Category Archives: Uncategorized

FDA Advisory Committee Recommends Against ACS Indication For Rivaroxaban Reply

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The FDA’s Cardiovascular and Renal Drugs Advisory Committee voted against adding an indication for acute coronary syndromes (ACS) to the label  of the anticoagulant rivaroxaban (Xarelto). The vote was 6 to 4 against approval, with 1 abstention.

The advisory panel spent most of the day trying to reconcile diametrically opposed views of the pivotal ATLAS ACS 2-TIMI 51 trial. On the one hand, the sponsor (Johnson & Johnson) and the TIMI investigators (Jessica Mega, C. Michael Gibson, and Eugene Braunwald) portrayed a robustly positive trial that strongly demonstrated the beneficial effects of low dose rivaroxaban in ACS when added to dual antiplatelet therapy. On the other hand, one FDA reviewer, Medical Team Leader Tom Marciniak, raised multiple questions about the validity of the trial and its conclusions because of an alarming amount of early withdrawals and missing data. His view was largely endorsed by several committee members, including Steve Nissen and Sanjay Kaul.

In a press release, J&J said it “will ensure the questions raised today are addressed with the FDA.”

See my previous post for a detailed live account of the advisory committee meeting.

Rivaroxaban For ACS Gets Positive FDA Review, But Questions About ATLAS Trial Conduct Persist 2

by • MI/ACS, Uncategorized • Tags: , ,

The FDA will offer generally positive but also highly mixed advice to the FDA’s Cardiovascular and Renal Drugs Advisory Committee  when it meets on Wednesday to consider the supplemental new drug application for rivaroxaban (Xarelto, Johnson & Johnson) for use in patients with acute coronary syndrome (ACS) already taking dual antiplatelet therapy. The FDA posted the briefing documents on its website this morning.

Although the primary clinical review and the statistical review support approval for the new indication (the drug is already approved for venous thromboembolism prophylaxis and stroke prevention in AF), one reviewer, Thomas Marciniak, the Medical Team Leader, issued a blistering memorandum suggesting that the supporting data, plagued by missing and inconsistent records in the pivotal ATLAS ACS 2-TIMI 51 trial, “may not support the favorable statistical results.”

The primary clinical reviewer, Karen Hicks, recommended approval for the 2.5 mg BID dose (but not the 5 mg dose) of rivaroxaban for ACS. She noted that the lower dose reduced the combined endpoint of CV death, nonfatal MI, or nonfatal stroke  in the ATLAS trial, with most of the benefit driven by a reduction in CV death, with little or no difference in MI or stroke. The higher 5 mg dose increased bleeding risk in the trial without providing additional efficacy, she concluded. She did not recommend a mortality indication for the label. Her views generally coincide with the reception of the ATLAS trial following its presentation and publication in the New England Journal of Medicine.

It should be noted that Hicks hedged her endorsement with a potentially significant caveat:
Click to continue reading…

Meta-Analysis Compares Drug-Eluting and Bare-Metal Stents for Primary Angioplasty Reply

by • Interventional Cardiology & Surgery, MI/ACS, Uncategorized • Tags: , , , , ,

A new meta-analysis comparing drug-eluting stents (DES) and bare-metal stents (BMS) in patients with myocardial infarction has provoked opposing take-away messages from an author of the study and an editorialist. The authors emphasize the reduction in target-vessel revascularization (TVR) associated with DES, but the editorialist focuses on several potential DES weaknesses suggested by the study.

In the paper, published in Archives of Internal Medicine, members of the Drug-Eluting Stent in Primary Angioplasty (DESERT) Cooperation pooled patient data from more than 11 clinical trials in which more than 8,600 patients were randomized to either sirolimus-eluting or paclitaxel-eluting stents or BMS.  After a mean follow-up of 1201 days, DES was associated with a significant reduction in TVR but there were no significant differences in death, reinfarction, or stent thrombosis (ST):

  • TVR: 12.7% for DES vs 20.1% for BMS, HR 0.57, CI 0.50-0.66, p<.001
  • Mortality: 8.5% vs 10.2%, HR 0.85, CI 0.70- 1.04, p = .11
  • Reinfarction: 9.4% vs 5.9%, HR 1.12, CI 0.88-1.41, p = .36
  • Stent thrombosis: 5.8% vs 4.3%, HR 1.13, CI 0.86-1.47, p = .38

However, after two years there was a significant increase in the risk of stent thrombosis associated with the DES group (HR 2.81, CI 1.28-6.19, p=0.04).

The findings, write the authors,

provide strong evidence of the beneficial effects of SES and PES during primary PCI in STEMI. With follow- up as late as 6 years, a robust and sustained decrease in TVR was noted with use of these DES. Although the rates of late reinfarction and ST progressively increased, with the difference becoming statistically significant after 2 years in patients receiving SES and PES, the HR for mortality, while not significantly different between DES and BMS, favored DES.

Click to continue reading, including a comment from Gregg Stone…

Improved Survival After Non-Shockable Cardiac Arrest With New CPR Guidelines Reply

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In recent years resuscitation guidelines have evolved to emphasize chest compressions. At the same time, a greater proportion of out-of-hospital cardiac arrest (OHCA) cases are now due to “nonshockable” rhythms, defined as asystole and pulseless electrical activity, but the effect of the new guidelines on these type of OHCA cases is unknown.

In a study published in Circulation, Peter J. Kudenchuk and colleagues report on more than 10 years of experience treating nearly 4,000 out-of-hospital patients with unshakable OHCA treated in King County, Washington. Midway through the study period the new AHA guidelines came into effect. Overall, outcomes were poor in both groups, but several important measures were significantly improved during the second half of the study:

  • 1-year survival: 2.7% in the first half versus 4.9% in the second half (adjusted hazard ratio: 1.85, CI 1.29-2.66)
  • Return of spontaneous circulation: 27% versus 34% (HR 1.50, CI 1.29–1.74)
  • Discharged from hospital: 4.6%) versus 6.8% (HR 1.53, CI 1.14–2.05)
  • Favorable neurological outcome: 3.4% versus 5.1 (HR 1.56, CI 1.11–2.18)

“By any measure — such as the return of pulse and circulation or improved brain recovery — we found that implementing the new guidelines in these patients resulted in better outcomes from cardiac arrest,” said Kudenchuk, in an AHA press release. He calculated that 2,500 lives could be saved each year in North America by fully implementing the new guidelines.
Click here to read the AHA press release…

Bariatric Surgery Turns Back the Clock on Diabetes 2

by • Prevention, Epidemiology & Outcomes, Uncategorized • Tags: , , ,

Two new randomized trials offer new evidence that bariatric surgery is highly effective in obese patients with diabetes. The results, according to Paul Zimmet and K. George M.M. Alberti, writing in an editorial in the New England Journal of Medicine, “are likely to have a major effect on future diabetes treatment.”

In the STAMPEDE trial, which was presented at the American College of Cardiology and published simultaneously in the New England Journal of Medicine,  150 obese patients with uncontrolled type 2 diabetes were randomized to medical therapy alone or medical therapy plus either Roux-en-Y gastric bypass or sleeve gastrectomy. Philip Schauer presented the main results.

Percent of patients with glycated hemoglobin level of 6% or less at 1 year:
Click to continue reading…

Rivaroxaban Found Safe and Effective for Pulmonary Embolism Reply

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In recent years rivaroxaban has been found to be effective in the prevention of venous thromboembolism (VTE) after orthopedic surgery, for the prevention of stroke in AF patients, and as additional therapy to conventional antiplatelet therapy in ACS patients. Now, a study presented at the American College of Cardiology meeting in Chicago and published simultaneously in the New England Journal of Medicine offers strong evidence that rivaroxaban is equally effective as standard therapy for the treatment of pulmonary embolism and may cause fewer bleeding complications.

EINSTEIN-PE was a randomized, open-label, non-inferiority study comparing rivaroxaban to conventional therapy with enoxaparin and a vitamin K antagonist in 4,833 patients with pulmonary embolism. Rivaroxaban met the predefined margin for noninferiority to conventional treatment with respect to both clinical efficacy and safety.

Primary efficacy endpoint (first symptomatic recurrent VTE):

  • 2.1%  for rivaroxaban patients versus 1.8% for standard therapy (HR 1.12, CI 0.75-1.68, p=0.0026 for noninferiority)

Principal safety outcome (major or clinically relevant bleeding):

  • 10.3% versus 11.4% (HR 0.90, CI 0.76-1.07, p=0.23 for noninferiority)

Major bleeding was significantly lower in the rivaroxaban group:

  •  1.1% versus 2.2% (HR 0.49, p=0.0032)

Net clinical benefit (VTE plus major bleeding):

  • 3.4% versus 4% (HR 0.85, CI 0.63-1.14, p=0.28)

“Physicians want to know about major bleeding, the most important safety outcome, and rivaroxaban was highly significantly superior. This was our most astonishing finding,” said EINSTEIN chair Harry Buller in an ACC press release. “Rivaroxaban is just as good as standard treatment for PE – these data are pretty convincing – and this is an oral-only approach, which makes it very simple. The subcutaneous injections can be hazardous as well.”

The EINSTEIN investigators concluded that, in conjunction with the earlier EINSTEIN trial in DVT, the EINSTEIN PE trial supports “the use of rivaroxaban as a single oral agent for patients with venous thromboembolism.”
Click here to read the press release from the ACC…

Study Supports CT Angiography to Rule Out CAD in Chest-Pain Patients Reply

by • MI/ACS, Uncategorized • Tags: , ,

Six million people each year in the US go to the emergency department (ED) with acute chest pain. Although only 10-15% of them turn out to have an acute coronary syndrome (ACS), most are admitted to the hospital. Coronary CT angiography (CCTA) has been proposed as a good method to quickly establish the presence or absence of coronary disease and  allow many of these patients to return home sooner.

In a presentation at the ACC and in a simultaneous publication in the New England Journal of Medicine, the ACRIN (American College of Radiology Imaging Network) investigators report the findings of ACRIN PA 4005, the largest trial to date of the strategy to use coronary CT angiography to allow more rapid rule out of coronary disease in patients with possible acute coronary syndrome, in which 1,370 patients with chest pain were randomized on a 2:1 basis to either CCTA or conventional treatment.

The primary outcome was the safety at 30 days of patients with a negative CCTA. Among the 640 patients who had a negative CCTA examination, there were no MIs or cardiac deaths at 30 days.

The investigators also observed that, compared with controls, patients in the CCTA group were more likely to be discharged from the emergency department (49.6% versus 22.7%) and to have a shorter length of stay (18 hours versus 24.8 hours). Coronary disease was also more likely to be detected in the CCTA group (9% versus 3.5%).

Utilization of healthcare resources was similar in both groups. The major drawback to CCTA is radiation, but ACRIN investigator Harold Litt pointed out that the radiation dose received by patients for CCTA is now lower than the dose received during nuclear imaging studies.

“We believe that a CCTA-based strategy can safely and efficiently redirect many patients home who would otherwise be admitted,” the authors concluded.

Study Supports PCI Without Onsite Surgical Backup Reply

by • Interventional Cardiology & Surgery, Uncategorized • Tags: ,

Here’s a great example of genuine medical progress: 10% of the first 50 patients who received balloon angioplasty from the developer of the procedure, Andreas Grüntzig, required emergency bypass surgery. By 2002 only 0.15% of PCI patients required emergency surgery, leading many to believe that surgical backup was no longer necessary.

Now a large new study provides strong evidence that PCI can in fact be performed safely and effectively at hospitals without surgical backup. In a presentation at the American College of Cardiology and published simultaneously in the New England Journal of Medicine. Thomas Aversano and colleagues in the Cardiovascular Patient Outcomes Research Team (C-PORT) report  the results of a trial that randomized 18,867 patients to undergo PCI at hospitals with or without surgical backup.

  • 6 week mortality was 0.9% at hospitals without surgical backup versus 1% at hospitals with surgical backup, which was well within the predefined margin of noninferiority of a 0.4% difference in risk (p=0.004).
  • The 9-month composite rate of death, Q-wave MI, or target-vessel revascularization was 12.1% and 11.2%, which met the predefined margin of noninferiority of a 1.8% difference in risk (p=0.05).

The authors noted that high risk patients were excluded from the study, raising the possibility that the study population may differ from the general PCI population.

“The study shows that under certain circumstances, non-primary angioplasty can be performed safely and effectively at hospitals without on-site cardiac surgery,” said Aversano, in an ACC press release.

At an ACC press conference, Aversano discussed the potential impact of the study and warned against interpreting the study as an open invitation to implement PCI without surgical backup:

It doesn’t say you ought to go out and do this and expand it willy nilly, that was not the purpose of this project… These hospitals did not simply buy stents and start doing angioplasty. They went through a formal development program.

 

Novel Antiplatelet Agent Reduces CV Events But Increases Bleeding 1

by • MI/ACS, Uncategorized • Tags: ,

Vorapaxar, the novel antiplatelet agent from Merck, appears to effectively reduce cardiovascular death and ischemic events in patients with MI, ischemic stroke, or peripheral vascular disease, but its potential utility is clouded by bleeding complications, including intracranial hemorrhage. Results from the TRA 2P-TIMI 50 (Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events) trial were presented in Chicago on Saturday at the American College of Cardiology and published simultaneously in the New England Journal of Medicine.

Results of TRA 2P-TIMI 50 were broadly consistent with the TRACER trial (published last November in the New England Journal of Medicine), which tested the same drug in patients with acute coronary syndromes. In that trial also, vorapaxar effectively reduced negative outcomes but at the cost of an increase in serious bleeding complications. Earlier optimism over the drug had been greatly reduced in January 2011 when the combined data and safety monitoring board (DSMB) of the two trials stopped the TRACER trial and curtailed the TRA 2P-TIMI 50 trial.

TRA 2P-TIMI 50 randomized 26,449 patients with a history of MI, ischemic stroke, or peripheral arterial disease to either vorapaxar or placebo in addition to standard therapy. Because of an increased risk of intracranial hemorrhage in patients with a history of stroke, at 2 years the DSMB stopped treatment with vorapaxar in patients with a history of stroke.

At 3 years the rate of CV death, MI, or stroke was significantly reduced by vorapaxar, but there were also more bleeding events associated with the drug:

CV death, MI, or stroke: 9.3% in the vorapaxar group versus 10.5% in the placebo group (HR 0.87, CI 0.80-0.94, p<0.001)

  • CV death: 2.7% versus 3.0% (HR 0.89, p=0.15)
  • MI: 5.2% versus 6.1% (HR 0.83, p=0.001)
  • Stroke: 2.8% in both groups

Moderate or severe bleeding: 4.2% versus 2.5% (HR 1.66, p<0.001)

  • Intracranial bleeding: 1% versus 0.5% (HR 1.94, p<0.001)

The TIMI investigators reported that in the subgroup of patients with a qualifying diagnosis of MI vorapaxar caused a 20% reduction in the primary endpoint. In light of the heightened risk for stroke patients, the investigators also performed a separate analysis of patients without a history of stroke and found “a significant benefit” in this group.

In an ACC press release, lead investigator David Morrow said: “In the lab, we have seen very compelling science showing the importance of thrombin’s action on platelets causing blood clots in arteries. This is the first study to show definitively that blocking this pathway reduces the risk of suffering another cardiovascular event.”

Click here to download a PDF of the ACC press release for TRA 2P-TIMI 50. Readers should note that the press release does not mention the bleeding complications until the second page of the press release.  In sharp contrast, the press release from Merck discloses the bleeding complications in the first paragraph.

Meta-Analysis Adds New Evidence For Cancer Benefits Of Daily Aspirin 1

by • Prevention, Epidemiology & Outcomes, Uncategorized • Tags: , ,

Although daily aspirin was originally proposed to reduce cardiovascular events, the effects on cancer of daily aspirin have become increasingly apparent while the vascular benefits, especially in primary prevention, have become less clear. Now a new meta-analysis in the Lancet adds significantly new details to our understanding about the effects of aspirin and increases the evidence in support of a long-term beneficial effect of aspirin in preventing cancer.

Peter Rothwell and colleagues analyzed data from 51 primary and secondary prevention trials including more than 80,000 patients. They reported several key findings

  • Daily aspirin reduced deaths from cancer by 15% (p=0·008).
  • After 5 years, there was a particularly striking 37% reduction in cancer deaths (p=0·0005), which largely accounted for a reduction in non-vascular deaths overall (p=0·003).
  • Aspirin was associated with an initial reduction in major vascular events, but this was offset by increases in major bleeding. With longer followup the vascular effects diminished, so that after 3 years only the reduced risk of cancer was significant.

The authors wrote that “in view of the very low rates of vascular events in recent and ongoing trials of aspirin in primary prevention, prevention of cancer could become the main justification for aspirin use in this setting…”

In an accompanying comment, Andrew Chan and Nancy Cook point out that the meta-analysis did not include the two largest primary prevention studies, the Women’s Health Study and the Physician’s Health Study, because they used alternate-day aspirin rather than daily aspirin. Both trials failed to find an effect on cancer. Nevertheless, they write, the researchers “show quite convincingly that aspirin seems to reduce cancer incidence and death across different subgroups and cancer sites, with an apparent delayed effect.”

“For most individuals, the risk-benefit calculus of aspirin seems to favour aspirin’s long-term anticancer benefit,” they state. However, current evidence does not support “a definitive conclusion about population-based recommendations regarding routine use of aspirin for cancer prevention.” They conclude that in the future guidelines “can no longer consider the use of aspirin for the prevention of vascular disease in isolation from cancer prevention.”
Click here to read the press release from the Lancet…

Eric Topol, Megamind 2

by • Prevention, Epidemiology & Outcomes, Uncategorized • Tags: , ,

Ralph Waldo Emerson famously wrote that “a foolish consistency is the hobgoblin of little minds.” If this is true then Eric Topol, who earlier today wrote a New York Times editorial highly critical of statins, is Megamind.

Here’s what he wrote in a 2004 editorial in the New England Journal of Medicine:

Even today, only a fraction of the patients who should be treated with a statin are actually receiving such therapy. It is estimated on the basis of the criteria in current national guidelines that 36 million people in the United States should be taking a statin, but only 11 million are currently being treated. Worldwide, the discrepancy is even more staggering; more than 200 million people meet the criteria for treatment, but fewer than 25 million take statins.

…

There will soon be a sea change in the prevention and management of atherosclerotic vascular disease. The proportional reduction in major clinical outcomes that results from aggressive statin therapy is of the same order of magnitude as that seen when statins were compared with placebo in controlled trials. Intensive therapy with statins, monitored by means of measurements of LDL cholesterol or biologic markers of inflammation, is likely to result in even greater steps toward actualizing the full benefit of this remarkable class of medicines.

To be fair, I think Topol deserves credit for being willing to change his mind. It’s a rare trait. But I’m not sure that every single current controversy in medicine should be seen in the light of a crusade in favor of genomics, so when a cardiologist with a long memory sent me this editorial I couldn’t resist posting this blast from the past.

Update: In all fairness, here is Dr. Topol’s response to the above post:

The op-ed on the risk of diabetes from statins had nothing to do with changing my mind. It has everything to do with new data that were not available in 2004. As I pointed out in the Times op-ed, the diabetes issue only surfaced in recent trials with higher doses (40 mg of Simvastatin) and atorvastatin (Lipitor) and rosuvastatin (Crestor). Prior to these trials, there was no signal about the risk of diabetes. The trial my NEJM editorial was written on in 2004–PROVE IT–showed no difference in diabetes for intensive vs moderate statins (5.9% in both groups). All of the subsequent intensive statin randomized trials–TNT, IDEAL, SEARCH showed an important excess. Even folding PROVE-IT to the mix, collectively the excess of an absolute 0.8% equates to developing diabetes in 1 of every 125 patients treated with intensive statins compared with moderate dose statins.

JUPITER, one of the largest trial of statins, with 17,802 patients, was not published until 2008, nor did we have diabetes data available from many of the other placebo-controlled trials until after 2004.The initial HPS trial primary report published in 2002 did not even mention the diabetes risk, which only came out much later!

Furthermore, this is not a crusade about genomics, which is a baseless point. This op-ed was aimed at consumers, who have every right to know the real data, the real risks and benefit of primary prevention with potent statins. The fact that we are in 2012, and have recognized the problem of statins engendering diabetes for the past 4-5 years, have no clue for why it occurs, and that nothing has been done about it in the medical community or by the life science industry, is truly remarkable.
Finally the author of this blog and I have a history of working together for many years on theheart.org — as a journalist he should recuse himself of writing on this subject with clearcut evidence of bias.

 

 

Metaanalysis Raises More Questions About Routine Use of Aspirin for Primary Prevention Reply

by • Prevention, Epidemiology & Outcomes, Uncategorized • Tags: , , ,

Although aspirin can reduce the risk of cardiovascular (CV) events, the associated increase in bleeding suggests that it should not be used routinely in  people without prior CV disease, say the authors of a new meta-analysis published in Archives of Internal Medicine.

Sreenivasa Rao Kondapally Seshasai and colleagues combined data from 9 clinical studies including more than 100,000 participants who were followed for a mean of 6 years. They found a significant reduction in CV events, but not CV mortality, and an increased risk of important bleeding events:
Click to continue reading…

Meta-Analysis Confirms Benefits Of Statins In Women Reply

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Although clinical trials have consistently found a beneficial effects for statins, some critics have questioned the strength of the evidence in women, who are often under-represented in clinical trials.  A large new meta-analysis published in the Journal of the American College of Cardiology provides the best evidence yet that the relative reductions in events observed in men also occur in women, but doesn’t provide evidence about the absolute risk benefit in women.

William Kostis and colleagues analyzed data from 18 randomized trials of primary and secondary prevention, including 141,235 men and 40,275 women.  The reduction in risk was similar for both groups:
Click to continue reading…

Consensus Document Provides Roadmap To Uptake Of TAVI In US 2

by • Interventional Cardiology & Surgery, Uncategorized • Tags: , , ,

Following the recent approval by the FDA of transcatheter aortic valve replacement (TAVR), the ACC, AATS, SCAI, and STS, in conjunction with several other medical organizations, have released a critical consensus document to guide use of the new landmark procedure.

“We have tried to collate the evidence into a coherent road map for judicious use, rational dispersion, and careful post-marketing scrutiny of this promising technology,” said Sanjay Kaul, vice chair of the writing committee, in a press release. “It is now the collective responsibility of all the stakeholders to optimize its full potential for improving the duration as well as the quality of survival in patients with severe symptomatic aortic valvular stenosis.”

Here are some of the key recommendations identified by the committee:

–Careful patient selection

–Team-based approach given the complexity of procedure coupled with the high-risk profile of suitable patients, many of whom have extensive comorbid conditions that require ongoing management

–Specialized heart centers and physician expertise in treating valve disorders; this includes use of proctors as needed to serve on the heart care team during the first few cases, as well as proper facilities (hybrid operating rooms or modified cath labs)

–TAVR screening tests to inform treatment decisions

–Enhanced patient and family education in the risk and benefits of this procedure

–Ongoing evaluation and participation in national TAVR registry to assess real world outcomes

The document also emphasizes the groups for whom TAVR is not recommended:

–An acceptable surgical risk for conventional surgical AVR

–Known bicuspid aortic valve

–Severe mitral annular calcification or severe MR

–Moderate AS

–Other (e.g., severe AR and subaortic stenosis)

Click here to read the press release from the ACC, AATS, SCAI, and STS…

ACC 2012 Roster of Late-Breaking Clinical Trials Reply

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The American College of Cardiology has released the roster of late-breaking clinical trials that will be presented in March at the ACC Scientific Sessions:

ACC.12 Opening Session and Late-Breaking Clinical Trials
Saturday, March 24, 2012, 8:00 a.m. – 10:00 a.m.

Effect of Transendocardial Autologous Bone Marrow Mononuclear Cell Delivery on Functional Capacity, Left Ventricular Function and Perfusion in Chronic Ischemic Heart Failure: The FOCUS Randomized Trial

  • Emerson C. Perin, James Willerson, Stephen Ellis, Timothy Henry, Carl Pepine, David Zhao, Dejian Lai, Barry Byrne, Antonis Hatzopoulos, Marc Penn, Jay Traverse, Adrian Gee, Marvin Kronenberg, Daniel Martin, James Thomas, Doris Taylor, Christopher Cogle, Sonia Skarlatos, Lem Moye, Robert Simari, Cardiovascular Cell Therapy Research Network (CCTRN), Houston, TX, USA

Evaluation of a Novel Antiplatelet Agent for Secondary Prevention in Patients with Atherosclerotic Disease: Results of the Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events (TRA 2°P): TIMI 50 Trial

  • David A. Morrow, Brigham & Women’s Hospital, Boston, MA, USA

Late-Breaking Clinical Trials II
Sunday, March 25, 2012, 8:00 a.m. – 9:30 a.m.

Outcomes of Non-Primary PCI at Hospitals with and without On-site Cardiac Surgery:CPORT-E Trial. Final Medical Outcomes

Click to continue reading…

NHLBI Launches Two Large Cardiac Arrest Treatment Trials Reply

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The NHLBI today announced the launch of two large clinical trials evaluating treatments for out-of-hospital cardiac arrest.

The Continuous Chest Compressions (CCC) trial will randomize 23,600 people with out-of-hospital cardiac arrest to either standard CPR or continuous chest compressions, both delivered by paramedics or fire fighters. In recent years, studies published in the New England Journal of Medicine,  JAMA, and the Lancet have provided evidence that continuous chest compressions may be preferable to traditional CPR. Graham Nichol is the principal investigator.

“The CCC trial will help to determine if continuous compressions is equal to or better than standard professional CPR when paramedics, who are better able to provide assisted breathing than bystanders, intervene,” said Nichol, in an NHLBI press release.

The Amiodarone, Lidocaine, or neither (Placebo) for Out-Of-Hospital Cardiac Arrest Due to Ventricular Fibrillation or Tachycardia study (ALPS) will randomize 3,000 people with shock-resistant VF to amiodarone, lidocaine or placebo. Although amiodarone and lidocaine are often given when shock treatment fails in VF patients, a beneficial effect of the drugs has never been demonstrated in this setting. Peter Kudenchuk is the principal investigator.

Both trials are part of the NIH-supported Resuscitation Outcomes Consortium (ROC), which the NIH describes as “the first large-scale clinical research network in the world designed to study, improve, and standardize how EMS teams deliver very early, pre-hospital interventions to improve patient survival after cardiac arrest or trauma.”

Click here to read the NHLBI press release…

Big Drop in Incidence and Fatality of MIs in England Reply

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Since 2002 in England the incidence of acute MI has dropped by one-half and the case fatality rate by one-third, according to a new study published in BMJ. The overall decline in deaths from MI are about equally due to improvements in the prevention of MI and the treatment of MI.

Kate Smolina and colleagues analyzed data from 861,134 acute MI patients in England from 2002 through December 2010. Over the course of the study period, the MI event rate declined:
Click to continue reading…

Huge Study Finds Risk Factors Do In Fact Predict Risk 1

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An enormous new meta-analysis confirms the important role that risk factors play over a lifetime in the development of cardiovascular disease. In a paper published in the New England Journal of Medicine, Jarett Berry and colleagues report on the new meta-analysis from the Cardiovascular Lifetime Risk Pooling Project, which contains data from 18 epidemiological studies including more than one-quarter of a million people whose risk factors– blood pressure, cholesterol level, smoking status, and diabetes status– were measured every decade between 45 and 75 years of age.

At age 55, compared to people with two or more risk factors, people with an optimal risk factor profile had a greatly reduced risk of death from CV disease  or CHD through the age of 80:
Click to continue reading…

FDA Rejects Proposed Chronic Kidney Disease Indication for Vytorin Reply

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The FDA rejected a new indication for Merck’s Vytorin and Zetia (ezetimibe plus simvastatin and ezetimibe alone) in chronic kidney disease patients. As a consolation prize, however, the agency approved a new label for Vytorin that will incorporate the results of SHARP (Study of Heart and Renal Protection), which found that Vytorin reduced the incidence of major vascular events in patients with chronic kidney disease.

Merck said that the indication was not approved because the “independent contributions of ezetimibe and simvastatin were not assessed.” In a press release, Merck stated:

Because SHARP studied the combination of simvastatin and ezetimibe compared with placebo, it was not designed to assess the independent contributions of each drug to the observed effect; for this reason, the FDA did not approve a new indication for VYTORIN or for ZETIA® (ezetimibe) and the study’s efficacy results have not been incorporated into the label for ZETIA.

The FDA decision appears to run counter to the advice it received from its own advisory committee last November, which voted 16-0 in favor of an indication for Vytorin in pre-dialysis patients. However, the committee also recommended against an indication for dialysis patients. The committee did not vote on an indication that would have included the entire SHARP population of pre-dialysis and dialysis patients.

Since its initial presentation in November 2010 and its subsequent publication in the Lancet in June 2011, the interpretation of SHARP has been the subject of considerable debate, much of it carried over from the earlier, even more intense debate about ARBITER 6, which centers on what, if any, additional benefit ezetimibe confers to statin therapy. In the end, the FDA appeared to adopt the perspective of James Stein, who provided the following perspective to CardioBrief on SHARP when it was initially presented:

… this study does not answer the question of whether or not they would have gotten the same result if they used simvastatin alone (ie, if ezetimibe had anything to do with the observed results) or if ezetimibe is safe, since a short study of individuals with advanced kidney disease is not the right context to study drug safety.  But, it is a nice study to re-assure us that even in people with advanced kidney disease, statins are helpful, and it is a mark in favor of ezetimibe,  because it is a RCT that used ezetimibe and reduced events.  It just does not tell us if simvastatin alone would have done the same thing.

Click here to read the press release from Merck…

Whistleblower Lawsuit Filed Against 5 Cardiologists in Pennsylvania Reply

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The US government has joined a cardiologist in a whistleblower lawsuit against Hamot Medical Center  in western Pennsylvania  and a group of cardiologists with whom he once practiced, Ed Palattella reports in the Erie Times-News.

Cardiologist Tullio Emanuele, who now practices in Kentucky, has accused five former colleagues, members of Medicor Associates Inc. and its affiliate, Flagship Cardiac, Vascular and Thoracic Surgery of Erie, of billing Medicare for unnecessary angioplasty and other procedures. Hamot Medical Center  is now affiliated with the University of Pittsburgh Medical Center.

The lawsuit, according to the Times-News, alleges that the contracts the cardiologists had with Hamot Medical Center were “sham arrangements intended to disguise the actual purpose of Hamot to pay kickbacks to Medicor and Flagship CVTS in exchange for patient referrals.”
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Black Tea Found To Lower Blood Pressure Reply

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A new study published in Archives of Internal Medicine provides the best evidence yet that drinking black tea can lower blood pressure. Jonathan M. Hodgson and colleagues randomized 95 regular tea drinkers to either 3 cups per day of either black tea (containing 429 mg of polyphenols and 96 mg of caffeine) or placebo.

At 3 and 6 months, the mean 24-hour ambulatory BP was lower in the tea group than in the placebo group:
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St Jude Medical Statement on the Riata ICD Lead Summit 2

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In response to the guest post summarizing the Riata ICD Lead Summit, St. Jude Medical sent the following statement to CardioBrief:

We recognize that the phenomenon of externalized conductors presents a complex patient management scenario for physicians who may be able to visualize an anomaly, but it is important to remember that most leads with externalized conductors continue to function properly.
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Rita Redberg and Roger Blumenthal Clash Over Statins for Primary Prevention in the Wall Street Journal 8

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The debate over whether statins should be used for primary prevention moved to the Wall Street Journal with opposing perspectives from cardiologists Roger Blumenthal and Rita Redberg.

Blumenthal argues that “there is a mountain of high-quality scientific evidence” to support the use of statins in people without known heart disease but “demonstrated to be at high risk for heart disease.”

Redberg argues that “for most healthy people, data show that statins do not prevent heart disease, nor extend life or improve quality of life. And they come with considerable side effects. That’s why I don’t recommend giving statins to healthy people, even those with higher cholesterol.”
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Guest Post: Report from the Riata ICD Lead Summit 7

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Second update: Click here to review the slides from the meeting (posted by the Minneapolis Heart Institute),

Update: Click here to read a statement from St Jude Medical in response to this post.

Editor’s Note: Edward J. Schloss (Twitter ID @EJSMD), the medical director of cardiac electrophysiology at the Christ Hospital in Cincinnati, OH, returned yesterday from the Riata ICD Lead Summit. Dr. Schloss has kindly forwarded his summary of the meeting to CardioBrief. “As the audience was restricted to clinicians and St. Jude personnel, this may be the first and only public account of this meeting,” wrote Dr. Schloss. (As the editor of CardioBrief, I would like to express my keen disappointment that a meeting of this general importance was closed to outside observers, including journalists, analysts, and representatives from other companies.)

 Report from the Riata ICD Lead Summit

by Dr. Edward J. Schloss

Sixty-three registered health care professionals and St. Jude Medical industry representatives gathered today at the Minneapolis Airport Marriott Hotel for the Riata ICD Lead Summit. This conference, organized by The Minneapolis Heart Institute Foundation and Mayo Clinic, was organized to review available data and develop a consensus regarding St. Jude ICD leads currently on recall or subject to increased scrutiny.

Course directors Robert G. Hauser, MD and David L. Hayes, MD presided over a series of lectures and panels of experts in the field.

Dr. Hayes first polled the conference attendees about the current landscape. A full 35% of attendees thought Riata leads posed a greater concern to them than the Medtronic Fidelis recall. In addition, 41% felt enough concern about the currently marketed Durata lead that they have elected not to implant this lead. The Durata lead, although not on recall, shares many design elements with the Riata ST.

Dr. Hauser reviewed available clinical and engineering data. The failures of Riata leads appears to be due to a unique “inside-out” form of lead insulation abrasion. In some, but not all cases, lead cables have been shown to externalize. Commonly, however, externalization is not associated with failure and vice versa. There is no single common sign of lead failure on electrical measurements.
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