Skip to main content

Advertisement

Log in

The effect of antihypertensive treatment on headache and blood pressure variability in randomized controlled trials: a systematic review

  • Review
  • Published:
Journal of Neurology Aims and scope Submit manuscript

Abstract

Antihypertensive drugs reduce headache but it is unclear whether there are differences between drug classes. Calcium channel blockers (CCBs) decrease variability in systolic blood pressure (SBPV) and stroke risk more than other classes, possibly due to decreased vascular tone. If so, there might be a correlation between drug-class effects on variability in SBP and on headache. We determined antihypertensive class effects on SBPV and headache during follow-up in a systematic review of randomized controlled trials. We determined pooled estimates of treatment effect on group variability in BP (variance ratio, VR) and on the odds ratio for headache (OR) by random-effects meta-analysis. Antihypertensive drugs reduced the incidence of headache compared to placebo (OR = 0.75, 95% CI 0.69–0.82, p < 0.0001, 198 comparisons, 43,672 patients), but there was significant heterogeneity between drug classes (p = 0.0007) with a greater effect of beta-blockers compared to placebo (VR = 0.49, 0.33–0.68, p < 0.0001, 16 trials) or all other drug classes (OR = 0.73, 0.62–0.85, p = 0.0002, 49 trials) and a lack of effectiveness of CCBs (vs. placebo-OR = 0.95, 0.79–1.15, 65 trials; vs. other drugs-OR = 1.19, 1.05–1.35, p = 0.009, 101 trials). Drug-class effects on headache were opposite to effects on variability in SBP (vs. other drugs: CCB-VR = 0.81, 0.71–0.85, p < 0.0001; beta-blocker VR = 1.17, 1.07–1.28, p < 0.0001), but were unrelated to differences in mean SBP. Antihypertensive drugs reduce headache but the effect differs between classes, corresponding to their effects on SBPV and the risk of stroke. This may partly be explained by consistent antihypertensive class effects on vascular tone in the peripheral (variability) and cerebrovascular circulations (headache).

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Rothwell PM (2010) Limitations of the usual BP hypothesis and importance of variability, instability, and episodic hypertension. Lancet 375:938–948

    Article  PubMed  Google Scholar 

  2. Rothwell PM, Howard SC, Dolan E, O’Brien E, Dobson JE, Dahlof B et al (2010) Prognostic significance of visit-to-visit variability, maximum systolic BP, and episodic hypertension. Lancet 375:895–905

    Article  PubMed  Google Scholar 

  3. Webb AJS, Fischer U, Mehta Z, Rothwell PM (2010) Effects of antihypertensive-drug class on interindividual variation in BP and risk of stroke: a systematic review and meta-analysis. Lancet 375:906–915

    Article  PubMed  CAS  Google Scholar 

  4. Rothwell PM, Howard SC, Dolan E, O’Brien E, Dobson JR, Dahlof B et al (2010) ASCOT-BPLA and MRC Trial investigators. Effects of β blockers and calcium-channel blockers on within-individual variability in BP and risk of stroke. Lancet Neurol 9:469–480

    Article  PubMed  CAS  Google Scholar 

  5. Webb AJS, Rothwell PM (2011) Effect of β-blocker selectivity on blood pressure variability and stroke. Neurology 77:731–737

    Article  PubMed  CAS  Google Scholar 

  6. Webb AJS, Rothwell PM (2011) Effect of dose and combination of antihypertensives on interindividual blood pressure variability: a systematic review. Stroke 42:2860–2865

    Article  PubMed  CAS  Google Scholar 

  7. Sare GM, Greenagage C, Bath PM (2009) High blood pressure in acute ischaemic stroke–broadening therapeutic horizons. Cerebrovasc Dis 27(Suppl 1):156–161

    Article  PubMed  Google Scholar 

  8. Law M, Morris JK, Jordan R, Wald M (2005) Headaches and the treatment of blood pressure: results from a meta-analysis of 94 randomized placebo-controlled trials with 24,000 participants. Circulation 112:2301–2306

    Article  PubMed  CAS  Google Scholar 

  9. Di Tullio M, Alli C, Avanzini F, Bettelli G, Colombo F, Devoto MA et al (1988) for the Gruppo di Studio Sulla Pressione Arteriosa Nell’ Anziano. Prevalence of symptoms generally attributed to hypertension or its treatment: study on blood pressure in elderly outpatients (SPAA). J Hypertens 6:S87–S90

    Google Scholar 

  10. Weiss NS (1972) Relation of high blood pressure to headache, epistaxis and selected other symptoms. NEJM 287:631–633

    Article  PubMed  CAS  Google Scholar 

  11. Kurszewski P, Bieniaszewski L, Neubauer J, Krupa-Wojciechowska B (2000) Headache in patients with mild to moderate hypertension is generally not associated with simultaneous blood pressure elevation. J Hypertens 18:437–444

    Article  Google Scholar 

  12. Hagen K, Stovner JL, Vatten L, Holmen J, Zvart J-A, Bovim G (2002) Blood pressure and risk of headache: a prospective study of 22,685 adults in Norway. J Neurol Neurosurg Psychiatry 72:463–466

    PubMed  CAS  Google Scholar 

  13. Fuschs FD, Gus M, Moreira LB, Moreira WD, Goncalves SC, Nunes G (2003) Headache is not more frequent among patients with moderate to severe hypertension. J Hum Hypertens 17:787–790

    Article  Google Scholar 

  14. Linde K, Rossnagel K (2004) Propranolol for migraine prophylaxis. Cochrane Database Syst Rev 2:CD003225

    Google Scholar 

  15. Solomon GD, Steel JG, Spaccavento LJ (1983) Verapamil prophylaxis of migraine: a double-blind, placebo controlled trial. JAMA 250:2500–2502

    Article  PubMed  CAS  Google Scholar 

  16. Tronvik E, Stovner LJ, Helde G, Sand T, Bovim G (2003) Prophylactic treatment of migraine with an angiotensin II receptor blocker: a randomised controlled trial. JAMA 289:65–69

    Article  PubMed  CAS  Google Scholar 

  17. Law MR, Morris JK, Wald NJ (2006) Calcium channel blockers and headache (Letter). Br J Clin Pharm 63:157–158

    Article  Google Scholar 

  18. Meyer JS, Waltz AG, Gotoh F (1960) Pathogenesis of cerebral vasospasm in hypertensive encephalopathy. I. Effects of acute increase in intraluminal blood pressure on pial blood flow. Neurology 10:735–744

    Article  Google Scholar 

  19. Troisi E, Attanasio A, Matteis M, Bragoni M, Monaldo BC, Caltagirone C, Silvestrini M (1998) Cerebral hemodynamics in young hypertensive subjects and effects of atenolol treatment. J Neurol Sci 159:115–119

    Article  PubMed  CAS  Google Scholar 

  20. Pieniazek W, Dimitrow PP, Jasinski T (2001) Comparison of the effect of perindopril and acebutolol on cerebral hemodynamics in hypertensive patients. Cardiovasc Drugs Ther 15:63–67

    Article  PubMed  CAS  Google Scholar 

  21. Hong KS, Kang DW, Bae HJ, Kim YK, Han MK, Park JM et al (2010) Effect of cilnidipine vs. losartan on cerebral blood flow in hypertensive patients with a history of ischemic stroke: a randomized controlled trial. Acta Neurol Scand 121:51–57

    Article  PubMed  CAS  Google Scholar 

  22. Semplicini A, Maresca A, Simonella C, Chierichetii F, Pauletto P, Meneghetti G et al (2000) Cerebral perfusion in hypertensives with carotid artery stenosis: a comparative study of lacidipine and hydrochlorothiazide. Blood Press 9:34–39

    Article  PubMed  CAS  Google Scholar 

  23. Walters MR, Bolster A, Dyker AG, Lees KR (2001) Effect of perindopril on cerebral and renal perfusion in stroke patients with carotid disease. Stroke 32:473–478

    Article  PubMed  CAS  Google Scholar 

  24. Hatazawa J, Shimosegawa E, Osaki Y, Ibaraki M, Oku N, Hasegawa S et al (2004) Long-term angiotensin-converting enzyme inhibitor perindopril therapy improves cerebral perfusion reserve in patients with previous minor stroke. Stroke 35:2117–2122

    Article  PubMed  CAS  Google Scholar 

  25. Claassen JA, Levine BD, Zhang R (2009) Cerebral vasomotor reactivity before and after blood pressure reduction in hypertensive patients. Am J Hypertens 22:384–391

    Article  PubMed  Google Scholar 

  26. Oku N, Kitagawa K, Imaizumi M, Takasawa M, Piao R, Kimura Y et al (2005) Hemodynamic influences of losartan on the brain in hypertensive patients. Hypertens Res 28:43–49

    Article  PubMed  CAS  Google Scholar 

  27. Nazir FS, Overell JR, Bolster A, Hilditch TE, Reid JL, Lees KR (2004) The effect of losartan on global and focal cerebral perfusion and on renal function in hypertensives in mild early ischaemic stroke. J Hypertens 22:989–995

    Article  PubMed  CAS  Google Scholar 

  28. Akopov SE, Simonian NA (1997) Comparison of isradipine and enalapril effects on regional carotid circulation in patients with hypertension with unilateral internal carotid artery stenosis. J Cardiovasc Pharmacol 30:562–570

    Article  PubMed  CAS  Google Scholar 

  29. Lisk DR, Grotta JC, Lamki LM, Tran HD, Taylor JW, Molony DA, Barron BJ (1993) Should hypertension be treated after acute stroke? A randomized controlled trial using single photon emission computed tomography. Arch Neurol 50:855–862

    Article  PubMed  CAS  Google Scholar 

  30. Osterloh IH (1991) An update on the safety of amlodipine. J Cardiovasc Pharmacol 17(Suppl 1):S65–S68

    Article  PubMed  Google Scholar 

  31. Waeber B, Borges ET, Christeler P, Guillaume-Gentil M, Hollenstein U, Mannhart M (1992) Amlodipine compare to nitrendipine in hypertensive patients: the effects on toleration in relationship to the onset of action. Cardiology 80(Suppl 1):46–53

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

Dr Alastair Webb is in receipt of an Medical Research Council Clinical Training Fellowship. Prof PM Rothwell is in receipt of an NIHR Senior Investigator award. The study itself received no specific funding.

Conflicts of interest

We declare that we have no conflicts of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Peter Malcolm Rothwell.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (PDF 1183 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Webb, A.J.S., Rothwell, P.M. The effect of antihypertensive treatment on headache and blood pressure variability in randomized controlled trials: a systematic review. J Neurol 259, 1781–1787 (2012). https://doi.org/10.1007/s00415-012-6449-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00415-012-6449-y

Keywords

Navigation