JAMA studies raise questions about CRP and other biomarkers Reply

Two large new studies published in JAMA shed important new light on CRP and other biomarkers, but are unlikely to result in significant changes in clinical practice.

In the first report, a large genome-wide association and replication study, followed by a mendelian randomization study, failed to find a causal role for CRP in coronary heart disease. The researchers, led by by Paul Elliott, said that the “this study suggests that development of therapeutic strategies targeting specific reductions in plasma levels of CRP are unlikely to be fruitful.”

In a comment to CardioBrief, leading CRP expert and proponent Paul Ridker responded: “I have always felt that CRP is a terrific clinical biomarker for inflammation (and high vascular risk) but that it is inflammation that is likely to be causal for atherosclerosis, not CRP itself.” [Ridker’s full comment is published in full below.]

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JACC White Paper urges cautious approach to triple antithrombotic therapy Reply

Many patients receiving dual antiplatelet therapy for ACS or after receiving a stent may also require anticoagulant therapy for stroke prevention, leading to increased usage of triple antithrombotic therapy (clopidogrel, aspirin, and warfarin). “But although triple therapy can prevent both thromboembolism and stent thrombosis, it is also associated with significant bleeding hazards,” write David Holmes and colleagues in a JACC White Paper on combining atiplatelet and anticoagulant therapies. “Furthermore, when bleeding events do occur, the challenge of balancing the risk of stent thrombosis or stroke and the need for hemostasis requires considerable expertise.”

Michael Jackson’s doctor: cardiologist or not? Reply

Although he is being called a “cardiologist” in the mainstream media, Michael Jackson’s personal physician was not a board-certified cardiologist.

Near the epicenter of the Michael Jackson media storm is Dr. Conrad Murray, a Las Vegas physician. Murray was with Jackson in his last hours and apparently attempted to revive him with CPR, according to multiple reports.

Although Murray’s practice was called Global Cardiovascular Associates, the New York Times reported he was not board-certified in either cardiology or internal medicine.

Takeda’s alogliptin delayed for at least 2 years Reply

Takeda announced today that approval for its DPP-4 inhibitor alogliptin will be delayed. At the request of the FDA the company will perform a cardiovascular safety trial. The drug will be delayed for at least two years.
Click here to read a story in the Asian Wall Street Journal.

EASD raises concerns about possible link between Lantus insulin and cancer 1

Studies from Europe are raising fears that an insulin analog, insulin glargine (Lantus), may raise the risk of cancer. You can find links to the published papers, a statement from Sanofi-Aventis, information for patients, as well as additional information, on the website of Diabetologia, a journal published by the European Association for the Study of Diabetes (EASD).

You can also read a story by Shirley Wang in the Wall Street Journal Health Blog.

Doug Zipes, AHA on Michael Jackson’s death Reply

We spoke briefly tonight with Doug Zipes about Michael Jackson’s death. Zipes, a former president of the American College of Cardiology, is a leading expert on arrhythmias and sudden death.

Zipes acknowledged that drugs may well have played a role in Jackson’s sudden death. If, as widely reported in the media, Jackson died of sudden cardiac arrest, the most likely drugs to cause such an effect would be amphetamines or cocaine.

“But I have no idea what role they played,” stressed Zipes. He emphasized that Jackson could well have died of sudden cardiac arrest without any involvement of drugs.

TRANSFER-AMI: “definitive” endorsement of early PCI after fibrinolysis Reply

Routine early transfer for PCI following fibrinolysis for MI is strongly supported by results of the TRANSFER-AMI trial published in the New England Journal of Medicine.

Framingham: first degree AV block not benign 1

First degree AV block (PR interval >200 ms) may not be as benign as commonly believed, according to new data from 7,575 participants in the Framingham Heart Study published in JAMA. The study found that patients with first degree AV block were twice as likely to develop AF and three times as likely to receive a pacemaker, and a moderate increase in all-cause mortality.

New percutaneous mitral repair device appears promising in small study Reply

A new percutaneous device to repair mitral regurgitation may be beneficial in symptomatic heart failure patients with functional MR, according to a new study appearing in in Circulation: Cardiovascular Interventions.

Boston Scientific says MADIT-CRT meets primary endpoint: CRT-D slows HF progression Reply

Boston Scientific announced today that MADIT-CRT had met its primary endpoint. NYHA Class I and II patients who received CRT-Ds had a significant 29% (p-0.003) reduction in death or heart failure interventions compared to patients who received traditional ICDs.

1,800 patients in 14 countries were enrolled in the trial. Arthur Moss is the PI.

Texas passes SHAPE bill requiring reimbursement for MI screening 1

[Updated with comments from George Diamond, Amit Khera, and PK Shah]– The SHAPE-inspired bill requiring reimbursement for MI screening has passed all the stages required to become law in Texas and will go into effect on September 1. The bill was first proposed two years ago, with strong support from the Society for Heart Attack Prevention and Eradication (SHAPE).

You can read the history and the text of the bill on the Texas Legislature website.

Braunwald, Shah: “tour de force” Japanese CTA study may be future “landmark” 2

Updated with comments from Roger Blumenthal and Valentin Fuster]– CT angiography may be able to identify atherosclerotic lesions that are likely to develop ACS, according to an intriguing new study from Japan appearing in JACC. “When more effective therapies” for vulnerable plaques become available, the paper will “surely become a landmark in the effort to prevent acute coronary events,” writes Eugene Braunwald, in an accompanying editorial. PK Shah told CardioBrief the study “is a major step forward in our quest for identifying at risk subjects.”

The Japanese team analyzed the atherosclerotic lesions from angiograms of 1,059 patients to assess the presence of positive vessel remodeling (PR) and low-attenuation plaques (LAP). “These 2 features,” the authors write, “have been observed in the lesions that have already resulted in ACS, but their prospective relation to ACS has not been previously described.”

ACS developed in 10 out of 45 (22.2%) patients showing plaque with both PR and LAP, compared to 1 out of 27 (3.7%) patients with only one feature, and 4 out of 820 (0.5%) patients with neither. There were no events in the 167 patients with normal angiograms.

Europace update: AF in athletes, drivers with ICDs, more… Reply

Europace 2009 is taking place right now in Berlin. Here are some of the interesting noncommercial press releases from the European Society of Cardiology coming out of the meeting:

• Implanted Defibrillators: New Recommendations for Drivers with ICDs
• Atrial fibrillation in endurance athletes still poses problems for sports cardiologists
• “Big disparities in the treatment of arrhythmias across Europe”

Here are the press releases:

FDA official defends integrity of prasugrel review 1

Responding to criticism, FDA official Tom Marciniak has defended the methodology used in his review of prasugrel for the Cardiorenal advisory committee meeting in February.

Many CardioBrief readers will be aware of the long and complicated history behind this controversy. (Click here for a detailed chronology.)

This latest episode begins with our story last week, which summarized Victor Serebruany’s Cardiology editorial. The editorial used data from the FDA briefing document to criticize the TRITON-TIMI 38 trial. We posted a response from Lilly and Serebruany’s rebuttal. We then received an off-the-record communication that was highly critical of the FDA review, alleging that the MI data in the review was erroneous, based on a flawed method of looking at the case reports. It also appeared that similar criticisms of the FDA review had been circulating informally within the cardiology research community.

We then forwarded the criticism to Marciniak, who provided the following response:

No recession in starting salaries for new cardiologists or recruiting bonuses 6

[Updated]– They may not be at the level of a Samin Sharma or Jeff Moses, but newly minted cardiologists probably won’t have to worry about the recession, according to a survey of new physician salaries by the Medical Group Management Association.

The median starting salary for invasive cardiologists in 2008 was $350,000, according to the survey. This represented a 1.41% decline from the 2007 salary of $355,000.

Court transcripts show cardiologists debating Vioxx in Australian trial Reply

Updated with a comment from Harlan Krumholz– Court transcripts from the ongoing Australian Vioxx trial provide a detailed view of the debate between prominent cardiologists over the issue of whether Vioxx causes heart attacks. As we reported previously, four cardiologists— two on each side— faced off against each other in the trial.

US cardiologist Douglas Zipes said that Vioxx played a “substantial contributing role” in the MI of a plaintiff who is suing Merck in Australia, according to a news report in the Australian. Zipes and Richard Harper, a Melbourne cardiologist, said that Vioxx “exacerbated” the plaintiff’s risk factors.

BP: “complex interplay” between genes and environment Reply

When it comes to blood pressure it’s not just genes and it’s not just environmental factors that matter. Instead it’s the “complex interplay between genes and environmental factors” that determines blood pressure regulation, according to a study by Franceschini and colleagues appearing in Circulation: Cardiovascular Genetics.

Using data from the 3,600 American Indians taking part in the Strong Heart Family Study, the researchers “identified important genetic interactions of education and behavior factors on BP phenotypes. In particular, we found evidence for distinct genetic effects on DBP and SBP among individuals with different levels of smoking and alcohol exposures, physical activity and education.”

Lowering BP: small steps, big results Reply

Small steps to improve blood pressure control can make an enormous difference, according to a new study published in Circulation: Cardiovascular Quality and Outcomes.

Researchers at the VA-Tennessee Valley Healthcare System undertook multiple initiatives to improve blood pressure education. Nurses in the study distributed over 30,000 blood pressure wallet cards to track clinic visits, document blood pressure, update medications and provide contact information.

Rivaroxaban in ACS: more bleeding, no benefit over dual therapy Reply

Following its presentation last November at the AHA, the ATLAS ACS-TIMI 46 trial has been published online in the Lancet, with an accompany editorial by Kim Eagle and Hininder Gurm.

ATLAS was a dose-ranging study designed to find the best dose of rivaroxaban in ACS. Nearly 3,500 patients were stratified by the choice of background antiplatelet therapy (dual antiplatelet therapy or aspirin monotherapy). Rivaroxaban caused significant increases in bleeding, with the biggest increase in patients receiving dual antiplatelet therapy. Although there were no overall significant differences in the primary endpoint of death, MI, stroke, or severe recurrent ischemia requiring revascularization, there was a significant benefit observed in the group of patients who received aspirin monotherapy. A phase III trial is now underway.

Triple antiplatelet therapy for primary PCI? Reply

Triple antiplatelet therapy may be superior to dual antiplatelet therapy in primary PCI, according to the findings of a retrospective analysis of over 4,200 STEMI patients enrolled in the Korean Acute Myocardial Infarction Registry (KAMIR) who underwent primary PCI with DES. The study by Chen et al  is published online in Circulation, with an accompanying editorial by Abdel-Latif and Moliterno.

Primary PCI patients who received cilostazol in addition to clopidogrel and aspirin had better outcomes than patients who received only clopidogrel and aspirin. Bleeding rates were similar between the two groups. At 8 months patients in the triple therapy group had lower rates of cardiac death, total death, and major adverse cardiac events.

Study links psoriasis and atherosclerosis Reply

Patients who have psoriasis are more likely to have ischemic heart disease, cerebrovascular disease, and peripheral disease than patients without psoriasis, according to a new study in the Archives of Dermatology.

“This result is not surprising, given the systemic nature of atherosclerosis,” the authors write. “It has tremendous and far-reaching clinical implications, as all of these vascular conditions represent a major financial cost to the health care system as well as a major cause of disability and death. The latter finding was corroborated by our analysis, whereby we concluded that psoriasis is an independent risk factor for mortality; i.e., we found a higher percentage of deaths among patients with psoriasis than among patients without psoriasis (19.6 percent vs. 9.9 percent).”

Pioglitazone to reduce restenosis: the next frontier? Reply

Pioglitazone after PCI may reduce the rate of target lesion revascularization, according to the results of a small Japanese study published in JACC: Cardiovascular Interventions.

97 type 2 diabetics undergoing PCI with bare metal stents were randomized to pioglitazone or control in the multicenter study. The angiographic restenosis rate was 17% in the pioglitazone group and 35% in the control group, a result that did not quite achieve statistical significance (p= 0.06). IVUS measurements demonstrated that pioglitazone treatment resulted in a significant suppression of in-stent neointimal prolfieration.

In an editorial comment, Steve Nissen, well-known for raising questions about a different TZD, rosiglitazone, wrote:

Dr. Obama diagnoses a cardiology syndrome 2

Barack Obama, cardiologist? Not yet, but he spoke to the AMA today and delved briefly into the world of cardiology. Here is the relevant portion of his speech:

“…too many doctors and patients are making decisions without the benefit of the latest research. A recent study, for example, found that only half of all cardiac guidelines are based on scientific evidence. Half. That means doctors may be doing a bypass operation when placing a stent is equally effective, or placing a stent when adjusting a patient’s drugs and medical management is equally effective – driving up costs without improving a patient’s health.”

Update: Since Obama clearly referenced COURAGE in his talk, we thought we’d ask COURAGE PI Bill Boden for a response to Obama’s speech. Here are his thoughts:

Lilly responds to Serebruany attack on TRITON-TIMI 38 2

In response to Victor Serebruany’s editorial in Cardiology criticizing TRITON-TIMI 38 (see our previous post), a Lilly spokesperson sent the following statement to CardioBrief:

What do FDA insiders really think of prasugrel? 3

The benefits of prasugrel in TRITON-TIMI 38 were greatly exaggerated by the “massive inclusion of ‘MIs” unreported by the trial investigators,” according to an editorial in Cardiology by Victor Serebruany. Serebruany’s severe criticism of prasugrel and TRITON will come as no surprise to CardioBrief readers. (See our prasugrel chronology for a detailed history of the controversy).

But what is extraordinary and possibly unprecedented is Serebruany’s acknowledgment at the end of the paper (normally the least interesting part of a paper). Here is the text of the acknowledgment:

“The author wishes to thank Norman Stockbridge, MD, PhD, Director, FDA Cardiovascular and Renal Products, and Thomas Marciniak, MD, FDA Medical Team Leader, for constructive dialog.”