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Aspirin in AMI — The Sooner, the Better

2002; Lippincott Williams & Wilkins; Volume: 24; Issue: 9 Linguagem: Inglês

10.1097/01.eem.0000334458.25555.57

1552-3624

W. Richard Bukata,

Peptidase Inhibition and Analysis

It is no secret that aspirin, lowly aspirin, remains one of the mainstays when it comes to treating myocardial infarction. Unfortunately, aspirin is too inexpensive for Bayer or any other company to be touting this drug heavily to physicians. The following study serves as an opportunity to reaffirm the value of this “wonder drug” in the care of MI patients. The particular focus in the study was the effect of aspirin dose timing on outcome. Aspirin given before thrombolytic therapy was compared with outcomes when aspirin was given after thrombolytics. Specifically, the mean timing of aspirin administration in the early and late treatment groups was 1.6 hours vs. 3.5 hours after symptom onset, a difference of only two hours. AMI patient mortality was much lower in those receiving aspirin before thrombolytic therapy than those receiving it after The results were dramatic. The mortality rate at seven days, 30 days, and one year in those getting “early” aspirin therapy was about half the rate in the “late” aspirin patients. Even when the effects of other treatment were taken into consideration, the benefits of early aspirin therapy were profound. Bottom line: early ASA, whether given in the ambulance or in the ED, is an essential part of MI management. Timing of Aspirin Administration as a Determinant of Survival of Patients with Acute Myocardial Infarction Treated with Thrombolysis Freimark D, et al Am J Card 2002;89(4):381 BACKGROUND: The time-dependent effect of thrombolytic agents on outcome in acute myocardial infarction (AMI) is well established. There are conflicting data regarding the time-dependent effect of aspirin treatment in this setting. METHODS: This Israeli study examined mortality among 1,200 patients with ST elevation AMI treated with rtPA or streptokinase, followed by heparin or the thrombin inhibitor, argatroban, according to the timing of first aspirin use. Early users (364) self-administered aspirin or received it in the ambulance, ED, or CCU before thrombolytic therapy. Late users (836), who had similar baseline characteristics, received 160 mg of aspirin within one hour after the initiation of thrombolytic therapy. All subjects subsequently received aspirin daily for 30 days. RESULTS: The median time from symptom onset to treatment with aspirin was 1.6 hours for early users vs. 3.5 hours for late users (p<0.001). Early users were more likely than late users to develop recurrent ischemia (36% vs. 24%), and ventricular tachycardia or fibrillation (16% vs. 10%). They were more likely to receive beta-blockers (72% vs. 63%), and to undergo coronary angiography (52% vs. 36%) and revascularization procedures (37% vs. 24%). Mortality rates were significantly lower in early aspirin users than in late users (2.5% vs. 5.6% at seven days [p=0.01], 3.3 percent vs. 7.3 percent at 30 days [p=0.008], and five percent vs. 10.6 percent at one year [p=0.002]). Benefits persisted when other treatment was taken into consideration. CONCLUSIONS: In these patients with AMI, mortality was much lower in those treated with aspirin before thrombolytic therapy than in those started on aspirin after initiation of thrombolytics. Ritual and LP Headache The practice of medicine is cloaked in ritual. Some rituals develop because their tenets seem reasonable. One such ritual is the belief that a variety of post-lumbar puncture practices will reduce the incidence and/or severity of post-LP headaches. The following review of the topic is just the most recent such paper that makes it clear that none of a variety of common practices significantly affects headache incidence or intensity — not the ritual mandatory supine position after the procedure, not forcing fluids, not using caffeine. The only thing that has been shown to matter is needle size — the smaller the better. Our LP trays come with a standard 20 gauge needle that I routinely swap for a 22. Studies of needles with holes not at the end but along the side have demonstrated substantially lower incidences of post-LP headaches. Although it makes theoretical sense, I've never seen a study proving that having the bevel parallel to the long axis of the spinal canal (which would appear to split dura fibers rather than transect them) makes a difference, although I do practice this ritual. Myth: Fluids, Bed Rest, and Caffeine are Effective in Preventing and Treating Patients with Post-Lumbar Puncture Headache Lin W, et al West J Med 2002;176:69 BACKGROUND: Post-lumbar puncture (LP) headache occurs in six to 36 percent of patients. The cause is uncertain; proposed mechanisms include low CSF pressure due to leakage at the puncture site, with stretching of pain-sensitive structures, and/or cerebral vasodilatation. METHODS: The authors from UCLA and Cedars Sinai Medical Center in Los Angeles reviewed the literature concerning prophylaxis and treatment of post-LP headache. RESULTS: The only prospective study of increased fluids found no effect of increased oral fluid intake (3L daily vs. 1.5L daily in controls for five days after LP) on the proportion of subjects who remained symptom-free. Several studies reported no difference in the rate of post-LP headache in patients assigned to bed rest or immediate ambulation after LP. Most support for administration of caffeine, hypothesized to be helpful due to decreased cerebral blood inflow secondary to vasoconstriction, is derived from a single study published in 1975 that contained numerous methodologic flaws. No evidence supports bed rest, fluids, or caffeine for preventing post- LP headache CONCLUSIONS: There is no firm evidence supporting a benefit of post-procedural bed rest, fluids, or caffeine for the prevention or treatment of post-LP headache. This is in contrast to use of a small needle, appropriate bevel direction, and stylet replacement, which have each been reported to be effective. Epidural blood patching (slow injection of 10–20 ml of the patient's blood into the epidural space at the location of the previous puncture) is a very effective treatment in 85 to 98 percent of cases, and is indicated for patients with moderate to severe post-LP headache lasting more than 24 hours. Support for NINDS The three-hour time limit in which thrombolytic therapy can be administered for stroke doesn't allow many patients the opportunity to receive this therapy (which, depending on your point of view regarding the merits of this treatment, may be bad or good). To determine if the time limit could be extended to six hours, the ATLANTIS trial was undertaken but discontinued after it was clear that the outcomes were much worse when the time limit was extended. As part of the ATLANTIS trial, however, there was a subgroup of patients (61) who were treated within the traditional three-hour window. Many have wanted to see what the outcome was in this subset because there has never been a duplication of the NINDS trial. (And there is not likely to be one in the future. Why take a chance that a new study will show negative results?) Years after the trial was terminated and years after tPA has become established, these data have finally been published. The results were not particularly consistent with the NINDS data when it comes to magnitudinal issues, perhaps because the number of patients is small. In any case, the study demonstrated complete recovery at 90 days in 61 percent of treated patients vs. 29 percent of controls (substantially better than the NINDS data), but the rate of symptomatic intracranial hemorrhage was twice as high as in NINDS (13% vs 0%). To make matters worse, there was a trend to greater overall mortality at 90 days with treatment (17% vs. 5%). So the jury is still out, at least for some physicians. It would be interesting to have someone combine the ATLANTIS data with the NINDS data. Atlantis Trial: Results for Patients Treated within Three Hours of Stroke Onset Albers GW, et al Stroke 2002;33:493 BACKGROUND: The NINDS trial reported a beneficial effect of IV tPA in ischemic stroke patients treated within three hours of symptom onset, and several large trials have found no benefit beyond this time frame. IV tPA within three hours of symptom onset yielded improved outcomes in patients with ischemic stroke METHODS: The Alteplase Thrombolysis for Acute Noninterventional Therapy in Ischemic Stroke (ATLANTIS) trial compared IV tPA and placebo in 755 ischemic stroke patients treated within six hours of symptom onset. The authors of the current study, supported by Genentech (with two principal authors receiving honoraria from Genentech and one being a former employee), analyzed data from 61 patients in the ATLANTIS trial who were randomized within three hours of symptom onset. RESULTS: The two groups had a comparable mean baseline stroke score, but stroke was more often mild or severe in the tPA patients and moderate in controls. The tPA group was more likely to experience complete recovery. Complete recovery at 90 days was reported in 79 percent of the tPA group compared with 56 percent of controls (OR 2.9) in the subgroup with mild to moderate stroke, and in 33 percent vs. five percent (OR 10.5) in the subgroup with moderate to severe stroke. The tPA group was more likely to develop symptomatic intracranial hemorrhage (ICH) by day 10 (13% vs. 0%, p=0.05), asymptomatic ICH (8.7% vs. 0%, p=0.06), and fatal ICH (13% [3/23] vs. 0, p=0.05), and was also more likely to have a fatal outcome (17% vs. 5% at 30 and 90 days, p=0.12). CONCLUSIONS: Findings in this small group of patients confirm improved functional outcomes in patients with ischemic stroke treated with IV tPA within three hours of symptom onset who survive, but also documented an increased rate of ICH and death. Police with AEDs Cut Defib Times Many of us are of the “load-and-go” school when it comes to prehospital care, while others favor the “stay-and-play” position. In Los Angeles County where I practice, there is a hospital well within a 15-minute drive for 90 percent of the population. This is the ideal “load-and-go” city. Yet, paramedics are still getting their 1800 hours of training, can quote from memory the components of the Glascow Coma Scale, and know how to ascertain whether the Babinski reflex is positive. In the rural area outside Philadelphia where my family lives, the nearest hospital is at least 30 minutes away, maybe more. In this setting, there are volunteer EMT ambulances where training consists of 80 hours. It would appear that given the differences in transport times, Los Angeles should have the EMTs and the rural countryside should have the PhD paramedics. Instead we have paramedics starting IVs per protocol on a ton of prehospital patients despite the hospital literally being minutes away, and the patient arriving with a full IV bag (which is to their benefit when the cause of their dyspnea is pulmonary edema). Clearly, I'm frustrated by some of the knee-jerk just-in-case approaches thrust upon paramedics by their medical supervisors who really ought to know better. What I do support aggressively is “taxicab” transport in prehospital care, the concept that you get patients as quickly to the hospital as safely feasible (no lights and sirens, thank you), and if it's a taxicab, fine; if it's a police car, fine; if it's a homeboy friend's lowrider, fine. The next paper focuses on the capabilities of the police not to drive people to the hospital but rather to get them shocked first when they have a v-fib arrest. Given that police generally arrive before ambulances, what advantage could be gained by having them defibrillate patients? The following study based in Detroit found that patients were shocked 1.8 minutes sooner, and there was a trend toward increased survival to discharge with v-fib (11.8% vs. 9.9%) when police carried defibrillators. Although on the face of it, this seems like a reasonable approach, a prior study found that police didn't want to be in the medical business. When they had defibrillators, they arrived at the scene more slowly than when they didn't have them. Estimated Cost-Effectiveness of a Police Automated External Defibrillator Program in a Suburban Community: Seven Years Experience Forrer CS, et al Resuscitation 2002;52(1):23 BACKGROUND: Providing police with automatic external defibrillators (AEDs) affords an opportunity for expanded public access defibrillation in out-of-hospital cardiac arrest. METHODS: This study from William Beaumont Hospital in Royal Oak, MI, estimated the cost-effectiveness of a police AED program. Prospectively recorded registry data were reviewed for 209 patients with prehospital cardiac arrest during three years before and seven years after initiation of the program (1989–1999). In all cases, the police were first responders (with or without AEDs), ALS was provided, and the patients were transported to the study facility. The data do not demonstrate any increase in survival for police first responders starting defibrillation RESULTS: In the first 81 cases, police had no access to an AED. The groups were similar in terms of ALS response, percentage of witnessed arrests and ventricular fibrillation, and patient age. The mean interval from the 9-1-1 emergency call to shock delivery were 8.4 vs. 6.6 minutes, and rates of survival to discharge were 9.9 percent and 11.8 percent, respectively (p=0.66). The estimated cost per life saved in association with the police AED program, based on an estimated increase in likelihood of survival with this degree of decrease in time to defibrillation, was $70,342, with an estimated cost per year of life saved of $16,060. CONCLUSIONS: Although there may have been confounding variables in this nonrandomized before-and-after comparison and although their own data did not demonstrate any statistical increase in survival, the authors feel that their suburban police AED program was cost-effective.