Systematic review of genuine versus spurious side-effects of beta-blockers in heart failure using placebo control: recommendations for patient information

Int J Cardiol. 2013 Oct 9;168(4):3572-9. doi: 10.1016/j.ijcard.2013.05.068. Epub 2013 Jun 21.


Background: Patients trying life-preserving agents such as beta-blockers may be discouraged by listings of harmful effects provided in good faith by doctors, drug information sheets, and media. We systematically review the world experience of side-effect information in blinded, placebo-controlled beta-blockade in heart failure. We present information for a physician advising a patient experiencing an unwanted symptom and suspecting the drug.

Methods: We searched Medline for double-blinded randomized trials of beta-blocker versus placebo in heart failure reporting side-effects. We calculated, per 100 patients reporting the symptom on beta-blockade, how many would have experienced it on placebo: the "proportion of symptoms non-pharmacological".

Results: 28 of the 33 classically-described side-effects are not significantly more common on beta-blockers than placebo. Of the 100 patients developing dizziness on beta-blockers, 81 (95% CI 73-89) would have developed it on placebo. For diarrhoea this proportion is 82/100 (70-95), and hyperglycaemia 83/100 (68-98). For only two side-effects is this under half (i.e. predominantly due to beta-blocker): bradycardia (33/100, CI 21-44) and intermittent claudication (41/100, 2-81). At least 6 so-called side-effects are less common on beta-blocker than placebo, including depression (reduced by 35%, p<0.01) and insomnia (by 27%, p=0.01).

Conclusions: Clinicians might reconsider whether it is scientifically and ethically correct to warn a patient that a drug might cause them a certain side-effect, when randomized controlled trials show no significant increase, or indeed a significant reduction. A better informed consultation could, in patients taking beta-blockers, alleviate suffering. In patients who might otherwise not take the drug, it might prevent deaths.

Keywords: Beta-blockers; Heart failure; Side-effects.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Adrenergic beta-Antagonists / adverse effects
  • Adrenergic beta-Antagonists / therapeutic use*
  • Diarrhea / chemically induced
  • Diarrhea / diagnosis
  • Dizziness / chemically induced
  • Dizziness / diagnosis
  • Heart Failure / diagnosis
  • Heart Failure / drug therapy*
  • Heart Failure / epidemiology
  • Humans
  • Hyperglycemia / chemically induced
  • Hyperglycemia / diagnosis
  • Placebo Effect
  • Practice Guidelines as Topic / standards*
  • Randomized Controlled Trials as Topic / methods


  • Adrenergic beta-Antagonists