Hypertension rebels voice doubts about ALISKIREN
New York, NY - Doubts about the effectiveness of the new renin inhibitor antihypertensive aliskiren (Tektura, Novartis) have been voiced in a somewhat controversial review article in the May 2007 issue of the American Journal of Hypertension [1].
The authors, Dr John Laragh (editor of the journal) and his wife and fellow hypertension researcher Dr Jean Sealey (New York Hospital/Cornell University Medical Center, New York), say that aliskiren is no more effective than current antihypertensives and suggest that its ability to lower blood pressure may be limited by reactive renin secretion, an effect that may actually increase blood pressure in certain patient groups.
In an interview with heartwire, Laragh said: "We don't have an urgent need for a new drug like this. It is not a breakthrough. It is a weak antihypertensive drug. It is no better than what we already have, and it will be much more expensive. In addition, aliskiren causes a greater reactive rise in renin production than any other antihypertensive, which could be dangerous for patients with the most highly reactive renin systems."
Laragh and Sealey are no strangers to controversy, having been at the center of a bitter row with the American Society of Hypertension (ASH), which resulted in the American Journal of Hypertension no longer being the official journal of ASH and the end of Laragh's and Sealey's involvement with ASH.
Thursday, May 17, 2007
Ruling Out Pulmonary Embolism With A Simple Bedside Protocol
Medical News Today
Ruling Out Pulmonary Embolism With A Simple Bedside Protocol
16 May 2007
Although clots in the lung (pulmonary embolism or PE) are the second-leading cause of sudden death in the United States, blood tests and ultrafast CT scanning to detect PE are being used on so many patients that over 90% of these tests are negative. In a paper to be presented at the 2007 Society for Academic Emergency Medicine (SAEM) Annual Meeting, Jeff Kline, MD, Carolinas Medical Center, Charlotte, NC, will show that the use of simple clinical criteria can eliminate the risk and expense of these unnecessary tests.
The Pulmonary Embolism Rule-out Criteria, or the PERC rule, functions as a way to rule out clots in the lung. The blood test, called D-Dimer, has a very low specificity for PE, leading to many false positives. The CT scan costs $2500, has the potential for kidney damage in 1 in 12 patients, and has a heavy radiation dose that increases lifetime risk of cancer. Yet, doctors are ordering these tests for 2-3% of all Emergency Department patients or 3.5 million cases per year. According to the author, the fear of medical malpractice has led to a culture of doing tests rather than using the data available through clinical evaluation.
The study looked at an 8,138 patient random sample from 13 hospitals. By using a Web-based real-time data collection method and an extremely rigorous study design, it was able to capture the doctor's beliefs at the time of treatment, prior to the time that results were available. Importantly, the study design captured the physicians "gestalt" or gut instinct of how likely they thought PE was on their list. The results showed that fully two thirds of all testing is done in patients where the physician believed that the probability of PE was less than 15%.
In the best case, this study could reduce testing for PE by approximately 20-25%. More importantly, this is a first step toward a culture change of using intelligent clinical criteria instead of expensive technology to rule out life-threatening disease. According to Dr. Kline, "I interpret our data as a manifestation of the erosion of the physician-patient relationship.
Physicians now believe more than ever that every patient with any hint of a life-threatening illness should have the most expensive, most technological 'standard-of-care' diagnostic test ordered to rule out that illness. This multicenter collaborative project shows that we can use a careful history and physical examination to achieve the same degree of certainty without the cost and side effects of diagnostic testing. Patients do not want a technician to check off tests on an order sheet while the physician hurries off to see the next patient. The ability to document 'PERC rule negative' on the chart will provide physicians with the scientific and medicolegal backstop they need to justify not ordering a test on every patient with any hint of PE in their history or physical examination."
The presentation is entitled "Prospective, Multicenter Validation of the Pulmonary Embolism Rule-Out Criteria" by Jeff Kline, MD, of the Carolinas Medical Center. This paper will be presented at the 2007 SAEM Annual Meeting, May 16-19, 2007, Chicago, IL on Wednesday, May 16th, in the Plenary Session beginning at 1:00 PM in Sheraton 4 & 5 of the Sheraton Chicago Hotel & Towers. Abstracts of the papers presented are published in Volume 14, Issue 5S, the May 2007 supplement of the official journal of the SAEM, Academic Emergency Medicine.
Ruling Out Pulmonary Embolism With A Simple Bedside Protocol
16 May 2007
Although clots in the lung (pulmonary embolism or PE) are the second-leading cause of sudden death in the United States, blood tests and ultrafast CT scanning to detect PE are being used on so many patients that over 90% of these tests are negative. In a paper to be presented at the 2007 Society for Academic Emergency Medicine (SAEM) Annual Meeting, Jeff Kline, MD, Carolinas Medical Center, Charlotte, NC, will show that the use of simple clinical criteria can eliminate the risk and expense of these unnecessary tests.
The Pulmonary Embolism Rule-out Criteria, or the PERC rule, functions as a way to rule out clots in the lung. The blood test, called D-Dimer, has a very low specificity for PE, leading to many false positives. The CT scan costs $2500, has the potential for kidney damage in 1 in 12 patients, and has a heavy radiation dose that increases lifetime risk of cancer. Yet, doctors are ordering these tests for 2-3% of all Emergency Department patients or 3.5 million cases per year. According to the author, the fear of medical malpractice has led to a culture of doing tests rather than using the data available through clinical evaluation.
The study looked at an 8,138 patient random sample from 13 hospitals. By using a Web-based real-time data collection method and an extremely rigorous study design, it was able to capture the doctor's beliefs at the time of treatment, prior to the time that results were available. Importantly, the study design captured the physicians "gestalt" or gut instinct of how likely they thought PE was on their list. The results showed that fully two thirds of all testing is done in patients where the physician believed that the probability of PE was less than 15%.
In the best case, this study could reduce testing for PE by approximately 20-25%. More importantly, this is a first step toward a culture change of using intelligent clinical criteria instead of expensive technology to rule out life-threatening disease. According to Dr. Kline, "I interpret our data as a manifestation of the erosion of the physician-patient relationship.
Physicians now believe more than ever that every patient with any hint of a life-threatening illness should have the most expensive, most technological 'standard-of-care' diagnostic test ordered to rule out that illness. This multicenter collaborative project shows that we can use a careful history and physical examination to achieve the same degree of certainty without the cost and side effects of diagnostic testing. Patients do not want a technician to check off tests on an order sheet while the physician hurries off to see the next patient. The ability to document 'PERC rule negative' on the chart will provide physicians with the scientific and medicolegal backstop they need to justify not ordering a test on every patient with any hint of PE in their history or physical examination."
The presentation is entitled "Prospective, Multicenter Validation of the Pulmonary Embolism Rule-Out Criteria" by Jeff Kline, MD, of the Carolinas Medical Center. This paper will be presented at the 2007 SAEM Annual Meeting, May 16-19, 2007, Chicago, IL on Wednesday, May 16th, in the Plenary Session beginning at 1:00 PM in Sheraton 4 & 5 of the Sheraton Chicago Hotel & Towers. Abstracts of the papers presented are published in Volume 14, Issue 5S, the May 2007 supplement of the official journal of the SAEM, Academic Emergency Medicine.
Friday, May 11, 2007
Reviewers Question First In-Class Rennin Inhibitor for Hypertension
Abstract:
Aliskiren, the First Renin Inhibitor for Treating Hypertension: Reactive Renin Secretion May Limit Its Effectiveness
American Journal of Hypertension, Volume 20, Issue 5, May 2007, Pages 587-597
Jean E. Sealey and John H. Laragh Jean E. Sealey and John H. LaraghDepartment of Cardiothoracic Surgery, New York Presbyterian Hospital and Weill Medical College of Cornell University, New York, New York.
A review of six clinical trials of aliskiren involving >5,000 patients with mild to moderate hypertension indicated that this first of a new class of orally active antihypertensive drugs is no more effective than angiotensin-converting enzyme inhibitors (CEIs), angiotensin receptor blockers (ARBs), or diuretics for lowering blood pressure. The starting dose is 150 mg; 300 mg is usually more effective, but 600 mg is no better than 300 mg. Aliskiren in combination with a diuretic appeared to lower blood pressure more than an aliskiren-ARB combination, but still failed to control blood pressure (<140/90) in 50% of the patients. Although aliskiren suppresses plasma renin activity, it causes much greater reactive rises in plasma renin concentration than does any other antihypertensive class tested.
Because aliskiren, like CEIs and ARBs, only blocks 90% to 95% of plasma renin, the pressor consequences of its greater reactive increases in plasma renin concentration appear to offset its net ability to lower blood pressure, especially with higher doses.
Patients with hyperreactive renin systems (renovascular, advanced, and malignant hypertension) were excluded from all of the trials.
Until the possibility is eliminated of inducing increases in blood pressure with aliskiren in patients with highly reactive renin levels, it seems safe and simple to stick to the less expensive, equally effective and widely available generic CEI drugs for treating the renin factor in hypertension.
Aliskiren, the First Renin Inhibitor for Treating Hypertension: Reactive Renin Secretion May Limit Its Effectiveness
American Journal of Hypertension, Volume 20, Issue 5, May 2007, Pages 587-597
Jean E. Sealey and John H. Laragh Jean E. Sealey and John H. LaraghDepartment of Cardiothoracic Surgery, New York Presbyterian Hospital and Weill Medical College of Cornell University, New York, New York.
A review of six clinical trials of aliskiren involving >5,000 patients with mild to moderate hypertension indicated that this first of a new class of orally active antihypertensive drugs is no more effective than angiotensin-converting enzyme inhibitors (CEIs), angiotensin receptor blockers (ARBs), or diuretics for lowering blood pressure. The starting dose is 150 mg; 300 mg is usually more effective, but 600 mg is no better than 300 mg. Aliskiren in combination with a diuretic appeared to lower blood pressure more than an aliskiren-ARB combination, but still failed to control blood pressure (<140/90) in 50% of the patients. Although aliskiren suppresses plasma renin activity, it causes much greater reactive rises in plasma renin concentration than does any other antihypertensive class tested.
Because aliskiren, like CEIs and ARBs, only blocks 90% to 95% of plasma renin, the pressor consequences of its greater reactive increases in plasma renin concentration appear to offset its net ability to lower blood pressure, especially with higher doses.
Patients with hyperreactive renin systems (renovascular, advanced, and malignant hypertension) were excluded from all of the trials.
Until the possibility is eliminated of inducing increases in blood pressure with aliskiren in patients with highly reactive renin levels, it seems safe and simple to stick to the less expensive, equally effective and widely available generic CEI drugs for treating the renin factor in hypertension.
Thursday, May 10, 2007
Guidelines for the Management of Spontaneous Intracerebral Hemorrhage in Adults. 2007 Update.
Guidelines for the Management of Spontaneous Intracerebral Hemorrhage in Adults. 2007 Update. A Guideline From the American Heart Association, American Stroke Association Stroke Council, High Blood Pressure Research Council, and the Quality of Care and Outcomes in Research Interdisciplinary Working Group
Joseph Broderick MD, FAHA, Chair; Sander Connolly MD, FAHA, Vice-Chair; Edward Feldmann MD, FAHA; Daniel Hanley MD, FAHA; Carlos Kase MD, FAHA; Derk Krieger MD; Marc Mayberg MD, FAHA; Lewis Morgenstern MD, FAHA; Christopher S. Ogilvy MD; Paul Vespa MD; and Mario Zuccarello MD
Purpose--The aim of this statement is to present current and comprehensive recommendations for the diagnosis and treatment of acute spontaneous intracerebral hemorrhage.
Methods--A formal literature search of Medline was performed through the end date of August 2006. The results of this search were complemented by additional articles on related issues known to the writing committee. Data were synthesized with the use of evidence tables. The American Heart Association Stroke Council’s Levels of Evidence grading algorithm was used to grade each recommendation. Prerelease review of the draft guideline was performed by 5 expert peer reviewers and by the members of the Stroke Council Leadership Committee. It is intended that this guideline be fully updated in 3 years’ time.
Results--Evidence-based guidelines are presented for the diagnosis of intracerebral hemorrhage, the management of increased arterial blood pressure and intracranial pressure, the treatment of medical complications of intracerebral hemorrhage, and the prevention of recurrent intracerebral hemorrhage. Recent trials of recombinant factor VII to slow initial bleeding are discussed. Recommendations for various surgical approaches for treatment of spontaneous intracerebral hemorrhage are presented. Finally, withdrawal-of-care and end-of-life issues in patients with intracerebral hemorrhage are examined.
The guidelines, published in the June issue of Stroke, Journal of the American Heart Association
COMMENTARIES:
Intracerebral hemorrhage, which causes 10% to 15% of first-ever strokes, has a 30-day mortality rate of 35% to 52%
The guidelines suggest that the hemorrhage should be removed as soon as possible if:
It's greater than 3 cm.
The patient is deteriorating neurologically.
The patient has brain stem compression, hydrocephalus from ventricular obstruction, or both.
There is some evidence that using recombinant activated factor VII within four hours of the stroke limits bleeding and may reduce the risk of death.
The guidelines also recommend that:
Appropriate antiepileptic therapy should always be used for treatment of seizures.
Sources of fever should be treated and antipyretic medications should be given as needed.
Early mobilization and rehabilitation are recommended in patients who are clinically stable.
A new aspect of the guidelines is discussion of withdrawal of care and end-of-life issues. The guidelines recommend that do-not-resuscitate orders not be initiated during the first 24 hours after the onset of stroke because they are associated with "an overall lack of aggressiveness of care."
Joseph Broderick MD, FAHA, Chair; Sander Connolly MD, FAHA, Vice-Chair; Edward Feldmann MD, FAHA; Daniel Hanley MD, FAHA; Carlos Kase MD, FAHA; Derk Krieger MD; Marc Mayberg MD, FAHA; Lewis Morgenstern MD, FAHA; Christopher S. Ogilvy MD; Paul Vespa MD; and Mario Zuccarello MD
Purpose--The aim of this statement is to present current and comprehensive recommendations for the diagnosis and treatment of acute spontaneous intracerebral hemorrhage.
Methods--A formal literature search of Medline was performed through the end date of August 2006. The results of this search were complemented by additional articles on related issues known to the writing committee. Data were synthesized with the use of evidence tables. The American Heart Association Stroke Council’s Levels of Evidence grading algorithm was used to grade each recommendation. Prerelease review of the draft guideline was performed by 5 expert peer reviewers and by the members of the Stroke Council Leadership Committee. It is intended that this guideline be fully updated in 3 years’ time.
Results--Evidence-based guidelines are presented for the diagnosis of intracerebral hemorrhage, the management of increased arterial blood pressure and intracranial pressure, the treatment of medical complications of intracerebral hemorrhage, and the prevention of recurrent intracerebral hemorrhage. Recent trials of recombinant factor VII to slow initial bleeding are discussed. Recommendations for various surgical approaches for treatment of spontaneous intracerebral hemorrhage are presented. Finally, withdrawal-of-care and end-of-life issues in patients with intracerebral hemorrhage are examined.
The guidelines, published in the June issue of Stroke, Journal of the American Heart Association
COMMENTARIES:
Intracerebral hemorrhage, which causes 10% to 15% of first-ever strokes, has a 30-day mortality rate of 35% to 52%
The guidelines suggest that the hemorrhage should be removed as soon as possible if:
It's greater than 3 cm.
The patient is deteriorating neurologically.
The patient has brain stem compression, hydrocephalus from ventricular obstruction, or both.
There is some evidence that using recombinant activated factor VII within four hours of the stroke limits bleeding and may reduce the risk of death.
The guidelines also recommend that:
Appropriate antiepileptic therapy should always be used for treatment of seizures.
Sources of fever should be treated and antipyretic medications should be given as needed.
Early mobilization and rehabilitation are recommended in patients who are clinically stable.
A new aspect of the guidelines is discussion of withdrawal of care and end-of-life issues. The guidelines recommend that do-not-resuscitate orders not be initiated during the first 24 hours after the onset of stroke because they are associated with "an overall lack of aggressiveness of care."
PCI in Silent Ischemia After Myocardial Infarction - SWISSI II
Effects of Percutaneous Coronary Interventions in Silent Ischemia After Myocardial Infarction The SWISSI II Randomized Controlled Trial
Paul Erne, MD; Andreas W. Schoenenberger, MD; Dieter Burckhardt, MD; Michel Zuber, MD; Wolfgang Kiowski, MD; Peter T. Buser, MD; Paul Dubach, MD; Therese J. Resink, PhD; Matthias Pfisterer, MD
JAMA. 2007;297:1985-1991.
Context The effect of a percutaneous coronary intervention (PCI) on the long-term prognosis of patients with silent ischemia after a myocardial infarction (MI) is not known.
Objective To determine whether PCI compared with drug therapy improves long-term outcome of asymptomatic patients with silent ischemia after an MI.
Design, Setting, and Participants Randomized, unblinded, controlled trial (Swiss Interventional Study on Silent Ischemia Type II [SWISSI II]) conducted from May 2, 1991, to February 25, 1997, at 3 public hospitals in Switzerland of 201 patients with a recent MI, silent myocardial ischemia verified by stress imaging, and 1- or 2-vessel coronary artery disease. Follow-up ended on May 23, 2006.
Interventions Percutaneous coronary intervention aimed at full revascularization (n = 96) or intensive anti-ischemic drug therapy (n = 105). All patients received 100 mg/d of aspirin and a statin.
Main Outcome Measures Survival free of major adverse cardiac events defined as cardiac death, nonfatal MI, and/or symptom-driven revascularization. Secondary measures included exercise-induced ischemia and resting left ventricular ejection fraction during follow-up.
Results During a mean (SD) follow-up of 10.2 (2.6) years, 27 major adverse cardiac events occurred in the PCI group and 67 events occurred in the anti-ischemic drug therapy group (adjusted hazard ratio, 0.33; 95% confidence interval, 0.20-0.55; P<.001), which corresponds to an absolute event reduction of 6.3% per year (95% confidence interval, 3.7%-8.9%; P<.001). Patients in the PCI group had lower rates of ischemia (11.6% vs 28.9% in patients in the drug therapy group at final follow-up; P = .03) despite fewer drugs. Left ventricular ejection fraction remained preserved in PCI patients (mean [SD] of 53.9% [9.9%] at baseline to 55.6% [8.1%] at final follow-up) and decreased significantly (P<.001) in drug therapy patients (mean [SD] of 59.7% [11.8%] at baseline to 48.8% [7.9%] at final follow-up). Conclusion Among patients with recent MI, silent myocardial ischemia verified by stress imaging, and 1- or 2-vessel coronary artery disease, PCI compared with anti-ischemic drug therapy reduced the long-term risk of major cardiac events. Conclusion Among patients with recent MI, silent myocardial ischemia verified by stress imaging, and 1- or 2-vessel coronary artery disease, PCI compared with anti-ischemic drug therapy reduced the long-term risk of major cardiac events.
COMMENTARIES:
For stable angina patients, the COURAGE trial found no advantage in any major cardiovascular endpoint for coronary stenting plus optimal medical therapy over medical therapy alone.
Another recent trial, the Open Artery Trial (OAT) reported at the American Heart Association meeting in November 2006, found no benefit for late percutaneous coronary intervention after heart attack over four years of follow up.
This study included a more select group of patients than the OAT study since all had viable myocardium.
"Taken together, these findings indicate a need for percutaneous coronary intervention after myocardial infarction only in the presence of symptomatic or silent ischemia but not without it," they wrote.
This trial was limited by lack of blinding (though all events were adjudicated by blinded physicians), a minority of female patients, and relatively small sample size.
LINKS: http://jama.ama-assn.org/cgi/content/short/297/18/1985?rss=1
Paul Erne, MD; Andreas W. Schoenenberger, MD; Dieter Burckhardt, MD; Michel Zuber, MD; Wolfgang Kiowski, MD; Peter T. Buser, MD; Paul Dubach, MD; Therese J. Resink, PhD; Matthias Pfisterer, MD
JAMA. 2007;297:1985-1991.
Context The effect of a percutaneous coronary intervention (PCI) on the long-term prognosis of patients with silent ischemia after a myocardial infarction (MI) is not known.
Objective To determine whether PCI compared with drug therapy improves long-term outcome of asymptomatic patients with silent ischemia after an MI.
Design, Setting, and Participants Randomized, unblinded, controlled trial (Swiss Interventional Study on Silent Ischemia Type II [SWISSI II]) conducted from May 2, 1991, to February 25, 1997, at 3 public hospitals in Switzerland of 201 patients with a recent MI, silent myocardial ischemia verified by stress imaging, and 1- or 2-vessel coronary artery disease. Follow-up ended on May 23, 2006.
Interventions Percutaneous coronary intervention aimed at full revascularization (n = 96) or intensive anti-ischemic drug therapy (n = 105). All patients received 100 mg/d of aspirin and a statin.
Main Outcome Measures Survival free of major adverse cardiac events defined as cardiac death, nonfatal MI, and/or symptom-driven revascularization. Secondary measures included exercise-induced ischemia and resting left ventricular ejection fraction during follow-up.
Results During a mean (SD) follow-up of 10.2 (2.6) years, 27 major adverse cardiac events occurred in the PCI group and 67 events occurred in the anti-ischemic drug therapy group (adjusted hazard ratio, 0.33; 95% confidence interval, 0.20-0.55; P<.001), which corresponds to an absolute event reduction of 6.3% per year (95% confidence interval, 3.7%-8.9%; P<.001). Patients in the PCI group had lower rates of ischemia (11.6% vs 28.9% in patients in the drug therapy group at final follow-up; P = .03) despite fewer drugs. Left ventricular ejection fraction remained preserved in PCI patients (mean [SD] of 53.9% [9.9%] at baseline to 55.6% [8.1%] at final follow-up) and decreased significantly (P<.001) in drug therapy patients (mean [SD] of 59.7% [11.8%] at baseline to 48.8% [7.9%] at final follow-up). Conclusion Among patients with recent MI, silent myocardial ischemia verified by stress imaging, and 1- or 2-vessel coronary artery disease, PCI compared with anti-ischemic drug therapy reduced the long-term risk of major cardiac events. Conclusion Among patients with recent MI, silent myocardial ischemia verified by stress imaging, and 1- or 2-vessel coronary artery disease, PCI compared with anti-ischemic drug therapy reduced the long-term risk of major cardiac events.
COMMENTARIES:
For stable angina patients, the COURAGE trial found no advantage in any major cardiovascular endpoint for coronary stenting plus optimal medical therapy over medical therapy alone.
Another recent trial, the Open Artery Trial (OAT) reported at the American Heart Association meeting in November 2006, found no benefit for late percutaneous coronary intervention after heart attack over four years of follow up.
This study included a more select group of patients than the OAT study since all had viable myocardium.
"Taken together, these findings indicate a need for percutaneous coronary intervention after myocardial infarction only in the presence of symptomatic or silent ischemia but not without it," they wrote.
This trial was limited by lack of blinding (though all events were adjudicated by blinded physicians), a minority of female patients, and relatively small sample size.
LINKS: http://jama.ama-assn.org/cgi/content/short/297/18/1985?rss=1
J Am Coll Cardiol, 2007; 49:1943-1950, doi:10.1016/j.jacc.2007.02.037 (Published online 30 April 2007
Admission B-Type Natriuretic Peptide Levels and In-Hospital Mortality in Acute Decompensated Heart Failure
Gregg C. Fonarow, MD, FACC*,*, William F. Peacock, MD , Christopher O. Phillips, MD, MPH , Michael M. Givertz, MD, FACC , Margarita Lopatin, MS ADHERE Scientific Advisory Committee and Investigators
Objectives: This study was designed to determine whether admission B-type natriuretic peptide (BNP) levels are predictive of in-hospital mortality in acute decompensated heart failure (HF).
Background: Levels of BNP have been demonstrated to facilitate the diagnosis of HF and predict mortality in chronic systolic HF.
Methods: B-type natriuretic peptide levels within 24 h of presentation were obtained in 48,629 (63%) of 77,467 hospitalization episodes entered in ADHERE (Acute Decompensated Heart Failure National Registry). In-hospital mortality was assessed by BNP quartiles in the entire cohort and in patients with reduced (n = 19,544) as well as preserved (n = 18,164) left ventricular systolic function using chi-square and logistic regression models.
Results: Quartiles (Q) of BNP were Q1 (<430), Q2 (430 to 839), Q3 (840 to 1,729), and Q4 ( 1,730 pg/ml). The BNP levels were <100 pg/ml in 3.3% of the total cohort. Patients in Q1 versus Q4 were younger, more likely to be women, and had lower creatinine and higher left ventricular ejection fraction. There was a near-linear relationship between BNP quartiles and in-hospital mortality: Q1 (1.9%), Q2 (2.8%), Q3 (3.8%), and Q4 (6.0%), p < 0.0001. B-type natriuretic peptide quartile remained highly predictive of mortality even after adjustment for age, gender, systolic blood pressure, blood urea nitrogen, creatinine, sodium, pulse, and dyspnea at rest, Q4 versus Q1 (adjusted odds ratio 2.23 [95% confidence interval 1.91 to 2.62, p < 0.0001]). The BNP quartiles independently predicted mortality in patients with reduced and preserved systolic function.
Conclusions: An elevated admission BNP level is a significant predictor of in-hospital mortality in acute decompensated HF with either reduced or preserved systolic function, independent of other clinical and laboratory variables.
COMMENTARIES:
Patients with acute decompensated heart failure (ADHF) whose brain natriuretic peptide (BNP) levels are elevated on admission to hospital are at increased risk of dying in hospital, report US researchers.
Measuring BNP levels on admission may therefore help physicians decide which patients need more intensive treatment and monitoring, they say.
The researchers compared in-hospital mortality rates across quartiles (Qs) of BNP levels. For Q1 (BNP <430 pg/ml), Q2 (430-839 pg/ml), Q3 (840-1729 pg/ml), and Q4 (≥1730 pg/ml) 6.0%, the rates were 1.9%, 2.8%, 3.8%, and 6.0%, respectively.
This reflected a near-linear relationship, and BNP was highly predictive of mortality after adjustment for age, gender, systolic blood pressure, blood urea nitrogen, creatinine, sodium, pulse, and dyspnea at rest. The odds ratio of in-hospital death for Q4 versus Q1 was 2.23.
Admission B-Type Natriuretic Peptide Levels and In-Hospital Mortality in Acute Decompensated Heart Failure
Gregg C. Fonarow, MD, FACC*,*, William F. Peacock, MD , Christopher O. Phillips, MD, MPH , Michael M. Givertz, MD, FACC , Margarita Lopatin, MS ADHERE Scientific Advisory Committee and Investigators
Objectives: This study was designed to determine whether admission B-type natriuretic peptide (BNP) levels are predictive of in-hospital mortality in acute decompensated heart failure (HF).
Background: Levels of BNP have been demonstrated to facilitate the diagnosis of HF and predict mortality in chronic systolic HF.
Methods: B-type natriuretic peptide levels within 24 h of presentation were obtained in 48,629 (63%) of 77,467 hospitalization episodes entered in ADHERE (Acute Decompensated Heart Failure National Registry). In-hospital mortality was assessed by BNP quartiles in the entire cohort and in patients with reduced (n = 19,544) as well as preserved (n = 18,164) left ventricular systolic function using chi-square and logistic regression models.
Results: Quartiles (Q) of BNP were Q1 (<430), Q2 (430 to 839), Q3 (840 to 1,729), and Q4 ( 1,730 pg/ml). The BNP levels were <100 pg/ml in 3.3% of the total cohort. Patients in Q1 versus Q4 were younger, more likely to be women, and had lower creatinine and higher left ventricular ejection fraction. There was a near-linear relationship between BNP quartiles and in-hospital mortality: Q1 (1.9%), Q2 (2.8%), Q3 (3.8%), and Q4 (6.0%), p < 0.0001. B-type natriuretic peptide quartile remained highly predictive of mortality even after adjustment for age, gender, systolic blood pressure, blood urea nitrogen, creatinine, sodium, pulse, and dyspnea at rest, Q4 versus Q1 (adjusted odds ratio 2.23 [95% confidence interval 1.91 to 2.62, p < 0.0001]). The BNP quartiles independently predicted mortality in patients with reduced and preserved systolic function.
Conclusions: An elevated admission BNP level is a significant predictor of in-hospital mortality in acute decompensated HF with either reduced or preserved systolic function, independent of other clinical and laboratory variables.
COMMENTARIES:
Patients with acute decompensated heart failure (ADHF) whose brain natriuretic peptide (BNP) levels are elevated on admission to hospital are at increased risk of dying in hospital, report US researchers.
Measuring BNP levels on admission may therefore help physicians decide which patients need more intensive treatment and monitoring, they say.
The researchers compared in-hospital mortality rates across quartiles (Qs) of BNP levels. For Q1 (BNP <430 pg/ml), Q2 (430-839 pg/ml), Q3 (840-1729 pg/ml), and Q4 (≥1730 pg/ml) 6.0%, the rates were 1.9%, 2.8%, 3.8%, and 6.0%, respectively.
This reflected a near-linear relationship, and BNP was highly predictive of mortality after adjustment for age, gender, systolic blood pressure, blood urea nitrogen, creatinine, sodium, pulse, and dyspnea at rest. The odds ratio of in-hospital death for Q4 versus Q1 was 2.23.
Wednesday, May 9, 2007
Aspirin Dose for the Prevention of Cardiovascular Disease - A Systematic Review
Aspirin Dose for the Prevention of Cardiovascular Disease
A Systematic Review
Charles L. Campbell, MD; Susan Smyth, MD, PhD; Gilles Montalescot, MD, PhD; Steven R. Steinhubl, MD
JAMA. 2007;297:2018-2024.
Context More than 50 million US adults take aspirin regularly for long-term prevention of cardiovascular disease, typically either 81 mg/d or 325 mg/d. Controversy remains regarding the most appropriate long-term daily dose.
Objective To review the mechanism of action of aspirin and the clinical literature for relationships among aspirin dosage, efficacy, and safety.
Evidence Acquisition A systematic review of the English-language literature was undertaken using MEDLINE and EMBASE (searched through February 2007) and the search term aspirin or acetylsalicylic acid and dose. The search was limited to clinical trials and was extended by a review of bibliographies of pertinent reports of original data and review articles. Published prospective studies using different aspirin dosages in the setting of cardiovascular disease were included.
Evidence Synthesis Although pharmacodynamic data demonstrate that long-term aspirin dosages as low as 30 mg/d are adequate to fully inhibit platelet thromboxane production, dosages as high as 1300 mg/d are approved for use. In the United States, 81 mg/d of aspirin is prescribed most commonly (60%), followed by 325 mg/d (35%).
The available evidence, predominantly from secondary-prevention observational studies, supports that dosages greater than 75 to 81 mg/d do not enhance efficacy, whereas larger dosages are associated with an increased incidence of bleeding events, primarily related to gastrointestinal tract toxicity.
Conclusions Currently available clinical data do not support the routine, long-term use of aspirin dosages greater than 75 to 81 mg/d in the setting of cardiovascular disease prevention. Higher dosages, which may be commonly prescribed, do not better prevent events but are associated with increased risks of gastrointestinal bleeding.
Author Affiliations: Gill Heart Institute, University of Kentucky, Lexington (Drs Campbell, Smyth, and Steinhubl); and Institut de Cardiologie—Centre Hospitalier Universitaire Pitié-Salpêtrière, Paris, France (Dr Montalescot).
LINKS: http://jama.ama-assn.org/cgi/content/short/297/18/2018?rss=1
JAMA.2007; 297: 2018-2024.
A Systematic Review
Charles L. Campbell, MD; Susan Smyth, MD, PhD; Gilles Montalescot, MD, PhD; Steven R. Steinhubl, MD
JAMA. 2007;297:2018-2024.
Context More than 50 million US adults take aspirin regularly for long-term prevention of cardiovascular disease, typically either 81 mg/d or 325 mg/d. Controversy remains regarding the most appropriate long-term daily dose.
Objective To review the mechanism of action of aspirin and the clinical literature for relationships among aspirin dosage, efficacy, and safety.
Evidence Acquisition A systematic review of the English-language literature was undertaken using MEDLINE and EMBASE (searched through February 2007) and the search term aspirin or acetylsalicylic acid and dose. The search was limited to clinical trials and was extended by a review of bibliographies of pertinent reports of original data and review articles. Published prospective studies using different aspirin dosages in the setting of cardiovascular disease were included.
Evidence Synthesis Although pharmacodynamic data demonstrate that long-term aspirin dosages as low as 30 mg/d are adequate to fully inhibit platelet thromboxane production, dosages as high as 1300 mg/d are approved for use. In the United States, 81 mg/d of aspirin is prescribed most commonly (60%), followed by 325 mg/d (35%).
The available evidence, predominantly from secondary-prevention observational studies, supports that dosages greater than 75 to 81 mg/d do not enhance efficacy, whereas larger dosages are associated with an increased incidence of bleeding events, primarily related to gastrointestinal tract toxicity.
Conclusions Currently available clinical data do not support the routine, long-term use of aspirin dosages greater than 75 to 81 mg/d in the setting of cardiovascular disease prevention. Higher dosages, which may be commonly prescribed, do not better prevent events but are associated with increased risks of gastrointestinal bleeding.
Author Affiliations: Gill Heart Institute, University of Kentucky, Lexington (Drs Campbell, Smyth, and Steinhubl); and Institut de Cardiologie—Centre Hospitalier Universitaire Pitié-Salpêtrière, Paris, France (Dr Montalescot).
LINKS: http://jama.ama-assn.org/cgi/content/short/297/18/2018?rss=1
JAMA.2007; 297: 2018-2024.
Tuesday, May 8, 2007
Guidelines for the Early Management of Adults With Ischemic Stroke
New Guidelines for Treatment of Acute Ischemic Stroke
April 19, 2007 — The American Heart Association/American Stroke Association has released new guidelines for the early management of acute ischemic stroke. The guidelines continue to endorse the use of intravenous tissue-type plasminogen activator (tPA) but note that other modalities such as intra-arterial tPA show promise. For the first time, the authors have included recommendations for palliative care.
"Our goal was to focus on the first few hours after stroke onset where we think time is so critical," Harold P. Adams Jr., MD, from the University of Iowa Stroke Center in Iowa City, chair of the guidelines writing committee, told Medscape. "The audience is primarily physicians, but we've also included information for general emergency medical services, and some things for the public as well, focusing on the idea that from the first symptom, time is brain, and everything we can do to expedite the process to hopefully treat the patients and reduce the likelihood of an unfavorable outcome is crucial," he said.
The guidelines were published in the April 12 Stroke ASAP issue and will appear in the May print issue of Stroke.
Dr. Adams has disclosed receiving research grants from Boehringer Ingelheim, Centocor (Johnson & Johnson), Eli Lilly, Merck, NMT Medical, Sanofi, Bristol-Myers Squibb, and GlaxoSmithKline, among other disclosures. Disclosure information for the other coauthors appears in the original article.
Stroke. 2007;38:1655-1711.
Study Highlights
- The rate of activation of emergency medical services among patients with acute stroke is as low as 29%. As emergency medical services offers the most prompt care, all patients with the acute onset of stroke symptoms should use services such as telephoning 911 (in the United States).
- During initial evaluation, the single most important point in the patient's history is the time of symptom onset. Patients with acute stroke symptoms should receive testing for blood glucose, coagulation times, and complete blood count with platelets, along with 12-lead electrocardiogram and serum cardiac enzymes. However, chest radiography may be withheld if there are no signs of pulmonary or cardiac disease. The evaluation of the patient should be concluded within 60 minutes of arrival in the emergency department.
- CT remains the most common imaging modality for the evaluation of acute stroke, and, besides hemorrhage, there is no CT finding that is specific enough to preclude treatment with recombinant tPA (rtPA). MRI also is acceptable in the evaluation of acute stroke.
- Patients' blood pressure may decline spontaneously in the first 24 hours after stroke. Patients who are candidates for rtPA should have their systolic blood pressure lowered to at least 185 mm Hg and their diastolic blood pressure lowered to at least 110 mm Hg. Consensus opinions state that patients with persistent elevations in systolic blood pressure higher than 220 mm Hg or diastolic blood pressure higher than 120 mm Hg should receive antihypertension therapy.
- Hyperglycemia in the range of 140 to 185 mg/dL in the stroke patient should prompt consideration of insulin therapy.
- Hyperbaric oxygen should not be used in the acute stroke patient except in cases of air embolus.
- rtPA is the treatment of choice for thrombolysis in acute stroke. Treatment with streptokinase is not recommended, and reteplase, urokinase, and other thrombolytic agents should not be used outside of the setting of a clinical trial.
- Intra-arterial thrombolysis may be used for patients with occlusions of the middle cerebral artery who can be treated within 6 hours of symptom onset.
- Urgent anticoagulation generally is not recommended in lieu of intravenous thrombolysis and should be withheld in patients with moderate or severe stroke because of an increased risk for intracranial hemorrhage.
- Aspirin therapy at a dose of 325 mg may be initiated within 24 to 48 hours after stroke onset. Based on current evidence, the authors recommend against the routine use of clopidogrel following stroke.
- During hospitalization, stroke patients should receive a swallowing evaluation as well as prophylaxis against deep venous thrombosis with heparin or low-molecular-weight heparin.
- Pearls for Practice
- The current guidelines recommend that the initial workup of patients with possible stroke include testing for blood glucose, coagulation times, intracranial imaging, and complete blood count, along with 12-lead electrocardiogram and serum cardiac enzymes. However, chest radiography may be withheld if there are no signs of pulmonary or cardiac disease.
- rtPA is the treatment of choice for patients who present within 3 hours of the onset of stroke symptoms.
Link: OVID - full text -
http://www.msd-brazil.com/msdbrazil/hcp/library/ovid.html?subpage=/ovidweb.cgi?T=JS&MODE=ovid&PAGE=toc&NEWS=n&amp;amp;amp;DBC=y&ID=mkla10000&PASSWORD=merckla&D=ovft&AN=00007670-000000000-00000
Monday, May 7, 2007
Decline in Rates of Death and Heart Failure in Acute Coronary Syndromes, 1999-2006
Decline in Rates of Death and Heart Failure in Acute Coronary Syndromes, 1999-2006
Keith A. A. Fox, MB, ChB, FRCP; Philippe Gabriel Steg, MD; Kim A. Eagle, MD; Shaun G. Goodman, MD, MSc; Frederick A. Anderson, Jr, PhD; Christopher B. Granger, MD; Marcus D. Flather, MBBS, FRCP; Andrzej Budaj, MD, PhD; Ann Quill, MA; Joel M. Gore, MD; for the GRACE Investigators
JAMA. 2007;297:1892-1900.
Context Randomized trials provide robust evidence for the impact of pharmacological and interventional treatments in patients with ST-segment elevation and non–ST-segment elevation acute coronary syndromes (NSTE ACS), but whether this translates to changes in clinical practice is unknown.
Objective To determine whether changes in hospital management of patients with ST-segment elevation myocardial infarction (STEMI) and NSTE ACS are associated with improvements in clinical outcome.
Design, Setting, and Patients In the Global Registry of Acute Coronary Events (GRACE), a multinational cohort study, 44 372 patients with an ACS were enrolled and followed up in 113 hospitals in 14 countries between July 1, 1999, and December 31, 2006.
Main Outcome Measures Temporal trends in the use of evidence-based pharmacological and interventional therapies; patient outcomes (death, congestive heart failure, pulmonary edema, cardiogenic shock, stroke, myocardial infarction).
Results Use of pharmacological medications increased over the study period ( -blockers, statins, angiotensin-converting enzyme inhibitors, thienopyridines with or without percutaneous coronary intervention [PCI], glycoprotein IIb/IIIa inhibitors, low-molecular-weight heparin; all P<.001).
Pharmacological reperfusion declined in patients with STEMI by –22 percentage points (95% confidence interval [CI], –27 to –17), whereas primary PCI increased by 37 percentage points (95% CI, 33-41). In patients with non-STEMI, rates of PCI increased markedly by 18 percentage points (95% CI, 15-20).
Rates of congestive heart failure and pulmonary edema declined in both populations: STEMI, –9 percentage points (95% CI, –12 to –6) and NSTE ACS, –6.9 percentage points (95% CI, –8.4 to –4.7). In patients with STEMI, hospital deaths decreased by 18 percentage points (95% CI, –5.3 to –1.9) and cardiogenic shock by –24 percentage points (95% CI, –4.3 to –0.5). Risk-adjusted hospital deaths declined –0.7 percentage points (95% CI, –1.7 to 0.3) in NSTE ACS patients. Six-month follow-up rates declined among STEMI patients: stroke by –0.8 percentage points (95% CI, –1.7 to 0.1) and myocardial infarction by –2.8 percentage points (95% CI, –6.4 to 0.9). In NSTE ACS, 6-month death declined –1.6 percentage points (95% CI, –3.0 to –0.1) and stroke by 0.7 percentage points (95% CI, –1.4 to 0.1).
Conclusions In this multinational observational study, improvements in the management of patients with ACS were associated with significant reductions in the rates of new heart failure and mortality and in rates of stroke and mycoardial infarction at 6 months.
Author Affiliations: Cardiovascular Research, Division of Medical and Radiological Sciences, The University of Edinburgh, Edinburgh, Scotland (Dr Fox); Hospital Bichat, Paris, France (Dr Steg); University of Michigan Health System, Ann Arbor (Dr Eagle); Canadian Heart Research Centre and Terrence Donnelly Heart Centre, Division of Cardiology, St Michael's Hospital, University of Toronto, Toronto, Ontario (Dr Goodman); University of Massachusetts Medical School, Worcester (Drs Anderson and Gore and Ms Quill); Royal Brompton & Harefield NHS Trust, London, England (Dr Flather); Postgraduate Medical School, Grochowski Hospital, Warsaw, Poland (Dr Budaj); and Duke University Medical Center, Durham, NC (Dr Granger).
LINK:
http://jama.ama-assn.org/current.dtl (This item is restricted. Subscribers have full text access and guests have some free access)
Sunday, May 6, 2007
Can Levosimendan Help in Acute Decompensated Heart Failure?
Can Levosimendan Help in Acute Decompensated Heart Failure?
A novel inotropic agent demonstrated no advantage over dobutamine in reducing mortality.
There were hopes that the new drug, levosimendan, would improve survival, because it uses a unique mechanism that makes heart muscle cells more sensitive to the calcium that causes them to contract. However, the study of 1,347 persons with acute decompensated heart failure, done at 75 centers in nine countries between March 2003 and December 2004, found essentially the same death rate for participants who got levosimendan as those who received an established medication, dobutamine, said a report in the May 2 issue of the Journal of the American Medical Association.
Levosimendan vs Dobutamine for Patients With Acute Decompensated Heart Failure
The SURVIVE Randomized Trial
Alexandre Mebazaa, MD, PhD; Markku S. Nieminen, MD, PhD; Milton Packer, MD; Alain Cohen-Solal, MD, PhD; Franz X. Kleber, MD; Stuart J. Pocock, PhD; Roopal Thakkar, MD; Robert J. Padley, MD; Pentti Põder, MD, PhD; Matti Kivikko, MD, PhD; for the SURVIVE Investigators
JAMA. 2007;297:1883-1891.
Context
Because acute decompensated heart failure causes substantial morbidity and mortality, there is a need for agents that at least improve hemodynamics and relieve symptoms without adversely affecting survival.
Objective
To assess the effect of a short-term intravenous infusion of levosimendan or dobutamine on long-term survival.
Design, Setting, and Patients
The Survival of Patients With Acute Heart Failure in Need of Intravenous Inotropic Support (SURVIVE) study was a randomized, double-blind trial comparing the efficacy and safety of intravenous levosimendan or dobutamine in 1327 patients hospitalized with acute decompensated heart failure who required inotropic support. The trial was conducted at 75 centers in 9 countries and patients were randomized between March 2003 and December 2004.
Interventions
Interventions
Intravenous levosimendan (n = 664) or intravenous dobutamine (n = 663).
Main Outcome Measure
All-cause mortality at 180 days.
Results
All-cause mortality at 180 days occurred in 173 (26%) patients in the levosimendan group and 185 (28%) patients in the dobutamine group (hazard ratio, 0.91; 95% confidence interval, 0.74-1.13; P = .40). The levosimendan group had greater decreases in B-type natriuretic peptide level at 24 hours that persisted through 5 days compared with the dobutamine group (P<.001 for all time points). There were no statistical differences between treatment groups for the other secondary end points (all-cause mortality at 31 days, number of days alive and out of the hospital, patient global assessment, patient assessment of dyspnea at 24 hours, and cardiovascular mortality at 180 days). There was a higher incidence of cardiac failure in the dobutamine group. There were higher incidences of atrial fibrillation, hypokalemia, and headache in the levosimendan group.
Conclusion
Despite an initial reduction in plasma B-type natriuretic peptide level in patients in the levosimendan group compared with patients in the dobutamine group, levosimendan did not significantly reduce all-cause mortality at 180 days or affect any secondary clinical outcomes.
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