Insulin Therapy, C. Diff Update, LMWH or UFH for Acute Coronary Syndrome

The Hospitalist. 2006 May;2006(05):

May 1, 2006 | The Hospitalist

Cate Ranheim, MD ; Scott Mead, MD ; Randall McVean, MD ; Robert Hoffman

The results of this study are sure to fuel more debate on ideal goals for blood sugar control in the critically ill. The study confirms previous findings that intensive insulin management improves mortality in patients with longer stays in the ICU.

LMWH or UFH for High-Risk Patients with ACS

Mahaffey KW, Cohen M, Garg J, et al. High-risk patients with acute coronary syndromes treated with low-molecular-weight or unfractionated heparin: outcomes at 6 months and 1 year in the SYNERGY trial. JAMA. 2005 Nov 23;294(20):2594-2600.

In July 2004 the SYNERGY (Superior Yield of the New Strategy of Enoxaparin, Revascularization, and Glycoprotein IIb/IIIa Inhibitors) trial reported 30-day post hospitalization data. This study compared low molecular weight heparin (LMWH) to unfractionated heparin (UFH) during acute coronary syndrome (ACS) and found it “at least as effective” as UFH. Further data extending to six months and 12 months was reported in November.

This prospective, randomized, open-labeled multicentered trial enrolled 9,978 patients and compared LMWH versus UFH in ACS. Enrolled patients had had active ischemic symptoms within 24 hours of enrollment, and met two of the following three criteria:

Age 60 or older;
Elevated cardiac enzymes; and
Ischemic ECG changes other than ST elevations.

All patients were treated with standard medical therapy with 50% in both groups receiving GIIb/IIIa inhibitors. Interventions were pursued equally in both groups of patients; 92% had angiograms within 24 hours, 47% had percutaneous interventions, and 19% underwent coronary artery bypass grafting during the index hospitalization.

Six-month and 12-month data confirmed that LMWH use was noninferior to UFH. At six months there was no significant difference between the groups in frequency of nonfatal MI, further revascularization, CVA, or hospitalization. At 12 months, all cause mortality was found to be equivalent between the two groups. Interestingly, nearly 18% died or experienced nonfatal MI through six months of follow-up and 7.4% died by one-year follow-up, despite aggressive coronary revascularization and high use of evidence-based therapies at the time of hospital discharge.

When compared with other trials, these higher than “normal” rates of death and MI were believed related to the high-risk patient population and a lower threshold of cardiac enzyme abnormality. In this high-risk group of patients, LMWH and UFH appear to be equally safe and efficacious for the treatment of ACS, with equivalent long-term outcomes.—RM TH

Classic Literature

Make No Assumptions About PE

McGinn S, White PD. Acute cor pulmonale resulting from pulmonary embolism. JAMA. 1935;104:1473-1480.

Clinical medicine is replete with “classic” signs and symptoms of disease that are based on little more than early case reports. The diagnosis of pulmonary embolism is no exception. For example, Westermark described several patients with acute pulmonary embolism in 1938 and established the standard for diagnosis by “roentgenexamination.” Similarly, McGinn and White provided the first description of what would become another classic sign of PE: S1Q3T3 changes in the 12-lead electrocardiogram (ECG).

Case reports from nine patients with pulmonary embolism were described in this early article. Of these, three were women, six were postoperative events, and diagnosis was confirmed at autopsy in three patients. In 1935, the only “definitive” treatment for pulmonary embolism was surgical thrombectomy. Most patients were confined to strict bed rest and managed symptomatically. ECGs were reviewed in eight patients. Six of the patients had a low origin of the ST complex in lead I, a Q wave in lead III and an inverted T wave in lead III. One additional patient had the S1 and T3 findings, but had a notched QRS in lead III. The one remaining patient had only T3 inversion.

As early as the late 1930s, S1Q3T3 became an expected sign in patients who presented with pulmonary embolism. Studies within the last 15 years have challenged the role of this classic diagnostic sign. One retrospective review of patients with pulmonary embolism found that the most common ECG finding was non-specific ST-T wave changes. More recent studies have demonstrated that anterior T wave inversions, sinus tachycardia and incomplete right bundle branch block are all more common than S1Q3T3.

Early contributions to the medical diagnostic literature, such as the ECG findings in patients with pulmonary embolism, are of both historic and clinical interest, but far too many of these have become deeply ingrained in medical education without clinical validation. Classic signs and symptoms of disease must be questioned, updated, or even discarded when they are supplanted by more rigorously obtained data.—CR