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Jose C. Nicolau

Bio: Jose C. Nicolau is an academic researcher from University of São Paulo. The author has contributed to research in topics: Myocardial infarction & Acute coronary syndrome. The author has an hindex of 57, co-authored 385 publications receiving 23006 citations. Previous affiliations of Jose C. Nicolau include University of Pavol Jozef Šafárik & Brigham and Women's Hospital.


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TL;DR: Antiinflammatory therapy targeting the interleukin‐1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid‐level lowering.
Abstract: BackgroundExperimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. MethodsWe conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. ResultsAt 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in t...

5,660 citations

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TL;DR: Among patients with heart failure and a reduced ejection fraction, the risk of worsening heart failure or death from cardiovascular causes was lower among those who received dapagliflozin than amongThose who received placebo, regardless of the presence or absence of diabetes.
Abstract: Background In patients with type 2 diabetes, inhibitors of sodium–glucose cotransporter 2 (SGLT2) reduce the risk of a first hospitalization for heart failure, possibly through glucose-ind...

3,541 citations

Journal ArticleDOI
TL;DR: In patients with a myocardial infarction more than 1 year previously, treatment with ticagrelor significantly reduced the risk of cardiovascular death, my Cardiac Infarction, or stroke and increased therisk of major bleeding.
Abstract: BACKGROUND The potential benefit of dual antiplatelet therapy beyond 1 year after a myocardial infarction has not been established. We investigated the efficacy and safety of ticagrelor, a P2Y 12 receptor antagonist with established efficacy after an acute coronary syndrome, in this context. METHODS We randomly assigned, in a double-blind 1:1:1 fashion, 21,162 patients who had had a myocardial infarction 1 to 3 years earlier to ticagrelor at a dose of 90 mg twice daily, ticagrelor at a dose of 60 mg twice daily, or placebo. All the patients were to receive low-dose aspirin and were followed for a median of 33 months. The primary efficacy end point was the composite of cardiovascular death, myocardial infarction, or stroke. The primary safety end point was Thrombolysis in Myocardial Infarction (TIMI) major bleeding. RESULTS The two ticagrelor doses each reduced, as compared with placebo, the rate of the primary efficacy end point, with Kaplan–Meier rates at 3 years of 7.85% in the group that received 90 mg of ticagrelor twice daily, 7.77% in the group that received 60 mg of ticagrelor twice daily, and 9.04% in the placebo group (hazard ratio for 90 mg of ticagrelor vs. placebo, 0.85; 95% confidence interval [CI], 0.75 to 0.96; P = 0.008; hazard ratio for 60 mg of ticagrelor vs. placebo, 0.84; 95% CI, 0.74 to 0.95; P = 0.004). Rates of TIMI major bleeding were higher with ticagrelor (2.60% with 90 mg and 2.30% with 60 mg) than with placebo (1.06%) (P<0.001 for each dose vs. placebo); the rates of intracranial hemorrhage or fatal bleeding in the three groups were 0.63%, 0.71%, and 0.60%, respectively. CONCLUSIONS In patients with a myocardial infarction more than 1 year previously, treatment with ticagrelor significantly reduced the risk of cardiovascular death, myocardial infarction, or stroke and increased the risk of major bleeding. (Funded by AstraZeneca; PEGASUS-TIMI 54 ClinicalTrials.gov number, NCT01225562.)

1,535 citations

Journal ArticleDOI
Paul M. Ridker1, Jean G. MacFadyen1, Tom Thuren2, Brendan M. Everett1, Peter Libby1, R J Glynn1, Paul Ridker3, Alberto J. Lorenzatti, Henry Krum, John Varigos, Peter Siostrzonek, Peter Sinnaeve, Francisco Antonio Helfenstein Fonseca, Jose C. Nicolau, Nina Gotcheva, Jacques Genest, Huo Yong, Miguel Urina-Triana, Davor Miličić, Renata Cifkova, Riina Vettus, Wolfgang Koenig, Stephan D Anker, Athanasios J. Manolis, Fernando Wyss, Tamás Forster, Axel Sigurdsson, Prem Pais, Alessandro Fucili, Hisao Ogawa, Hiroaki Shimokawa, Irina Veze, Birute Petrauskiene, Leon Salvador, John J.P. Kastelein, Jan H. Cornel, Tor Ole Klemsdal, Félix Medina, Andrzej Budaj, Luminita Vida-Simiti, Zhanna Kobalava, Petar Otasevic, Daniel Pella, Mitja Lainscak, Ki-Bae Seung, Patrick J. Commerford, Mikael Dellborg, Marc Y. Donath, Juey-Jen Hwang, Hakan Kultursay, Marcus Flather, Christie M. Ballantyne, Seth Bilazarian, William Chang, Cara East, Brendan Everett3, Les Forgosh, Robert J. Glynn1, Barry Harris, Monica Ligueros, Erin A. Bohula, Bindu Charmarthi, Susan Cheng, Sherry Chou, Jacqueline Danik, Graham McMahon, Bradley Maron, MingMing Ning, Benjamin Olenchock, Reena Pande, Todd Perlstein, Aruna D. Pradhan, Natalia Rost, Aneesh Singhal, Viviany Taqueti, Nancy Wei, Howard A. Burris, Angela Cioffi, Anne Marie Dalseg, Nilanjan Ghosh, Julie R. Gralow, Tina Mayer, Hope S. Rugo, Vance G. Fowler, Ajit P. Limaye, Sara Cosgrove, Donald Levine, Renato D. Lopes, John D. Scott, Robert Hilkert, Georgia Tamesby, Carolyn Mickel, Brian Manning, Julian Woelcke, Monique Tan, Sheryl Manfreda, Tom Ponce, Jane Kam, Ravinder Saini, Kehur Banker, Thomas Salko, Panjat Nandy, Ronda Tawfik, Greg O'Neil, Shobha Manne, Pravin Jirvankar, Shankar Lal, Deepak Nema, Jaison Jose, Rory Collins, Kent Bailey, Roger S. Blumenthal, Helen M. Colhoun, Bernard J. Gersh 
TL;DR: The hypothesis-generating data suggest the possibility that anti-inflammatory therapy with canakinumab targeting the interleukin-1β innate immunity pathway could significantly reduce incident lung cancer and lung cancer mortality.

839 citations

Journal ArticleDOI
TL;DR: Inhibition of PAR-1 with vorapaxar reduced the risk of cardiovascular death or ischemic events in patients with stable atherosclerosis who were receiving standard therapy, however, it increased therisk of moderate or severe bleeding, including intracranial hemorrhage.
Abstract: BACKGROUND: Thrombin potently activates platelets through the protease-activated receptor PAR-1. Vorapaxar is a novel antiplatelet agent that selectively inhibits the cellular actions of thrombin through antagonism of PAR-1. METHODS: We randomly assigned 26,449 patients who had a history of myocardial infarction, ischemic stroke, or peripheral arterial disease to receive vorapaxar (2.5 mg daily) or matching placebo and followed them for a median of 30 months. The primary efficacy end point was the composite of death from cardiovascular causes, myocardial infarction, or stroke. After 2 years, the data and safety monitoring board recommended discontinuation of the study treatment in patients with a history of stroke owing to the risk of intracranial hemorrhage. RESULTS: At 3 years, the primary end point had occurred in 1028 patients (9.3%) in the vorapaxar group and in 1176 patients (10.5%) in the placebo group (hazard ratio for the vorapaxar group, 0.87; 95% confidence interval [CI], 0.80 to 0.94; P<0.001). Cardiovascular death, myocardial infarction, stroke, or recurrent ischemia leading to revascularization occurred in 1259 patients (11.2%) in the vorapaxar group and 1417 patients (12.4%) in the placebo group (hazard ratio, 0.88; 95% CI, 0.82 to 0.95; P=0.001). Moderate or severe bleeding occurred in 4.2% of patients who received vorapaxar and 2.5% of those who received placebo (hazard ratio, 1.66; 95% CI, 1.43 to 1.93; P<0.001). There was an increase in the rate of intracranial hemorrhage in the vorapaxar group (1.0%, vs. 0.5% in the placebo group; P<0.001). CONCLUSIONS: Inhibition of PAR-1 with vorapaxar reduced the risk of cardiovascular death or ischemic events in patients with stable atherosclerosis who were receiving standard therapy. However, it increased the risk of moderate or severe bleeding, including intracranial hemorrhage. (Funded by Merck; TRA 2P-TIMI 50 ClinicalTrials.gov number, NCT00526474.).

816 citations


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08 Dec 2001-BMJ
TL;DR: There is, I think, something ethereal about i —the square root of minus one, which seems an odd beast at that time—an intruder hovering on the edge of reality.
Abstract: There is, I think, something ethereal about i —the square root of minus one. I remember first hearing about it at school. It seemed an odd beast at that time—an intruder hovering on the edge of reality. Usually familiarity dulls this sense of the bizarre, but in the case of i it was the reverse: over the years the sense of its surreal nature intensified. It seemed that it was impossible to write mathematics that described the real world in …

33,785 citations

Journal ArticleDOI
TL;DR: Authors/Task Force Members: Piotr Ponikowski* (Chairperson) (Poland), Adriaan A. Voors* (Co-Chair person) (The Netherlands), Stefan D. Anker (Germany), Héctor Bueno (Spain), John G. F. Cleland (UK), Andrew J. S. Coats (UK)

13,400 citations

01 Jan 2014
TL;DR: These standards of care are intended to provide clinicians, patients, researchers, payors, and other interested individuals with the components of diabetes care, treatment goals, and tools to evaluate the quality of care.
Abstract: XI. STRATEGIES FOR IMPROVING DIABETES CARE D iabetes is a chronic illness that requires continuing medical care and patient self-management education to prevent acute complications and to reduce the risk of long-term complications. Diabetes care is complex and requires that many issues, beyond glycemic control, be addressed. A large body of evidence exists that supports a range of interventions to improve diabetes outcomes. These standards of care are intended to provide clinicians, patients, researchers, payors, and other interested individuals with the components of diabetes care, treatment goals, and tools to evaluate the quality of care. While individual preferences, comorbidities, and other patient factors may require modification of goals, targets that are desirable for most patients with diabetes are provided. These standards are not intended to preclude more extensive evaluation and management of the patient by other specialists as needed. For more detailed information, refer to Bode (Ed.): Medical Management of Type 1 Diabetes (1), Burant (Ed): Medical Management of Type 2 Diabetes (2), and Klingensmith (Ed): Intensive Diabetes Management (3). The recommendations included are diagnostic and therapeutic actions that are known or believed to favorably affect health outcomes of patients with diabetes. A grading system (Table 1), developed by the American Diabetes Association (ADA) and modeled after existing methods, was utilized to clarify and codify the evidence that forms the basis for the recommendations. The level of evidence that supports each recommendation is listed after each recommendation using the letters A, B, C, or E.

9,618 citations

Journal ArticleDOI
TL;DR: The once-in-a-lifetime treatment with Abciximab Intracoronary for acute coronary syndrome and a second dose intravenously for atrial fibrillation is recommended for adults with high blood pressure.
Abstract: ACE : angiotensin-converting enzyme ACS : acute coronary syndrome ADP : adenosine diphosphate AF : atrial fibrillation AMI : acute myocardial infarction AV : atrioventricular AIDA-4 : Abciximab Intracoronary vs. intravenously Drug Application APACHE II : Acute Physiology Aand Chronic

7,519 citations