Обзор американских кардиологических журналов за неделю (ссылки)

[Chevychelov]

Simple or Complex Stenting for Bifurcation Coronary Lesions
A Patient-Level Pooled-Analysis of the Nordic Bifurcation Study and the British Bifurcation Coronary Study
[Ссылки доступны только зарегистрированным пользователям ]

In-vivo detection of the frequency and distribution of thin-cap fibroatheroma and ruptured plaques in patients with coronary artery disease: an optical coherence tomographic study
[Ссылки доступны только зарегистрированным пользователям ]

Neurologic and Cardiac Benefits of Therapeutic Hypothermia
[Ссылки доступны только зарегистрированным пользователям ]

[Chevychelov]

HERCULES: BNP not predictive of reduced systolic BP in stented renal artery stenosis patients

Society for Cardiovascular Angiography and Interventions 2011 Scientific Sessions

BALTIMORE — Results presented in a late-breaking trial session demonstrated that elevated pretreatment brain natriuretic peptides were not predictive of reduction in systolic BP in patients treated with renal artery stenting.

“The results are disappointingly negative,” said HERCULES trial investigator Michael R. Jaff, DO, medical director of the Vascular Center at Massachusetts General Hospital in Boston, and a member of the Cardiology Today Editorial Board, while presenting the findings at the 2011 Society for Cardiovascular Angiography and Interventions Scientific Sessions. “I must tell you, this is a field struggling for predictive help,” Jaff said, “but we weren’t able to find it.”

The prospective, multicenter trial evaluating the safety and effectiveness of the RX Herculink Elite Renal Stent System (Abbott Vascular) reviewed outcomes for 202 patients (241 lesions, 39 bilateral lesions) with uncontrolled hypertension who were treated with a renal artery stent between August 2007 and October 2009.

The primary endpoint was a 9-month binary restenosis rate as determined by duplex ultrasound or angiographic analysis; the performance goal was 28.6%. Secondary endpoints were changes in systolic BP, antihypertensive medications and renal function between baseline and 9 months. Measurements of brain natriuretic peptide (BNP) were taken at baseline, 24 hours and 30 days’ post-procedure.

The investigators found that systolic BP decreased after stenting with no adjustment to medications. A BNP level of more than 80 pg/mL was found in 66% of patients; baseline serum creatinine was 1.2 ± 0.4; 61.5% of participants had an estimated glomerular filtration rate (eGFR) of less than 60. At 9 months, eGFR was stable. Despite a reduction in mean systolic BP, mean BNP levels remained elevated at 1 month.

There was no correlation between BNP levels at baseline and systolic BP reduction, nor between BNP reduction and systolic BP response. The restenosis rate was 10.5% at 9 months (P<.0001). The study device, procedure and clinical success rates were 96%, 99.2% and 98%, respectively. Freedom from medical error and reintervention was 94.8%.

“The clinical results are promising, as we found very low restenosis rates and a significant drop in BP following renal artery stenting,” Jaff said in a press release, but because the study’s goal was to help predict which patients will have the best outcomes after the procedure, “the search must continue.” – by Whitney McKnight
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ST-DETECT: High-risk patients with ICDs show low spontaneous coronary event rate

Society for Cardiovascular Angiography and Interventions 2011 Scientific Sessions

BALTIMORE — The addition of high-fidelity intracardiac electrogram signals in implantable cardioverter defibrillators provided data indicating that high-risk CVD patients experienced low rates of spontaneous coronary events.

“The events are shockingly low,” said study investigator Timothy D. Henry, MD, of the Minneapolis Heart Institute at Abbott Northwestern Hospital. “The results suggest that the [patients’] disease was well managed by a combination of medical therapy and revascularization.” Henry made his remarks while presenting the results of the ST Segment Detection Study (ST-DETECT) at the 2011 Society for Cardiovascular Angiography and Interventions Scientific Sessions.

After implantation of an ICD programmed with high-fidelity intracardiac electrogram (EGM) signals, 175 patients from 32 participating centers were monitored for 24 months. Investigators in this prospective, non-randomized study evaluated whether spontaneous coronary events and exercise-induced cardiac ischemia precipitated detectable changes on the intracardiac EGM signals.
Patients qualified if they had experienced an MI in the previous 6 months, had previously undergone stenting or a percutaneous coronary intervention procedure, had multivessel disease (>1 coronary arteries, >60% stenosis) or had a recent positive stress test with suspected CAD. Antiplatelets were in use by 93% of the study group; 88% were using anti-hyperlipidemia medication; 93% were using beta-blockers; 84% were using ACE inhibitors/angiotensin receptor antagonists; 60% were using diuretics; and 35% were using vasodilators/nitrates.

A blinded, external endpoint committee determined that of the 361 recorded adverse events, based on 174.7 patient-years from 121 patients, 181 were CV-related. The trial, which was based on a 4% annual acute MI rate, was discontinued early.

“This trial illustrates that to implement the potential of this new technology, we need to further study the complex relationship between clinical events, surface ECG and EGM changes,” Henry said. – by Whitney McKnight

[Chevychelov]

New hemodynamic device improved outcomes for high-risk PCI patients

Society for Cardiovascular Angiography and Interventions 2011 Scientific Sessions

BALTIMORE — An analysis of data showed that the Abiomed Impella 2.5 device offered better hemodynamic support than the intra-aortic balloon pump traditionally used in high-risk percutaneous coronary intervention patients.
William O’Neill, MD, executive dean for clinical affairs at the University of Miami Miller School of Medicine, presented data from the aborted PROTECT II trial during the Society for Cardiovascular Angiography and Interventions 2011 Scientific Sessions. After the trial was halted, investigators continued to follow the population for 90 days. They determined that in the Impella arm (n=213), 21.6% experienced major adverse events compared with 31% in the balloon device arm (n=210).

Between November 2007 and November 2010, 452 of an intended 654 patients were prospectively enrolled in a multicenter, randomized trial to determine the type of hemodynamic support that provides the best clinical outcomes during high-risk PCI. Patients with three-vessel disease and left ventricular ejection fraction <30% or with unprotected left main or last patent conduit and LVEF <35% during PCI were included. Prophylactic support was initiated before the intervention and halted as soon as it was efficacious after the procedure. The revascularization procedure was at the discretion of the clinician. The primary endpoint was a composite of major adverse events at 30 days; the primary endpoint follow-up was assessed at 90 days.

Due to futility on the primary analysis at the first interim mark, the Data Safety Monitoring Board recommended the study be terminated. The patient population (n=452) at interim was 66 ± 10 years of age and included those with diabetes (52%), active angina (66%) and renal insufficiency (25%). Class NYHA III/IV patients numbered 56%; 67% were not candidates for surgery. Patients had syntax scores of 31 ± 14 and their LVEF was 24 ± 6%.

O’Neill also presented data on the effect of operator learning curve: 90-day outcomes in the intent-to-treat population (n=447) saw a major adverse event rate for the Impella device of 47.8% in 2008; 39.1% in 2009; and 37.3% in 2010. “I can’t fault the Data Safety Monitoring Board for halting the trial,” O’Neill said. “The thing we didn’t take into full consideration was the learning curve of the trial.”
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Prevalence of wake-up strokes found in large population
Mackey J. Neurology. 2011;76:1662–1667.

Almost 15% of all strokes that occurred in a recent study were found to be wake-up strokes. This study, according to researchers, was the first large and population-based study to examine the event rate of wake-up strokes.

Jason Mackey, MD, and fellow colleagues studied all first-time and recurrent ischemic strokes among 1.3 million residents of the Cincinnati/northern Kentucky region in 2005. Only patients aged at least 18 years who were evaluated in an ED were included in the analysis.

Overall, 1,778 residents were identified with 1,854 first-ever and recurrent ischemic strokes. Of these, 273 (14.3%) were wake-up strokes, resulting in an adjusted wake-up stroke event rate of 26 per 100,000 people. Among those who experienced a wake-up stroke, at least 35.9% would have been eligible for thrombolysis had arrival time not been a factor.

Additional analysis also revealed that those who had wake-up strokes tended to be older (72.3 ± 0.83 years vs. 70 ± 0.48 years; P=.01) and had a higher baseline retrospective NIH Stroke Scale score (median interquartile ratio,4 vs. 3; P=.004).

Despite these factors, study researchers said there were no obvious features distinguishing between wake-up and nonwake-up strokes.

In addition, they said: “Wake-up strokes constitute a significant percentage of ischemic strokes and are ineligible for thrombolytic therapy due to the current time-based restrictions, which is unfortunate because it is likely that some of these events occurred immediately prior to awakening. Efforts are ongoing to develop better methods of identifying those patients most likely to benefit from treatment while at the same time minimizing exposure to undue risk.”
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FDA approves carotid stenting system in standard-risk patients

The FDA has recently approved the use of the RX Acculink carotid stenting system for patients at standard surgical risk for carotid endarterectomy, expanding the use of the system beyond the former indication of those who are at high risk with the procedure.

This approval follows the FDA advisory panel’s 7-3 vote in January that the benefits of an expanded indication of the RX Acculink system (Abbott Vascular) outweigh the risks. Both the advisory panel and the FDA’s vote were based on the findings of the 10-year Carotid Revascularization Endarterectomy Vs. Stenting Trial (CREST), which demonstrated similar results among patients treated with carotid stenting vs. carotid endarterectomy.

According to a press release, a condition of this approval is that Abbott will conduct a post-approval study on the device, following new patients treated with the system for at least 3 years to confirm the results of CREST. Also stated in the release, this upcoming study will be consistent with recommendations made by the panel and will evaluate how patients aged at least 80 years respond to the treatment, as well as whether success is affected by physician experience and whether those with symptoms before treatment have a different outcome compared with those who are asymptomatic.

[Chevychelov]

REVEAL: Epoetin alfa potentially harmful in patients with STEMI after PCI

Najjar S. JAMA. 2011;305:1863-1872.
Bhatt D. JAMA. 2011;305:1908-1909.

Epoetin alfa administered to patients with STEMI within 4 hours of successful percutaneous coronary intervention was shown to increase the rate of adverse CV events while having no benefit on infarct size.

The Reduction of Infarct Expansion and Ventricular Remodeling with Erythropoietin after Large Myocardial Infarction (REVEAL) trial was a phase 2 study that included 222 patients with STEMI who were successfully treated with PCI. Patients were randomly assigned to either treatment with IV epoetin alfa or matching placebo delivered within 4 hours of the procedure. Physicians then measured infarct size with cardiac MRI between 2 to 6 days after drug administration and then again 12 weeks later, and they expressed findings as percent of left ventricular mass.

According to results, infarct size at both first (epoetin alfa, 15.8% vs. placebo, 15%) and second (epoetin alfa, 10.6% vs. placebo, 10.4%) MRI scan did not differ between those given 60,000 units of epoetin alfa and placebo. However, for patients aged at least 70 years, mean infarct size in the first week was larger among those in the epoetin alfa group (19.9% vs. 11.7%; P=.03).

The researchers then performed safety analysis, which included a dose escalation of epoetin alfa (15,000 units, 30,000 units and 60,000 units), which revealed a higher rate of any adverse event in those who received epoetin alfa (55.2% vs. 41.2%; P=.04), which was also true of serious adverse events (20% vs. 10.3%; P=.05). Furthermore, the composite outcome of death, MI, stroke or stent thrombosis occurred only in the epoetin alfa group (4% vs. 0%; P=.04).

Considering the results of this study, Deepak L. Bhatt, MD, MPH, with the VA Boston Healthcare System, wrote in an accompanying editorial that it may not be worth taking epoetin alfa into phase 3 trials.

“Several compounds to limit infarct size or to mitigate reperfusion injury have appeared promising in animal models, only to fail when tested in humans,” Bhatt said. “Use of cardiac MRI may allow screening of several future candidate compounds in studies with reasonable sample sizes and may reveal those that appear most promising for reducing infarct size. Investigators can then conduct large clinical trials to evaluate those approaches that are likely to yield benefit and not cause harm.”
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CONFIRM: Novel ablation approach promising treatment for AF

Heart Rhythm Society 32nd Annual Scientific Sessions

SAN FRANCISCO — Compared with conventional ablation alone, patients who had focal impulse and rotor modulation ablation followed by conventional ablation had improved freedom from atrial fibrillation at 2 years, suggested new data.
The Conventional Ablation for Atrial Fibrillation With or Without Focal Impulse and Rotor Modulation (CONFIRM) included 103 patients with AF, of which 67% had persistent AF, which, according to Sanjiv Narayan, MD, PhD, study researcher and associate professor of medicine in residence at the University of California, San Diego School of Medicine, is a more difficult disease to treat and makes the present study different from some previous research which included mostly earlier stage disease. The patients were either treated with focal impulse and rotor modulation (FIRM) ablation prior to conventional ablation for pulmonary vein isolation (n=32) or conventional ablation alone (n=71).

According to results, rotors and focal drivers were observed in 98% of AF patients. FIRM ablation led to termination of or substantially slowed AF within 10 minutes of ablation when preceding conventional ablation. FIRM also dramatically improved two-year freedom from AF when compared with conventional ablation alone (84% vs. 50%).

“The promising results of the CONFIRM study show that with a single procedure we can improve the success rate of conventional ablation,” said Narayan in a press conference. “This means we should reevaluate the way we are thinking about AF as a rhythm and potentially ablating it.”

[Chevychelov]

Ambulatory blood pressure monitoring in diabetic patients: new data, new questions
[Ссылки доступны только зарегистрированным пользователям ]

Cardiovascular Outcomes in Framingham Participants With Diabetes
[Ссылки доступны только зарегистрированным пользователям ]

Have You Checked Your Blood Pressure Today?
[Ссылки доступны только зарегистрированным пользователям ]

Prevalence and Risk Factors Associated With Prehypertension: Identification of Foci for Primary Prevention of Hypertension
[Ссылки доступны только зарегистрированным пользователям ]

Cardiometabolic Risk in Community-Dwelling Persons With Chronic Spinal Cord Injury
[Ссылки доступны только зарегистрированным пользователям ]

[Chevychelov]

Influence of COURAGE trial on optimal medical therapy use small

Borden WB. JAMA. 2011;305:1882-1889.

During the years after the publication of the COURAGE trial results, few changes were observed in the practice patterns of optimal medical therapy use among patients with stable coronary artery disease undergoing percutaneous coronary intervention, according to a new study.

In 2007, Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) data indicated that PCI and optimal medical therapy (OMT) did not improve survival or prevent MI in patients with stable CAD compared with OMT alone.

In the current analysis, researchers set out to find the influence of these results on clinical practice. The observational study featured 467,211 patients (37.1% before, 62.9% after COURAGE publication) with stable CAD undergoing PCI from the National Cardiovascular Data Registry between Sept. 1, 2005, and June 30, 2009. Researchers defined OMT as either being prescribed or having a documented contraindication to medicines, including antiplatelet agents, beta-blockers and statins.

Overall, 206,569 patients were treated with OMT before PCI and 303,864 were treated at discharge after PCI. Before the COURAGE trial, OMT before PCI was used in 43.5% of patients (n=75,381), whereas after the trial, it was used in 44.7% of patients (n=131,188). Additionally, OMT use at discharge after PCI was 63.5% before the COURAGE trial and 66% after the trial.

“Collectively, these findings suggest a significant opportunity for improvement and a limited effect of an expensive, highly publicized clinical trial on routine clinical practice,” the researchers wrote, later concluding that the results “support a call for innovations in how OMT is incorporated into interventional strategies and for improving the translation of clinical evidence into practice.” – by Brian Ellis

It is a paper of some interest. It would appear to be disappointing that the rates of OMT were low and little affected by COURAGE trial results. However, there are significant limitations beyond those reported. The institutions reporting were not constant. Also the purpose of the NCDR CathPCI database is primarily to examine PCI outcomes. The medications and contraindications to medications may not have been as complete or careful as one would hope. Also, while these patients did not have acute coronary syndromes, there may have been some urgency to their care, limiting ability to place patients on OMT prior to their procedures. We should be glad to see a 20% absolute increase in OMT after the procedure given that these patients generally have a length of stay of 1 day and are often not even formally hospital admissions. So, while we should not be complacent and need to do better, let us also not overestimate the problem
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Cardiac rehabilitation improved mortality in patients after PCI

Goel K. Circulation. 2011;doi:10.1161/CIRCULATIONAHA.110.983536.

Findings from a retrospective study have suggested that patients who participated in cardiac rehabilitation within 3 months of percutaneous coronary intervention had a decreased rate of mortality. However, rates of MI and revascularization were not influenced by participation.

“Our results provide supportive evidence for the decision by Centers for Medicare and Medicaid Services to cover cardiac rehabilitation in PCI patients and for the recommendations in clinical practice guidelines and performance measures that support cardiac rehabilitation for all PCI patients,” the researchers wrote.

In the study, investigators from the Mayo Clinic in Rochester, Minn., examined consecutive patients (n=2,395) from a prospectively collected registry who underwent PCI in Olmsted County, Minnesota. During the 3 months after PCI, 964 patients (40%) participated in at least one outpatient cardiac rehabilitation session.

During a median follow-up of 6.3 years, 503 deaths (199 cardiac-related), 394 MIs and 755 revascularization procedures were reported. Patients who took part in cardiac rehabilitation had a noted reduction in all-cause mortality by all three statistical techniques employed, including propensity score-matched analysis (HR=0.54), propensity score stratification (HR=0.53) and regression adjustment with propensity score in a 3-month landmark analysis (HR=0.55; P<.001 for all three). A trend toward a reduction in cardiac-related mortality among those participated was also reported; however, only propensity score stratification documented a significant reduction (P=.016).
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Mortality, adverse events found higher in patients with elevated biomarkers after nonemergent PCI

Feldman D. Catheter Cardiovasc Interv. 2011;doi:10.1002/ccd.22962.

Elevation of cardiac troponin I and troponin T among patients who underwent nonemergent percutaneous coronary intervention was predictive of long-term all-cause mortality and a composite of adverse events in a new study.

All patients (n=22,353) in the analysis were compiled from 22 studies published between 1998 and 2009 that reported on the prognostic effect of cardiac troponin I (cTnI) and troponin T (cTnT). All-cause mortality was defined as the study’s primary endpoint.

In all, post-PCI cTnT or cTnI was elevated in 32% of patients. During a mean follow-up of 17.7 months, the primary endpoint was noticeably higher for patients with cTnI or cTnT elevation after PCI compared with patients without cTnI or cTnT elevation (OR=1.45; 95% CI, 1.22–1.72). Similarly, the composite of adverse events of all-cause mortality and MI in patients with cTnI or cTnT elevation was also higher (OR=1.77; 95% CI, 1.48-2.11).

“Our meta-analysis supports the ACC/AHA recommendation to monitor cTn markers post-PCI as to assess long-term clinical outcomes and to identify patients with high-risk coronary artery features,” the researchers wrote. “Further studies are needed to determine if peri-procedural efforts to minimize cTn elevations and more intensive outpatient monitoring/treatment of patients with elevated cTn levels after nonemergent PCI will result in improved long-term outcomes.” – by Brian Ellis

Meta-analyses can be very valuable but can also be misleading. One of the major problems with almost all of the studies in this area is that they use a baseline value that with rare exception is markedly above the recommended cut off value of the 99th percentile. When one does this one ignores the prognostic significance of the baseline value and also fails to understand that the values are most often rising. Thus, the results post procedure are substantially more elevated. Some would say most of the increase is due the natural rise of the elevated baseline value and most often not the procedure. If one uses the 99th percentile value as to define normality at baseline, it turns out that most if not all of the prognostic significance resides in the baseline value and there is modest or perhaps no additional contribution of the post-intervention values either short- or long- term. Lack of attention to this critical metric has confounded all of the meta-analyses and most of the studies. If one uses the 99th percentile value to define a normal baseline as in the Prasad study, there is no additional prognostic value in the post-PCI values. Unfortunately, that is the only study that uses that value at baseline. Thus, one needs to consider this meta-analysis with great caution.

[Chevychelov]

Genetic defects predictive of adverse events in patients with long QT syndrome

Jons C. Sci Transl Med. 2011;3:76ra28.

Mutations that caused a slow activation of the potassium current channel strongly correlated with an increased risk for cardiac events in patients with long QT type 1 syndrome, one of the most common forms of long QT syndrome.

In a recent study, Coeli M. B. Lopes, PhD, and fellow researchers examined 17 mutations found in 387 patients with long QT type 1 (LQT1) syndrome from four long QT syndrome international registries. They correlated the clinical phenotype of patients (n=314) with cellular electrophysiological characteristics resulting from an array of mutations in the slow potassium current channel alpha-subunit KCNQ1 to determine whether there was an association between channels with a decreased rate of current activation and an increased risk for cardiac events, which included syncope, aborted cardiac arrest requiring defibrillation and sudden cardiac death.

They found there was a direct association between channels with a decreased rate of current activation and an increased risk for events (HR=2.02). This association was independent of the clinical parameters used for risk stratification.

Furthermore, for patients with moderate QT prolongation, which was defined as a QT interval of less than 500 ms, slower activation independently predicted an increased risk for cardiac events (HR=2.10), although length of QT interval did not.

“The appropriate clinical care for LQT1 patients with modest corrected QT prolongation is not well established, with many patients remaining untreated,” Lopes and colleagues wrote. “Identification of high-risk mutations in this population could lead to more aggressive treatment in the population at risk and better patient care.”
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Prescription adherence with CVD medications complex process in US

Choudhry N. Arch Intern Med. 2011;171:814-822.
Salanitro A. Arch Intern Med. 2011;171:822-823.

A new study appearing in the Archives of Internal Medicine has highlighted the complexity involved with prescription adherence with CVD medications in the United States, leading researchers to conclude that it may be necessary to reduce this complexity to improve adherence.

“Because nonadherence is associated with excess morbidity and mortality, our findings suggest that therapeutic complexity may undermine the goals of chronic disease management,” they wrote. “In addition, these results highlight an essential aspect of the therapeutic cascade that may be particularly burdensome and which few clinicians likely consider when making prescribing decisions.”

Researchers used prescription claims data from CVS Caremark, a pharmacy benefit manager in Rhode Island with more than 50 million beneficiaries in the United States, to generate these results. The study population consisted of individuals who were prescribed a statin (n=1,827,395) or an ACE inhibitor or renin angiotensin receptor blocker (n=1,480,304) from June 1, 2006, to May 30, 2007. Complexity was determined by measuring the number of medications, pharmacies, pharmacy visits, prescribers and refill consolidation for 3 months after first prescription.

Overall, 80% of medication users in both cohorts were prevalent users, meaning they had received a prescription for a member of the therapeutic class within the prior 12 months. During a 1-year period, researchers found that statin users (mean age, 63 years; 51% female) filled 11.4 prescriptions for 6.3 different medications, had prescriptions written by two prescribers and made five visits to the pharmacy. Data for angiotensin receptor blocker and ACE inhibitor users was similar.

According to adjusted models, patients who had the least refill consolidation, which was determined by measuring the number of visits per fill, had 8% lower adherence rates in the year than patients with the greatest refill consolidation.

For Amanda H. Salanitro, MD, and Sunil Kripalani, MD, with the department of medicine, Vanderbilt University, Nashville, Tenn., and authors of the accompanying editorial, even with the study’s limitations, they wrote that it provides a valuable step forward in measuring the complexities of prescription medication management, as well as its effect on adherence.

“Based on the results of this study, additional research is needed to determine if a reduction in therapeutic complexity (ie, fewer prescribers and/or pharmacies or maximal refill consolidation) positively affects adherence,” they said. “Few published adherence interventions have addressed complexity comprehensively. Such programs are most likely to benefit patients with multi-morbidity and complex medication regimens.”

Disclosures: Dr. Kripalani is a consultant to and holds equity in PictureRx, LLC, and has served as a consultant to Pfizer and Bristol-Myers Squibb/Sanofi-Aventis. Dr. Salanitro reports no relevant financial disclosures.

[Chevychelov]

New combination therapy offers promising approach for hypertension management

American Society of Hypertension 2011 Annual Scientific Meeting

NEW YORK — Among patients with stage II systolic hypertension, azilsartan medoxomil, a newly approved angiotensin II receptor antagonist, plus chlorthalidone led to greater reductions in systolic BP compared with olmesartan plus hydrochlorothiazide, according to findings presented here at the American Society of Hypertension 2011 Annual Scientific Meeting and Exposition.

According to study investigator William C. Cushman, MD, of the University of Tennessee College of Medicine in Memphis, this was the first large, forced titration study of an angiotensin II receptor blocker fixed-dose combination.

“This [study] gives the maximum comparison in terms of the effectiveness of these products … and demonstrates superior efficacy of the [azilsartan medoxomil-chlorthalidone] fixed-dose combinations compared with [olmesartan-hydrochlorothiazide],” Cushman said in a press conference.

In the phase 3, multicenter, double blind, randomized study, the effects of two doses of azilsartan medoxomil (AZL-M; Edarbi, Takeda Pharmaceuticals) plus chlorthalidone (CLD) were compared with olmesartan (OLM) plus hydrochlorothiazide (HCTZ). The study design called for force titrating to maximum doses for all three arms during a 12-week interval: 20 mg AZL-M/12.5 mg CLD to 40 mg AZL-M/25 mg CLD (n=355); 40 mg AZL-M/12.5 mg CLD to 80 mg AZL-M/25 mg (n=352); and 20 mg OLM/12.5 mg HCTZ to 40 mg OLM/25 mg HCTZ (n=364). Only patients aged at least 18 years and with post-washout clinic systolic BP of between 160 mm Hg and 190 mm Hg were included.

At 12 weeks, the study’s primary endpoint of change in clinic systolic BP favored both the 40/25-mg (–42.5 mm Hg) and 80/25-mg AZL-M arms (–44 mm Hg) vs. the OLM arm (–37.1 mm Hg; P<.001 for both comparisons). Similarly, change in 24-hour mean systolic BP also favored the 40/25-mg (–33.9 mm Hg) and 80/25-mg AZL-M arms (–36.3 mm Hg) compared with the OLM arm (–27.5 mm Hg; P<.001 for both).

Overall, adverse events appeared more frequently in the 40/25-mg (71.3%) and 80/25-mg (70.7%) AZL-M groups vs. the OLM group (60.2%). However, serious adverse events were least common in the 40/25-mg group (0.3%), followed by OLM (2.2%) and ALZ 80/25 mg (2.8%).

The study was sponsored by Takeda. – by Brian Ellis

Disclosure: In the past 12 months, Dr. Cushman reports receiving grant/research support from Merck, GlaxoSmithKline and Novartis and has consulted for Takeda, Novartis and Noven.

For more information:
Cushman W. LB-OR-03. Presented at: American Society of Hypertension 2011 Annual Scientific Meeting and Exposition; May 21-24, 2011; New York.

This certainly is an impressive study. AZL-M as mono-therapy seems to be an absolutely superb angiotensin II receptor blocker. It has been shown to lower BP more efficaciously than 40 mg of OLM, which is a very good angiotensin II receptor blocker as we know. However, why AZL-M is so much better than the others is not entirely clear.

It is important to consider, though, that there was no placebo in this study. There would certainly be a placebo reduction [in systolic BP] of about 10 mm HG. Therefore what you would then see when you then look at 24-hour BP is much more realistic, but still extremely good.

Another point is that we have shown that CLD is absolutely more powerful than HCTZ. It has been established in quite a few studies, though never in a combination, so we cannot say this is a good way of comparing the two. But it is my suspicion that the good anti-hypertensive effects of AZL-M and CLD are obviously synergistic and will beat the competition.
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High prevalence of masked hypertension confirmed among blacks

American Society of Hypertension 2011 Annual Scientific Meeting

NEW YORK — New research presented here has confirmed previous data that indicated a high prevalence of masked hypertension among blacks and further reinforces the importance of ambulatory BP monitoring to help identify patients with high BP who do not present as such at doctors’ office visits.

The preliminary study included 38 black patients (mean age, 51 years; 86.8% women) from the Philadelphia region who were sedentary, nondiabetic, nonsmoking, not on antihypertensive medication and did not have CVD. Office BP measurements were taken during three visits on an average of three readings per visit, whereas ambulatory BP monitoring was performed on a typical day of the patient and was set to go off at 30-minute intervals during the day (6 a.m. to 10 p.m.) and 60-minute intervals during the night (10 p.m. to 6 a.m.).

According to study data, the BP measurements at the office were 124.4 mm Hg/79.1 mm Hg for the first visit, 126.4 mm Hg/80.1 mm Hg for the second visit 1 week later and 128.7 mm Hg/79.7 mm Hg for the third, whereas the mean ambulatory BP monitoring for 24 hours was 126.7 mm Hg/78.5 mm Hg (daytime, 128.4 mm Hg/80.2 mm Hg; nighttime, 116.8 mm Hg/68.6 mm Hg). The prevalence of masked hypertension decreased with each visit, from 59% on the first visit to 40% on the second visit and 38% on the third visit. Additionally, as an average for all three BP office measurements, roughly 45% of the population consistently had masked hypertension.

“The take-home message is office BP may not be sufficient, especially in this cohort,” study researcher Praveen Veerabhadrappa, MD, MS, research fellow, International Society of Hypertension Doctoral Candidate, Hypertension Molecular & Applied Physiology Lab, said in a press conference. “Close to 45% had masked hypertension, and they were not even aware they had hypertension. They may require some kind of intervention, whether it be nonpharmacological or pharmacological.” – by Brian Ellis

If you look at end-organ damage for African Americans compared with whites for the same level of office BP, African Americans have significantly higher rates of stroke, kidney disease and HF. This is probably the reason (for reasons that we don’t quite understand yet) that African Americans have higher BP outside the office than inside the office. The implication then is we can’t be complacent with a normal BP for an African American in the office. We are going to have to do more ambulatory BP monitoring and home monitoring.

[Chevychelov]

FDA panel advises clinical trial, revised labeling of fenofibric acid

The FDA Endocrinologic and Metabolic Drugs Advisory Committee unanimously recommended a clinical trial to assess the cardiovascular benefits of adding fenofibric acid to statin treatment in high-risk men and women with high triglycerides and low HDL.

The panel also narrowly advised for revision of the fenofibric acid (Trilipix, Abbott) drug labeling regarding co-administration to include recent data from the Action to Control Cardiovascular Risk Diabetes (ACCORD) Lipid Trial.

Results of two subgroup analyses conducted during the ACCORD-Lipid trial were at the center of the panel discussion. One analysis revealed a higher rate of CV events, especially myocardial infarction, in women taking fenofibrate plus statin vs. men taking the same combination (HR=1.38 vs. HR=0.82). Henry Ginsberg, MD, lead research for the ACCORD-Lipid trial and director of the Irving Institute for Clinical and Translational Research at Columbia University, noted no difference in baseline lipids or lipid response after 48 months between men and women. He said this issue warrants further investigation.

A second subgroup analysis of patients with dyslipidemia revealed a lower rate of major adverse cardiac events among participants with triglycerides in the highest tertile and HDL in the lowest tertile compared with the entire study cohort.

Despite the results of the ACCORD-lipid analyses, as a whole, the panel was hesitant to make recommendations for subgroups because ACCORD-Lipid was a negative trial overall. Consequently, the panel unanimously voted for a clinical trial to be conducted using major adverse cardiac events as an endpoint to test the benefit of adding fenofibrate to statin therapy in high-risk patients with high triglycerides and low HDL.

"In reviewing the data for fibrates, it's not clear to me if these drugs are beneficial or not," William R. Hiatt, MD, professor of medicine at the University of Colorado Denver, said at the meeting.

The committee was divided regarding fenofibric acid's labeling indication for co-administration with a statin. Three members voted to continue marketing and maintain the current indication; four voted to withdraw that particular indication; and six voted to revise the indication for co-administration to incorporate the principal findings from ACCORD.

Edward W. Gregg, PhD, from the division of diabetes translation at the CDC, voted to revise the indication. he said the available evidence indicates potential negative effects, but the data are not strong enough to warrant complete removal. Nevertheless, he said, "I think there should be a more specific indication to prevent overmarketing to people who may not benefit."

In response to the committee's decision, Eugene Sun, MD, vice president of Global Pharmaceutical Clinical Development of Abbott, said in a press release: "We also appreciate the request for more clinical data and look forward to further discussions with the FDA."

ACCORD-Lipid is a randomized, double blind, placebo-controlled, add-on trial that evaluated the efficacy and safety of adding fenofibrate to simvastatin (Zocor, Merck) therapy in more than 5,500 patients with type 2 diabetes. During an average 4.7 years, researchers found no significant difference in the proportion of patients treated with simvastatin plus placebo (11.3%) vs. simvastatin plus fenofibrate (10.5%) who experienced a major adverse cardiac event (HR=0.92; 95% CI, 0.79-1.08).

Fenofibric acid is the active ingredient of fenofibrate. Fenofibrate is a peroxisome proliferator-activated receptor-alpha agonist (PPAR-alpha) that was approved for the treatment of hypertriglyceridemia in 1993. In 2009, the FDA approved the new drug application for fenofibric acid in combination with a statin.

While the FDA is not required to follow the recommendations of the advisory committee, it usually does. - by Melissa Foster
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Echocardiographic measurements promising for predicting improvement after elective PCI
Djordjevic-Dikic A. J Am Soc Echocardiogr. 2011;24:573-581.

Among patients with previous MI, evaluation of basal coronary blood flow pattern and diastolic deceleration time measurements were shown to predict myocardium improvement after elective percutaneous coronary intervention.

The study featured 50 patients (mean age, 53 years; 82% men) with previous MI who underwent elective PCI. Researchers measured their coronary flow using transthoracic Doppler echocardiography before PCI, as well as both 24 hours and 3 months after. Recovery from PCI was determined by an improvement in resting wall motion score index of more than 0.20.

Researchers reported that patients with recovered left ventricular function (n=32) had a longer diastolic deceleration time (DDT) before the procedure compared with patients without improvement in LV function (n=18; 841 ± 286 ms vs. 435 ± 80 ms; P<.001). Furthermore, coronary flow reserve 24 hours after PCI was higher in the recovered group (2.60 ± 0.70 vs. 2.16 ± 0.34, P=.034). Among the univariate predictors of LV functional recovery were end-diastolic and end-systolic volumes, global and regional wall motion scores, as well as DDT before PCI and coronary flow reserve 24 hours after PCI.

Additionally, multivariate analysis also indicated that DDT (P=.003) and regional wall motion score (P=.007) were independent predictors of LV recovery during follow-up.

Commenting on the clinical implications of the study, the researchers wrote that although transthoracic Doppler echocardiography could not be considered as a substitute for other techniques that can directly assess transmurality of myocardial viability, such as MRI or myocardial contrast imaging, it could be useful in providing additional information about coronary pathophysiology and prognosis, considering the broad availability and low cost of the method.

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Younger physicians may be more likely to prescribe CVD drugs

Tocci G. Int J Clin Pract. 2011;65:649-657.

In an analysis of the EFFECTUS trial, researchers observed that outpatients of younger physicians had a higher prevalence of vascular diseases and, as a result, were prescribed more medications for CVDs than patients of older physicians.

Investigators of the study, appearing in the International Journal of Clinical Practice, looked at data collected during the cross-sectional phase of the EFFECTUS program. The study population was composed of 9,904 outpatients (mean age, 67 years) observed by 1,078 physicians in Italy. The physicians were stratified into three age groups — no older than 45 years (n=219), 46 to 55 years (n=658) and older than 55 years (n=201) — and asked to provide clinical data on the first 10 adult outpatients seen in May 2006.

Investigators found higher rates of MI (P=.003), cerebrovascular disease, primarily stroke (P=.008) and transient ischemic attack (P=.031) in outpatients of physicians aged younger than 45 years vs. physicians aged older than 46 years. Physicians aged younger than 46 years were also more likely to prescribe several CVD medications, including ACE inhibitors (P=.006), antihypertensive drugs (P=.005), beta-blockers (P=.016), insulin (P=.005) and antiplatelet agents (P=.013), as opposed to older physicians who more commonly recommended lifestyle changes.

Additionally, information on CV risk factors were far more regularly recorded by physicians aged older than 45 years, whereas those who were younger provided more updated information on organ damage detection.

As a possible explanation for these discrepancies, the researchers wrote that the relatively low rate of data collection and registration found in younger physicians suggests a potential way to improve global CV risk management in the daily clinical practice.

“On the basis of these considerations, specific training and educational programs for specialized physicians should be carefully considered, to improve quality of care, reduce doctor’s inertia and ameliorate the clinical management of CVDs in Italy,” they said.
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Sleep-disordered breathing increased arrhythmias in patients with ICDs

Zeidan-Shwiri T. Heart Rhythm. 2011;8:657-662.

A study in the journal Heart Rhythm has found that patients with implantable cardioverter defibrillators who had sleep-disordered breathing were at significantly higher risk for ventricular arrhythmias compared with those without sleep-disordered breathing.

The prospective study involved 45 patients with an ICD who were enrolled from August 2007 to March 2009. Twenty-six of these patients had sleep-disordered breathing (SDB), defined as an apnea-hypopnea index of morethan 10 events per hour as determined by an overnight sleep study. The current study’s primary endpoint was appropriate ICD therapy during a 1-year follow-up.

During this time, 62% of patients had one or more episodes of ventricular fibrillation or ventricular tachycardia. Researchers reported a higher rate of appropriate ICD therapies in patients with SDB vs. those without (73% vs. 47%; P=.02), with further analysis proving SDB to be a predictor of any ICD therapy (OR=4.4; P=.01). Cited as the cause of the increased risk for ventricular arrhythmias in patients with SDB was the increase in events that occurred between midnight and 6 a.m. (OR=5.6; P=.001), which was not seen during non-sleeping hours.

“These findings provide a rationale for SDB screening in patients with appropriate ICD therapy if device interrogation reveals a predominance of nocturnal onset of arrhythmias,” the researchers concluded. “Future studies are warranted to evaluate whether treatment of SDB reduces the risk of appropriate ICD therapy.”

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EMPHASIS HF: eplerenone shown to reduce atrial fibrillation (AF)
EMPHASIS-HF trial was presented at the Heart Failure Congress 2011, organized by the Heart Failure Association of the European Society of Cardiology (ESC).

Topics: Heart Failure (HF)
Date : 22 May 2011
“This latest analysis makes an even stronger case for the use of eplerenone in patients with mild heart failure because in addition to reducing mortality it also reduces the incidence of AF. AF is a condition which both increases morbidity and complicates the care of patients with heart failure,” says Karl Swedberg, ESC spokesperson.

May 22, 2011- Gothenburg, Sweden : The aldosterone antagonist eplerenone (Inspra, Pfizer) significantly reduced the development of new onset atrial fibrillation and flutter (AFF) in patients with class 2 heart failure, concludes a sub-analysis of the EMPHASIS-HF trial, presented at the Heart Failure Congress 2011, organized by the Heart Failure Association of the European Society of Cardiology (ESC). The analysis, presented in Late Breaking Session 1, furthermore showed that the beneficial effects of eplerenone in reducing major CV events were similar in patients with and without AFF at the start of the study.

The Eplerenone in Mild Patients Hospitalization And Survival Study in Heart Failure study (EMPHASIS-HF) - presented first at the American Heart Association Meeting in 2010 and published simultaneously on-line in the New England Journal of Medicine ¹ - showed that eplerenone in comparison to placebo produced a 37% reduction in the primary end point of the composite of death from cardiovascular causes or hospitalization for heart failure, a 24% reduction in cardiovascular death, and a 42% reduction in hospitalization for heart failure for patients with class 2 heart failure.

While previous studies had shown that aldosterone blockade delivered significant benefits in patients with class 3-4 heart failure (The RALES study) or in post MI patients with left ventricular dysfunction (The EPHESUS study), what had been unknown until EMPHASIS-HF was whether the benefits could be extended to the far larger population of patients with mild heart failure (class1-2). The RALES study used spironolactone, while the EPHESUS study used the newer, more selective eplerenone.

The EMPHASIS-HF trial - which involved 2737 patients from 278 centres with NYHA class 2 heart failure and ejection fractions of no more than 35% - set out to address the question of whether eplerenone was effective in patients with mild heart failure. Patients were randomized to receive eplerenone (25mg once daily, up titrated to 50 mg daily if required) or placebo in addition to recommended therapy. The trial was stopped after 21 months due to the significant benefits in the eplerenone group. In the current presentation, the investigators have re-analyzed the original data to explore the development of new onset atrial fibrillation or flutter (AFF) in patients who had no history of AFF at baseline. The study also set out to determine whether eplerenone worked as well in patients who already had AFF at baseline as those who did not.

Results at an average follow-up of two years showed that new onset AFF occurred in 25/911 (2.7%) of the patients in the group randomized to eplerenone versus 40/883 (4.5%) in the group randomized to placebo (hazard ratio (HR) 0.58 95% CI 0.35-0.96, p=0.034). The analysis also showed that the risk of cardiovascular (CV) death or hospital admission for worsening heart failure (the primary endpoint of the original study) was not significantly different in patients with and without AFF at baseline (P=0.33).

Commenting on the results study presenter Karl Swedberg, from the University of Gothenburg, Sweden, said, “This latest analysis makes an even stronger case for the use of eplerenone in patients with mild heart failure because in addition to reducing mortality it also reduces the incidence of AF. AF is a condition which both increases morbidity and complicates the care of patients with heart failure.”

Use of eplerenone in patients with mild heart failure, he added, will be considered for inclusion in the ESC guidelines when they are updated at the end of 2011.

Eplerenone
Eplerenone, which has been called a "cleaner, safer" version of spironolactone, is approved for hypertension and for use in addition to optimal medical therapy early after acute MI in patients with congestive heart failure (CHF), on the basis of the Eplerenone Post-AMI Heart Failure Efficacy and Survival Study (EPHESUS) study. It has, however, yet to be approved for patients with mild HF.
While eplerenone is available generically in the US, the drug is still under patent in Europe and Canada.

Authors:
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References
Zannad F, McMurray JJV, Krum H, et al. Eplerenone in patients with systolic heart failure and mild symptoms. New Eng J Med 2011: 364:11-21. Available at: [Ссылки доступны только зарегистрированным пользователям ].

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MADIT: study defines patient group most likely to benefit from cardiac resynchronisation therapy (CRT)
The CRT-MADIT-CRT trial - was presented at the Heart Failure Congress 2011, organized by the Heart Failure Association of the European Society of Cardiology (ESC) in Late Breaking Session 1.

Topics: Heart Failure (HF)
Date : 22 May 2011
Patients with dyssynchronous yet viable ventricles are most likely to benefit from cardiac resynchronization therapy combined with defibrillation, concludes the latest analysis of the MADIT CRT trial.

Patients with dyssynchronous yet viable ventricles are most likely to benefit from cardiac resynchronization therapy combined with defibrillation, concludes the latest analysis of the MADIT CRT trial. The CRT-MADIT-CRT trial - presented at the Heart Failure Congress 2011, organized by the Heart Failure Association of the European Society of Cardiology (ESC) in Late Breaking Session 1 - showed that CRT produced improvements in both synchrony and contractile function, and that the extent of this benefit relates to subsequent outcomes.

The Multicentre Automatic Defibrillator Implantation Trial-CRT (MADIT-CRT) set out to determine whether patients with mild heart failure (NYHA class I or II) would do better if they got implanted with a CRT-D device (which combines cardiac resynchronization therapy with defibrillation), than if they only received the traditional ICD defibrillation. In earlier studies CRT-D devices had been approved for use in patients with severe heart failure (NYHA class III/IV).

In the MADIT-CRT study, funded by Boston Scientific, 1820 patients with Class I and II heart failure, wide QRS and left ventricular dysfunction were randomized 3:2 to receive CRT-D (n=1089) or ICD alone (n=731). Results, presented at the 2009 ESC Annual Conference in Barcelona after a follow period averaging 2.4 years, demonstrated a greater than 40% reduction in the primary endpoint of death or heart failure in patients receiving CRT-D. However, in virtually all studies of CRT-D approximately 30% of patients do not respond to therapy.

In the current study, Dr Scott D Solomon (Brigham and Women’s Hospital, Boston, MA) and colleagues set out to investigate whether the degree of synchrony – the extent to which the walls of the left ventricle contract in unison – might influence the likelihood of patients responding to CRT-D. “It’s important to target patients in whom CRT-D works well because the technology is quite expensive,” explained Soloman.

In this latest analysis of MADIT-CRT, investigators analyzed echocardiograms from 1077 patients enrolled in MADIT-CRT (CRT-D n=66; ICD, n=416) who had echocardiographic images of sufficient quality to allow analysis of synchrony and contractile function. Researchers were blinded to the randomization and study outcomes.

Results showed that patients with mild to moderate dyssynchrony at baseline (defined as a time-to peak transverse strain SD of 142-230 ms) and greater baseline contractile function (longitudinal strain < -8.7%) improved to a greater extent when randomised to the CRT-D group than the ICD only group.

The study showed that over a year each 10 ms decrease in LV dyssynchrony was associated with a 3% reduction in the primary outcome of death or heart failure, and each 5 point absolute increase in LV strain was associated with a 75% reduction in the primary outcome.

“These results suggest that the patients who are most likely to benefit from CRT-D are those with at least some dyssynchrony who have relatively preserved contractile function,” said Solomon, adding that the observation that improvements in synchrony and contractile function were associated with reduced death and heart failure events, suggests that the benefits delivered by CRT relate to improvements in these factors. “Future studies will continue to try to identify the patients who are most likely to benefit from this expensive but highly effective therapy,” he said.

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AIM-HIGH study halted prematurely by NIH

The NIH has stopped the AIM-HIGH trial 18 months earlier than planned due to a lack of efficacy in reducing CV events of a combined treatment of niacin and statin compared with statin alone.

In the Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides (AIM-HIGH) trial, 3,414 patients from the United States and Canada with a history of CVD were either treated with a combination of a high-dose, extended release niacin and statin or stain therapy alone. Over the study’s 32 months of follow-up, patients who took the combined therapy had increased HDL cholesterol and lowered triglyceride levels. Despite this, the combination treatment failed to reduce fatal or non-fatal heart attacks, strokes, revascularization procedures or hospitalizations for acute coronary syndrome.

The FDA, in an official statement released in an email, noted that the role niacin may have played in the reported imbalance in ischemic stroke was not yet clear.

“At this time, FDA has made no new conclusions or recommendations regarding the use of extended-release niacin alone or in combination with simvastatin or other statins,” they wrote in the statement. “The Agency will conduct a comprehensive review of the AIM-HIGH trial data as soon as they become available to determine their impact on the approved indications for extended-release niacin.”

The study was funded by NHBLI with additional support from Abbott. The full NIH press release is available here.

I would hope that this information improves the quality of life for those patients who are repeatedly encouraged to continue to take these preparations despite their very annoying cutaneous side effects.
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Biomarkers associated with mortality in elderly patients with HF symptoms

Alehagen U. JAMA. 2011;305:2088-2095.

An increased concentration of copeptin, a surrogate marker for vasopressin, alone or combined with N-terminal pro–B-type natriuretic peptide was associated with an increased risk for all-cause mortality in elderly patients with symptoms of HF.

Researchers from Sweden and Denmark performed the study by looking at 470 elderly patients (mean age, 72.6 years) from the primary health care population in Sweden. All patients had HF symptoms, including shortness of breath, fatigue and/or peripheral edema during 1996. Physicians performed clinical examination, echocardiography and peptide measurements.

During follow-up, which lasted through December 2009, 226 all-cause and 146 CV-related deaths were reported. Patients with more than 18 pmol/L of copeptin (fourth quartile; n=118) compared with those with less than 5.70 pmol/L (first quartile; n=117) had a greater risk for both all-cause (HR=2.04; 95% CI, 1.38-3.02) and CV mortality (HR=1.94; 95% CI, 1.20-3.13).

When researchers looked at levels of copeptin combined with N-terminal pro–B-type natriuretic peptide (NT-proBNP), they found a similar correlation with all-cause mortality (copeptin fourth quartile, HR=1.63; 95% CI, 1.08-2.47; NT-proBNP fourth quartile, HR=3.17; 95% CI, 2.02-4.98). Furthermore, use of biomarkers simultaneously to evaluate CV mortality resulted in significant associations for both copeptin in the presence of NT-proBNP (P=.048) and for NT-proBNP (fourth quartile, HR=4.68; 95% CI, 2.63-8.34).

These results, the researchers concluded, suggest that vasopressin may be a potential target for therapeutic intervention.
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More primary care physicians yielded better patient outcomes

Chang C. JAMA. 2011;305:2096-2105.
Lower mortality rates were observed among a cohort of Medicare beneficiaries in areas of the US with more primary care physicians compared with areas with fewer primary care physicians, according to study results.

Researchers from several sites in the US attempted to outline clearer links between the adult PCP work force and individual patient outcomes.

The study population included 5,132,936 fee-for-service Medicare beneficiaries aged at least 65 years. The analysis involved 6,542 primary care service areas.

The researchers used two measures of adult PCPs (including general internists and family physicians): American Medical Association Masterfile nonfederal, office-based physicians per total population; and office-based primary care clinical full-time equivalents per Medicare beneficiary derived from Medicare claims.

Outcome measures included mortality, ambulatory care sensitive condition hospitalizations and Medicare program spending. These outcomes were adjusted for individual patient characteristics and geographic area variables.

Although there was variability in the PCP work force across geographical areas, low correlation was observed between the two primary care work force measures (Spearman rank correlation coefficient=0.056; P<.001).

Data from the AMA Masterfile counts indicated that beneficiaries in areas with the highest quintile of PCPs had fewer ambulatory care sensitive condition hospitalizations than those in areas in the lowest quintile, 74.9 vs. 79.61 per 1,000 beneficiaries (RR=0.94; 95% CI, 0.93-0.95). Lower mortality rates (5.38 vs. 5.47 per 100 beneficiaries; RR=0.98; 95% CI, 0.97-0.997) also were observed in the highest quintile compared with the lowest quintile.

No significant difference in total Medicare spending ($8,722 vs. $8,765 per beneficiary; RR=1.00; 95% CI, 0.99-1.00) was observed between the lowest quintile and the highest quintile.

In the analysis of primary care full-time equivalents per beneficiary, those residing in the highest-quintile areas had lower mortality rates compared with those residing in lowest-quintile areas, 5.19 vs. 5.49 per 100 beneficiaries (RR=0.95; 95% CI, 0.93-0.96). Also, in the full-time equivalents analysis, fewer ambulatory care sensitive condition hospitalizations (72.53 vs. 79.48 per 1,000 beneficiaries; RR=0.91; 95% CI, 0.90-0.92) and higher overall Medicare spending ($8,857 vs. $8,769 per beneficiary; RR=1.01; 95% CI, 1.004-1.02) were observed among beneficiaries residing in areas of the highest quintile compared with those in the lowest quintile.

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Patients with pneumonia at increased risk for early cardiac arrest

Patients hospitalized for pneumonia may be at increased risk for early cardiac arrest and may present with little or no warning symptoms, according to data presented at the American Thoracic Society 2011 International Conference.

“We found a compelling signal that some patients with pneumonia may develop cardiac arrest outside of the intensive care unit, without apparent shock or respiratory failure,” Gordon Carr, MD, pulmonary and critical care fellow at the University of Chicago Medical Center, said in a press release. “If this is true, then we need to improve how we assess risk in pneumonia.”

Carr and colleagues pooled data from the American Heart Association’s Get with the Guidelines database among 44,416 in-hospital cardiopulmonary arrest cases who went into early cardiac arrest within 72 hours of hospital admission. Of these, 5,367 patients had pre-existing pneumonia. The median time from hospital admission to in-hospital cardiopulmonary arrest was 20.7 hours.

Of these patients, 77.2% of cardiac arrests occurred in an ICU step-down unit, and 19.3% occurred in the general patient area. At the time of cardiac arrest, only 40% of patients with pre-existing pneumonia received mechanical ventilation, and 36.3% received infusions of vasoactive therapies, according to the study abstract.

Causes of in-hospital cardiopulmonary arrest included arrhythmia (65%), respiratory insufficiency (53.9%) and hypotension/hypoperfusion (49.8%).

“While our study design precluded definitive analyses of incidence or cause and effect, our main finding was that some patients with pneumonia and cardiac arrest did not appear to experience a premonitory period of overt critical illness,” Carr said. “There appears to be an important group of patients with pneumonia who develop cardiac arrest without respiratory failure or shock.”

Carr said future studies should “examine the incidence and cause of sudden, early cardiovascular collapse in patients with pneumonia and other forms of sepsis, and address ways to measure and mitigate this risk. In the meanti
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Polypill linked with improved BP, LDL levels

PILL Collaborative Group. PLoS One. 2011;doi:10.1371/journal.pone.0019857.

A pill containing aspirin plus BP- and cholesterol-lowering agents was linked to reductions in systolic BP and LDL, according to recent results.

The pill contains 75 mg of aspirin, 10 mg of lisinopril, 12.5 mg of hydrochlorothiazide and 20 mg of simvastatin. There were 378 eligible participants who had no indication for any component of the pill but who had an estimated 5-year CVD risk of more than 7.5%.

Baseline data indicated that the mean BP was 134 mm Hg/81 mm Hg and the mean LDL cholesterol was 3.7 mmol/L.

A 9.9 mm Hg reduction in systolic BP (95% CI, 7.7-12.1) was linked to polypill treatment at 12 weeks’ follow-up. The pill also was associated with a reduction in LDL cholesterol of 0.8 mmol/L (95% CI, 0.6-0.9).

Patients in the treatment group discontinued at a rate of 23% vs. an 18% discontinuation rate in the placebo group (RR=1.33; 95% CI, 0.89-2.00).

Adverse events were reported in 58% of recipients and 42% of placebo recipients (P=.001). These events were evident early on in the trial but generally did not warrant cessation of treatment, according to the researchers.

The primary outcomes of the randomized, double blind, placebo-controlled trial were systolic BP, LDL cholesterol and tolerability (proportion discontinued randomized therapy) by 12 weeks.

“This polypill achieved sizeable reductions in [systolic] BP and LDL cholesterol but caused side effects in about one in six people,” the researchers wrote. “The halving in predicted cardiovascular risk is moderately lower than previous estimates and the side effect rate is moderately higher. Nonetheless, substantial net benefits would be expected among patients at high risk.”

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Racial disparity in quality of PCI hospital observed among Medicare beneficiaries
Popescu I. Circulation. 2011;doi:10.1161/circulationaha.110.973628.

Researchers of a study appearing in Circulation have found that black Medicare beneficiaries are significantly less likely to undergo percutaneous coronary intervention in high-quality and revascularization hospitals compared with white beneficiaries.

The California and Iowa-based researchers performing the analysis pooled data from 1,244 US hospitals that had at least 50 black admissions in 2005. The 65,633 patients included in the study were either black (n=8,291) or white (n=57,342) and all had acute MI. Hospital quality was determined by a composite score composed of hospital risk-adjusted 30-day mortality and acute MI performance measures, with the top 20% designating high quality and the lowest 20% representing low quality.

Overall, blacks lived closer to revascularization (3.8 vs. 6.8 miles), high-quality (5.6 vs. 9.7 miles) and low-quality hospitals (25.5 vs. 36.9 miles; P<.001 for all three). After adjustment for distance, blacks had a significantly lower likelihood of being admitted to revascularization (RR=0.87) and high-quality hospitals (RR=0.88) while also having a higher likelihood of being admitted to low-quality hospitals (RR=1.17; P<.001 for all three).

Despite the study having several limitations, including lack of data on patient preferences and the inclusion of only white and black Medicare beneficiaries, the researchers wrote that the findings provide important information on factors contributing to racial disparities in acute MI treatment.

“The study confirms the role of differential access to hospitals with revascularization services and high quality of care as a plausible source of disparity,” they said. “However, racial differences in access to high-quality hospitals appear to be primarily driven not by race in itself, but by differences in where the majority of blacks and whites live and seek care. Effective policy recommendations aimed at reducing disparities need to take local socioeconomic and health care system factors into consideration.”
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Tonsillectomy and appendectomy as a child may increase MI risk

Janszky I. Eur Heart J. 2011;doi:10.1093/eurheartj/ehr137.

A link may exist between undergoing a tonsillectomy or appendectomy as a child and an increased risk for MI as an adult, results of a new study indicate.

Although the tonsils and appendix are not considered vital to the body, Swedish researchers have found that those who had them removed before the age of 20 years may have a slightly greater risk for premature acute MI.

“Given the strong biological and epidemiological evidence linking inflammation with coronary heart disease, one might anticipate that surgical removal of the tonsils and appendix, with their consequent effects on immunity, might also have a long-term effect on coronary heart disease,” Imre Janszky, MD, of the department of public health science at the Karolinska Institute in Stockholm, Sweden, said in a news release from the European Society of Cardiology. “However, we were aware of no studies evaluating the potential effects of appendectomy or tonsillectomy on atherosclerosis or coronary heart disease risk.”

For the prospective matched-cohort study, the researchers identified 54,449 appendectomies and 27,284 tonsillectomies performed on Swedish residents aged younger than 20 years; participants were born between 1955 and 1970. The patients were followed for an average of 23.5 years to determine how many would suffer fatal or non-fatal MIs.

Within the follow-up period, 89 of the participants who underwent appendectomies and 47 of those who underwent tonsillectomies experienced an acute MI, the investigators found.

The research team derived HRs from proportional hazard models adjusted for parental occupation and parental history of acute MI. Operations before the patient was aged 20 years were associated with an increased risk for acute MI (417 and 216 events in the appendectomy and tonsillectomy datasets, respectively), with adjusted HRs of 1.33 (95% CI, 1.05-1.70) for appendectomy and 1.44 (95% CI, 1.04-2.01) for tonsillectomy.

“These results are consistent with the hypothesis that subtle alterations in immune function following these operations may alter the subsequent cardiovascular risk, but further studies are needed to confirm these findings and to explore possible mechanisms,” the researchers wrote.

Because the study was limited to childhood procedures and participants were relatively young during the follow-up period, the findings may not apply to older people at greater risk for heart disease, they concluded.