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Calcium channel blockers for primary Raynaud's phenomenon

  1. Holly Ennis1,
  2. Marina E Anderson2,
  3. Jack Wilkinson3,
  4. Ariane L Herrick1,*

Editorial Group: Cochrane Vascular Group

Published Online: 30 JAN 2014

Assessed as up-to-date: 8 FEB 2013

DOI: 10.1002/14651858.CD002069.pub4


How to Cite

Ennis H, Anderson ME, Wilkinson J, Herrick AL. Calcium channel blockers for primary Raynaud's phenomenon. Cochrane Database of Systematic Reviews 2014, Issue 1. Art. No.: CD002069. DOI: 10.1002/14651858.CD002069.pub4.

Author Information

  1. 1

    University of Manchester, Manchester Academic Health Science Centre, Centre for Musculoskeletal Research, Institute of Inflammation and Repair, Manchester, UK

  2. 2

    University of Liverpool, Institute of Ageing and Chronic Disease, Liverpool, UK

  3. 3

    University of Manchester, Manchester Academic Health Science Centre, Biostatistics, Institute of Population Health, Manchester, UK

*Ariane L Herrick, Centre for Musculoskeletal Research, Institute of Inflammation and Repair, University of Manchester, Manchester Academic Health Science Centre, Stopford Building, Oxford Road, Manchester, M13 9PT, UK. ariane.herrick@manchester.ac.uk.

Publication History

  1. Publication Status: New
  2. Published Online: 30 JAN 2014

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References

References to studies included in this review

  1. References to studies included in this review
  2. References to studies excluded from this review
  3. Additional references
Ettinger 1984 {published data only}
  • Ettinger WH, Wise RA, Schaffhauser D, Wigley FM. Controlled double-blind trial of dazoxiben and nifedipine in the treatment of Raynaud's phenomenon. American Journal of Medicine 1984;77(3):451-6.
  • Malamet R, Wise RA, Ettinger EH, Wigley FM. Nifedipine in the treatment of Raynaud's phenomenon. Evidence for inhibition of platelet activation. American Journal of Medicine 1985;78(4):602-8.
  • Wigley FM, Malamet R, Wise RA. Reproducibility of cold provocation in patients with Raynaud's phenomenon. Journal of Rheumatology 1987;14(4):751-5.
Kahan 1987 {published data only}
Rodeheffer 1983 {published data only}
RTS 2000 {published data only}
  • Maricq HR, Jennings JR, Valter I, Frederick M, Thompson B, Smith EA, et al. Evaluation of treatment efficacy of Raynaud phenomenon by digital blood pressure response to cooling. Raynaud's Treatment Study Investigators. Vascular Medicine 2000;5(3):135-40.
  • Middaugh SJ, Haythornthwaite JA, Thompson B, Hill R, Brown KM, Freedman RR, et al. The Raynaud's Treatment Study: biofeedback protocols and acquisition of temperature biofeedback skills. Applied Psychophysiology and Biofeedback 2001;26(4):251-78.
  • Raynaud's Treatment Study Investigators. Comparison of sustained-release nifedipine and temperature biofeedback for treatment of primary Raynaud phenomenon. Results from a randomized clinical trial with 1-year follow-up. Archives of Internal Medicine 2000;160(8):1101-8.
  • Thompson B, Geller NL, Hunsberger S, Frederick M, Hill R, Jacob RG, et al. Behavioral and pharmacologic interventions: the Raynaud's Treatment Study. Controlled Clinical Trials 1999;20(1):52-63.
Sarkozi 1986 {published data only}
  • Sarkozi J, Bookman AA, Mahon W, Ramsay C, Detsky AS, Keystone EC. Nifedipine in the treatment of idiopathic Raynaud's syndrome. Journal of Rheumatology 1986;13(2):331-6.
Vayssairat 1991 {published data only}
  • Vayssairat M, Boccalon H, Ginestet MC, Priollet P, Franco A, Carpentier P, et al. Controlled multicenter double-blind trial of nicardipine in the treatment of primary Raynaud phenomenon. American Heart Journal 1991;122(1 Suppl 2):352-5.
Wollersheim 1991 {published data only}
  • Wollersheim H, Thien T. Double-blind placebo-controlled crossover study of oral nicardipine in the treatment of Raynaud's phenomenon. Journal of Cardiovascular Pharmacology 1991;18(6):813-8.

References to studies excluded from this review

  1. References to studies included in this review
  2. References to studies excluded from this review
  3. Additional references
Agnelli 1984 {published data only}
  • Agnelli G, Parise P, Colangeli C. Pilot evaluation of flunarizine in Raynaud's disease: A placebo- controlled, double blind cross-over study. Acta Therapeutica 1984;10(2):153-62.
Aldoori 1986 {published data only}
Baadsgaard 1983 {published data only}
  • Baadsgaard O, Schmidt JF, Ironmann L. The effect of nifedipin (adalat) on Raynaud's phenomenon. Ugeskrift for Laeger 1983;145(49):3814-6.
Brotzu 1989 {published data only}
  • Brotzu G, Falchi S, Mannu B, Montisci R, Petruzzo P, Staico R. The importance of presynaptic beta receptors in Raynaud's disease. Journal of Vascular Surgery 1989;9(6):767-71.
Caglayan 2012 {published data only}
  • Caglayan E, Axmann S, Hellmich M, Moinzadeh P, Rosenkranz S. Vardenafil for the treatment of Raynaud phenomenon: A randomized, double-blind, placebo-controlled crossover study. Archives of Internal Medicine 2012;172(15):1182-4.
Challenor 1987 {published data only}
Challenor 1989 {published data only}
Choi 2009 {published data only}
  • Choi WS, Choi CJ, Kim KS, Lee JH, Song CH, Chung JH, et al. To compare the efficacy and safety of nifedipine sustained release with Ginkgo biloba extract to treat patients with primary Raynaud's phenomenon in South Korea; Korean Raynaud study (KOARA study). Clinical Rheumatology 2009;28(5):553-9.
Codella 1989 {published data only}
Coleiro 2001 {published data only}
  • Coleiro B, Marshall SE, Denton CP, Howell K, Blann A, Welsh KI, et al. Treatment of Raynaud's phenomenon with the selective serotonin reuptake inhibitor fluoxetine. Rheumatology 2001;40(9):1038-43.
Corbin 1986 {published data only}
  • Corbin DO, Wood DA, Macintyre CC, Housley E. A randomized double blind cross-over trial of nifedipine in the treatment of primary Raynaud's phenomenon. European Heart Journal 1986;7(2):165-70.
  • Corbin DOC, Wood DA, Macintyre CCA, Housley El. A randomised double blind cross-over trial of nifedipine in the treatment of primary Raynaud's phenomenon [abstract]. Clinical Science 1985; Vol. 69, issue Suppl 12:21P.
Costantini 1987 {published data only}
  • Costantini A, Martelli E, Bavera P, Agus GB. Slow release nifedipine in the treatment of Raynaud's phenomenon. International Angiology 1987;6(4):359-63.
Creager 1984 {published data only}
  • Creager MA, Pariser KM, Winston EM, Rasmussen HM, Miller KB, Coffman JD. Nifedipine-induced fingertip vasodilation in patients with Raynaud's phenomenon. American Heart Journal 1984;108(2):370-3.
Csiki 2011 {published data only}
  • Csiki Z, Garai I, Shemirani AH, Papp G, Zsori KS, Andras C, et al. The effect of metoprolol alone and combined metoprolol-felodipin on the digital microcirculation of patients with primary Raynaud's syndrome. Microvascular Research 2011;82(1):84-7.
Da Costa 1987 {published data only}
  • Da Costa J, Gomes JA, Espirito Santo J, Queiros M. Inefficacy of diltiazem in the treatment of Raynaud's Phenomenon with associated connective tissue disease: a double blind placebo controlled study. Journal of Rheumatology 1987;14(4):858-9.
Denton 1999 {published data only}
  • Denton CP, Bunce TD, Dorado MB, Roberts Z, Wilson H, Howell K, et al. Probucol improves symptoms and reduces lipoprotein oxidation susceptibility in patients with Raynaud's phenomenon. Rheumatology 1999;38(4):309-15.
Dompeling 1992 {published data only}
  • Dompeling EC, Smit AJ. Assessment of pinacidil in patients with primary Raynaud's phenomenon. Vasa Supplementum 1992;34:34-7.
Dziadzio 1999a {published data only}
  • Dziadzio M, Denton CP, Smith R, Howell K, Blann A, Bowers E, et al. Losartan therapy for Raynaud's phenomenon and scleroderma: clinical and biochemical findings in a fifteen-week, randomized, parallel-group, controlled trial. Arthritis and Rheumatism 1999;42(12):2646-55.
Ferri 1992 {published data only}
  • Ferri C, Cecchetti R, Cini G, Gambini I, La Civita L, Bernini L, et al. Slow-releasing nicardipine in the treatment of Raynaud's phenomena without underlying diseases. Clinical Rheumatology 1992;11(1):76-80.
Finch 1986 {published data only}
  • Finch MB, Johnston GD, Dawson J. The peripheral vascular effects of nifedipine in Raynaud's disease. British Journal of Clinical Pharmacology 1985; Vol. 21:100P-1P.
  • Finch MB, Johnston GD, Dawson J. The peripheral vascular effects of nifedipine in Raynaud's disease associated with scleroderma: a double blind crossover study.. Clinical Rheumatology 1986; Vol. 5, issue 4:493-8.
Finch 1988 {published data only}
Gjorup 1986a {published data only}
  • Gjorup T, Kelbaek H, Hartling OJ, Nielsen SL. Controlled double-blind trial of the clinical effect of nifedipine in the treatment of idiopathic Raynaud's phenomenon. American Heart Journal 1986;111(4):742-5.
Gjorup 1986b {published data only}
  • Gjorup T, Hartling OJ, Kelbaek H, Nielsen SL. Controlled double blind trial of nisoldipine in the treatment of idiopathic Raynaud's phenomenon. European Journal of Clinical Pharmacology 1986;31(4):387-9.
Gush 1987 {published data only}
Hawkins 1986 {published data only}
Kahan 1981 {published data only}
Kahan 1983a {published data only}
  • Kahan A, Weber S, Amor B, Menkes CJ, Hodara M, Degeorges M. Nifedipine and Raynaud's phenomenon associated with connective tissue diseases. International Angiology 1985;4(2):221-3.
  • Kahan A, Weber S, Amor B, Menkes CJ, Saporta L, Hodara M, et al. Calcium entry blocking agents in digital vasospasm (Raynaud's phenomenon). European Heart Journal 1983;4(Suppl C):123-9.
  • Kahan A, Weber S, Amor B, Saporta L, Hodara M, Degeorges M. Controlled study of nifedipine in the treatment of Raynaud's phenomenon. Revue du Rhumatisme et des Maladies Osteo-Articulaires 1982;49(5):337-43.
Kahan 1983b {published data only}
Kahan 1985a {published data only}
Kahan 1985b {published data only}
  • Kahan A, Foult JM, Weber S, Amor B, Menkes CJ, Degeorges M. Nifedipine and alpha1-adrenergic blockade in Raynaud's phenomenon. European Heart Journal 1985;6(8):702-5.
Kahan 1986 {published data only}
  • Kahan A, Amor B, Menkes CJ, Weber S, Guerin F, Degeorges M. Controlled double-blind trial of nicardipine in the treatment of Raynaud's phenomenon. International Journal of Clinical Pharmacology and Therapeutics 1986; Vol. 39, issue 2:202.
Kallenberg 1987 {published data only}
  • Kallenberg CG, Wouda AA, Kuitert JJ, Tijssen J, Wesseling H. Nifedipine in Raynaud's phenomenon: Relationship between immediate, short term and longterm effects. Journal of Rheumatology 1987;14(2):284-90.
  • Kallenberg CG, Wouda AA, Kuitert JJ, Tijssen J, Wesseling H. Treatment of Raynaud's phenomenon with nifedipine short-term and long-term effects. Vasa Supplementum 1987;18:68-70.
La Civita 1993 {published data only}
  • La Civita L, Pitaro N, Rossi M, Gambini I, Giuggioli D, Cini G, et al. Amlodipine in the treatment of Raynaud's phenomenon. British Journal of Rheumatology 1993;32(6):524-5.
  • La Civita L, Pitaro N, Rossi M, Giuggioli D, Gambini I, Cini G, et al. Amlodipine in the treatment of Raynaud's phenomenon. A double-blind placebo-controlled crossover study. Clinical Drug Investigation 1997;13(Suppl 1):126-31.
La Civita 1996 {published data only}
  • La Civita L, Giuggioli D, Del Chicca MG, Longombardo G, Pasero G, Ferri C. Effect of isradipine on endothelin-1 plasma concentrations in patients with Raynaud's phenomenon [letter]. Annals of the Rheumatic Diseases 1996;55(5):331-2.
Leppert 1989 {published data only}
  • Leppert J, Jonasson T, Nilsson H, Ringqvist I. The effect of isradipine, a new calcium-channel antagonist, in patients with primary Raynaud's phenomenon: A single-blind dose-response study. Cardiovascular Drugs Therapy 1989;3(3):397-401.
Lewis 1987 {published data only}
  • Lewis P, Psaila JV, Morgan RH, Davies WT, Woodcock JP. Nifedipine in patients with Raynaud's syndrome - effects on radial artery flow. European Heart Journal 1987;8(Suppl K):83-6.
Martinez 1999 {published data only}
  • Martinez S, Lozano P, Pallares L, Julia J, Artigues I, Plaza A, et al. Usefulness of photoplethysmography and indexes of digital pressure in Raynaud phenomenon. Medicina Clinica 1999;113(9):327-30.
Mascagni 1994 {published data only}
  • Mascagni B, Sardina M, Alvino S, Berruti V, Bazzi S, Scorza R. Effects of iloprost in comparison to nifedipine in patients with Raynaud's phenomenon secondary to progressive systemic sclerosis. International Angiology 1994; Vol. 13, issue Suppl 1:81.
Morgan 1987 {published data only}
  • Morgan RH, Psaila JV, Davies WT, Carolan G, Woodcock JP. Digital and radial artery blood flow in patients with Raynaud's phenomenon in response to nifedipine. European Journal of Vascular Surgery 1987;1(6):403-8.
Moriau 1993 {published data only}
  • Moriau M, Lavenne-Pardonge E, Crasborn L, Von Frenckell R, Col-Debeys C. Treatment of Raynaud's phenomenon with piracetam. Arzneimittel-Forschung 1993;43(5):526-35.
Müller-Bühl 1983 {published data only}
  • Diehm C, Müller-Bühl U, Mörl H, Schettler G. Calcium antagonists in Raynaud's phenomenon [Calciumantagonistum beim Raynaud-phanomen]. Zeitschrift fur Kardiologie 1982; Vol. 71, issue 9:Abstract 86.
  • Müller-Bühl U, Diehm C, Scheuermann W, Mörl H. Calcium antagonists for the treatment of Raynaud's phenomenon. Deutsche Medizinische Wochenschrift 1983;108(47):1795-7.
Nilsson 1987 {published data only}
Pisenti 1984 {published data only}
Redondo 1986 {published data only}
  • Rivera Redondo J, Noguerado Asensio A, López Bote JP, Alvaro-Gracia Alvaro JM, Ossorio Castellanos C. Nifedipine treatment of Raynaud's phenomenon: a double blind controlled clinical study. Revista Espanola de Reumatologia 1986;13:121-3.
Rhedda 1985 {published data only}
  • Rhedda A, McCans J, Willan AR, Ford PM. A double blind placebo controlled crossover randomized trial of diltiazem in Raynaud's phenomenon. Journal of Rheumatology 1985;12(4):724-7.
Rupp 1987 {published data only}
  • Rupp PA, Mellinger S, Kohler J, Dorsey JK, Furst DE. Nicardipine for the treatment of Raynaud's phenomena: A double blind crossover trial of a new calcium entry blocker. Journal of Rheumatology 1987;14(4):745-50.
Sauza 1984 {published data only}
  • Sauza J, Kraus A, González-Amaro R, Alarcón-Segovia D. Effect of the calcium channel blocker nifedipine on Raynaud's Phenomenon. A controlled double blind trial. Journal of Rheumatology 1984;11(3):362-4.
Schmidt 1989 {published data only}
Scorza 2001 {published data only}
  • Scorza R, Caronni M, Mascagni B, Berruti V, Bazzi S, Micallef E, et al. Effects of long-term cyclic iloprost therapy in systemic sclerosis with Raynaud's phenomenon. A randomized, controlled study. Clinical and Experimental Rheumatology 2001;19(5):503-8.
Shcherbakov 1987 {published data only}
Smith 1982 {published data only}
Stefenelli 1986 {published data only}
  • Stefenelli T, Silberbauer K, Glogar D. Pentoxifylline/placebo/nifedipine in patients with Raynaud's phenomenon: influence on frequency of attacks and rewarming time. Klinische Wochenschrift 1986;64:1155-6.
Van Heereveld 1988 {published data only}
Varela-Aguilar 1997 {published data only}
  • Varela-Aguilar JM, Sanchez-Roman J, Talegon Melendez A, Castillo Palma MJ. [Comparative study of misoprostol and nifedipine in the treatment of Raynaud's phenomenon secondary to systemic diseases. Hemodynamic assessment with Doppler duplex]. Revista Clinica Espanola 1997;197(2):77-83.
Waller 1986 {published data only}
  • Francis DA, Waller DG, Challenor VF, Roath OS. Red cell deformability in patients with Raynaud's phenomenon treated with nifedipine. Clinical Hemorheology 1985; Vol. 5, issue 5:742.
  • Waller DG, Challenor VF, Francis DA, Roath OS. Clinical and rheological effects of nifedipine in Raynaud's phenomenon. British Journal of Clinical Pharmacology 1986;22(4):449-54.
Wasir 1983 {published data only}
  • Wasir HS, Singh G, Kaul R, Sachdeva U, Khan WA, Chhina GS, et al. A comparative study of trifluoperazine a calmodulin inhibitor, nifedipine, dipyridamole and intraarterial reserpine in the treatment of Raynaud's phenomenon: A double blind randomised controlled trial. Indian Heart Journal 1983; Vol. 35, issue 5:306.
Weber 1990 {published data only}
White 1986 {published data only}
Wigley 1987a {published data only}
Winston 1983 {published data only}
Wise 1987 {published data only}
  • Wise RA, Malamet R, Wigley FM. Acute effects of nifedipine on digital blood flow in human subjects with Raynaud's phenomenon: a double blind placebo controlled trial. Journal of Rheumatology 1987;14(2):278-83.
Wollersheim 1987 {published data only}
  • Wollersheim H, Thien T, Van't Laar A. Acute and chronic effects of nifedipine in Raynaud's phenomenon. European Journal of Clinical Investigation 1986;16(Suppl):A16.
  • Wollersheim H, Thien T, Van't Laar A. Nifedipine in primary Raynaud's phenomenon and in scleroderma: oral versus sublingual hemodynamic effects. Journal of Clinical Pharmacology 1987;27(11):907-13.

Additional references

  1. References to studies included in this review
  2. References to studies excluded from this review
  3. Additional references
Allen 1932
  • Allen EV, Brown GE. Raynaud's disease: a critical review of minimal requisites for diagnosis. American Journal of Medical Science 1932;183(2):187-200.
ATC classification
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Block 2001
Dziadzio 1999
  • Dziadzio M, Denton CP, Smith R, Howell K, Blann A, Bowers E, et al. Losartan therapy for Raynaud's phenomenon and scleroderma: clinical and biochemical findings in a fifteen-week, randomized, parallel-group, controlled trial. Arthritis and Rheumatism 1999;42(12):2646-55.
Elbourne 2002
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Harding 1998
  • Harding SE, Tingey PC, Pope J, Fenlon D, Furst D, Shea B, et al. Prazosin for Raynaud's phenomenon in progressive systemic sclerosis. Cochrane Database of Systematic Reviews 1998, Issue 2. [DOI: 10.1002/14651858.CD000956]
Herrick 2005
Higgins 2003
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.
Hirschl 2006
  • Hirschl M, Hirschl K, Lenz M, Katzenschlager R, Hutter HP, Kundi M. Transition from primary Raynaud's phenomenon to secondary Raynaud's phenomenon identified by diagnosis of an associated disease; results of ten years of prospective surveillance. Arthritis and Rheumatism 2006;54(6):1974-81.
Koenig 2008
  • Koenig M, Joyal F, Fritzler MJ, Roussin A, Abrahamowicz M, Boire G, et al. Autoantibodies and microvascular damage are independent predictive factors for the progression of Raynaud's phenomenon to systemic sclerosis: a twenty year prospective study of 586 patients, with validation of proposed criteria for early systemic sclerosis. Arthritis and Rheumatism 2008;58(12):3902-12.
LeRoy 1992
  • LeRoy EC, Medsger TA Jr. Raynaud's phenomenon: a proposal for classification. Clinical and Experimental Rheumatology 1992;10(5):458-8.
Maricq 1988
Maricq 1997
  • Maricq HR, Carpentier PH, Weinrich MC, Keil JE, Palesch Y, Biro C, et al. Geographic variation in the prevalence of Raynaud's phenomenon: a 5 region comparison. Journal of Rheumatology 1997;24(5):879-89.
Merkel 2002
  • Merkel PA, Herlyn K, Martin RW, Anderson JJ, Mayes MD, Bell P, et al. Scleroderma Clinical Trials Consortium. Measuring disease activity and functional status in patients with scleroderma and Raynaud's phenomenon. Arthritis and Rheumatism 2002;46(9):2410-20.
Priollet 1987
R Development Core Team 2012
  • R Development Core Team. R: A language and environment for statistical computing. Vienna: R Foundation for Statistical Computing, 2012.
RevMan 2012
  • The Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager (RevMan). 5.2. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2012.
Schunemann 2006
  • Schunemann HJ, Jaeschke R, Cook DJ, Bria WF, El-Solh AA, Ernst A, et al. ATS Documents Development and Implementation Committee. An official ATS statement: grading the quality of evidence and strength of recommendations in ATS guidelines and recommendations. American Journal of Respiratory and Critical Care Medicine 2006;174(5):605-14.
Silman 1990
Sturgill 1998
  • Sturgill MG, Seibold JR. Rational use of calcium-channel antagonists in Raynaud's phenomenon. Current Opinion in Rheumatology 1998;10(6):584-8.
Suter 2005
Thompson 2005
Wigley 2002