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 Biofilm discovery suggests new way to prevent dangerous infections
23.05.2017 | University of Texas at Austin

nachricht Another reason to exercise: Burning bone fat -- a key to better bone health
19.05.2017 | University of North Carolina Health Care

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: A quantum walk of photons

Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.

The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....

Im Focus: Turmoil in sluggish electrons’ existence

An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.

We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...

Im Focus: Wafer-thin Magnetic Materials Developed for Future Quantum Technologies

Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.

Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...

Im Focus: World's thinnest hologram paves path to new 3-D world

Nano-hologram paves way for integration of 3-D holography into everyday electronics

An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...

Im Focus: Using graphene to create quantum bits

In the race to produce a quantum computer, a number of projects are seeking a way to create quantum bits -- or qubits -- that are stable, meaning they are not much affected by changes in their environment. This normally needs highly nonlinear non-dissipative elements capable of functioning at very low temperatures.

In pursuit of this goal, researchers at EPFL's Laboratory of Photonics and Quantum Measurements LPQM (STI/SB), have investigated a nonlinear graphene-based...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Marine Conservation: IASS Contributes to UN Ocean Conference in New York on 5-9 June

24.05.2017 | Event News

AWK Aachen Machine Tool Colloquium 2017: Internet of Production for Agile Enterprises

23.05.2017 | Event News

Dortmund MST Conference presents Individualized Healthcare Solutions with micro and nanotechnology

22.05.2017 | Event News

 
Latest News

Physicists discover mechanism behind granular capillary effect

24.05.2017 | Physics and Astronomy

Measured for the first time: Direction of light waves changed by quantum effect

24.05.2017 | Physics and Astronomy

Marine Conservation: IASS Contributes to UN Ocean Conference in New York on 5-9 June

24.05.2017 | Event News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>