Prolongation of Survival in Congestive Cardiomyopathy by Beta-Receptor Blockade

Swedberg, Karl; Hjalmarson, Å; Waagstein, Finn; Wallentin, I

doi:10.1016/s0140-6736(79)92010-5

Cited by 386 publications

(100 citation statements)

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“…The Göteborg group went on in 1975 to describe successful results in seven dilated cardiomyopathy patients, six of whom who were treated with oral practolol. 39 After removal of practolol from the market for oculomucocutaneous syndrome, in 1979 the Göteborg group reported results in 24 patients, the last 11 of whom were treated with the ␤ 1 -selective blocker metoprolol, 40 an approximately 80-fold ␤ 1 selective 38 "hometown" drug developed in Astra's Mölndal facility near Göteborg. In this study, 40 mortality versus a constructed life table of patients not treated with ␤-blockers was apparently better, with a 55% versus 20% survival at 3 years.…”

Section: Pharmacological Characterization Of the ␤-Adrenergic Neuroefmentioning

confidence: 99%

“…39 After removal of practolol from the market for oculomucocutaneous syndrome, in 1979 the Göteborg group reported results in 24 patients, the last 11 of whom were treated with the ␤ 1 -selective blocker metoprolol, 40 an approximately 80-fold ␤ 1 selective 38 "hometown" drug developed in Astra's Mölndal facility near Göteborg. In this study, 40 mortality versus a constructed life table of patients not treated with ␤-blockers was apparently better, with a 55% versus 20% survival at 3 years. In 1980, Swedberg et al 42 reported that 28 patients treated with ␤-blockade, 17 of whom received metoprolol, had a 10 EF unit improvement in LV ejection fraction, the first description of reverse remodeling by a ␤-blocker.…”

Section: Pharmacological Characterization Of the ␤-Adrenergic Neuroefmentioning

confidence: 99%

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Treatment of Chronic Heart Failure With β-Adrenergic Receptor Antagonists

Bristow

2011

Circulation Research

151

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ReviewTranslational Success Stories highlight how basic discoveries have led to clinical advances (such as the use of new drugs or diagnostic modalities in patients). This initiative reflects the renewed emphasis of our journal on translational research. It is hoped that these articles will stimulate efforts to translate basic insights into clinical practice. Treatment of Chronic Heart Failure With ␤-AdrenergicReceptor Antagonists A Convergence of Receptor Pharmacology and Clinical CardiologyMichael R. BristowAbstract: Despite the absence of a systematic development plan, ␤-blockers have reached the top tier of medical therapies for chronic heart failure. The successful outcome was due to the many dedicated investigators who produced, over a 30-year period, increasing evidence that ␤-blocking agents should or actually did improve the natural history of dilated cardiomyopathies and heart failure. It took 20 years for supportive evidence to become undeniable, at which time in 1993 the formidable drug development resources of large pharmaceutical companies were deployed into Phase 3 trials. Success then came relatively quickly, and within 8 years multiple agents were on the market in the United States and Europe. Importantly, there is ample room to improve antiadrenergic therapy, through novel approaches exploiting the nuances of receptor biology and/or intracellular signaling, as well as through pharmacogenetic targeting. (Circ Res. 2011;109:1176-1194.)Key Words: heart failure Ⅲ adrenergic receptors Ⅲ ␤-blockers Ⅲ norepinephrine Ⅲ drug development "I love it when a plan comes together" -Colonel John "Hannibal" Smith, The A-Team ␤ -Adrenergic blocking agents are now considered firstline therapy for chronic heart failure. 2 Between 1971 and 2001, ␤-blockers as a drug class went from contraindicated to being universally declared a highly effective new therapy for chronic heart failure with systolic dysfunction. As depicted in Figure 1, this 180-degree turn required the convergence of initially disconnected lines of basic and clinical investigation, none of which was systematically planned by the usual purveyors of drug development, large pharmaceutical companies. However, as for the typical outcome of Colonel Hannibal Smith's unconventional and dubious tactical schemes, 1 the end result was highly successful. This review provides some of the historical highlights, summarizes current knowledge, and provides thoughts on the future of ␤-blocker and antiadrenergic therapy. Historical Highlights Discovery of Adrenergic ReceptorsIn 1948, Raymond Ahlquist reported evidence for two types of adrenergic receptors, 3 which, "for convenience," he termed alpha and beta. The evidence was based on 2 distinct rank orders of agonist potency for a variety of pharmacological responses, plus the ability to inhibit the vasoconstrictor or uterine contraction responses of the ␣ group, with 3 different compounds (dibenamine, ergotoxine, or tolazoline) that would later be termed ␣-blocking agents. At the time of Ahlquist's landmark work, the...

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Section: Pharmacological Characterization Of the ␤-Adrenergic Neuroefmentioning

confidence: 99%

Section: Pharmacological Characterization Of the ␤-Adrenergic Neuroefmentioning

confidence: 99%

Treatment of Chronic Heart Failure With β-Adrenergic Receptor Antagonists

Bristow

2011

Circulation Research

151

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“…Since the pioneering work in the 1970s [54], it took two decades until β-blockers turned from contraindication to standard treatment in heart failure [55] ( [58], respectively,) show a similar reduction in the risk of death by a third or more in patients with CHF who were already receiving ACE inhibitors and diuretics, a benefit greater than of any other drug used in heart M A N U S C R I P T…”

Section: β-Ar Blocking Drugsmentioning

confidence: 99%

Pharmacological modulation of β-adrenoceptor function in patients with coexisting chronic obstructive pulmonary disease and chronic heart failure

Matera

Martuscelli

Cazzola

2010

Pulmonary Pharmacology & Therapeutics

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“…34 Almost 2 decades was necessary to reverse the well-established, although erroneous, conventional wisdom on this point and bring these drugs into the therapeutic armamentarium for the treatment of heart failure. Given the rapid pace of current experimental efforts, a much more rapid assessment of ␤ 2 AR augmentation and ␤ARK inhibition as novel therapeutic modalities in heart failure seems likely.…”

Section: ␤Ark Inhibitionmentioning

confidence: 99%