What is the role, if any, for beta-blockers as initial therapy for uncomplicated hypertension?

Pedersen, Michala; Cockcroft, John R.

doi:10.1097/hco.0b013e32832c129c

“…Unfortunately, there have been no studies evaluating the effect of nebivolol on morbidity and mortality in adults with hypertension 48. However, the results of the present study coupled with other studies demonstrating nebivolol‐induced improvement in endothelial vasodilator capacity and reduction vasoconstrictor tone39, 49 are encouraging and provide additional support for ancillary cardiovascular benefits of nebivolol in adults with elevated BP 50. Second, our results were obtained in the brachial artery and not a coronary artery.…”

Section: Discussionsupporting

confidence: 63%

Nebivolol, But Not Metoprolol, Treatment Improves Endothelial Fibrinolytic Capacity in Adults With Elevated Blood Pressure

Stauffer

¹

,

Dow

²

,

Diehl

³

et al. 2017

JAHA

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BackgroundVascular endothelial fibrinolytic function is impaired in adults with prehypertension and hypertension and plays a mechanistic role in the development of atherothrombotic events. The influence of β‐blockers on endothelial fibrinolysis is unknown. This study compared the effects of chronic nebivolol and metoprolol treatment on endothelial tissue‐type plasminogen activator (t‐PA) release in adults with elevated blood pressure (BP).Methods and ResultsForty‐four middle‐aged adults (36% women) with elevated BP completed a 3‐month, double‐blind, randomized, placebo‐controlled trial comparing nebivolol (5 mg/d), metoprolol succinate (100 mg/d), and placebo. Net endothelial t‐PA release was determined in vivo in response to intrabrachial infusions of bradykinin and sodium nitroprusside before and after each intervention. In a subset, the dose‐response curves to bradykinin and sodium nitroprusside were repeated with a coinfusion of the antioxidant vitamin C. At baseline, resting BP and endothelial t‐PA release were comparable between the 3 groups. BP decreased to a similar extent (≈10 mm Hg) in the nebivolol‐ and metoprolol‐treated groups. There was a substantial increase (≈30%; P<0.05) in the capacity of the endothelium to release t‐PA following chronic treatment with nebivolol but not metoprolol or placebo. Mitigating oxidant stress with vitamin C coinfusion potentiated t‐PA release (90%; P<0.05) at baseline in all groups. However, after the intervention, t‐PA release was unchanged by vitamin C coinfusion in the nebivolol group only.ConclusionsNebivolol but not metoprolol improves endothelial t‐PA release in adults with elevated BP. This may be an important vascular benefit of nebivolol.Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT01595516.

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“…However, metaanalyses do not show that one class of agent is clearly better than another for major cardiovascular outcomes in older adults, and they have not focused on those over age 80 [47]. Similarly, a treatment preference is not clear in other possible outcomes, but many investigators are convinced that β-adrenergic antagonists may be less effective than other agents, especially once-a-day atenolol [48][49][50].…”

Section: Randomized Trials Of Hypertension In the Elderlymentioning

confidence: 99%

Blood pressure control in the elderly: Can you have too much of a good thing?

Hyman

¹

,

Taffet²

2009

Current Science Inc

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Hypertension (especially systolic hypertension) is very common in older persons. Systolic hypertension occurs because large conduit arteries become stiffer with age. Strong evidence from randomized trials suggests that treating systolic blood pressures initially higher than 160 mm Hg is extremely beneficial, and a recent trial extended this conclusion to healthy persons over 80 years of age. However, the only trial that has directly tested the use of more aggressive treatment goals (< 140 mm Hg) in the elderly did not show benefit in those older than 75. Risks of overtreating hypertension for the elderly include falls and orthostatic hypotension, and the most compromised older persons may be the most likely to experience adverse effects. Our current state of knowledge requires clinical judgment that balances the immediacy of adverse effects versus the potential but unproven benefits of treatment in deciding whether to treat the elderly more aggressively than the goals used in randomized trials.

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“…

The low-energy collision-induced dissociation product ion spectra of protonated beta-blockers reveal an analogy to fragmentation behaviour under electron ionisation conditions Beta-blockers are a class of pharmaceutical compounds used in the therapy of numerous cardiovascular disorders including the treatment of hypertension, [1,2] for cardioprotection post-myocardial infarction, [3] in the management of angina pectoris [4] and for the regulation of heart rate in patients with cardioarrhythmia.[5] They are also used in the treatment of chronic kidney disease [6] and the relief of intraocular pressure in glaucoma sufferers. [7] A recent study in our laboratories involved the investigation of the lowenergy collision-induced dissociation (CID) pathways of protonated beta-blockers on a quadrupole ion trap (QIT) mass spectrometer and revealed an interesting analogy to fragmentation behaviour under electron ionisation (EI) conditions.

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mentioning

confidence: 99%

“…

The low-energy collision-induced dissociation product ion spectra of protonated beta-blockers reveal an analogy to fragmentation behaviour under electron ionisation conditions Beta-blockers are a class of pharmaceutical compounds used in the therapy of numerous cardiovascular disorders including the treatment of hypertension, [1,2] for cardioprotection post-myocardial infarction, [3] in the management of angina pectoris [4] and for the regulation of heart rate in patients with cardioarrhythmia. [5] They are also used in the treatment of chronic kidney disease [6] and the relief of intraocular pressure in glaucoma sufferers.

…”

mentioning

confidence: 99%

The low‐energy collision‐induced dissociation product ion spectra of protonated beta‐blockers reveal an analogy to fragmentation behaviour under electron ionisation conditions

Holman

¹

,

Wright

²

,

Langley

³

2011

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The low-energy collision-induced dissociation product ion spectra of protonated beta-blockers reveal an analogy to fragmentation behaviour under electron ionisation conditions Beta-blockers are a class of pharmaceutical compounds used in the therapy of numerous cardiovascular disorders including the treatment of hypertension, [1,2] for cardioprotection post-myocardial infarction, [3] in the management of angina pectoris [4] and for the regulation of heart rate in patients with cardioarrhythmia.[5] They are also used in the treatment of chronic kidney disease [6] and the relief of intraocular pressure in glaucoma sufferers. [7] A recent study in our laboratories involved the investigation of the lowenergy collision-induced dissociation (CID) pathways of protonated beta-blockers on a quadrupole ion trap (QIT) mass spectrometer and revealed an interesting analogy to fragmentation behaviour under electron ionisation (EI) conditions. Fourteen beta-blockers (acebutolol, alprenolol, atenolol, betaxolol, carteolol, celiprolol, esmolol, levobunolol, metoprolol, nadolol, oxprenolol, pindolol, propranolol and timolol) were provided by Pfizer Global Research and Development (Sandwich, UK). Solutions were prepared at 10 mg mL À1 in either liquid chromatography-mass spectrometry grade methanol and analytical grade formic acid [99.9:0.1, v/v] (Fisher Scientific UK Ltd., Loughborough, UK) or in >99.5% deuterated methanol and 99.5% deuterated formic acid [99.9:0.1, v/v] (Apollo Scientific Limited, Stockport, UK). 'In-time' low-energy CID product ion spectra of either the protonated or fully exchanged, deuterated molecule (i.e. all acidic protons exchanged for deuterons) for each compound were acquired using a LCQ Classic QIT mass spectrometer (Thermo Fisher Scientific, San Jose, CA, USA). Positive ion electrospray ionisation was performed by infusing the solutions directly into the ion source at a constant flow rate of 3 mL min À1. Nitrogen was used as the sheath and auxiliary gas. The ion source conditions were: sheath gas, 25 arbitrary units; auxiliary gas, 0 arbitrary units; spray voltage, 4.5 kV; capillary voltage, 10 V; capillary temperature, 160 C; tube lens offset, À5 V. Lowenergy CID product ion spectra were acquired using an isolation width of 6 m/z units (1 m/z unit for the solution-phase H/D exchange experiments to ensure only the fully exchanged, deteurated molecule was selected to undergo CID), an activation Q of 0.250 and an activation time of 30 ms. The normalised collision energy was set to either 50% or 60% to cause complete dissociation of the precursor ion.[8] Acquisitions were performed for 20 scans with WideBand activation both on and off.[8] Helium was used as the buffer gas. Data acquisition was performed using XCalibur version 1.2 (Thermo Fisher Scientific, San Jose, CA, USA).A common structural feature of beta-blockers is the oxypropanolamine side chain, which can either terminate in an isopropyl or a tert-butyl group.[9] The compounds in this study were split into two sets (Compound sets 1 and 2, Figs...

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What is the role, if any, for beta-blockers as initial therapy for uncomplicated hypertension?

Cited by 11 publications

References 68 publications

Nebivolol, But Not Metoprolol, Treatment Improves Endothelial Fibrinolytic Capacity in Adults With Elevated Blood Pressure

Nebivolol, But Not Metoprolol, Treatment Improves Endothelial Fibrinolytic Capacity in Adults With Elevated Blood Pressure

Blood pressure control in the elderly: Can you have too much of a good thing?

The low‐energy collision‐induced dissociation product ion spectra of protonated beta‐blockers reveal an analogy to fragmentation behaviour under electron ionisation conditions

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