Expanding on findings from world-renowned TIMI trials, Cardiovascular Center research is improving treatment and outcomes for patients with cardiovascular disease.
Physicians at the Brigham and Women’s Hospital (BWH) Cardiovascular Center are leaders in clinical research that has contributed to improved treatments and better outcomes for patients with heart attack and cardiovascular disease.
The TIMI (Thrombolysis in Myocardial Infarction) Study Group has been the source for many of these findings. The internationally-respected multi-site TIMI trials, begun in 1984 under the direction of Eugene Braunwald, MD, BWH Chairman of Medicine from 1972-1996, and researcher Carolyn McCabe, have grown to a major research endeavor, with 40 completed trials, eight enrolling trials, and more in the planning stages. (For more information on the TIMI trials, visit www.timi.org or call 1-800-385-4444.)
Latest findings
First presented at the American College of Cardiology’s annual scientific session in March 2006, important findings from ExTRACT-TIMI 25 showed that a new therapy – using enoxaparin (a low molecular weight heparin) – significantly reduces risk of repeat heart attack and death. ExTRACT-TIMI 25 is one of the largest heart attack trials ever conducted with 20,506 patients enrolled at 674 sites in 48 countries.
Elliott M. Antman, MD, Director of the Coronary Care Unit at BWH, senior investigator in the TIMI Study Group, and international principal investigator for the recently completed ExTRACT-TIMI 25 says, “The results of this trial are dramatic and significant; a strategy using enoxaparin prevents more patients from dying or having a second heart attack within 30 days of treatment compared to the strategy using unfractionated heparin, which up to now has been considered the standard blood thinner regimen used to support fibrinolytic therapy.” He continues, “Enoxaparin, a modified form of unfractionated heparin, interrupts the clotting system more efficiently and more reliably than unfractionated heparin. By doing so, enoxaparin prevents blood clots from forming again in arteries that carry blood to the heart muscle.”
ExTRACT-TIMI 25 was a randomized, double-blind double-dummy study comparing the outcomes for patients treated with fibrinolytics and antiplatelet medications plus unfractionated heparin (UFH) with those for patients treated with fibrinolytics and antiplatelet medications plus enoxaparin, a low molecular weight heparin (LMWH) thatis simpler than UHF to administer.In the trial enoxaparin reduced the chance of dying orhaving a second heart attack, which is highly significant. There was a 33 percent reduction in the chance of a second heart attack in the first 48 hours. The study has critical importance for the treatment of most patients who suffer a heart attack. Dr. Antman says. “Although opening a blocked coronary artery witha balloon-tipped catheter, or percutaneous coronary intervention, has been shown to be an effective treatment for heart attack patients who come to specialized centers, the vast majority of patients worldwide receive clot-busting medications to treat their heart attack.”
Expanding on findings from world-renowned TIMI trials, Cardiovascular Center research is improving treatmentand outcomes for patients with cardiovascular disease. Eugene Braunwald, MD, and Christopher Cannon, MD “Based on the results of the ExTRACT-TIMI 25 trial, we believe that the enoxaparin strategy is now the preferred anticoagulant regimen to use in heart attack patients who receive clot-busting drugs,” says Dr. Braunwald, who is also Chairman of the TIMI Study Group.
Current research
Building on TIMI research, IMPROVE IT is an on-going study being conducted at BWH. IMPROVE IT. Christopher Cannon, MD, a senior investigator for the TIMI Study Group at BWH, says, IMPROVE IT will build on previous research, which demonstrated that patients who had suffered coronary syndromes within the past 10 days and were on aggressive statin therapy experienced a reduced risk for death, a subsequent cardiovascular event and the requirement for subsequent angioplasty or bypass as compared with patients on moderate statin therapy. Risk reduction was apparently related to lowering levels of LDL cholesterol and the inflammatory marker C-reactive protein (CRP). IMPROVE-IT, anticipated to enroll 10,000 patients in 25 countries, is designed to study whether lowering levels of LDL cholesterol as low as 50 mg/dl and reducing levels of CRP below currently recommended levels will be beneficial. Dr. Braunwald will be national study chairman for IMPROVE IT, and Marc Sabatine, MD, is the principal investigator at BWH. (For more information, visit www.timi.org or call 1-800-385-4444.)
Researchers at the Center for Cardiovascular Disease Prevention are studying therapies specifically designed to prevent first ever heart attacks and strokes. The JUPITER study seeks to add to the burgeoning body of knowledge regarding the role of CRP in predicting and preventing heart attack and stroke. Despite enormous advances in cardiovascular medicine, half of all heart attacks and strokes occur in apparently normal risk patients with low or normal cholesterol levels. Over the last decade, BWH physicians and scientists have demonstrated in a number of different studies that measuring CRP is an effective and inexpensive way to improve prediction of heart attack and stroke across all populations and other risk factors.
Paul M. Ridker, MD, Director of BWH’s Center for Cardiovascular Disease Prevention and international principal investigator for JUPITER, notes, “Adding high sensitivity C-reactive protein (hsCRP) measurement to cardiac risk stratification reclassifies 25 to 35 percent of people into a risk group higher or lower than they currently think they’re in.”
Studies in patients who have already experienced a heart attack have shown that statins are effective in reducing both cholesterol and hsCRP; that patients who lowered their hsCRP below 2 mg/l did better than those who did not, regardless of cholesterol levels; and that patientswho lowered both LDLcholesterol levels and hsCRP levels had the best outcomes.
The JUPITER study seeks to address the broader question of whether patients with normal cholesterol and highhsCRP should be on statin therapy to prevent first-ever heart attack, stroke, and cardiac death. More than 7,000 of the expected 15,000 patients have already been enrolled and randomized to receive either statins or a placebo for a minimum of three years. Dr. Ridker says, “Between 30 and 40 million Americans with low cholesterol and elevated CRP levels currently sit outside accepted treatment guidelines, yet we believe they are at risk. The JUPITER results will determine whether these patients should be treated and may radically change the way we approach prevention strategies.” (For more information, visit www.jupiterstudy.com or call 1-800-660-8254.)
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