Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Commentary
  • Published:

Using placebo in hypertension clinical trials: new information and new opportunities

Journal of Human Hypertension volume 22, pages 653–655 (2008)Cite this article

On the basis of epidemiologic and clinical trials’ evidence, it is broadly believed that people with high blood pressure are at increased risk of fatal and non-fatal cardiovascular events and strokes. For this reason, there have been concerns about the conduct of clinical trials of antihypertensive agents in which the blood pressure-lowering efficacy of active treatments compared with placebo. In particular, is it safe, or ethical, to randomize hypertensive patients to placebo treatment in such trials, even if for periods of just a few weeks?

Certainly, those charged with official oversight of patient safety—typically, institutional review boards or ethics committees—understandably ponder whether such study designs are appropriate. At the same time, regulatory agencies charged with the responsibility of evaluating and approving new antihypertensive drugs generally demand that such agents demonstrate blood pressure-lowering efficacy that differs significantly from placebo.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

References

  1. DeFelicie A, Willard J, Lawrence J, Hung J, Gordon M, Karkowsky A et al. The risks associated with short-term placebo-controlled anti-hypertensive clinical trials: a descriptive meta-analysis. J Hum Hypertension 2008, in press.

  2. Dahlof B, Devereux RB, Kjeldsen SE, Julius S, Beevers G, deFaire U, et al., for the LIFE study group. Cardiovascular morbidity and mortality in the losartan intervention for endpoint reduction in hypertension study (LIFE): a randomized trial against atenolol. Lancet 2002; 359: 996–1003.

    Google Scholar 

  3. Julius S, Kjeldsen SE, Weber MA, Brunner HR, Ekman S, Hansson L, et al., VALUE Trial Group. Outcomes in hypertensive patients at high cardiovascular risk treated with regimens based on valsartan or amlodipine: the VALUE randomised trial. Lancet 2004; 363: 2022–2031.

    Article  CAS  Google Scholar 

  4. The ALLHAT Officers. Coordinators for the ALLHAT Collaborative Research Group: major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA 2002; 288: 2981–2997.

  5. SHEP Cooperative Research Group. Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension. Final results of the Systolic Hypertension in the Elderly Program (SHEP). JAMA 1991; 265: 3255–3264.

  6. Staessen JA, Fagard R, Thijs L, Celis H, Arabidze GG, Birkenhager WH, et al., for the systolic hypertension in Europe (Syst-Eur) trial investigators. Randomised double-blind comparison of placebo and active treatment for older patients with isolated systolic hypertension. Lancet 1997; 350: 757–764.

    Article  CAS  Google Scholar 

  7. Weber MA, Julius S, Kjeldsen SE, Brunner HR, Ekman S, Hansson L et al. Blood pressure dependent and independent effects of antihypertensive treatment on clinical events in the VALUE Trial. Lancet 2004; 363: 2049–2051.

    Article  CAS  Google Scholar 

  8. Lewington S, Clarke R, Qizilbash N, Peto R, Collins R . Prospective Studies Collaboration. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet 2002; 360: 1903–1913.

    Article  Google Scholar 

  9. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL, et al., the National High Blood Pressure Education Program Coordinating Committee. The seventh report of the Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure. The JNC7 Report. JAMA 2003; 289: 2560–2572.

    Article  CAS  Google Scholar 

  10. Mancia G, De Backer G, Dominiczak A, Cifkova R, Fagard R, Germano G et al. Task force for the management of arterial hypertension. J Hypertens 2007; 25: 1105–1187.

    Article  CAS  Google Scholar 

  11. Hansson L, Zanchetti A, Carruthers SG, Dahlof B, Elmfeldt D, Julius S, et al., for the HOT study group. Effects of intensive blood pressure-lowering and low-dose aspirin in patients with hypertension: Principal results of the Hypertension Optimal Treatment (HOT) randomized trial. Lancet 1998; 351: 1755–1762.

    Article  CAS  Google Scholar 

  12. UK Prospective Diabetes Study Group. efficacy of atenolol and captopril in reducing risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. BMJ 1998; 317: 703–713.

  13. Turnbull F, Blood Pressure Lowering Treatment Trialists’ Collaboration. Effects of different blood-pressure-lowering regimens on major cardiovascular events: results of prospectively designed overviews of randomized trials. Lancet 2003; 362: 1527–1535.

    Article  CAS  Google Scholar 

  14. Weber MA . The ethics of using placebo in hypertension clinical trials. J Hypertens 1999; 17: 5–8.

    Article  CAS  Google Scholar 

  15. Dahlöf B, Sever PS, Poulter NR, Wedel H, Beevers DG, et al., for the ASCOT Investigators. Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding bendroflumethiazide as required, in the Anglo-Scandanavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA): a multicentre randomized controlled trial. Lancet 2005; 366: 895–906.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medicine, SUNY Downstate Medical Center, Brooklyn, NY, USA

    M A Weber

Authors
  1. M A Weber
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to M A Weber.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Weber, M. Using placebo in hypertension clinical trials: new information and new opportunities. J Hum Hypertens 22, 653–655 (2008). https://doi.org/10.1038/jhh.2008.53

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/jhh.2008.53

Search

Advanced search

Quick links