International Scam by Oxford Professors Kills
77
Two Oxford professors have evidently run an international scam
in 30 countries to make a cheap, effective heart medicine look
bad and promote the sales of expensive alternative medicines.
Apparently, deliberate overdosing killed 77 patients. Drug
companies gave the professors $9 million for their "study".
Isis-4 (Fourth International Study of Infarct Survival,
directed from Oxford, England) compared the effectiveness of
magnesium, Captopril, and nitroglycerine in preventing deaths
after heart attacks. The American Heart Association summarized
the Mg effects of ISIS-4 thus: Analysis of mortality data
revealed 4 more deaths per 1000 patients treated with magnesium.
(Journal of Myocardial Ischemia, Vol 6, No. 2, Feb. 1994) If 1/3
of the 58,050 patients received Mg, that would mean 77 deaths
were caused by the administration of Mg in ISIS-4.
Dr. Richard Peto, the ISIS-4 coordinator crowed, "This was the
biggest, and hence the most reliable, drug trial ever done,
involving 58,000 acute heart attack patients in 1084 hospitals in
30 countries. ... These results will disappoint those who had
trusted the positive claims from previous small trials of
magnesium..." Press Release, Radcliffe Infirmary, Oxford, Nov. 7,
1993.
As a medical writer/editor, I couldn't believe it, so I dug
deeper, and found that ISIS-4 was fatally flawed--apparently
deliberately. Here are the facts:
1. ISIS-4 infused an excessive amount of Mg into the veins of
these patients in a very short period of time, contrary to all
previous experience of what worked best. I have been told by a
prominent researcher that he and several other researchers had
told the ISIS-4 coordinators that they were setting up the study
wrong while they were still in the planning stage, but the
coordinators wouldn't heed them.
2. Magnesium was only given for a day, while the expensive,
competing drugs were administered for at least a month.
3. The ISIS-4 coordinators claimed all the drugs were
administered within 24 hours after the heart attack, but other
researchers have reportedly said that Mg was often not given
until much later.
4. The $9 million cost of ISIS-4 was paid by the makers of the
expensive heart-drugs Captopril (enzyme inhibitor made by
Bristol-Myers Squibb) and Imdur (nitroglycerine made by
Astra-Hassle).
5. In regard to the competing medication, Captopril, the
coordinators stated, "Benefits might be even greater if treatment
could be started as soon as possible after the attack." No such
sentiments were expressed about Mg, but then Mg was not paying
for the study.
6. I wrote the ISIS-4 coordinators about their timing of Mg
administration compared to the successful use of Mg in Dr.
Rasmussen's previous study. One ISIS-4 coordinator, Dr. Rory
Collins, wrote me back that Dr. Rasmussen's study "probably did
not enroll patients particularly early after onset."
7. However, Dr. Rasmussen's published work stated, "All
patients were included in the study less than 3 hours after they
had been admitted to hospital. (Rasmussen HS, et al. The Lancet,
Feb 1, 1986, p 234-6). Dr. Rasmussen's study showed that Mg
reduced mortality by 50% when given promptly.
8. Dr. Richard Peto, co-coordinator of ISIS-4, unsuccessfully
asked the editor of the New England Journal of Medicine to
dedicate an issue in honor of Dr. Bernard Fisher, after Fisher
had falsified research evidence in another study. Dr. Peto wrote
that the journal should also "explain why large-scale, randomized
evidence is so important." Business Week, Aug. 22, 1994, p
71.
9. As a result of Dr. Fisher's falsified study, the U. S.
Congress doubled the budget for auditing the truthfulness of such
trials. Dr. Peto petulantly stated, "They're going to make all
sorts of extra rules. It'll reduce the number of patients in
random trials and the number of doctors who do them. Unless these
people are stupid, they've got to realize this."
10. Professor James B. Pierce wrote a book that discussed Dr.
Peto's previous ISIS-2 study: "Discrepancies need to be
investigated, and this should be done by disinterested
researchers whose work is not funded by the big drug companies.
Heart Healthy Magnesium, 1994, p 98.
11. Dr. Alan Gaby, Medical Editor of the Townsend Letter For
Doctors, (May, 1996) expressed the following thoughts (Paragraphs
11,12,13). "Magnesium infusions were given for only 24 hours in
ISIS-4, compared to 48 hours or more in the other studies. Since
prevention of life-threatening arrhythmias is one of the effects
of magnesium and, since some of these arrhythmias occur after the
first 24 hours, the shorter duration of treatment may have
reduced the effectiveness of magnesium.
12. Many of the patients in ISIS-4 did not receive magnesium
until after they had been given fibrinolytic drugs. It is well
known that when blood flow is rapidly restored to the heart by
these drugs, a situation known as "reperfusion injury" can occur.
The rapid restoration of blood flow causes the release of so many
free radicals that the heart can be damaged. One of the possible
benefits of magnesium is that it may prevent reperfusion injury.
However, for that benefit to be realized, magnesium has to be
given before or during fibrinolytic therapy, not later on as in
ISIS-4.
13. Perhaps the most important difference between ISIS-4 and
the "positive" studies was in the dosage of magnesium used. In
the studies in which magnesium was most effective, the dose
during the first 24 hours was 50-65 mmol. The most effective dose
appeared to be 55 mmol. It is well known that an overdose of
intravenous magnesium can cause hypotension and bradyarrhythmia;
potentially serious side effects for a patient with compromised
cardiac function. Results of a previous study had suggested that
75 mmol/day of magnesium is the threshold for toxicity. However,
patients in ISIS-4 received 80 mmol of magnesium during the first
24 hours. It should therefore not be surprising that
magnesium-treated patients in ISIS-4 had an increased incidence
of second- or third-degree heart block and significant increases
in heart failure and deaths due to cardiogenic shock. Those
adverse effects are exactly what might be expected from an
overdose of magnesium. Even the LIMIT-2 study, in which magnesium
reduced mortality, may have pushed the limits of safety by
administering 73 mmol of magnesium in 24 hours. That could
explain why there was only a 24% reduction in mortality in
LIMIT-2, compared with reductions of 70% or more in trials that
used 50-65 nmol of magnesium. Apparently, the benefits of
magnesium diminish as the optimal dose is exceeded and, past a
certain point, the treatment becomes harmful.
14. The ISIS-4 coordinator stated misleadingly, "The IV
magnesium infusion used in ISIS-4 was similar to that used in the
Second Leicester Intravenous Magnesium Intervention Trial
(Limit-2) namely, an 8-mmol bolus given over approximately 15
minutes, followed by 72 mmol infused over 24 hours." The truth is
that Limit-2 gave 73 mmo1 over 24 hours, while ISIS-4 gave 80
mmol over 24 hours. The most effective dose appears to be 55
mmol. Why did ISIS-4 overdose contrary to known "good practices"?
Why did the coordinator conceal the overdose under the rubric of
"similar"?
It is unfortunate that so many millions of dollars were spent
on a study that failed to replicate the protocols used in earlier
work. Misfortune notwithstanding, ISIS-4 does not negate the
results of the other studies. When used properly, magnesium still
appears to be a safe, effective, and inexpensive treatment for
AMI, wrote Dr. Gaby.
It appears that 77 lives were deliberately sacrificed to
enlarge drug company profits and make cheap magnesium look bad.
Several thousand more Mg test-subjects may have died because Mg
was not used to best effect.
This apparent mass-murder may never be investigated or brought
to trial, since it involves 58,050 patients in 1084 hospitals in
30 countries. Who would have jurisdiction? Scotland Yard?
Interpol? The cost of such a trial, involving thousands of
witnesses in 30 countries would probably be more than the $9
million that ISIS-4 cost, and I don't believe any jurisdiction is
willing to spend that kind of money. The drug companies have
deeper pockets than do the prosecutors.
Deliberately biased research is worse than no research.
Instead of saving lives, it costs lives.
Additional background material can be found at:
http://www.mgwater
http://www.thorne.com/townsend/may/magnesiummay96.html
THE JOURNAL OF MYOCARDIAL ISCHEMIA, VOL 6, NO 2, Feb. 1994
American Heart Journal, Aug 1966, Vol 132, No. 2, Part 2 (Am
Heart J gives 6 articles reviewing ISIS-4)
This page was first uploaded to The Magnesium Web Site on
April 9, 2000
http://www.mgwater.com/
Healthy Water
Association--USA