We still do not understand some of the most basic aspects of drug development and trial design. Selecting a dose, or range of doses, to test remains a relatively arbitrary process and may have resulted in problems with a number of the therapies discussed above. Targeting therapy has been mentioned earlier, but will the sponsors of large trials, the pharmaceutical industry, encourage this? Can we ethically find ways of comparing proven therapies with new ones even though that may mean that patients do not receive the former during the trial?
Will conventional clinical trials with a mortality end point become enormously large and prohibitively expensive as more effective therapies are added to existing ones? We may need to think of not only new approaches to trial design but also new end points for trials, perhaps refocusing on patient well-being rather than just adverse clinical events.
The past 20 years have seen enormous progress in our understanding of the pathophysiology of CHF and its treatment. Pathophysiological progress has suggested therapeutic approaches, and the successes and failures of clinical trials have refined pathophysiological concepts as well as the science of trial design and conduct. The next 2 decades will present at least as many challenges as the past 2 and perhaps less prospect of the same enormous breakthroughs with pharmacological agents.
Nevertheless, our patients with CHF can still expect further improvement in their quantity and quality of life. This is Part II of a 2-part article. Part I appeared in the April 30, , issue of the journal Circulation. Both authors have received research support for clinical trials and honoraria for advisory boards, lectures, and other activities related to a number of the pharmacological agents mentioned in this review.
Home Circulation Vol. View PDF. Tools Add to favorites Download citations Track citations Permissions. Jump to. Marc A. Pfeffer Marc A. Download figure Download PowerPoint. Correspondence to Dr John J. Basic mechanisms in heart failure: the cytokine hypothesis. J Card Fail. Beneficial effects of pentoxifylline in patients with idiopathic dilated cardiomyopathy treated with angiotensin-converting enzyme inhibitors and carvedilol.
Immunomodulating therapy with intravenous immunoglobulin in patients with chronic heart failure. Cardiac remodeling: concepts and clinical implications: a consensus paper from an international forum on cardiac remodeling. J Am Coll Cardiol.
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Matrix metalloproteinases in pathophysiology and treatment of heart failure. Clinical effects of early angiotensin-converting enzyme inhibitor treatment for acute myocardial infarction are similar in the presence and absence of aspirin: systematic overview of individual data from 96, randomized patients.
Heart failure in a prophesy revisited. Am J Cardiol. A controlled trial with a novel anti-ischemic agent, ranolazine, in chronic stable angina pectoris that is responsive to conventional antianginal agents. Ranolazine Study Group. Low-level inotropic stimulation with type III phosphodiesterase inhibitors in patients with advanced symptomatic chronic heart failure receiving beta-blocking agents.
Curr Cardiol Rep. Acute hemodynamic and clinical effects of levosimendan in patients with severe heart failure. The effect of correction of mild anemia in severe, resistant congestive heart failure using subcutaneous erythropoietin and intravenous iron: a randomised controlled study. BG CVT , an A1 adenosine receptor antagonist, protects against the decline in renal function observed with diuretic therapy.
Are we ready for pharmacogenomics in heart failure? Eur J Pharmacol. Racial differences in the response to drugs: pointers to genetic differences. N Engl J Med. Racial profiling in medical research.virtegocomsi.tk
The Molecular Biology of Chronic Heart Failure
Racial differences in response to therapy for heart failure: analysis of the vasodilator-heart failure trials. Lesser response to angiotensin-converting-enzyme inhibitor therapy in black as compared with white patients with left ventricular dysfunction. Effect of carvedilol on survival in severe chronic heart failure. A trial of the beta-blocker bucindolol in patients with advanced chronic heart failure. Race and the response to adrenergic blockade with carvedilol in patients with chronic heart failure.
Treatment of heart failure guided by plasma aminoterminal brain natriuretic peptide N-BNP concentrations. A systematic review of randomized trials of disease management programs in heart failure. Am J Med. Team management of patients with heart failure: a statement for healthcare professionals from the Cardiovascular Nursing Council of the American Heart Association. Chronic myocardia hibernation. What is the optimal medical management of ischaemic heart failure?
Prog Cardiovasc Dis. Eur J Heart Fail. Google Scholar 27 Jones RH. Is it time for a randomized trial of surgical treatment of ischemic heart failure?
NEUROHORMONAL ACTIVATION IN CHRONIC HEART FAILURE
Exercise training in heart failure. Curr Control Trials Cardiovasc Med. Pacing for heart failure. Effects of multisite biventricular pacing in patients with heart failure and intraventricular conduction delay. The implantable cardioverter defibrillator. Long-term use of a left ventricular assist device for end-stage heart failure.
Team examines molecular-level problems of heart disease -- ScienceDaily
Prospects for gene therapy for heart failure. Circ Res. Myoblast transplantation for heart failure. Cell transplantation as future therapy for cardiovascular disease? Chimerism of the transplanted heart. Myocardial gene expression of regulators of myocyte apoptosis and myocyte calcium homeostasis during hemodynamic unloading by ventricular assist devices in patients with end-stage heart failure.
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Changes in notions about heart failure. Congestive heart failure with normal left ventricular systolic function: clinical approaches to the diagnosis and treatment of diastolic heart failure. Interrupting or reversing cardiac remodelling is a major therapeutic goal of HF therapies. The role of molecules and molecular pathways in cardiac remodelling and HF has been extensively studied. Multiple approaches are now used or investigated in HF therapy, including pharmacological therapy, device therapy, gene therapy, cell therapy and biological therapy targeting cytokines and growth factors.
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