CardioExchange Archive

Recent publications, including a scientific advisory in Circulation on rosiglitazone, the industry response to a Senate Finance Committee’s report on the drug, as well as a commentary in Forbes by Harlan Krumholz, have made me consider further the role that pharmaceutical companies play in the context of fellowship training programs.

The relationships between training programs and these companies, and their potential influence, have undergone significant changes over the past several years. Practices that were in place when I was in training (about 10 years ago) no longer exist. Beyond industry’s self-imposed restrictions, many medical institutions have placed significant restrictions, both personal and financial, on the access to fellows by pharmaceutical companies and their representatives. Still, pharmaceutical companies have many avenues by which they can influence fellows. Some of these may be fairly trivial, such as providing lunch or breakfast for conferences, and others reach further, such as funding support for CME conferences, grant support for career development, and salary support for fellowship positions.

Restrictions, including those here at my own institution, have greatly changed the access that pharmaceutical companies and their representatives have with fellows, but whether these restrictions have changed industry influence remains unclear. Several issues here merit discussion. Are you, as fellows, comfortable with the role that pharmaceutical companies have in your training?  Are the imposed changes adequate or unnecessary?  Or do they not go far enough?

Issues concerning the role of pharmaceutical companies in your research also merit discussion. As you advance towards junior faculty positions, what role should industry support have in your research and career development? In terms of grant applications, how do you perceive funding support from industry?  Are you leery of clinical trials because of the influence of pharmaceutical companies? We are eager to hear what you think.

ECGs and Young Athletes: In recent years, opinion has divided over the role of ECG screening in young athletes. Two studies and an editorial in Annals of Internal Medicine shed new light on the topic. Baggish et al. found that ECGs increased the sensitivity of preparticipation cardiovascular screening, but at the cost of a higher rate of false-positive results. Taking a different perspective, Wheeler et al. found that adding an ECG test to preparticipation screening may be cost-effective. Finally, an accompanying editorial by Barry Maron acknowledges that the addition of ECG screening is attractive but recommends “prudent restraint.”

Diet and Atherosclerosis: People at high risk for atherosclerosis who participated in a two-year weight loss program had a significant 5% regression in average carotid artery wall volume, according to a new report appearing in Circulation. Different diets — low-carbohydrate, low-fat, or Mediterranean — were equally effective in reversing atherosclerosis in the 140 Israeli subjects. A drop in blood pressure caused by weight loss was closely tied to the carotid ultrasound findings.


Reducing Sodium: Smith-Spangler et al. estimate that national strategies to reduce sodium intake in the U.S. could substantially reduce the rate of stroke and MI and save billions of dollars in medical expenses. The study appears in Annals of Internal Medicine.

Vitamin D Supplements: Two meta-analyses in Annals of Internal Medicine (Pittas et al. and Wang et al.) suggest that vitamin D supplements may reduce the risk for heart disease, but an accompanying editorial by Guallar et al. warns that the data “are very limited” and that “trials of antioxidant vitamins have taught us that we cannot anticipate small risks of presumed safe interventions.”

Results of the Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST) were presented in San Antonio at the American Stroke Association’s International Stroke Conference 2010. The trial compared carotid endarterectomy to carotid stenting in 2,502 patients at centers in the US and Canada. The primary outcome—the 30 day rate of stroke, death, and MI combined with the rate of ipsilateral stroke over the next 4 years—occurred in 7.2% of patients in the stent group versus 6.8% of patients in the surgery group. The 30 day stroke rate was higher in the stent group, while the 30 day MI rate was higher in the surgery group. Patients over 70 did better with surgery.

Carotid Stenting vs. Endarterectomy: The International Carotid Stenting Study (ICSS) is an ongoing randomized trial comparing carotid stenting to carotid endarterectomy in 1,713 patients. The primary endpoint is the 3-year rate of fatal or disabling stroke. The ICSS investigators report in the Lancet the results of an interim safety analysis. The rate of stroke, death, or procedural MI at 120 days was 8.5% in the stenting group versus 5.2% in the endarterectomy group. Until completion of the trial, the investigators conclude that “carotid endarterectomy should remain the treatment of choice for patients suitable for surgery.”

A related article in Lancet Neurology contains the results of a blinded analysis of 231 ICSS patients who received MRI scans before and after treatment. New ischemic lesions were found three times more often in the stenting group than in the endarterectomy group. Neuroprotective devices offered no benefit.

Remote Ischemic Preconditioning in MI: Bøtker et al. randomized 333 patients with a first acute MI to receive remote ischemic preconditioning, consisting of 4 cycles of intermittent arm ischemia, or to not receive remote preconditioning. The median salvage index of the patients who completed the trial was 0.75 in the remote conditioning group versus 0.55 in the control group, for a median difference of 0.10, p=0.0333. The investigators, writing in the Lancet, conclude that “the intervention’s simplicity, low cost, and effectiveness make it attractive for testing in large-scale clinical trials.” An accompanying comment by Michel Ovize and Eric Bonnefoy cautions that “any enthusiasm arising from this encouraging study must, however, be tempered by the need to show actual clinical benefit in larger-scale clinical studies.”

Krumholz on Avandia: CardioExchange editor-in-chief Harlan Krumholz wrote an editorial in Circulation: Cardiovascular Quality and Outcomes (where he is also the editor-in-chief) about the AHA/ACC science advisory statement, and said that “it is hard to make a case for rosiglitazone.” He concludes that the “simplest message” might be “the avoidance of rosiglitazone until more reassuring evidence for the drug becomes available.”

Separately, Krumholz wrote a commentary for Forbes in which he criticizes GlaxoSmithKline, the manufacturer of Avandia, for behavior that “is eroding the public trust in the pharmaceutical industry.” Krumholz proposes that after a drug is approved, “all data relevant to drug safety should be placed in the public domain and independent investigators across the country should be able to use it.”

The American College of Cardiology and the American Heart Association, collaborating with the American Medical Association’s Physician Consortium for Performance Improvement (PCPI), have drafted an updated set of clinical performance measures for assessing and improving the quality of ambulatory care of patients with hypertension and stable coronary artery disease. These measures, which assess processes of care (e.g., medication prescription) and intermediate outcomes (e.g., risk factor levels), are designed to address either quality improvement or accountability. They will be submitted for endorsement by the National Quality Forum (NQF) when completed.

The measures defined in each condition are listed below. An * indicates a new measure introduced since the last update.

A) Hypertension

Measure #1: Blood pressure control

B) Coronary artery disease

Measure #1: Blood Pressure Control
Measure #2: Lipid Control
Measure #3: Symptom & Activity Assessment
Measure #4: Symptom Management*
Measure #5: Tobacco Cessation and Intervention
Measure #6: Antiplatelet Therapy
Measure #7: Beta-Blocker Therapy — Prior Myocardial Infarction or Left Ventricular Systolic Dysfunction (LVEF) <40%
Measure #8: ACE Inhibitor or ARB Therapy — Diabetes or LVEF <40%
Measure #9: Patient Referral to Cardiac Rehabilitation from an Outpatient Setting*
Measure #10: Overuse of Stress Testing*

These measures were developed to support the delivery of high quality health care by meeting criteria in the Institute of Medicine’s six domains of quality improvement: Safe, Effective, Patient-centered, Timely, Efficient, and Equitable.

The ACC/AHA/PCPI have made draft versions of these measures available for public comment. All practitioners who care for outpatients with hypertension and coronary artery disease have an interest in understanding these measures and in providing recommendations on how to improve them. Make sure that your opinion is heard — visit http://www.ama-assn.org/ama/pub/physician-resources/clinical-practice-improvement/clinical-quality/physician-consortium-performance-improvement/public-comments.shtml to download draft versions of the measures and submit your comments.

Of course, we also welcome comment on these measures here in your responses to this post.

Dr. Masoudi is the Chair of the ACC/AHA Performance Measures Task Force, which commissioned these measures in collaboration with the PCPI.

AHA/ACC Publish Science Advisory on Thiazolidinedione Drugs: Apparently in response to the renewed controversy over rosiglitazone (Avandia), the AHA and the ACC published a science advisory on thiazolidinedione drugs and cardiovascular risks. The advisory contains a highly detailed and balanced analysis of the issue. The authors, led by Sanjay Kaul, conclude that “an association between rosiglitazone and IHD outcomes has not yet been firmly established,” but acknowledges that “sufficient evidence has emerged to raise concerns about a potential adverse effect.”

GlaxoSmithKline White Paper: GlaxoSmithKline published a 30 page White Paper in response to the Senate Finance Committee report released on Saturday. The senate report “mischaracterizes and distorts” GSK’s efforts to monitor the safety and efficacy of Avandia, the document claims. 

Avandia Stays in the News: Responding to all the news last weekend about rosiglitazone (Avandia), the FDA announced an ongoing review of the cardiovascular safety of Avandia based on the RECORD trial and published a safety announcement along with additional information for patients and healthcare professionals. Adding even more drama to events, a New York Times story by Gardiner Harris tells how Cleveland Clinic cardiologist Steve Nissen secretly recorded a meeting with GlaxoSmithKline executives in 2007, immediately prior to the publication of the NEJM meta-analysis that started the Avandia controversy.

Dutch Study Questions Platelet Function Tests: A study in JAMA from the Netherlands compared six platelet function tests in low-risk patients undergoing elective PCI. Three of the tests — light transmittance aggregometry, VerifyNow, and Plateletworks — were found to have “a modest ability” to predict outcomes. The authors say the study “does not support the use of platelet function testing to guide clinical practice in a low-risk population of patients undergoing elective PCI.”

IOM Report on Hypertension: The Institute of Medicine released a report on hypertension. Noting that nearly one-third of American adults have high blood pressure, the report calls for population-based strategies to reduce the incidence of this “neglected disease,” and says medical professionals need to do a better job in diagnosing and treating patients with hypertension.

Distal Protection for Primary PCI: The DEDICATION (Drug Elution and Distal Protection in STElevation Myocardial Infarction Trial) trial has turned up a troubling suggestion of an increased risk for stent thrombosis in STEMI patients who received distal protection (DP) adjunctive to primary PCI. In a study appearing in the Journal of the American College of Cardiology, the incidence of stent thrombosis at 15 months was 11 out of 312 patients randomized to DP versus 4 out of 314 who received conventional therapy. The Danish investigators concluded: “Together with the results of previous studies evaluating DP, the results of the DEDICATION trial demonstrate that routine use of a filter wire in its present form cannot be advocated and probably should be avoided with primary PCI for STEMI.”

1 Million Stroke Patients Who Got the Guidelines: An article in Circulation: Cardiovascular Quality and Outcomes reports on the first 1 million stroke patients treated at hospitals participating in the Get With the Guidelines-Stroke program.  Lead author Gregg Fonarow said in an AHA press release that the study found “overall composite care improving substantially from 72 percent in 2003 to 93 percent in 2009. Stroke and TIA patients receiving all of the care measures for which they were eligible increased from 44 percent in 2003 to 84 percent in 2009.”

A front page story in the New York Times reports that U.S. Senators and FDA officials are raising new questions about Avandia (rosiglitazone). A soon-to-be-released Senate report asks whether it is ethical to continue the ongoing 16,000 patient TIDE trial, while several FDA officials recommend that the drug should be removed from the market.

In response to the Times story, the US Senate posted the full 334 page staff report and an accompanying (and much shorter) press release. GlaxoSmithKline, the manufacturer of Avandia, rejected the attacks and issued its own press release.

(See the RECORD interim analysis on cardiovascular risk with rosiglitazone in NEJM from 2007, a related meta-analysis by Nissen and Wolski, and this summary of the research from Journal Watch General Medicine.)