Rationale and design of the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist Trial: A randomized, controlled study of spironolactone in patients with symptomatic heart failure and preserved ejection fraction

Desai, Akshay S.; Lewis, Eldrin F.; Li, Rebecca; Solomon, Scott D.; Assmann, Susan F.; Boineau, Robin; Clausell, Nadine Oliveira; Dı́az, Rafael; Fleg, Jerome L.; Гордеев, И. Г.; McKinlay, Sonja M.; O’Meara, Eileen; Shaburishvili, Tamaz; Pitt, Bertram; Pfeffer, Marc A.

doi:10.1016/j.ahj.2011.09.007

Cited by 248 publications

(236 citation statements)

References 38 publications

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“…The aldosterone antagonist, spironolactone, was used in an open-label preliminary trial in 11 women with HFpEF and resulted in significant improvement in symptoms, exercise capacity and the E/E ratio [147]. Encouraged by these preliminary results, spironolactone is currently being tested in a large multicenter randomized placebo-controlled trial -the Treatment Of Preserved Cardiac function heart failure with an Aldosterone antagonist (TOPCAT) trial -whose results are expected in 2013 [148]. Amongst the novel agents being tested is alagebrium chloride -a compound that breaks advanced glycation end products cross-links -which showed favorable effects on various diastolic function parameters and reduced LV mass as well as improved quality of life after 16 weeks of drug administration in a small study [149].…”

Section: Future Directions and Emerging Therapiesmentioning

confidence: 99%

Heart Failure with Preserved Ejection Fraction

Čulić

2017

N Engl J Med

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Heart failure with preserved ejection fraction (HFpEF) has recently emerged as a major cause of cardiovascular morbidity and mortality. Contrary to initial beliefs, HFpEF is now known to be as common as heart failure with reduced ejection fraction (HFrEF) and carries an unacceptably high mortality rate. With a prevalence that has been steadily rising over the past two decades, it is very likely that HFpEF will represent the dominant heart failure phenotype over the coming few years. The scarcity of trials in this semi-discrete form of heart failure and lack of unified enrolment criteria in the studies conducted to date might have contributed to the current absence of specific therapies. Understanding the epidemiological, pathophysiological and molecular differences (and similarities) between these two forms of heart failure is cornerstone to the development of targeted therapies. Carefully designed studies that adhere to unified diagnostic criteria with the recruitment of appropriate controls and adoption of practical end-points are urgently needed to help identify effective treatment strategies.

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Section: Future Directions and Emerging Therapiesmentioning

confidence: 99%

Heart Failure with Preserved Ejection Fraction

Čulić

2017

N Engl J Med

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“…Major exclusions were uncontrolled hypertension, serum potassium ≥5.0 mmol/L, creatinine ≥2.5 mg/dL, or estimated glomerular filtration rate <30 mL/min per 1.73 m 2 body surface area, recent acute events, and other severe comorbidities defined previously. 15 …”

Section: Design and Study Populationmentioning

confidence: 99%

“…The design and primary findings have been published. 14,15 Patients with symptomatic heart failure and a left ventricular ejection fraction ≥45% who provided written informed consent were eligible. Each patient had to have either a hospitalization within 12 months before randomization with heart failure as a major component of care or, if not, an elevated brain natriuretic peptide (BNP; BNP ≥100 pg/ mL or N-terminal pro-BNP ≥360 pg/mL) within 60 days before randomization.…”

Section: Design and Study Populationmentioning

confidence: 99%

Regional Variation in Patients and Outcomes in the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT) Trial

et al. 2015

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Background— Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT) patients with heart failure and preserved left ventricular ejection fraction assigned to spironolactone did not achieve a significant reduction in the primary composite outcome (time to cardiovascular death, aborted cardiac arrest, or hospitalization for management of heart failure) compared with patients receiving placebo. In a post hoc analysis, an ≈4-fold difference was identified in this composite event rate between the 1678 patients randomized from Russia and Georgia compared with the 1767 enrolled from the United States, Canada, Brazil, and Argentina (the Americas). Methods and Results— To better understand this regional difference in clinical outcomes, demographic characteristics of these populations and their responses to spironolactone were explored. Patients from Russia/Georgia were younger, had less atrial fibrillation and diabetes mellitus, but were more likely to have had prior myocardial infarction or a hospitalization for heart failure. Russia/Georgia patients also had lower left ventricular ejection fraction and creatinine but higher diastolic blood pressure (all P <0.001). Hyperkalemia and doubling of creatinine were more likely and hypokalemia was less likely in patients receiving spironolactone in the Americas with no significant treatment effects in Russia/Georgia. All clinical event rates were markedly lower in Russia/Georgia, and there was no detectable impact of spironolactone on any outcomes. In contrast, in the Americas, the rates of the primary outcome, cardiovascular death, and hospitalization for heart failure were significantly reduced by spironolactone. Conclusions— This post hoc analysis demonstrated greater potassium and creatinine changes and possible clinical benefits with spironolactone in patients with heart failure and preserved ejection fraction from the Americas. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00094302.

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“…В качестве положительного примера можно привести исследование TOPCAT, в которое были включены пациен-ты с симптомами СН в возрасте ≥ 50 лет, с ФВ ≥ 45%, а также госпитализацией в течение прошлого года для лечения сердечной недостаточности или повышенной концентрации в плазме натрийуретических пептидов (BNP ≥100 пг/мл или NT-proBNP ≥360 пг/мл) [47], [48]. BNP является гормоном, который вырабатывают кардиомио-циты в ответ на увеличение конечного диастолического давления, как это наблюдается в условиях сердечной недостаточности.…”

Section: прогнозирование заболеваний пациента на основе анализа генетunclassified

Personalized Medicine in Cardiology: State, Problems and Prospects

2017

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ФАРМАКОГЕНЕТИКАВозможность владеть генетической информацией позволила начать внедрение персонализированной медицины в клиническую практику. Генетические иссле-дования начали показывать, что некоторые лекарства в определенных условиях очень эффективны для одних пациентов и неэффективны, а иногда даже опасны -для других. Поэтому на стыке фармакологии и генетики воз-никла фармакогенетика -наука, изучающая роль генети-ческих факторов в формировании фармакологического ответа организма человека на лекарственное средство [1]. Это может дать возможность врачу персонализиро-ванно выбрать как само лекарство, так и дозу у конкрет-ного больного и обеспечить максимальную эффектив-ность и безопасность препарата.Роль наследственности в формировании индивиду-ального ответа на лекарственные средства была известна давно, понимание механизмов влияния гене-тических факторов на эффективность и безопасность фармакотерапии стало возможным лишь с развитием методов молекулярной биологии и реализацией меж-дународной программы «Геном человека». Последние данные, имеющиеся о строении генома человека, явно показывают, что существует множество вариаций генов, которые объясняют различия в абсорбции пре-парата, распределении, метаболизме, выведении и в итоге ответную реакцию организма на фармацевтиче-ский препарат. Такие предварительные успехи дали понять, что подобное исследование позволит получить такую медицину, которая окажется и индивидуальной, и точной. Personalized medicine appeared about three decades ago. Even then many scientists, researchers, doctors were interested into it. However, only after the full opening of the human genome in 2001, personalized medicine could to give the opportunity for some pathologies (oncology, rheumatology, cardiology) to choose the most effective treatment with minimal adverse drug reactions for a specific patient. The opportunity to own genetic information gives the chance to suspect, to predict, to expect the onset of the disease. Personalized medicine is able in some cases to say exactly whether the drug can work for the patient, moving us to «treat not a disease, but the patient.» But doctors to this day when determining risk factors focus on individual characteristics of the patient, such as age, gender, body weight, co-morbidities, and based on that prescribe medications, correct dose and in case of ineffectiveness change the treatment regimen. Apparently they don't believe in personalized medicine, afraid of it and I don't want to associate with it, because as many think on the basis of their experience and knowledge they can decide which drug and what dose to prescribe. Also, there are a number of reasons related to privacy, security, problem of training, which will soon need to be addressed.

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Rationale and design of the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist Trial: A randomized, controlled study of spironolactone in patients with symptomatic heart failure and preserved ejection fraction

Cited by 248 publications

References 38 publications

Heart Failure with Preserved Ejection Fraction

Heart Failure with Preserved Ejection Fraction

Regional Variation in Patients and Outcomes in the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT) Trial

Personalized Medicine in Cardiology: State, Problems and Prospects

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