Stents Lose In Comparisons With Surgery And Medical Therapy Reply

Despite the enormous increase in the use of stents in recent decades, there is little or no good evidence comparing their use to the alternatives of CABG surgery or optimal medical therapy in patients also eligible for these strategies. Now two new meta-analyses published in JAMA Internal Medicine provide new evidence that the alternatives to PCI remain attractive and that some of the growth in PCI may have been unwarranted.

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New Test Could Speed Heart Attack Treatment In The Emergency Department Reply

Only 1 in 10 patients with acute chest pain in the emergency department turn out to have an actual heart attack (myocardial infarction), yet many are not released from the hospital until after 6-12 hours of cardiac monitoring and multiple ECG and troponin tests. The search for a test that can rule out MI early in the process has proved elusive.

The Biomarkers in Cardiology-8 (BIC-8) trial, presented at the European Society of Cardiology meeting in Amsterdam, was designed to determine the utility of the combination of troponin and copeptin testing. Copeptin is a marker of severe hemodynamic stress. After an acute MI copeptin levels increase rapidly. In earlier observational studies the combination test was found to have a negative predictive value of 99%.

902 patients with suspected ACS who were troponin negative were randomized to standard treatment or an experimental strategy in which patients with a negative  copeptin test were discharged early. At 30 days there were no significant differences in the rate of major adverse cardiovascular events between the two groups:

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Study Fails To Support Broader Patient Population For Cardiac-Resynchronization Therapy Reply

Cardiac-resynchronization therapy (CRT) has been shown to be beneficial in heart failure (HF) patients with a wide QRS interval. These benefits have not been reproduced so far in patients with narrow QRS intervals, though many such patients have ventricular dyssynchrony. Now a new study, presented at the European Society of Cardiology in Amsterdam and published simultaneously in the New England Journal of Medicine, once again has failed to find benefits for CRT in a broader patient population.

The EchoCRT Study Group randomized HF patients with a QRS duration < 130 msec and left ventricular dyssnchrony upon echocardiography. All patients received a CRT-D device; half the patients were randomized to have the CRT feature activated.

The study was stopped prematurely after 809 patients had been randomized and followed for nearly 20 months.

Click here to read the full story on Forbes.

Automatic Wireless Monitoring Shows Benefits in Chronic Heart Failure Reply

Following in the wake of studies that failed to find benefits associated with remote wireless monitoring of heart failure (HF) patients, the In-Time trial, presented at the European Society of Cardiology meeting in Amsterdam, is the first trial to show that home monitoring of HF patients may be beneficial.

Gerhard Hindricks, the coordinating investigator of the trial, said that In-Time was designed to test whether automatic remote home monitoring can detect events that precede clinical events and thereby spark interventions to help reduce hospitalizations for HF. In the trial, 664 chronic HF patients with an indication for an ICD were randomized to home monitoring plus standard care or standard care alone.

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Cardiovascular Outcome Studies in Diabetes Drugs Finally Arrive Reply

For many years critics have bemoaned the absence of outcome studies for the many diabetes drugs used to lower blood glucose levels. Now, finally, two large trials with different drugs have been presented at the European Society of Cardiology meeting in Amsterdam and published simultaneously in The New England Journal of Medicine. The good news is that the drugs appear safe. Both trials turned up no evidence for the adverse cardiovascular events that some had feared. The bad news is that neither drug appeared to improve cardiovascular outcomes, though cardiovascular disease is the cause of death in most people with diabetes.

SAVOR-TIMI 53

A total of 16,492 people with type 2 diabetes at high risk for a cardiovascular event were studied in SAVOR-TIMI 53. Participants were randomized to the DPP-4 inhibitor saxagliptin (Onglyza, Bristol-Myers Squibb and AstraZeneca) or placebo.

Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care (EXAMINE)

In the EXAMINE trial, 5,380 people with a recent acute coronary syndrome (ACS) were randomized to alogliptin (Nesina, Takeda Pharmaceuticals) or placebo.

These trials represent the first round of FDA-mandated cardiovascular outcomes trials for diabetes drugs, a major result of the rosiglitazone controversy. In an accompanying perspective in NEJM, William Hiatt, Sanjay Kaul, and Robert Smith, all members of the FDA advisory committees that debated the fate of rosiglitazone, discuss the complicated recent history of diabetes drugs at the FDA.

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Pretreatment with Prasugrel Not Indicated in NSTEMI Reply

Although current guidelines strongly recommend that dual antiplatelet therapy be administered early in treating patients with non-ST-segment-elevation acute myocardial infarction (NSTEMI), it is unclear whether pretreatment is beneficial,especially with the newer, more potent and more rapidly acting antiplatelet agents prasugrel (Effient, Lilly) and ticagrelor (Brilinta, AstraZeneca). Now a large new study, ACCOAST, presented at the European Society of Cardiology in Amsterdam and published simultaneously in the New England Journal of Medicine, offers strong evidence that pretreatment with prasugrel should not be performed in this situation.

Near the end of the enrollment period, the trial was stopped prematurely on the advice of the independent data and safety monitoring committee because of an increase in major and life-threatening bleeding, but no reduction in cardiovascular events, among patients in the pretreatment group.

A total of 4033 patients scheduled for coronary angiography were randomized to receive pretreatment with prasugrel or no prasugrel. There were no significant differences in the primary endpoint, (death from CV causes, MI, stroke, urgent revascularization, or glycoprotein IIb/IIIa bailout at 7 days). However, TIMI major bleeding was significantly more common in the pretreatment group at 7 days. Similar findings were observed at 30 days.

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A Disruptive TASTE of the Future? Getting the Best of Randomized Trials AND Observational Studies Reply

A new study  from Scandanavia may influence the treatment of acute myocardial infarction. But it also may end up having a much bigger impact on the entire field of medicine by pointing the way to an entirely new way of performing randomized clinical trials rapidly and inexpensively. One expert said the trial design may represent “a new paradigm,” and for once the use of the p-word may actually be appropriate.

Thrombus aspiration for ST-segment elevation myocardial infarction (STEMI) has been kicking around for a long time, but its utility has never been definitively evaluated. The procedure uses a dedicated catheter to suck the clot out of the vessel prior to stent implantation. In an accompanying editorial, Robert Byrne and Adnan Kastrati write that thrombus extraction “is an intuitively attractive strategy and one that is simple to carry out.”

The  Scandanavian study has its origins in an earlier study, TAPAS, which found an unexpected benefit on mortality at one year for thrombus aspiration, though the trial was not designed to assess mortality. On the basis of TAPAS, thrombus aspiration was given a level IIA endorsement in both European and U.S. guidelines.

TASTE (Thrombus Aspiration in ST-Elevation Myocardial Infarction in Scandinavia) was presented at the European Society of Cardiology meeting in Amsterdam and published simultaneously in the New England Journal of MedicineThe investigator-initiated randomized trial was performed as part of the Swedish Coronary Angiography and Angioplasty Registry (SCAAR), which in this case included 1 center each in Iceland and Denmark. After obtaining consent, patients were randomized through “an online randomization module within the SCAAR database.”

A total of 7244 STEMI patients were randomized, representing a striking 60% of all STEMI patients referred for PCI in Sweden and Iceland during the study period. All-cause mortality at 30 days was not significantly different between the two groups:

  • 2.8% in the thrombus aspiration group versus 3% of the PCI-only group (hazard ratio 0.94, CI 0.72-1.22, p=0.63)

A similar result was observed in the per-protocol analysis.

There were no significant differences in the rate of rehospitalization due to reinfarction, stent thrombosis, target-lesion revascularization, target-vessel revascularization, neurological complications, or other clinical outcomes, though there were trends in favor of thrombus aspiration in hospitalization for MI and stent thrombosis. The results were consistent across all major subgroups.

In their editorial, Byrne and Kastrati hold out hope that thrombus aspiration may turn out to be beneficial. They predict that “many interventional cardiologists will continue to perform thrombus aspiration for now,” based on hints of efficacy and the lack of any safety issues found in the trial.

Furthermore, they write, 30-day followup may not be long enough to detect a benefit, since the benefit in the TAPAS trial only emerged at 1 year. They urge the TASTE investigators to report the 12-month findings of their trial, and note that another large-scale randomized trial is nearing completion. “For now,” however, “the hope that this simple, easy-to-use, intuitively attractive technology could save the lives of patients presenting with myocardial infarction remains an unmet aspiration.”

A New Paradigm?

But the sweetest part of TASTE may be that the investigators were able to conduct a rapid and low-cost trial utilizing a new model, “a registry-based randomized clinical trial,” by incorporating the trial within the already existing framework of SCAAR: “The data were monitored and adjudicated as part of the regular registry validation; we did not perform separate, dedicated monitoring and adjudication of the data for the TASTE trial.”

In an accompanying Perspective, Michael Lauer and Ralph D’Agostino, Sr. ask whether randomized registry trials may be “the next disruptive technology in clinical research.” Current trials are expensive and “too complex and difficult to apply.” The usual alternative, traditional observational studies utilizing registries, “lack the rigor of randomization.”

TASTE, they write, represents “a new paradigm… that can potentially release us from the circular (and expensive) trap of the randomized-versus-registry debate.”

“The TASTE investigators designed a large-scale trial to answer an important clinical question and carried it out at remarkably low cost by building on the platform of an already-existing high-quality observational registry. With this clever design, which leveraged clinical information that was already being gathered for the registry and for other preexisting databases, the investigators were able to quickly identify potential participants, to enroll thousands of patients in little time…, to avoid filling out long case-report forms, to obtain accurate follow-up with minimal effort, and to report their findings, all for less than the amount of a typical modular R01 grant…”

friet

Disappointing Results with Dabigatran for Mechanical Valves 1

Despite being more durable than bioprosthetic valves, mechanical heart valves are often not chosen because of the requirement for lifelong anticoagulant therapy. It has been hoped that the newer generation of oral anticoagulants might eventually replace warfarin, making anticoagulation more tolerable and better accepted, since these agents don’t require continuous monitoring and have much fewer serious interactions with other drugs and food. So far, however, there has been no convincing demonstration that the the newer agents are as safe and effective as warfarin for this indication.

RE-ALIGN was a phase 2 dose-validation study of dabigatran in patients with mechanical heart valves. Results of the trial were presented at the European Society of Cardiology meeting in Amsterdam and published simultaneously in the New England Journal of Medicine.  Patients in the trial were randomized to dabigatran or warfarin.

After 252 patients had been randomized, the trial was stopped early due to an increase in thromboembolic and bleeding events in the dabigatran group:

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Positive Results for New Anticoagulant From Daiichi Sankyo Reply

A new entrant in the growing oral anticoagulant field shows promise for the treatment of venous thromboembolism (VTE) and pulmonary embolism (PE). The drug, edoxaban, is a new, once-daily Factor Xa inhibitor with a rapid onset of action that is under development by Daiichi Sankyo. Results of the Hokusai-VTE trial were presented at the European Society of Cardiology meeting in Amsterdam and published simultaneously in the New England Journal of Medicine.

The Hokusai-VTE investigators randomized 4921 patients with VTE and 3319 patients with PE to either warfarin or edoxaban. The trial differed from some earlier trials with new oral anticoagulants in that patients were treated following a lead-in period with heparin. In addition, patients were treated for as short as three months or as long as a year at the discretion of the physician, though patients were followed for a full year. Patients with low body weight or renal impairment received a half dose of edoxaban. The investigators said the design was intended to reflect the full spectrum of conditions clinicians see in real life.

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European Heart Guidelines Based On Disgraced Research May Have Caused Thousands Of Deaths 1

Despite a 2-year-old scandal discrediting key evidence, current guidelines relying on this evidence have not been revised. As a result of physicians following these guidelines, some researchers say, it is possible that thousands of patients may have died each year in the UK alone. It is unlikely that a true understanding of the damage will ever be known.

Current European Society of Cardiology guidelines recommend that beta-blockers be given to many patients having surgery for noncardiac reasons to protect the heart during surgery. (US guidelines are somewhat less aggressive in their endorsement of perioperative beta-blockade.) The guidelines, which were published in 2009, were based on analyses of the available trials. The strongest evidence came from the DECREASE family of trials, which appeared to strongly support perioperative beta-blockade, and one other large trial, POISE, which raised concerns that beta-blockers might lead to an increase in deaths. When the ESC committee combined all the data they found a neutral effect on mortality but a strong benefit due to significant reductions in non-fatal MI and stroke with beta blocker use. This was the basis for the strong recommendation in the ESC guidelines.

In 2011, however, faith in the reliability of the DECREASE trials was shattered as a result of a scientific misconduct scandal centering on the principal investigator of the studies, the now disgraced Dutch researcher Don Poldermans. The issue was further complicated because, in addition to his key role in the trials, Poldermans was the chairman of the committee that drafted the guidelines.

Now, a group of UK researchers, led by Darrel Francis, have published in the journal Heart the results of a meta-analysis of the remaining non-DECREASE trials that tested perioperative beta-blockade. With the removal of the DECREASE trials the findings were strikingly different from the earlier analyses. In a combined population of 10,529 patients taken from 9 trials there was a statistically significant increase in the risk of death in the group of patients randomized to beta-blockers…

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Don Poldermans
Darrel Francis

Sex And The Cardiac Patient Should Not Be A Taboo Subject 3

It’s not an easy conversation to have. After a heart attack or other major cardiac event, talking about sex is awkward, and often avoided by patients, their partners, and physicians. But a new consensus statement from several major cardiology organizations urges physicians to get over their reluctance or embarrassment and counsel their cardiac patients about this important, but often neglected, aspect of their lives.

After a patient has a heart attack, stroke, cardiac surgery, cardiac device implantation, or is newly diagnosed with a cardiovascular condition, physicians and other healthcare professionals should provide individually tailored information and advice about a wide variety of issues relating to sexual activity, according to the consensus document developed by the American Heart Association (AHA) and the European Society of Cardiology and published in Circulation and the European Heart Journal. The advice “should address topics such as when to resume sex, specific methods and recommended positions, and the role of intimacy without sex,” said the American Heart Association in a press release.

The statement cites numerous concerns, both psychological and physiological, that patients may have after a coronary event, including “general anxiety, fear of having another MI, feeling unwanted by their partner or not good enough, changes in self-perceptions, inadequate knowledge regarding the impact of heart medications, and finally, partner concerns.”

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Paper Raises Hundreds Of Questions About The Integrity Of Stem Cell Research Group 2

Serious questions have been raised about the integrity and validity of research performed by a well-established German stem cell research group. A paper published in the International Journal of Cardiology exhaustively details a multitude of discrepancies and contradictions in papers from the researcher’s group. Further, the revelation of such widespread misconduct may lead to broader disturbing questions about the reliability of scientific publications and the ability of the clinical research system to police itself.

In “Autologous bone marrow-derived stem cell therapy in heart disease: Discrepancies and contradictions,” Darrel Francis and colleagues scrutinize 48 papers from the research group of Bodo-Eckehard Strauer. According to Francis et al, the 48 papers from Strauer’s group contained reports on only 5 actual clinical studies, or “families” of reports, and that duplicate or overlapping reports were common. The paper contains details about more than 200 errors in the papers, including contradictory descriptions of the design, protocol and results of the trials. Francis et al write:

“Readers cannot always tell whether a study is randomised versus not, open-controlled or blinded placebo-controlled, or lacking a control group. There were conflicts in recruitment dates, criteria, sample sizes, million-fold differences in cell counts, sex reclassification, fractional numbers of patients and conflation of competitors’ studies with authors’ own.

Contradictory results were also common. These included arithmetical miscalculations, statistical errors, suppression of significant changes, exaggerated description of own findings, possible silent patient deletions, fractional numbers of coronary arteries, identical results with contradictory sample sizes, contradictory results with identical sample sizes, misrepresented survival graphs and a patient with a negative NYHA class.”

Click here to read the full post on Forbes.

Bodo-Eckehard Strauer

Top Line Results: No Cardiovascular Benefits Found For Saxagliptin Reply

Top line results of a large phase 4 study with saxagliptin (Onglyza, Bristol-Myers Squibb and AstraZeneca) demonstrate that the drug is safe but has no cardiovascular benefits. AstraZeneca and Bristol-Myers Squibb today announced the top line results for the SAVOR-TIMI-53 Cardiovascular Outcomes Trial of Onglyza®. The full results are scheduled to presented at the  annual meeting of the European Society of Cardiology in Amsterdam on September 2 by Deepak Bhatt.

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New European Hypertension Guidelines Released With Simplified Blood Pressure Target Reply

New hypertension guidelines from the European Society of Hypertension and the European Society of Cardiology were released in Milan today at the European Meeting on Hypertension & Cardiovascular Protection.

The authors of the guidelines write that “despite overwhelming evidence that hypertension is a major cardiovascular risk, studies show that many are still unaware of the condition, that target blood pressure levels are seldom achieved”. They report that hypertension affects 30-45% of people in Europe.

Perhaps the biggest single change in the new document is the adoption of a single systolic blood pressure target for almost all patients: 140 mmHg, This replaces the previous, more complicated target, which included both systolic and diastolic recommendations for different levels of risk (140/90 mmHg for moderate to low risk patients and 130/80 mmHg target for high risk patients).  One of the authors, Robert Fagard, commented: “there was not enough evidence to justify two targets.”

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European Heart Journal Retracts Main Paper Of The Kyoto Heart Study 1

The editors of the European Heart Journal have retracted the 2009 paper reporting the main results of the Kyoto Heart Study, a randomized, open-labeled study testing the add-on effect of valsartan to conventional therapy in high-risk hypertension. The retraction notice gave no details about the problems that led to the retraction. Here is the full text of the retraction notice:

“This article has been retracted by the journal. Critical problems existed with some of the data reported in the above paper. The editors of the European Heart Journal hereby retract this paper and discourage citations of it.”

Click here to read the full story on Forbes.

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