RxPG News : Myocardial Infarction

Therapeutic Hypothermia - Cooling therapy protects brain after cardiac arrest

Mon, 07 Dec 2009 15:20:49 PST

( from http://www.rxpgnews.com ) Revival of the heart after it stops may save a patient's life, but it permanently damages the brain. Cooling the patient for some time is known to mitigate this harmful effect and improve survival, under a procedure known as therapeutic hypothermia.

Cardiac arrest interrupts the blood supply, depriving cells of oxygen and causing the body to release toxic compounds, that can overwhelm the organs and result in long-term brain injury.

Therapeutic hypothermia slows the body's production of these compounds, reducing risk for brain injury. The therapy has been used successfully in adult cardiac arrest patients, and has been beneficial for newborns, who have received insufficient oxygen at birth.

Now, in the first large-scale multicentre study, physician-scientists are evaluating the effectiveness of the technique in infants and children.

'Cardiac arrest can occur in children either as a complication from a serious medical condition or due to an accident or sudden illness,' warns Charles Schleien, paediatrician and anesthesiologist at New York-Presbyterian Morgan Stanley Children's Hospital.

'While arrest in children is rare, currently no therapies have been shown to improve their chances of recovering,' adds Schleien, who is also the executive vice-chairman of paediatrics at Columbia University College of Physicians and Surgeons.

'In this new study, we aim to show that therapeutic hypothermia can give these children a better chance at survival and long-term quality of life,' says Schleien.

Those receiving hypothermia will have their body temperature reduced to between 89.6 degrees and 93.2 degrees Fahrenheit - for two days, then slowly increased to a normal body temperature and maintained for another three days, says a New York-Presbyterian release.

Co-led by Frank W. Moler at the University of Michigan C.S. Mott Children's Hospital and Michael Dean at the University of Utah, the six-year study involves a total of 16 study sites in North America.

Height loss may increase heart attack risk

Thu, 14 Dec 2006 16:59:49 PST

( from http://www.rxpgnews.com ) London, Dec 14 - Men who lose height by three cm or more as they age could face the risk of heart attack, says a British study that suggests they should stay as active as possible into old age.

Goya Wannamethee, reader in epidemiology at the Royal Free and University College Medical School in London, and other researchers studied 4,200 men.

They found that those who lost three cm in height were 64 percent more likely to die than those who lost less than one cm, although the researchers say they don't know why height loss seems to be linked with an increased risk of coronary heart disease.

The study was part of the British Regional Heart Study, which enrolled men between 1978 and 1980 and then followed them up 20 years later when they were in their 60s and 70s.

It's been well established that shortness is associated with cardiovascular disease so we were interested to see whether height loss itself could influence mortality, the researchers said.

Over the 20-year period the men lost an average of 1.67 cm of height. But 1,400 of the men lost more than two cm.

Many of the additional deaths in men who had lost height were due to cardiovascular disease, respiratory disease or other non-cancer diseases.

Height loss was associated with a 42 percent increased risk of coronary events such as heart attacks, even in men who had no history of cardiovascular disease, thy said.

'It gives us an interesting starting point that could be explored with further research, helping us to identify those at greatest risk,' said June Davison, cardiac nurse at the British Heart Foundation.

The study is published in the bi-monthly professional medical journal 'Archives of Internal Medicine'.

Few athletes survive sudden cardiac arrest (SCA)

Tue, 20 Jun 2006 21:32:37 PST

( from http://www.rxpgnews.com ) Cardiopulmonary resuscitation (CPR) and automated external defibrillators (AED's) had surprisingly little effect on the survival rates for young athletes who experience sudden cardiac arrest (SCA), according to a new study published in the July 2006 edition of Heart Rhythm. Of the nine intercollegiate athletes the study examined between 1999 and 2005, eight did not survive.

The study is the first of its kind to look at the timing and details of resuscitating young competitive athletes who experienced SCA, a sudden and lethal arrhythmia causing an abrupt loss of heart function.

"The findings of this small cohort raise concerns regarding the effectiveness of early defibrillation in young athletes," said Jonathan A. Drezner, MD, Associate Director of the Sports Medicine Fellowship in the Department of Family Medicine at the University of Washington in Seattle and lead author of the study. "The survival rates in these young athletes are significantly lower than expected, despite appropriate and timely response."

In all cases, the athletes suffered a witnessed collapse, meaning there were bystanders who were able to respond immediately to the athlete, and they all received CPR. AED's were applied to all the athletes by athletic trainers or by responding emergency medical services (EMS) and in seven cases, a shock was deployed. Nevertheless, only one out of nine athletes in the study survived, a striking finding considering the young age, otherwise good health and physical conditioning of the athletes, and early defibrillation.

The authors stated that several factors could explain the low survival rate. Most importantly, the underlying cause of SCA in the athletes might have influenced their lack of response to resuscitation and defibrillation. While there has been convincing evidence of successful SCA survival rates due to public access to AED's, the benefit of these programs has been shown in an older population that was more likely to have experienced SCA due to atherosclerosis, or narrowing of the coronary arteries.

In comparison, the underlying cause of SCA in the majority of athletes in this study was attributed to structural heart disease, namely hypertrophic cardiomyopathy, a condition in which the muscle of the heart is abnormally enlarged. "These results suggest that SCA caused by structural heart disease may be more resistant to defibrillation," Dr. Drezner remarked.

Delayed recognition of cardiac arrest by first responders, duration and intensity of exercise prior to arrest, metabolic and physiologic adaptations during exercise and vascular changes are other potential factors that may have affected survival.

Dr. Drezner emphasized that improved emergency planning with training in CPR and access to AED's is critical to saving lives. "It's possible that in this young athletic population our response time needs to be even shorter, and our CPR even better. Immediate recognition of a cardiac arrest, early CPR, and prompt access to defibrillators are still needed in the hope of preventing these catastrophic events."

The authors concluded that the study findings reinforce a need for future research on SCA in young athletes and the effect of early defibrillation on young patients with structural heart disease. "Clearly, we need to understand this better," noted Dr. Drezner.

PlGF involved in Post Myocardial Infarction Healing Process

Sat, 15 Apr 2006 18:29:37 PST

( from http://www.rxpgnews.com ) Heart attack patients produce higher levels of a natural substance in the body that plays a role in the growth of new blood vessels and this over-expression of placental growth factor (PlGF) may help reduce damage to the heart muscle, according to a new study in the April 18, 2006, issue of the Journal of the American College of Cardiology.

"Because the degree of PlGF production released from the heart after a heart attack correlated with the improvement of cardiac function, we think PlGF becomes a potential treatment of myocardial infarction. Furthermore, previous studies have shown that PlGF enhances angiogenesis and arteriogenesis in ischemic tissue, also PlGF appears to promote mobilization of flt-1-positive hematopoietic stem cells from bone marrow to the peripheral circulation. We have started further experiments to evaluate this hypothesis," said Shiro Uemura, M.D. from the Nara Medical University in Kashihara, Japan.

The researchers, including first author Hajime Iwama, M.D., compared 55 heart attack patients to 43 control subjects. The heart attack patients had significantly higher levels of PlGF than the healthy subjects. Also, the patients with higher levels of PlGF three days after a heart attack had lower left ventricular ejection fractions, indicating more heart muscle damage. The researchers wrote that it is likely that the degree of injury is a key determinant of how much PlGF the body produces.

Dr. Uemura said it appears that PlGF is involved in the healing process after a heart attack, including the mobilization of stem cells

"From these results, it seems likely that cardiac production of PlGF promoted the mobilization of bone marrow derived monocytes, possibly including endothelial progenitor cells, which might be involved in tissue repair of injured myocardium," he said.

The researchers also performed an experiment on laboratory mice. They found that in mice that underwent a procedure that interrupted coronary blood flow, similar to what happens during a heart attack, PlGF levels shot up to 23 times the levels seen in control mice.

Although the researchers say their results suggest that PlGF should be studied as a potential heart attack treatment, they pointed out that studies of a similar substance, called VEGF, produced some disappointing results. Although early studies indicated that VEGF could spur the development of new blood vessels (angiogenesis), many of the new blood vessels did not work properly.

"The possibility of VEGF treatment for heart attack has been extensively studied because of its established angiogenic capacity, but previous in vivo studies with VEGF gene or recombinant VEGF protein were not always successful in the preservation of ventricular function because of the development of non-functioning or unstable capillary vessels. On the other hand, PlGF is previously reported to enhance not only capillary, but also collateral formation in ischemic tissue. According to our observation in this study, we speculate that PlGF becomes the alternative molecule to enhance tissue repair after acute myocardial infarction,"

The key elements for success in the rapid treatment of heart attacks

Wed, 01 Mar 2006 17:21:37 PST

( from http://www.rxpgnews.com ) Some of the key elements for success in the rapid treatment of heart attacks have been identified by researchers at Yale School of Medicine in a recent issue of Circulation: Journal of the American Heart Association.

Eleven hospitals consistently delivered therapy to restore blood flow to heart attack patients in 90 minutes or less. The researchers studied how staff at these hospitals, including Yale-New Haven Hospital, regularly delivered such speedy treatment, which can save lives.

The authors write that many of the nation's hospitals do not respond as quickly as national guidelines suggest, even though speed is important in restoring blood flow to reduce the amount of damage to heart muscle. Faster "door-to-balloon" time--time elapsed from a patient's arrival to treatment with angioplasty--translates into better survival and less disability.

The researchers visited each of the 11 hospitals and conducted extensive interviews with staff--from the top administrators to technical support staff-- and identified a set of common themes.

"We found that success involved much more than skilled individual doctors and nurses," said lead author Elizabeth Bradley, associate professor in the Department of Epidemiology and Public Health at Yale. "What distinguished these hospitals was how well they were organized, how teams functioned together, how the culture rewarded quality improvement and how they dealt with setbacks."

Bradley added, "The themes also reflect the ability of the top performing hospitals to pursue simultaneously contrasting approaches and balance the tensions between them. For example, having standardized protocol but retaining flexibility to refine them continuously, or having intense and individualized data feedback but a no-blame culture. The ability to balance these paradoxes may be a critical aspect of bouncing back from the speed bumps in the process of improvement."

"All of these top hospitals share eight common characteristics that drive their ability to deliver fast, effective treatment to patients with ST-elevation acute myocardial infarction (STEMI)," said senior author Harlan M. Krumholz, M.D., the Harold H. Hines, Jr. Professor of Medicine. "This study has direct and important information for hospitals around the country."

Each of the hospitals had explicit commitment to reduce delays throughout the process, senior management support for quality improvement efforts, innovative protocols and flexibility in refining those protocols and collaborative teams across nursing, cardiology and emergency services, real-time data feedback to measure success, and an organizational culture that made hospitals resilient to setback.

Daily cocoa intake can save you from heart attack

Tue, 28 Feb 2006 21:31:37 PST

( from http://www.rxpgnews.com ) Regular intake of cocoa by elderly men has been found to reduce their risk of dying from a heart attack, but excess consumption could be harmful, say scientists.

Brian Buijsse, at the Dutch National Institute for Public Health and the Environment in Amsterdam, and other researchers studied 470 men aged over 65 and asked them questions about their dietary intake of cocoa.

The men were placed in three groups according to their level of cocoa consumption and data about their health was collected. During the 15 years' study at five-year intervals, 314 men died - 152 due to cardiovascular disease, reported the online edition of New Scientist.

"The men in the group that consumed the least cocoa were twice as likely to die from a heart attack as those in the group that consumed the most cocoa - at least four grams per day - and the risk remained lower even when other factors such as smoking, physical exercise and weight were taken into account," researchers said.

"And men in the study who consumed the most cocoa were less likely to die of any cause."

"The key thing to remember about such studies is that chocolate is more often part of the problem, not the solution," Cathy Ross, a medical spokeswoman of the British Heart Foundation (BHF), said.

"Cocoa is rarely tolerable in large amounts in its raw state and therefore to consume the suggested therapeutic amount you would have to have 100g of dark chocolate per day.

"This would mean an average intake of 500 calories per 100g with an average of 30 percent fat content," she points out.

Heartbreaks can trigger heart attacks in the healthy

Tue, 14 Feb 2006 19:48:37 PST

( from http://www.rxpgnews.com ) Cardiologists in Singapore have issued a sober Valentine's Day warning that severe emotional or work stress can trigger heart attacks in healthy people.

A study conducted by the National University Hospital (NUH) in Singapore, along with other cardiac centres, appeared to confirm what men have long suspected - that women's hearts break more easily.

Women account for more than nine in 10 emotional heart attacks, according to the findings published in The Straits Times.

A "heartbreak" attack is different from a regular heart attack, which is usually caused by blocked arteries that restrict blood flow to the rest of the body, the cardiologists said.

An attack induced by emotion or stress is triggered by a surge of hormones, which causes only the top part of the heart to contract, reducing blood flow. This phenomenon was first discovered by Japanese researchers in 2001.

When an angiogram reveals the cause, a balloon pump helps the heart push blood to the rest of the body.

Time can help the victims of heartbreak, physically as well as emotionally.

Physicians recommended a victim be rushed to a hospital. If he or she gets there in time, the chances are very good that the heart will have recovered its resilience within a month, resulting in a full recovery and no side effects.

"We have come across cases like this before, but we thought it was caused by a very small clot, which disintegrated," senior cardiologist Tan Huay Cheem, one of the researchers, was quoted as saying.

The victims tend to have typical heart attack symptoms, such as chest pains. When doctors investigate, they find none of the classic problems such as blocked or narrowed arteries.

Chronic noise exposure increase risk of heart attacks

Fri, 25 Nov 2005 05:58:38 PST

( from http://www.rxpgnews.com ) Research published online today (Thursday 24 November) in European's leading cardiology journal, European Heart Journal, links exposure to chronic noise with an increased risk of heart attack. Furthermore, the risk seems to be associated more with the physiological effect of environmental and work noise than with the annoyance it causes individuals, although there are differences in effects between men and women.

Findings have prompted researchers from Charité University Medical Centre in Berlin, Germany, to call for the level requiring workplace ear protection to be lowered from the current 85 decibels, widely used in western Europe, to somewhere between 65 and 75 decibels. They believe this is especially important for people with existing cardiovascular disease.

In a case-control study involving all 32 hospitals in Berlin between 1998 and 2001, the researchers compared over 2,000 heart attack patients with over 2,000 control patients admitted to trauma and general surgery departments. Of the 4,115 total, about three-quarters were men and a quarter was women. The mean age of the men was 56 and the mean age of the women was 58.

The NaRoMI (Noise and Risk of Myocardial Infarction) study was designed to determine the association between chronic noise and the risk of heart attacks in men and in women and to assess the risks of subjective annoyance and objective noise levels in the environment and the workplace. The research team used interviews and independent environmental and work noise assessments in their analysis. The findings apply to men and women under 70 living in cities, who had non-fatal heart attacks.

Lead author Dr Stefan Willich, Director of the Institute for Social Medicine, Epidemiology and Health Economics at the medical centre, said: "Our results demonstrate that chronic noise exposure is associated with a mildly to moderately increased risk of heart attack. The increase appears more closely associated with actual sound levels rather than with subjective annoyance. However, there were differences between men and women and these need further investigation."

General environmental noise, such as that of traffic, affected both sexes, increasing the risk of heart attack by nearly 50% for men and by about three-fold for women. Workplace noise levels increased the risk for men by nearly a third, but did not affect women's risk.

Where the individual's subjective reaction of annoyance was concerned, environmental noise had no effect on men, but marginally increased women's risk. However, the situation was reversed for workplace noise, with the risk for men from annoyance rising by nearly a third but with no effect in women.

Dr Willich said that the differences between men and women may be because women tend to spend more time at home and were generally less exposed to loud workplace noise. Most previous studies on noise had concentrated on men and this was the first to find evidence of an effect in women, so the results on women needed confirming. "However, gender-specific reaction and pathophysiological response also seems possible and we should investigate this," he said.

The researchers also found that risk did not rise in concert with rising noise levels. "This means we seem to be looking at a threshold at which risk occurs and remains constant above this, and this appears to be around 60 decibels," said Dr Willich. Sixty decibels is the level of noise typically experienced, for example, in a busy large office.

The findings were consistent with a hypothesis that there is an association between long-term noise exposure and risk of cardiovascular disease, according to Dr Willich. (The study did not look at transitional exposure, such as driving to work. Nor did it include rural populations or people over 70).

A mechanism that might explain the link, said Dr Willich, was that noise could increase psychological stress and anger, leading to physiological changes in the body such as increased levels of adrenaline and noradrenaline, which are associated with increased blood pressure and plasma lipids.

"Such a mechanism may be further modified by personal parameters smoking or pressure from meeting deadlines. In that case, chronic noise would be the equivalent of an outside risk factor contributing to atherosclerosis and cardiovascular disease."

His team plan further studies. But, in the meantime, their findings have convinced them that the current levels of 85 decibels (equivalent to road construction equipment, for example) are too high. "We should definitely be looking at something lower. The exact value is unclear, but somewhere between 65 and 75 decibels," he said. "It is particularly important to focus on people with known cardiovascular disease to improve prevention for them, either by not exposing them chronically to heavy noise or by lowering the threshold for protective wear."

Sweat is good indicator of impending heart attack

Wed, 23 Nov 2005 21:40:38 PST

( from http://www.rxpgnews.com ) Sweating during physical activity or in hot weather is healthy. But when individuals begin perspiring while experiencing discomfort in their chest, arm, neck or jaw -- with little or no exertion -- it could be the onset of a heart attack, according to a new study at the University of Illinois at Chicago.

"We can stop a heart attack during the process, but you have to get to the hospital first," said Catherine Ryan, research assistant professor of medical surgical nursing. "The real push for improved survival is to get them there early."

Time is of the essence during a heart attack, and doctors have urged people who experience common symptoms -- shortness of breath, cold sweats, nausea, lightheadedness, or discomfort in the chest, arm, neck or jaw -- to get to a hospital as quickly as possible. But delay in seeking treatment is common, and worsens the outcome after a heart attack, Ryan said.

Ryan sought to determine whether delay was related to the symptom cluster individuals experienced during a heart attack. Earlier studies about the delay, she said, focused on only one symptom, not clusters, or on demographic characteristics of the patients.

She asked the authors of 10 such studies to send her their data, and eight groups of authors in the United States and Great Britain complied. The data had been collected in interviews with 1,073 patients who had had heart attacks.

Ryan studied 12 common symptoms: chest discomfort; shoulder, arm, or hand discomfort; neck or jaw discomfort; back discomfort; abdominal discomfort; indigestion; nausea and vomiting; shortness of breath; sweating; dizziness and light-headedness; weakness; and fatigue.

Her analysis showed that individuals with the shortest delays (a mean of 9.78 hours) had a greater probability of experiencing the largest number of symptoms. Individuals with the longest delays (a mean of 22.77 hours) had moderate probability of experiencing chest pain and shortness of breath.

Sweating may be a key variable in the symptom cluster prompting individuals to seek treatment, Ryan said. But the research could not determine whether sweating is an indication of a more serious heart attack.

Darbepoietin offers significant protection to heart tissue from injury due to ischemia

Sun, 20 Nov 2005 23:10:38 PST

( from http://www.rxpgnews.com ) A drug has been shown to provide some protection to the heart from injury even if given as much as 24 hours after a heart attack, Jefferson Medical College researchers report.

Walter Koch, Ph.D., director of the Center for Translational Medicine in the Department of Medicine at Jefferson Medical College of Thomas Jefferson University in Philadelphia, and his co-workers knew that the drug Darbepoietin alpha would protect the ischemic heart. Darbepoietin is a long-acting cousin of erythropoietin (EPO), which has been shown to offer some protection to the heart from injury from ischemia, or a lack of oxygen. In previous studies, Dr. Koch had given EPO at the time of simulated heart attack in an another animal model, and found it protected the animals.

But in further studies, Dr. Koch gave Darbepoietin to animals at the time of ischemia and heart attack, one to two hours after, and 24 hours later. In each case, the scientists saw that the drug offered significant protection to heart tissue, and even helped improve cardiac function.

Dr. Koch believes the results may be quickly translated into clinical trials. He and his team present their findings on November 16, 2005 at the American Heart Associations Scientific Sessions 2005 in Dallas.

Waist-to-hip ratio determines risk of a heart attack

Sun, 06 Nov 2005 11:30:38 PST

( from http://www.rxpgnews.com ) Waist-to-hip ratio, not body mass index (BMI), is the best obesity measure for assessing a person's risk of heart attack, concludes a global study published in this week's issue of The Lancet.
If obesity is redefined using waist-to-hip ratio instead of BMI the proportion of people at risk of heart attack increases by threefold, calculate the authors.

Previous research has shown that obesity increases the risk of heart disease. However, these studies have mainly been done in populations of European and North American origin. The evidence for other populations is therefore sparse. In the latest study, Dr. Salim Yusuf, director of the Population Health Research Institute at McMaster University and Hamilton Health Sciences, and colleagues aimed to assess whether other markers for obesity, especially waist-to-hip ratio, would be a stronger predictor of heart attack than the conventional measure of BMI in different ethnic populations.

The investigators looked at BMI, waist-to-hip ratio, waist measure, and hip measure in more than 27,000 people from 52 countries. Half the participants had previously had a heart attack and half were age and sex-matched controls (individuals who had not had a heart attack and were the same age and sex as cases). The team found that BMI was only slightly higher in heart attack patients than in controls, with no difference in the Middle East and South Asia. By contrast, heart attack patients had a strikingly higher waist-to-hip ratio than controls, irrespective of other cardiovascular risk factors. The researchers found that this observation was consistent in men and women, across all ages, and in all regions of the world.

The authors' state that compared with BMI, waist-to-hip ratio is three times stronger than BMI in predicting the risk of a heart attack. Larger waist size (which reflects the amount of abdominal fat) was harmful, whereas larger hip size (which may indicate the amount of lower body muscle) was protective.

The waist-to-hip ratio is calculated by dividing the waist measure by the hip measure. The cut off point for cardiovascular risk factors is less than 0.85 for women and 0.90 for men. A higher number denotes more risk

Dr. Yusuf concludes: "Our findings suggest that substantial reassessment is needed of the importance of obesity for cardiovascular disease in most regions of the world."

Dr. Yusuf is a professor of medicine of the Michael G. DeGroote School of Medicine at McMaster University, a cardiologist at Hamilton Health Sciences. He also holds the Heart and Stroke Foundation of Ontario Chair in Cardiology at McMaster University. The study was funded by the Canadian Institutes of Health Research, the Heart and Stroke Foundation of Ontario and 37 other funding sources, including unrestricted support from several pharmaceutical companies.

In an accompanying published comment Charlotte Krageland of the University of Oslo, Norway states: "The main message from the new report is that current practice with body mass index as the measure of obesity is obsolete. For the assessment of risk associated with obesity, the waist-to-hip ratio, and not the body mass index, is the preferred simple measure."

Dr. John Kelton, dean of the Michael G. DeGroote School of Medicine and dean and vice-president, Faculty of Health Sciences, McMaster University, said: "The results of this study will change, on an international scope, how we evaluate patients' risks for heart disease. Being able to easily identify the risk will have a beneficial effect on awareness and treatment."

Dr. Alan Bernstein, president of the Canadian Institutes of Health Research, said: "We've long been aware of the link of obesity and cardiovascular disease. Thanks to the research conducted by Dr. Yusuf, we now have a better understanding of the risk related to obesity which can lead to more effective health interventions.

Laura Syron, vice-president of research for the Heart and Stroke Foundation of Ontario, said: "For the Foundation it is immensely gratifying to see yet another in a series of successes by Dr. Yusuf and his team. We have supported this initiative from the beginning and it has been wonderful to follow the tale of the tape from Ontario to the world."

Murray Martin, President and CEO of Hamilton Health Sciences, said: "Part of our mission as a teaching hospital is to advance health care through education and research. Dr. Yusuf's commitment to finding answers to important heart health questions that affect people around the world exemplifies the leadership we embrace at Hamilton Health Sciences."

Ambient air pollution linked with acute myocardial infarction

Mon, 26 Sep 2005 21:16:38 PST

( from http://www.rxpgnews.com ) Scientists have discovered a link between ambient air pollution and acute myocardial infarction, or heart attack.

An article published in the Journal of Thrombosis and Haemostasis looks specifically at airborne particulate matter resulting mainly from the combustion of fuel, including coal and also from forest fires.

Evidence shows that both short- and long-term exposure to these particulates is associated with death from cardiovascular and respiratory illnesses, and more specifically from myocardial infarction.

Additionally, this research, based on a previous study, reveals that those patients with damaged arteries are most at risk to suffer from lung inflammation and fatal blood clots.

Each year, 1.1 million people experience myocardial infarction, which results from the obstruction of a diseased coronary artery.

NORVIT Trial- High dose B vitamins do not lower stroke or MI risk

Thu, 08 Sep 2005 00:02:38 PST

( from http://www.rxpgnews.com ) Researchers from Norway have found that treating patients who have had a heart attack with high doses of B vitamins does not lower the risk of getting another heart attack or stroke. Contrary to expectations, B vitamins may do more harm than good.

NORVIT, the Norwegian Vitamin Trial, is the first trial to examine whether high doses of B vitamins prevent recurrent heart disease in patients who have had a myocardial infarction. A total of 3749 patients were recruited from 35 Norwegian hospitals. The patients were assigned to take B vitamins or placebo for more than three years in addition to standard treatments after a heart attack. The NORVIT trial was conducted by researchers at the University of Tromsø, Norway, in cooperation with researchers at the University of Bergen, Norway, and doctors and nurses at 35 Norwegian hospitals. It was a low-budget trial financed by the Norwegian Research Council, the Council on Health and Rehabilitation, the Norwegian Council on Cardiovascular Research, and other non-profit organizations.

Professor Kaare Harald Bønaa MD, University of Tromsø, Norway, principal investigator of the NORVIT trial, comments, "The results of the NORVIT trial are important because they tell doctors that prescribing high doses of B vitamins will not prevent heart disease or stroke. B vitamins should be prescribed only to patients who have B vitamin deficiency diseases."

The participants in the NORVIT trial were divided at random into four groups that received either 0.8 mg folic acid (a B vitamin) per day, 40 mg vitamin B-6 per day, both 0.8 mg folic acid and 40 mg vitamin B-6 per day, or a placebo capsule per day. Those who took folic acid or vitamin B-6 alone had a small increase in the risk of cardiovascular disease. However, among those who took both vitamins the risk increased by 20 percent.

During the last 15 years interest in vitamin B research has rocketed worldwide because studies indicated that folic acid and vitamin B-6 could prevent heart disease and stroke. Researchers have believed that this was due to the ability of B vitamins to lower the blood level of an amino acid called homocysteine. It was thought that high levels of homocysteine may damage the lining of arteries and increase clotting of the blood. This can cause fatal blockages of arteries in the heart and brain.

"Some doctors have found the previous data so compelling that they have already started to treat patients with B vitamins to lower the homocysteine level. However, in the NORVIT trial, homocysteine levels were lowered by 30%, but this did not lower the patients' risk of cardiovascular disease", said Kaare Harald Bønaa MD.

There were no subgroups of patients in the NORVIIT trial who benefited from taking B vitamins. Harmful effects were seen in particular among those who had high levels of homocysteine at the start of the trial, among patients with impaired renal function, and among those who reported that they used other vitamin supplements in addition to the study medication.

The results of the NORVIT trial are supported by results of a recent, smaller study which used similar doses of B vitamins as those given in NORVIT. That study showed that B vitamins increased the risk of reocclusion of coronary arteries that had been opened by percutaneous revascularization.

One patient in every three who suffers a heart attack has a recurrent heart attack or stroke within three years after the first attack, even if they get the best medical treatment available. It was hoped that B vitamins could lower the risk of recurrence. The NORVIT trial showed, however, that B vitamins offer no protection against cardiovascular disease.

Commenting on the results Professor Peter Weissberg, Medical Director of the British Heart Foundation, said:

"People should not be taking folic acid and vitamin B6 to stop them having a heart attack because it wont. The study shows a significant increase in heart attacks and strokes.

"There is no reason for pregnant women and those hoping to conceive to avoid taking folic acid by itself. It has a proven track record in preventing birth defects and is very important.

"Coronary heart disease seldom affected women in their 30s and 40s, which had led to breast cancer becoming a bigger fear for young women. The problem is that women may have got into bad lifestyle habits such as smoking and taking too little exercise which become even more difficult to change later in life when they catch up with the risk faced by men.

"Men have probably become aware of the threat of heart disease from a much younger age than women and this may help them to seek and get help."

Early statin treatment in MI cut mortality by 50 percent

Mon, 29 Aug 2005 22:18:38 PST

( from http://www.rxpgnews.com ) In the largest clinical study of its kind, UCLA researchers found that early treatment with a statin drug within 24 hours of having a heart attack reduced in-hospital mortality rates by over 50 percent.

The new study, published in the Sept. 1 issue of the American Journal of Cardiology, demonstrates that early statin therapy may be essential for reducing mortality and other complications in heart attack victims.

"We've known that long-term statin therapy is beneficial, but this study provides the strongest clinical evidence to date supporting the early cardioprotective effects of statins immediately following a heart attack," said Dr. Gregg C. Fonarow, lead study author, The Eliot Corday Chair in Cardiovascular Medicine and Science and professor of cardiology, David Geffen School of Medicine at UCLA.

Researchers used data from over 170,000 patients taken from the National Registry of Mycocardial Infarction 4, a national database of patients who were admitted to a hospital due to a heart attack.

Researchers found that patients who had received statin therapy before hospitalization and within 24 hours following a heart attack had a 54 percent lower risk of in-hospital mortality compared to patients not on statin therapy.

Patients who had not received previous statin therapy, but who were newly started on the medication within 24 hours of hospitalization had a 58 percent reduction in mortality compared to patients not on statin therapy.

"We were surprised that early statin therapy showed such a striking effect immediately after a heart attack,"said Fonarow, director, Ahmanson-UCLA Cardiomyopathy Center. "We also found that statins provided additional protection from other heart attack complications as well."

The study showed that early statin use was associated with a lower incidence of cardiac arrest, cardiac shock, cardiac rupture and ventricular fibrillation that can all occur following a heart attack.

According to Fonarow, statins work by increasing nitric oxide in the cardiovascular system, which offers a number of benefits including reducing inflammation that may help limit cell damage from a heart attack.

The next step is to develop a clinical trial to corroborate these strong observational findings. Fonarow believes that early statin use within 24 hours of a heart attack may become a standard treatment. "As statins are already routinely started in myocardial infarction patients prior to hospital discharge, it would be relatively easy to administer this medication on arrival to the emergency department." This year 1.5 million Americans will have a new or recurrent heart attack.

Hot cup of cocoa or red wine?

Wed, 10 Aug 2005 12:43:38 PST

( from http://www.rxpgnews.com ) Throughout history, cocoa has been described as a medicine for many ailments. New research suggests that cocoa may also have a beneficial effect on heart disease and stroke. A research team in Southampton in England, led by Dr Denise O'Shaugnessy, has shown that drinking a cup of cocoa can prevent potentially fatal blood clots. Dr O'Shaughnessy will present this data at the XXth Congress of the International Society on Thrombosis & Haemostasis in Sydney tomorrow.
When blood clots lodge in our brain or heart there are potentially fatal consequences such as stroke or heart attack. Cells in our blood called platelets are necessary for clotting to occur and O'Shaughnessy's research team showed that cocoa inhibits platelet function.

O'Shaughnessy said, "Cocoa contains a substance called flavinoids, which are also present in red wine. Flavinoids can be preventive for coronary heart disease; however our research has uncovered another ingredient in cocoa which may be responsible for the platelet inhibition. This finding may well lead to important new therapies to prevent heart disease and stroke. But it may also mean that a nice hot cup of cocoa may also take on new importance for people in high risk categories."

BLOOD TYPES and DVT DO THEY MATTER? Research out of the Netherlands has shown that your blood type can increase the risk of suffering deep vein thrombosis (DVT). Blood types in humans include A, B, AB or O. The study showed that people with blood type A, B or AB had an increased risk of DVT.

Researcher, Dr Vania Morelli, from the Leiden University Medical Center in The Netherlands, said "A non-O blood type strongly increases the risk in people who carry a variant of a protein (called Factor V Leiden) involved in blood clotting. This variant protein is found in around 3% of people of European descent".

"Our research suggests that information on blood type may have a role in the management of DVT, especially in carriers of this variant protein. It is obviously important to know what your blood group is!" said Morelli.

Dr Morelli will present this research at the XXth Congress of the International Society on Thrombosis & Haemostasis in Sydney .

Invasive treatment may have better outcomes for some heart attack patients

Wed, 15 Jun 2005 15:21:38 PST

( from http://www.rxpgnews.com ) Invasive treatment including stenting may have better outcomes than conventional treatments for heart attack patients who arrive at the hospital more than 12 hours after symptoms began, according to a study in the June 15 issue of JAMA.

In patients with acute ST-segment elevation myocardial infarction (STEMI - a certain finding on an electrocardiogram, suggesting a heart attack), numerous studies have demonstrated that early reperfusion (restoration of blood flow) within 12 hours of symptom onset is associated with increased myocardial (heart muscle) salvage, preservation of left ventricular function, and improved survival, according to background information in the article. Due to time-dependent reduction in the efficacy of thrombolysis (administration of medications to help dissolve blood clots), the application of this reperfusion method after 12 hours from symptom onset of acute myocardial infarction (MI, heart attack) offers little or no benefit and may be even harmful. Between 8.5 percent to 40 percent of patients with acute MI present late after symptom onset, thus being no longer eligible for thrombolysis.

Despite efforts to reduce time to presentation, recent studies have demonstrated that time-to-arrival at the hospital after the onset of symptoms has not changed or has even increased. Several findings suggest that reperfusion therapy may be beneficial even among patients with acute MI who present late after symptom onset. Current guidelines do not recommend reperfusion treatment in these patients. No specifically designed studies have addressed the role of primary percutaneous coronary intervention (PCI) in patients with STEMI presenting more than 12 hours after symptom onset.

Albert Schömig, M.D., of Technische Universität, Munich, Germany, and colleagues conducted a study to assess whether an invasive strategy based on PCI with stenting is associated with reduction of infarct (dead tissue from lack of blood) size in patients with acute STEMI presenting more than 12 hours after the symptom onset, compared with a conventional conservative treatment strategy.

The study, conducted from May 23, 2001, to December 15, 2004, included 365 patients aged 18 to 80 years, without persistent heart attack symptoms admitted with the diagnosis of acute STEMI between 12 and 48 hours from symptom onset. Patients were randomized to receive either an invasive strategy (n=182) based predominantly on coronary stenting plus the intravenous medication abciximab or a conventional conservative treatment strategy (n=183), which included an intravenous infusion of heparin.

The researchers found that the final left ventricular infarct size was significantly smaller in patients assigned to the invasive group (median, 8.0 percent) vs. those assigned to the conservative group (median, 13.0 percent). The average difference in final left ventricular infarct size between the invasive and conservative groups was ?-6.8 percent. The outcomes of death, recurrent MI, or stroke at 30 days occurred in 8 patients in the invasive group (4.4 percent) and 12 patients in the conservative group (6.6 percent) (a 33 percent lower risk of these outcomes for patients in the invasive group).

"This finding increases the level of evidence in support of the invasive strategy and deserves consideration when current treatment guidelines for this category of patients will be reassessed," the researchers conclude.

In an accompanying editorial, Raymond J. Gibbons, M.D., and Cindy L. Grines, M.D., of Mayo Clinic and Foundation, Rochester, Minn.; and William Beaumont Hospital, Detroit, comment on the findings of Schömig et al, the BRAVE-2 trial.

"Should the next update of STEMI Clinical Practice Guidelines consider PCI to be generally indicated (a class I indication) for all patients presenting with STEMI after 12 hours? Probably not yet. Existing guidelines consider the presence of ongoing symptoms after 12 hours to be a class IIa indication for PCI. On the basis of BRAVE-2, it would seem appropriate to expand this class IIa indication. Although it seems reasonable to consider acute PCI in all patients with STEMI who present 12 hours or longer after the onset of chest pain, regardless of whether they have ongoing pain, this single small trial does not provide sufficient evidence to warrant a class I indication. Such an indication would require confirmation at least in a second small trial using infarct size as an end point or preferably in a larger trial using clinical end points."

"Should patients with STEMI presenting after 12 hours be considered 'medical emergencies' requiring acute mobilization of the catheterization laboratory in the middle of the night? Probably not. Although the BRAVE-2 investigators proceeded with urgent PCI in the patients who were included in this trial, the trial results do not reveal whether this urgency was justified."

"The BRAVE-2 trial results are a noteworthy challenge to existing dogma and an important contribution to current knowledge. However, the results do not yet justify a revolution in clinical practice," the authors conclude.

FDA Approves Nitroglycerin Lingual Aerosol for Acute Relief of Angina Pectoris

Fri, 03 Jun 2005 10:47:38 PST

( from http://www.rxpgnews.com ) NovaDel Pharma Inc. (AMEX:NVD) received an approvable letter from the U.S. Food and Drug Administration regarding its New Drug Application (NDA) for NitroMist(TM) (nitroglycerin lingual aerosol), indicated for acute relief of an attack or acute prophylaxis of angina pectoris due to coronary artery disease.

The company believes that the Food and Drug Administration will give final approval once the company completes its previously agreed-to manufacturing process validation commitments. The FDA is not requiring any additional clinical studies for approval.

"We are extremely pleased with this approvable letter which validates our lingual spray technology and our ability to successfully bring a product through the development and regulatory processes. Furthermore, it confirms the appropriateness of the 505(b)(2) NDA regulatory path for our lingual spray products which can reduce the time to approval," said Gary Shangold M.D., President and CEO of NovaDel. "We are already moving towards completion of the process-validation work required for approval and believe a complete response can be submitted to FDA in an expeditious manner."

DG-031 Lowers Inflammatory Markers Associated with Risk of MI

Thu, 12 May 2005 17:53:38 PST

( from http://www.rxpgnews.com ) A preliminary study suggests that use of a drug that inhibits a specific protein in patients with certain genetic variants that increase their risk for heart attack reduced their levels of inflammatory markers associated with heart attack risk, according to a study in the May 11 issue of JAMA.

Myocardial infarction (MI - heart attack) is one of the leading causes of death in the world, according to background information in the article. The researchers in this study previously reported the identification of a gene variant that predisposes patients to MI. The gene encodes the 5-lipoxygenase activating protein (FLAP) and its risk variant results in an almost 2-fold increased risk of MI.

Hakon Hakonarson, M.D., Ph.D., of Decode genetics Inc., Reykjavik, Iceland and colleagues conducted a study to determine whether the biological perturbation (disruption) caused by the gene variants that predispose patients to MI through the leukotriene (an inflammatory protein) pathway could be compensated by inhibiting FLAP. The branch of the leukotriene pathway linked to risk of MI, through the activity of FLAP, leads to the production of leukotriene B4, which is a potent mediator of arterial inflammation. The researchers' previously published findings indicate that MI patients, both those with and without the at-risk variants of the FLAP gene, produce more leukotriene B4 than do controls. This suggests that the up-regulation of the leukotriene pathway contributes to risk of the disease, both through genetic and environmental factors, primarily, the researchers believe, by promoting inflammation in atherosclerotic plaques and increasing their propensity to rupture. By inhibiting the function of FLAP and thereby down-regulating the activity of the leukotriene pathway, the risk of MI may be decreased. Of several available inhibitors of FLAP, the researchers used DG-031, which had been used in asthma clinical trials and was shown to be safe and well-tolerated.

The trial included MI patients who carry at-risk variants in the FLAP gene or in the leukotriene A4 hydrolase gene. Of 268 patients screened, 191 were carriers of at-risk variants in FLAP (87 percent) or leukotriene A4 hydrolase (13 percent). Individuals were enrolled in April 2004 and were followed up by designated cardiologists from the Landspitali University Hospital in Iceland until September 2004. Patients were first randomized to receive 250 mg/d of DG-031, 500 mg/d of DG-031, 750 mg/d of DG-031, or placebo. After a 2-week washout period, patients received DG-031 if they had received placebo first or placebo if they had received DG-031 first. Treatment periods lasted for 4 weeks.

The researchers found that levels of several biomarkers linked to arterial inflammation and risk of MI decreased. In response to 750 mg/d of DG-031, production of leukotriene B4 was significantly reduced by 26 percent and myeloperoxidase was significantly reduced by 12 percent. The higher 2 doses of DG-031 produced a nonsignificant reduction in C-reactive protein (16 percent) at 2 weeks. However, there was a more pronounced reduction (25 percent) in C-reactive protein at the end of the washout period that was significant and persisted for another 4 weeks thereafter. An 8-day, open-label follow-up study with 75 patients with the same genetic and disease profile as in the Phase IIa was conducted to further examine the effect of DG031 on CRP and myeloperoxidase. The results of this study showed that the 750mg/d dose of DG031, when administered as 250 mg 3 times daily resulted in a 38 percent reduction in CRP levels, as well as a 31 percent reduction in myeloperoxidase levels measured 6 hours after dosing on day 8. In both studies, the FLAP inhibitor DG-031 was well-tolerated and was not associated with any serious adverse events.

"When taken together, the data from our MI gene-isolation study and the clinical trial reported herein show that DG-031 is a safe and well-tolerated drug that affects a biochemical defect that confers a relative risk of acute cardiovascular events, which is similar to or greater than that conferred by the top quartile of LDL cholesterol. Our data suggest that DG-031 reduces serum levels of CRP, serum amyloid A, and myeloperoxidase and these effects are in addition to any effects attributed to statins. Our hypothesis is that this will cause reduction in the risk of MI. To put these results in a historical context, we believe the promise of the beneficial role of DG-031 in cardiovascular disease may, at least in part, reflect that of the statins in the late 1980s when it had been shown that they could lower LDL cholesterol but it had not been shown that lowering LDL cholesterol leads to a decrease in the risk of MI. A study examining clinical outcomes is in the planning stages to determine whether DG-031 does indeed affect the risk of MI," the authors conclude.

Drug-Eluting Stents Effective in Acute Myocardial Infarction: STRATEGY trial

Wed, 04 May 2005 17:41:38 PST

( from http://www.rxpgnews.com ) A type of coronary artery stent that releases a medication appears to result in better outcomes than traditional stents for heart attack patients, according to a study in the May 4 issue of JAMA.

Sirolimus, a substance that is thought to help prevent reclosure of coronary arteries, can be released from certain types of stents (metal devices inserted to keep a coronary artery open after angioplasty) to greatly reduce the need for target-vessel revascularization (TVR) compared with bare-metal stents (i.e., stents without medication), according to background information in the article. These drug-eluting stents have the potential to further improve long-term clinical outcome after primary percutaneous coronary intervention (PCI), such as angioplasty. However, the lack of randomized trials to assess the safety and long-term efficacy of sirolimus-eluting stent implantation in patients with acute ST-segment elevation (a certain measurement on an electrocardiogram) myocardial infarction (STEMI), in conjunction with the expected financial consequences, currently limit use of sirolimus-eluting stents in this setting. Current clinical guidelines specifically recommend the drug abciximab during primary PCI. At current European list prices, the use of the drug tirofiban instead of abciximab would absorb the difference in cost between stenting with sirolimus-eluting vs. bare-metal stents.

Marco Valgimigli, M.D., of the University of Ferrara, Italy and colleagues compared angiographic and clinical outcomes for the treatments of high-dose tirofiban plus sirolimus-eluting stenting vs. a current preferred strategy for STEMI treatment, pretreatment with abciximab plus bare-metal stenting. The STRATEGY trial included 175 patients presenting to a single referral center in Italy with STEMI or presumed new left bundle-branch block between March 6, 2003 and April 23, 2004. Patients received either tirofiban regimen plus sirolimus-eluting stenting (n = 87) or abciximab plus bare-metal stenting (n = 88).

The researchers found that 14 of 74 patients (19 percent) in the tirofiban plus sirolimus-eluting stent group and 37 of 74 patients (50 percent) in the abciximab plus bare-metal stent group reached the primary end point (death, nonfatal heart attack, stroke, or binary restenosis [narrowing of artery] at 8 months). The cumulative incidence of death, reinfarction, stroke, or TVR was significantly lower in the tirofiban plus sirolimus-eluting stent group (18 percent) vs. the abciximab plus bare-metal stent group (32 percent), predominantly reflecting a reduction in the need for TVR. Binary restenosis was present in 6 of 67 (9 percent) and 24 of 66 (36 percent) patients in the tirofiban plus sirolimus-eluting stent and abciximab plus bare-metal stent groups, respectively.

"In conclusion, our study provides proof of concept for a new treatment strategy in STEMI that incorporates unrestricted use of sirolimus-eluting stenting but results in no (European market) or only a modest (U.S. market) increase in medical expenditure," the authors write.

Race and Ethnicity Play a Role in Heart Attack Symptoms

Mon, 02 May 2005 13:26:38 PST

( from http://www.rxpgnews.com ) A computerized tool to help emergency room physicians determine whether a patient is having a heart attack may not work as well among some racial and ethnic groups, according to research of almost 12,000 patients at nine medical centers.

"It's notorious that women and elderly patients have markedly different heart attack symptoms from the younger male patient," said Chadwick D. Miller, M.D., from Wake Forest University School of Medicine. "This study shows us that race and ethnicity also play a role in symptoms."

Results from the research, conducted at Wake Forest and eight other medical centers, are reported in the May issue of Academic Emergency Medicine. The researchers studied a computerized risk stratification tool, called the Acute Coronary Ischemia-Time Insensitive Predictive Instrument (ACI-TIPI), which is designed to predict whether a patient is having a heart attack. Although ACI-TIPI itself is not widely used clinically, its elements form the basis of many other risk assessment tools.

There is no single, definitive test to diagnose heart attacks, making it difficult to evaluate chest pain patients. Risk assessment tools have become popular because they allow doctors to make "evidence-based" decisions based on age, gender, health history, questions about chest pain and an electrocardiogram.

"These tools have mostly been tested in an American, mixed-race population of patients. For example, a typical study population may be comprised of 60 percent Caucasian, 30 percent African-American and 10 percent Hispanic patients," said Miller, an instructor in emergency medicine at Wake Forest's School of Medicine, which is part of Wake Forest University Baptist Medical Center. "This design does not detect subtle differences that may exist among the groups."

It has been demonstrated that race and ethnicity influence both the perception of chest pain and the time it takes people to seek treatment. Miller said these differences may make the risk assessment tools inaccurate if they are applied to other population groups.

The study compared how well the tool performed in a mixed-race population in the United States versus an Asian population in Singapore.

"What we found was that in Singapore, patients were less likely to exhibit the typical symptom of heart attack: chest pain." Miller said. "Age and male gender also had little predictive power in evaluating whether these patients were having a heart attack."

Miller said the results suggest that doctors should consciously consider the effects of racial or ethnic differences when they use the tools. In addition, they point to the importance of taking ethnic differences into consideration when designing new tools.

"Given the previously demonstrated differences in ethnic groups, combined with our findings, one must question the utility of population-based cardiac risk assessment," said Miller. "We know that typical American patient presents with crushing chest pain. But, this approach doesn't take into the account the different ethnicities that might present differently."

For the study, the researchers analyzed data from a registry of patients with cardiac symptoms who came to the emergency departments of eight U.S. medical centers and one medical center in Singapore. Any patient who came in with symptoms that might be cardiac chest pain, shortness of breath, etc. was included in the study. The researchers looked at the accuracy of ACI-TIPI in predicting acute coronary syndrome (ACS).

Misdosing Of Clotbusters in Heart Attack Patients & Complications

Thu, 14 Apr 2005 15:51:38 PST

( from http://www.rxpgnews.com ) 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.