Emerging Therapies for Congestive Heart Failure

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Excerpt

Over the last several decades, the development of a variety of novel cardiovascular therapeutics coupled with lifestyle modifications, such as smoking cessation, has resulted in a remarkable 30–35% decline in cardiovascular mortality and up to a 65% reduction in cardiovascular events.1 Such statistics have led to the perception that cardiovascular disease has been “cured” however, cardiovascular disease accounts for more than one of every three deaths in the US2 and ischemic heart disease remains the leading cause of death both worldwide and in the US. This is especially true in the elderly, where cardiovascular disease accounts for over 50% of all deaths in patients over age 75 and over 3‐fold more deaths than cancer in patients over age 85.2
As the treatment of acute myocardial infarction (MI) and chronic ischemic heart disease continues to improve, the burden of heart failure (HF) is accumulating both in terms of incidence and cost, with an estimated 38 million patients with this condition worldwide.3 Current projections estimate that the prevalence of HF will increase by up to 46% over the next 18 years. By 2023, it is estimated that over 8 million patients in the US alone will have a diagnosis of congestive HF (CHF).2
CHF remains the most common and expensive diagnosis in the Medicare system, with over 1 million annual hospitalizations for CHF in both the US and Europe. With the aging patient population, this number is expected to grow by over 50% in the next 15 years.4 In addition, within 60 days of hospitalization for CHF, 30–50% of patients either die or are rehospitalized, with 20–30% mortality at 1 year and 40–50% mortality by 5 years.5
The majority of medications that have been successful in treating CHF (angiotensin converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), beta‐blockers, aldosterone antagonists) target chronic neurohormonal aberrations that occur in response to this condition. While this approach was initially extremely effective, further attempts at continued targeting of the neurohormonal axis have been largely disappointing, and only neprilysin inhibition has translated into improvements in clinical outcomes.6
Meanwhile, the fundamental pathology of HF, the loss of contractile capacity due to loss of cardiomyocytes, remains unaddressed. The lack of therapies targeting the underlying loss of contractility inherent in HF offers an opportunity to fundamentally change the way HF is approached.
One method to address this deficiency is the use of regenerative therapies to stimulate either native repair processes or to regenerate and replace injured myocardium de novo. Given the high mortality in high‐risk patients with CHF, this seems like an ideal target for regenerative therapies aimed at directly addressing the need for improved cardiac performance.
In this article we briefly review the preclinical basis for such an approach, discuss the most advanced clinical development programs aiming to bring this approach to patients, and highlight next‐generation technologies.

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