Identifying the Stroke Victim at Risk for Hemorrhage During Thrombolysis
Diabetes mellitus, cardiac disease, increasing stroke severity, old age, antiplatelet agents other than aspirin used before stroke, and high blood pressure before treatment increase the risk of brain hemorrhage in stroke patients undergoing thrombolysis with recombinant tissue-type plasminogen activator (rtPA), according to researchers who participated in the Multicenter rt-PA Acute Stroke Survey. The report of that study appears in this week’s issue of Circulation (Circulation. 2002;105:1679–1685OpenUrl).
Identifying patients at highest risk of intracerebral hemorrhage after thrombolysis is particularly important because such bleeding is extremely dangerous. Many in the emergency medicine and cardiology communities have said there is a need to identify the subsets of patients who should and should not undergo thrombolysis for stroke.
In their study, the researchers noted that 60% of patients with symptomatic intracerebral hemorrhage died. Of those with asymptomatic intracerebral hemorrhage, 17% died, and of those with no hemorrhage, 10% died. The rate of severe disability was 32% in the group with symptomatic intracerebral hemorrhage, 29% in the asymptomatic group, and 26% in the group without brain hemorrhage. Excellent outcomes were recorded in 4% of the group with symptomatic brain hemorrhage, 21% of those with asymptomatic hemorrhage, and 34% of those with no hemorrhage.
The group, which included researchers from Israel, Pennsylvania, Canada, Minnesota, Germany, and New York, was led by David Tanne, MD, of the Stroke Unit in the Department of Neurology at Chaim Sheba Medical Center in Tel-Hashomer, Israel. The group identified 1205 patients who received rtPA within 3 hours of stroke symptom onset. Of these, 72 patients (6%) developed symptomatic intracerebral hemorrhage, and 86 (7%) had asymptomatic intracerebral hemorrhage that was identified by CT scan.
Dr Tanne and his colleagues also found that when baseline CT and laboratory findings were included in analyses, the main factors associated with intracerebral hemorrhage were early ischemic CT changes (particularly if exceeding one third of middle cerebral artery territory), very severe stroke, diabetes, or elevated serum glucose and lower platelet counts.
The authors concluded, “At present, the factors identified should not dissuade physicians from treating patients according to accepted treatment guidelines. These associations may be indicators of higher risk situations rather than features causally related to intracerebral hemorrhage.”
Aspirin is one of those drugs that fills so many roles that the idea of being resistant to it is almost abhorrent. It is a pain reliever, a fever reducer, an antiinflammatory, and a blood thinner. However, in this week’s issue of Circulation (Circulation. 2002;105:1650–1655), Canadian and Australian researchers found that patients in whom there was failure of suppression of thromboxane generation (a marker of aspirin resistance) faced an increased risk of a future heart attack or cardiovascular death.
In their study, the researchers, led by Jeffrey L. Weitz, MD, and Salim Yusuf, DPhil, of McMaster University in Hamilton, Canada, obtained baseline urine samples from 5529 Canadian patients enrolled in the Heart Outcomes Prevention Evaluation (HOPE) Study. They measured urinary 11-dehydro thromboxane B2 levels (a marker of in vivo thromboxane generation) in 488 patients who had been treated with aspirin and had experienced a myocardial infarction, stroke, or cardiovascular death during the 5 years of follow-up. They also measured the chemical in the urine of 488 sex- and age-matched controls who experienced no such event during the 5-year period.
They found that the higher the level of the 11-dehydro thromboxane B2, the greater the patient’s risk for heart attack, stroke, or cardiovascular death. Those in the upper quartile (the highest levels of the chemical) had a 2-fold higher risk of cardiovascular death than did those in the lower quartile.
The researchers said that 11-dehydro thromboxane B2 might in the future be used as a marker of aspirin resistance, identifying those patients who would benefit from additional antiplatelet treatments that would specifically target thromboxane activity. However, they cautioned that further work is necessary to determine the extent to which 11-dehydro thromboxane B2 can be used as a marker, and that further studies of its biological variation and other characteristics must be performed.
Stents Are the CADILLAC of Care
Investigators in the Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications (CADILLAC) concluded that stents with or without abciximab therapy should not be considered the routine therapy in reperfusion (N Engl J Med. 2002;346:957–966).
In the study, 2082 patients with acute myocardial infarction who were to undergo percutaneous transluminal coronary angioplasty (PTCA) were randomly assigned to one of 4 groups: PTCA alone, PTCA plus abciximab, stenting alone (MultiLink stent), or stenting plus abciximab. The primary result of restoring normal flow to the artery was achieved in at least 94.5% of cases, regardless of the group to which the patients were assigned.
Six months later, the story was much different. The composite end point of death, reinfarction, disabling stroke, and urgent revascularization of the target vessel had occurred in 20% of patients who had undergone PTCA alone, 16.5% of those who had had PTCA plus abciximab, 11.5% of those who had received a stent, and 10.2% of those who had received a stent and abciximab. The significant difference actually occurred in the rates of target-vessel revascularization, which ranged from 15.7% (PTCA alone) to 5.2% (stent plus abciximab).
The authors, led by Greg Stone, MD, of the Cardiovascular Research Foundation of New York, and Cindy Grines, MD, of William Beaumont Hospital in Royal Oak, Michigan, wrote, “The principal finding of our study is that routine stent implantation results in higher rates of event-free survival and better angiographic outcomes than does PTCA (with stenting performed only in the event of suboptimal results). The clinical benefits of stenting were consistent in all clinical subgroups, independent of abciximab use, and attributable primarily to lower rates of early and late stenosis and reocclusion of the infarct-related artery. . . . The use of abciximab reduced the rates of subacute thrombosis and recurrent ischemia leading to repeated revascularization of the target vessel during the first several weeks after primary PTCA or stenting. Abciximab did not, however, significantly improve TIMI flow rates or reduce the rates of angiographic restenosis, late reocclusion of the infracted artery, or late cardiac events.”⇓
Vitamins and Donor Hearts
Vitamins C and E given twice daily appear to have delayed the onset of arteriosclerosis in donor hearts in the first year after transplantation, according to a trial by James Fang, MD, and colleagues from The Brigham and Women’s Hospital in Boston, Mass (Lancet. 2002;359:1108–1113).
In this study, published in the March 30, 2002, issue of Lancet, researchers sought to deal with the problem of arteriosclerosis that affects 70% of patients within 3 years of heart transplantation. In their study, 40 patients who had received a transplant within 2 years were randomly assigned to receive 500 mg of vitamin C and 400 IU of vitamin E twice daily or placebo for a year.
The study’s primary end point was the change in the average intimal index (plaque area divided by vessel area) measured by intravascular ultrasonography. During the first year, the intimal index increased by 8% in the placebo group but did not change significantly in the treatment group. Coronary endothelial function remained stable in the 2 groups.
“Our results suggest that vitamins C and E provide a clinically useful approach to reducing arteriosclerosis after cardiac transplantation. Antioxidant therapy with these vitamins also may be useful in other solid-organ allografts, such as kidney, lung, and liver transplants, in which obliteration of vascular or tubular structures limits long-term success. Further investigations are warranted to investigate whether the beneficial effects of vitamins C and E are sustained over many years when most of the clinical complications resulting from transplant-associated arteriosclerosis occur,” said Dr Fang.