Обзор американских кардиологических журналов за неделю (ссылки)

[Chevychelov]

The status of coronary artery lesions in patients with conduction disturbance
[Ссылки доступны только зарегистрированным пользователям ]

Long-QT Syndrome
[Ссылки доступны только зарегистрированным пользователям ]

Original Research: Blood Transfusion: The Patient's Experience
[Ссылки доступны только зарегистрированным пользователям ]

[Chevychelov]

The Obesity Society
Orlando • October 1 - 5, 2011

No-Cal Drinks Yield Bigger Weight Loss
ORLANDO -- Replacing calorie-laden beverages with water or diet drinks may be effective at shedding weight and improving other cardiometabolic parameters in the short term, a randomized trial showed.
[Ссылки доступны только зарегистрированным пользователям ]

Girls Happy With Their Bodies Don’t Binge Eat
ORLANDO -- Among overweight adolescent girls, those who are more satisfied with their bodies appear to be less likely to develop binge eating disorder, researchers found.
[Ссылки доступны только зарегистрированным пользователям ]

Sleep Apnea Cut With Weight-Loss Program
ORLANDO -- An intensive lifestyle intervention to get obese patients with type 2 diabetes to lose weight had long-lasting effects on obstructive sleep apnea as well, according to results from an ancillary study to the Look AHEAD trial.
[Ссылки доступны только зарегистрированным пользователям ]

CVD Risk Cut With Rejected Weight-Loss Drug
ORLANDO -- It appears that the investigational weight-loss combination of naltrexone standard release and bupropion standard release (Contrave) reduces the predicted 10-year risk of cardiovascular events, an analysis of four phase III trials showed.
[Ссылки доступны только зарегистрированным пользователям ]

Three Questions May Peg Type 2 Diabetes Risk
ORLANDO -- A simple, three-item instrument may be enough to accurately identify those individuals who are at high risk for type 2 diabetes in the next five years, researchers found.
[Ссылки доступны только зарегистрированным пользователям ]

Teens Clueless About Fast Food Content
ORLANDO -- The vast majority of adolescents underestimate the number of calories contained in the meals they purchase at fast food restaurants, researchers found.
[Ссылки доступны только зарегистрированным пользователям ]

School Lunches Healthier than Homemade
ORLANDO -- Meals offered by the National School Lunch Program appear to be healthier than those packed at home, a study of second graders showed.
[Ссылки доступны только зарегистрированным пользователям ]

Weight Counseling by PCPs Found Lacking
ORLANDO -- Even as rates of overweight and obesity rise, primary care physicians appear to be cutting back on weight counseling for their adult patients, researchers found.
[Ссылки доступны только зарегистрированным пользователям ]

When Kids Are Young Moms Exercise Less
ORLANDO -- Mothers of young children get less exercise than women who do not have children at home, researchers found.
[Ссылки доступны только зарегистрированным пользователям ]

Weight Linked to Home Address
ORLANDO -- Exposure to high levels of air pollution from motor vehicles and secondhand smoke appears to be associated with an increase in body mass index in adolescents, researchers found.
[Ссылки доступны только зарегистрированным пользователям ]

Mother, Baby Risk Factors Predict Child’s Obesity
ORLANDO -- Targeting four modifiable maternal and infant risk factors may make a large impact on reducing childhood obesity, researchers found.
[Ссылки доступны только зарегистрированным пользователям ]

Stepped Approach to Weight Loss Works
ORLANDO -- Stepping up the intensity of a weight-loss intervention only for those patients who fail to reach their goal may be a viable alternative to standard lifestyle approaches, a randomized trial showed.
[Ссылки доступны только зарегистрированным пользователям ]

[Chevychelov]

NT-proBNP-guided therapy reduced CV complications

Januzzi J. J Am Coll Cardiol. 2011;58:1881-1889.

Adding regular testing for blood levels of amino-terminal pro–B-type natriuretic peptide was associated with reductions in event rates, improved quality of life and favorable effects on cardiac remodeling in patients with HF due to left ventricular systolic dysfunction, when compared with standard management, according to results of a newly published study.

Researchers randomly assigned 151 patients with HF and LV systolic dysfunction to standard HF care or standard care plus a goal to reduce and sustain amino-terminal pro–B-type natriuretic peptide (NT-proBNP) concentrations to 1,000 pg/mL or less. A blood sample for standard laboratory testing and NT-proBNP measurement was obtained from both groups.

A reduction of total CV events — the primary outcome of the study — was observed in the NT-proBNP group (58 events) vs. the standard care group (100 events) during a mean follow-up period of 10 months (P=.009). NT-proBNP group patients with concentrations below 1,000 pg/mL had a lower frequency of events (0.45 events) vs. those with concentrations between 1,000 pg/mL and 2,000 pg/mL (1.1 events), concentrations between 2,000 pg/mL and 3,000 pg/mL (1.25 events) and concentrations greater than 3,000 pg/mL (two events).

According to study results, “NT-proBNP-guided patients had greater improvements in quality of life,” with large improvements seen in quality of life scores vs. standard care patients (61.2% vs. 38.8%; P=.03). “Greater relative improvements in LV ejection fraction and more significant improvements in both LV end-systolic and end-diastolic volume indexes” were also found in the NT-proBNP group vs. the standard care group. Kaplan-Meier curves favored NT-proBNP guided care vs. standard care, demonstrating significant differences in time to first event (P=.03).

When looking at age differences, researchers found that elderly patients benefited similarly from NT-proBNP-guided care as younger patients.

“These results represent a turning point in our understanding of biomarker-guided care for HF,” James Januzzi Jr., MD, from the cardiology division at Massachusetts General Hospital, said in a press release. “The major lessons learned from our study are that setting and achieving low NT-proBNP goals is essential and when those goals are met through excellent patient care, we can expect substantial improvements in outcomes compared to standard care.”

Disclosure: Dr. Januzzi has received research grants and consultancy fees from Roche Diagnostics, Siemens Diagnostics and Critical Diagnostics, and has received speaker’s fees from Roche Diagnostics and Siemens Diagnostics.

__________________________________________________ _________________________

CVD risk increased after spinal cord injury

To reduce morbidity and mortality due to CVD after a spinal cord injury, treatment should focus on autonomic dysfunction and lifestyle modification, a presenter said at the 2011 Canadian Cardiovascular Congress.

“In [people with spinal cord injuries] we should be looking at whether they have autonomic dysfunction, because this causes a higher risk for heart disease,” Rianne Ravensbergen, a PhD candidate at Simon Fraser University, said in a press release. “Spinal cord injury in humans is never clear-cut. We [do not] exactly know which pathways are affected … [or] how control of the CV system is affected.”

Ravensbergen and colleagues conducted a study to determine the relationships between severity of autonomic dysfunction after spinal cord injury and risk factors for CVD. The study included 20 participants with spinal cord injury and 14 without. Those with spinal cord injury were divided into subgroups of participants with or without autonomic dysfunction.

The spinal cord injury group had decreased glucose tolerance and increased total and abdominal fat mass. The researchers also found an association between low frequency systolic arterial pressure power, noradrenaline levels and glucose intolerance in that group.

When the researchers examined the subgroups with and without autonomic dysfunction, they found that both groups had high cholesterol, but that with autonomic dysfunction also had problems with blood glucose. “These are people in a prediabetic state, which elevates their risk for heart disease,” Ravensbergen said.

Other results showed that participants with impaired glucose tolerance had increased adiposity and larger waist circumferences. Lower physical activity levels were also associated with glucose tolerance, but not with severity of autonomic dysfunction. Moreover, severity of autonomic dysfunction was not associated with measures of adiposity.

The data indicate that after the recovery period, there is value in screening the autonomic system to evaluate the CV system of spinal cord patients. Whether an increased risk for CVD is truly due to the spinal cord injury or related to patient characteristics after such injury remains to be sorted out.

Further research is needed to investigate the role that autonomic nerves play; how to better measure and improve autonomic function; and the best ways to prevent CVD after spinal cord injury, the researchers concluded.

__________________________________________________ ________________________

HF hospitalizations among Medicare patients have declined substantially

From 1998 to 2008, HF-related hospitalizations declined substantially for fee-for-service Medicare beneficiaries; however, 1-year mortality rates declined slightly and remain high, researchers wrote in a new study published in the Journal of the American Medical Association.

“Although the HF hospitalization rate has decreased nationally, our results demonstrate this has occurred unevenly across race-sex categories, especially for black men, who had the lowest rate of decline,” researchers wrote. “Similarly, 1-year mortality declined for all race-sex categories except for non-white non-black women.”

Hospitalization data

CMS National Claims History files, which included patient demographics, admission and discharge dates, and principal and secondary diagnosis codes, were used to identify all fee-for-service Medicare beneficiaries hospitalized for HF from 1998 to 2008 in the US and Puerto Rico. Overall, 55,097,390 patients were identified and had clinical characteristics examined. Participants were stratified according to age (65-74 years; 75-84 years; 85 years or older), sex and race (white, black, other).

The researchers found a relative decline of 29.5% of the overall risk-adjusted HF hospitalization rate from 1998 (2,845 per 100,000 person-years) to 2008 (2,007 per 100,000 person-years; P<.001). During the study period, HF patients who were hospitalized at least once in a given year decreased from 2,014 per 100,000 person-years to 1,462 per 100,000.

Age-adjusted HF hospitalization rates declined over the study period for all race-sex categories, with black men having the lowest rate of decline, according to a press release. Black men had the lowest rate of decline (4,142 to 3,201 per 100,000 person-years) of all race-sex categories; this persisted after the researchers adjusted for age (incidence rate ratio=0.81; 95% CI, 0.79-0.84).

In addition, risk-adjusted 1-year mortality decreased from 31.7% to 29.6% between 1999 and 2008, a relative decline of 6.6%, with substantial variation by state. For example, four states had a statistically significant decline in 1-year risk-standardized mortality between 1998 and 2008 and five states had a statistically significant increase. Moreover, decreases in unadjusted 1-year mortality occurred in patients aged 65-74 years (23.8% to 22%) and 75-84 years (31.1% to 30.3%); however, there was an increase in 1-year mortality among patients aged 85 years and older (42.3% to 42.7%; P<.001).

Overall, risk-standardized HF hospitalization rates in 1998 and 2008 varied significantly by state. The decline in this rate was significantly higher than the change in the national rate in 16 states and significantly lower in three states (Wyoming, Rhode Island and Connecticut).

The researchers said the overall decline in HF hospitalization rate was primarily because of fewer individuals being hospitalized with HF rather than a reduction in the frequency of HF hospitalizations. Also, they noted that the substantial geographic variation in HF hospitalization and 1-year mortality rates represent marked differences in outcomes that cannot be explained by insurance status, according to the press release.

[Chevychelov]

Two Afib Ablation Devices Up for FDA Panel Review

By Emily P. Walker, Washington Correspondent,
Reviewed by
October 25, 2011

Review

WASHINGTON -- One cardiac ablation device appeared safe and worked well to restore normal heart rhythm in atrial fibrillation patients during surgery, while a separate ablation system posed some troubling safety risks, FDA staff wrote in two separate reviews released this week.

The agency's Circulatory System Devices Panel meets Wednesday to discuss and vote on AtriCure's Synergy Ablation System and again on Thursday to discuss and vote on the approvability of Medtronic's Cardiac Ablation System.

First up: AtriCure's device, which is already approved for ablation of heart tissue during surgery. According to briefing documents posted by AtriCure, the device is already used off-label in a procedure called Maze IV, in which a heart surgeon creates cardiac lesions during open-heart surgery or valve surgery in patients that also have atrial fibrillation.

But since the device's current label doesn't mention atrial fibrillation, AtriCure can't train doctors on how to use the device to achieve heart rhythm control or discuss atrial fibrillation in any way, so the company is seeking expanded approval to indicate the device should also be used to restore normal heart rhythm in patients with atrial fibrillation.

The FDA's panel of outside cardiac experts will review AtriCure's ABLATE trial, which examined the outcomes of 55 patients with atrial fibrillation, all of whom received surgery.

The study size was very small, making it difficult to draw firm conclusions. But as the FDA pointed out, it's challenging to get adequate enrollment in larger, randomized atrial fibrillation trials because neither investigators nor patients are willing to face the potential of being randomized to treatment with drugs when the patient was already scheduled for surgery to treat atrial fibrillation.

In the ABLATE trial, 74% of the patients met the primary endpoint of having no episode of atrial fibrillation that lasted longer than five minutes (at least 60% of patients had to meet that endpoint for the study to be considered a success by the FDA).

However, there were four patients with paroxysmal or intermittent atrial fibrillation, so they may have been healthier than persistent atrial fibrillation patients. When those patients are included in the analysis, the primary endpoint is just missed, the FDA said.

As for safety, 50 of the 55 patients had some sort of adverse event six months after surgery; six events were considered major adverse cardiac events. One patient had a stroke, and four patients died. Those rates are to be expected, the FDA said.

"There appears to be no safety signal in this limited cohort of patients," the FDA reviewers wrote.

Wednesday's panel will vote on whether the benefits outweigh the risks for expanding the indication of the ablation system to treat patients with atrial fibrillation.

On Thursday, the panel will turn its attention to a separate atrial fibrillation device: Medtronic's Cardiac Ablation System, which is indicated for the treatment of symptomatic, drug-refractory, persistent atrial fibrillation.

The panel will review Medtronic's TTOP-AF (Tailored Treatment of Persistent Atrial Fibrillation) trial, which involved 210 atrial fibrillation patients randomized to receive either treatment with the ablation system or one of several anti-arrhythmic drugs.

After six months, 56% of patients in the catheter group had fewer heart irregularities, compared with only 26% in the medication group.

But the study revealed troubling safety issues: slightly more than one in five patients had a serious side effect shortly after surgery, including stroke, heart failure, and pneumonia. Five patients experienced a stroke within one month of having the procedure, while no patients in the medication arm had a stroke after six months.

In addition, the FDA reviewers pointed to three recently-published papers reporting that one of the catheters used in Medtronic's ablation system was linked to a 38% to 42% incidence of new asymptomatic cerebral embolic lesions identified on postprocedural MRI after the catheter was used for pulmonary vein isolation for the treatment of atrial fibrillation.

"FDA is concerned about the overall safety profile of the system," FDA reviewers concluded, adding that 38 out of 176 patients experiencing a serious device-or-procedure-related event is too high.

In Medtronic's briefing document, the company wrote its clinical trail "demonstrated the effectiveness of the system while providing a reasonable assurance of safety in the treatment of adult subjects with drug-refractory, symptomatic, persistent AF."

At the end of Thursday's meeting, the panel of cardiac experts will vote on the safety and effectiveness of Medtronic's device.

The FDA is not required to follow the advice of its advisory committees, but it often does.

[Chevychelov]

Effect of Increased Warfarin Use on Warfarin-Related Cerebral Hemorrhage
A Longitudinal Population-Based Study
[Ссылки доступны только зарегистрированным пользователям ]

Common Variants in Epithelial Sodium Channel Genes Contribute to Salt Sensitivity of Blood Pressure
The GenSalt Study
[Ссылки доступны только зарегистрированным пользователям ]

Cardiovascular Protection by Initial and Subsequent Combination of Antihypertensive Drugs in Daily
Life Practice
[Ссылки доступны только зарегистрированным пользователям ]

Impact of Sirolimus-Eluting Stent Fracture on 4-Year Clinical Outcomes
[Ссылки доступны только зарегистрированным пользователям ]

Early Repolarization Pattern in Competitive Athletes
Clinical Correlates and the Effects of Exercise Training
[Ссылки доступны только зарегистрированным пользователям ]

[Chevychelov]

Daily Aspirin Cuts Colorectal Cancer in High-Risk Adults

By John Gever, Senior Editor, Charles Bankhead, Staff Writer, 0
October 27, 2011

Action Points
Explain that a randomized, placebo-controlled trial in Lynch syndrome carriers found a significant decrease in colon cancer incidence in patients who took 600 mg per day of aspirin for at least two years compared to placebo.


Note that Lynch syndrome is caused by a rare genetic defect but results in a high risk for development of colorectal cancers.
Review
Chemoprevention with aspirin cut development of colorectal cancer by 60% in patients at high risk for the disease because of a genetic defect, according to results of a randomized, placebo-controlled trial.

Relative to placebo, the hazard ratio for colorectal cancer in carriers of Lynch syndrome was 0.41 (95% CI 0.19 to 0.86) when they took 600 mg/day of aspirin for at least two years and were followed for up to 11 years, according to John Burn, MD, of Newcastle University in England, and colleagues.

Patients with Lynch syndrome are estimated to account for about 3% of all colorectal cancer cases.



"Our results, taken in conjunction with recent research, provide a basis for recommendation of aspirin chemoprevention in Lynch syndrome as standard of care," the researchers wrote online in The Lancet.

They added that a follow-on trial would examine in more depth the optimal dosage and duration of treatment necessary to reduce the risk in this population.

The current trial, called CAPP2 (as the second trial conducted in the U.K.'s Colorectal Adenoma/Carcinoma Prevention Programme), randomized 861 individuals with Lynch syndrome to take daily aspirin or placebo for up to four years.

Lynch syndrome involves loss-of-function mutations in a DNA mismatch repair gene. These mutations are rare, but approximately 80% of individuals with them will develop colorectal cancer eventually.

Cancers in Lynch syndrome patients also tend to develop at an earlier age than sporadic tumors.

As a result, the CAPP investigators believed a chemoprevention study could be conducted more economically in Lynch syndrome patients than in the general population, requiring fewer participants and a shorter time necessary to see a treatment effect.

The tradeoff, of course, is that the results may not apply to the general population.

CAPP2 Results

On an intent-to-treat basis, the risk of colorectal cancer in CAPP2 was cut by a nonsignificant 37% in the daily aspirin group (HR 0.63, 95% CI 0.35 to 1.13) relative to placebo.

But when the statistical analysis was adjusted for multiple primary events in individual patients, the protective effect became significant (incidence rate ratio 0.56, 95% CI 0.32 to 0.99), Burn and colleagues reported.

Restricting the analysis to the 508 patients who stayed on treatment for at least two years yielded the hazard ratio of 0.41.

For participants who took aspirin for less than two years there was no apparent benefit (HR 1.07, 95% CI 0.47 to 2.41) relative to placebo.

In this per-protocol analysis, there was also a strong trend toward reduction of non-colorectal cancers with aspirin (HR 0.47, P=0.07).

Burn and colleagues noted that previous epidemiological and observational studies had suggested that aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) were beneficial in cutting colorectal cancer risk.

Support from Another Observational Study

Just this week, researchers presented data from another observational study that came to a similar conclusion about colorectal cancer mortality.

According to data from the Women's Health Initiative (WHI), regular long-term use of NSAIDs was associated with a significant reduction in the risk of death from colorectal cancer in postmenopausal women.

WHI participants who reported "continued use" of NSAIDs at baseline and three years later had a 28% lower hazard for colorectal cancer mortality compared with women who did not use NSAIDs regularly.

The mortality benefit increased to 36% for women who had taken NSAIDs regularly for at least 10 years.

Those findings were reported at the American Association for Cancer Research's Frontiers in Cancer Prevention Research meeting.

NSAID dosage did not influence mortality risk except in the subgroup of women who reported taking more than 325 mg a day, according to Anna E. Coghill, MPH, of Fred Hutchinson Cancer Research Center in Seattle, and colleagues in a poster presentation.

At baseline and approximately three years later, WHI participants completed questionnaires that addressed medication use. Participants who reported any NSAID use at enrollment were defined as baseline users, and the same criterion was applied to define NSAID users at three years. Reported NSAID use on both occasions classified patients as "continued users."

As of the end of 2010, the researchers had accumulated outcome data for 115,400 women from WHI and its extension phase. During a mean follow-up of 11 years, 2,119 WHI participants developed colorectal cancer. Of 15,608 women who died during follow-up, 432 died of colorectal cancer.

Among the women who reported NSAID use at baseline, fewer than half reported continued use three years later. Coghill and colleagues found that about 20% of NSAID users had used one or more drugs in the class for at least 10 years, and 10% reported continued use for 15 years or longer.

As in the CAPP2 study, duration of NSAID use was a factor, though to a smaller degree.

Women who used NSAIDs for less than three years showed no benefit in colorectal cancer risk.

Continued use from three to six years was associated with an 18% reduction in the colorectal cancer mortality hazard compared with nonusers. The benefit increased to 25% among WHI participants who reported continued use for six years or longer.

However, none of the values achieved statistical significance, nor did the trend analysis across different durations of NSAID use.

"Our results suggest that NSAID use is associated with lower colorectal cancer mortality among postmenopausal women who use these medications more consistently and for longer periods of time," Coghill and colleagues concluded.

"Our observation of the importance of longer periods of use is in agreement with evidence from randomized trials and epidemiological studies demonstrating that the association between NSAID use and colorectal neoplasia is duration dependent."

Paradox for Polyps Versus Tumors

However, previous randomized trials of aspirin had cast doubt on whether the drug itself was responsible for these benefits.

The CAPP investigators had started the program with a trial that evaluated aspirin for reducing intestinal polyps in people with familial adenomatous polyposis -- another genetic condition, in this case leading to a propensity for early development of polyps and subsequently colorectal cancer.

That trial, CAPP1, showed only a small benefit restricted to adenoma progression -- there was no reduction in polyp number associated with aspirin.

Pooled data from a series of other trials indicated that aspirin reduces polyp incidence by about 17% (95% CI 4% to 28%) -- a much smaller effect than CAPP2 yielded for colorectal cancer incidence.

CAPP2 did not evaluate polyps, but Burn and colleagues, operating on the assumption that aspirin's effect on polyp development is relatively minor, speculated that aspirin's anticancer activity in Lynch syndrome patients may be focused on polyps with the highest malignant potential.

Alternatively, they suggested, perhaps colorectal cancers in Lynch syndrome do not arise from polyps.

In a commentary accompanying the Lancet report, two U.S. cancer specialists said the CAPP2 results fall short of what would ideally underpin a recommendation for aspirin as chemoprevention in the general population.

A major problem was that the intention-to-treat analysis failed to show a significant benefit even in the Lynch syndrome patients, wrote Andrew T. Chan, MD, of Massachusetts General Hospital in Boston, and Scott Lippman, MD, of the University of Texas M.D. Anderson Cancer Center in Houston.

But, they added, "as the first randomized trial of aspirin with colorectal cancer as the primary endpoint, CAPP2 ... certainly moves us closer to a more definitive answer on aspirin's overall role in the prevention of colorectal cancer."

Chan and Lippman argued that a randomized trial of aspirin for cancer prevention in a general-population sample is probably impossible from a logistical standpoint.

Hence the CAPP2 results along with the earlier studies may be as good as it gets for evidence, they suggested.

That body of research "arguably support[s] more general recommendations to consider aspirin for prevention of colorectal cancer in the context of individualized risk-benefit assessments," Chan and Lippman wrote.

[Chevychelov]

Death Risk Linked to QT Length a Progressive Thing

By Chris Kaiser, Cardiology Editor,
October 27, 2011

Action Points
Note that both the long QT syndrome and short QT syndrome are inherited diseases that alter myocardial ion channels and both can lead to syncope or cardiac arrest caused by ventricular arrhythmias.


Point out that this study indicates that mortality risk in the general adult population varies as a U-shaped function of the QT interval within the reference range.
Review

Both prolonged and shortened QT-interval durations are associated with a mortality risk, but so is movement along the continuum toward those ends, a population-based study found.

Compared with the middle quintile (401 to <410 ms QT duration), those above the 95th percentile (≥439 ms) had a greater risk of all-cause mortality, cardiovascular disease mortality, coronary heart disease mortality, and non-cardiac mortality, reported Eliseo Guallar, MD, DrPH, of Johns Hopkins University Bloomberg School of Public Health, and colleagues.

In addition, those below the 5th percentile (<377 ms) also had an increased risk of cardiovascular and non-cardiovascular death compared with the reference middle quintile, according to the study published online in the Archives of Internal Medicine.

But the association was U-shaped, and the risk of death "progressively increased with longer and shorter QT interval duration compared with the population average with no clear threshold for risk change," investigators wrote.

For example, the risk for all-cause mortality increases up to 20% as the QT duration moves from the middle reference quintile (HR 1.00) toward the 95th percentile. The risk for cardiovascular mortality increases by 10% and for noncardiovascular death, by 27%.

The researchers noted that the association with mortality of the extreme variations of QT duration are known and validated, as they are closely linked with genetic mutations. But the risks associated with smaller changes in QT duration are less understood.

"As often happens in medicine, the first recognized cases of [long and short QT syndrome] had extreme QT prolongation or shortening, but it is now clear that considerable overlapping exists between the QTc [QT interval corrected by heart rate] values of the healthy population and those of the genetically impaired, so that no single QT value reliably separates 'normal' from 'short' or 'long'," wrote Sami Viskin, MD, from Tel-Aviv Sourasky Medical Center in Israel, and colleagues in an accompanying editorial.

Viskin and colleagues noted that the present study reports how mortality risk varies as a function of the QT interval -- but within the full spectrum of QT values -- in a large cohort of non-hospitalized adults.

They also highlighted how Guallar and colleagues used the residual method to neutralize possible confounders.

"They first defined R-R interval, race/ethnicity, age, and sex as possible confounders and then determined the variance explained by the confounders by building regression models for each one of them separately. The residual model represents the part of the QT that is not explained by the confounders," the editorialists wrote.

For the study, Guallar and colleagues analyzed the QT duration of 7,828 men and women, ages 40 years and older from the Third National Health and Nutrition Examination Survey (NHANES). The average follow-up was 13.7 years, but follow-up was not continued after age 90.

Researchers divided the participants according to QT-interval duration, with cutoffs at the 5th (377 to <391 ms), 20th (391 to <401 ms), 40th (401 to <410 ms), 60th (410 to <421 ms), 80th (421 to <439) and 95th percentiles (≥439). They defined below the 5th percentile as short duration and above the 95th percentile as long duration. The remaining categories were considered as a whole and divided into quintiles, with the middle quintile (reference) comprising those between the 40th and 60th percentiles.

Compared with the middle quintile, participants above the 95th percentile had greater hazard ratios (HR), including:
2.03 (95% CI 1.46 to 2.81) for total mortality
2.55 (95% CI 1.59 to 4.09) for cardiovascular disease mortality
1.63 (95% CI 0.96 to 2.75) for coronary heart disease mortality
1.65 (95% CI 1.16 to 2.35) for non-cardiovascular mortality


The corresponding hazard ratios for participants below the 5th percentile were:
1.39 (95% CI 1.02 to 1.88) for total mortality
1.35 (95% CI 0.77 to 2.36) for CVD mortality
1.02 (95% CI 0.44 to 2.38) for CHD mortality
1.42 (95% CI 0.97 to 2.08) for non-CVD mortality

The hazard ratios for the 5th through the 80th percentiles for total mortality ranged from 0.99 to 1.20; for cardiovascular mortality from 0.86 to 1.10; for coronary heart mortality from 0.78 to 0.73; and for noncardiovascular death from 1.08 to 1.27.

There were no mortality differences between men and women. In addition, when researchers excluded those with diabetes or heart failure, those who had had an MI, or those receiving QT-prolonging medication, the results did not change.

Guallar and colleagues concluded that, in a general U.S. population sample, the mortality risk associated with QT-interval duration is U-shaped, indicating that risk is apparent along the spectrum of QT duration values.

Because previous studies have been inconsistent in results and methods, they suggested that similar studies need to "carefully select the cut points and the reference category to avoid masking nonlinear dose-response relationships."

Limitations to the study include having only a baseline measurement of the QT-interval duration, determining the cause of death based on death certificates, and not having detailed information of arrhythmic sudden cardiac deaths.

[Chevychelov]

EU Says Pradaxa Treatment Requires Kidney Test

By John Gever, Senior Editor,
Reviewed by
October 28, 2011

Review

The manufacturer of dabigatran etexilate (Pradaxa) will tell European prescribers that renal function testing is a must when starting patients on the drug.

Boehringer Ingelheim agreed that renal function testing was necessary under an agreement with the European Union's top drug regulator.

"The communication to be sent to healthcare professionals strengthens that patients taking Pradaxa should have their renal function evaluated prior to treatment initiation," the company said in a press release.

"While on treatment, renal function should be assessed in clinical situations where a decline in renal function is suspected (e.g. hypovolemia, dehydration, and with certain co-medications)," the statement continued. "In patients older than 75 or with renal impairment, renal function should be assessed at least yearly whilst on treatment. Given Pradaxa is mainly excreted renally, the treatment should not be prescribed to patients with severe renal impairment (creatinine clearance less than 30 ml/min)."

The company said the communication was developed in consultation with the European Medicines Agency, the EU's equivalent to the FDA. Dabigatran's European label and medication guides will also be updated with the same information.

Because dabigatran is cleared renally, impaired kidney function could lead to abnormally high levels of the drug in circulation, leading to excessive risk of bleeding.

The drug is approved in Europe for prevention of stroke and systemic embolism in adult patients with non-valvular atrial fibrillation and one or more risk factors, such as a history of cardiovascular events; and also for primary prevention of venous thromboembolism (VTE) in adult patients having elective total hip replacement surgery or total knee replacement surgery.

In the U.S., dabigatran is approved for the afib indication without the stipulation on risk factors, but not for VTE prevention after joint replacement.

[Chevychelov]

New Strategies for Preventing Stroke, a Clinical Context Report

By Chris Kaiser, Cardiology Editor,
October 30, 2011

Action Points
New oral anticoagulants, dabigatran, rivaroxaban, and apixaban, have been shown to be non-inferior (rivaroxaban) or superior (dabigatran and apixaban) to warfari in subjects with atrial fibrillation.


These agents have wide therapeutic ranges and do not require INR monitoring.
Review
In this exclusive video report, Freek Verheugt, MD, of the University of Nijmegen in the Netherlands reviews the emerging field of oral anticoagulants for stroke prevention in patients with non-valvular atrial fibrillation with MedPage Today Cardiology Editor Chris Kaiser. Here is a transcript of their conversation.

CHRIS KAISER: I'm Chris Kaiser with MedPage Today's Clinical Context for Stroke Prevention and Atrial Fibrillation. I'm here today at the European Society of Cardiology meeting in Paris with Dr. Freek Verheugt, who is a Professor of Cardiology at the University of Nijmegen in Amsterdam, the Netherlands. Welcome Dr. Verheugt, thank you for being with us.

FREEK VERHEUGT, MD: Thank you, Chris.



KAISER: First, I'd like to ask you to give us a broad overview of what is particularly new and important regarding stroke prevention in atrial fibrillation.

VERHEUGT: The most effective strategy to prevent stroke and atrial fibrillation is the use of warfarin. We know that now for 60 years trials have shown an unequivocal benefit of warfarin therapy .

Warfarin, as you might know, is a very nasty drug to use. You need frequent laboratory testing, it causes bleeding, and it's a pain in the neck for the patients -- and the doctors too, because they have to see these patients quite often.

Therefore, we were in need of better protection.

The first antiplatelet drug has been tested, aspirin alone, which proved to be far inferior. And then dual antiplatelet therapy, aspirin and clopidogrel, which also proved to be inferior to warfarin, and so we were stuck with good old warfarin.

And then the new drugs came and these are designer drugs.

They were designed to block the activity of several clotting factors, whereas warfarin prevents production of the clotting factors in the liver. These drugs, they actively block the activity of either thrombin factor IIa, or factor Xa, which is a little bit higher in the clotting cascade. Both technologies have been tested, first in smaller trials and now in three huge, 15,000-plus patient studies, comparing directly, these new drugs against the standard of care, warfarin.

KAISER: So they're finding that these new class of anticoagulants are noninferior or slightly superior to warfarin.

VERHEUGT: Yes.

There have been three meg trials, showing that they are at least non-inferior to warfarin, with regard to stroke prevention, and they are generally safer than warfarin with regard to cerebral bleeding, which is the worst complication you can have with warfarin.

They are noninferior in ischemic stroke prevention and, in general, they are also safer with regard to extracranial bleeds, like skin bleeds.

Two out of three [of these new agents] do increase gastrointestinal bleeding, compared to warfarin, and one even prevents this but not in a significant way.

So, in general, you may say that all three agents tested are noninferior to warfarin, so they are effective against stroke. In general, you might say they are also safer and specifically safer with regard to intracerebral bleeding.

KAISER: In Europe, how many of those drugs are approved now, for stroke prevention and Afib?

VERHEUGT: It depends a little bit on the country you live in, in Europe.

It is a very diverse continent, as you may know. I think dabigatran is now available in all countries.

Rivaroxaban is also available but not approved for this indication, Afib. And apixaban, but I don't -- so it's not been approved at all.

KAISER: And give us a sense of the adoption of dabigatran in Europe, since it's been approved.

VERHEUGT: That's a good point. Of course, cost is very important.

It is now, the cost for dabigatran, as far as I know, has been dramatically reduced compared to the indication of deep vein thrombosis after orthopedic surgery.

That was quite a high price to pay. Now the price has come down for common protection in Afib.

But yet, it will always be more expensive than warfarin. Warfarin, the drug itself, is almost without price. But the testing, of course, the monitoring needs some money. In my country, it's about 300 euros, or three hundred dollars per year, to monitor a chronic Afib patient on warfarin. In other countries, it may be different, because the system may be different. Maybe you should go to a physician to have it tested, which is always more expensive than to do it at a community laboratory. So the cost is an important issue.

Second, the patient's preference and then the doctor's preference.

But the patient preference, you would think that all patients would like to stop their warfarin. That's not true. Most patients on warfarin are stable. They are so used to this frequent monitoring that they start even to like it, because they see physicians, they see nurses, they see fellow patients, usually of the same advanced age, and so there's also a social aspect.

So I think the transition to the newer drugs, especially in those who are on warfarin for a longer period of time, will be very, very slow, at least in countries where the laboratory monitoring is very well organized, like my country, like Sweden, Norway, Denmark, France, Germany.

I think in countries where it's less well organized, maybe the transition will be faster.

KAISER: But isn't it true that even among the people who are on warfarin, who like it, still the time within the therapeutic range, even in the best clinical trials, it's about 65%, and it's generally about 55%?

And given that, wouldn't you say that they would be better off on one of these new oral anticoagulants?

VERHEUGT: Yes, agreed.

You may say half of all the patients are not well maintaining their time in therapeutic range, but yet warfarin is very effective against stroke. Now, the new drugs are supposed to be effective in 100% of patients, but we don't know that. So, I'm not so worried about the time in therapeutic range, and there is not a clear association of time in therapeutic range in the new trials, the blinded warfarin with regard to stroke prevention.

So, I'm not so worried about it, absolutely not. I'm worried about the slow transition of the new drugs and, also, how should we transfer the patients to the new drug. Are you going to slow down warfarin and then start the new drugs, or are you going to stop it cold turkey and start immediately, the new drug?

Then you have at least a few days that you are over-anticoagulating and maybe that can be very dangerous. We don't know. So there are many questions left when you go over to the new drugs.

KAISER: It might be a generational thing, because you mentioned the people that are on warfarin, they're comfortable with it, they want to go in and interact with their doctors.

But what I'm hearing is that many of the newly diagnosed patients, they might quickly want to go on one of these once a day or twice a day oral factor Xa inhibitors.

VERHEUGT: Sure. I think you should make a clear distinction between patients who are currently on warfarin, and those which are not currently on the drug.

If you see a patient with heavily symptomatic Afib, a newcomer with Afib, with palpitations or dyspnea or fatigue, then first you do is cardioversion.

For cardioversion, you need one month of oral anticoagulation, and with the new drugs possibly shorter, but in those cases, patients have never experienced what it is to be on warfarin. I think this is a particularly good group for the new drugs, the newcomers. It was shown in the trials, that there was no difference in benefit between patients who were taken off warfarin and put on the new drugs, or those who were just newcomers and haven't seen any warfarin before, and those who were on warfarin all the time.

So I think good candidates for the new drugs are the newcomers, those who hate to be on warfarin, or those who are not very well maintainable on warfarin. Those are the candidates. The patients on long-term warfarin doing well, have no bleeds, are well maintainable within the therapeutic range, just keep them on it.

KAISER: Okay, thank you Dr. Verheugt.

VERHEUGT: It was a pleasure to do it.

KAISER: It's been my pleasure as well.

So, in summary:
Warfarin maintenance has challenges
A newer class of oral anticoagulants, including dabigatran, rivaroxaban, and apixaban, will challenge the dominance of warfarin
These novel agents have proven either noninferior or superior to warfarin in large clinical trials
It's currently unknown how quickly these new drugs will be adopted

I'm Chris Kaiser with MedPage Today, for clinical context.

[Chevychelov]

Chondroitin Eases Pain, Boosts Function in Arthritic Hands

By Nancy Walsh, Staff Writer,
November 01, 2011

Action Points
Explain that six months of treatment with chondroitin led to significant improvements in pain and function among patients with hand osteoarthritis (OA).


Point out that a secondary outcome favoring chondroitin was duration of morning stiffness.
Review
Six months of treatment with chondroitin led to significant improvements in pain and function among patients with osteoarthritis (OA) in their hands, a single-center randomized trial found.

Global hand pain rated on a 100-mm visual analog scale fell by 20 mm for patients taking chondroitin, compared with 11.3 mm for patients receiving placebo, for a between-group difference in change of −8.7 mm (P=0.016), according to Cem Gabay, MD, of University Hospitals of Geneva in Switzerland, and colleagues.

In addition, scores on the 30-point Functional Index for Hand OA decreased by 2.9 points in the chondroitin group and by 0.7 points in the placebo group, giving a between-group difference in change of −2.14 (P=0.008), the researchers reported in the November Arthritis & Rheumatism.


More than half of people older than 60 experience hand OA, with the most commonly involved joints being the distal and proximal interphalangeal, the trapeziometacarpal, and the thumb interphalangeal.

But the therapeutic options are few and data on the efficacy of these therapies are scarce, the authors stated.

Oral nonsteroidal anti-inflammatory drugs (NSAIDs) are helpful for pain relief, but they can cause gastrointestinal side effects and their long-term use is hampered by potentially serious cardiovascular adverse effects.

Topical anti-inflammatory agents also can be somewhat effective, but are not generally convenient for use in a chronic condition.

Acetaminophen is another option, although in the population most affected by hand OA, this drug can have negative effects on blood pressure.

To explore the potential clinical benefits of chondroitin, Gabay and colleagues enrolled 162 patients with severely symptomatic OA, assigning them to six months of daily chondroitin (800 mg) or placebo. Chondrotin is marketed as a dietary supplement in the U.S., but licensed as a prescription OA treatment in much of Europe.

The study drug contained purified chondroitin sulfate derived from fish sources.

Patients all had baseline pain scores of at least 40 mm on the 100-mm visual analog scale and had at least two joints with radiographic evidence of OA.

They were allowed to take rescue acetaminophen in maximum daily doses up to 4 grams.

Their mean age was 63, and two-thirds were women.

Mean pain score at baseline in the target hand was 54 and mean functional score was 11.

The mean number of painful flares during the previous year was 35 in the chondroitin group and 30 in the placebo group.

Patients who had erosive arthritis and involvement of the basal thumb joint had worse functional scores at baseline, but their pain scores were not significantly increased.

These features did not influence treatment outcome, however, on multivariate analysis.

A secondary outcome favoring chondroitin was duration of morning stiffness, which decreased by 4.8 minutes in the active treatment group but increased by 0.3 minutes in the placebo group (between-group difference in change −5.1, P=0.031).

Physician global assessment of efficacy increased during the trial for the chondroitin group, while between-group differences were not seen on acetaminophen use or change in hand grip strength.

Adverse events were reported by 42.5% of the chondroitin patients and by 41.5% of the placebo group.

Two patients in each group experienced serious adverse events, with only one case of abdominal pain in a placebo patient being considered possibly related to treatment.

Three patients in the active treatment group withdrew because of adverse events, as did eight patients in the placebo group.

At the end of the study, tolerability was rated as good or excellent in 96.3% of the active treatment patients and 90.8% of placebo patients.

Chondroitin has not been directly compared with NSAIDs, but the overall magnitude of effect appears to be similar, according to the researchers.

The effect size for pain was "relatively modest," but the improvement in functional scores seen at six months "is indicative of a positive clinical effect of [chondroitin] in this study population," they observed.

They noted that the advantage of anti-inflammatory drugs is prompt relief of symptoms, with the drawback of long-term safety concerns.

"In contrast, the benefits of [chondroitin] appear to take several months to develop, but with hardly any side effects, and this could help reduce the need for long-term [NSAID] therapy in patients with hand OA," they explained.

Limitations of the study included an inadequate numbers of patients to detect differences in some secondary outcomes and in subgroups of patients. Also, a restriction to patients with severe disease.

[Chevychelov]

ACE, ARB May Benefit Aortic Regurg

By Crystal Phend, Senior Staff Writer,
October 31, 2011

Action Points
Explain that angiotensin-renin blockade in patients with moderate-to-severe aortic regurgitation may reduce heart failure and mortality risks according to a retrospective, nonrandomized, observational study.


Point out that aortic regurgitation patients who received an ACE inhibitor or ARB were less likely to suffer heart failure-related death, hospitalization, or aortic valve replacement during the study period.
Review

Angiotensin-renin blockade in moderate-to-severe aortic regurgitation may reduce heart failure and mortality risks, a large population-based study suggested.

The odds of dying from any cause were a significant 44% lower during 4.4 years of follow-up for those who received an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) among the more than 2,200 such patients studied by Chim C. Lang, of the University of Dundee, Scotland, and colleagues.

The risk of heart failure hospitalizations, heart failure deaths, or aortic valve replacement was 32% lower with an ACE or ARB drug (P<0.01), the group reported in the Nov. 8 issue of the Journal of the American College of Cardiology.

The idea of intervening medically when left ventricular ejection function hasn't yet declined and patients remain asymptomatic is appealing to try to prevent heart failure and need for aortic valve replacement, noted an accompanying editorial.

A randomized clinical trial, though, will be necessary to definitively answer whether drugs can influence the natural history of severe aortic regurgitation, editorialist Linda Gillam, MD, MPH, of the Morristown Medical Center in Morristown, N.J., cautioned.

The retrospective results aren't sufficient to justify changing current aortic regurgitation treatment guidelines, she added.

The American Heart Association and ACC recommend reserving vasodilators for patients who are symptomatic or have left ventricular dysfunction and who are not candidates for valve replacement, and for short-term use while such a procedure is pending.

Use for asymptomatic patients with normal left ventricular systolic function but left ventricular dilation has a Class IIB indication.

The study included all 2,266 patients with at least moderate aortic regurgitation diagnosed from 1993 to 2008 in a population-based echocardiographic database maintained by a hospital in Tayside, Scotland.

During a mean follow-up of 4.4 years, 31% of the patients filled a prescription for an ACE inhibitor or ARB at least twice.

After adjustment for other factors, these aortic regurgitation patients were less likely to die of any cause compared with those not given an ACE inhibitor or ARB (15% versus 33%, P<0.01).

This benefit accrued to both moderate and severe cases, but particularly for severe regurgitation with a hazard ratio of 0.4 (P<0.01).

Cardiovascular death or hospitalization was 23% less likely with ACE inhibitor or ARB use (39% versus 52%, adjusted hazard ratio 0.77, P<0.01).

There were differences in comorbidities between the two groups, but these, if anything, suggested higher risk in the ACE inhibitor- and ARB-treated group.

"It is likely that the presence of diabetes, hypertension, and previous cardiovascular events may have led to the prescription of ACE inhibitors or ARBs," Lang's group wrote.

All the apparent benefits of angiotensin-renin blockade remained significant and actually became stronger in a propensity-matched analysis.

Blood pressure was similar at baseline between treatment groups.

Subgroup analyses for left ventricular diastolic dimension and systolic dysfunction didn't modify the overall result, the researchers noted.

They cautioned that the study couldn't separate out the impact of individual ACE inhibitors or ARBs, because often times they are given concomitantly with other drugs.

Possible mechanisms include direct or indirect effects on left ventricular wall stress and remodeling or simply a general cardioprotective effect, the group speculated.

They also warned about the inherent limitations of a retrospective, nonrandomized, observational study as well as the likelihood of confounding from things like lack of data on symptoms, the limited number of aortic valve replacements included in the database, and lack of standardized echocardiographic follow-up data.

Gillam added to the list of limitations, pointing out potential biases from not limiting the cohort to patients with pure aortic regurgitation such that concomitant aortic stenosis may have been important.

Another concern was the "validity of the echocardiographic grading of aortic regurgitation and the possibility of information bias in the diagnosis of patients with moderate or severe regurgitation," she noted.

[Chevychelov]

Cardiovascular
Most Read Stories This Week

Red Wine Sipping Can Impact Heart Function read more
[Ссылки доступны только зарегистрированным пользователям ]

An Egg a Day Raises Risk of Diabetes read more
[Ссылки доступны только зарегистрированным пользователям ]

FDA Approves Device for Nonsurgical Aortic Valve Repair read more
[Ссылки доступны только зарегистрированным пользователям ]

Pradaxa Bleeding Deaths Raise Concern read more
[Ссылки доступны только зарегистрированным пользователям ]

Airport Metal Detectors Safe for Pacemakers read more
[Ссылки доступны только зарегистрированным пользователям ]

Aspirin Holiday Is a Bad Idea read more
[Ссылки доступны только зарегистрированным пользователям ]

FDA Panel Says Vytorin Okay for Some Kidney Disease Patients read more
[Ссылки доступны только зарегистрированным пользователям ]

FDA Okays Xarelto for Stroke Prevention read more
[Ссылки доступны только зарегистрированным пользователям ]

Sharp Drop in Heart Failure Admissions, First Ever read more
[Ссылки доступны только зарегистрированным пользователям ]

More Blood Clots Seen With Newer Birth Control Pills read more
[Ссылки доступны только зарегистрированным пользователям ]

Sleepless Nights May Tax the Heart read more
[Ссылки доступны только зарегистрированным пользователям ]

Airport Metal Detectors Safe for Pacemakers read more
[Ссылки доступны только зарегистрированным пользователям ]

Stroke Prevention in Patients With Atrial Fibrillation, a Clinical Context Report read more
[Ссылки доступны только зарегистрированным пользователям ]

[Chevychelov]

FDA NEWS RELEASE

For Immediate Release: Nov. 2, 2011
Media Inquiries: Karen Riley, 301-796-4674, [Ссылки доступны только зарегистрированным пользователям ]
Consumer Inquiries: 888-INFO-FDA

FDA approves first artificial aortic heart valve placed without open-heart surgery

The U.S. Food and Drug Administration today approved the first artificial heart valve that can replace an aortic heart valve damaged by senile aortic valve stenosis without open-heart surgery.

Senile aortic valve stenosis is a progressive, age-related disease caused by calcium deposits on the aortic valve that cause the valve to narrow. As the heart works harder to pump enough blood through the smaller valve opening, the heart eventually weakens, which can lead to problems such as fainting, chest pain, heart failure, irregular heart rhythms (arrhythmias), or cardiac arrest.

Once symptoms of senile aortic stenosis occur, more than half of patients die within two years. To restore normal blood flow, patients with severe aortic valve stenosis need open-heart surgery to replace the diseased valve. However, the procedure is too risky for some patients.

“Surgery to replace the aortic valve is an effective treatment for severe senile aortic valve stenosis. The Sapien Transcatheter Heart Valve (THV) is an example of an innovative new device that will provide some people with this condition who can’t undergo open heart surgery with the option of valve replacement,” said Jeffrey Shuren, M.D., director of the FDA’s Center for Devices and Radiological Health. “The agency remains committed to working with companies who are developing breakthrough treatments that will have a significant impact on patient care in the U.S.”

The Sapien THV is made of cow tissue and polyester supported with a stainless steel mesh frame. To replace the diseased valve, the Sapien THV is compressed into the end of a long, thin, tube-like device called a delivery catheter. The delivery catheter, which is slightly wider than a pencil, and the Sapien THV are inserted into the femoral artery through a small cut in the leg and threaded to the site of the diseased valve. The heart valve is then released from the delivery catheter and expanded with a balloon and is immediately functional.

The FDA’s approval of the Sapien THV is based on a study in 365 patients who were not eligible for open-heart surgery. Half of the patients received the Sapien valve. The other study patients received another treatment that did not require open-heart surgery. One alternative procedure involved enlarging the aortic valve opening by stretching it with a balloon (balloon valvuloplasty).

Patients receiving the Sapien valve experienced two and a half times more strokes and eight times as many vascular and bleeding complications than patients who did not receive the implant; however, they were more likely to survive one year after surgery. After a year, 69 percent of the Sapien patients were alive compared with 50 percent of those who received an alternative treatment.

Edwards Lifescience, the manufacturer of the Sapien THV, will continue to evaluate the outcomes with the Sapien THV through a national Transcatheter Valve Therapy (TVT) registry. The Society of Thoracic Surgeons and the American College of Cardiology have been working with the FDA and the Centers for Medicare and Medicaid Services to facilitate the creation of the national TVT registry that will serve as a platform for continued evaluation of post market experience with this and future transcatheter devices and procedures for the treatment of aortic stenosis.

The most common serious and potentially life-threatening side effects in patients receiving the Sapien valve and the procedure to implant the valve include death, stroke, perforation of the blood vessels, ventricle or valvular structures, damage to the conduction system in the heart, significant bleeding, and leaks around the new valve.

The Sapien THV is approved for patients who are not eligible for open-heart surgery for replacement of their aortic valve and have a calcified aortic annulus (calcium build-up in the fibrous ring of the aortic heart valve). The product label advises that a heart surgeon should be involved in determining if the Sapien THV is an appropriate treatment for the patient.

It is not approved for patients who can be treated by open-heart surgery. Patients who have congenital heart valve anomalies, have masses or an infection in their hearts, or cannot tolerate anticoagulation/antiplatelet therapy should not receive the Sapien THV.

Edwards Lifescience is located in Irvine, Calif.
For more information:
FDA: Medical Devices


The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.

[Chevychelov]

FDA Okays Xarelto for Stroke Prevention

By Todd Neale, Senior Staff Writer,
Reviewed by
November 04, 2011

Review

The FDA has approved rivaroxaban (Xarelto) for prevention of stroke in patients with nonvalvular atrial fibrillation, making it the first oral direct factor Xa inhibitor win an indication for stroke prevention.

The drug had already been approved for prevention of deep vein thrombosis in patients undergoing joint replacement surgery at a dose of 10 mg once a day.

For the new indication, the FDA approved doses of 15 and 20 mg daily depending on creatinine clearance. Patients with a creatinine clearance greater than 50 mL/min should take the 20-mg dose and those with a creatinine clearance of 15 to 50 mL/min should take the 15-mg dose with the evening meal, according to the updated label.

Patients with a creatinine clearance level below 15 mL/min should not take the drug.

The approval was supported by findings from the ROCKET-AF trial, which showed that the 20-mg dose of rivaroxaban was as effective as warfarin at preventing stroke and systemic embolism in patients with nonvalvular atrial fibrillation. Rivaroxaban was associated with a similar rate of major bleeding but a significantly lower rate of intracranial hemorrhage.

However, one of three FDA reviewers who scoured the trial data felt that drugmaker Janssen Pharmaceuticals, a Johnson & Johnson company, failed to prove that the drug is as effective as warfarin because of suboptimal warfarin administration in the trial.

The reviewer recommended against approval in documents prepared for the FDA's Cardiovascular and Renal Drugs Advisory Committee meeting in September.

Nevertheless, the committee -- by a vote of 9-2 with one abstention -- recommended approval for the stroke prevention indication.

Rivaroxaban had already been approved by the FDA in July for the prevention of deep vein thrombosis in patients undergoing knee or hip replacement surgery. That okay was based mainly on the RECORD 1, 2, and 3 trials, which showed that rivaroxaban was significantly better than enoxaparin at preventing deep vein thrombosis.

Rivaroxaban becomes the second in a wave of new anticoagulants aimed at improving on warfarin's success in preventing stroke in patients with atrial fibrillation to be approved by the FDA. Last year, dabigatran (Pradaxa), a direct thrombin inhibitor, received approval.

Added to the existing boxed warning regarding risk of spinal and epidural hematomas in patients receiving neuraxial anesthesia or undergoing spinal puncture is a warning about an increased risk of thrombotic events in patients with nonvalvular atrial fibrillation who discontinue rivaroxaban.

If the drug needs to be discontinued for any reason other than pathological bleeding, another anticoagulant should be considered, according to the warning.


According to a statement from Janssen, the FDA has required a Risk Evaluation and Mitigation Strategy (REMS) for rivaroxaban to communicate the risks of thrombotic events, including stroke, if the drug is discontinued without an alternative anticoagulant and also to alert to the potential decreased efficacy if the drug is not taken with the evening meal.

There are other oral direct factor Xa inhibitors under development for stroke prevention in atrial fibrillation, including apixaban, which was recently shown to be superior to warfarin in the ARISTOTLE trial, and edoxaban, which is currently being evaluated in the ENGAGE trial.

[Chevychelov]

Echo May Not Provide Best Picture for TAVI

By Chris Kaiser, Cardiology Editor,
November 07, 2011

Action Points
Explain that cardiac magnetic resonance imaging (MR) and computed tomography (CT) more accurately and reproducibly measured aortic root dimensions than transthoracic echocardiography (TTE) in patients undergoing transcatheter aortic valve implantation (TAVI).


Note that MR and CT measurements better predicted severity of aortic regurgitation following TAVI than TTE.
Review

Cardiac MR and CT imaging may offer a better and more reproducible assessment of the aortic root than transthoracic echocardiography (TTE) for patients undergoing transcatheter aortic valve implantation (TAVI), a single-center study found.

Both cardiac MR and CT measurements of the aortic valve annulus prior to TAVI were better predictors of the severity of aortic regurgitation following TAVI compared with TTE, reported Raad H. Mohiaddin, MD, PhD, of the Royal Brompton Hospital in the U.K., and colleagues.

Researchers also found that MR- and CT-derived annulus eccentricity indices were not associated with aortic regurgitation following TAVI, according to the study published in the November 15 issue of the Journal of the American College of Cardiology.

In contrast, measurements derived from TTE tended to have higher variability than MR- and CT-derived measurements, and TTE significantly underestimated the aortic valve annulus size.

These results have "clinical implications for predicting outcome after TAVI," Mohiaddin and colleagues wrote in conclusion.

This conclusion is especially pertinent to interventional cardiologists and surgeons in the U.S. as the FDA earlier this month approved the Sapien valve for treatment of patients too frail to be treated surgically.

Mohiaddin and colleagues noted that there is not yet a gold standard imaging modality for measuring aortic valve annulus diameter prior to TAVI.

The problem with TTE, although it is widely used for this application, is that it doesn't account for the ellipsoid nature of the annulus, they said. Cardiac MR and CT are better suited for this measurement because they produce three-dimensional images.

For this reason, both MR and CT in this study of 202 patients had similarly low inter- and intraobserver variability. In addition MR and CT both showed similarly larger annulus diameter measurements compared with TTE.

Although pre-procedural imaging can be predictive of aortic regurgitation and other complications following TAVI, studies examining imaging's role in TAVI have been small or have only included one imaging modality, researchers said.

To help understand potential differences between cardiac MR, cardiac CT, and TTE, researchers prospectively recruited 202 patients from the Royal Brompton Hospital who had severe aortic regurgitation. All patients underwent both cardiac MR and TTE, while 133 also underwent cardiac CT.

All cases involved a multidisciplinary team that comprised cardiothoracic surgeons, cardiologists, and radiologists.

Ultimately, only 87 patients underwent TAVI (79 receiving the CoreValve and eight the Sapien valve).

The mean patient age was 79, 56% were men, and the mean ejection fraction was 59%.

Cardiac MR had the lowest intra- and interobserver variability compared with CT and TTE, as the following examples demonstrate:
Aortic valve annulus -- 1.7% MR, 3.6% CT, and 6.8% TTE intraobserver, and 5.1% MR, 10.6 CT, and 8.9% interobserver
Sinus of ******** -- 0.6% MR, 2.7% CT, and 3.9% TTE intraobserver, and 2.7% MR, 4.7% CT and 4.7% TTE interobserver
Ascending aorta -- 1.4% MR, 4.5% CT, and 10.3% TTE intraobserver, and 2.1% MR, 4.8% CT, and 10.4% TTE interobserver


Researchers noted the close agreement between MR and CT, particularly among the smallest (0.38 mm bias), largest (0.39 mm bias), and average (0.48 mm bias) annulus sizes.

On the other hand, transthoracic echo significantly underestimated the largest aortic valve annulus diameter (4.52 mm bias) compared with both MR and CT (P<0.0001).

Of the 133 patients in whom all three imaging exams were performed, MR and CT agreed on the same TAVI size (based on the manufacturer sizing for the CoreValve) in 67 patients, while MR and TTE agreed in 18 patients and CT and TTE in 25 patients.

"This study demonstrates that aortic root measurements made by both cardiac MR and cardiac CT are highly reproducible and show close agreement," researchers concluded. "In contrast, TTE-derived measures display higher variability and significantly underestimate aortic valve annulus size compared with cardiac MR and cardiac CT."

They noted that optimal coverage of the entire aortic valve annulus helps prevent aortic regurgitation and achieving optimal coverage will be especially important as a greater range of valve sizes comes to market.

The best way to achieve optimal coverage, researchers said, is by using the largest aortic valve annulus diameter. And in this study, MR and TTE agreed on size selection in 14%, while CT and TTE agreed in 19%.

"Given this poor agreement, we suggest a 3-D imaging modality be used to determine the largest annulus size and corresponding appropriate TAVI," they concluded.

A limitation of the study is that the authors did not evaluate transesophageal echocardiography, which is associated with good TAVI-sizing results, or 3-D TTE.

Also, given the differences between MR and CT -- namely a more rapid assessment with CT but with the potential for contrast-induced nephropathy -- researchers suggested that studies be conducted to determine which patients are best suited for each modality.

Another limitation of the study was the small (9%) number of patients who received the Sapien valve. Investigators therefore did not assess between-group differences.