WITHHOLDING WARFARIN SAFE FOR PROSTHETIC HEART VALVE PATIENTS WITH MAJOR BLEEDING
Anticoagulation therapy be can safely withheld or reversed during the treatment
of patients with prosthetic heart valves who are hospitalized for major bleeding,
according to a report in the February issue of Chest.
EXTENDED-RELEASE NIACIN ENHANCES THE LIPID-LOWERING EFFECTS OF STATIN THERAPY
Niaspan, an extended-release formulation of niacin, appears to be safe when
used in conjunction with high to moderate doses of statins.
IPRATROPIUM NOT HELPFUL IN CHILDREN HOSPITALIZED FOR ASTHMA
Routine addition of ipratropium bromide to standard treatment of children hospitalized
because of status asthmaticus appears to have no significant clinical benefit.
LA TIMES: FDA OFFICIALS, WARNER-LAMBERT KNEW OF REZULIN RISKS
Warner-Lambert downplayed the potentially fatal risks associated with Rezulin
during the approval process and received help from federal drug regulators in
pushing the drug toward marketing approval, according to an article published
in Sunday's edition of the Los Angeles Times.
Withholding Warfarin Safe for Prosthetic Heart
Valve Patients With Major Bleeding
WESTPORT, CT (Reuters Health) Mar 09 - Anticoagulation therapy be can safely withheld
or reversed during the treatment of patients with prosthetic heart valves who
are hospitalized for major bleeding, according to a report in the February issue
Dr. Howard S. Rosman, from St. John Medical Center, Detroit, and colleagues retrospectively
reviewed the medical records of 28 patients with prosthetic heart valves hospitalized
for major bleeding from 1990 to 1997. Among these patients, 25 had gastrointestinal
or retroperitoneal hemorrhage, two had intracranial hemorrhage and one patient
had a subdural hematoma.
Warfarin therapy was stopped on hospital admission in all the patients, and to
reverse anticoagulation five patients received vitamin K and seven patients received
fresh frozen plasma, the researchers report.
During the mean 15 days when warfarin was withheld, none of the patients had thromboembolic
complications, Dr. Rosman's group found. Four of the patients died in-hospital,
and 22 resumed warfarin therapy when they were discharged from the hospital. In
10 of the 19 patients still on warfarin, recurrent gastrointestinal bleeding was
seen at 6-month follow-up, according to the report.
"Although definite recommendations regarding the duration of safely withholding
warfarin cannot be made from our small series, approximately 2 weeks of withholding
anticoagulation seemed to be associated with no thromboembolic events," Dr.
Rosman and colleagues conclude.
Extended-Release Niacin Enhances the Lipid-Lowering
Effects of Statin Therapy
WESTPORT, CT (Reuters Health) Mar 09 - Niaspan, an extended-release formulation
of niacin, appears to be safe when used in conjunction with high to moderate doses
According to a report in the February 15th issue of the American Journal of Cardiology,
the combination improves the lipid profiles of patients who have not reached their
low-density lipoprotein (LDL) cholesterol target, or have elevated triglycerides
and decreased levels of high-density lipoprotein (HDL) cholesterol, on statin
Dr. Daniel J. Rader and colleagues, from the University of Pennsylvania, Philadelphia,
retrospectively reviewed the charts of 66 patients who had been on statin therapy
for at least 6 weeks before Niaspan was added to their regimen.
The addition of 1 g of Niaspan to the patient's statin therapy resulted in a mean
decrease in total cholesterol of 8%, an 8% decrease in LDL cholesterol and a 24%
decrease in triglycerides. In addition, HDL cholesterol was increased by 23%,
according to the group's report.
When the dose of Niaspan was titrated to 2 g in some patients, there was a mean
decrease of 21% in total cholesterol, a 31% decrease in LDL cholesterol, a 27%
increase in HDL cholesterol and a 27% decrease in triglycerides, Dr. Rader and
Putting these results in context, they say that adding Niaspan to the statin regimens
"had a modest effect on total and LDL cholesterol (similar to that of doubling
the dose of a statin)." However, for patients who had LDL cholesterol above
130 mg/dL on statin therapy alone, the addition of 1 g of Niaspan decreased LDL
cholesterol by a mean of 19%, "about 3 times that expected with a statin."
Furthermore, compared with the 17% increase in HDL cholesterol reported with Niaspan
monotherapy, the average increase of 24% in HDL cholesterol seen "when Niaspan
is given in combination with the statin suggests that the statin and Niaspan may
have complementary effects," Dr. Rader's group notes.
Safety data showed no significant increases in liver enzymes, glucose, or uric
acid levels with the addition of either a 1-g or 2-g dose of Niaspan.
Am J Cardiol 2001;87:476-479.
Ipratropium Not Helpful in Children Hospitalized
WESTPORT, CT (Reuters Health) Mar 12 - Routine addition of ipratropium bromide
to standard treatment of children hospitalized because of status asthmaticus appears
to have no significant clinical benefit.
Dr. Daniel Craven, of Rainbow Babies and Childrens Hospital in Cleveland, Ohio,
and colleagues note that although anticholinergic agents such as ipratropium bromide
"are often used in the hospital treatment of patients with status asthmaticus,
their efficacy in this setting remains uncertain."
Reporting in the January issue of the Journal of Pediatrics, the investigators
report that they conducted a double-blind study of 210 children with acute asthma
who were randomized to ipratropium or placebo treatment.
Both groups received nebulized albuterol, systemic corticosteroids and oxygen
according to a standardized inpatient asthma care algorithm. The intervention
group also received doses of nebulized ipratropium bromide, 250 mcg, combined
with albuterol, 2.5 mg. The placebo group was given isotonic saline.
Although children older than 6 years in the ipratropium group had a shorter mean
length of hospital stay and a more rapid progression through the asthma care path,
after adjustment for baseline differences, this observed benefit "no longer
reached statistical significance."
The additional treatment had no adverse effects, and although the researchers
point out that ipratropium "may benefit select individual children,"
routine use, they conclude, "confers no significant enhancement of clinical
J Pediatr 2001;138:51-58.
LA Times: FDA Officials, Warner-Lambert Knew of
NEW YORK (Reuters Health) Mar 12 - Warner-Lambert downplayed the potentially fatal
risks associated with Rezulin during the approval process and received help from
federal drug regulators in pushing the drug toward marketing approval, according
to an article published in Sunday's edition of the Los Angeles Times.
The Times obtained company and government documents, as well as e-mail communications,
which showed that Warner-Lambert officials had collaborated closely with certain
senior officials within the US Food and Drug Administration during the approval
process and later, when the company was being pressured to take the drug off the
Rezulin (troglitazone) was initially approved by the FDA in January 1997 for treatment
of type 2 diabetes. The drug was pulled from the market in March 2000 due to the
number of reports of liver failure associated with use of the drug. At an FDA
advisory committee meeting last year, regulators reported that there were 90 cases
of liver failure among patients taking the drug since its launch.
Pfizer said on Monday that of the roughly 1.9 million patients who were prescribed
Rezulin, fewer than 100 reported acute liver failure that lead to death or transplant.
According to the LA Times, Warner-Lambert executives knew that some patients in
clinical studies had sustained life-threatening liver damage, but they assured
an FDA panel that the risk was trivial. The paper reported that Warner-Lambert's
Dr. Randall W. Whitcomb told an FDA advisory committee on December 11, 1996 that
occurrences of liver damage among Rezulin patients was "comparable to placebo"
in the clinical studies.
In fact, the paper reports, the incidence of liver damage among users of Rezulin
was more than three times higher than patients given a placebo. Among patients
taking Rezulin, 2.2% experienced liver injury compared with 0.6% of patients who
received a placebo.
Whitcomb now serves as a consultant to Pfizer, which purchased Warner-Lambert
In addition, the paper details efforts by Murray M. Lumpkin, the former second
in command of the FDA's Center for Drug Evaluation and Research who tendered his
resignation in October 2000, to help curtail criticism of the drug by other FDA
officials. The Times cites an e-mail from Warner-Lambert's executive vice president
for regulatory affairs, Irwin G. Martin, that suggested Lumpkin cancelled a scheduled
speech by FDA medical officer Dr. Robert I. Misbin about liver toxicity associated
with Rezulin use in 1998.
In addition, FDA officials had pulled Dr. John L. Gueriguian, the medical officer
assigned to review Rezulin in the early 1990s, off of the review after Warner-Lambert
complained that he used profanity to describe Rezulin. Dr. Gueriguian had expressed
concern as early as 1994 about potential toxicities related to Rezulin. He was
removed from the review of Rezulin roughly 1 month before the drug was presented
to the advisory committee.
In addition, according to the paper, Lumpkin told Warner-Lambert officials that
Gueriguian's review would not be made available under the Freedom of Information
Act, thus keeping its content out of the view of the media and public. Members
of the advisory committee were allegedly unaware of the existence of Gueriguian's
review when they met to vote on a recommendation for approval.
The paper also details the cooperation of Dr. Henry G. Bone III, chairman of the
FDA advisory committee that reviewed Rezulin, in keeping the drug on the US market,
even after the committee reviewed reports of the serious adverse events associated
with the drug.
Neither Lumpkin nor Bone returned calls to the LA Times seeking comment. Lumpkin
has been considered a candidate for the FDA Commissioner slot that has yet to
be filled in the Bush administration.
As of mid-October, Pfizer faced 383 lawsuits in state and federal courts related
to Rezulin. In addition, the US attorney's office in Greenbelt, Maryland, has
questioned FDA officials about the approval process for the drug.
From the time of its approval to market withdrawal, Rezulin brought in revenues
of $2.1 billion for Warner-Lambert.
In a statement issued on Monday afternoon, Pfizer said that it "strongly
disagrees" with the LA Times' characterization of Warner-Lambert's behavior.
"While it does not comment in detail on matters related to current litigation,
Pfizer affirmed today that Warner-Lambert appropriately disclosed the risk of
adverse liver events before Rezulin...was commercially marketed," the statement
The company also said that Warner-Lambert had disclosed post-marketing adverse
events to the FDA in a timely manner, revised Rezulin's label to reflect the new
information and sent a letter to physicians advising them of the reports of adverse
The statement also cited comments made by FDA's Dr. Misbin at a public hearing
in April 1999, which said that Warner-Lambert's Parke-Davis division had provided
complete cooperation shortly after receiving the first report of liver failure.
According to Pfizer, Dr. Misbin said at that hearing, "speculation that there
was foot dragging here is totally without foundation."
Calls to the FDA were not returned to Reuters Health on Monday.
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