December 21st, 2011
Study Examines Changes in Resting Heart Rate Over Time
Larry Husten, PHD
Although resting heart rate (RHR) has been long known to be associated with cardiovascular risk, change in RHR over time has not been well studied. A new paper from Norway published in JAMA demonstrates that an increase in RHR over 10 years helps predict the risk of all-cause and ischemic heart disease (IHD) death.
Javaid Nauman and colleagues analyzed data from nearly 30,000 Norwegian adults without known cardiovascular disease who had their RHR measured at baseline and at 10 years.
During a mean follow-up of 12 years, IHD mortality and adjusted hazard ratios (AHR) according to RHR were as follows:
- RHR <70 bpm on both measurements: 8.2 deaths/10,000 person-years.
- RHR <70 bpm on the first measurement, RHR >85 bpm on the second measurement: 17.2 deaths/10,000 person-years, AHR 1.9 (CI 1.0-3.6).
- RHR 70-85 bpm on the first measurement, RHR >85 bpm on the second measurement: 17.4 deaths/10,000 person-years, AHR 1.8 (CI 1.2-2.8).
The data were less clear about people who had a decrease in RHR over time. Overall, no benefit was observed among those whose RHR decreased, but a 40% reduction in IHD mortality was observed in a subgroup of people with RHR between 70 and 85 bpm followed by an RHR below 70 bpm.
The authors concluded that “information on RHR and its time-related changes are easy to obtain and follow-up and may be useful in identifying asymptomatic people who could benefit from measures of primary prevention.”
December 20th, 2011
22 Years Later, Study Shows Life-Prolonging Effect of Antihypertensive Therapy
Larry Husten, PHD
After more than 20 years, the benefits of antihypertensive therapy are still evident, according to a new paper published in JAMA. John Kostis and colleagues performed a 22-year follow-up study on patients enrolled between 1985 and 1988 in the Systolic Hypertension in the Elderly Program (SHEP) trial.
In 1991, SHEP found that low-dose chlorthalidone in 4736 elderly patients with isolated systolic hypertension reduced the incidence of stroke and major cardiovascular events at 5 years, compared with placebo. Now, with 22 years of follow-up data, the SHEP investigators report that patients who received active treatment during the trial had a significant gain in life expectancy. Each month of active treatment resulted in about one day extra in life expectancy.
Life-expectancy gain:
- All-cause mortality: 105 days (CI −39 to 242, p=0.07)
- Cardiovascular death: 158 days (CI 36-287, p=0.009)
At 22 years, overall mortality was not significantly different between the groups, but cardiovascular death was lower with active treatment:
- All-cause mortality: 59.9% in the active treatment group versus 60.5% in the placebo group (p=0.24)
- Cardiovascular death: 28.3% versus 31.0% (p=0.03)
In their discussion, the authors said that the “gain in life expectancy is important, because it occurred among persons with a mean age of 72 years at baseline.”
December 20th, 2011
ALTITUDE Study of Aliskiren Terminated Early by Novartis
Larry Husten, PHD
Novartis announced today the early termination of the ALTITUDE trial, which was testing the effect of the direct renin inhibitor aliskiren (Tekturna, Rasilez) in patients with type 2 diabetes and renal impairment at high risk for cardiovascular and renal events. The action was based on the recommendation of the independent Data Monitoring Committee, after it found an increased risk for nonfatal stroke, renal complications, hyperkalemia, and hypotension in patients taking aliskiren after 18-24 months. Patients in ALTITUDE were randomized to receive aliskiren or placebo in addition to an ACE inhibitor or an angiotensin receptor blocker (ARB).
The company is also recommending that physicians not prescribe drugs containing aliskiren with either an ACE inhibitor or an ARB. Patients who are already taking a combination pill should be switched to an alternative antihypertensive regimen, according to the company.
The action represents a major setback for a drug that was once believed to have blockbuster potential. Novartis said it was immediately ceasing all promotion of products containing aliskiren for use in combination with an ACE inhibitor or ARB, and said it was talking with health authorities about the implications of the findings.
Aliskiren was first approved in 2007 for the treatment of hypertension. Novartis said that total sales for Tekturna and Rasilez were $449 million for the first 9 months of 2011.
December 19th, 2011
More Uncertainty About Vitamin D Supplements
Larry Husten, PHD
Although many experts believe that vitamin D deficiency may play a significant role in cardiovascular disease, there is little evidence to support the use of vitamin D supplements for the prevention of cardiovascular disease. In a narrative review published in Annals of Internal Medicine, Cora McGreevy and David Williams write that the few available studies have been inconclusive and difficult to interpret. More and bigger studies are needed to test the possible beneficial effects of vitamin D supplements, they write.
A second publication in Annals presents an updated meta-analysis of studies of vitamins D and calcium supplements for fracture and cancer protection. The results will inform forthcoming draft recommendations from the USPSTF. Analysis of data from 19 trials and 28 observational studies found that for fracture prevention vitamin D alone was not effective, but that the combination of vitamin D and calcium supplements was effective in older patients. The evidence for vitamin D in cancer prevention is inconclusive, write the authors. An additional area of concern is the proper dosing of vitamin D, since too much vitamin D may cause renal and urinary tract stones.
December 19th, 2011
FDA Adds New Warnings to Dronedarone (Multaq) Label
Larry Husten, PHD
In an updated safety communication, the FDA announced on Monday that it is adding new warnings to the dronedarone (Multaq, Sanofi) label. On the basis of results from the PALLAS trial, which was discontinued early due to safety concerns, the drug label will now warn:
Healthcare professionals should not prescribe Multaq to patients with AF who cannot or will not be converted into normal sinus rhythm (permanent AF), because Multaq doubles the rate of cardiovascular death, stroke, and heart failure in such patients.
In addition, the label will state that people taking dronedarone should have an ECG every 3 months. The drug should be stopped if a patient is found to be in AF or, if clinically indicated, the patient should undergo cardioversion.
The FDA also performed a new analysis of the ATHENA trial, which included only patients with non-permanent AF, and which formed the basis for the drug’s approval and labeling. The analysis reaffirmed the benefits of dronedarone in ATHENA, finding that the drug reduced hospitalizations and was not associated with an increased risk of cardiovascular death, stroke or heart failure.
December 19th, 2011
Should All Children Age 9 to 11 Undergo Cholesterol Screening?
Bruce M Psaty, MD, PhD, Justin P Zachariah, MD MPH and Sarah D. De Ferranti, MD, MPH
The NHLBI (with the endorsement of the American Academy of Pediatrics) has issued new guidelines for cholesterol testing in children. It recommends that all children age 9 to 11 should undergo cholesterol screening and that screening should be repeated at ages 17 and 21. We asked a small panel of experts to review the new guidelines and discuss whether they agree with the recommendation to do cholesterol screening for all children age 9 to 11. Here’s how they responded:
Bruce M. Psaty, University of Washington
Cholesterol screening for children age 9 to 11, even though the NHLBI report emphasizes lifestyle modifications as the first line-therapy, is likely to result in the use of drug treatment in a large number of children. The findings of the statin trials in adults may well not be generalizable to children, and the studies in children are all small, short-term trials. Although the evidence that lipids are major risk factors for cardiovascular disease is strong and consistent, the risk/benefit profile for long-term drug treatment in children remains uncertain. Moreover, there appear to be no plans to evaluate this screening effort, as Frederick Rivara and I noted in a recent JAMA article.
Justin Zachariah, Children’s Hospital Boston
Universal lipid screening of children will be beneficial. The most important benefit is identifying the 1 in 500 children with asymptomatic familial hypercholesterolemia (FH). Since appropriate treatment of FH reduces cardiovascular disease risk to levels approaching those in the general population, kids with FH deserve to be identified and treated. In addition, nearly 2 in 10 children have other lipid abnormalities that may be identified by universal screening. These kids deserve extra attention, follow-up, and dietary modification that targets their specific lipid profiles. Of course, lipid levels can vary with a child’s age and false positives will occur, but on balance I support the new guidelines recommending universal screening of children.
Sarah D. de Ferranti, Children’s Hospital Boston
Childhood cholesterol screening is currently aimed primarily at identifying familial hypercholesterolemia (FH). FH is a relatively common disorder of high LDL (1 in 300 to 500 individuals), much more common than many diseases for which newborns are screened. And we know that lipid-lowering drugs, if started early enough, help reduce CVD risk in patients with FH.
But universal cholesterol screening of children age 9 to 11 will undoubtedly detect lifestyle-related lipid abnormalities as well. The vast majority of children with such abnormalities have high triglyceride and low HDL levels, which do not require pharmacotherapy. The fear, then, is that children with poor lifestyle habits will be prescribed statins as a “quick fix,” but NHANES data suggest that only 1% will meet medication criteria. In fact, the new NHLBI guidelines recommend that practitioners spend much more time counseling about nutrition and exercise than prescribing medications. Such post-screening lifestyle counseling could reduce the complication rate associated with the obesity epidemic, and I believe it’s the kind of care that our patients deserve.
Do you agree with the members of our panel?
December 15th, 2011
The Good, the Bad, and the Ugly: AHA Releases Update of Heart and Stroke Statistics
Larry Husten, PHD
Once again, statistics on the cardiovascular health of the United States portray a complicated picture of improvement and decline. On the one hand, deaths from cardiovascular disease continue to decline. On the other hand, ominous trends, many stemming from the increase in obesity, suggest that the good news may not last much longer. The full picture is contained in the American Heart Association’s Heart Disease and Stroke Statistics — 2012 Update, published in Circulation.
Here are a few key items from the update:
- The overall rate of death attributable to CV disease in 2008 was 244.8 per 100,000.
- CV disease accounted for one third (32.8%) of all deaths.
- Deaths from CV disease declined by 30.6% from 1998 to 2008.
- One third of deaths from CV occur before the age of 75.
- One in nine death certificates mentions heart failure.
- One third (33.5%) of U.S. adults have hypertension.
- Some 21.2% of adult men and 17.5% of adult women smoke cigarettes.
- Fifteen percent of U.S. adults have total serum cholesterol levels of 240 mg/dL or greater.
- Eight percent of the adult population has diagnosed diabetes, while more than a third of the population (36.8%) has abnormal fasting glucose levels.
- Two thirds of U.S. adults (67.3%) are overweight or obese.
- One third of children (31.7%) are overweight or obese.
December 15th, 2011
PCI and On-Site CABG: Out of Site, Out of Mind?
L. David Hillis, MD and Richard A. Lange, MD, MBA
According to a recent meta-analysis of studies in patients undergoing PCI, rates of in-hospital mortality and emergency CABG for primary and non-primary PCI were similar at centers with and without on-site surgery. At least, that’s the story the press is spreading around.
However, several caveats should be noted . . .
1. The study included patients undergoing primary PCI (for STEMI, n=124,074) and those undergoing non-primary PCI (elective or urgent, n=914,288).
- After “adjustment for publication bias,” the mortality rates for non-primary PCI were approximately 25% higher at centers without on-site surgery than at centers with on-site surgery.
- In patients undergoing primary PCI, the emergency CABG rates were lower at sites without on-site surgery than at those with on-site surgery, raising the concern that “borderline” stable patients with suboptimal PCI results may have been kept at their local facility instead of being transported emergently to a surgical center.
2. Few of the studies reported a composite end point of death and emergency CABG surgery; therefore, it is possible that one outcome was exchanged for the other (i.e., failure to transfer precluded emergency CABG and increased death rates in patients undergoing PCI at sites without on-site CABG).
3. The relationship between outcomes and PCI volume of centers or operators was not examined.
Based on what you know, would you be willing to have an elective PCI at a center without on-site CABG capability?
December 14th, 2011
Study Examines New-Onset Atrial Fibrillation After TAVI
Larry Husten, PHD
The broad enthusiasm for TAVI (transcatheter aortic valve implantation) as it enters the marketplace has been partially offset by concerns about an increased risk for stroke associated with the procedure. The role of one major cause of stroke, atrial fibrillation (AF), has not been the subject of close scrutiny. Now a study from Quebec, published in the Journal of the American College of Cardiology, provides new information about the rate of new-onset AF following TAVI.
Ignacio Amat-Santos and colleagues followed 138 patients with no history of AF who underwent TAVI. Some 32% (44 patients) developed new-onset AF while in the hospital at a median of 48 hours after the procedure. More than 80% of the AF episodes occurred within the first 3 days after implantation. One third of the episodes lasted less than an hour. Larger left atrial size and the transapical approach significantly increased the risk for AF. TAVI patients who developed AF had a higher rate of stroke or systemic embolism at 30 days and 1 year compared with those who did not develop AF, but no differences in mortality were observed between the groups in this small series.
In an accompanying editorial comment, Bernard Iung, Dominique Himbert, and Alec Vahanian write that the study “raises questions regarding the most appropriate antithrombotic therapy following TAVI,” but that the high number of patients with only a brief episode of AF does not support routine aggressive anticoagulation following any episode of AF.
December 13th, 2011
Meta-Analysis Finds No Danger for PCI Performed at Centers Without Surgical Backup
Larry Husten, PHD
On-site surgical backup for PCI has long been mandated by guidelines, though its necessity in the modern era has been questioned, and the most recent PCI guidelines published last month lack a specific recommendation about surgical backup. Now a large meta-analysis, published in JAMA, suggests that PCI performed without surgical backup may be safe.
Examining data from 40 studies, Mandeep Singh and colleagues found no significant differences in in-hospital mortality or emergency CABG between centers with and without on-site surgery:
Among 124,074 STEMI patients:
- In-hospital mortality: 4.6% for no surgical backup vs. 7.2% for surgical backup (OR 0.96, CI 0.88-1.05)
- Emergency bypass: 0.22% vs. 1.03% (OR 0.53, CI 0.35-0.79)
Among 914,288 elective and urgent PCI patients:
- In-hospital mortality: 1.4% vs. 2.1% (OR 1.15, CI 0.93-1.41)
- Emergency bypass: 0.17% vs. 0.29% (OR 1.21, CI 0.52-2.85)
In an accompanying editorial, Scott Kinlay notes that the rate of emergency CABG is now 10 times lower than in the early balloon angioplasty era. The results of the meta-analysis, along with previous studies, he writes, “suggest that the current patterns of judicious PCI by operators in hospitals without CABG surgery leads to risks that are similar to those of hospitals with CABG surgery.”
Kinlay concludes:
The prevention of adverse events is arguably less dependent on the presence of on-site CABG surgery and more dependent on an operator’s skill to select appropriate patients, their technical skill to complete PCI, and their commitment to maintain skills through continued education and participation in quality assurance programs.
Please note that TheHeart.Org and U.S. News & World Report have released the findings of a survey about this topic.
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