Current Hypertension Reports

, Volume 12, Issue 4, pp 282–289

Antihypertensive Effects of Aspirin: What is the Evidence?

Article

Abstract

Nonsteroidal anti-inflammatory drugs are known to increase blood pressure and blunt the effect of antihypertensive drugs. Surprisingly, it has been suggested recently that aspirin lowers blood pressure and could be used for preventing hypertension. This review summarizes published data on the effects of aspirin on blood pressure. Trials suggesting that aspirin administered at bedtime lowers blood pressure are uncontrolled, unmasked, and potentially biased. They also conflict with cohort studies showing an 18% increase in the risk of hypertension among aspirin users. Fortunately, short-term use of aspirin does not seem to interfere with antihypertensive drugs. Regardless of its effect on blood pressure, low-dose aspirin effectively prevents cardiovascular events in patients with and without hypertension, but its benefits should be carefully weighed against a potential increase in the risk of adverse effects such as gastric bleeding and hemorrhagic stroke, as well as a small increase in the risk of hypertension.

Keywords

Nonsteroidal anti-inflammatory agents Aspirin Blood pressure Hypertension Antihypertensive treatment Meta-analysis Drug chronotherapy 

References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. 1.
    Vane JR: Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nat New Biol 1971, 231:232–235.PubMedGoogle Scholar
  2. 2.
    Dubois RN, Abramson SB, Crofford L, et al.: Cyclooxygenase in biology and disease. FASEB J 1998, 12:1063–1073.PubMedGoogle Scholar
  3. 3.
    Harris RC, Breyer MD: Physiological regulation of cyclooxygenase-2 in the kidney. Am J Physiol Renal Physiol 2001, 281:F1–F11.PubMedGoogle Scholar
  4. 4.
    Ajani UA, Ford ES, Greenland KJ, et al.: Aspirin use among U.S. adults: behavioral risk factor surveillance system. Am J Prev Med 2006, 30:74–77.CrossRefPubMedGoogle Scholar
  5. 5.
    Pignone M, Anderson GK, Binns K, et al.: Aspirin use among adults aged 40 and older in the United States: results of a national survey. Am J Prev Med 2007, 32:403–407.CrossRefPubMedGoogle Scholar
  6. 6.
    Berger JS, Roncaglioni MC, Avanzini F, et al.: Aspirin for the primary prevention of cardiovascular events in women and men: a sex-specific meta-analysis of randomized controlled trials. JAMA 2006, 295:306–313.CrossRefPubMedGoogle Scholar
  7. 7.
    Antithrombotic Trialists’ Collaboration: Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ 2002, 324:71–86.CrossRefGoogle Scholar
  8. 8.
    Johnson AG, Nguyen TV, Day RO: Do nonsteroidal anti-inflammatory drugs affect blood pressure? A meta-analysis. Ann Intern Med 1994, 121:289–300.PubMedGoogle Scholar
  9. 9.
    Pope JE, Anderson JJ, Felson DT: A meta-analysis of the effects of nonsteroidal anti-inflammatory drugs on blood pressure. Arch Intern Med 1993, 153:477–484.CrossRefPubMedGoogle Scholar
  10. 10.
    MacMahon S, Peto R, Cutler J, et al.: Blood pressure, stroke, and coronary heart disease. Part 1, Prolonged differences in blood pressure: prospective observational studies corrected for the regression dilution bias. Lancet 1990, 335:765–774.CrossRefPubMedGoogle Scholar
  11. 11.
    Dersimonian R, Kacker R: Random-effects model for meta-analysis of clinical trials: an update. Contemp Clin Trials 2007, 28:105–114.CrossRefPubMedGoogle Scholar
  12. 12.
    Hermida RC, Fernandez JR, Ayala DE, et al.: Time-dependent effects of ASA administration on blood pressure in healthy subjects. Chronobiologia 1994, 21:201–213.PubMedGoogle Scholar
  13. 13.
    Hermida RC, Fernandez JR, Ayala DE, et al.: Influence of aspirin usage on blood pressure: dose and administration-time dependencies. Chronobiol Int 1997, 14:619–637.CrossRefPubMedGoogle Scholar
  14. 14.
    Hermida RC, Ayala DE, Calvo C, Lopez JE: Aspirin administered at bedtime, but not on awakening, has an effect on ambulatory blood pressure in hypertensive patients. J Am Coll Cardiol 2005, 46:975–983.CrossRefPubMedGoogle Scholar
  15. 15.
    Hermida RC, Ayala DE, Calvo C, et al.: Differing administration time-dependent effects of aspirin on blood pressure in dipper and non-dipper hypertensives. Hypertension 2005, 46:1060–1068.CrossRefPubMedGoogle Scholar
  16. 16.
    • Hermida RC, Ayala DE, Mojon A, Fernandez JR: Ambulatory blood pressure control with bedtime aspirin administration in subjects with prehypertension. Am J Hypertens 2009, 22:896–903. A noncontrolled trial of the effect of aspirin administered at bedtime in patients with prehypertension.CrossRefPubMedGoogle Scholar
  17. 17.
    Hermida RC, Ayala DE, Calvo C, et al.: Response: Aspirin administered at bedtime as opposed to upon wakening has an effect on ambulatory blood pressure: further evidence. Hypertension 2004, 43:e22–e23.CrossRefGoogle Scholar
  18. 18.
    Parati G, Staessen JA: Hypertension drug trials based on ambulatory blood pressure monitoring: When is a double-blind controlled design needed? J Hypertens 2003, 21:1237–1239.CrossRefPubMedGoogle Scholar
  19. 19.
    Gould BA, Mann S, Davies AB, et al.: Does placebo lower blood-pressure? Lancet 1981, 2(8260–8261):1377–1381.CrossRefPubMedGoogle Scholar
  20. 20.
    Mancia G, Omboni S, Parati G, et al.: Lack of placebo effect on ambulatory blood pressure. Am J Hypertens 1995, 8:311–315.CrossRefPubMedGoogle Scholar
  21. 21.
    Staessen JA, Thijs L, Bieniaszewski L, et al.: Ambulatory monitoring uncorrected for placebo overestimates long-term antihypertensive action. Hypertension 1996, 27:414–420.PubMedGoogle Scholar
  22. 22.
    Howe P, Phillips P, Saini R, Kassler-Taub K: The antihypertensive efficacy of the combination of irbesartan and hydrochlorothiazide assessed by 24-hour ambulatory blood pressure monitoring. Irbesartan Multicenter Study Group. Clin Exp Hypertens 1999, 21:1373–1396.CrossRefPubMedGoogle Scholar
  23. 23.
    Hansson L, Hedner T, Dahlof B: Prospective randomized open blinded end-point (PROBE) study. A novel design for intervention trials. Prospective Randomized Open Blinded End-Point. Blood Press 1992, 1:113–119.CrossRefPubMedGoogle Scholar
  24. 24.
    Smith DH, Neutel JM, Lacourciere Y, Kempthorne-Rawson J: Prospective, randomized, open-label, blinded-endpoint (PROBE) designed trials yield the same results as double-blind, placebo-controlled trials with respect to ABPM measurements. J Hypertens 2003, 21:1291–1298.CrossRefPubMedGoogle Scholar
  25. 25.
    Hansson L, Zanchetti A, Carruthers SG, et al.: Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial. HOT Study Group. Lancet 1998, 351:1755–1762.CrossRefPubMedGoogle Scholar
  26. 26.
    Mansoor GA, White WB: Contribution of ambulatory blood pressure monitoring to the design and analysis of antihypertensive therapy trials. J Cardiovasc Risk 1994, 1:136–142.PubMedGoogle Scholar
  27. 27.
    • Parker RA: Studies should be controlled, randomized, and blinded. Clin Pharmacol Ther 2009, 85:461–463. A review of arguments in favor of the use of placebo control groups and masking of treatment in randomized clinical trials.CrossRefPubMedGoogle Scholar
  28. 28.
    Chrischilles EA, Wallace RB: Nonsteroidal anti-inflammatory drugs and blood pressure in an elderly population. J Gerontol 1993, 48:M91–M96.PubMedGoogle Scholar
  29. 29.
    Whelton A: Nephrotoxicity of nonsteroidal anti-inflammatory drugs: physiologic foundations and clinical implications. Am J Med 1999, 106:13S–24S.CrossRefPubMedGoogle Scholar
  30. 30.
    Gainer JV, Morrow JD, Loveland A, et al.: Effect of bradykinin-receptor blockade on the response to angiotensin-converting-enzyme inhibitor in normotensive and hypertensive subjects. N Engl J Med 1998, 339:1285–1292.CrossRefPubMedGoogle Scholar
  31. 31.
    Magagna A, Abdel-Haq B, Favilla S, et al.: Hemodynamic and humoral effects of low-dose aspirin in treated and untreated essential hypertensive patients. Blood Press 1994, 3:236–241.CrossRefPubMedGoogle Scholar
  32. 32.
    Avanzini F, Palumbo G, Alli C, et al.: Effects of low-dose aspirin on clinic and ambulatory blood pressure in treated hypertensive patients. Collaborative Group of the Primary Prevention Project (PPP)–Hypertension study. Am J Hypertens 2000, 13:611–616.CrossRefPubMedGoogle Scholar
  33. 33.
    Nawarskas JJ, Townsend RR, Cirigliano MD, Spinler SA: Effect of aspirin on blood pressure in hypertensive patients taking enalapril or losartan. Am J Hypertens 1999, 12:784–789.CrossRefPubMedGoogle Scholar
  34. 34.
    Smith SR, Coffman TM, Svetkey LP: Effect of low-dose aspirin on thromboxane production and the antihypertensive effect of captopril. J Am Soc Nephrol 1993, 4:1133–1139.PubMedGoogle Scholar
  35. 35.
    Polónia J, Boaventura I, Gama G, et al.: Influence of non-steroidal anti-inflammatory drugs on renal function and 24 h ambulatory blood pressure-reducing effects of enalapril and nifedipine gastrointestinal therapeutic system in hypertensive patients. J Hypertens 1995, 13:925–931.CrossRefPubMedGoogle Scholar
  36. 36.
    Guazzi MD, Campodonico J, Celeste F, et al.: Antihypertensive efficacy of angiotensin converting enzyme inhibition and aspirin counteraction. Clin Pharmacol Ther 1998, 63:79–86.CrossRefPubMedGoogle Scholar
  37. 37.
    Moore TJ, Crantz FR, Hollenberg NK, et al.: Contribution of prostaglandins to the antihypertensive action of captopril in essential hypertension. Hypertension 1981, 3:168–173.PubMedGoogle Scholar
  38. 38.
    Tison P, Ulicna L, Jakubovska Z, et al.: Effects of dihydropyridines and their combination with aspirin on blood pressure and circadian platelet activity in patients with essential hypertension. Am J Hypertens 1994, 7:46S–49S.PubMedGoogle Scholar
  39. 39.
    Fisman EZ, Grossman E, Motro M, Tenenbaum A: Clinical evidence of dose-dependent interaction between aspirin and angiotensin-converting enzyme inhibitors. J Hum Hypertens 2002, 16:379–383.CrossRefPubMedGoogle Scholar
  40. 40.
    Boger RH, Bode-Boger SM, Kramme P, et al.: Effect of captopril on prostacyclin and nitric oxide formation in healthy human subjects: interaction with low dose acetylsalicylic acid. Br J Clin Pharmacol 1996, 42:721–727.CrossRefPubMedGoogle Scholar
  41. 41.
    Zanchetti A, Hansson L, Leonetti G, et al.: Low-dose aspirin does not interfere with the blood pressure-lowering effects of antihypertensive therapy. J Hypertens 2002, 20:1015–1022.CrossRefPubMedGoogle Scholar
  42. 42.
    Dubach UC, Rosner B, Sturmer T: An epidemiologic study of abuse of analgesic drugs. Effects of phenacetin and salicylate on mortality and cardiovascular morbidity (1968 to 1987). N Engl J Med 1991, 324:155–160.PubMedGoogle Scholar
  43. 43.
    Dedier J, Stampfer MJ, Hankinson SE, et al.: Nonnarcotic analgesic use and the risk of hypertension in US women. Hypertension 2002, 40:604–608.CrossRefPubMedGoogle Scholar
  44. 44.
    Forman JP, Stampfer MJ, Curhan GC: Non-narcotic analgesic dose and risk of incident hypertension in US women. Hypertension 2005, 46:500–507.CrossRefPubMedGoogle Scholar
  45. 45.
    Curhan GC, Willett WC, Rosner B, Stampfer MJ: Frequency of analgesic use and risk of hypertension in younger women. Arch Intern Med 2002, 162:2204–2208.CrossRefPubMedGoogle Scholar
  46. 46.
    Kurth T, Hennekens CH, Sturmer T, et al.: Analgesic use and risk of subsequent hypertension in apparently healthy men. Arch Intern Med 2005, 165:1903–1909.CrossRefPubMedGoogle Scholar
  47. 47.
    • Forman JP, Rimm EB, Curhan GC: Frequency of analgesic use and risk of hypertension among men. Arch Intern Med 2007, 167:394–399. This cohort study showed an increase in the risk of developing hypertension in regular users of aspirin and discussed potential sources of bias in this and previous studies of this hypothesis.CrossRefPubMedGoogle Scholar
  48. 48.
    Wang J, Mullins CD, Mamdani M, et al.: New diagnosis of hypertension among celecoxib and nonselective NSAID users: a population-based cohort study. Ann Pharmacother 2007, 41:937–943.CrossRefPubMedGoogle Scholar
  49. 49.
    Bautista LE, Lopez-Jaramillo P, Vera LM, et al.: Is C-reactive protein an independent risk factor for essential hypertension? J Hypertens 2001, 19:857–861.CrossRefPubMedGoogle Scholar
  50. 50.
    Sesso HD, Buring JE, Rifai N, et al.: C-reactive protein and the risk of developing hypertension. JAMA 2003, 290:2945–2951.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Population Health SciencesUniversity of Wisconsin Medical SchoolMadisonUSA
  2. 2.Departamento de Salud Publica, Universidad Industrial de Santander, Escuela de MedicinaBucaramangaColombia

Personalised recommendations