FDA Approves First SGLT2 Inhibitor For Diabetes 1

The FDA said today that it had approved canaglifozin (Invokana, Johnson & Johnson), the first of a new class of diabetes drugs known as sodium-glucose co-transporter 2 (SGLT2) inhibitors. Canaglifozin is indicated to improve glycemic control in adults with type 2 diabetes in conjunction with diet and exercise. The drug has been studied as monotherapy and in combination with other common treatments for type 2 diabetes including metformin, sulfonylurea, pioglitazone, and insulin.

Click here to read the full post on Forbes.

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79-Year-Old Cardiologist Sentenced To 6 Years In Prison For Fen-Phen Fraud Reply

A 79-year-old Florida cardiologist has been sentenced to 7 years in prison for his participation in the Fen-Phen fraud, according to a report by John Martin on Philly.Com. The article notes that other cardiologists have been convicted for similar reasons in the Fen-Phen case, but Tai’s case is unusual because of the length of the sentence.

The cardiologist, Dr. Abdur Razzak Tai, was convicted last September. Here is how the US Department of Justice summarized the case at the time:

Between 1997 and 2009, Tai… reviewed the echocardiograms of more than 1,100 patients who filed claims with the American Home Product Settlement Trust in Philadelphia and falsely certified that the patients’ tests showed that they had sustained heart damage. In reality, many of those claimants had not been harmed.

Click here to read the full story on Forbes.

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Guest Post: Case Report Of Durata Lead Failure Raises Fresh Concerns Reply

Editor’s Note: The following guest post is published with the permission of its author,  Edward J. Schloss, MD, (Twitter ID @EJSMD) the medical director of cardiac electrophysiology at Christ Hospital in Cincinnati, OH.

Case Report Of Durata Lead Failure Raises Fresh Concerns

by Edward J. Schloss, MD

 A case report of a failed St. Jude Medical Durata ICD lead was published yesterday, raising suspicions that this lead may share some of the same potential failure mechanisms of its troubled predecessor, the Riata lead.

St. Jude’s ICD lead troubles date back to early case reports involving the Riata and Riata ST leads that ultimately led to FDA recall in December 2011.  These leads have since been well documented to be subject both to increased electrical failures and structural breakdown of the lead as has been previously reported.

St. Jude’s Durata lead was designed as a successor to the Riata ST lead and continues to be marketed and implanted.  The Durata lead shared a similar design to the predecessor Riata ST lead with the most notable difference being the addition of a outer coating made of the proprietary co-polymer Optim.  This design modification has been promoted to improve abrasion resistance.  It is hoped that this modification, would prevent the most prominent failure mechanism of the Riata family, inside-out abrasion and cable externalization.
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Controversial NIH Chelation Trial Published In JAMA Reply

Final results of the troubled NIH-sponsored TACT trial testing chelation therapy for coronary disease have now been published in JAMA. Last November, when the preliminary results were presented at the American Heart Association meeting, the positive finding in favor of chelation therapy surprised many observers, though the investigators and senior AHA representatives expressed considerable caution  about the proper interpretation of the results. Full publication of the main results should now allow for a more thorough consideration of the trial.

The Trial to Assess Chelation Therapy (TACT) was initially funded by the NIH more than a decade ago to test chelation therapy with EDTA, an alternative medicine therapy received by more than 100,000 people every year but with no evidence base for support. The highly controversial trial was temporarily suspended in 2008 in response to ethical concerns but was then allowed to resume. The trial was also hampered by slow enrollment, eventually resulting in a downsizing of the trial population. To maintain the trial’s power to achieve a meaningful result the follow-up time was increased. (Because of this change, and because the data and safety monitoring board reviewed the data multiple times over the course of the study, the threshold for statistical significance was lowered to 0.036.)

TACT was a double-blind study testing active or placebo infusions of chelation in 1,708 stable patients with a history of MI.  The primary endpoint of the trial– the composite of death, MI, stroke, coronary revascularization, or hospitalization for angina– was significantly lowered in the chelation group:

  • 26% in the chelation group versus 30% in the placebo group (HR 0.82, 0.69-0.99, p=0.035)

Nissen

Steve Nissen

The editorial by the JAMA editors is itself evidence of the extraordinary sensitivity of the TACT trial. The JAMA editors, in a highly unusual situation, discuss their detailed review of TACT and explain their decision to publish the trial. Although they acknowledge multiple limitations of the trial, they defend its value: “reports of rigorous investigations should not be censored because of preexisting ideological positions,” they write.

In his editorial, Steve Nissen agrees with the JAMA editors decision to publish the trial but issues a fierce indictment of the trial and its conduct. The TACT paper, Nissen writes, “represents a situation in which many important limitations in the design and execution of a clinical trial compromise the reliability of the study and render the results difficult to interpret. Unfortunately, the efforts of these investigators fell short of the minimum level of quality necessary to adequately answer the question they sought to investigate.”

Daniel Mark

Daniel Mark

TACT investigator Daniel Mark provided CardioBrief with the following detailed response to Nissen’s criticism. (Nissen declined to respond to Mark.)

In his editorial, Dr. Nissen asserts that the “logical” explanation for the greater withdrawals in the placebo group is that patients were unblinded. He further implies that the CAM sites were more likely to be responsible for such unmasking.

His editorial is written from the perspective of someone who is absolutely sure that the trial results are wrong and his mission is to identify where the flaws originate.

Click here to read the full story on Forbes.

Once Again FDA Rejects Oral Treprostinil For Pulmonary Arterial Hypertension Reply

For the second time the FDA has issued a complete response letter rejecting the new drug application (NDA) of oral treprostinil for the treatment of pulmonary arterial hypertension (PAH) . The manufacturer of the drug, United Therapeutics, said in a press release that it planned to discuss the decision with the FDA.

“We remain confident that oral treprostinil will play an important role in treating PAH and we are committed to working collaboratively with the FDA to accomplish this goal in the most timely and appropriate manner,” said the company’s chairman and CEO.

Treprostinil is a prostacyclin vasodilator that is already approved for the treatment of PAH in an injectable form (Remodulin) and in an inhalable form (Tyvaso). The FDA initially rejected the NDA for the drug last October.

 

Emerging Biomarkers: How Reliable Is The Evidence? Reply

Novel biomarkers are the subject of intense controversy, with a bewildering variety of factions and perspectives seeking to elevate or dismiss any of a large number of proposed new measures. Now a new examination of the literature published online in JAMA Internal Medicine suggests that the evidence base used to evaluate novel biomarkers may be seriously compromised by selective reporting bias.

John Ioannidis led a team of researchers who analyzed 56 meta-analyses of new candidate cardiovascular biomarkers. 49 of the studies had statistically significant results, but 9 studies were compromised by very large heterogeneity, 13 studies were compromised by small-study effects, and 29 studies had an excess of studies with statistically significant results. Only 13 studies had more than 1,000 cases, achieved statistical significance, and had none of the other deficiencies listed above. The meta-analyses that emerged unscathed examined the associations of  glomerular filtration rate and albumin to creatinine ratio in general and high-risk populations with cardiovascular disease mortality and of non–high-density lipoprotein cholesterol, serum albumin, Chlamydia pneumoniae IgG, glycosylated hemoglobin, nonfasting insulin, apolipoprotein B/AI ratio, erythrocyte sedimentation rate, and lipoprotein- associated phospholipase mass or activity with coronary heart disease.

The authors summarized their finding as suggesting that “the effect of biomarkers is exaggerated because the largest studies— which one would expect to produce the most stable estimates— consistently showed smaller effects. In most meta-analyses, too many single studies had reported ‘positive’ results compared with what would be expected on the basis of the results of the largest studies. This suggests that small studies with ‘negative’ results remain unpublished or that their results are distorted during analysis and reporting to seem more prominent.”

In an invited commentary, Steve Nissen writes that evidence-based medicine has been put on a “golden pedestal” but publication basis “is a dark secret that corrupts nearly every aspect of our profession and undermines societal efforts to promote evidence-based medicine.” He cites carotid intima-medial thickness and apolipoprotein B as just two biomarkers in which “the magnitude of the association is probably much smaller than suggested by the definitive meta-analysis.”

Nissen urges investigators to register their studies with ClinicalTrials.Gov, but points out that the site does not support large data sets. “Therefore,” he argues, “society must consider funding the National Library of Medicine to create a public website where authors can post the detailed results of findings that they were unable to publish despite submitting to multiple journals. Finally, we must emphasize to colleagues and trainees that all studies contribute to scientific understanding. We have a moral obligation to our patients to make all research findings available to the broader scientific community.”

 

Embers Of Poldermans Case Still Smoldering Reply

Poldermans

Don Poldermans

A prominent US cardiologist has rebuked Don Poldermans, the cardiovascular researcher at the center of a research scandal in the Netherlands. As reported here previously, Poldermans was fired for scientific misconduct by the Erasmus Medical Center in Rotterdam, where he had been a professor of medicine and the head of perioperative cardiac care. He was widely published and active in the field, serving as a member of the European Society of Cardiology committee for practice guidelines and as the chairperson of the ESC guidelines on pre-operative cardiac risk assessment and perioperative cardiac management in non-cardiac surgery. He was also the lead author of the influential (but controversial) 1999 New England Journal of Medicine DECREASE study on the use of bisoprolol during vascular surgery. An investigation at Erasmus found that Poldermans used patient data without written permission, used fictitious data, and submitted two reports to conferences which included knowingly unreliable data.

The new episode has its origins in a review article published last October by prominent cardiologist University of Michigan cardiologist Kim Eagle, and a colleague, Vineet Chopra, in the American Journal of Medicine. The article, “Perioperative Mischief: The Price of Academic Misconduct,” discusses the “caustic” effects of the Poldermans case, noting the dilemma facing clinicians “now that a considerable portion of the literature is enshrouded in uncertainty.” Now (as first reported by Retraction Watch) Poldermans and the Michigan cardiologists have exchanged letters in the April issue of the journal.

In his letter responding to Eagle and Chopra’s review article, Poldermans is critical of the Michigan authors for accusing him of “scientific fraud.” Poldermans acknowledges in his letter that he made various mistakes, including failure to obtain written informed consent and “negligent” data collection. He denies, however, that he fabricated data or published any results based on the compromised data. He writes that Eagle and Chopra assumed he was guilty despite the fact that the final report from the Erasmus Medical Center had not been released. He notes that in the final report Erasmus had concluded that “no evidence was found for any manipulation of the research results by the researchers in the sense of deliberate steering of results into a particular direction.”

In their response, Eagle and Chopra said that in their article they had stated that the accusations of fraud were still allegations. More importantly, Poldermans missed the larger point of their paper:

Click here to read the full story on Forbes.

Kim Eagle

Kim Eagle

 

 

 

FDA Proposes Higher Regulatory Scrutiny For Automatic External Defibrillators Reply

Automated external defibrillators (AEDs) will have a more difficult time getting on the market if a new FDA proposal is finalized. The agency today proposed a new rule that will require AED manufacturers to submit pre-market approval (PMA) applications.

“Automated external defibrillators save lives,” said cardiologist William Maisel, deputy director of science and chief scientist at the FDA’s Center for Devices and Radiological Health, in an FDA press release. “However, the agency is concerned about the number of recalls and manufacturing problems that have been associated with these devices and we’re committed to working with manufacturers to address these issues.”

Click here to read the full story on Forbes.

 

#984 Airport not in Japan

CHMP And FDA Diverge On Mipomersen And Rivaroxaban Reply

The US FDA and Europe’s Committee for Medicinal Products for Human Use (CHMP) have taken opposite views of two important and controversial new cardiovascular drugs. Although earlier this month the FDA rejected— for the second time– an ACS indication for the oral anticoagulant rivaroxaban (Xarelto), CHMP announced today that it had adopted a positive opinion for the same indication. In contrast, although the FDA recently approved the new cholesterol-lowering agent mipomersen (Kynamro, Isis and Genzyme), CHMP, after reviewing its previous negative position, reaffirmed today that it would not recommend approval of the drug in Europe.

Click here to read the full post on Forbes.

 

European Medicines Agency

 

FDA Panel Gives Tepid Endorsement To Abbott’s MitraClip Reply

The FDA’s Circulatory System Devices advisory panel today gave a tepid endorsement to Abbott Laboratories’ MitraClip device. The panel met to evaluate use of the novel device in patients with significant symptomatic mitral regurgitation (MR) who  have been determined by a cardiac surgeon to be too high risk for open mitral valve surgery and in whom existing co-morbidities would not preclude the expected benefit from correction of the MR.

At the end of the day, after a long and torturous discussion, the panel voted 5-3 in favor of the device, saying that the benefits outweighed the risks. The panel agreed unanimously that the device was safe (8-0) but by a narrow margin (5-4) said there was not a “reasonable assurance” that it was effective. The panel struggled over how to use the available data to identify patient groups that could benefit from the device.

Click here to read the full story on Forbes.

 

Mitraclip

Controversial PFO Closure Trials Published In NEJM Reply

Two controversial trials testing PFO closure with the Amplatzer PFO Occluder (St. Jude Medical) in patients with cryptogenic stroke, first presented last fall at the TCT meeting, have now been published in the New England Journal of Medicine. Both trials missed their primary endpoints but contained suggestions of possible benefit. The results appear unlikely to resolve the ongoing controversy over the value, or lack of value, of this procedure, but, as an accompanying editorial states, both advocates and critics of PFO closure will find source material for their arguments in these papers.

In the accompanying editorial, Steven Messé and David Kent write that both trials suffered from slow enrollment, “which was probably due to widespread off-label use of atrial septal closure devices.” They note that RESPECT and PC, like the only other randomized trial in the field, CLOSURE 1, did not show significant benefits in the main intention-to-treat analysis, but did present some evidence of possible benefit.

They conclude:

…we are left for the moment to make decisions under conditions of uncertainty. In such circumstances, evidentiary standards vary among decision makers — patients, clinicians, authors of practice guidelines, and regulatory authorities — depending not only on the interpretation of the results, but also on the potential consequences of their decisions. Some of them may interpret the data as supporting closure of a patent foramen ovale as a viable therapeutic option, even while conceding the failure of trials to show the superiority of closure over medical therapy. Yet given the prevalence of patent foramen ovale in the general population, the enormous potential for overuse of percutaneous closure of a patent foramen ovale, and the relatively low risk of stroke in patients who are treated medically, the routine use of this therapy seems unwise without a clearer view of who, if anyone, is likely to benefit…. Randomized studies of closure may come to an end, however, if the Amplatzer device is approved. Thus, all eyes will be on the regulatory agencies to see how they will interpret these results in light of their own evidentiary standards.

Click here to read the entire story on Forbes.

 

Amplatzer

 

 

 

High Potency Statins Linked To Increased Risk For Acute Kidney Injury Reply

Although the beneficial effects of high-potency statins have been well-characterized in clinical trials, these same trials have lacked the power to illuminate rare but potentially important adverse events. A suggestion of one such area of concern, acute kidney injury, was first raised in the JUPITER trial. Now, a new study published in BMJ provides further information about this area.

Researchers in the Canadian Network for Observational Drug Effect Studies (CNODES) performed a retrospective observational analysis of administrative databases in Canada, the UK and the US containing more than 2 million patients newly treated with statins.  59,636 of the subjects already had chronic kidney disease. One-third of the subjects received high potency statins, defined as ≥10 mg rosuvastatin, ≥20 mg atorvastatin, and ≥40 mg simvastatin.

Within 120 days of starting treatment there were 4691 hospitalizations for acute kidney injury in patients without pre-existing kidney disease and 1896 hospitalizations in patients with pre-existing disease. Patients without pre-existing disease on high potency statins were 34% more likely to be hospitalized with acute kidney injury than patients on other statin regimens. Patients with pre-existing disease did not have a significant increase in risk if they were taking high potency statins.

The authors estimated that 1,700 patients without pre-existing kidney disease would need to be treated with a high potency statin instead of a low potency statin to cause one additional acute kidney injury requiring hospitalization. The findings, according to the authors, are broadly consistent with the JUPITER trial. They write:

Given what is likely to be a small magnitude of incremental cardiovascular benefit of high potency statins over low potency statins in reality, a pressing question is how to identify patients for whom the risk-benefit balance for high potency statin treatment is unfavourable.

In an accompanying editorial, Robert Fassett and Jeff Coombes write that “clinicians should use low potency statins whenever possible to provide cardiovascular benefits without the increased risk of acute kidney injury.” Further, they note, “despite extensive experience with the use of statins over many years, optimization of doses to derive benefit but minimize risk is still evolving.”

Vena Cava Filters: Little Evidence And Wide Variation In Use Reply

Despite the absence of any evidence demonstrating benefit or showing how best to use them, vena cava filters (VCF) are used in most hospitals. Now a new study published in JAMA Internal Medicine suggests that this same lack of evidence results in an extremely broad rate of use in different hospitals. An accompanying viewpoint raises the question: “how could a medical device be so well accepted without any evidence of efficacy?”

Researchers conducted a retrospective observational study that compared the frequency of VCF use in 236 California hospitals by analyzing data from 130,643 acute VTE hospitalizations over four years. Overall, the rate of VCF placement was 14.95%, but there was a very broad variation in the percentage of acute VTE cases in which a VCF was placed, from 0% to 38.96%. The authors said that this finding places VCF “among surgical procedures with the greatest variation in geographic studies in the United States.” Even after adjusting for differences in patient populations between hospitals, the variation between hospitals remained significant.

Click here to read the full story on Forbes.

English: Taken by user:BozMo URL at http://cat...

English: Taken by user:BozMo URL at http://catesfamily.org.uk Picture of used inferior vena cava filter, showing the hook at top for removal via Jugular Vein, the umbrella structure and the leg spikes to fix in place. (Photo credit: Wikipedia)

The PREVAIL Fail Revisited: Spinning The Truth 1

SPIN
The biggest story at the American College of Cardiology meeting last week was the missing story. As reported here and just about everywhere else, the PREVAIL trial, probably the most-anticipated late-breaker of the meeting, was pulled from the program at the last minute by the ACC leadership after Boston Scientific broke the embargo by issuing a press release several hours before the scheduled presentation.

To understand this event we first need to know what happened in the week before the ACC. And there’s a major gap in the story that has not come out before that I think holds the key to a full understanding of the story.

More than a week before the scheduled presentation I received an email invitation from a PR firm representing Boston Scientific:

“If you have any interest in speaking about the trial under embargo with Dr. Ken Stein, chief medical officer, Cardiac Rhythm Management, Boston Scientific, I have a few slivers of availability early next week. As you know, the embargo lifts at the time of presentation and I’ll need written confirmation of your embargo agreement.”

Now I’ve been down this road before, as some of you may recall. Several years ago I was offered embargoed access to data from an important upcoming trial by Medtronic (suggesting that this is a systemic problem) under the condition that I agree to a briefing from a trial investigator. I told the company that I would respect the embargo but that I wanted to review the data on my own and that I would get back to them if I had any questions. Their response: no briefing, no data.

Here’s the problem in both cases: forcibly linking access to the trial data with a company-arranged briefing is an egregious perversion of the embargo system.

Click here to read the full post on Forbes.

 

FDA Officials Calm Concerns Over Excessive Bleeding With Dabigatran 1

Concerns over excessive bleeding complications with dabigatran (Pradaxa, Boehringer Ingelheim) as compared with warfarin are most likely due to the heightened sensitivity and vigilance that can accompany a new drug, according to FDA officials in a perspective published online in the New England Journal of Medicine.

“We believe that the large number of reported cases of bleeding associated with dabigatran provides a salient example of stimulated reporting,” write Mary Ross Southworth, Marsha Reichman, and Ellis Unger. “In this case, such reporting provided a distorted estimate of the comparative bleeding rates associated with dabigatran and warfarin in clinical practice.”

Click here to read the full story on Forbes.

 

Radiotherapy For Breast Cancer Increases Heart Disease Risk 1

A new study published in the New England Journal of Medicine offers the best look yet at the increased risk for heart disease produced by radiotherapy for breast cancer. Further, this increased risk may just be the tip of the iceberg of more radiation-related problems, warns a cardio-oncologist in an accompanying editorial.

The new study, based on data from Sweden and Denmark of women treated with radiotherapy for invasive breast cancer, found a linear increase in the rate of heart disease associated with the dose of radiation received by the heart. Starting 5 years after radiotherapy, and with no sign of a threshold,  the risk for major coronary events increased by 7.4% per gray. The mean dose of radiation was 4 Gy. Although the relative risk was consistent throughout the study, the increase in absolute risk was greatest in women with cardiac risk factors or established heart disease.

Findings from the study, according to the authors, “make it possible to estimate” a patient’s risk for heart disease related to radiation. “This absolute risk can be weighed against the probable absolute reduction in her risk of recurrence or death from breast cancer that would be achieved with radiotherapy.” The authors estimated that for a 50-year-old woman without preexisting risk factors and with a mean radiation exposure of 3 Gy, her risk for death from ischemic heart disease by age 80 would rise from 1.9% to 2.4% and her risk for an acute coronary event would rise from 4.5% to 5.4%. The risk for death by age 80 for an otherwise similar woman with existing risk factors would rise from 3.4% to 4.1%. Women exposed to larger doses of radiation would be exposed to even greater risks.

In the accompanying editorial, Javid Moslehi writes that results of the study suggest that “cardiac risk factors should be assessed and aggressively managed — starting at the time of radiation treatment (or even before) and continuing throughout survivorship.” To make matters worse, the findings “may represent just the tip of the iceberg.” Radiation may also cause increases in pericardial disease, peripheral vascular disease, cardiomyopathy, valvular dysfunction, and arrhythmias, according to Moslehi, and other breast cancer therapies, such as anthracyclines and hormonal therapies, may have “additional cardiotoxic effects.”

Moslehi, who is in the Cardio-Oncology Program at the Dana–Farber Cancer Institute, writes about the emerging new discipline of “cardio-oncology”:

Given the widespread use of radiation therapy in the treatment of breast cancer, and the continually expanding arsenal of novel therapies, the current study calls for greater collaboration between oncologists and cardiologists. An important lesson for the oncologist may be that the time to address concerns about cardiovascular “survivorship” is at the time of cancer diagnosis and before treatment rather than after completion of therapy. Similarly, cardiologists need to assess prior exposure to radiation therapy as a significant cardiovascular risk factor in survivors of breast cancer.

Two Trials Explore On-Pump Versus Off-Pump Bypass Surgery Reply

Two large trials presented at the American College of Cardiology meeting in San Francisco and published simultaneously in the New England Journal of Medicine provide important new information about the ongoing debate over whether CABG should be performed with or without cardiopulmonary bypass. The combined results suggest that both techniques can be effective, and that surgeons should choose the technique with which they are most familiar and comfortable.

Previous 30-days results from CORONARY (CABG Off or On Pump Revascularization Study), which randomized 4,752 patients to on-pump or off-pump CABG, showed no significant difference in the primary outcome (death, MI, stroke, or new renal failure requiring dialysis) between the two groups. However, patients in the off-pump group required more repeat revascularization procedures, though they had lower rates of bleeding, acute kidney injury, and respiratory complications.

Now, one-year results from CORONARY have found no significant difference in the primary outcome between the groups at 1 year (12.1% in the off-pump group versus 13.3% in the on-pump group (HR 0.91, CI 0.77-1.07, p=0.24). There were also no significant differences in the individual components of the endpoint. In addition, there were no significant differences in recurrent angina (1% versus 0.9%) or the need for repeat revascularization (1.4% versus 0.8%).

A quality of life substudy found no differences between the two groups at any time point in the first year. A neurocognitive substudy found less deterioration in one assessment of neurocognitive function in the off-pump group at discharge but found no significant differences at 30 days or at 1 year. There were no differences at any time between the two groups in two other tests of neurocognitive function.

“The CORONARY study shows that off-pump bypass is just as good as on-pump. Therefore, surgeons should tailor their surgical approach to their technical expertise and expected technical difficulty,” said Andre Lamy, lead author of the study, in an ACC press release.

In the GOCABE (German Off-Pump Coronary Artery Bypass Grafting in Elderly Patients) study, 2,539 patients 75 years of age or older were randomized to on-pump or off-pump CABG. The primary endpoint was the composite of death, stroke, MI, repeat revascularization, or new renal-replacement therapy at 30 days and one year.

At 30 days there was no significant difference in the primary endpoint: 7.8% for the off-pump group versus 8.2% for the on-pump group (OR 0.95, CI 0.71-1.28, p=0.74). However, there were more repeat revascularizations in the off-pump group at 30 days: 1.3% versus 0.4%, OR 2.42, CI 1.03-5.72, p=0.04. At one year there were no significant differences between the groups in the composite endpoint (13.1% versus 14%, HR 0.93, CI 0.76-1.16, p=0.48) or in any of the individual components of the composite endpoint.

The authors write that their trial “does not support the assumption that off-pump CABG can improve the early outcome in high-risk patients.”

During the discussion section lead investigators for both studies, Anno Diegeler for GOCABE and Andre Lamy for CORONARY, emphasized that their results depended on having expert surgeons highly qualified in both techniques.

Choice of the technique, said Diegeler, should depend on clinical characteristics, patient choice, and surgeon experience.

Chris Cannon, a panel discussant, asked the question:”why would you want to do off-pump since it’s no better and it’s harder to do?” At the ACC news conference, Mark Davies said that “these trials may temper our enthusiasm for off-pump surgery.” In the US, with the advent of publicly reported STS (Society for Thoracic Surgeons) scores for individual hospitals and amateurs, there will no room for amateurs. “If you’re an amateur at it you should give it up.” Neil Kleiman had a recommendation: “if you’re going to do it you damn well better be good at it… there’s no room for sloppiness.”

 

Was Atherosclerosis The Real Curse Of The Mummy? 2

From a growing evidence base of mummies, researchers are now concluding that atherosclerosis may have been common in people who lived in premodern times. A new study presented at the ACC in San Francisco and published simultaneously in the Lancet appears likely to challenge the common belief that atherosclerosis is largely a phenomenon of the modern era.

MummySeveral years ago investigators first reported finding evidence of atherosclerosis in 20 of 44 Egyptian mummies. Now an international group of researchers has extended this research and performed whole body CT scans on 137 mummies from four different places and times– ancient Egypt, ancient Peru, southwest America, and the Aleutian Islands.

Probable or definite atherosclerosis was observed in 34% (47) of the 137 mummies:

  • 38% (29 of 76) from ancient Egypt.
  • 25% (13 of 51) from ancient Peru
  • 40% (2 of 5) from Ancestral Puebloans
  • 60% (3 of 5) from Unangan hunter gatherers

Atherosclerosis was found in a variety of vascular beds and was correlated with the age of the mummy at the time of death. The authors wrote:

“Our findings greatly increase the number of ancient people known to have atherosclerosis and show for the first time that the disease was common in several ancient cultures with varying lifestyles, diets, and genetics, across a wide geographical distance and over a very long span of human history. These findings suggest that our understanding of the causative factors of atherosclerosis is incomplete, and that atherosclerosis could be inherent to the process of human ageing.”

Although the populations from which the mummies came did not smoke cigarettes, the authors point out that “the need for fire and thus smoke inhalation could have played a part in the development of atherosclerosis.” They also speculate that high levels of infections might have contributed to the development of atherosclerosis in this population.

Another Negative Trial With Darbepoetin Alfa 1

Once again a trial testing the erythropoiesis-stimulating agent darbepoetin alfa (Aranesp, Amgen) has produced a negative result. Results of the RED-HF (Reduction of Events by Darbepoetin Alfa in Heart Failure) trial were presented at the ACC in San Francisco and published simultaneously in the New England Journal of Medicine.

A total of 2278 patients with systolic heart failure and mild-to-moderate anemia were randomized to darbepoetin alfa (Aranesp, Amgen) or placebo. As expected, treatment with darbepoetin alfa significantly improved hemoglobin levels. However, no significant improvements in outcomes were associated with darbepoetin alfa.

Click here to read the full story on Forbes.

 

Eplerenone May Help Prevent Heart Failure In Acute STEMI Patients Reply

A new trial presented at the ACC in San Francisco suggests that the mineralocorticoid receptor antagonist eplerenone Pfizer, Inspra) may help prevent the development of heart failure when given acutely in STEMI patients without preexisting heart failure.

In the REMINDER trial 1,012 STEMI patients were randomized to eplerenone or placebo. After 10.5 months of followup, the primary endpoint– the time to CV mortality, rehospitalization or extended initial hospital stay due to diagnosis of HF, sustained ventricular tachycardia or fibrillation, EF ≤40% after 1 month, or an elevation of BNP/NT-proBNP after 1 month– occurred in 18.4% of the eplerenone group versus 29.6% of the placebo group ((HR, 0.581; 95% CI; 0.449-0.753; P<0.0001).

Click here to read the full story in Forbes.

Fibrinolysis May Benefit Late-Arriving STEMI Patients Reply

Although primary PCI has emerged as the best treatment for STEMI, most patients don’t receive this treatment within the early time frame when it is known to be most beneficial. Delay in presentation is one important factor. Another is that most patients don’t arrive at a PCI-capable hospital and cannot be transferred fast enough to a PCI hospital.

The STREAM (Strategic Reperfusion Early after Myocardial Infarction) trial was planned as a proof-of-concept study to assess whether fibrinolysis was a beneficial alternative in this difficult group. Results were presented at the ACC in San Francisco and published simultaneously in the New England Journal of Medicine.

Click here to read the full story on Forbes.

Cangrelor During PCI May Reduce Ischemic Events Reply

In the Cangrelor versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition (CHAMPION PHOENIX) trial, the intravenous platelet inhibitor cangrelor was tested for its effect on ischemic events associated with PCI. Cangrelor is a potent, fast-acting and reversible  agent. Results of the trial were presented at the ACC in San Francisco and published simultaneously in the New England Journal of Medicine.

A total of 11,145 PCI patients were randomized to a bolus and infusion of cangrelor or to a loading dose of clopidogrel. A primary endpoint event — death, MI, ischemia-driven revascularization, or stent thrombosis at 48 hours — occurred in 4.7% of the cangrelor group versus 5.9% of the clopidogrel group (adjusted OR, 0.78; 95% CI, 0.66-0.93; P=0.005). The authors calculated that 84 patients would need to be treated with cangrelor instead of clopidogrel to prevent one primary endpoint event.

Note to readers: Don’t miss this fascinating post on CardioExchange in which CHAMPION PHOENIX co-chair Deepak Bhatt responds to questions raised by Rick Lange and David Hillis in their New England Journal of Medicine editorial.

Click here to read the full story on Forbes.

HPS2-THRIVE: A ‘Disappointing But Clear’ Result Reply

The results of HPS2-THRIVE were “disappointing but clear,”  said Jane Armitage, who presented the results this morning at the ACC in San Francisco.

HPS2-THRIVE randomized 25,673 high-risk patients who could tolerate niacin to either placebo or extended-release niacin plus laropiprant (Tredaptive, Merck), an anti-flushing agent, in addition to background therapy. The primary endpoint was the time to first major vascular event, defined as the composite of non-fatal MI or coronary death, any stroke or any arterial revascularization.

Major vascular events occurred in 13.2% of the niacin arm and 13.7% of the placebo arm (p=0.29), despite causing average reductions in LDL of 10 mg.dL and triglycerides of 33 mg/dL, in addition to a 6 mg/dL increase in HDL. Armitrage reported that based on data from previous trials and observational studies, “it was anticipated such lipid differences might translate into a 10-15% reduction in vascular events.”

HPS2-THRIVE study chairman, Rory Collins, responded to a question in the press conference: “To the question is niacin dead? Well, it’s not healthy!”

Click here to read the full story on Forbes.

 

Following An Embargo Break PREVAIL Trial Won’t Be Presented At ACC 2

UPDATED–The already complicated story behind the PREVAIL trial, which was designed to confirm the safety and efficacy of the Watchman left atrial appendage closure device, just got even more complicated. This morning, after the trial’s sponsor, Boston Scientific, prematurely distributed to investors a press release summarizing the results of the trial, the ACC announced that the scheduled presentation of the results at the main opening session of the meeting would not take place.

 

By way of background, last week the trial’s sponsor, Boston Scientific, first announced that the  principal investigator of the trial, David Holmes, would only “present the acute procedural safety results” from the trial. Then the company reversed itself two days later and announced that Holmes would present all three co-primary endpoints.

Holmes intended presentation this morning at the ACC in San Francisco makes clear why there was so much confusion. (The slides from his presentation have been made available to the media.) Although the trial results appear largely positive, the trial missed one of its three primary endpoints, and experts will likely spend a lot of time and energy trying to interpret the results.

Click here to read the full story on Forbes.

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Hospitals Seeing Rapidly Growing Numbers Of Adults With Congenital Heart Disease 3

Hospitals are treating increasing numbers of adults with congenital heart disease, thanks to tremendous progress in treatment for this condition in recent decades. A clear picture of this dramatic change emerges in a new study, presented at the ACC in San Francisco and published simultaneously in JAMA.

Jared O’Leary and colleagues analyzed data from the Nationwide Inpatient Sample and compared congenital heart disease hospital admissions from 1998 through June 30, 2004, with those from July 1, 2004, through 2010. From the first period to the second, adult admissions grew much more rapidly than pediatric admissions.

  • Adult admissions increased by 87.8%, from 331,162 in the first half to 622,084 in the second half.
  • Pediatric admissions increased by 32.8%, from 815,471 to 1,082,540.

Adults constituted a growing percentage — from 28.9% to 36.5% — of congenital heart disease admissions.

The authors wrote that the “observed trend is likely due to a number of independent forces including better congenital heart disease survival, an aging population, and accumulating comorbidities. Limited availability of quality outpatient services may also contribute.”