Of 55 million deaths globally every year, about 30 percent are from cardiovascular diseases. Of these, 40 percent to 50 percent are likely to be due to acute myocardial infarction (AMI – heart attack). Primary percutaneous coronary intervention (PCI - procedures such as angioplasty in which a catheter-guided balloon is used to open a narrowed coronary artery) offers benefits over thrombolytic therapy (medication that breaks up clots), but access to this procedure, particularly in developing countries, is limited. Advances in treatments are likely to have a greater public health and clinical impact if they are effective, safe, simple to administer, affordable, and applicable to a widely diverse spectrum of economic and health care settings, according to background information in the article. Trials of medications such as unfractionated heparin (UFH), direct thrombin inhibitors, and enoxaparin have thus far failed to demonstrate reductions in the death rate, and bleeding is substantially increased when these agents are used with aspirin and thrombolytic therapy. There is a clear need for an effective, inexpensive, and safe antithrombotic agent for patients with STEMI (ST-segment elevation myocardial infarction – a certain characteristic pattern on an electrocardiogram associated with a heart attack).
Salim Yusuf, D.Phil., F.R.C.P.C., F.R.S.C., of McMaster University and Hamilton Health Services, Ontario, Canada, and colleagues with the OASIS-6 Trial conducted a study to evaluate the effect of fondaparinux compared with standard approaches to antithrombotic therapy in patients with STEMI in preventing death or reinfarction (additional heart attack) at 30 days. These outcomes were also assessed at 9 days and at study end (minimum of 3 and maximum of 6 months). The study included 12,092 patients with STEMI from 447 hospitals in 41 countries who were randomized to receive fondaparinux 2.5 mg once daily for up to 8 days or usual care (placebo in those in whom UFH is not indicated or UFH for up to 48 hours followed by placebo for up to 8 days in patients with STEMI).
The researchers found that death or reinfarction at 30 days was significantly reduced from 11.2 percent of 6,056 patients in the control group to 9.7 percent of 6,036 patients in the fondaparinux group, a risk reduction of 14 percent. These benefits were observed at 9 days (8.9 percent) placebo vs. (7.4 percent) fondaparinux, a 17 percent risk reduction; and at study end (14.8 percent) placebo vs. (13.4 percent) fondaparinux, a 12 percent reduction. Risk of death was significantly reduced throughout the study. However, there was no benefit in those undergoing primary PCI. There was a tendency to fewer severe bleeding events in the fondaparinux group.
"In summary, fondaparinux reduces mortality and reinfarction early, and this benefit persists long term," the authors write. "… results from … OASIS-6 confirm the value and safety of fondaparinux as a simple and widely applicable antithrombotic therapy in a broad group of patients with acute coronary syndrome."
(Available pre-embargo to the media at www.jamamedia.org)
Editor's Note: For funding/support information and the financial disclosures of the authors, please see the JAMA article.
Editorial: The Drug, the Strategy, the Environment, or All of the Above?
In an accompanying editorial, Robert M. Califf, M.D., of Duke Clinical Research Institute, Durham, N.C., comments on the OASIS-6 Trial results.
"The results of the OASIS 6 trial are certain to lead to an outburst competitive pronouncements by companies and by leaders in the clinical community about the question of which regimen is truly best. The multiple permutations and combinations of antithrombotic drugs are increasingly confusing to clinicians seeking the best options for their patients. How do physicians find a way out of this maze? Hopefully, the era in which individual clinical trials are considered to be the definitive answer to questions of clinical practice is coming to an end. Rather, clinical practices should be organized in a manner that allows for continuous learning based on observation of practice through collection of data, with randomized trials embedded within observational databases to answer specific questions about pragmatic choices in medical care. Just a few years ago, this would have seemed impossible but the impending widescale availability of electronic health records and professional databases promises to make the data readily available – the challenges are no longer technical. The largest advances in STEMI treatment are the findings that reperfusion is beneficial, that direct PCI is superior to lysis [dissolution of clots], and that treatment with aspirin, beta-blockers, and angiotensin-system modulators in appropriate patients all save lives."
"Due to the outstanding contributions of the OASIS 6 investigators, another degree of certainty can be added to the understanding that anticoagulation is also an essential element of STEMI care. True knowledge of the best mix of antithrombotics for each patient will come with development of a global network that truly provides an unbiased assessment of multiple medical permutations as part of a continuous learning effort."
(Available pre-embargo to the media at www.jamamedia.org)
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