Antianginal Efficacy of Omapatrilat in Patients With Chronic Angina Pectoris

Chaitman, Bernard R.; Ivleva, A. Ya.; Ujda, Marek; Lenis, J; Tóth, Csaba; Stieber, David M.; Reisin, Leonardo; Pangerl, Andreas; Friedman, Julie B.; Lawrence, John H.

doi:10.1016/j.amjcard.2005.01.069

Cited by 16 publications

(10 citation statements)

References 21 publications

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“…These vasoactive peptides are inactivated by neprilysin, and bradykinin is also degraded by angiotensin-converting enzyme [79]. In a proof-of-concept study, omapatrilat, a potent vasopeptidase inhibitor with selective and competitive inhibitory activity of angiotensin-converting enzyme and neprilysin, was tested in 348 patients with stable angina [80]. Treatment with omapatrilat significantly increased total exercise capacity, time to onset of angina, and time to onset of ischemic ST-segment depression at peak plasma concentrations, with fewer patient reports of exercise-induced angina, compared with placebo.…”

Section: Novel Therapies For Anginamentioning

confidence: 99%

“…As with the entire spectrum of coronary disease, optimal medical therapy and risk factor modification provides important prognostic and symptomatic benefit in these patients. A wide array of pharmacological armamentarium is now available to manage the patients with chronic stable angina as outlined in Table 1 [27, 31–36, 38–40, 42, 43, 45, 50, 51, 53, 54, 67, 72, 78, 80, 82–84, 87–92, 95, 97, 102, 107, 132–144]. …”

Section: Expert Opinionmentioning

confidence: 99%

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Antagonist molecules in the treatment of angina

Gupta

Winchester

Pepine

2013

Expert Opinion on Pharmacotherapy

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Introduction Management of chronic angina has evolved dramatically in the last few decades with several options for pharmacotherapy outlined in various evidence-based guidelines. Areas covered There is a growing list of drugs that are currently being investigated for treatment of chronic angina. These also include several herbal medications, which are now being scientifically evaluated as potential alternative or even adjunctive therapy for angina. Gene- and cell-based therapies have opened yet another avenue for management of chronic refractory angina in ‘no-option’ patients who are not candidates for either percutaneous or surgical revascularization and are on optimal medical therapy. An extensive review of literature using PUBMED, Cochrane database, clinical trial databases of USA and European Union was done and summarized in this review. This review will attempt to discuss the traditional as well as novel therapeutic agents for angina. Expert opinion Several pharmacological and non-pharmacological therapeutic options are now available for treatment and management of chronic refractory angina. Renewed interest in traditional therapies and cell- and gene-based modalities with targeted drug delivery systems will open the doors for personalized therapy for patients with chronic refractory angina.

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Section: Novel Therapies For Anginamentioning

confidence: 99%

Section: Expert Opinionmentioning

confidence: 99%

Antagonist molecules in the treatment of angina

Gupta

Winchester

Pepine

2013

Expert Opinion on Pharmacotherapy

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“…We randomized 348 patients with chronic angina to omapatrilat or placebo in a double-blind placebo controlled multicenter trial. 21 Omapatrilat increased total exercise capacity, time to onset of angina, and time to onset of ischemic ST segment depression at peak plasma concentrations and a significantly fewer number of patients reported angina during the test. Antianginal/antiischemic effects were markedly attenuated at trough plasma concentrations 24 h postdosing.…”

Section: Vasopeptidase Inhibitionmentioning

confidence: 99%

“…14 -19 Other compounds have been investigated for potential treatment (e.g., rho-kinase and vasopeptidase inhibition) but are not commercially available. 20,21 Nonpharmacological supplemental therapies, such as EECP and spinal cord stimulation, are also additions to the armamentarium. The focus of this review is to discuss some of the newer pharmacological therapies approved in the United States and Europe and their application as treatment options for chronic angina.…”

Section: Introductionmentioning

confidence: 99%

Novel therapeutic approaches to treating chronic angina in the setting of chronic ischemic heart disease

Chaitman

Sano

2007

Clin Cardiol

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SummaryPharmacologic therapy to alleviate symptoms in chronic angina has been enhanced by the recent approval of several novel compounds that complement the traditional approach using beta-adrenergic blocking drugs, calcium antagonists, and long-acting nitrates. In the United States, ranolazine, a drug that inhibits late I Na , was approved for patients with chronic angina that remain symptomatic on beta-blockers, calcium antagonists, or long-acting nitrates, on the basis of an acceptable safety profile and efficacy in several randomized placebo controlled studies. A slight increase in the QT interval is observed (< 10 ms on average) at the maximum approved dose of 1,000 mg twice daily. Therefore, an ECG should be acquired at baseline and during follow-up, and the drug should not be used in patients with QT prolongation or those who are on QT prolonging drugs unless longer term randomized outcome data demonstrates no excess risk. The MERLIN trial of non-ST-elevation acute coronary syndrome (NSTE ACS) randomized 6,560 patients to assess the potential benefit of ranolazine in reducing the composite endpoint of cardiovascular death, myocardial infarction, and recurrent ischemia, with results expected in 2007. In Europe, ivabradine, a drug that inhibits the hyperpolarizationactivated mixed sodium/potassium inward I f current, which slows the rest and exercise heart rate, was approved in 2005. Ivabradine at a dose of 10 mg twice daily has been shown to have similar efficacy to amlodipine 10 mg once daily or atenolol 100 mg once daily in alleviating chronic angina symptoms. In this review, several other novel investigational approaches are presented and patient selection considerations for the most recent approved drugs for chronic angina are discussed.

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“…The idea to explore the role of ACEI as antianginal factors was tested in 2005, when omapatrilat, a combined ACE and NEP inhibitor, was found to alleviate chronic angina . Unfortunately, omapatrilat had to be retracted because of the high incidence of angioedema among its side‐effects.…”

mentioning

confidence: 99%