Latest Drugwonks' Blog
Grace, that is, as in Grace-Marie Turner, a member of the President's Medicaid Commission and herself President of the Galen Institute.
Yesterday, in front of the House Energy and Commerce Committee's Subcommittee on Health, Grace-Marie presented cogent and important testimony on the Protecting the Medicaid Safety Net Act of 2008 (H.R. 5613).
She made many valid, technically savvy comments and recommendations, but it was her conclusion that should strike at the best bipartisan angels of our legislative nature.
"The president and CEO of the Mayo Clinic, Dr. Denis Cortese, spoke in Washington recently about health reform. Mayo is renowned worldwide for its expertise in medical diagnosis, and Dr. Cortese drew on these capabilities to help policymakers think more strategically about health reform. He said in medical care and in public policy, change must focus on putting the needs of the patient first. Patients want personal, high-value health care, and we need to provide better incentives for programs and providers to provide that care.
Micromanagement of the system through rules and regulations is not putting the patient first. Instead, we need to focus on new financial incentives to encourage patients, providers, program administrators, and the states to make sure they are getting the best value in health spending. Rethinking Medicaid’s financial structure, I believe, is needed.
Our commission heard many, many witnesses testify that patients want a medical home. The worst place to get routine medical care is in a crowded hospital emergency room, but too many Medicaid recipients have no other choice. Having a medical home would mean that someone is working on their behalf to coordinate care. Medicaid doesn’t support the kind of coordination that would lead to better care and more efficient spending.
After hearing hours and hours of testimony during my service on the Medicaid Commission, I believe we must begin the process of transforming this fragmented, procedure-oriented program to one that is focused on coordinated care, results, and outcomes. Quality of care for Medicaid recipients will be improved when health care providers are responding to patients’ needs and not to bureaucratic program rules and regulations.
For Medicaid to become more patient-focused and to more effectively meet the distinctive needs of populations with different needs, Medicaid programs must begin funding health care in a new way. Achieving better quality of care is integrally connected to creating new incentives to achieve better outcomes. This means that new funding mechanisms should be tied to the success of providers and health plans in coordinating patient care, gathering sharable information on the patient’s medical care, and giving patients more information and responsibility to be partners in managing their health.
Focusing on these goals and on putting patients first would assure taxpayers, states, and most importantly, patients, that the system is supporting quality care."
Words well put -- and worth heeding.
Here's a link to Grace-Marie's complete testimony:
Download file
And if you want to consider yourself in the know, my suggestion is this -- read it.
Yesterday, in front of the House Energy and Commerce Committee's Subcommittee on Health, Grace-Marie presented cogent and important testimony on the Protecting the Medicaid Safety Net Act of 2008 (H.R. 5613).
She made many valid, technically savvy comments and recommendations, but it was her conclusion that should strike at the best bipartisan angels of our legislative nature.
"The president and CEO of the Mayo Clinic, Dr. Denis Cortese, spoke in Washington recently about health reform. Mayo is renowned worldwide for its expertise in medical diagnosis, and Dr. Cortese drew on these capabilities to help policymakers think more strategically about health reform. He said in medical care and in public policy, change must focus on putting the needs of the patient first. Patients want personal, high-value health care, and we need to provide better incentives for programs and providers to provide that care.
Micromanagement of the system through rules and regulations is not putting the patient first. Instead, we need to focus on new financial incentives to encourage patients, providers, program administrators, and the states to make sure they are getting the best value in health spending. Rethinking Medicaid’s financial structure, I believe, is needed.
Our commission heard many, many witnesses testify that patients want a medical home. The worst place to get routine medical care is in a crowded hospital emergency room, but too many Medicaid recipients have no other choice. Having a medical home would mean that someone is working on their behalf to coordinate care. Medicaid doesn’t support the kind of coordination that would lead to better care and more efficient spending.
After hearing hours and hours of testimony during my service on the Medicaid Commission, I believe we must begin the process of transforming this fragmented, procedure-oriented program to one that is focused on coordinated care, results, and outcomes. Quality of care for Medicaid recipients will be improved when health care providers are responding to patients’ needs and not to bureaucratic program rules and regulations.
For Medicaid to become more patient-focused and to more effectively meet the distinctive needs of populations with different needs, Medicaid programs must begin funding health care in a new way. Achieving better quality of care is integrally connected to creating new incentives to achieve better outcomes. This means that new funding mechanisms should be tied to the success of providers and health plans in coordinating patient care, gathering sharable information on the patient’s medical care, and giving patients more information and responsibility to be partners in managing their health.
Focusing on these goals and on putting patients first would assure taxpayers, states, and most importantly, patients, that the system is supporting quality care."
Words well put -- and worth heeding.
Here's a link to Grace-Marie's complete testimony:
Download file
And if you want to consider yourself in the know, my suggestion is this -- read it.
Pharmalot blogs on the Consumer's Union report that one out of six people have had a bad enough reaction from a drug that they went to the hospital.
http://www.pharmalot.com/
Which raises the question: are people and doctors taking enough responsibility for how they take their medicines? Another question: are companies doing enough to treat consumers of medicines as customers, resolving problems, addressing side effects on an individualized basis instead of behind a battalion of lawyers..
My guess is the answer is no. Therefore simply dialing up the FDA to complain about one own's sloppy behavior is no way to resolve the issue. A better way would be to get patients with similar meds, conditions and characteristics to report and share information about their experience with all drugs, OTC, prescription, supplements within a virtual community. Then that information can be scrubbed and reviewed for trends and safety signals.
Which is why CMPI is a proud sponsor of http://www.iguard.org the first patient created and patient centered source of information on how drugs are affecting people like you and me.
The Consumers Union recommendation is well intentioned but old school. The way and wave of the future is http://www.iguard.org
http://www.pharmalot.com/
Which raises the question: are people and doctors taking enough responsibility for how they take their medicines? Another question: are companies doing enough to treat consumers of medicines as customers, resolving problems, addressing side effects on an individualized basis instead of behind a battalion of lawyers..
My guess is the answer is no. Therefore simply dialing up the FDA to complain about one own's sloppy behavior is no way to resolve the issue. A better way would be to get patients with similar meds, conditions and characteristics to report and share information about their experience with all drugs, OTC, prescription, supplements within a virtual community. Then that information can be scrubbed and reviewed for trends and safety signals.
Which is why CMPI is a proud sponsor of http://www.iguard.org the first patient created and patient centered source of information on how drugs are affecting people like you and me.
The Consumers Union recommendation is well intentioned but old school. The way and wave of the future is http://www.iguard.org
Peter Huber notes that new medicines replace what Lewis Thomas termed as half-way technology or palliative care and eliminates jobs and buildings along the way..
"Diagnosis used to be almost all doctor; now it's almost all lab--and the lab technicians rely on higher-caliber dipsticks, assays and reagents developed and mass-produced by the same teams of top-tier doctors, research hospitals and big drug companies.
When drugs get good enough, they displace hours of ineffectual (but remunerative) human monitoring and palliative care. Drugs displace doctors, nurses and hospital beds because they really work and because they often work long before bad chemistry morphs into clots, plaques, lumps and other symptoms that require scalpels and beds. In the first half of the 20th century almost all medically supplied gains in health and life expectancy came from germ-killing vaccines and antibiotics. All the important gains since have come from arrays of drugs that target clogged arteries, strokes, cancer and other diseases rooted in our own human chemistry. Human eyes can't see and human hands can't handle most of the things that make us sick--bacteria, viruses, white blood cells, antibodies, proteins, enzymes, fats and genes."
This is a variation of Lewis Thomas wrote over 30 years ago: "A multiplicity of new variants of antibiotics and chemotherapeutic agents has appeared on the market, but one would not expect that the rational use of this technology, even allowing for the high cost of development and marketing, would have proven to be anything like the previous cost of hospital care in the absence of such a technology..typhoid was a 12 to 16 week illness; meningitis often require several months of care through convalesence; these and other common infectious diseases can now be aborted promptly, within just a few days..."
Thomas concludes: If our society wishes to be rid of the diseases, fatal and non-fatal, that plague us the most, there is really little prospect of doing so by mounting a still larger healthcare system at still greater cost for delivering essentially today's kid of technology on a larger scale....The harvest of new information from the biological revolution of the past quarter century is just now coming in, and we can probably begin to figure out the mechanisms of major diseases which were black mysteries a few years back as accurately and profitably as was done for the infectious diseases earlier in the century."
In the 30 years or so since Thomas wrote that, his prediction has come to pass. We still have more to harvest however. And as Huber points out, to think we can do it without commercializing research reflects a hostility to capitalism and protectionism of the worst sort.
Read Full Article
"Diagnosis used to be almost all doctor; now it's almost all lab--and the lab technicians rely on higher-caliber dipsticks, assays and reagents developed and mass-produced by the same teams of top-tier doctors, research hospitals and big drug companies.
When drugs get good enough, they displace hours of ineffectual (but remunerative) human monitoring and palliative care. Drugs displace doctors, nurses and hospital beds because they really work and because they often work long before bad chemistry morphs into clots, plaques, lumps and other symptoms that require scalpels and beds. In the first half of the 20th century almost all medically supplied gains in health and life expectancy came from germ-killing vaccines and antibiotics. All the important gains since have come from arrays of drugs that target clogged arteries, strokes, cancer and other diseases rooted in our own human chemistry. Human eyes can't see and human hands can't handle most of the things that make us sick--bacteria, viruses, white blood cells, antibodies, proteins, enzymes, fats and genes."
This is a variation of Lewis Thomas wrote over 30 years ago: "A multiplicity of new variants of antibiotics and chemotherapeutic agents has appeared on the market, but one would not expect that the rational use of this technology, even allowing for the high cost of development and marketing, would have proven to be anything like the previous cost of hospital care in the absence of such a technology..typhoid was a 12 to 16 week illness; meningitis often require several months of care through convalesence; these and other common infectious diseases can now be aborted promptly, within just a few days..."
Thomas concludes: If our society wishes to be rid of the diseases, fatal and non-fatal, that plague us the most, there is really little prospect of doing so by mounting a still larger healthcare system at still greater cost for delivering essentially today's kid of technology on a larger scale....The harvest of new information from the biological revolution of the past quarter century is just now coming in, and we can probably begin to figure out the mechanisms of major diseases which were black mysteries a few years back as accurately and profitably as was done for the infectious diseases earlier in the century."
In the 30 years or so since Thomas wrote that, his prediction has come to pass. We still have more to harvest however. And as Huber points out, to think we can do it without commercializing research reflects a hostility to capitalism and protectionism of the worst sort.
Read Full Article
Being on a program called "the Infinite Mind" is humbling -- especially when the host is Dr. Fred Goodwin -- and on NPR no less.
Here are the program notes:
In the wake of new high-profile violent acts by people taking anti-depressant medications, including the recent Northern Illinois University shootings, and new research on antidepressant medications and their possible link to "suicidality," we look at the science on the connection between antidepressants and violent behavior.
Is there a link between antidepressants and suicide?
The answer may surprise you.
Joining us are Nada Stotland, president-elect of the American Psychiatric Association; Peter Pitts, a former FDA official who participated in the administration’s labeling of antidepressants as dangerous; and Andrew Leuchter, Director of the Laboratory of Brain, Behavior, and Pharmacology and Senior Research Scientist at UCLA, who has studied how press coverage and public alarm about antidepressants affects the nation’s health and willingness to be treated for real, life threatening illnesses.
And here's a link to the actual program:
http://www.lcmedia.com/mind524.htm
In addition to the program, this link also provides some very good commentary on the topics of depression and SSRIs.
Here are the program notes:
In the wake of new high-profile violent acts by people taking anti-depressant medications, including the recent Northern Illinois University shootings, and new research on antidepressant medications and their possible link to "suicidality," we look at the science on the connection between antidepressants and violent behavior.
Is there a link between antidepressants and suicide?
The answer may surprise you.
Joining us are Nada Stotland, president-elect of the American Psychiatric Association; Peter Pitts, a former FDA official who participated in the administration’s labeling of antidepressants as dangerous; and Andrew Leuchter, Director of the Laboratory of Brain, Behavior, and Pharmacology and Senior Research Scientist at UCLA, who has studied how press coverage and public alarm about antidepressants affects the nation’s health and willingness to be treated for real, life threatening illnesses.
And here's a link to the actual program:
http://www.lcmedia.com/mind524.htm
In addition to the program, this link also provides some very good commentary on the topics of depression and SSRIs.
Two wrongs don't make a right. So while Schering's behavior appears to mimic that of Steve Nissen and Atherogenics when it came to fiddling with imaging data or at least sitting on it, this is no way to win, earn, retain, build the trust of doctors and consumers in your products.
It won't be enough for Schering and Merck to launch a $5 million PR campaign on the product. This sullies the reputation of all other companies and calls into question the integrity of the conduct of clinical trials in general. Just as the blockbuster era is over, so too is the closed door approach to clinical trials at an end. The need for collaboration, transparency, sharing of data -- particularly about what doesn't work and for who -- is paramount. Further, we need to move beyond the "bet-the-farm" mentality where the fate and fortune of a drug hinges on the outcome of one large trial. ENHANCE was a study of the impact of a specific drug for a selective population. It raised more questions than it answered, as much of scientific research does. There are better ways to get at such information, which is what the Critical Path is all about.
I don't think Schering did anything wrong...it is likely given the advances in imaging technology and shifts in opinion about the reliability of intravascular scans (pro and con) an independent data monitoring board would have come to the same conclusion. But when faced with the complexities it should have handed it over to an independent panel. No one was thinking about the larger repercussions of not doing so. Or maybe they were and made the wrong choice. Now heads will roll and rightly so.
It won't be enough for Schering and Merck to launch a $5 million PR campaign on the product. This sullies the reputation of all other companies and calls into question the integrity of the conduct of clinical trials in general. Just as the blockbuster era is over, so too is the closed door approach to clinical trials at an end. The need for collaboration, transparency, sharing of data -- particularly about what doesn't work and for who -- is paramount. Further, we need to move beyond the "bet-the-farm" mentality where the fate and fortune of a drug hinges on the outcome of one large trial. ENHANCE was a study of the impact of a specific drug for a selective population. It raised more questions than it answered, as much of scientific research does. There are better ways to get at such information, which is what the Critical Path is all about.
I don't think Schering did anything wrong...it is likely given the advances in imaging technology and shifts in opinion about the reliability of intravascular scans (pro and con) an independent data monitoring board would have come to the same conclusion. But when faced with the complexities it should have handed it over to an independent panel. No one was thinking about the larger repercussions of not doing so. Or maybe they were and made the wrong choice. Now heads will roll and rightly so.
Have you seen the article by Darlene Elias and Eric Topol (European Journal of Human Genetics)?
The title says it all, "Warfarin Pharmacogenomics: A big step forward for individualized medicine: enlightened dosing of warfarin."
Here's a link:
http://www.nature.com/ejhg/journal/vaop/ncurrent/full/5201945a.html
They applaud advances in genetic testing ... and ask some tough questions:
"In the meantime, however, a real dilemma exists for treating physicians and patients taking warfarin. Who to test and how to manage? What dosing nomogram to use? The clinical availability of the genetic testing is limited but presumed soon to be expanding. How or will the genotyping be reimbursed, given these commercially available tests are quite expensive for both CYP2C9 and VKORC1. And should all this be coordinated centrally, since studies have shown that warfarin monitoring can be improved and INR is more frequently in range with the adverse event rates lower when a centralized anticoagulation service is used compared to usual individual physician care."
We must all face these and similar issues and commence our difficult journey down the Critical Path. The future of the public health demands no less.
The title says it all, "Warfarin Pharmacogenomics: A big step forward for individualized medicine: enlightened dosing of warfarin."
Here's a link:
http://www.nature.com/ejhg/journal/vaop/ncurrent/full/5201945a.html
They applaud advances in genetic testing ... and ask some tough questions:
"In the meantime, however, a real dilemma exists for treating physicians and patients taking warfarin. Who to test and how to manage? What dosing nomogram to use? The clinical availability of the genetic testing is limited but presumed soon to be expanding. How or will the genotyping be reimbursed, given these commercially available tests are quite expensive for both CYP2C9 and VKORC1. And should all this be coordinated centrally, since studies have shown that warfarin monitoring can be improved and INR is more frequently in range with the adverse event rates lower when a centralized anticoagulation service is used compared to usual individual physician care."
We must all face these and similar issues and commence our difficult journey down the Critical Path. The future of the public health demands no less.
Remember the media assault on Eli Lilly for suspending it's study of prasugrel last year, assuming malfeasance, substandard results, etc? Let's roll the tape from Matt Herper's dark commentary entitled "Lilly's Scary Silence":
"It's hard to see how that could be any comfort to investors. As is often true, there is a big downside risk to investors ahead of the data release on Nov. 4. But investors should be equally concerned about whether or not Lilly is giving straight answers about its data. If these studies do bode badly for prasugrel, investors have a right to know now. If they don't, Lilly still needs to give a clearer explanation. If the company can't do that, the safest thing is probably to assume the worst and sell the stock."
http://www.forbes.com/sciencesandmedicine/2007/10/25/pharmacuticals-prasugrel-lilly-biz-sci-cx_mh_1026lilly1.html?boxes=relstories
Science doesn't just snap to the whims of investors and reporters...but in case anyone cares here's an update from http://www.fiercebiotech.com
Study Results Show Investigational Drug, Prasugrel, Cuts Risk of Stent-Related Clots by More than Half Versus Clopidogrel
March 29, 2008
Reductions seen as soon as three days and out to 450 days in patients who received either bare metal or drug-eluting stents
CHICAGO, March 29, 2008 /PRNewswire-FirstCall via COMTEX News Network/ -- The investigational antiplatelet drug prasugrel plus aspirin produced a marked and highly statistically significant reduction in the risk of coronary stent thrombosis (ST) - a major concern for physicians and patients with potentially fatal consequences - in patients who received a stent as compared to standard therapy with clopidogrel (Plavix®) plus aspirin (1.13 percent vs. 2.35 percent, p<0.0001), according to a stent analysis from the head-to-head TRITON-TIMI 38 trial.
The findings were presented today by Dr. Stephen Wiviott, an assistant professor of medicine at Harvard Medical School and investigator with the Thrombolysis in Myocardial Infarction (TIMI) Study Group, at the Society for Cardiovascular Angiography and Interventions Scientific Sessions with the American College of Cardiology's Innovation in Intervention: i2 Summit, in Chicago. In addition, the manuscript was simultaneously published online by the British medical journal, The Lancet.
In the TRITON-TIMI 38 trial, whose overall results were previously published, 12,844 of the 13,608 enrolled patients received at least one intracoronary stent. Of those patients, 6,461 received a bare metal stent (BMS), 5,743 patients received a drug-eluting stent (DES), and 640 patients received both BMS and DES at the time of enrollment. Stent thrombosis was a pre-defined secondary endpoint in the trial.
Prasugrel reduced the relative risk of coronary stent thrombosis (a new clot at the implanted stent site) over clopidogrel by 52 percent (1.13 percent vs. 2.35 percent, p<0.0001). In patients who received drug-eluting stents (DES), treatment with prasugrel reduced relative risk by 64 percent over clopidogrel (0.84 percent vs. 2.31 percent, p<0.0001), and by 48 percent in patients who received bare metal stents (BMS) (1.27 percent vs. 2.41 percent, p=0.0009).
In the analysis, prasugrel was consistent in reducing stent thrombosis, compared to clopidogrel, whether assessment occurred early or late (<30 days and greater than or equal to 30 days, out to 450 days, the median duration of therapy), regardless of the type of stent used (bare metal or drug-eluting), and regardless of which academic research consortium (ARC) definition of stent thrombosis was used - definite/confirmed stent thrombosis, definite/confirmed plus probable stent thrombosis, and definite/confirmed plus probable plus possible stent thrombosis. Definite/probable stent thrombosis was reduced by 59 percent in prasugrel-treated patients within 30 days of stent placement (0.64 percent vs. 1.56 percent, p<0.0001), and by 40 percent after 30 days (out to 450 days, 0.49 percent vs. 0.82 percent, p=0.03).
"Stent thrombosis is very serious, given the high risk of mortality. In TRITON, among 210 patients with definite or probable stent thrombosis, 186 (89 percent) either died or experienced an MI as a result of the event," said Francis Plat, M.D., vice president, clinical development, Daiichi Sankyo Company, Limited. "We were excited by the results of this study and the possibility that prasugrel may someday provide an alternative treatment for ACS patients undergoing PCI and receiving coronary stents."
A 19 percent reduction in risk was observed with prasugrel compared with clopidogrel among all patients receiving a stent (9.7 percent vs. 11.9 percent, p=0.0001) in TRITON's primary endpoint of cardiovascular death, non- fatal heart attack, or non-fatal stroke. A 20 percent relative reduction favoring prasugrel was observed in the primary endpoint in patients who received only a bare metal stent (10.0 percent vs. 12.2 percent, p=0.003), and in patients who received only a drug-eluting stent, results showed an 18 percent relative reduction in the primary endpoint favoring prasugrel (9.0 percent vs. 11.1 percent, p=0.019). Fatal stent thrombosis occurred in 18 (0.28 percent) patients treated with prasugrel and 29 (0.46 percent) patients treated with clopidogrel (p=0.10). Of note, of the 210 patients with stent thrombosis, 89 percent either died or had a myocardial infarction associated with the event.
The rate of major bleeding was higher in all patients receiving a stent treated with prasugrel vs. clopidogrel (2.4 percent vs. 1.9 percent, p=0.06). Major bleeding in both DES and BMS prasugrel-treated groups when compared to clopidogrel-treated patients was 3 percent vs. 2 percent (p=0.34 DES) and 2 percent vs. 2 percent (p=0.09 BMS).
In addition to a reduction in the primary endpoint (CV death, non-fatal heart attack, or non-fatal stroke), a significantly lower rate of the composite endpoint of cardiovascular death, heart attack or urgent target vessel revascularization (UTVR) was observed with prasugrel vs. clopidogrel for both bare metal stents (10 percent vs. 12 percent, p=0.009) and for drug- eluting stents (9 percent vs. 11 percent, p=0.004). A significant reduction was also seen in heart attack alone (8 percent vs. 10 percent, p=0.003, BMS and 7 percent vs. 9 percent, p=.006, DES). In DES-implanted patients, regardless of those receiving only sirolimus-eluting or paclitaxel-eluting stents, there was a similar magnitude of event reduction with prasugrel compared to clopidogrel.
For the entire cohort, sub-acute stent thrombosis (24 hours to 30 days) was 0.36 percent in prasugrel-treated patients vs. 1.19 percent in clopidogrel-treated patients (p<0.0001). DES-implanted patients had lower rates of stent thrombosis compared to BMS-implanted patients, and prasugrel was shown to significantly reduce stent thrombosis in DES-implanted patients within the first three days compared to clopidogrel (0.14 percent vs. 0.63 percent, p=0.003) as well as for thromboses that occurred >30 days following the DES implantation (0.42 percent vs. 0.91 percent, p=0.04).
"The reduction in risk seen in patients in this analysis treated with prasugrel over patients treated with clopidogrel is encouraging for high-risk patients with acute coronary syndrome being managed with PCI," said J. Anthony Ware, M.D., Lilly vice president for cardiovascular/acute care.
"It's hard to see how that could be any comfort to investors. As is often true, there is a big downside risk to investors ahead of the data release on Nov. 4. But investors should be equally concerned about whether or not Lilly is giving straight answers about its data. If these studies do bode badly for prasugrel, investors have a right to know now. If they don't, Lilly still needs to give a clearer explanation. If the company can't do that, the safest thing is probably to assume the worst and sell the stock."
http://www.forbes.com/sciencesandmedicine/2007/10/25/pharmacuticals-prasugrel-lilly-biz-sci-cx_mh_1026lilly1.html?boxes=relstories
Science doesn't just snap to the whims of investors and reporters...but in case anyone cares here's an update from http://www.fiercebiotech.com
Study Results Show Investigational Drug, Prasugrel, Cuts Risk of Stent-Related Clots by More than Half Versus Clopidogrel
March 29, 2008
Reductions seen as soon as three days and out to 450 days in patients who received either bare metal or drug-eluting stents
CHICAGO, March 29, 2008 /PRNewswire-FirstCall via COMTEX News Network/ -- The investigational antiplatelet drug prasugrel plus aspirin produced a marked and highly statistically significant reduction in the risk of coronary stent thrombosis (ST) - a major concern for physicians and patients with potentially fatal consequences - in patients who received a stent as compared to standard therapy with clopidogrel (Plavix®) plus aspirin (1.13 percent vs. 2.35 percent, p<0.0001), according to a stent analysis from the head-to-head TRITON-TIMI 38 trial.
The findings were presented today by Dr. Stephen Wiviott, an assistant professor of medicine at Harvard Medical School and investigator with the Thrombolysis in Myocardial Infarction (TIMI) Study Group, at the Society for Cardiovascular Angiography and Interventions Scientific Sessions with the American College of Cardiology's Innovation in Intervention: i2 Summit, in Chicago. In addition, the manuscript was simultaneously published online by the British medical journal, The Lancet.
In the TRITON-TIMI 38 trial, whose overall results were previously published, 12,844 of the 13,608 enrolled patients received at least one intracoronary stent. Of those patients, 6,461 received a bare metal stent (BMS), 5,743 patients received a drug-eluting stent (DES), and 640 patients received both BMS and DES at the time of enrollment. Stent thrombosis was a pre-defined secondary endpoint in the trial.
Prasugrel reduced the relative risk of coronary stent thrombosis (a new clot at the implanted stent site) over clopidogrel by 52 percent (1.13 percent vs. 2.35 percent, p<0.0001). In patients who received drug-eluting stents (DES), treatment with prasugrel reduced relative risk by 64 percent over clopidogrel (0.84 percent vs. 2.31 percent, p<0.0001), and by 48 percent in patients who received bare metal stents (BMS) (1.27 percent vs. 2.41 percent, p=0.0009).
In the analysis, prasugrel was consistent in reducing stent thrombosis, compared to clopidogrel, whether assessment occurred early or late (<30 days and greater than or equal to 30 days, out to 450 days, the median duration of therapy), regardless of the type of stent used (bare metal or drug-eluting), and regardless of which academic research consortium (ARC) definition of stent thrombosis was used - definite/confirmed stent thrombosis, definite/confirmed plus probable stent thrombosis, and definite/confirmed plus probable plus possible stent thrombosis. Definite/probable stent thrombosis was reduced by 59 percent in prasugrel-treated patients within 30 days of stent placement (0.64 percent vs. 1.56 percent, p<0.0001), and by 40 percent after 30 days (out to 450 days, 0.49 percent vs. 0.82 percent, p=0.03).
"Stent thrombosis is very serious, given the high risk of mortality. In TRITON, among 210 patients with definite or probable stent thrombosis, 186 (89 percent) either died or experienced an MI as a result of the event," said Francis Plat, M.D., vice president, clinical development, Daiichi Sankyo Company, Limited. "We were excited by the results of this study and the possibility that prasugrel may someday provide an alternative treatment for ACS patients undergoing PCI and receiving coronary stents."
A 19 percent reduction in risk was observed with prasugrel compared with clopidogrel among all patients receiving a stent (9.7 percent vs. 11.9 percent, p=0.0001) in TRITON's primary endpoint of cardiovascular death, non- fatal heart attack, or non-fatal stroke. A 20 percent relative reduction favoring prasugrel was observed in the primary endpoint in patients who received only a bare metal stent (10.0 percent vs. 12.2 percent, p=0.003), and in patients who received only a drug-eluting stent, results showed an 18 percent relative reduction in the primary endpoint favoring prasugrel (9.0 percent vs. 11.1 percent, p=0.019). Fatal stent thrombosis occurred in 18 (0.28 percent) patients treated with prasugrel and 29 (0.46 percent) patients treated with clopidogrel (p=0.10). Of note, of the 210 patients with stent thrombosis, 89 percent either died or had a myocardial infarction associated with the event.
The rate of major bleeding was higher in all patients receiving a stent treated with prasugrel vs. clopidogrel (2.4 percent vs. 1.9 percent, p=0.06). Major bleeding in both DES and BMS prasugrel-treated groups when compared to clopidogrel-treated patients was 3 percent vs. 2 percent (p=0.34 DES) and 2 percent vs. 2 percent (p=0.09 BMS).
In addition to a reduction in the primary endpoint (CV death, non-fatal heart attack, or non-fatal stroke), a significantly lower rate of the composite endpoint of cardiovascular death, heart attack or urgent target vessel revascularization (UTVR) was observed with prasugrel vs. clopidogrel for both bare metal stents (10 percent vs. 12 percent, p=0.009) and for drug- eluting stents (9 percent vs. 11 percent, p=0.004). A significant reduction was also seen in heart attack alone (8 percent vs. 10 percent, p=0.003, BMS and 7 percent vs. 9 percent, p=.006, DES). In DES-implanted patients, regardless of those receiving only sirolimus-eluting or paclitaxel-eluting stents, there was a similar magnitude of event reduction with prasugrel compared to clopidogrel.
For the entire cohort, sub-acute stent thrombosis (24 hours to 30 days) was 0.36 percent in prasugrel-treated patients vs. 1.19 percent in clopidogrel-treated patients (p<0.0001). DES-implanted patients had lower rates of stent thrombosis compared to BMS-implanted patients, and prasugrel was shown to significantly reduce stent thrombosis in DES-implanted patients within the first three days compared to clopidogrel (0.14 percent vs. 0.63 percent, p=0.003) as well as for thromboses that occurred >30 days following the DES implantation (0.42 percent vs. 0.91 percent, p=0.04).
"The reduction in risk seen in patients in this analysis treated with prasugrel over patients treated with clopidogrel is encouraging for high-risk patients with acute coronary syndrome being managed with PCI," said J. Anthony Ware, M.D., Lilly vice president for cardiovascular/acute care.
And speaking of vapid coverage, an accompanying article in the NEJM that claims the higher use of Vytorin in the US was due to DTC provides no evidence of cause and effect or association. Rather, it does put it's finger on the real reason: Canada health system delayed and restricted access:
"Vytorin has been available in the United States since July 2004 but is still not available on the Canadian market. The use of ezetimibe-containing products in the United States increased sharply with the introduction of Vytorin. Some U.S. clinicians may have adopted the combination cholesterol-lowering product to improve adherence to dual therapy, but this option was not available in Canada. Third, in Canada, publicly funded provincial drug formularies have been conservative in their coverage of ezetimibe. Two of the three provincial government-funded formularies that serve three provinces (Ontario, Quebec, and British Columbia), in which approximately 75% of Canada's population lives, list ezetimibe with prescribing criteria that limit its use to patients in whom the target level of LDL cholesterol has not been achieved with a statin and patients who cannot tolerate or have a contraindication to statins; a third formulary does not even list ezetimibe as a benefit, although it is currently under review. These formulary criteria appear to be consistent with guideline recommendations that favor medication classes for which data on outcomes are available. Public formulary listings often influence medication coverage in private Canadian drug plans.
Oh.
But watch how many media articles cite DTC as the culprit. This is typical of the the quality of the case against DTC.
http://content.nejm.org/cgi/content/full/NEJMsa0801461
"Vytorin has been available in the United States since July 2004 but is still not available on the Canadian market. The use of ezetimibe-containing products in the United States increased sharply with the introduction of Vytorin. Some U.S. clinicians may have adopted the combination cholesterol-lowering product to improve adherence to dual therapy, but this option was not available in Canada. Third, in Canada, publicly funded provincial drug formularies have been conservative in their coverage of ezetimibe. Two of the three provincial government-funded formularies that serve three provinces (Ontario, Quebec, and British Columbia), in which approximately 75% of Canada's population lives, list ezetimibe with prescribing criteria that limit its use to patients in whom the target level of LDL cholesterol has not been achieved with a statin and patients who cannot tolerate or have a contraindication to statins; a third formulary does not even list ezetimibe as a benefit, although it is currently under review. These formulary criteria appear to be consistent with guideline recommendations that favor medication classes for which data on outcomes are available. Public formulary listings often influence medication coverage in private Canadian drug plans.
Oh.
But watch how many media articles cite DTC as the culprit. This is typical of the the quality of the case against DTC.
http://content.nejm.org/cgi/content/full/NEJMsa0801461
It would great if, just once, coverage about clinical trials focused on the unpredictability of science and the inherent difficulty of designing "real world" studies of the effect of drugs that produce desired results, particularly a measurable reversal in biochemistry that contributes to death.
That will not happen with Vytorin, except in the breach. To be sure the original:" these findings plus future biologic and clinical evidence could confirm that the benefits of lowering LDL cholesterol may depend not only on "how low you go" but also on "how you get there."
http://content.nejm.org/cgi/content/full/NEJMe0801608
This is a point that Eric Topol has been making since the first wave of ENHANCE data was released. See Eric's video on his blog:
http://blogs.theheart.org/posts/temple-of-the-ldl-cholesterol
In the end, Vytorin use will fall but for the wrong reasons. Absent information about "how to get there" before prescribing, LDL treatment will still be hit or miss. That's all the ENHANCE study showed. We know that reducing LDL is important but we still lack targeted treatments.
That will not happen with Vytorin, except in the breach. To be sure the original:" these findings plus future biologic and clinical evidence could confirm that the benefits of lowering LDL cholesterol may depend not only on "how low you go" but also on "how you get there."
http://content.nejm.org/cgi/content/full/NEJMe0801608
This is a point that Eric Topol has been making since the first wave of ENHANCE data was released. See Eric's video on his blog:
http://blogs.theheart.org/posts/temple-of-the-ldl-cholesterol
In the end, Vytorin use will fall but for the wrong reasons. Absent information about "how to get there" before prescribing, LDL treatment will still be hit or miss. That's all the ENHANCE study showed. We know that reducing LDL is important but we still lack targeted treatments.
Center for Medicine in the Public Interest is a nonprofit, non-partisan organization promoting innovative solutions that advance medical progress, reduce health disparities, extend life and make health care more affordable, preventive and patient-centered. CMPI also provides the public, policymakers and the media a reliable source of independent scientific analysis on issues ranging from personalized medicine, food and drug safety, health care reform and comparative effectiveness.
