining these subscriptions.
* To view the online text from the book, please navigate to SpringerLink or use the DVD to access electronic content. SpringerLink is a subscription service. For further information, click here.

Further information: Treatment of Acute ST-Elevation Myocardial Infarction (see p963) from Cardiovascular Medicine, 3rd Edn*

Investigators of the Study of Platelet Inhibition and Patient Outcomes (PLATO) trial conducted a study of patients presenting with acute coronary syndromes (ACS) to evaluate which oral antagonist (thienopyridine) of the adenosine diphosphate receptor P2Y12, ticagrelor or clopidogrel, is more protective in preventing cardiovascular events [1]. PLATO was a multicenter, randomized, double-blind trial conducted in 862 centers in 43 countries from October 2006 through July 2008.

In this study, patients were eligible if hospitalized for an ACS with or without ST-segment elevation within the past 24 hours, and 18,624 patients were recruited. In the ticagrelor group, patients were given a 180 mg loading dose and 90 mg twice-daily, and in the clopidogrel group, patients were given a 300–600 mg loading dose and 75 mg/day thereafter. The primary composite end point was death from vascular causes, myocardial infarction (MI), or stroke, and it occurred in 9.8% of patients in the ticagrelor group as compared with 11.7% of patients receiving clopidogrel.

The rates of death from any cause were 4.5 % with ticagrelor and 5.9% with clopidogrel, representing a significant relative risk reduction of 22%. Although there was no major difference in the rates of major bleeding between the ticagrelor group and the clopidogrel group (11.6% and 11.2%, respectively, P=0.43), ticagrelor was associated with a higher rate of major bleeding not related to coronary-artery bypass grafting (4.5% vs. 3.8%, P=0.03), such as fatal intracranial bleeding.

An important Editorial [2] accompanied the Wallentin et al paper, and it compared three thienopyridines: clopidogrel, prasugrel, and ticagrelor. Of the three, prasugrel and ticagrelor are the newest medications to be developed. An earlier paper [3] was provided as an update on the journal’s website, and this reported the findings of the TRITON-TIMI 38 trial regarding prasugrel. The editorial provides a balanced and thorough comparison of the three medications.

1. Wallentin L, Becker RC, Budaj A et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2009;361:1045-1057

2. Schomig, A. Ticagrelor — is there a need for a new player in the antiplatelet-therapy field? N Engl J Med 2009;361:1108-1111

3. Wiviott SD, Braunwald E, McCabe CH et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2007;357:2001-2015

Note: You may need subscriptions to access content from links on this page. You are responsible for obtaining these subscriptions.

* To view the online text from the book, please navigate to SpringerLink or use the DVD to access electronic content. SpringerLink is a subscription service. For further information, click here.