American Heart Association, 2006 Scientific Sessions: Fondaparinux Reduces Mortality and Re-infarction in Non-reperfused STEMI Patients

Posted by James

Speaker: Lars C. Wallentin, MD, PhD, Professor of Cardiology, Uppsala Clinical Research Centre, Uppsala, Sweden

In non-reperfused patients with acute ST-segment elevation myocardial infarction (STEMI), fondaparinux (Arixtra, GlaxoSmithKline), an anticoagulant that inhibits activated Factor X, reduced mortality and re-infarction without increasing bleeding or stroke when it was administered for eight days, compared with unfractionated heparin (UFH) for 48 hours or placebo.

Approximately 30% of patients with STEMI do not receive fib-rinolytic therapy. An analysis was designed to evaluate the effect of fondaparinux 2.5 mg once daily for up to eight days in 2,864 patients who did not receive reperfusion therapy in the Organization for the Assessment of Strategies for ischemic Syndromes-6 (OASIS-6) trial.

The original trial was a randomized, double-blind comparison of fondaparinux 2.5 mg once daily versus placebo if UFH was not indicated or versus UFH for up to 48 hours, followed by placebo for up to eight days if UFH was indicated. The trial included 12,092 patients with STEMI from 447 hospitals in 41 countries; patients were followed for 180 days, from September 2003 to January 2006. canadian antibiotics

At 30 days, mortality and re-infarction rates were reduced from 15.1°% in the controls (212 of 1,409 patients) to 12.2°% in the fondaparinux patients (178 of 1,458 patients) (P = .027). These benefits were observed at nine days and at the study’s end at 180 days.

There was no significant difference in the incidence of stroke or major bleeding. At 30 days, the composite outcome of death, re-infarction, or severe bleeding, however, was significantly reduced with fondaparinux (15.3% vs. 12.6% for controls; P = .037). At the end of the study, the composite outcome was significantly reduced by 20.5% with treatment and by 17% in the control group (P = .023).

Valsartan and Prevention of New-Onset Atrial Fibrillation in Hypertension

Speaker: Roland E. Schmieder, MD, Professor of Medicine, Medizinische Klinik 4, Nephrology and Hypertension, University Erlangen Ntirburg, Erlangen, Germany

Valsartan (Diovan tablet, Novartis)-based antihypertensive therapy was more effective in preventing new-onset atrial fibrillation (AF) in hypertensive patients than amlodipine (Canadian Norvasc, Pfizer)-based therapy.

The Valsartan Antihypertensive Long-Term Use Evaluation (VALUE) trial enrolled 15,245 patients at high cardiovascular risk. This prospective, double-blind, active-controlled study was conducted at 934 clinical sites in 31 countries. Patients were randomly assigned to take either valsartan 80 mg – 160 mg/day or amlodipine 5 mg – 10 mg/day, combined with additional antihypertensive agents (e.g., diuretics, beta blockers, and others) for an indefinite period of time (as of this date, up to four years).

The original study’s findings suggested no statistically significant disparity between the two treatment groups in the primary endpoint of cardiac mortality and morbidity rates (10.6% for valsartan; 10.4% for amlodipine), despite unintended differences in blood pressure (especially early in the trial) that favored the amlodipine-based therapy.

Because AF increases cardiovascular risk in patients with hypertension, an analysis of the data was performed according to a secondary prespecified objective to compare the effect of both treatments on new-onset AF. Electrocardiography (ECG) recordings were obtained every year and were analyzed at a central laboratory for left ventricular (LV) hypertrophy and new-onset AF.

At the initial baseline evaluation, AF was diagnosed in 2.6% of the valsartan patients and in 2.6% of the amlodipine patients. During antihypertensive treatment, the incidence of at least one documented occurrence of new-onset AF was 3.6% in the canadian valsartan patients and 4.34% in the amlodipine patients (odds ratio, 0.84; P = .044). For the next four years, the corresponding odds ratios were as follows:

• 0.690 (P = 0.035) in the first year
• 0.694 (p = .0108) in the second year
• 0.708 (P = .011) in the third year
• 0.832 (P = .120) in the fourth year

The incidence of persistent AF was 1.35% for valsartan and 1.97% for amlodipine (odds ratio, 0.681; P = .005). Taking potentially confounding factors such as age, a history of coronary artery disease, and LV hypertrophy into account, the incidence of AF remained significant (higher with generic amlodipine than with valsartan) for at least one case of AF and for persistent AF.