CardioExchange Archive

Update on IMPROVE-IT: IMPROVE-IT is the much anticipated and highly controversial ongoing study evaluating ezetimibe. In response to the controversy over the drug (see, for example, here and here), and to address the questions that “have been raised about whether the trial will be completed,” the trial investigators have written an editorial that has now been published online in the American Heart Journal.


Califf and colleagues now estimate that the last of the 18,000 subjects will be enrolled in June 2010. Because of the “trial’s prolonged duration” there is a greater number of patients than originally anticipated who have stopped taking the study drug, and this will “cause the estimated treatment effect to be diminished.” Despite the numerous concerns that have been raised in the last few years, the authors report that both the Lipid Monitoring Committee and the Data and Safety Monitoring Board “have consistently recommended that the study continue without design alteration.” The investigators now predict that the trial will be completed in June 2013, which is when their model predicts they will achieve 5,250 primary endpoint events with at least 2.5 years of follow-up for all subjects.

Olympic Hearts: The long-term effects on the heart of intensive athletic training have never been conclusively determined. Italian, U.S., and Japanese investigators, led by Barry Maron, studied 114 Olympic athletes “who experienced particularly intensive and uninterrupted training” over 4 to 17 years. They report in the April 13 issue of the Journal of the American College of Cardiology that they found no significant changes or deterioration in LV function or morphology and no evidence of cardiovascular symptoms or events. “Our findings support the benign nature of physiologic heart remodeling in trained athletes and the safety of long-term and intense sports participation, even at the highest competitive level,” they conclude.

Atrial Fibrillation and Dementia Linked: The aging of the population will be accompanied by inevitable increases in the incidence of diseases like dementia and atrial fibrillation (AF). Now an epidemiologic study of more than 37,000 consecutive patients from the Intermountain Heart Collaborative Study has found that AF is independently associated with all types of dementia. The report by Bunch et al in Heart Rhythm also found that the risk of developing Alzheimer’s Disease was highest in younger patients with AF. In addition, patients with dementia who had AF had a greater risk of dying.

Predicting Mortality after PCI: Using data from the National Cardiovascular Data Registry, Peterson et al developed a model to predict the risk of mortality following PCI. In their report in the Journal of the American College of Cardiology, the researchers observed an in-hospital mortality rate ranging from 0.65% for elective PCI to 4.91% for STEMI patients. “We anticipate that these models will have multiple applications (including bedside risk estimation using the simplified risk score, comparison of hospital performance, and risk adjustment),” they concluded. In an accompanying editorial, Dean Kereiakes said the new score “accurately predicts the risk of in-hospital death following either elective or primary PCI” but noted several obstacles that may prevent its immediate adoption in widespread clinical practice.

A front page story in Wednesday’s New York Times questions the expanding use of statins, and particularly rosuvastatin, in “healthy people.” Following the recent approval of broad new indications for the drug based on results from the JUPITER trial, Times reporter Duff Wilson notes that millions of people may now take the drug “largely as prevention” and that some experts “suggest the benefits may not outweigh any side effects.”

The article quotes Stanford’s Mark Hlatky: “It’s a good thing to be skeptical about whether there may be long-term harm from healthy people taking a drug like this.”

By contrast, JUPITER principal investigator and longtime advocate of CRP, Paul Ridker, told Wilson: “We found a 55 percent reduction in heart attacks, 48 percent reduction in stroke, 45 percent reduction in angioplasty bypass surgery.” His view is supported by Steve Nissen: “If somebody comes into my office and meets the criteria, am I going to deny them a drug that reduces their chance of a heart attack or stroke by 40 or 50 percent?”

But, the article notes, the absolute difference in heart attacks in JUPITER was only 0.2%.

A quote from a cardiologist in Rockville Centre, NY, Steven Seiden, concludes the article: “It just turns a lot of healthy people into patients and commits them to a lifetime of medication.”

FDA Issues Complete Response Letter For Certriad: The FDA issued a complete response letter for the NDA for Certriad, Abbot’s and AstraZeneca’s combination pill composed of rosuvastatin and fenofibric acid delayed release. The companies did not release any details of the letter, but analysts think it will mean the drug’s approval will likely be delayed until next year at least. (Press release.)

U.K.’s NICE Goes Easier on Dronedarone: Following an earlier negative recommendation, the U.K.’s National Institute for Health and Clinical Excellence has revised its preliminary recommendations for dronedarone. The new draft guidance recommends the use of the drug only as a second-line therapy in high-risk AF patients without unstable NYHA class III or class IV heart failure. (NICE appraisal consultation document.)

U.S. Justice Dep’t & SEC Look Into Boston Scientific ICD Recall: The Wall Street Journal reports (subscription required) that the U.S. Department of Justice and the Securities and Exchange Commission are each undertaking an investigation of Boston Scientific’s recent recall of its ICDs. On Monday, the company released a transcript of a conference call with physicians in which the company explained the recall and provided assurances about the company’s future.

Screening for Type 2 Diabetes: Kahn et al. used a sophisticated computer model to assess the impact of 8 different screening strategies to detect type 2 diabetes in the US. The researchers concluded that screening is cost effective when started between the ages of 30 and 45 years of age, with screening repeated every 3–5 years. The study appears online in the Lancet. In an accompanying comment, Guy Rutten write that the study “provides further evidence that screening for diabetes should be combined with screening for hypertension and lipid tests.”

FDA Cracks Down on Unapproved Nitroglycerin: Last week the FDA ordered two companies to stop selling unapproved nitroglycerin tablets. A New York Times story over the weekend explored the larger dimension of the story, pointing out that only one nitroglycerin tablet, Pfizer’s Nitrostat, has undergone the FDA approval process, and that 80% of the nitroglycerin used in the US has never been subject to regulatory scrutiny. The Times story quotes Harry Lever, a cardiologist at the Cleveland Clinic: “If it’s not approved and no one has tested it, we can’t be sure that it’s safe and effective.”

Although alcohol septal ablation (ASA) for the treatment of obstructive hypertrophic cardiomyopathy is now gaining increasing acceptance in many parts of the world, a new study finds that it may cause more problems than traditional surgical myectomy. Investigators from the Netherlands, led by Patrick Serruys, studied 91 consecutive ASA patients and compared them to 40 consecutive patients who underwent myectomy during the same period. The 1-, 5-, and 8-year survival free from the composite endpoint of cardiac death and aborted sudden cardiac death was 96%, 86%, and 67%, respectively, in ASA patients compared to 100%, 96%, and 96%, respectively, in the surgical patients, according to the article in Circulation: Heart Failure. In a multivariate model, ASA was an independent predictor of the primary endpoint. In their conclusion, the authors write that “since a randomized study between ASA and myectomy is unlikely to be performed we can only rely on registries in single centers. Our data show that ASA is effective but has potentially adverse long-term effects.” Despite the growing adoption of ASA in clinical practice, the authors “recommend myectomy as the preferred treatment of choice in patients with symptomatic obstructive HCM.”

Hospital Volume and Mortality: Using Medicare data, Ross et al. investigated the association between hospital volume and the 30-day death rate for patients admitted for acute MI, heart failure, and pneumonia. In their report in the New England Journal of Medicine, the researchers found that increased volume was associated with reduced rates of death for all three conditions, but they observed a volume threshold after which the effect was attenuated. The threshold was reached when the annual patient volume was 610 for acute MI, 500 for heart failure, and 210 for pneumonia. (The senior author of the study was Harlan Krumholz, editor-in-chief of CardioExchange.)Coronary Artery Fistula Closure: Coronary artery fistula closure is associated with a high rate of complications. In a report in Circulation, Valente et al. reviewed the records and angiograms of 76 patients who underwent diagnostic angiography for CAF. Drainage of the CAF into the coronary sinus was the only angiographic feature that predicted an adverse outcome.