Because D-dimer levels were only measured once at the time of the patients’ enrollment in the study, it is unknown if patients with normal levels of D-dimer might progress to abnormal D-dimer levels and, therefore, to a potentially higher risk of VTE. This question could be answered with serial testing of D-dimer levels. The study was not powered enough to detect relative risk of bleeding from anticoagulation alone. Thus, these results were taken as a composite with the VTE events.
This study argues that anticoagulation in VTE patients with abnormal D-dimer levels measured after a month of stopping a standard three-month course of anticoagulation should be continued. What is not clear is whether we should continue treating people with normal D-dimer levels. Although not statistically significant, the absolute rate of VTE of 6.2% in these patients was higher than the 2.9% rate in patients with high D-dimer levels who continued anticoagulation.
Early Administration of ACE Inhibitors in MI Patients
Borghi C, Bacchelli S, Degli Esposti D, et al. Effects of early angiotensin-converting enzyme inhibition in patients with non-ST-elevation acute anterior myocardial infarction. Am Heart J. 2006 Sep;152(3):470-477.
Angiotensin-converting enzyme inhibitors (ACEIs) have demonstrated efficacy in improving long-term survival, particularly in patients with ST-elevation MI (STEMI) with left ventricular dysfunction (LVD) and/or congestive heart failure (CHF). There is less information available from clinical trial data, however, regarding the early use of ACEIs with non-ST-elevation MI (NSTEMI) patients, who are believed to be at an overall lower risk of in-hospital morbidity and mortality than STEMI patients.
Researchers focused on the question of ACEI efficacy in NSTEMI in a post hoc analysis of the patients enrolled in the Survival of Myocardial Infarction Long-term Evaluation (SMILE) study. The original study enrolled 1,556 patients with anterior acute MI (AMI) who were admitted to 154 coronary care units in Italy. Participants were patients who presented with chest pain within 24 hours, who demonstrated electrocardiographic signs of anterior wall AMI, and who were not eligible for thrombolytic therapy or reperfusion. These patients did receive beta blockers, nitrates, analgesic agents, inotropic drugs, diuretic agents, and anticoagulation agents as deemed appropriate.
Exclusion criteria included cardiogenic shock, systolic blood pressure below 100 mm Hg, serum creatinine above 2.5 mg per deciliter, a history of CHF, prior treatment with ACEI, and contraindication to the use of ACEI. Patients were randomized to either placebo or the short-acting ACEI zofenopril, with a starting dose of 7.5 mg every 12 hours. The dose was progressively doubled until the final target dose of 30 mg twice a day was reached. Upon completion of a six-week double-blind period, the study medications were stopped, but the patients continued taking their other medications for approximately 48 additional weeks, at which time vital status was blindly obtained by questionnaire or from registry offices. The primary endpoints were the occurrence of death or CHF during the treatment period.
In this post hoc analysis, only the 526 patients with anterior MI were studied. The baseline characteristics of the placebo and zofenopril group were closely matched but were predominantly male. The primary endpoint of this analysis was the combined occurrence of death or severe CHF during the six weeks of treatment with zofenopril or placebo, both given in addition to conventional treatment. Secondary endpoints were the six-week occurrence of severe CHF, nonfatal MI or angina, and cumulative one-year mortality.
The findings of this analysis indicate a relative risk reduction (RRR) of 65% (95% CI 20%80%, 2P=0.003) of a major cardiovascular event using zofenopril in the first 6 weeks of treatment. Cumulative incidence of combined death and CHF was significantly (P=0.017) greater in the placebo group than in the group of patients given zofenopril. In addition, occurrence of severe CHF was lower in the zofenopril group (RRR 84%, 95% CI 33%97%), as was one-year mortality (RRR 43%, 95% CI 14%-57%, 2P=0.36). During the six weeks, there was a slightly lower usage of beta blockers in the zofenopril group, as well as lower usage of calcium channel blockers and diuretics in this same group at one year. Systolic blood pressure (SBP) and heart rate did not differ between the two groups.