The controversy surrounding the FDA’s cardiorenal advisory committee meeting, and in particular the “disinvitation” of Sanjay Kaul from the meeting, has prompted two separate congressional investigations. (Click here to see CardioBrief’s chronology of events.)
As reported by Susan Heavey in Reuters, Rep. Bart Stupak, the chairman of the House Energy and Commerce Subcommittee on Oversight and Investigations is writing letters of inquiry to the FDA and to Lilly.
Separately, Rep. Maurice Hinchey, a member of the House Appropriations Subcommittee on Agriculture, Rural Development, FDA, and Related Agencies, which allocates the FDA’s budget, sent a letter to the FDA’s Janet Woodcock, in which he asks:
“How can we trust the FDA if a drug maker like Eli Lilly can get a potential agency advisor that it doesn’t like disqualified from submitting an opinion?”
Click here to view Rep. Hinchey’s press release and letter to Janet Woodcock.
Astellas Pharma announced today that it was launching a hostile takeover for CV Therapeutics, the company that manufactures ranolazine (Ranexa) and regadenoson (Lexiscan).
As we reported back in January, CV Therapeutics previously rejected a friendly bid at the same price from Astellas. Astellas already markets regadenoson in the US.
Astellas offered an explanation for the hostile takeover: “While we continue to prefer to reach a negotiated agreement with CV Therapeutics’ Board, their refusal to engage with us regarding our proposal has left us with no alternative but to take our offer directly to CV Therapeutics’ stockholders. We believe our offer provides CV Therapeutics’ stockholders with immediate cash value that exceeds what the company could reasonably expect to deliver on it own, particularly given current uncertain market conditions and execution risks inherent in CV Therapeutics’ standalone strategy.”
Click here to read the Astellas press release…
Using data from the Framingham Heart Study, researchers have developed a predictive tool that can help identify people who are at risk of atrial fibrillation, according to a new study in the Lancet. In addition to age, other factors associated with AF were sex, BMI, systolic BP, treatment for hypertension, PR interval, clinically significant heart murmur, and heart failure.
“Primary prevention of atrial fibrillation has not been on our radar; even secondary prevention of the arrhythmia has not been recommended in the wake of the AFFIRM,” note David Brieger and Ben Freedman in Australia, in an accompanying comment. Given that AF “is associated with a doubling of the… mortality rate…particularly within the first 4 months of diagnosis…. few would argue against the assertion that an ounce of prevention is worth a pound of cure. This predictive model is the first step in that direction.”
Click to read the Lancet’s press release…
Just in case you haven’t heard anything about prasugrel in the last 10 minutes, the STEMI substudy from TRITON-TIMI 38 has been published in the Lancet, along with an accompanying editorial by Gregg Stone. The results are consistent with the main study. The authors conclude that “prasugrel is an especially attractive alternative to clopidogrel to support PCI in the course of management of patients with STEMI.”
In his editorial, Stone agrees that the overall results of the trial are applicable to the STEMI subgroup, but notes that the trial was conducted in the era before the 600 mg clopidogrel dose became standard in primary PCI. In addition, Stone points out that patients who received secondary PCI did not benefit from clopidogrel preloading. By applying “the art of clinical decision making,” Stone concludes that “balancing ischaemic and haemorrhagic risk through careful selection of patients and personalised pharmacotherapy should result in improved outcomes.”
Click here to read commentary from Harlan Krumholz and a press release from Lilly…
The FDA provided CardioBrief with a transcript of a news conference that took place on February 23 with Janet Woodcock, director of the Center of Drug Evaluation and Research, and John Jenkins, Office of New Drugs. They spoke with reporters from Bloomberg, Reuters, and Dow Jones.
Although the transcript does not contain any significant information not already published, it might provide CardioBrief readers with a deeper insight into the thought process of the FDA.
Click here for more…
Cardiovascular events account for nearly half of all deaths among dialysis patients. Although antihypertensive agents have been found to reduce CV events in the general population, their effect in dialysis patients has been uncertain. Now a new meta-analysis in The Lancet shows that treating dialysis patients with antihypertensive agents could reduce all cause mortality by 20%, and cardiovascular events and mortality by 29%.
However, an accompanying comment by Charles Tomson, of Southmead Hospital in Bristol, UK, notes that many nephrologists will remain “reluctant to prescribe antihypertensive drugs” to dialysis patients except for those with high blood pressure throughout “the dialysis cycle becasue of permanent but subclinical volume expansion.”
In a comparison of diets that were high or low in fat, carbohydrates, or protein, no significant differences were observed after two years, according to a new study in the New England Journal of Medicine. Weight loss in the 811 patients randomized in the study reached an average of 6 kg at 6 months. By 1 year patients began to put weight back on. At 2 years the average weight loss was 4 kg.
Click here for commentary on the study…
It’s starting to become clear that there won’t be a cardiologist in charge of the FDA. Duke’s Rob Califf, the last of two cardiologists rumored to be in the running for FDA commissioner, is no longer a contender for the influential position, according to The Washington Post and The Scientist. (The Cleveland Clinic’s Steve Nissen had earlier been viewed as another prime candidate.)
In the Washington Post item, Al Kamen reports that the two finalists are now Joshaua Sharfstein, who is the Baltimore health commissioner, and new entry Margaret Hamburg, an assistant secrety of HHS in the Clinton administration. The Scientist notes that Califf’s candidacy was derailed after Tom Daschle’s candidacy for HHS secretary was itself derailed.
Over the years there’s been an explosion in ACC/AHA guideline recommendations, but the evidence to support most recommendations has declined, according to a new report in JAMA.
The authors, including major cardiology leaders Sidney Smith and Robert Califf, conclude: “Our finding that a large proportion of recommendations in ACC/AHA guidelines are based on lower levels of evidence or expert opinion highlights deficiencies in the sources of definitive data available for the generation of cardiovascular guidelines. To remedy this problem, the medical research community needs to streamline clinical trials, focus on areas of deficient evidence, and expand funding for clinical research. In addition, the process of developing guidelines needs to be improved with information about the impact that recommendations based on lower levels of evidence has on clinical practice. Finally, clinicians need to exercise caution when considering recommendations not supported by solid evidence.”
An accompanying editorial, by Terrence Shaneyfelt and Robert Centor, is harshly critical of the current situation:
Click here to continue reading…
The failure rate of Medtronic’s Sprint Fidelis leads may be much higher than previous estimates, according to a new report by Robert Hauser and David Hayes in HeartRhythm. The two investigators (Hauser was the first to spot the problems with the Medtronic leads) looked at the rate of lead failure among patients who received the leads at the Mayo Clinic and the Minneapolis Heart Institute. Lead failure was significantly higher in the group that received the Sprint Fidelis leads (3.75%/year vs 0.58%).
Click here to continue reading…
In response to our post yesterday, in which we reported that Columbia University’s Jeffrey Moses $2.5 million compensation package in 2006-2007 vaulted him to 8th place in the Chronicle of Higher Education’s list of highest total compensation at private colleges for 2006-2007, CardioBrief received a message from Mt. Sinai’s Samin Sharma. According to WikiPedia, Sharma performs 1,500 complex coronary interventions each year, which apparently is an American record. Sharma wanted to let us know that the Chronicle‘s list failed to include Sharma’s own salary of $2.75 million, which would have put him ahead of Moses. Click here for more, including the salaries of NYC’s top cardiac surgeons…
Anger can increase the risk of sudden death, at least in patients who already have ICDs, according to a new study published in the Journal of the American College of Cardiology. Yale investigators gave T-wave alternans tests to ICD patients during a mental stress protocol. Patients with positive TWA tests were much more likely to have ICD shocks than patients with negative TWA tests.
“More research is needed, but these data suggest that therapies focused on helping patients deal with anger and other negative emotions may help reduce arrhythmias and, therefore, sudden cardiac death in certain patients,” said Yale’s Rachel Lampert, in an ACC press release. It’s important to note, however, that the study provides no evidence whatsoever for the therapeutic effects of anger management and similar therapies.
Click here to read the ACC press release…
Medtronic announced today that it has entered into an agreement to acquire CoreValve, and that it had acquired Ventor Technologies. Both companies develop transcatheter aortic valves.
Medtronic said the Ventor acquisiton “adds two technologies to Medtronic’s transcatheter valve portfolio: a minimally invasive, surgical transapical technology and a next generation percutaneous, transfemoral technology.” CoreValve is a leader in the emerging field of percutaneous aortic valve replacement.
Medtronic will pay at least $700 million for CoreValve and paid $325 for Ventor.
Click here to read 2 press releases from Medtronic…
Prasugrel has gained European approval for the prevention of atherothrombotic events in patients with ACS undergoing PCI, according to the drug’s sponsors, Daiichi Sankyo and Lilly. The drug will be marketed under the brand name Efient.
Earlier this month prasugrel received a positive recommendation for approval from the FDA’s Cardiorenal advisory committee, although the hearing has generated a certain amount of controversy. (See the right hand column for a complete list of our previous coverage.)
Click here to read the Daiichi Sankyo/Lilly press release…
A football coach tops the list at $4.4 million, and a Columbia dermatologist followed closely at $4.4 million, but Jeffrey Moses $2.5 million salary was enough to put him in 8th place in the Chronicle of Higher Education‘s list of highest total compensation at private colleges for 2006-2007. The article notes that college president’s salaries are often outstripped by medical faculty, traditionally the biggest earners, and financial officers. Five of the top 20 salaries went to specialists in in vitro fertilization, all of whom worked at NYU or Weill Medical College of Cornell University.
Moses, a well known interventional cardiologist at New York-Presbyterian Hospital, is the director of the Center for Interventional Vascular Therapy and director of the Cardiac Catheterization Lab, as well as a Professor of Medicine and the vice president of the Cardiovascular Research Foundation.
The Chronicle assembled the data on pay based on data from the IRS Form 990. You can also read a story in the New York Times.
Rosuvastatin can cut the risk of stroke by nearly half, according to the results of a substudy from JUPITER presented at the International Stroke Conference in San Diego.
“Today’s analysis of the JUPITER data clearly indicated that people who were smokers, over 70 years of age, had high blood pressure, or were at greater overall risk for cardiovascular disease, as well as those with elevated hsCRP levels, received notable benefit from treatment with rosuvastatin 20mg,” said Dr. Jacques Genest, Director, Cardiology Division, McGill University Health Centre, in a press release from AstraZeneca Canada.
As in the main trial, the absolute numbers are somewhat less impressive than the relative risk reduction, however. According to Mark Alberts, MD, as quoted by Susan Jeffrey in a Medscape Medical News story:
“While the relative risk reduction was fairly impressive, the absolute risk reduction, because the event rates were very low, is obviously more modest. So I think the challenge for clinicians and researchers is to figure out what characteristics put those roughly 100 people at increased risk for having stroke so you can better target therapy.”
Click here to read the AstraZeneca press release…
Initial phase 2 results for an anti-atherosclerotic agent that inhibits sPLA2 are encouraging, according to a new report and commentary published in the Lancet. In a dose-ranging study of 393 patients with stable coronary disease, the experimental drug A-002 (Anthera Pharmaceuticals) reduced sPLA2 by 87% and also caused reductions in LDL cholesterol and CRP levels.
Click to continue reading
The US Department of Justice has joined two whistleblower lawsuits against Johnson & Johnson, “alleging that the companies marketed the cardiac drug Natrecor for a use not approved by the Food and Drug Administration (FDA) and caused false and fraudulent claims to be submitted to the federal health care programs,” according to a Justice Dep’t press release.
Click to continue reading…
In response to queries from CardioBrief, an FDA spokesperson, Sandy Walsh, has provided the most detailed explanation yet of the sequence of events leading to the withdrawal of Sanjay Kaul from the Cardiorenal advisory committee meeting for prasugrel.
Previously the FDA told CardioBrief that “the FDA did not receive sufficient information until much later than we would prefer…” In response, we observed that according to our understanding FDA committee members undergo a very detailed and rigorous review process over a period of several months.
The FDA has now modified its earlier position about this. Here is the spokesperson’s response:
Click to continue reading…
The globalization of clinical research is raising a number of troubling ethical and scientific concerns, according to a new article by Duke researchers in the New England Journal of Medicine. The problems discussed in the article include patient selection, transparency of results, regulatory oversight, experience of clinical investigators, and IRB quality. Coauthors of the paper include well-known Duke cardiologists Eric Peterson, Robert Harrington, and Robert Califf.
Click to continue reading…
The SYNTAX trial, which compared CABG to PCI in patients with 3-vessel or left main coronary disease, has been published in the NewEngland Journal of Medicine. The trial found that CABG was superior to PCI at one year, but the results have generated considerable controversy. As always, the devil is in the details.
An editorial by Richard Lange and L. David Hillis concludes that patient data needs to be reviewed by both a cardiac surgeon and an interventional cardiologist “to determine the likelihood of safe and effective revascularization with PCI and with CABG.” The implication here, then, is that “revascularization should not be performed at the time of diagnostic angiography.” This of course would entail an enormous change in standard clinical practice, at least in the United States. The SYNTAX score, which is largely an assessment of complex coronary anatomy, should play an important role in the decision in most patients who do not have a clear indication or contraindication for either procedure.
The NEJM also posted an online discussion about SYNTAX with Betsy Nabel and David Hillis moderated by Thomas Lee. Nabel notes that the difference in the primary endpoint of SYNTAX was driven largely by an increase in the need for revascularization in the PCI group, while in the CABG group there was a higher incidence of stroke.
Click here to view a discussion about SYNTAX with Patrick Serruys and C. Michael Gibson on ClinicalTrialResults.Com.
David Kandzari commented on the trial for CardioBrief:
Click here to continue reading…
Despite a marginal advantage at 4 months, after two years PCI does not improve the quality of life when compared to medical therapy after late opening after MI, according to a new report from the Occluded Artery Trial Investigators published in the New England Journal of Medicine. In addition, PCI, as expected, is more expensive than the medical approach.
In a separate report, published in Circulation earlier this week, OAT investigators reported the electrophysiologic effects of late PCI in their trial. They found that late PCI had no effect on heart rate variability, signal-averaged ECG, or T-wave variability. Click here to view the OAT slideset on ClinicalTrialResults.Com.
Click here to read commentary on OAT from William Boden and David Kandzari…
Using a pharmacogenetic algorithm to estimate the initial warfarin dose is better than using the usual clinical or fixed-dose approaches, according to a new study from the Imternational Warfarin Pharmacogenetics Consortium published in the New England Journal of Medicine. The benefits of the pharmacogenetic algorithm were especially noticeable in those…
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Raising HDL, by itself, has no effect on coronary heart disease rates, according to a large new analysis in the British Medical Journal. An international team analyzed 108 clinical trials including nearly 300,000 patients and found no correlation between changes in HDL and outcome. By contrast, changes in LDL were strongly associated with outcome. The authors write: “Raising high density lipoprotein cholesterol without considering effects on high density lipoprotein function seem to have little promise for the prevention of cardiovascular events.”