Dutasteride lowers the incidence of prostate cancer, but not high-grade tumors, according to a New England Journal of Medicine study.
In a double-blind study designed by dutasteride's manufacturer, some 6700 high-risk men underwent randomization to either daily dutasteride or placebo. At entry, subjects were 50 to 75 years old, had PSA levels between 2.5 and 10 ng/mL, and had had a negative biopsy.
During 4 years' follow-up, the incidence of biopsy-detected cancer was lower in the treatment group than in controls (20% vs. 25%). The number of high-grade tumors, however, was significantly higher in the treatment group during the last 2 years of follow-up.
An editorialist concludes that the 5-alpha-reductase inhibitors like dutasteride "do not prevent ... but merely temporarily shrink tumors that have a low potential for being lethal." He adds that, because the drugs suppress PSA levels, "men may have a false sense of security," thus delaying diagnosis.
Saturday, August 28, 2010
Tuesday, August 24, 2010
Broad Review of FDA Trials Suggests Antidepressants Only Marginally Better than Placebo
August 24, 2010 — A new review of 4 meta-analyses of efficacy trials submitted to the US Food and Drug Administration (FDA) suggests that antidepressants are only "marginally efficacious" compared with placebo and "document profound publication bias that inflates their apparent efficacy."
In addition, when the researchers also analyzed the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial, "the largest antidepressant effectiveness trial ever conducted," they found that "the effectiveness of antidepressant therapies was probably even lower than the modest one reported...with an apparent progressively increasing dropout rate across each study phase.
"We found that out of the 4041 patients initially started on the SSRI [selective serotonin reuptake inhibitor] citalopram in the STAR*D study, and after 4 trials, only 108 patients had a remission and did not either have a relapse and/or dropped out by the end of 12 months of continuing care," lead study author Ed Pigott, PhD, a psychologist with NeuroAdvantage LLC in Clarksville, Maryland, told Medscape Medical News.
Sustained Benefit "Jaw Dropping"
"In other words, if you're trying to look at sustained benefit, you're only looking at 2.7%, which is a pretty jaw-dropping number," added Dr. Pigott.
Overall, "the reviewed findings argue for a reappraisal of the current recommended standard of care of depression," write the study authors.
"I believe there are likely some people where [antidepressants] are truly beneficial beyond placebo. The problem right now is that we simply have no way of knowing who those people are," noted Dr. Pigott. "My hope is that this kind of analysis creates 'more oxygen' for looking at other kinds of approaches to treatment."
The study was published in the August issue of Psychotherapy and Psychosomatics.
When registering new drug application trials with the FDA, drug companies must prespecify the primary and secondary outcome measures, the investigators report. "Prespecification is essential to ensure the integrity of a trial and enables the discovery of when investigators selectively publish the measures that show the outcome the sponsors prefer following data collection and analysis, a form of researcher bias known as HARKing or 'hypothesizing after the results are known'," they write.
For this article, Dr. Pigott and his team reviewed the following meta-analyses:
•1. Rising and colleagues (reviewed all efficacy trials for new drugs between 2001 and 2002)
•2. Turner and colleagues (reviewed 74 past trials of 12 antidepressants)
•3. Kirsch and colleagues, 2002 (reviewed 47 trials of 6 FDA-approved antidepressants)
•4. Kirsch and colleagues, 2008 (reviewed depression severity and efficacy in 35 trials)
The researchers also sought to reevaluate the methods and findings of STAR*D, a randomized, controlled trial of patients with depression. Its prespecified primary outcome measure was the Hamilton Rating Scale for Depression (HRSD), whereas the Inventory of Depressive Symptomatology–Clinician-Rated (IDS-C30) was secondary for identifying remitted and responder patients.
"STAR*D was designed to identify the best next-step treatment for the many patients who fail to get adequate relief from their initial SSRI trial," the study authors write.
"When I first read about STAR*D's step 1 phase, it just seemed biased to me," explained Dr. Pigott. "I thought of it as the 'tag, you're healed' research design. Patients who were scored as having a remission during the first 4 to 6 weeks of up to 14 weeks of acute care treatment were counted as remitted, taken out of the subject pool, and put into the follow-up care phase. In other words, they didn't have the ability to have a relapse. But as most people know, depression ebbs and flows.
"So what made me want to continue to follow this study was that it became clear that the only way that people were really going to be able to evaluate the antidepressants' effectiveness was to wait for the publication of the follow-up findings," he added. "After their major final summary study was published, I felt as though the results weren't really being portrayed in a manner that was consistent with the study's prespecified criteria."
High Dropout, Low Remission Rates
In addition to reporting on low efficacy of antidepressants compared with placebo, the 4 meta-analyses "also document a second form of bias in which researchers fail to report the negative results for the prespecified primary outcome measure submitted to the FDA, while highlighting in published studies positive results from a secondary or even a new measure, as though it was their primary measure of interest," the investigators write.
For example, they note, the meta-analysis from Rising and colleagues found that studies with favorable outcomes were almost 5 times more likely to be published and that over 26% of primary outcome measures were left out of journal articles. Turner and colleagues found that antidepressant studies were 16 times more likely to be published if favorable compared with those with unfavorable outcomes.
In reanalyzing the STAR*D methods, the researchers found that the high dropout rate resulted in frequently missed exit HRSD and IDS-C30 interviews. So the revised statistical analytical plan dropped the IDS-30 for the Quick Inventory of Depressive Symptomatology-Self Report (QIDS-SR), which was given at each visit.
"Even with the extraordinary care of STAR*D, only about one fourth of patients achieved remission in step 1 [and] the dropout rate was slightly larger than the success rate," the study authors write. Steps 2 through 4 also each showed increasingly fewer success rates and larger dropout rates.
Of the 4041 patients at the study's initiation, 370 (9.2%) dropped out within 2 weeks, and only 1854 patients (45.9%) obtained remission "using the lenient QIDS-SR criteria." Of these, 670 dropped out within a month of their remission, and only 108 "survived continuing care" and underwent the final assessment.
Dr. Pigott described reanalyzing STAR*D as being "a bit like an onion. Each time we thought we understood the results, we found another layer. It wasn't until about a year and a half ago that we discovered that the secondary outcome measure, the QIDS-SR, was not originally supposed to be used as a research measure. What was particularly disconcerting to me was that in their summary article, they basically used the QIDS-SR to report all of the results, which clearly had an inflationary effect on the outcome."
He also noted that STAR*D did not have a placebo design. "Because the patients knew they were receiving the active medication, I would have expected a higher remission rate than what you'd find normally in a placebo-controlled study.
"The inescapable conclusion from the STAR*D results is that we need to explore more seriously other forms of treatment (and combination thereof) that may be more effective. This effort will require developing new service delivery models to ensure that as treatments are identified, they are widely implemented," the investigators conclude.
Need for Biomarkers
"For STAR*D, we wanted to do a study that other people could then reanalyze and look at. So I'm very glad that these authors reexamined it and saw it slightly differently, which came mainly from ways of analyzing data," Maurizio Fava, MD, STAR*D trial investigator and executive vice chair of the Department of Psychiatry at Massachusetts General Hospital in Boston, told Medscape Medical News.
"I think their analysis is reasonable and not incompatible with what we had reported," added Dr. Fava, who was not involved with this review.
He noted that the review's message for clinicians is that "there's been a failure of the field to demonstrate robust advantages of antidepressants over placebo. It's doesn't mean that clinicians shouldn't use antidepressants, but they should recognize that there's a limitation. On the other hand, we have very plausible, reasonable explanations for such failure, including the fact that patients who don't actually have the disease have often been enrolled in the studies. Therefore, this failure may have to do with imperfect clinical trial design and conduct."
In addition, Dr. Fava said that the review points to a lack of long-term efficacy for antidepressants, although "this may be due to things such as inadequate management of patients without dose adjustments and other things that can increase the likelihood of remaining well.
"Regardless of how you look at it, this study suggests the importance of developing biomarkers to identify patients who really need these antidepressants both in the short and the long term," concluded Dr. Fava. "I'd say there's a real opportunity here for that."
Dr. Pigott reports consulting in the past 3 years for CNS Response, Midwest Center for Stress and Anxiety, and SmartBrain Technologies. Dr. Fava reports several disclosures, which are listed in the original STAR*D papers
In addition, when the researchers also analyzed the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial, "the largest antidepressant effectiveness trial ever conducted," they found that "the effectiveness of antidepressant therapies was probably even lower than the modest one reported...with an apparent progressively increasing dropout rate across each study phase.
"We found that out of the 4041 patients initially started on the SSRI [selective serotonin reuptake inhibitor] citalopram in the STAR*D study, and after 4 trials, only 108 patients had a remission and did not either have a relapse and/or dropped out by the end of 12 months of continuing care," lead study author Ed Pigott, PhD, a psychologist with NeuroAdvantage LLC in Clarksville, Maryland, told Medscape Medical News.
Sustained Benefit "Jaw Dropping"
"In other words, if you're trying to look at sustained benefit, you're only looking at 2.7%, which is a pretty jaw-dropping number," added Dr. Pigott.
Overall, "the reviewed findings argue for a reappraisal of the current recommended standard of care of depression," write the study authors.
"I believe there are likely some people where [antidepressants] are truly beneficial beyond placebo. The problem right now is that we simply have no way of knowing who those people are," noted Dr. Pigott. "My hope is that this kind of analysis creates 'more oxygen' for looking at other kinds of approaches to treatment."
The study was published in the August issue of Psychotherapy and Psychosomatics.
When registering new drug application trials with the FDA, drug companies must prespecify the primary and secondary outcome measures, the investigators report. "Prespecification is essential to ensure the integrity of a trial and enables the discovery of when investigators selectively publish the measures that show the outcome the sponsors prefer following data collection and analysis, a form of researcher bias known as HARKing or 'hypothesizing after the results are known'," they write.
For this article, Dr. Pigott and his team reviewed the following meta-analyses:
•1. Rising and colleagues (reviewed all efficacy trials for new drugs between 2001 and 2002)
•2. Turner and colleagues (reviewed 74 past trials of 12 antidepressants)
•3. Kirsch and colleagues, 2002 (reviewed 47 trials of 6 FDA-approved antidepressants)
•4. Kirsch and colleagues, 2008 (reviewed depression severity and efficacy in 35 trials)
The researchers also sought to reevaluate the methods and findings of STAR*D, a randomized, controlled trial of patients with depression. Its prespecified primary outcome measure was the Hamilton Rating Scale for Depression (HRSD), whereas the Inventory of Depressive Symptomatology–Clinician-Rated (IDS-C30) was secondary for identifying remitted and responder patients.
"STAR*D was designed to identify the best next-step treatment for the many patients who fail to get adequate relief from their initial SSRI trial," the study authors write.
"When I first read about STAR*D's step 1 phase, it just seemed biased to me," explained Dr. Pigott. "I thought of it as the 'tag, you're healed' research design. Patients who were scored as having a remission during the first 4 to 6 weeks of up to 14 weeks of acute care treatment were counted as remitted, taken out of the subject pool, and put into the follow-up care phase. In other words, they didn't have the ability to have a relapse. But as most people know, depression ebbs and flows.
"So what made me want to continue to follow this study was that it became clear that the only way that people were really going to be able to evaluate the antidepressants' effectiveness was to wait for the publication of the follow-up findings," he added. "After their major final summary study was published, I felt as though the results weren't really being portrayed in a manner that was consistent with the study's prespecified criteria."
High Dropout, Low Remission Rates
In addition to reporting on low efficacy of antidepressants compared with placebo, the 4 meta-analyses "also document a second form of bias in which researchers fail to report the negative results for the prespecified primary outcome measure submitted to the FDA, while highlighting in published studies positive results from a secondary or even a new measure, as though it was their primary measure of interest," the investigators write.
For example, they note, the meta-analysis from Rising and colleagues found that studies with favorable outcomes were almost 5 times more likely to be published and that over 26% of primary outcome measures were left out of journal articles. Turner and colleagues found that antidepressant studies were 16 times more likely to be published if favorable compared with those with unfavorable outcomes.
In reanalyzing the STAR*D methods, the researchers found that the high dropout rate resulted in frequently missed exit HRSD and IDS-C30 interviews. So the revised statistical analytical plan dropped the IDS-30 for the Quick Inventory of Depressive Symptomatology-Self Report (QIDS-SR), which was given at each visit.
"Even with the extraordinary care of STAR*D, only about one fourth of patients achieved remission in step 1 [and] the dropout rate was slightly larger than the success rate," the study authors write. Steps 2 through 4 also each showed increasingly fewer success rates and larger dropout rates.
Of the 4041 patients at the study's initiation, 370 (9.2%) dropped out within 2 weeks, and only 1854 patients (45.9%) obtained remission "using the lenient QIDS-SR criteria." Of these, 670 dropped out within a month of their remission, and only 108 "survived continuing care" and underwent the final assessment.
Dr. Pigott described reanalyzing STAR*D as being "a bit like an onion. Each time we thought we understood the results, we found another layer. It wasn't until about a year and a half ago that we discovered that the secondary outcome measure, the QIDS-SR, was not originally supposed to be used as a research measure. What was particularly disconcerting to me was that in their summary article, they basically used the QIDS-SR to report all of the results, which clearly had an inflationary effect on the outcome."
He also noted that STAR*D did not have a placebo design. "Because the patients knew they were receiving the active medication, I would have expected a higher remission rate than what you'd find normally in a placebo-controlled study.
"The inescapable conclusion from the STAR*D results is that we need to explore more seriously other forms of treatment (and combination thereof) that may be more effective. This effort will require developing new service delivery models to ensure that as treatments are identified, they are widely implemented," the investigators conclude.
Need for Biomarkers
"For STAR*D, we wanted to do a study that other people could then reanalyze and look at. So I'm very glad that these authors reexamined it and saw it slightly differently, which came mainly from ways of analyzing data," Maurizio Fava, MD, STAR*D trial investigator and executive vice chair of the Department of Psychiatry at Massachusetts General Hospital in Boston, told Medscape Medical News.
"I think their analysis is reasonable and not incompatible with what we had reported," added Dr. Fava, who was not involved with this review.
He noted that the review's message for clinicians is that "there's been a failure of the field to demonstrate robust advantages of antidepressants over placebo. It's doesn't mean that clinicians shouldn't use antidepressants, but they should recognize that there's a limitation. On the other hand, we have very plausible, reasonable explanations for such failure, including the fact that patients who don't actually have the disease have often been enrolled in the studies. Therefore, this failure may have to do with imperfect clinical trial design and conduct."
In addition, Dr. Fava said that the review points to a lack of long-term efficacy for antidepressants, although "this may be due to things such as inadequate management of patients without dose adjustments and other things that can increase the likelihood of remaining well.
"Regardless of how you look at it, this study suggests the importance of developing biomarkers to identify patients who really need these antidepressants both in the short and the long term," concluded Dr. Fava. "I'd say there's a real opportunity here for that."
Dr. Pigott reports consulting in the past 3 years for CNS Response, Midwest Center for Stress and Anxiety, and SmartBrain Technologies. Dr. Fava reports several disclosures, which are listed in the original STAR*D papers
Saturday, August 14, 2010
National Center for Complementary and Alternative Medicine
Criticism
Critics attest that despite the publicized intentions at its founding, NCCAM and its predecessor, the Office of Alternative Medicine, have spent more than $800 million on such research since 1991 but have neither succeeded in demonstrating the efficacy of a single alternative method nor declared any alternative medicine treatment ineffective. "The NCCAM continues to fund and promote pseudoscience. Political pressures and the Center's charter would seem to make this inevitable," said Kimball C. Atwood IV, M.D.[5]
A policy forum in Science stated,
We believe that NCCAM [National Center for Complementary and Alternative Medicine] funds proposals of dubious merit; its research agenda is shaped more by politics than by science; and it is structured by its charter in a manner that precludes an independent review of its performance...In view of the popularity of alternative therapies, it is appropriate to evaluate the efficacy and safety of selected treatments.
but research falls below the standards of other NIH institutes. NCCAM budget for 2005 was $123.1 million. The charter said that 12 of the 18 members of the NCCAM Advisory Council "shall be selected from among the leading representatives of the health and scientific disciplines...in the area of complementary and alternative medicine. Nine of the members shall be practitioners licensed in one or more of the major systems with which the Center is involved". Clinical trials of St. John's wort, echinacea, and saw palmetto have been published; none was more effective than placebo, but manufacturers said the studies were flawed, and these studies are unlikely to change practices. 70% said they would continue using a supplement that a government agency said was ineffective. NCCAM is funding a study of EDTA chelation therapy for coronary artery disease with 2,300 patients, even though smaller controlled trials have found chelation ineffective. Another negative trial won't modify the practice of individuals who choose to ignore existing negative evidence. NCCAM is also funding a trial of gemcitabine with the Gonzalez regimen for stage II to IV pancreatic cancer, in the belief that cancer is caused by a deficiency of pancreatic proteolytic enzymes that would normally eliminate toxins; severe adverse effects are associated with the Gonzalez regimen. No evidence in peer-reviewed journals supports the plausibility or efficacy of chelation therapy or the Gonzalez protocol[6] and a test of the protocol reported in 2009 found patients receiving the treatment had worse quality of life and died faster than conventionally treated counterparts.[7]
Critics attest that despite the publicized intentions at its founding, NCCAM and its predecessor, the Office of Alternative Medicine, have spent more than $800 million on such research since 1991 but have neither succeeded in demonstrating the efficacy of a single alternative method nor declared any alternative medicine treatment ineffective. "The NCCAM continues to fund and promote pseudoscience. Political pressures and the Center's charter would seem to make this inevitable," said Kimball C. Atwood IV, M.D.[5]
A policy forum in Science stated,
We believe that NCCAM [National Center for Complementary and Alternative Medicine] funds proposals of dubious merit; its research agenda is shaped more by politics than by science; and it is structured by its charter in a manner that precludes an independent review of its performance...In view of the popularity of alternative therapies, it is appropriate to evaluate the efficacy and safety of selected treatments.
but research falls below the standards of other NIH institutes. NCCAM budget for 2005 was $123.1 million. The charter said that 12 of the 18 members of the NCCAM Advisory Council "shall be selected from among the leading representatives of the health and scientific disciplines...in the area of complementary and alternative medicine. Nine of the members shall be practitioners licensed in one or more of the major systems with which the Center is involved". Clinical trials of St. John's wort, echinacea, and saw palmetto have been published; none was more effective than placebo, but manufacturers said the studies were flawed, and these studies are unlikely to change practices. 70% said they would continue using a supplement that a government agency said was ineffective. NCCAM is funding a study of EDTA chelation therapy for coronary artery disease with 2,300 patients, even though smaller controlled trials have found chelation ineffective. Another negative trial won't modify the practice of individuals who choose to ignore existing negative evidence. NCCAM is also funding a trial of gemcitabine with the Gonzalez regimen for stage II to IV pancreatic cancer, in the belief that cancer is caused by a deficiency of pancreatic proteolytic enzymes that would normally eliminate toxins; severe adverse effects are associated with the Gonzalez regimen. No evidence in peer-reviewed journals supports the plausibility or efficacy of chelation therapy or the Gonzalez protocol[6] and a test of the protocol reported in 2009 found patients receiving the treatment had worse quality of life and died faster than conventionally treated counterparts.[7]
Phenfen pbs frontline
In our documentary segment about the Fen Phen disaster, we met Dr. Stuart Rich, a respected cardiologist and pulmonologist from the Rush Heart Institute in Chicago. During the mid-1990s, Rich played a central role in conducting the International Primary Pulmonary Hypertension study -- a large study of European men and women who were taking diet drugs, including Pondimin, which was on the market in the United states, and a closely-related "sister drug," Redux, which was not yet on the American market.
One of the main goals of the study was to evaluate the connection between these drugs and pulmonary hypertension, a devastating side effect that reduces the lung's ability to absorb oxygen, leading to constant shortness of breath and ultimately death. While a few cases had been reported around the world, drug manufacturers had long claimed that Pondimin and Redux only rarely caused pulmonary hypertension. Furthermore, they said, the benefit of losing weight was far more significant than the risk of developing the side effect.
In their three-year study, Dr. Rich and his colleagues found that Pondimin and Redux posed a "significant risk of dying from pulmonary hypertension," according to Rich. "And the risk went up the longer you took the drugs." Those results, and the fact that on average most people only lost a small amount of weight when they took these medicines, made Rich an opponent of FDA approval for Redux -- particularly for long-term use.
While Rich was appalled by the drug company's determination to put its drug on the American market, he was even more upset when the FDA acquiesced and approved the drug in the summer of 1996. "My reaction was despair," he told us. "Why despair? My specialty is I treat patients with pulmonary hypertension. These are the sickest cardiovascular patients that exist. They're young people. They're tragic stories. We have some treatments … but it's a death sentence. And it's a slow death, drowning, months to years."
Rich's only comfort was knowing that the European study would soon be published in The New England Journal of Medicine -- one of the most prestigious medical journals in the world. The drug company may have pushed this controversial product onto the market, thought Rich, and the FDA may have gone along with the idea, but doctors would soon read the study's findings about Redux when the Journal came out. Then, he hoped, doctors would stop prescribing the drug so often.
But getting out a clear message to consumers and the medical community about the risks posed by these diet drugs proved to be more difficult than Rich imagined.
• • •
The day before his article officially came out, Rich got a phone call from a newspaper reporter who had received an advance copy of the Journal and wanted Rich's reaction to an accompanying editorial -ã which Rich hadn't seen yet. (As was the custom at The New England Journal of Medicine, the magazine's editors had invited two prominent scientists to write an editorial about the European study to put it into perspective and help doctors determine whether and when the risk of using the diet drugs would be justified by the benefits.) Much to Dr. Rich's dismay, the editorial claimed that the benefits of using Pondimin and Redux far outweighed any risks and compared the risk of taking the diet drugs to taking penicillin for an infection. In effect, the editorial advised the medical community not to pay too much attention to Rich's study, and not to stop prescribing the drugs.
When Rich heard who the authors of the editorial were -- Dr. JoAnn Manson and Dr. Gerald Faich -- he realized immediately that both had financial ties to the drug companies that were making and/or selling Redux. And both had done work with those companies specifically in connection with Redux. "This was one of the greatest scandals that ever hit The New England Journal of Medicine," says Rich.
To guard against such potential conflicts of interest, it had been the Journal's policy to always ask editorial writers whether they had any "ongoing financial associations" with the company producing the product. In this case, the two scientists who authored the diet drug study editorial had told the magazine's editors -- in writing -- that they had "no financial interest or equity in any pharmaceutical company producing anti-obesity agents."
As word of the editorial controversy spread, the Journal's editors asked the two scientists to explain their written statement that they didn't have any financial interest in the company. In their defense, both authors downplayed their financial connections to the companies, and pointed out that the Journal had defined "ongoing financial associations" as "equity interest, regular consultancies, or major research support" and that their associations were neither "regular" nor "ongoing" but more occasional and not relevant to their editorial.
Despite the authors' explanations, a few weeks after publishing the pulmonary hypertension study the Journal's editors, Dr. Marcia Angell and Dr. Jerome Kassirer, ran a new editorial acknowledging that the authors may have misinterpreted the Journal's definition of "financial associations," but the editors also cast doubt on the credibility of any editorial written by someone with the kinds of financial ties that the authors had. (You can read the original Journal article [free registration required to read the full text] on the study and the accompanying editorial on the New England Journal's Web site. And you can also read the editors' follow-up editorial.)
But by that time, the damage may have been done. Thanks to the editorial that had run with the study article, many doctors around the world may well have dismissed the study's results and decided not to worry about prescribing Pondimin and Redux.
• • •
The Journal affair wasn't the only development that interfered with getting the story out about the European diet drug study, says Rich. The drug manufacturer, he says, tried to stop him from talking to the general public.
The news that popular diet drugs carried significant risks prompted NBC's Today show to invite Rich to appear on their morning program to talk about the study. Host Bryant Gumbel asked him to tell the country about the study and put it in perspective. "What I said," Rich recalls, "was nothing that was not mentioned in the paper: that the drug carried a very high risk of developing this fatal disease, that it should not be prescribed lightly."
A couple of hours after the live broadcast, Rich returned to his office where, he says, he received a phone call from a senior executive at Wyeth Pharmaceuticals.
"He told me he saw my interview on the Today show and warned me that it was very dangerous for me to talk to the press about that, that if I had any issues regarding their product that I wanted to publish in a scientific journal, so be it. But if I spoke to the media about their drug, bad things would happen. 'Bad things would happen' was the exact phrase he used. ... And I never talked to the press again. Because I didn't know what they had in mind. ... They are a very big, a very powerful company."
Rich has told his story under oath in several legal depositions as part of lawsuits brought by Fen Phen victims against the company.
For his part, the senior Wyeth executive has testified under oath in at least one deposition and denied having ever threatened Rich.
We will never know whose version of the facts is correct -- because none of the parties can prove one way or the other that they are being truthful. One thing is certain, however. Dr. Rich didn't speak to the popular press about Redux and Pondimin for many years after that appearance on the Today show -- and until now, he never told anybody in the media the details about that phone call.
One of the main goals of the study was to evaluate the connection between these drugs and pulmonary hypertension, a devastating side effect that reduces the lung's ability to absorb oxygen, leading to constant shortness of breath and ultimately death. While a few cases had been reported around the world, drug manufacturers had long claimed that Pondimin and Redux only rarely caused pulmonary hypertension. Furthermore, they said, the benefit of losing weight was far more significant than the risk of developing the side effect.
In their three-year study, Dr. Rich and his colleagues found that Pondimin and Redux posed a "significant risk of dying from pulmonary hypertension," according to Rich. "And the risk went up the longer you took the drugs." Those results, and the fact that on average most people only lost a small amount of weight when they took these medicines, made Rich an opponent of FDA approval for Redux -- particularly for long-term use.
While Rich was appalled by the drug company's determination to put its drug on the American market, he was even more upset when the FDA acquiesced and approved the drug in the summer of 1996. "My reaction was despair," he told us. "Why despair? My specialty is I treat patients with pulmonary hypertension. These are the sickest cardiovascular patients that exist. They're young people. They're tragic stories. We have some treatments … but it's a death sentence. And it's a slow death, drowning, months to years."
Rich's only comfort was knowing that the European study would soon be published in The New England Journal of Medicine -- one of the most prestigious medical journals in the world. The drug company may have pushed this controversial product onto the market, thought Rich, and the FDA may have gone along with the idea, but doctors would soon read the study's findings about Redux when the Journal came out. Then, he hoped, doctors would stop prescribing the drug so often.
But getting out a clear message to consumers and the medical community about the risks posed by these diet drugs proved to be more difficult than Rich imagined.
• • •
The day before his article officially came out, Rich got a phone call from a newspaper reporter who had received an advance copy of the Journal and wanted Rich's reaction to an accompanying editorial -ã which Rich hadn't seen yet. (As was the custom at The New England Journal of Medicine, the magazine's editors had invited two prominent scientists to write an editorial about the European study to put it into perspective and help doctors determine whether and when the risk of using the diet drugs would be justified by the benefits.) Much to Dr. Rich's dismay, the editorial claimed that the benefits of using Pondimin and Redux far outweighed any risks and compared the risk of taking the diet drugs to taking penicillin for an infection. In effect, the editorial advised the medical community not to pay too much attention to Rich's study, and not to stop prescribing the drugs.
When Rich heard who the authors of the editorial were -- Dr. JoAnn Manson and Dr. Gerald Faich -- he realized immediately that both had financial ties to the drug companies that were making and/or selling Redux. And both had done work with those companies specifically in connection with Redux. "This was one of the greatest scandals that ever hit The New England Journal of Medicine," says Rich.
To guard against such potential conflicts of interest, it had been the Journal's policy to always ask editorial writers whether they had any "ongoing financial associations" with the company producing the product. In this case, the two scientists who authored the diet drug study editorial had told the magazine's editors -- in writing -- that they had "no financial interest or equity in any pharmaceutical company producing anti-obesity agents."
As word of the editorial controversy spread, the Journal's editors asked the two scientists to explain their written statement that they didn't have any financial interest in the company. In their defense, both authors downplayed their financial connections to the companies, and pointed out that the Journal had defined "ongoing financial associations" as "equity interest, regular consultancies, or major research support" and that their associations were neither "regular" nor "ongoing" but more occasional and not relevant to their editorial.
Despite the authors' explanations, a few weeks after publishing the pulmonary hypertension study the Journal's editors, Dr. Marcia Angell and Dr. Jerome Kassirer, ran a new editorial acknowledging that the authors may have misinterpreted the Journal's definition of "financial associations," but the editors also cast doubt on the credibility of any editorial written by someone with the kinds of financial ties that the authors had. (You can read the original Journal article [free registration required to read the full text] on the study and the accompanying editorial on the New England Journal's Web site. And you can also read the editors' follow-up editorial.)
But by that time, the damage may have been done. Thanks to the editorial that had run with the study article, many doctors around the world may well have dismissed the study's results and decided not to worry about prescribing Pondimin and Redux.
• • •
The Journal affair wasn't the only development that interfered with getting the story out about the European diet drug study, says Rich. The drug manufacturer, he says, tried to stop him from talking to the general public.
The news that popular diet drugs carried significant risks prompted NBC's Today show to invite Rich to appear on their morning program to talk about the study. Host Bryant Gumbel asked him to tell the country about the study and put it in perspective. "What I said," Rich recalls, "was nothing that was not mentioned in the paper: that the drug carried a very high risk of developing this fatal disease, that it should not be prescribed lightly."
A couple of hours after the live broadcast, Rich returned to his office where, he says, he received a phone call from a senior executive at Wyeth Pharmaceuticals.
"He told me he saw my interview on the Today show and warned me that it was very dangerous for me to talk to the press about that, that if I had any issues regarding their product that I wanted to publish in a scientific journal, so be it. But if I spoke to the media about their drug, bad things would happen. 'Bad things would happen' was the exact phrase he used. ... And I never talked to the press again. Because I didn't know what they had in mind. ... They are a very big, a very powerful company."
Rich has told his story under oath in several legal depositions as part of lawsuits brought by Fen Phen victims against the company.
For his part, the senior Wyeth executive has testified under oath in at least one deposition and denied having ever threatened Rich.
We will never know whose version of the facts is correct -- because none of the parties can prove one way or the other that they are being truthful. One thing is certain, however. Dr. Rich didn't speak to the popular press about Redux and Pondimin for many years after that appearance on the Today show -- and until now, he never told anybody in the media the details about that phone call.
dangerous prescription pbs
Nov. 13, 2003
Whenever you make a television documentary, inevitably you shoot more material than can possibly fit into a one-hour program. That certainly happened to us in making "Dangerous Prescription." After we had researched our program and begun filming a broad story about drugs that had recently come off the market, current and former Food and Drug Administration employees began coming forward, little by little, to give us a powerful critique of what was going on inside the agency. Our story gradually began to evolve, and rather than making a documentary about drug safety in general, we ended up shifting our focus to the FDA.
But drug safety isn't just in the hands of the FDA. Americans -- and the Food and Drug Administration itself -- rely on pharmaceutical companies to be honest about what works and what doesn't. The ways in which pharmaceutical companies can "spin" bad news about their products, or influence the distribution of that news, in order to control damage and impede important information from reaching consumers and doctors, are revealed in two cases that didn't make it into the program.
What Bad News?
The first of these stories is about patients getting "less effective drugs" when better choices are available. If your doctor prescribes a less effective drug, you're not being helped as much as you could be helped. And when you think about it, that means you are being harmed.
About 50 million Americans have hypertension (commonly known as high blood pressure) -- and an estimated 30 million need some sort of medical treatment to bring their problem under control. Patients who fail to lower their blood pressure face increased risk of heart attacks, strokes and diabetes -- so the treatment of hypertension has become one of the largest markets for drugs in America and everywhere else in the developed world.
By some estimates, there are as many as 180 different prescription medications used in the United States to treat hypertension. Almost every major drug company has at least one product for lowering blood pressure, and doctors are generally happy to have these choices. But having so many choices does create a problem. Some drugs are bound to be more effective than others -- so doctors urgently want to know what's best.
Unfortunately, pharmaceutical companies rarely conduct clinical trials that fairly and objectively compare other companies' drugs against their own. And the FDA doesn't conduct such trials either, because the agency is not in the business of doing medical research -- only reviewing the results submitted by pharmaceutical companies.
• • •
With Americans spending $16 billion a year on blood pressure medicines, and no objective information to show which ones were most effective at reducing the problems caused by high blood pressure, about 10 years ago the National Heart Lung and Blood Institute (a division of the National Institutes of Health) started a long-term clinical trial that would honestly and fairly compare the effectiveness of the leading types of blood pressure medicines. The study, called ALLHAT (short for Anti-Hypertensive and Lipid-Lowering treatment to prevent Heart Attack Trial) enrolled over 42,000 Americans, lasted for some eight years, and cost over $140 million.
It was the kind of study that only a government agency could organize -- comparing four major classes of competing hypertension drugs, each of which lowers blood pressure in its own unique way. The drugs included: a diuretic (one of the oldest and cheapest treatments for hypertension, and widely available as a generic drug); Lisinopril (one of the popular, widely prescribed "ACE inhibitors," a class of drugs that includes Capoten, Vasotec Lotensin, Monopril, Univasc, Aceon, Accupril, Altace, Mavic); Norvasc (a "calcium channel blocker" made by Pfizer and the country's largest selling treatment for hypertension according to a Pfizer annual report); and Cardura (an "alpha blocker").
According to ALLHAT's principal investigator, Dr. Curt Furberg, "since the early 1990s, ACE inhibitors and calcium channel blockers had captured maybe a third or maybe 40 percent of the market" for treating high blood pressure, cutting into the prescriptions for older drugs that had a long track record of effectiveness and that were much cheaper. "And there wasn't good evidence that the newer drugs were better, or even as good," says Furberg, "so this study was undertaken to help us figure that out."
About six years into the study, its organizers halted treatment with one of the drugs, Cardura, because an early data analysis showed that patients on Cardura were 25 percent more likely to develop cardiovascular disease than patients on diuretics, and twice as likely to develop heart failure. It wasn't that Cardura was bad, but for most people it was clear that diuretics were significantly better.
The study continued with the three remaining drugs until the summer of 2002, and then in December of last year the results were announced at a packed press conference in Washington. The news was dramatic.
While all the drugs helped lower patients' blood pressure to about the same degree, according to the ALLHAT results patients on Norvasc -- an expensive and highly-advertised product -- were 38 percent more likely to develop heart failure than patients on the cheap, tried-and-true diuretics. And patients on Lisinopril (also more expensive than diuretics, and just coming off patent) were 15 percent more likely to develop strokes, 19 percent more likely to develop heart failure, and 11 percent more like to have angina than patients on diuretics. So, as a first-line treatment, the cheapest, oldest and least-promoted drug was significantly better at preventing the serious problems that can arise from having high blood pressure.
"ALLHAT demonstrated that, in the past, we didn't spend our drug dollars wisely," says Furberg. "We put too much money into drugs that are now shown to be inferior. And we need to learn more from that. And I think it's important for society to step in and not just leave it to drug companies to promote their drugs."
In Furberg's opinion, the fact that millions of people took -- and are still taking -- less effective drugs means that tens of thousands of Americans have been developing health problems that could have been prevented by a more effective drug.
"If you eliminated all the ACE inhibitors and calcium antagonists [calcium channel blockers] for the first-line treatment of hypertension," says Furberg, and if patients were put on diuretics, "we would avert maybe 60,000 events per year -- 60,000 heart failures or strokes. These are devastating complications. So, if you want to know what has happened over the past five years, we'll you can multiply by five. So we're talking about a large number of people who unnecessarily have suffered these events because we didn't have the knowledge we have today."
Furberg does note that many patients need to combine two or more different drugs to adequately lower their blood pressure -- so there's an important role for less effective drugs. And some patients don't tolerate diuretics so they need other options. But for the vast majority of people who have just been diagnosed with high blood pressure, according to ALLHAT, diuretics were the best as a first-line treatment -- and also the cheapest.
• • •
Given the ALLHAT data about calcium channel blockers and ACE inhibitors, the question was, how to get doctors to change their prescribing habits? For that to happen, first they would have to get the news.
But as Furberg soon discovered, the maker of one of the less effective but highly popular hypertension drugs wasn't going to let its market share slip away without a fight.
On the same day that the NIH scientists announced their results to the nation, Pfizer, the manufacturer of Norvasc, started a quiet campaign to counter the study results. First, the company issued a press release highlighting all of the study findings that were positive for Norvasc -- but leaving out the findings that were negative. (The release did mention that patients should first be started on diuretics, but it didn't mention that starting patients on Norvasc would lead to more heart failure.)
See the Pfizer video release on ALLHAT in which Dr. Berelowitz speaks
Then the company sent to television stations a videotaped interview with Dr. Michael Berelowitz, vice president of Pfizer's Metabolic and Cardiovascular Group, who declared that the ALLHAT study was an affirmation for Norvasc. "This study confirms what I think we have felt all along," Dr. Berelowitz says on the tape. "And that is that Norvasc is a safe, effective, well-tolerated agent for lowering blood pressure. … Accepting that diuretics are safe and effective and decreased cardiovascular disease, ALLHAT looked to see how the new agents -- calcium channel blockers like Norvasc, and an ACE inhibitor -- compared to the diuretic. And these agents were equally effective."
Read a letter from Berelowitz responding to FRONTLINE's request for an interview.
Compare Dr. Berelowitz's statement in the video to a statement made by the NIH research team that conducted the study. "Each of the newer drugs had significantly higher rates of one or more forms of cardiovascular disease," the ALLHAT team said. They went on: "Because of their superiority in preventing one or more forms of cardiovascular disease and their lower cost … diuretics should be the drugs of choice for the initial treatment of hypertension in most patients requiring drug therapy."
In the eyes of Curt Furberg, who had spent almost 10 years organizing and supervising the ALLHAT study, Pfizer was not telling the whole story. "I have problems with any drug company pushing an inferior product," says Furberg. "I don't think that's in the best interest of the patients. This is a difficult issue that somehow I have to deal with, society has to deal with: how we handle the situation where we have good knowledge that there is a difference between drugs and whether we should allow both of them to be out there competing, or whether we should put some restriction on the inferior drugs."
It's not hard to imagine why Pfizer might have responded to the ALLHAT study the way it did. Norvasc is a very profitable drug. According to the company's summer 2002 quarterly report, "Sales of Norvasc, the world's largest-selling medicine for hypertension and angina and the fourth-largest selling pharmaceutical of any kind grew 8% … to $931 million in the first quarter, compared to the same period in 2001."
Watch a video clip in which Dr. Curt Furberg appears on a radio show called "The People's Pharmacy" to talk about the ALLHAT study.
In light of Pfizer's campaign to put its own positive spin on the ALLHAT study, Furberg decided to hit the road and start a "counter campaign" -- to make sure that doctors and patients got the entire story about ALLHAT. That meant getting himself booked on radio talk shows and traveling to medical conferences to set the record straight on the study.
Unfortunately, Furberg says, he has to play the same public-relations game the pharmaceutical companies play, or his message is going to get lost in the company's PR campaign. He has to go to the media, visit the offices of influential doctors -- and get them to look at the data. "One of our biggest problems, to tell you the truth," he says, "is that diuretics don't have any champions. They're all generic drugs nowadays and drug companies don't make much profit on them. By and large, companies are only going to promote what earns them profits. And sometimes that's not good for your health and safety."
Whenever you make a television documentary, inevitably you shoot more material than can possibly fit into a one-hour program. That certainly happened to us in making "Dangerous Prescription." After we had researched our program and begun filming a broad story about drugs that had recently come off the market, current and former Food and Drug Administration employees began coming forward, little by little, to give us a powerful critique of what was going on inside the agency. Our story gradually began to evolve, and rather than making a documentary about drug safety in general, we ended up shifting our focus to the FDA.
But drug safety isn't just in the hands of the FDA. Americans -- and the Food and Drug Administration itself -- rely on pharmaceutical companies to be honest about what works and what doesn't. The ways in which pharmaceutical companies can "spin" bad news about their products, or influence the distribution of that news, in order to control damage and impede important information from reaching consumers and doctors, are revealed in two cases that didn't make it into the program.
What Bad News?
The first of these stories is about patients getting "less effective drugs" when better choices are available. If your doctor prescribes a less effective drug, you're not being helped as much as you could be helped. And when you think about it, that means you are being harmed.
About 50 million Americans have hypertension (commonly known as high blood pressure) -- and an estimated 30 million need some sort of medical treatment to bring their problem under control. Patients who fail to lower their blood pressure face increased risk of heart attacks, strokes and diabetes -- so the treatment of hypertension has become one of the largest markets for drugs in America and everywhere else in the developed world.
By some estimates, there are as many as 180 different prescription medications used in the United States to treat hypertension. Almost every major drug company has at least one product for lowering blood pressure, and doctors are generally happy to have these choices. But having so many choices does create a problem. Some drugs are bound to be more effective than others -- so doctors urgently want to know what's best.
Unfortunately, pharmaceutical companies rarely conduct clinical trials that fairly and objectively compare other companies' drugs against their own. And the FDA doesn't conduct such trials either, because the agency is not in the business of doing medical research -- only reviewing the results submitted by pharmaceutical companies.
• • •
With Americans spending $16 billion a year on blood pressure medicines, and no objective information to show which ones were most effective at reducing the problems caused by high blood pressure, about 10 years ago the National Heart Lung and Blood Institute (a division of the National Institutes of Health) started a long-term clinical trial that would honestly and fairly compare the effectiveness of the leading types of blood pressure medicines. The study, called ALLHAT (short for Anti-Hypertensive and Lipid-Lowering treatment to prevent Heart Attack Trial) enrolled over 42,000 Americans, lasted for some eight years, and cost over $140 million.
It was the kind of study that only a government agency could organize -- comparing four major classes of competing hypertension drugs, each of which lowers blood pressure in its own unique way. The drugs included: a diuretic (one of the oldest and cheapest treatments for hypertension, and widely available as a generic drug); Lisinopril (one of the popular, widely prescribed "ACE inhibitors," a class of drugs that includes Capoten, Vasotec Lotensin, Monopril, Univasc, Aceon, Accupril, Altace, Mavic); Norvasc (a "calcium channel blocker" made by Pfizer and the country's largest selling treatment for hypertension according to a Pfizer annual report); and Cardura (an "alpha blocker").
According to ALLHAT's principal investigator, Dr. Curt Furberg, "since the early 1990s, ACE inhibitors and calcium channel blockers had captured maybe a third or maybe 40 percent of the market" for treating high blood pressure, cutting into the prescriptions for older drugs that had a long track record of effectiveness and that were much cheaper. "And there wasn't good evidence that the newer drugs were better, or even as good," says Furberg, "so this study was undertaken to help us figure that out."
About six years into the study, its organizers halted treatment with one of the drugs, Cardura, because an early data analysis showed that patients on Cardura were 25 percent more likely to develop cardiovascular disease than patients on diuretics, and twice as likely to develop heart failure. It wasn't that Cardura was bad, but for most people it was clear that diuretics were significantly better.
The study continued with the three remaining drugs until the summer of 2002, and then in December of last year the results were announced at a packed press conference in Washington. The news was dramatic.
While all the drugs helped lower patients' blood pressure to about the same degree, according to the ALLHAT results patients on Norvasc -- an expensive and highly-advertised product -- were 38 percent more likely to develop heart failure than patients on the cheap, tried-and-true diuretics. And patients on Lisinopril (also more expensive than diuretics, and just coming off patent) were 15 percent more likely to develop strokes, 19 percent more likely to develop heart failure, and 11 percent more like to have angina than patients on diuretics. So, as a first-line treatment, the cheapest, oldest and least-promoted drug was significantly better at preventing the serious problems that can arise from having high blood pressure.
"ALLHAT demonstrated that, in the past, we didn't spend our drug dollars wisely," says Furberg. "We put too much money into drugs that are now shown to be inferior. And we need to learn more from that. And I think it's important for society to step in and not just leave it to drug companies to promote their drugs."
In Furberg's opinion, the fact that millions of people took -- and are still taking -- less effective drugs means that tens of thousands of Americans have been developing health problems that could have been prevented by a more effective drug.
"If you eliminated all the ACE inhibitors and calcium antagonists [calcium channel blockers] for the first-line treatment of hypertension," says Furberg, and if patients were put on diuretics, "we would avert maybe 60,000 events per year -- 60,000 heart failures or strokes. These are devastating complications. So, if you want to know what has happened over the past five years, we'll you can multiply by five. So we're talking about a large number of people who unnecessarily have suffered these events because we didn't have the knowledge we have today."
Furberg does note that many patients need to combine two or more different drugs to adequately lower their blood pressure -- so there's an important role for less effective drugs. And some patients don't tolerate diuretics so they need other options. But for the vast majority of people who have just been diagnosed with high blood pressure, according to ALLHAT, diuretics were the best as a first-line treatment -- and also the cheapest.
• • •
Given the ALLHAT data about calcium channel blockers and ACE inhibitors, the question was, how to get doctors to change their prescribing habits? For that to happen, first they would have to get the news.
But as Furberg soon discovered, the maker of one of the less effective but highly popular hypertension drugs wasn't going to let its market share slip away without a fight.
On the same day that the NIH scientists announced their results to the nation, Pfizer, the manufacturer of Norvasc, started a quiet campaign to counter the study results. First, the company issued a press release highlighting all of the study findings that were positive for Norvasc -- but leaving out the findings that were negative. (The release did mention that patients should first be started on diuretics, but it didn't mention that starting patients on Norvasc would lead to more heart failure.)
See the Pfizer video release on ALLHAT in which Dr. Berelowitz speaks
Then the company sent to television stations a videotaped interview with Dr. Michael Berelowitz, vice president of Pfizer's Metabolic and Cardiovascular Group, who declared that the ALLHAT study was an affirmation for Norvasc. "This study confirms what I think we have felt all along," Dr. Berelowitz says on the tape. "And that is that Norvasc is a safe, effective, well-tolerated agent for lowering blood pressure. … Accepting that diuretics are safe and effective and decreased cardiovascular disease, ALLHAT looked to see how the new agents -- calcium channel blockers like Norvasc, and an ACE inhibitor -- compared to the diuretic. And these agents were equally effective."
Read a letter from Berelowitz responding to FRONTLINE's request for an interview.
Compare Dr. Berelowitz's statement in the video to a statement made by the NIH research team that conducted the study. "Each of the newer drugs had significantly higher rates of one or more forms of cardiovascular disease," the ALLHAT team said. They went on: "Because of their superiority in preventing one or more forms of cardiovascular disease and their lower cost … diuretics should be the drugs of choice for the initial treatment of hypertension in most patients requiring drug therapy."
In the eyes of Curt Furberg, who had spent almost 10 years organizing and supervising the ALLHAT study, Pfizer was not telling the whole story. "I have problems with any drug company pushing an inferior product," says Furberg. "I don't think that's in the best interest of the patients. This is a difficult issue that somehow I have to deal with, society has to deal with: how we handle the situation where we have good knowledge that there is a difference between drugs and whether we should allow both of them to be out there competing, or whether we should put some restriction on the inferior drugs."
It's not hard to imagine why Pfizer might have responded to the ALLHAT study the way it did. Norvasc is a very profitable drug. According to the company's summer 2002 quarterly report, "Sales of Norvasc, the world's largest-selling medicine for hypertension and angina and the fourth-largest selling pharmaceutical of any kind grew 8% … to $931 million in the first quarter, compared to the same period in 2001."
Watch a video clip in which Dr. Curt Furberg appears on a radio show called "The People's Pharmacy" to talk about the ALLHAT study.
In light of Pfizer's campaign to put its own positive spin on the ALLHAT study, Furberg decided to hit the road and start a "counter campaign" -- to make sure that doctors and patients got the entire story about ALLHAT. That meant getting himself booked on radio talk shows and traveling to medical conferences to set the record straight on the study.
Unfortunately, Furberg says, he has to play the same public-relations game the pharmaceutical companies play, or his message is going to get lost in the company's PR campaign. He has to go to the media, visit the offices of influential doctors -- and get them to look at the data. "One of our biggest problems, to tell you the truth," he says, "is that diuretics don't have any champions. They're all generic drugs nowadays and drug companies don't make much profit on them. By and large, companies are only going to promote what earns them profits. And sometimes that's not good for your health and safety."
Expensive New Blood Pressure Meds No Better Than Generics, According to Long-Term Data
ScienceDaily (Aug. 14, 2010) — Expensive brand-name medications to lower blood pressure are no better at preventing cardiovascular disease than older, generic diuretics, according to new long-term data from a landmark study.
Paul Whelton, MB, MD, MSc, reported the results on Aug. 13 at the plenary session of the China Heart Congress and International Heart Forum in Beijing. Whelton is president and CEO of Loyola University Health System and chairman of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heat Attack Trial (ALLHAT), which has examined the comparative value of different blood pressure-lowering medications.
More than 33,000 patients with high blood pressure were randomly assigned to take either a diuretic (chlorthalidone) or one of two newer drugs, a calcium channel blocker (amlodipine) or an ACE inhibitor (lisinopril).
In 2002, ALLHAT researchers reported that among patients followed for four-to-eight years, the diuretic was better than the calcium channel blocker in preventing heart failure and better than the ACE inhibitor in preventing stroke, heart failure and overall cardiovascular disease.
In the new study, researchers followed ALLHAT participants for an additional four to five years after completion of the trial, bringing the total follow-up period to between eight and 13 years. During this longer follow-up period, the differences between the three drugs narrowed -- by most measures they were a statistical dead heat.
But the diuretic still was superior in two measures: Compared with the diuretic group, the ACE inhibitor group had a 20 percent higher death rate from stroke, and the calcium channel blocker group had a 12 percent higher rate of hospitalizations and deaths due to heart failure.
Diuretics, sometimes called "water pills," are the traditional medications for high blood pressure. They cause kidneys to remove sodium and water from the body, thereby relaxing blood vessel walls. ACE inhibitors such as lisinopril (brand names, Prinivil® and Zestril®) decrease chemicals that tighten blood vessels. Calcium channel blockers such as amlodipine (brand name, Norvasc®) relax blood vessels.
Diuretics cost $25 to $40 per year, while newer brand-name hypertension drugs can cost $300 to $600 per year.
The National Heart, Lung and Blood Institute recommends patients control their blood pressure by first controlling their weight, exercising, reducing sodium, increasing potassium and drinking alcohol in moderation. The institute says that if lifestyle changes are not sufficient, diuretics then normally should be the drug of first choice.
However, newer, higher-priced drugs are heavily marketed, and diuretics account for only about 30 percent of prescriptions written for high blood pressure medications, Whelton said.
Whelton is senior author of a study published in the May 24, 2010, Archives of Internal Medicine that found that using techniques similar to those employed by pharmaceutical sales reps can help persuade doctors to prescribe diuretics.
Like drug sales representatives, researchers in the study met with small groups of doctors, especially opinion leaders. They detailed guidelines for treating high blood pressure, and handed out studies, newsletters, exam room posters, etc. An examination of prescribing patterns found that this technique, known as "academic detailing," influenced what drugs doctors prescribed.
ALLHAT is sponsored by the National Heart, Lung and Blood Institute. "We are continuing to mine data that we collected during the trial," Whelton said.
Paul Whelton, MB, MD, MSc, reported the results on Aug. 13 at the plenary session of the China Heart Congress and International Heart Forum in Beijing. Whelton is president and CEO of Loyola University Health System and chairman of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heat Attack Trial (ALLHAT), which has examined the comparative value of different blood pressure-lowering medications.
More than 33,000 patients with high blood pressure were randomly assigned to take either a diuretic (chlorthalidone) or one of two newer drugs, a calcium channel blocker (amlodipine) or an ACE inhibitor (lisinopril).
In 2002, ALLHAT researchers reported that among patients followed for four-to-eight years, the diuretic was better than the calcium channel blocker in preventing heart failure and better than the ACE inhibitor in preventing stroke, heart failure and overall cardiovascular disease.
In the new study, researchers followed ALLHAT participants for an additional four to five years after completion of the trial, bringing the total follow-up period to between eight and 13 years. During this longer follow-up period, the differences between the three drugs narrowed -- by most measures they were a statistical dead heat.
But the diuretic still was superior in two measures: Compared with the diuretic group, the ACE inhibitor group had a 20 percent higher death rate from stroke, and the calcium channel blocker group had a 12 percent higher rate of hospitalizations and deaths due to heart failure.
Diuretics, sometimes called "water pills," are the traditional medications for high blood pressure. They cause kidneys to remove sodium and water from the body, thereby relaxing blood vessel walls. ACE inhibitors such as lisinopril (brand names, Prinivil® and Zestril®) decrease chemicals that tighten blood vessels. Calcium channel blockers such as amlodipine (brand name, Norvasc®) relax blood vessels.
Diuretics cost $25 to $40 per year, while newer brand-name hypertension drugs can cost $300 to $600 per year.
The National Heart, Lung and Blood Institute recommends patients control their blood pressure by first controlling their weight, exercising, reducing sodium, increasing potassium and drinking alcohol in moderation. The institute says that if lifestyle changes are not sufficient, diuretics then normally should be the drug of first choice.
However, newer, higher-priced drugs are heavily marketed, and diuretics account for only about 30 percent of prescriptions written for high blood pressure medications, Whelton said.
Whelton is senior author of a study published in the May 24, 2010, Archives of Internal Medicine that found that using techniques similar to those employed by pharmaceutical sales reps can help persuade doctors to prescribe diuretics.
Like drug sales representatives, researchers in the study met with small groups of doctors, especially opinion leaders. They detailed guidelines for treating high blood pressure, and handed out studies, newsletters, exam room posters, etc. An examination of prescribing patterns found that this technique, known as "academic detailing," influenced what drugs doctors prescribed.
ALLHAT is sponsored by the National Heart, Lung and Blood Institute. "We are continuing to mine data that we collected during the trial," Whelton said.
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