Blood pressure lowering efficacy of dual alpha and beta blockers for primary hypertension
- PMID: 26306578
- PMCID: PMC6486308
- DOI: 10.1002/14651858.CD007449.pub2
Blood pressure lowering efficacy of dual alpha and beta blockers for primary hypertension
Abstract
Background: Drugs with combined alpha and beta blocking activity are commonly prescribed to treat hypertension. However, the blood pressure (BP) lowering efficacy of this class of beta blockers has not been systematically reviewed and quantified.
Objectives: To quantify the dose-related effects of various types of dual alpha and beta adrenergic receptor blockers (dual receptor blockers) on systolic and diastolic blood pressure versus placebo in patients with primary hypertension.
Search methods: We searched the Cochrane Hypertension Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and ClinicalTrials.gov for randomized controlled trials up to October 2014. The WHO International Clinical Trials Registry Platform (ICTRP) is searched for inclusion in the Group's Specialised Register.
Selection criteria: Randomized double blind placebo controlled parallel or cross-over trials. Studies contained a beta blocker monotherapy arm with a fixed dose. Patients enrolled in the studies had primary hypertension at baseline. Duration of the studies was from three to 12 weeks. Drugs in this class of beta blockers are carvedilol, dilevalol and labetalol.
Data collection and analysis: Two review authors (GW and AL) confirmed the inclusion of studies and extracted the data independently. RevMan 5.3 was used to synthesize data.
Main results: We included eight studies examining the blood pressure lowering efficacy of carvedilol and labetalol in 1493 hypertensive patients. Five of the included studies were parallel design; three were cross-over design. The two largest included studies were unpublished carvedilol studies. The estimates of BP lowering effect (systolic BP/diastolic BP millimeters of mercury; SPB/DBP mm Hg) were -4 mm Hg (95% confidence intervals (CI) -6 to -2)/-3 mm Hg (95% CI -4 to -2) for carvedilol (>1000 subjects) and -10 mm Hg (95% CI -14 to -7)/-7 mm Hg (95% CI -9 to -5) for labetalol (110 subjects). The effect of labetalol is likely to be exaggerated due to high risk of bias. Carvedilol, within the recommended dose range, did not show a significant dose response effect for SBP or DBP. Carvedilol had little or no effect on pulse pressure (-1 mm Hg) and did not change BP variability. Overall, once and twice the starting dose of carvedilol and labetalol lowered BP by -6 mm Hg (95% CI -7 to -4) /-4 mm Hg (95% CI -4 to -3) (low quality evidence) and lowered heart rate by five beats per minute (95% CI -6 to -4) (low quality evidence). Five studies (N = 1412) reported withdrawal due to adverse effects; the risk ratio was 0.88 (95% CI 0.54 to 1.42) (moderate quality evidence).
Authors' conclusions: This review provides low quality evidence that in patients with mild to moderate hypertension, dual receptor blockers lowered trough BP by an average of -6/-4 mm Hg and reduced heart rate by five beats per minute. Due to the larger sample size from the two unpublished studies, carvedilol provided a better estimate of BP lowering effect than labetalol. The BP lowering estimate from combining carvedilol once and twice the starting doses is -4/-3 mm Hg. Doses higher than the recommended starting dose did not provide additional BP reduction. Higher doses of dual receptor blockers caused more bradycardia than lower doses. Based on indirect comparison with other classes of drugs, the blood pressure lowering effect of dual alpha- and beta-receptor blockers is less than non-selective, beta1 selective and partial agonist beta blockers, as well as thiazides and drugs inhibiting the renin angiotensin system. Dual blockers also had little or no effect on reducing pulse pressure, which is similar to the other beta-blocker classes, but less than the average reduction of pulse pressure seen with thiazides and drugs inhibiting the renin angiotensin system. Patients taking dual receptor blockers were not more likely to withdraw from the study compared to patients taking placebo.
Conflict of interest statement
Gavin Wong: Nothing to declare.
Alexandra Laugerrotte: Nothing to declare.
James M Wright: Nothing to declare.
Figures
![1](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/6486308/bin/nCD007449-AFig-FIG01.gif)
![2](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/6486308/bin/nCD007449-AFig-FIG02.gif)
![1.1](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/6486308/bin/nCD007449-CMP-001-01.gif)
![1.2](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/6486308/bin/nCD007449-CMP-001-02.gif)
![1.3](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/6486308/bin/nCD007449-CMP-001-03.gif)
![1.4](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/6486308/bin/nCD007449-CMP-001-04.gif)
![2.1](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/6486308/bin/nCD007449-CMP-002-01.gif)
![2.2](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/6486308/bin/nCD007449-CMP-002-02.gif)
![2.3](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/6486308/bin/nCD007449-CMP-002-03.gif)
![2.4](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/6486308/bin/nCD007449-CMP-002-04.gif)
![3.1](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/6486308/bin/nCD007449-CMP-003-01.gif)
![3.2](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/6486308/bin/nCD007449-CMP-003-02.gif)
![3.3](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/6486308/bin/nCD007449-CMP-003-03.gif)
![3.4](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/6486308/bin/nCD007449-CMP-003-04.gif)
![3.5](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/6486308/bin/nCD007449-CMP-003-05.gif)
![4.1](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/6486308/bin/nCD007449-CMP-004-01.gif)
![4.2](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/6486308/bin/nCD007449-CMP-004-02.gif)
![4.3](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/6486308/bin/nCD007449-CMP-004-03.gif)
![4.4](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/6486308/bin/nCD007449-CMP-004-04.gif)
Update of
- doi: 10.1002/14651858.CD007449
Similar articles
-
Blood pressure lowering efficacy of beta-1 selective beta blockers for primary hypertension.Cochrane Database Syst Rev. 2016 Mar 10;3(3):CD007451. doi: 10.1002/14651858.CD007451.pub2. Cochrane Database Syst Rev. 2016. PMID: 26961574 Free PMC article. Review.
-
Blood pressure lowering efficacy of partial agonist beta blocker monotherapy for primary hypertension.Cochrane Database Syst Rev. 2014 Nov 27;2014(11):CD007450. doi: 10.1002/14651858.CD007450.pub2. Cochrane Database Syst Rev. 2014. PMID: 25427719 Free PMC article. Review.
-
Blood pressure lowering efficacy of nonselective beta-blockers for primary hypertension.Cochrane Database Syst Rev. 2014 Feb 28;2014(2):CD007452. doi: 10.1002/14651858.CD007452.pub2. Cochrane Database Syst Rev. 2014. PMID: 24585007 Free PMC article. Review.
-
Blood pressure-lowering efficacy of monotherapy with thiazide diuretics for primary hypertension.Cochrane Database Syst Rev. 2014 May 29;2014(5):CD003824. doi: 10.1002/14651858.CD003824.pub2. Cochrane Database Syst Rev. 2014. PMID: 24869750 Free PMC article. Review.
-
Blood pressure lowering efficacy of beta-blockers as second-line therapy for primary hypertension.Cochrane Database Syst Rev. 2010 Jan 20;(1):CD007185. doi: 10.1002/14651858.CD007185.pub2. Cochrane Database Syst Rev. 2010. PMID: 20091622 Review.
Cited by
-
Breastfeeding and Later-Life Cardiometabolic Health in Women With and Without Hypertensive Disorders of Pregnancy.J Am Heart Assoc. 2023 Mar 7;12(5):e026696. doi: 10.1161/JAHA.122.026696. Epub 2023 Feb 27. J Am Heart Assoc. 2023. PMID: 36847057 Free PMC article.
-
Vaccine Targeting Alpha 1D-Adrenergic Receptor Improved Metabolic Syndrome in Mice.Cardiovasc Drugs Ther. 2024 Jun;38(3):539-554. doi: 10.1007/s10557-022-07418-9. Epub 2023 Jan 19. Cardiovasc Drugs Ther. 2024. PMID: 36656412 Free PMC article.
-
Caged-carvedilol as a new tool for visible-light photopharmacology of β-adrenoceptors in native tissues.iScience. 2022 Sep 13;25(10):105128. doi: 10.1016/j.isci.2022.105128. eCollection 2022 Oct 21. iScience. 2022. PMID: 36185381 Free PMC article.
-
The affinity and selectivity of α-adrenoceptor antagonists, antidepressants and antipsychotics for the human α2A, α2B, and α2C-adrenoceptors and comparison with human α1 and β-adrenoceptors.Pharmacol Res Perspect. 2022 Apr;10(2):e00936. doi: 10.1002/prp2.936. Pharmacol Res Perspect. 2022. PMID: 35224877 Free PMC article.
-
Current and Emerging Classes of Pharmacological Agents for the Management of Hypertension.Am J Cardiovasc Drugs. 2022 May;22(3):271-285. doi: 10.1007/s40256-021-00510-9. Epub 2021 Dec 8. Am J Cardiovasc Drugs. 2022. PMID: 34878631 Free PMC article. Review.
References
References to studies included in this review
Carvedilol GSK B100 {unpublished data only}
-
- GlaxoSmithKline. A multicenter, double‐blind, placebo‐controlled comparison of Carvedilol (SK&F) 6.25 mg, 12.5 mg, and 25.0 mg administered twice daily in patients with mild and moderate hypertension.. http://www.gsk‐clinicalstudyregister.com/result_detail.jsp?protocolId=105517%2F021&stud... (accessed ‐ day month year) updated 13 September 2005. [GSK protocol ID 105517/021; GSK study no. GSK B100]
Carvedilol GSK B101 {unpublished data only}
-
- GlaxoSmithKline. A multicenter, double‐blind, placebo‐controlled comparison of carvedilol (SK&F 105517) 6.25mg, 12.5mg, 25mg, and 50mg administered once daily in patients with mild to moderate hypertension.. http://www.gsk‐clinicalstudyregister.com/result_detail.jsp?protocolId=105517%2F022&stud... (accessed day month year ) Updated: 13 September 2005. [GSK protocol ID 105517/022 ; GSK study no. B101]
Frick 1976 {published data only}
Kane 1976 {published data only}
-
- Kane J, Gregg I, Richards DA. A double blind trial of labetalol. British Journal of Clinical Pharmacology 1976;Suppl:737‐41. - PubMed
Lechi 1982 {published data only}
-
- Lechi A, Pomari S, Berto R, Buniotto P, Parrinello A, Marini F, et al. Clinical evaluation of labetalol alone and combined with chlorthalidone in essential hypertension: a double blind multicenter controlled study. European Journal of Clinical Pharmacology 1982;22:289‐93. - PubMed
McPhillips 1988 {published data only}
-
- McPhillips JJ, Schwemer GT, Scott DI, Zinny M, Patterson D. Effect of Carvedilol on Blood pressure in patients with mild to moderate hypertension. A dose response study. Drugs 1988;36(Suppl 6):82‐91. - PubMed
Rouffy 1986 {published data only}
-
- Rouffy J, Bakir R, Chanu B, Djian F, Goy‐Loeper J, Henry Amar M, et al. Effect of 400 mg/day labetalol on lipids, lipoproteins and apoproteins in hypertensive patients. Pathologie Biologie 1986;34(4):253‐8. - PubMed
Weber 2006 {published data only}
-
- Weber MA, Sica DA, Tarka EA, Iyengar M, Fleck R, Bakris GL. Controlled Release Carvedilol in the treatment of essential hypertension. American Journal of Cardiology 2006;98 Suppl:32L‐8L. - PubMed
References to studies excluded from this review
Dupont 1987 {published data only}
-
- Dupont AG, Niepen P, Taeymans Y, Ingels M, Piepsz A, Bossuyt AM, et al. Effect of carvedilol on ambulatory blood pressure, renal hemodynamics, and cardiac function in essential hypertension. Journal of Cardiovascular Pharmacology 1987;10 Suppl 11:S130‐6. - PubMed
Horvath 1979 {published data only}
-
- Horvath JS, Caterson RJ, Collett P, Duggin GG, Kelly DH, Tiller DJ. Labetalol and bendrofluazide: comparison of their antihypertensive effects. Medical Journal of Australia 1979;1:626‐8. - PubMed
Kubik 1984 {published data only}
-
- Kubik MM, Coote JH. Propranolol vs metoprolol vs labetalol: A comparative study in essential hypertension. European Journal of Clinical Pharmacology 1984;26:1‐6. - PubMed
Additional references
Chen 2010a
Chen 2010b
eCPS
-
- Canadian Pharmacist Association. e‐Therapeutics. Available from https://www.e‐therapeutics.ca/cps.showMonograph.action (accessed October 2012) 2012.
FDA
-
- U.S. Food, Drug Administration. FDA Online Label Repository. Available from http://labels.fda.gov/ (accessed May 2013) 2013.
Goodman 2011
-
- Westfall TC, Westfall DP. Chapter 8: Neurotransmission: The Autonomic and Somatic Motor Nervous Systems. In: Brunton L, Chabner B, Knollman B editor(s). Goodman & Gilman's The Pharmacological Basis of Therapeutics. 12. New York: The McGraw‐Hill Companies, Inc. , 2011:188‐227.
Heran 2008a
Heran 2008b
Higgins 2011
-
- Higgins JPT, Green S, editors. Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane‐handbook.org.
Jadad 1996
-
- Jadad AR, Moore RA, Carrol D, Jenkinson C, Reynolds DJ, Gavaghan DJ, et al. Assessing the quality of reports of randomized clinical trials: Is blinding necessary?. Controlled Clinical Trials 1996;17:1‐12. - PubMed
Law 2005
-
- Law M, Morris JK, Jordan R, Wald N. Headaches and the treatment of blood pressure results from a meta‐analysis of 94 randomized placebo‐controlled trials with 24 000 participants. Circulation 2005;112:2301‐6. - PubMed
Magee 2003
McTavish 1993
-
- McTavish D, Campoli‐Richards D, Sorkin EM. Carvedilol: A review of its pharmacodynamic, pharmacokinetic properties and therapeutic efficacy. Drugs 1993;45(2):232‐58. - PubMed
Musini 2008
Musini 2009
Musini 2014
NY Times 2013
-
- Thomas K. Breaking the Seal on Drug Research. Available from: http://www.nytimes.com/2013/06/30/business/breaking‐the‐seal‐on‐drug‐res... (accessed 14 October 2014) June 29, 2013.
Wisonge 2007
Wong 2008
Wong 2014a
Wong 2014b
Wright 2000
Wright 2009
Xue 2015
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical