Saturday, April 28, 2007

Impact Factors

Thursday, October 05, 2006

Journal Impact Factors for 2005

Impact Factors for leading medical and science journals in 2005 are listed below.(Source: ISI Journal Citation Reports impact factors tabulated from each journal's public website)

Journal Impact Factors(note: review journals are not included)

General (internal) medicine

1. New England Journal of Medicine 44.0
2. Nature Medicine 28.9
3. The Lancet 23.4
4. Journal of the American Medical Association (JAMA) 23.3
5. Annals of Internal Medicine 13.3
6. British
Medical Journal (BMJ) 9.0
7. Public Library of Science (PLOS) Medicine 8.4
8. Archives of Internal Medicine 8.0
9. Canadian Medical Association Journal (CMAJ) 7.4
10. Medicine 5.0
11. Am J Medicine 4.4
12. J Internal Medicine 4.0

Impact Factors of Cardiovascular Journals

Below are 2005 journal IMPACT FACTORS for cardiovascular disease-related journals.

Cardiovascular Diseases

Circulation 11.6
Blood 10.1
Circulation Research 9.4
J American College Cardiology 9.2
European Heart J 7.3
ATVB 7.1
Hypertension 6.3
Stroke 5.9
Cardiovascular Research 5.3
J Hypertension 5.2
Atherosclerosis 3.8
Am Heart J 3.5
Am J Hypertension 3.5
Thromb Haemost 3.1
Am J Cardiology 3.0
Eur J Cardiov Prev R 2.3

O "fator de impacto" (FI) de um periódico científico tem sido considerado parâmetro de sua influência no universo científico em que se insere.

Idealizado em 1955 por Eugene Garfield nos Estados Unidos da América, o "fator de impacto para periódicos" foi criado no início dos anos 60 para auxiliar na seleção de periódicos para o Science Citation Index, então existente.

Na SciELO o FI é calculado com base em 2 ou 3 anos. O indicador de fator de impacto foi definido pelo Institute for Scientific Information (ISI), atualmente Thomson Scientific, nos Estados Unidos e é divulgado anualmente através do Journal Citation Reports (ISI/JCR).

O cálculo do factor de impacto para dois anos consiste em dividir o total de citações recebidas pela revista num determinado ano (por exemplo, 2005) a artigos publicados nos 2 anos anteriores (por exemplo, 2003 e 2004) pelo total de artigos publicados nos mesmos anos anteriores.

Citações recebidas por uma revista em 2005 para
artigos publicados em 2003 = 200
artigos publicados em 2004 = 150

2003 + 2004 = 350

Artigos publicados em 2003 = 120
Artigos publicados em 2004 = 130
Total = 250

Fator de impacto em 2005= 350/250 = 1.4

Em 2005, dezessete publicações brasileiras constam do Journal of Citation Reports:

Journal of the Brazilian Chemical Society (1,097)
Brazilian Journal of Medical and Biological Research (0,859)
Memórias do Instituto Oswaldo Cruz (0,847)
Anais da Academia Brasileira de Ciências (0,653)
Química Nova (0,650); Brazilian Journal of Physics (0,445)
Arquivos de Neuro-psiquiatria (0,430)
Brazilian Journal of Chemical Engineering (0,385)
Genetics and Molecular Biology (0,373)
Bulletin of the Brazilian Mathematical Society (0,340
Revista Brasileira de Ciência do Solo (0,289)
Revista Brasileira de Zootecnia-Brazilian Journal of Animal Science (0,250)
Pesquisa Veterinária Brasileira (0,239)
Pesquisa Agropecuária Brasileira (0,181)
Brazilian Journal of Microbiology (0,165)
Brazilian Archives of Biology and Technology (0,131)
Arquivo Brasileiro de Medicina Veterinária e zootecnia (0,114).

Friday, April 27, 2007

Cardiologists 'main recipient of pharmaceutical industry disbursements'

Cardiovascular News

Cardiologists 'main recipient of pharmaceutical industry disbursements'

26 April 2007

MedWire News: Cardiologists are more likely than other hospital physicians, and twice as likely as family practitioners, to be remunerated by the pharmaceutical industry for consulting, giving lectures, or enrolling patients on trials, and have the costs of attending meetings reimbursed, a survey of US clinicians suggests.

There has been substantial interest in the relationships between physicians and the pharmaceutical, medical device, and other medically related industries in recent years. However, data on the extent and predictors of such relationships are uncommon, despite the availability of the relevant information.

To investigate further, Eric Campbell, from Harvard Medical School in Boston, Massachusetts, USA, and colleagues surveyed 3167 physicians from across the USA working in anesthesiology, cardiology, family practice, general surgery, internal medicine, and pediatrics between 2003 and 2004. The weighted response rate was 58%.

The results, published in the New England Journal of Medicine, show that 94% of physicians had a relationship with the pharmaceutical industry in one form or another, with 83% receiving food in the workplace and 78% being given drug samples. Reimbursements for costs linked to professional meetings or continuing medical education were paid to 35% of respondents, while 28% had payments for consulting, giving lectures, or enrolling patients in clinical trials.

Analysis showed that, on multivariate analysis, cardiologists were more than twice as likely as family practice physicians to have received payments, and were more likely to have received samples, gifts, or reimbursements than family practitioners, at odds ratios of 1.64, 1.14, and 1.04, respectively.

Interestingly, pediatricians were less likely than family practitioners to have benefited in these ways, at odds ratios of 0.46, 0.67, 0.59, and 0.51 for samples, gifts, reimbursements, and payments, respectively. Anesthetists were, overall, even less likely to have a relationship with the pharmaceutical industry than family physicians, at respective odds ratios of 0.05, 0.89, 0.31, and 0.21.

The findings also showed that family practitioners more frequently met with representatives of the pharmaceutical industry than other physicians, and physicians working in solo, two-person, and group practices more often met with representatives than did those working in hospitals.

The researchers conclude: "Our data show that physician–industry relationships are common in medicine, as are relationships between professionals and industrial organizations in the health sciences and many other sectors of the US economy. Furthermore, our data suggest that physicians' relationships with industry vary according to physicians' personal and professional characteristics and according to the practice setting."

They add: "We can only speculate about the reasons for these variations by specialty. Further research should consider factors such as the number and costs of drugs prescribed by physicians in the specialties in question, the accessibility of physicians in each specialty to company representatives, and the influence of physicians on the prescribing practices of their peers."


Full text:
N Engl J Med 2007; 356: 1742–1750

Wednesday, April 25, 2007

ACC.07 Highlights: Panel discussion covering trials on lipids and atherosclerosis

Congress Reports

ACC.07: 56th Annual Scientific Session of the American College of Cardiology

ACC.07 Highlights: Panel discussion covering trials on lipids and atherosclerosis

MedWire ACC - (New Orleans, LA, USA) - March 27, 2007: Here, an informal convergence of 13 experts, with a mandate to debate and challenge key data were, presented at this year’s ACC Scientific Sessions and i2 Summit Meeting.

Here, Dr. John Stein (University of Wisconsin, Madison, WI, USA) briefly highlighted the outcomes from a number of vascular clinical trials presented at the ACC.07. He stated, “we really got bad news for drugs that attempted to raise HDL cholesterol (HDL-C) levels,” saying that the first drug, torcetrapib, which was tested in conjunction with atorvastatin in the ILLUSTRATE and RADIANCE I & II trials, was shown to raise HDL-C levels by approximately 60% and lower LDL-C levels by approximately 20%. However, this did not slow atherosclerosis progression.

He added that in the Effect of recombinant HDL on Atherosclerosis - Safety and Efficacy (ERASE) trial, the novel agent CSL111, was found to be no better than placebo at regressing atherosclerosis, although as Dr. Stein commented, “there were some signs of benefits in some of the secondary endpoints”.

Finally, he added, a powerful PPAR-97 agonist, LY518674, proved to be no better than a currently-used fibrate, but it also raised serum creatinine and had a very powerful and unusual dose response. While these data did not bring good news for HDL-raising agents, Dr. Stein suggested that “we have an excellent HDL-cholesterol-raising drug already available, which is niacin.”

In response, a panelist pointed out that “one of the most intriguing aspects of these data was the implication for surrogate endpoints, and given the progression of disease that was reported, it would appear that the surrogates may still provide a basic, quick, relatively inexpensive way to screen drugs.”

Concurring, Dr. Stein said that “by conducting morbidity and mortality trials in conjunction with imaging trials, the imaging trials really serve as a data safety monitoring referendum about agent safety,” in particular, if they are not shown to slow atherosclerosis, they may truly cause cardiac events.

The news was considerably better for drugs that do lower LDL-C. Dr. Stein reported that in METEOR, the benefits of statin therapy were extended to patients at apparent low risk (Framingham score <10%),>. He also said that a new drug, ISI 30102, was shown to lower LDL-C and triglycerides by 50% when added on top of statin therapy. “So, I think that this shows us that we’ve been on the right track,” said Dr. Stein. “It extends the population of patients in whom aggressive lipid-lowering therapy can be beneficial, and it provides some insight into what the future is going to look like - very specific compounds that go right to the liver and block Apo B production.”

Noting that METEOR was also good news for screening tests, Dr. Stein said that the study included patients who were apparently low risk with one risk factor, or two risk factors with Framingham score <10% for both groups. Despite having normal risk factors, they had increased carotid media thickness and responded positively to lipid-lowering therapy. Dr. Stein suggested that these data confirm that people with advanced atherosclerosis can benefit from aggressive lipid-lowering therapy. He also highlighted an additional study presented this week, suggesting that an abbreviated carotid IMT scan that just focuses on plaque screening and the common carotid artery could do just as well for clinical purposes as a research protocol.

Continuing, Dr. Stein stated how the MESA data showed that increased coronary calcium predicted future cardiac events in four major US ethnic groups, and that importantly, this filled in a major gap in the literature with regards to offering data on a large, relatively unselected group of people that included African Americans, Hispanic Americans, and Asian Americans. And finally, he noted “the Dallas Heart Study wraps it up, and shows us that up to a third of patients with calcium scores above 400, actually have low Framingham risk scores.”

When asked by another panelist about the direction of statin therapy in light of data in low-risk patients, Dr. Stein commented that “we need to be smarter about identifying who, among low-risk patients, need to be treated.”

“After all,” he said, “most heart attacks occur in people who are at low-risk. And perhaps noninvasive imaging and perhaps some new biomarkers can help us be smarter about who we treat rather than just treating more people.”

The MERLIN-TIMI 36 Randomized Trial


Effects of Ranolazine on Recurrent Cardiovascular Events in Patients With Non–ST-Elevation Acute Coronary Syndromes

The MERLIN-TIMI 36 Randomized Trial

David A. Morrow, MD, MPH; Benjamin M. Scirica, MD, MPH; Ewa Karwatowska-Prokopczuk, MD; Sabina A. Murphy, MPH; Andrzej Budaj, MD; Sergei Varshavsky, MD; Andrew A. Wolff, MD; Allan Skene, PhD; Carolyn H. McCabe, BS; Eugene Braunwald, MD; For the MERLIN-TIMI 36 Trial Investigators

JAMA. 2007;297:1775-1783.

Context Ranolazine is a novel antianginal agent that reduces ischemia in patients with chronic angina but has not been studied in patients with acute coronary syndromes (ACS).

Objective To determine the efficacy and safety of ranolazine during long-term treatment of patients with non–ST-elevation ACS.

Design, Setting, and Patients A randomized, double-blind, placebo-controlled, multinational clinical trial of 6560 patients within 48 hours of ischemic symptoms who were treated with ranolazine (initiated intravenously and followed by oral ranolazine extended-release 1000 mg twice daily, n = 3279) or matching placebo (n = 3281), and followed up for a median of 348 days in the Metabolic Efficiency With Ranolazine for Less Ischemia in Non–ST-Elevation Acute Coronary Syndromes (MERLIN)-TIMI 36 trial between October 8, 2004, and February 14, 2007.

Main Outcome Measures The primary efficacy end point was a composite of cardiovascular death, myocardial infarction (MI), or recurrent ischemia through the end of study. The major safety end points were death from any cause and symptomatic documented arrhythmia.

Results The primary end point occurred in 696 patients (21.8%) in the ranolazine group and 753 patients (23.5%) in the placebo group (hazard ratio [HR], 0.92; 95% confidence interval [CI], 0.83-1.02; P = .11). The major secondary end point (cardiovascular death, MI, or severe recurrent ischemia) occurred in 602 patients (18.7%) in the ranolazine group and 625 (19.2%) in the placebo group (HR, 0.96; 95% CI, 0.86-1.08; P = .50). Cardiovascular death or MI occurred in 338 patients (10.4%) allocated to ranolazine and 343 patients (10.5%) allocated to placebo (HR, 0.99; 95% CI, 0.85-1.15; P = .87). Recurrent ischemia was reduced in the ranolazine group (430 [13.9%]) compared with the placebo group (494 [16.1%]; HR, 0.87; 95% CI, 0.76-0.99; P = .03). QTc prolongation requiring a reduction in the dose of intravenous drug occurred in 31 patients (0.9%) receiving ranolazine compared with 10 patients (0.3%) receiving placebo. Symptomatic documented arrhythmias did not differ between the ranolazine (99 [3.0%]) and placebo (102 [3.1%]) groups (P = .84). No difference in total mortality was observed with ranolazine compared with placebo (172 vs 175; HR, 0.99; 95% CI, 0.80-1.22; P = .91).

Conclusions The addition of ranolazine to standard treatment for ACS was not effective in reducing major cardiovascular events. Ranolazine did not adversely affect the risk of all-cause death or symptomatic documented arrhythmia. Our findings provide support for the safety and efficacy of ranolazine as antianginal therapy.

Author Affiliations: TIMI Study Group, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, Mass (Drs Morrow, Scirica, and Braunwald, and Mss Murphy and McCabe); CV Therapeutics, Palo Alto, Calif (Dr Karwatowska-Prokopczuk); Postgraduate Medical School, Department of Cardiology, Grochowski Hospital, Warsaw, Poland (Dr Budaj); Evidence Clinical and Pharmaceutical Research, St Petersburg, Russia (Dr Varshavsky); Cytokinetics, San Francisco, Calif (Dr Wolff); and Nottingham Clinical Research Limited, Nottingham, United Kingdom (Dr Skene).

This Week in JAMAJAMA. 2007;297:1747. FULL TEXT

Does Ranolazine Have a Place in the Treatment of Acute Coronary Syndromes?L. Kristin Newby and Eric D. Peterson JAMA. 2007;297:1823-1825. EXTRACT FULL TEXT

Does Ranolazine Have a Place in the Treatment of Acute Coronary Syndromes?Newby and PetersonJAMA 2007;297:1823-1825.FULL TEXT
Links: comentário no The

Tuesday, April 24, 2007

Antibiotic prophylaxis seldom needed for dental procedures, say updated recommendations

Apr 19, 2007

Dallas, TX - Prophylactic antibiotic therapy for dental procedures is unlikely to prevent many cases of infective endocarditis and should be restricted to patients who would be at highest risk from the infection, such as those with prosthetic valves or certain congenital heart defects, according to updated guidelines issued this week by the American Heart Association (AHA) and published online April 19, 2007 in Circulation [1].

"We've concluded that if giving prophylactic antibiotics prior to a dental procedure works at all—and there's no evidence that it does work—we should reserve that preventive treatment only for those people who would have the worst outcomes if they get infective endocarditis," according to the chair of the new guidelines' writing group, Dr Walter R Wilson (Mayo Clinic, Rochester, MN), as quoted in a statement issued by the AHA. "This changes the whole philosophy of how we have constructed these recommendations for the past 50 years."

Based on an analysis of available literature, the document concludes that "random bacteremia" resulting from routine daily activities, such as chewing food or tooth brushing, is far more likely to cause infective endocarditis than bacteremia secondary to dental procedures.

"There should be a shift in emphasis away from a focus on a dental procedure and antibiotic prophylaxis toward a greater emphasis on improved access to dental care and oral health in patients with underlying cardiac conditions associated with the highest risk of adverse outcome from infective endocarditis and those conditions that predispose to the acquisition of infective endocarditis," according to the updated guidelines.

Prophylactic antibiotics, they state, should not be given based on a lifetime risk of infective endocarditis but are recommended for high-risk patients undergoing "procedures that involve manipulation of gingival tissue or the periapical region of teeth or perforation of the oral mucosa." Such "high-risk" patients, according to the report, include recipients of cardiac transplants who develop cardiac valvulopathy and patients with:

  • Prior infective endocarditis.
  • Prosthetic cardiac valves.
  • Unrepaired cyanotic congenital heart defects, including palliative shunts and conduits.
  • Congenital heart defects completely repaired with prosthetic material or a device, whether placed by surgery or by catheter intervention, during the first six months after the procedure.
  • Repaired congenital defects with residual defects at the site or adjacent to the site of a prosthetic patch or prosthetic device.
Patient groups that may have received routine antibiotic prophylaxis in the past but are now inappropriate for it include those with mitral and aortic valve disease, rheumatic heart disease, or structural disorders like ventricular or atrial septal defects or hypertrophic cardiomyopathy, according to the AHA statement.

The revised guidelines were developed with the participation of and have been endorsed by the American Dental Association, the Infectious Diseases Society of America, and the American Academy of Pediatrics.

Disclosures of potential conflicts of interest for the writing group and the document's reviewers are included in the report


Wilson W, Taubert KA, Gewitz M, et al. Prevention of infective endocarditis guidelines from the American Heart Association. A guideline from the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee, Council on Cardiovascular Disease in the Young, and the Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and the Quality of Care and Outcomes Research Interdisciplinary Working Group. Circulation 2007. DOI:10.1161/CIRCULATIONAHA.106.183095. Available at:

Related links

Homocysteine-lowering Therapy Not Effective for Prevention of Cardiovascular Disease

Homocysteine-lowering therapy does not prevent recurrent cardiovascular disease after acute myocardial infarction (level 1 [likely reliable] evidence), based on a randomized trial of 3,749 patients ages 30-85 years who received either folic acid 0.8 mg plus vitamin B12 0.4 mg vs. vitamin B6 40 mg vs. combination of both vs. placebo (NEJM 2006 Apr 13;354(15):1578).

In another trial, homocysteine-lowering therapy (folic acid 2.5 mg, vitamin B6 50 mg and vitamin B12 1 mg) was not associated with an overall difference in vascular events (level 2 [mid-level] evidence), based on a randomized trial of 5,522 patients > 55 years old with vascular disease or diabetes (NEJM 2006 Apr 13;354(15):1567).

Noncoronary vascular surgery in high-CV-risk patients: Add PCI or CABG?

Noncoronary vascular surgery in high-CV-risk patients: Add PCI or CABG?
April 20, 2007

Washington, DC - Perioperative PCI or CABG makes little clinical impact in high-cardiovascular-risk patients with ischemic heart disease who undergo major noncoronary vascular surgery, suggests a randomized but inconclusive study [1].

Designed to clarify feasibility and safety considerations for any future larger, definitive exploration of the strategy, the study wasn't statistically strong enough to show whether adding perioperative coronary revascularization makes a clinical difference, caution the authors, led by Dr Don Poldermans (Erasmus Medical Center, Rotterdam, the Netherlands).

But having set the stage for a larger trial, according to the group as well as an accompanying editorial [2], the pilot study raises questions about CV screening before noncardiac surgery and the clinical importance of any discovered coronary stenoses that would be targeted by perioperative revascularization as compared with, for example, vulnerable plaques that are angiographically invisible.

The trial's neutral findings may relate to histopathologic evidence "that the pathophysiology surrounding fatal MI in the perioperative period after noncardiac surgery often includes unstable plaque and plaque disruption," write the editorialists, Drs Mauro Moscucci and Noah Jones (University of Michigan, Ann Arbor). "Thus, it is possible that revascularization of stable coronary artery stenosis might not add significantly to the effect of optimal medical therapy, similar to what has been shown for other low-risk patients with stable coronary artery disease."

The findings from the fifth Dutch Echocardiographic Cardiac Risk Evaluation Applying Stress Echocardiography (DECREASE-5) pilot study and its accompanying editorial are published online April 13, 2007 by the Journal of the American College of Cardiology. They follow similar results from the Coronary Artery Revascularization Prophylaxis (CARP) trial, published in 2004 and reported by heartwire at the time, that compared the invasive and conservative perioperative strategies in a lower-risk CAD population [3].

Conducted in four European countries and Brazil over five years ending in 2005, DECREASE-5 randomized 101 patients with CAD who were scheduled for open abdominal aortic or infrainguinal arterial surgeries to receive either perioperative PCI or CABG (32 and 17 patients, respectively) or medical therapy (52 patients). Patients had been required to have at least three major cardiac risk factors (eg, angina, evidence of prior MI or neurologic events, heart failure, diabetes, or renal dysfunction) as well as stress-test-documented myocardial ischemia. Beta blockers were initiated for any patient not already on them.

In the PCI/CABG group, two patients died from ruptured aortic aneurysms prior to their noncoronary surgical procedures, "consistent with the fact that urgent or emergency vascular surgery in unstable patients should not be delayed by revascularization," Moscucci and Jones caution.

Rates of the primary end point, a 30-day composite of all-cause mortality and nonfatal MI, were 43% and 33%, respectively (p=0.30). Even out to one year, the rates were similar, at 49% and 44%, respectively (p=0.48). Incidences of the primary-end-point components did not differ between the groups. None in the medical-management group required coronary revascularization within a year of the noncoronary vascular surgery.

As none of the conservatively managed patients underwent diagnostic catheterization, yet their outcomes were similar to those managed with PCI or CABG, write the editorialists, "effective beta blockade and medical therapy might be sufficient, raising the question of whether stable patients scheduled for major vascular surgery should even be screened with stress testing."

However, they conclude, "the debate on screening and revascularization for patients with peripheral arterial disease and scheduled for major vascular surgery continues to be far from settled." DECREASE-5 provided safety and sample-size information needed for a larger exploration of the issue, they write. "It is now time to move forward with such a trial."

Moscucci reports receiving consulting fees from Pfizer and Boston Scientific, lecture fees from Pfizer, and grant support from Cordis


1. Poldermans D, Schouten O, Vidakovic R, et al. A clinical randomized trial to evaluate the safety of a noninvasive approach in high-risk patients undergoing major vascular surgery: The DECREASE-V pilot study. J Am Coll Cardiol 2007; DOI:10.1016/j.jacc.2006.11.052. Available at:
2. Moscucci M, Jones N. Coronary revascularization before noncardiac vascular surgery: One more step forward in understanding its role. J Am Coll Cardiol 2007; DOI:10.1016/j.jacc.2007.01.068 . Available at:
3. McFalls EO, Ward HB, Moritz TE, et al. Coronary-artery revascularization before elective major vascular surgery. N Eng J Med 2004; 351:2795-2804.

Related links

Risk for death, stroke increased with combined CABG and CEA [Other News > Medscape Medical News; Jan 16, 2007]
Higher risk of stroke and death in patients undergoing combined CEA-CABG surgery vs CABG alone [HeartWire > Other News; Apr 25, 2005]
No benefit from revascularization before vascular surgery: CARP published [HeartWire > Other News; Dec 29, 2004]

Contemporary Biomarkers - Massachusetts General Hospital

Dr. Thomas J. Wang, Cardiologist, Medicine Department, Massachusetts General Hospital

Should Biomarkers Be Assessed in All Healthy People?

Although the New England Journal of Medicine study confirmed that contemporary biomarkers are associated with the risk of CVD and death, Dr. Wang says that these biomarkers add only moderately to traditional risk factors when assessing the future risk of cardiovascular events in healthy people. “Even in cases when individuals had increased levels of the biomarkers we assessed, they were unlikely to experience an event during the follow-up period. Our data reemphasize the importance of assessing traditional risk factors for each individual. Our results don’t support the idea of screening large populations of healthy people for high levels of these biomarkers.”

Routine measurement of novel biomarkers would be justified if they added to clinicians’ ability to predict risk of death and future CVD events, according to Dr. Wang. “These biomarkers appeared to add only modestly to our predictive ability in the community-based population of people we examined.” However, Dr. Wang adds that it is important to note that the study assessed only healthy individuals. He concedes that the investigators did not examine patients who already had CVD. “Our conclusions cannot and do not exclude the possibility that these biomarkers could be useful in specific patient groups. For example, these biomarkers might more accurately stratify patients at intermediate risk as determined by traditional risk factors.”

The Next Mission: Identify New Biomarkers

Dr. Wang says that the next step in trying to identify healthy patients who are at risk for CVD is to continue using traditional risk factors in prediction models and to identify new biomarkers related to CVD. “There is hope that other biomarkers that have yet to be discovered may better predict and assess cardiovascular risk in healthy individuals,” he says. “While the traditional biomarkers we assessed in our study do contribute to CVD prediction when patients have the disease, they are not good enough to predict risk in healthy people.” Other possible biomarker candidates related to CVD have been identified in recent investigations. “The key now,” Dr. Wang says, “is to study these other biomarkers and determine if it’s possible that some of them may do a better job in healthy cohorts. More research is required, but there is optimism in that our current list of CVD biomarkers will increase in the next five to 10 years. When that happens, we may be able to substantially increase our ability to predict CVD risk in the general population.” Thomas J. Wang, MD has indicated to Physician’s Weekly that he has or has had no financial interests to report.

Contemporary Biomarkers

N Engl J Med 2007; 356:1472-1475, Apr 5, 2007

Multiple Biomarkers for the Prediction of First Major Cardiovascular Events and Death

Thomas J. Wang, M.D., Philimon Gona, Ph.D., Martin G. Larson, Sc.D., Geoffrey H. Tofler, M.D., Daniel Levy, M.D., Christopher Newton-Cheh, M.D., M.P.H., Paul F. Jacques, D.Sc., Nader Rifai, Ph.D., Jacob Selhub, Ph.D., Sander J. Robins, M.D., Emelia J. Benjamin, M.D., Sc.M., Ralph B. D'Agostino, Ph.D., and Ramachandran S. Vasan, M.D.


Background Few investigations have evaluated the incremental usefulness of multiple biomarkers from distinct biologic pathways for predicting the risk of cardiovascular events.
Methods We measured 10 biomarkers in 3209 participants attending a routine examination cycle of the Framingham Heart Study: the levels of C-reactive protein, B-type natriuretic peptide, N-terminal pro–atrial natriuretic peptide, aldosterone, renin, fibrinogen, D-dimer, plasminogen-activator inhibitor type 1, and homocysteine; and the urinary albumin-to-creatinine ratio.

Results During follow-up (median, 7.4 years), 207 participants died and 169 had a first major cardiovascular event. In Cox proportional-hazards models adjusting for conventional risk factors, the following biomarkers most strongly predicted the risk of death (each biomarker is followed by the adjusted hazard ratio per 1 SD increment in the log values): B-type natriuretic peptide level (1.40), C-reactive protein level (1.39), the urinary albumin-to-creatinine ratio (1.22), homocysteine level (1.20), and renin level (1.17). The biomarkers that most strongly predicted major cardiovascular events were B-type natriuretic peptide level (adjusted hazard ratio, 1.25 per 1 SD increment in the log values) and the urinary albumin-to-creatinine ratio (1.20). Persons with "multimarker" scores (based on regression coefficients of significant biomarkers) in the highest quintile as compared with those with scores in the lowest two quintiles had elevated risks of death (adjusted hazard ratio, 4.08; P<0.001) p="0.02)." color="#000099">
Source Information From the Framingham Heart Study, Framingham, MA (T.J.W., P.G., M.G.L., D.L., C.N.-C., S.J.R., E.J.B., R.B.D., R.S.V.); the Division of Cardiology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School (T.J.W., C.N.-C.), and the Department of Mathematics and Statistics, Boston University (P.G., M.G.L., R.B.D.) — both in Boston; the Royal North Shore Hospital, Sydney (G.H.T.); the National Heart, Lung, and Blood Institute, Bethesda, MD (D.L.); and the Jean Mayer Department of Agriculture Human Nutrition Research Center on Aging, Tufts University (P.F.J., J.S.), the Department of Laboratory Medicine, Children's Hospital, Harvard Medical School (N.R.), and the Preventive Medicine and Cardiology Sections (D.L., E.J.B., R.S.V.) and the Division of Endocrinology, Nutrition, and Diabetes (S.J.R.), Boston Medical Center, Boston University School of Medicine — all in

Texto completo (p/ assinantes):

Friday, April 20, 2007

Low salt intake reduces risk of cardiovascular disease

Br Med J 2007; Advance online publication

MedWire News: People could reduce their long-term risk of cardiovascular events by reducing their dietary sodium intake, US researchers say.

"The observed reduction in cardiovascular risk associated with this sodium decrease was substantial and provides strong support for population-wide reduction in dietary sodium intake to prevent cardiovascular disease," the authors write in the British Medical Journal.

Nancy Cook (Harvard Medical School, Boston, Massachusetts) and colleagues followed-up 2415 participants in two randomized trials – the trial of hypertension prevention phase I (TOHP I) and phase II (TOHP II) – for cardiovascular disease and mortality over a period of 10-15 years.

Patients with prehypertension were randomly assigned to an active sodium-reduction intervention or usual care control for 18 months in the TOPH I, and 36-48 months in the TOPH II trial. Net sodium reductions in the intervention groups were 44 and 33 mmol/24 hours, respectively.

The primary outcome was cardiovascular disease, a composite of myocardial infarction, stroke, coronary artery bypass graft, percutaneous transluminal coronary angioplasty, or cardiovascular death.

Patients in the sodium-reduction intervention group had a 25% lower risk of cardiovascular disease compared with those in the control group (relative risk [RR]=0.75, p=0.04), after adjustment for trial, clinic, age, ethnic background, and gender.

Further adjustments for baseline weight and sodium excretion revealed a 30% reduction of cardiovascular disease risk among patients in the sodium intervention group (RR=0.70, p=0.02), compared with controls.

Overall, 35 patients in the sodium group and 42 patients in the control group died, with 10 and 15 of the deaths, respectively, induced by cardiovascular disease. Results were similar for each trial.

Intention to treat analysis showed a mortality risk reduction of 20% among patients in the sodium reduction intervention, compared with those in the control group (RR=0.80, p=0.25).
Cook and co-workers conclude: "People with prehypertension assigned to a sodium reduction intervention experienced a 25-30% lower risk of cardiovascular outcomes in the 10 to 15 years after the trial.

"Sodium reduction, previously shown to lower blood pressure and prevent hypertension, also seems to prevent cardiovascular disease."


Free full text [PDF]

Thursday, April 19, 2007

Brain Natriuretic Peptide (BNP) and Heart Failure

Protein Monitoring Improved Heart Failure Treatment French trial found fewer deaths and hospital stays

WEDNESDAY, April 18 (HealthDay News) -- A trial that used blood levels of a biomarker called brain natriuretic peptide (BNP) to guide treatment of heart failure more than halved the incidence of death or hospitalization for the condition over 15 months, French cardiologists report.

Just 24 percent of the 110 trial participants whose drug treatment was adjusted according to BNP levels reached those critical end points of death or hospitalization. That compared to 52 percent of those who did not get BNP monitoring.

There were seven deaths from heart failure in the BNP-monitored group, compared to 11 in the non-monitored patients. The overall incidence of hospitalization was about the same in both groups, but just 22 hospital stays due to heart failure complications in the monitored group compared to 48 among patients whose BNP levels were not monitored.

The major difference in medical treatment was use of higher doses of beta-blocker and ACE inhibitor drugs in the BNP-monitored group, the researchers said.

BNP is a protein produced by the muscle cells of the heart ventricles as a response to excess stretching of those cells. Tests of BNP blood levels are used to help diagnosis heart failure, a condition in which the heart progressively loses its ability to pump blood, and to assess the prognosis for people with heart failure. Most drugs used to treat heart failure lower BNP levels.

The study participants, whose average age was 65, had essentially similar symptoms at the start of the trial, although those in the BNP-monitored group had a slightly lower average ejection fraction, which measures the heart's blood-pumping ability.

The findings are published in the April 24 issue of the Journal of the American College of Cardiology .

Wednesday, April 18, 2007

Cardiovascular Disease Prevention in Women: Evidence-Based Guidelines for: 2007 Update

Updated guidelines advise focusing on women's lifetime heart risk

Update gives definitive answers on HRT, aspirin, supplements

DALLAS, Feb. 20, 2007 – Healthcare professionals should focus on women’s lifetime heart disease risk, not just short-term risk, according to updated American Heart Association guidelines.

The 2007 Guidelines for Preventing Cardiovascular Disease in Women – published today in a special women’s health issue of Circulation: Journal of the American Heart Association – also include new directions for using aspirin, hormone therapy and vitamin and mineral supplements in heart disease and stroke prevention in women.

Highlights of the changes include:

  • Recommended lifestyle changes to help manage blood pressure include weight control, increased physical activity, alcohol moderation, sodium restriction, and an emphasis on eating fresh fruits, vegetables and low-fat dairy products.

  • Besides advising women to quit smoking, the 2007 guidelines recommend counseling, nicotine replacement or other forms of smoking cessation therapy.

  • Physical activity recommendations for women who need to lose weight or sustain weight loss have been added – minimum of 60–-90 minutes of moderate-intensity activity (e.g., brisk walking) on most, and preferably all, days of the week.

  • The guidelines now encourage all women to reduce saturated fats intake to less than 7 percent of calories if possible.

  • Specific guidance on omega-3 fatty acid intake and supplementation recommends eating oily fish at least twice a week, and consider taking a capsule supplement of 850–1000 mg of EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) in women with heart disease, two to four grams for women with high triglycerides.

  • Hormone replacement therapy and selective estrogen receptor modulators (SERMs) are not recommended to prevent heart disease in women.

  • Antioxidant supplements (such as vitamin E, C and beta-carotene) should not be used for primary or secondary prevention of CVD.

  • Folic acid should not be used to prevent CVD – a change from the 2004 guidelines that did recommend it be considered for use in certain high-risk women.

  • Routine low dose aspirin therapy may be considered in women age 65 or older regardless of CVD risk status, if benefits are likely to outweigh other risks. (Previous guidelines did not recommend aspirin in lower risk or healthy women.)

  • The upper dosage of aspirin for high-risk women increases to 325 mg per day rather than 162 mg. This brings the women’s guidelines up to date with other recently published guidelines.

  • Consider reducing LDL cholesterol to less than 70 mg/dL in very high-risk women with heart disease (which may require a combination of cholesterol-lowering drugs).

This 2007 update provides the most current clinical recommendations for preventing CVD in women 20 and older and are based on a systematic search of the highest quality science interpreted by experts in the fields of cardiology, epidemiology, family medicine, gynecology, internal medicine, neurology, nursing, public health, statistics and surgery.
The authors note that these guidelines cover the primary and secondary prevention of chronic atherosclerotic vascular diseases.

Tuesday, April 17, 2007

Australian Prescriber - Evidence, risk and the patient

Australian Prescriber - Evidence, risk and the patient

Brain hypertension role identified

(Hypertension 2007; Advance online publication)

17 April 2007MedWire News: Inflammation in the brain may play a role in hypertension, scientists report.

They found that a protein, called junctional adhesion molecule (JAM)-1, was elevated in the nucleus tractus solitarii (NTS) of rats with hypertension. Furthermore, engineering normal rats to express high levels of JAM-1 in this region of the brain led to increases in their blood pressure. JAM-1 is known to be involved in leukocyte and platelet adhesion in peripheral circulation.

The authors say that hypertension may therefore develop as a result of inflammatory cytokines activating the sympathetic nervous system. If proven, this could lead to novel approaches to treating hypertension.

Julian Paton (University of Bristol, UK) and colleagues studied JAM-1 expression in rats, having already found it was upregulated in prehypertensive animals. They found significantly higher levels of JAM-1 messenger RNA in the NTS of spontaneous hypertensive (SH) rats compared with normotensive Wistar-Kyoto (WKY) rats. The NTS plays a pivotal role in arterial pressure regulation, the team notes. Adenoviral-mediated expression of JAM-1 in the NTS of WKY rats led to a significant increase in systolic blood pressure, from 120 mmHg to 132 mmHg (p<0.01). color="#000099">

Associate medical director of the British Heart Foundation, Jeremy Pearson, said: "This exciting study is important because it suggests there are unexpected causes of high blood pressure related to blood supply to the brain. It therefore opens up the possibility of new ways to treat this common, but often poorly managed, condition."

Hypertension 2007; Advance online publication

ILLUSTRATE - Considerações

Title: Effect of Torcetrapib on the Progression of Coronary Atherosclerosis

Nissen SE, Tardif JC, Nicholls SJ, et al., on behalf of the ILLUSTRATE Investigators.

Citation: N Engl J Med. 2007;356:1304-1316.

Study Question: Does torcetrapib, a novel cholesteryl ester transfer protein (CETP) inhibitor that raises high-density lipoprotein cholesterol (HDL-C) by more than 50%, impact progression of coronary atherosclerosis?

Methods: A total of 1,188 patients with coronary disease underwent intravascular ultrasonography (IVUS). After treatment with atorvastatin to reduce levels of low-density lipoprotein cholesterol (LDL-C) to <100 mg/dl (2.59 mmol/L), patients were randomly assigned to receive either atorvastatin monotherapy or atorvastatin plus 60 mg of torcetrapib daily. After 24 months, disease progression was measured by repeated IVUS in 910 patients (77%). Each target site for the primary analysis was required to have <50% obstruction throughout a segment of 40 mm or longer.
Results: Mean age was 57 years, 70% were men, and 91% were on a statin at baseline. Baseline mean LDL-C was 84 mg/dl and HDL-C was 45.5 mg/dl, and median LDL-C:HDL-C was 1.89. After 24 months, as compared with atorvastatin monotherapy, the effect of torcetrapib–atorvastatin therapy was an approximate 61% relative increase in HDL-C (43.9 mg/dl vs. 72.1 mg/dl) and a 20% relative decrease in LDL-C, reaching a ratio of LDL-C to HDL-C of <1.0. Torcetrapib was also associated with an increase in systolic blood pressure of 4.6 mm Hg. The percent atheroma volume (the primary efficacy measure) increased by 0.19% in the atorvastatin-only group and by 0.12% in the torcetrapib–atorvastatin group (p = 0.72). A secondary measure, the change in normalized atheroma volume, showed a small favorable effect for torcetrapib (p = 0.02), but there was no significant difference in the change in atheroma volume for the most diseased vessel segment.
Conclusions: The CETP inhibitor torcetrapib was associated with a substantial increase in HDL-C and decrease in LDL-C. It was also associated with an increase in blood pressure, and there was no significant decrease in the progression of coronary atherosclerosis. The lack of efficacy may be related to the mechanism of action of this drug class or to molecule-specific adverse effects.

Perspective: Previous similar IVUS studies have shown that intense lowering of LDL-C by statins decreases the total atheroma volume by as much as 14.7 mm3 at 24 months, and the infusion of A-1 Milano resulted in a 14.1 mm3 reduction in atheroma volume at 1 month. It would appear that increasing HDL particle cholesterol content with a CETP inhibitor does not result in better functioning HDL particles, and there are experimental data that these cholesterol-rich HDL particles may have proinflammatory effects. The clinical morbidity–mortality trial of torcetrapib–atorvastatin was prematurely terminated because of an increase in event rates that might be explained by both the increase in systolic blood pressure and dysfunctional HDL particles. In addition to niacin, several novel drugs/devices are currently being studied in randomized trials to determine their effect on atherosclerosis progression and events. Melvyn Rubenfire, M.D., F.A.C.C.

Thursday, April 12, 2007

Effect of Cocoa and Tea Intake on Blood Pressure

Effect of Cocoa and Tea Intake on Blood Pressure
A Meta-analysis

Dirk Taubert, MD, PhD; Renate Roesen, PhD; Edgar Schömig, MD
Arch Intern Med. 2007;167:626-634.

Background Epidemiological evidence suggests blood pressure–lowering effects of cocoa and tea. We undertook a meta-analysis of randomized controlled trials to determine changes in systolic and diastolic blood pressure due to the intake of cocoa products or black and green tea.

Methods MEDLINE, EMBASE, SCOPUS, Science Citation Index, and the Cochrane Controlled Trials Register were searched from 1966 until October 2006 for studies in parallel group or crossover design involving 10 or more adults in whom blood pressure was assessed before and after receiving cocoa products or black or green tea for at least 7 days.

Results Five randomized controlled studies of cocoa administration involving a total of 173 subjects with a median duration of 2 weeks were included. After the cocoa diets, the pooled mean systolic and diastolic blood pressure were –4.7 mm Hg (95% confidence interval [CI], –7.6 to –1.8 mm Hg; P = .002) and –2.8 mm Hg (95% CI, –4.8 to –0.8 mm Hg; P = .006) lower, respectively, compared with the cocoa-free controls. Five studies of tea consumption involving a total of 343 subjects with a median duration of 4 weeks were selected. The tea intake had no significant effects on blood pressure. The estimated pooled changes were 0.4 mm Hg (95% CI, –1.3 to 2.2 mm Hg; P = .63) in systolic and –0.6 mm Hg (95% CI, –1.5 to 0.4 mm Hg; P = .38) in diastolic blood pressure compared with controls.

Conclusion Current randomized dietary studies indicate that consumption of foods rich in cocoa may reduce blood pressure, while tea intake appears to have no effect.

Author Affiliations: Department of Pharmacology, University Hospital of Cologne, Cologne, Germany.

This meta-analysis involved only a few studies with small sample sizes and short duration, limiting the statistical power and generalizability to long-term outcomes.

The researchers also cautioned that potential weight gain with the high-caloric cocoa diets "may reverse any blood pressure reductions during long-term habitual intake of cocoa products."

"We believe that any dietary advice must account for the high sugar, fat, and calorie intake with most cocoa products," they cautioned, but added, "it appears reasonable to allow phenol-rich cocoa products such as dark chocolate for calorie-balanced substitution of high-fat dairy products, sugar confectionary, or cookies of the usual diet."
The researchers reported no financial conflicts of interest


Taubert D, et al "Effect of Cocoa and Tea Intake on Blood Pressure: A Meta-analysis" Arch Intern Med. 2007;167:626-634.

Wednesday, April 11, 2007


Recém publicado:

Abstrast and Full Text: FREE.

New England Journal of Medicine
Volume 356:1503-1516 April 12, 2007 Number 15

Optimal Medical Therapy with or without PCI for Stable Coronary Disease

Full Text:

Tuesday, April 10, 2007

Antioxidant vitamins increase mortality

Qual o impacto que um trabalho como esse poderá trazer à prática médica brasileira?

Antioxidant vitamins increase mortality

Copenhagen, Denmark - The largest analysis of data on antioxidant vitamins ever conducted has shown that beta-carotene, vitamin A, and vitamin E probably increase mortality [1]. Two other antioxidant substances—vitamin C and selenium—had no effect on mortality.

The meta-analysis of 68 randomized trials with a total of 232 606 participants, published in the February 28, 2007 issue of the Journal of the American Medical Association, was conducted by a group led by Dr Goran Bjelakovic (Copenhagen University Hospital, Denmark).

Coauthor Dr Christian Gluud (Copenhagen University Hospital) commented to heartwire: "This is the most comprehensive collection of data on antioxidant vitamins ever conducted, and we have shown that on the whole these agents have no benefit. Indeed, vitamin A, vitamin E, and beta-carotene are associated with an increase in mortality at the doses studied. Vitamin A and beta-carotene seem to have a dose-related effect, with mortality increasing as doses increase, whereas vitamin E does not appear to have a dose-related effect, with all doses associated with increased mortality."

Jury still out on vitamin C and selenium

Gluud added that the jury is still out on vitamin C and selenium. "Vitamin C does not appear to be detrimental, but it is not beneficial either, and all the trials of selenium together suggest a small benefit, but when only the well-conducted trials are included, there appears to be neither benefit nor harm.

"Our data show that antioxidant vitamins should not be taken in an effort to prevent illness. People should instead eat a balanced diet and take regular exercise," he said.

In the paper, the authors note that many people are taking antioxidant supplements in the belief that they improve health and prevent diseases. Many primary- or secondary-prevention trials of antioxidant supplements have been conducted to investigate the prevention of several diseases—mainly cardiovascular disease and cancer—but results have generally not been positive, with some trials showing increases in mortality.

To find out more, they conducted the current systematic review to analyze the effects of antioxidant supplements on all-cause mortality of adults included in primary- and secondary-prevention trials. They included all primary- and secondary-prevention published trials in adults randomized to receive beta-carotene, vitamin A, vitamin C, vitamin E, or selenium vs placebo or no intervention.

Results showed that when all trials of antioxidant supplements were pooled together, there was no significant effect on mortality, but when the 47 trials said to have a low risk of bias (in a total of 180 938 participants) were analyzed alone, the antioxidant supplements as a whole significantly increased mortality, and beta-carotene, vitamin A, and vitamin E were all associated with increased mortality when given alone or in combination. Vitamin C and selenium had no significant effect on mortality.

The researchers note that more than two thirds of the included trials fell into the category of those with a low risk of bias, which they say highlights the validity of their results. "Antioxidant supplements not only seem to be one of the most researched topics in the world, they also seem to be one of the most adequately researched clinical questions," they say.

They point out that a large number of unpublished trials on supplements may exist, but as unpublished trials are more likely to have been either neutral or negative than to have shown beneficial effects, this suggests their estimate of a 5% increase in mortality is likely to be conservative.

Substantial public-health consequences

Noting that 10% to 20% of the adult population (80 million-160 million people) in North America and Europe may consume these supplements, Bjelakovic et al say the public-health consequences may be substantial.

Speculating on possible mechanisms, they point out that although oxidative stress has a hypothesized role in the pathogenesis of many chronic diseases, it may be the consequence of pathological conditions, and that eliminating free radicals may interfere with some essential defensive mechanisms.

In an interview with heartwire, Gluud also suggested that the antioxidant vitamins could actually also have pro-oxidant effects. "We don't know exactly how they are doing harm, but rather than preventing cardiovascular disease and cancer, they actually seem to be accelerating these conditions."

Lessons learned

He said these observations were "a huge disappointment" but added that at least it has been discovered. "We must see the positives in this. The question has been thoroughly addressed and we now know the answer—these agents are harmful. The companies selling these antioxidant vitamins have been able to dodge the issue for a long time, saying that any negative data have not been comprehensive. They cannot do this any longer. There are lessons to be learned here— for example, the importance of conducting trials with these agents and publishing the results."

Gluud added that food supplements should be regulated in the same way as medical products. "The governments of the world now have the responsibility to inform people of these results. They have been too slow in the past in requesting that health supplements be properly evaluated before allowing these products to be added to foods. People have been buying these supplements and foods advertised as having these supplements added under the impression that they are good for them, when in actual fact they are harmful. Any potential health supplements should not be allowed to be added to foods unless they have been shown to be beneficial or at least proven not to be harmful."

Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial.

Resultado do Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial.
Publicado noNew England Journal of MedicinePublished at March 26, 2007 (10.1056/NEJMoa070829) Optimal Medical Therapy with or without PCI for Stable Coronary Disease

William E. Boden, M.D., Robert A. O’Rourke, M.D., Koon K. Teo, M.B., B.Ch., Ph.D., Pamela M. Hartigan, Ph.D., David J. Maron, M.D., William J. Kostuk, M.D., Merril Knudtson, M.D., Marcin Dada, M.D., Paul Casperson, Ph.D., Crystal L. Harris, Pharm.D., Bernard R. Chaitman, M.D., Leslee Shaw, Ph.D., Gilbert Gosselin, M.D., Shah Nawaz, M.D., Lawrence M. Title, M.D., Gerald Gau, M.D., Alvin S. Blaustein, M.D., David C. Booth, M.D., Eric R. Bates, M.D., John A. Spertus, M.D., M.P.H., Daniel S. Berman, M.D., G.B. John Mancini, M.D., William S. Weintraub, M.D., for the COURAGE Trial Research Group

Background: Permenece uma incerteza se em pacientes com Doença Arterial Coronariana (DAC) estável, a utilização de métodologia invasiva como a Intervenção Coronariana Percutânea (PCI) associada a terapia farmacológica e intervenção no estilo de vida (terapia médica ótima) é superior a terapia médica ótima (TMO) isoladamente na redução de eventos

Métodos: Os pesquisadores conduziram um trial randomizado envolvendo 2287 pacientes com evidência de isquemia miocárdica e DAC em 50 centros americanos e canadenses. Entre 1999 e 2004 foram especificados 1149 pacientes para serem submetidos a PCI com terapia médica ótima e 1138 para receber apenas terapia médica ótima. O desfecho primário foi morte por qualquer causa e não-fatal infarto do miocárdio durante um follow-up de 2.5 a 7.0 anos (média de 4.6 anos)

Resultados: Aconteceram 211 eventos primários no grupo PCI e 202 eventos no grupo TMO. A taxa de eventos cumulativos de 4.6 anos foi de 19% no grupo PCI e 18.5% no grupo TMO (Hazard Ratios para o grupo PCI, 1.05; 95% intervalo de confiança [IC], 0.87 to 1.27; p=0.62). Não houveram diferenças significativas entre o grupo PCI e o grupo TMO na composição de mortes, infarto do miocárdio e acidente vascular encefálico (20.0% vs. 19.5%; hazard ratio, 1.05; 95% CI 0.87 to 1.27; p=0.62); hospitalização para síndromes coronarianas agudas (12.4% vs. 11.8%; hazard ratio 1.07; 95% CI 0.84 to 1.37; p=0.56; ou infarto do miocárdio ((13.2% vs. 12.3%; hazard ratio, 1.13; 95% CI, 0.89 to 1.43; P=0.33).

Conclusão: PCI quando associado a TMO não reduz o risco de morte, infarto do miocárdio ou outros eventos cardiovasculares maiores, quando utilizado como terapêutica inicial em pacientes com DAC estável. ( number, NCT00007657 [] .)

Texto completo desse artigo:

The results COURAGE trial were presented at the American College of Cardiology, 27 March 2007 annual scientific sessions being held in New Orleans, Louisiana, and were published simultaneously advance online by the New England Journal of Medicine.

The REACH (Reduction of Atherothrombosis for Continued Health

One-Year Cardiovascular Event Rates in Outpatients With Atherothrombosis

Reference: JAMA 2007; 297: 1197-1206,

This study suggests that outpatients with established atherosclerotic arterial disease and those with multiple risk factors for atherosclerosis, experience relatively high annual CVD event rates. These findings reinforce the continued efforts that need to be directed toward the primary and secondary prevention of underlying atherosclerosis so that fatal and nonfatal events can be prevented or delayed to an older age.

Authors: PG Steg, DL Bhatt, PWF Wilson, R D'Agostino, EM Ohman, J Röther, C-SLiau, AT Hirsch, J-L Mas, Y Ikeda, MJ Pencina, S Goto, for the REACH RegistryInvestigators

Reviewer: Robert Goldberg, PhD, ProCOR Contributing Editor

Problem addressed: Contemporary natural history of outpatients with atherosclerotic disease or multiple risk factors for CVD.Purpose of study: To examine contemporary, and multinational, one year even trates of CVD in outpatients with established arterial disease or with multiple coronary risk factors.

Location of study: Paris, France.

Study design: Prospective

Results: The REACH (Reduction of Atherothrombosis for Continued Health) registry includes data on adult (>= 45 years) outpatients with established CVD, CAD, or peripheral vascular disease, as well as in those with at least three riskf actors for atherothrombosis being present. These high-risk patients were recruited from nearly 5600 physician practices in 44 countries between December 2003 and June 2004. Follow-up data were collected at approximately one year after study enrollment and information was collected about the occurrence of fatal and non-fatal eventsof stroke, MI, or CVD in the study sample. A total of nearly 65,000 patients were enrolled in this study. Approximately two-thirds were men, 44% had a history of diabetes, 82% had prior hypertension, nearly one in three were obese, and the average age of the study sample was 69 years. Approximately three quarters of study enrollees were being treated with antiplatelet therapy, nearly half were prescribed beta blockers, 69% were on statin therapy, and nearly 40% were on an antidiabetic agent at the time of study entry. As expected, both the frequency of coronary risk factors and treatment practices varied between the different geographic locales under study.Over the course of the one-year follow-up, all-cause mortality was 2.6%; the death rates were nearly twice as high in those with established arterial diseaseas compared to those with multiple coronary risk factors (2.8% vs. 1.5%). The overall rate of combined events of CVD death, MI, or stroke was 4.2%, again being approximately two fold higher in those with established atheroscleroticarterial disease (4.7%) as compared to those with multiple risk factors only(2.2%). Moreover, the one-year event rates of CVD, MI, stroke, or related hospitalizations also varied inversely with the presence of established arterial disease as compared to those with multiple risk factors only.In addition to the occurrence of these fatal and nonfatal events, the frequency of the pooled CVD endpoint increased with the number of symptomatic arterial disease locations present. For example, 5.3% of patients with multiple CHD riskfactors developed this aggregate endpoint compared to 12.6%, 21.1%, and 26.3% of patients with one, two, and three symptomatic arterial disease locations,respectively. In terms of geographic variation, participants from Japan experienced the lowest rates of all study endpoints whereas the highest event rates were observed in the Middle East and Eastern Europe.

Discussion: The results of this large multi-site international study suggestthat outpatients with established atherosclerotic arterial disease, as well as those with multiple risk factors for atherosclerosis, experience relatively high annual event rates of CVD, with these rates varying according to the underlying burden of disease. Indeed, over the course of the one-year follow-up period, approximately one in every seven patients with underlying arterial disease experienced either a hard CVD endpoint or required hospitalization for anatherosclerotic event. These events were noted despite the relatively high use of secondary preventive modalities in the study sample, though the utilization of several agents was less than optimal, and relatively few patients were attarget goals for body weight, BP, or serum cholesterol levels.The present results clearly identify groups at increased risk for adverse events in whom lifestyle modifications and more optimal management with proven treatment regimens remain needed. These findings reinforce the continued efforts that need to be directed toward the primary and secondary prevention of underlying atherosclerosis so that both fatal and nonfatal events of the various manifestations of this disease process can be prevented or delayed to an olderage.

Colin Rose MD PhD, Cardiologist, Associate Professor of Medicine, McGill University, faz severas crítcas ao artigo e particularmente questões vinculadas aos conflitos de intereese (financial disclosure) dos pesquisadores e também do editorialista da JAMA.

Readers should be made aware of the disclosure of Dr. McDermott, the editorialist:

Financial Disclosures: Dr McDermott reports that she has received honoraria from Bristol-Myers Squibb, Sanofi-Aventis, NicOx, and Otsuka Pharmaceutical, has served as a consultant for Hutchinson Technology, and is currently receiving support from research grants from the National Heart, Lung, and Blood Institute.

Comentários de Colin Rose:

Why couldn’t JAMA find an editorialist with no connection to “industry”, particularly the company funding the study which was editorialized?

If you wonder why this is a “free” publication just look at the disclosures and funding:

Financial Disclosures:
Dr Bhatt reports that he has received honoraria for consulting on scientific advisory boards from AstraZeneca, Bristol-Myers Squibb, Centocor, Eisai, Eli Lilly, GlaxoSmithKline, Millennium, Otsuka, Paringenix, PDL, Sanofi-Aventis, Schering Plough, The Medicines Company; honoraria for lectures from Bristol-Myers Squibb, Sanofi-Aventis, and The Medicines Company; and provided expert testimony regarding clopidogrel (the compensation was donated to a nonprofit organization).
Dr Röther reports that he has received honoraria from Bristol-Myers Squibb and Sanofi-Aventis. Dr Steg reports that he has received honoraria from Bristol-Myers Squibb and Sanofi-Aventis and has received research grants from Sanofi-Aventis.
Dr Steg reports having served as a member of the speakers’ bureau for Boehringer Ingelheim, Servier, GlaxoSmithKline, Merck, Sharp & Dohme, and Nycomed and also on a consultant ad board for AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Merck, Sharp & Dohme, Sanofi-Aventis, Servier, and Takeda.
Dr Ohman reports that he has received research grants from Berlex, Sanofi-Aventis, Schering-Plough, Eli Lilly, Bristol-Myers Squibb, and Millennium. Dr Ohman reports that he has stock ownership in Medtronic, Savacor, and Response Biomedical and is a consultant for Invoise, Response Biomedical, Savacor, and Liposcience.
Dr Hirsch reports that he has received research grants from Bristol-Myers Squibb and Sanofi-Aventis; honoraria from Sanofi-Aventis; and speaker’s bureau fees for Sanofi-Aventis.
Dr Wilson reports that he has received a grant from Sanofi-Aventis.
None of the other authors reported disclosures.

Funding/Support: The REACH Registry is sponsored by Sanofi-Aventis, Bristol-Myers Squibb, and the Waksman Foundation (Tokyo, Japan), who assisted with the design and conduct of the study and data collection.

Comentários de Colin Rose:

Call me paranoid but I have a suspicion that the conclusion of the next paper from REACH will be that “dual anti-platelet” therapy (read ASA and Plavix) is underused. Thus the “reduction” in REACH.

Comentários finais do Dr. Colin Rose:

In the final analysis, what is the point in studying atherosclerosis in a population in which 80% are overweight or obese, 44% are diabetic, 82% are hypertensive and 16% are smoking? The causes of their atherosclerosis are obvious, food and/or tobacco addictions as we have known for many years.

If sanofi-aventis and Bristol-Myers Squibb really want to reduce “atherothrombosis” and improve health they should fund programs for fighting these addictions instead of doing more surveys to try to justify more drug sales. From their own data it is clear that drugs do not increase life expectancy.