Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Bad outcomes related to, but not caused by, misdosing of clotbusters in heart attack patients

13.04.2005


The deaths or clinical complications in heart attack patients given potent drugs to re-open clogged arteries is more likely to be due to individual patient characteristics than to modest misdosing of the drugs, researchers from the Duke Clinical Research Institute (DCRI) have determined. Thus, they said, physicians should not be overly worried about the possibility of minor errors in dosing -- a concern that the Duke physicians said likely contributes to insufficient prescribing of the drugs to treat heart attacks.



These findings are important, the researchers said, because approximately one in three patients rushed to emergency rooms with heart attack symptoms do not receive these potentially life-saving drugs. One reason cited for this under-usage is that many physicians may be overly – albeit sometimes justifiably -- concerned about potential adverse events due to incorrect dosing, the researchers said.

The drugs, known as fibrinolytic agents, have been proven effective in clinical trials in breaking apart blood clots in coronary arteries, restoring blood flow to heart and saving heart muscle. The doses of some of the drugs in this class are determined by a calculation that includes body weight, which must often be estimated in emergency situations. The amount of drug administered is crucial, the researchers said, since too much can cause unwanted bleeding events, while too little will not dissolve the blood clot.


"Many physicians have assumed that modest errors in dosing errors of these fibrinolytic drugs can cause harm, which made them afraid to give the drugs altogether," said Duke University Medical Center cardiologist Christopher Granger, M.D., senior member of the research team that published the results of their analysis in the April 13, 2005 issue of the Journal of the American Medical Association. The DCRI’s Rajendra Mehta, M.D. was the first author of the paper.

"We have found that there does not appear to be a cause-and-effect relationship between small dosing errors and worse outcomes for patients," Granger continued. "These findings should be somewhat reassuring to busy physicians in emergency rooms who can assume that as long as the drugs are given carefully to the right patients, small misdosings should not lead to bad outcomes. These are a class of drugs that can save lives, but tend to be underused."

For their study, the Duke team analyzed the results of the 16,949-patient clinical trial concluded in 1998 known as ASSENT-2 (Assessment of the Safety and Efficacy of a New Thrombolytic). The trial compared the effectiveness of tissue plasminogen activator (t-PA) and TNK, a newer genetically altered version of t-PA. t-PA works by dissolving blood clots and is most effective when administered within hours of heart attack symptoms.

Using the data collected from ASSENT-2, the researchers analyzed to what extent incorrect dosing – whether over or under – was responsible for death, stroke or major bleeding within 30 days of treatment.

"Like previous studies, our analysis showed that about five percent of the patients in ASSENT-2 received incorrect doses of t-PA," Mehta said. "What is so fascinating is that we found the nearly same excess risk of misdoses of placebo that we found in misdosing t-PA. This suggests that most, if not all, of the associations between incorrect dosing of t-PA and adverse events were due to other confounding factors."

When the researchers adjusted the data for these confounding factors, they found that the association was greatly reduced. The patient-specific factors that appeared to bestow the greatest risks for adverse events included advanced age, female gender, being African-American, shorter stature, lower body weight, and lower blood pressure.

Specifically, the 30-day mortality rate for those who received a t-PA overdose was 9.8 percent, and 19.5 percent for those receiving an underdose. Those receiving a correct dose had a mortality rate of 5.4 percent. Conversely, those who received an overdose of placebo had a 10 percent mortality rate, and 23.5 percent rate for underdose. Those who received the correct dose of placebo also had a 5.4 percent mortality rate.

"These findings are counterintuitive – when given the wrong dose of placebo, there was much worse outcome," Granger said. "This is clearly a remarkable finding, as well as a reason to pause – whenever we see a relationship between a treatment and an outcome, we must be careful in ascribing cause and effect. Other factors may also be involved, and additional studies are needed to better understand what these factors may be."

Granger cited as a similar example the issue of hormone replacement therapy (HRT) for post-menopausal women. Earlier observational studies of thousands of women indicated an association between HRT and a lowered risk of heart attack.

"However, when the randomized, scientific studies were done the opposite was proven to be true, that there was in fact an increased risk of blood clots and stroke," Granger said. "Another example is vitamin E. At first, earlier studies appeared to show that vitamin E was associated with better outcomes, but when the proper studies were conducted, it turned out not to be the case."

While Granger does not believe that the results of this analysis will change clinical practice, he does believe that hospitals and physicians should not withhold beneficial drugs because of concern over misdosing, as long as the drugs are given carefully and errors minimized. Less concern about minor misdosing could lead to an increased usage of the drugs. Additionally, he said that the patients at the highest risk for adverse outcomes should be closely monitored while they are receiving fibrinolytic therapy.

Mehta believes that the results of this study could also have an impact on medical malpractice litigation, which is often driven by adverse outcomes.

"This study finds that adverse outcomes following modest errors in fibrinolytic dosing are often times not caused by the error, but by clinical factors that may contribute to higher likelihood of the error occurring," Mehta said.

The ASSENT-2 trial was funded by Boehringer Ingelheim and Genentech, Inc. Granger’s analysis of the ASSENT-2 data was supported by theDCRI.

Other members of the team, from the DCRI, were John Alexander, M.D., Karen Pieper, Jyotsna Garg, and Robert Califf, M.D. Other colleagues were Frans Van de Werf, M.D., University Hospital Lueven, Belgium, and Paul Armstrong, M.D., University of Alberta, Edmonton.

Richard Merritt | EurekAlert!
Further information:
http://www.mc.duke.edu

More articles from Health and Medicine:

nachricht Investigators may unlock mystery of how staph cells dodge the body's immune system
22.09.2017 | Cedars-Sinai Medical Center

nachricht Monitoring the heart's mitochondria to predict cardiac arrest?
21.09.2017 | Boston Children's Hospital

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: The pyrenoid is a carbon-fixing liquid droplet

Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.

A warming planet

Im Focus: Highly precise wiring in the Cerebral Cortex

Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.

The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...

Im Focus: Tiny lasers from a gallery of whispers

New technique promises tunable laser devices

Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...

Im Focus: Ultrafast snapshots of relaxing electrons in solids

Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!

When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...

Im Focus: Quantum Sensors Decipher Magnetic Ordering in a New Semiconducting Material

For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.

Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

Rainbow colors reveal cell history: Uncovering β-cell heterogeneity

22.09.2017 | Life Sciences

Penn first in world to treat patient with new radiation technology

22.09.2017 | Medical Engineering

Calculating quietness

22.09.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>