The low molecular weight heparin enoxaparin (Lovenox, Sanofi-Aventis) is superior to unfractionated heparin as an adjunct
to thrombolytic therapy in patients with ST elevation myocardial infarction (MI), researchers reported at the 55th Annual
Scientific Session of the American College of Cardiology (ACC). The meeting was held in Atlanta last month.
The data, from the Enoxaparin & Thrombosis Reperfusion for Acute Myocardial Infarction Treatment-Thrombolysis in Myocardial
Infarction (ExTRACT-TIMI 25) trial, were published recently in an early release paper in the New England Journal of Medicine (NEJM). The enoxaparin strategy significantly reduced the primary end point of death or nonfatal recurrent MI through 30 days but
was associated with increased bleeding.
"The findings have broad implications as most MI patients worldwide are treated with thrombolytic therapy, and only those
who are transported to specialty centers are treated with percutaneous coronary interventions," said principal investigator
Elliott Antman, M.D., director of the Samuel A. Levine Cardiac Unit at Brigham and Women's Hospital in Boston. His group randomized
20,506 MI patients who received thrombolytic therapy to treatment with enoxaparin throughout the index hospitalization or
the standard strategy of infusing unfractionated heparin for at least 48 hours.
The primary end point occurred in 12% of patients randomized to unfractionated heparin and 9.9% of patients assigned to enoxaparin,
for a 17% risk reduction. The risk of recurrent nonfatal MI was significantly reduced by 33% in patients receiving enoxaparin
compared with unfractionated heparin (3% and 4.5% in the two groups, respectively).
Overall, 7.5% of the unfractionated heparin group died versus 6.9% of the enoxaparin group. Major bleeding occurred in 2.1%
of the enoxaparin group versus 1.4% of the unfractionated heparin group. Despite the increased bleeding, a net clinical benefit
was seen in the enoxaparin arm, Antman said.
At the ACC meeting, researchers also reported that high-dose rosuvastatin (Crestor, AstraZeneca) causes a significant regression
of coronary atherosclerosis. These findings from ASTEROID (A Study to Evaluate the Effect of Rosuvastatin on Intravascular
Ultrasound-Derived Coronary Atheroma Burden) were published on-line on March 13 in JAMA (Journal of the American Medical Association)-Express. They show that the treatment significantly decreases low-density lipoprotein (LDL) cholesterol and increases high-density
lipoprotein (HDL) cholesterol.
"While atherosclerosis has been historically viewed as a chronic progressive disease that could be slowed by therapy, we have
now shown for the first time that maximally intensive lipid-lowering treatment can partially reverse the atherosclerotic disease
process," said principal investigator Steven Nissen, M.D., who is medical director of the Cleveland Clinic Cardiovascular
Coordinating Center.
The 507 participants, all of whom had coronary atherosclerosis, were treated with the highest approved dose of rosuvastatin,
40 mg/day, for two years. Intravascular ultrasound (IVUS) was used to measure percent atheroma volume (PAV), which is considered
the most stringent IVUS measure of disease progression and regression.
Results in 329 rosuvastatin patients with evaluable IVUS examinations showed that LDL cholesterol decreased from 130.4 mg/dl
to 60.8 mg/dl, for a mean reduction of 53.2%. HDL cholesterol increased from 43.1 mg/dl to 49.0 mg/dl, or 14.7%. "These are
the largest cholesterol improvements ever reported," Nissen observed. The mean change in PAV for the entire vessel was 0.98%
versus baseline. Overall, 63.6% of patients demonstrated regression of atherosclerosis. The statin regimen was well tolerated.
Nissen emphasized that the study did not address whether the rosuvastatin-induced coronary regression translates into decreased
morbidity and mortality.
In another study, researchers found that dual antiplatelet therapy using aspirin plus clopidogrel (Plavix, Sanofi-Aventis/Bristol-Myers
Squibb) is no better than aspirin alone for preventing atherothrombotic events. According to the results of the Clopidogrel
for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance (CHARISMA) trial, while the combination
increases the rate of bleeding compared with aspirin alone when used in patients with multiple atherothrombotic risk factors,
combination therapy may have a possible benefit in patients with established cardiovascular disease.
The data were simultaneously released in the on-line edition of NEJM.
Deepak Bhatt, M.D., director of the Interventional Cardiology Fellowship at the Cleveland Clinic Foundation, and colleagues
elsewhere randomized 15,603 patients at high risk of atherothrombotic events to clopidogrel, 75 mg/day, plus low-dose aspirin
(75 to 162 mg/day) or placebo plus low-dose aspirin. The median follow-up was 28 months.
The primary efficacy end point—a composite of MI, stroke, or death from cardiovascular causes—occurred in 6.8% of patients
on combination therapy and 7.3% of patients assigned to placebo plus aspirin.
Overall, 16.7% of patients on combination therapy and 17.9% of aspirin-only patients had to be hospitalized due to ischemic
events. Severe bleeding occurred in 1.7% and 1.3% of the two groups, respectively.
In a subgroup with established cardiovascular disease, clopidogrel seemed to provide an advantage. That is, only 6.9% of the
combination therapy group had an MI, stroke, or died during follow-up versus 7.9% on aspirin monotherapy. Bhatt emphasized,
however, it is possible that further analysis of the data may not corroborate this finding.
Analysis of the subgroup with multiple risk factors revealed that 6.6% of them had an MI, stroke, or died compared with 5.5%
of the aspirin-only group. Notably, nearly twice as many patients in this subgroup who were on combination therapy died from
cardiovascular causes (3.9% vs. 2.2% for the two groups, respectively). The combination group also had a higher rate of moderate
bleeding (2.2% vs. 1.4%) and severe bleeding (2% vs. 1.2%).
"This dichotomous result in the two subgroups is intriguing," Bhatt noted at a news conference. "But our overall findings
do not support the use of dual antiplatelet therapy across the broad population tested."
THE AUTHOR is a Paris-based freelance clinical writer.
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