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Clinician Article

Association between antihypertensive treatment and adverse events: systematic review and meta-analysis.



  • Albasri A
  • Hattle M
  • Koshiaris C
  • Dunnigan A
  • Paxton B
  • Fox SE, et al.
BMJ. 2021 Feb 10;372:n189. doi: 10.1136/bmj.n189. (Review)
PMID: 33568342
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Disciplines
  • Endocrine
    Relevance - 7/7
    Newsworthiness - 6/7
  • Nephrology
    Relevance - 7/7
    Newsworthiness - 5/7
  • Family Medicine (FM)/General Practice (GP)
    Relevance - 6/7
    Newsworthiness - 5/7
  • General Internal Medicine-Primary Care(US)
    Relevance - 6/7
    Newsworthiness - 5/7
  • Cardiology
    Relevance - 5/7
    Newsworthiness - 5/7
  • Internal Medicine
    Relevance - 5/7
    Newsworthiness - 4/7

Abstract

OBJECTIVE: To examine the association between antihypertensive treatment and specific adverse events.

DESIGN: Systematic review and meta-analysis.

ELIGIBILITY CRITERIA: Randomised controlled trials of adults receiving antihypertensives compared with placebo or no treatment, more antihypertensive drugs compared with fewer antihypertensive drugs, or higher blood pressure targets compared with lower targets. To avoid small early phase trials, studies were required to have at least 650 patient years of follow-up.

INFORMATION SOURCES: Searches were conducted in Embase, Medline, CENTRAL, and the Science Citation Index databases from inception until 14 April 2020.

MAIN OUTCOME MEASURES: The primary outcome was falls during trial follow-up. Secondary outcomes were acute kidney injury, fractures, gout, hyperkalaemia, hypokalaemia, hypotension, and syncope. Additional outcomes related to death and major cardiovascular events were extracted. Risk of bias was assessed using the Cochrane risk of bias tool, and random effects meta-analysis was used to pool rate ratios, odds ratios, and hazard ratios across studies, allowing for between study heterogeneity (t2).

RESULTS: Of 15 023 articles screened for inclusion, 58 randomised controlled trials were identified, including 280 638 participants followed up for a median of 3 (interquartile range 2-4) years. Most of the trials (n=40, 69%) had a low risk of bias. Among seven trials reporting data for falls, no evidence was found of an association with antihypertensive treatment (summary risk ratio 1.05, 95% confidence interval 0.89 to 1.24, t2=0.009). Antihypertensives were associated with an increased risk of acute kidney injury (1.18, 95% confidence interval 1.01 to 1.39, t2=0.037, n=15), hyperkalaemia (1.89, 1.56 to 2.30, t2=0.122, n=26), hypotension (1.97, 1.67 to 2.32, t2=0.132, n=35), and syncope (1.28, 1.03 to 1.59, t2=0.050, n=16). The heterogeneity between studies assessing acute kidney injury and hyperkalaemia events was reduced when focusing on drugs that affect the renin angiotensin-aldosterone system. Results were robust to sensitivity analyses focusing on adverse events leading to withdrawal from each trial. Antihypertensive treatment was associated with a reduced risk of all cause mortality, cardiovascular death, and stroke, but not of myocardial infarction.

CONCLUSIONS: This meta-analysis found no evidence to suggest that antihypertensive treatment is associated with falls but found evidence of an association with mild (hyperkalaemia, hypotension) and severe adverse events (acute kidney injury, syncope). These data could be used to inform shared decision making between doctors and patients about initiation and continuation of antihypertensive treatment, especially in patients at high risk of harm because of previous adverse events or poor renal function.

REGISTRATION: PROSPERO CRD42018116860.


Clinical Comments

Cardiology

This study may help clinicians in indicating BP reduction. That is beneficial in terms of reduction of cardiovascular events. Also it has a not negligible incidence of adverse effects.

Cardiology

I'm sometimes worried about systematic reviews and meta-analysis. Definition of outcome may have slight differences and some outcomes may be overlapping. That could be the case here. Syncope frequently is associated with a fall. How can one be sure that syncope has occurred without a fall and vice-versa? The authors use the expression fainting as a synonym of syncope, but I (as others) think it represents a different clinical manifestation.

Endocrine

Meta analysis of 58 RCT with 280638 participants indicates an association between antihypertensive treatment and adverse effects (acute kidney injury, hypekalemia, hypotension and syncope) and no association with falls and fractures. The data can help in making decisions about initiation and continuation of antihypertensive treatment.

Internal Medicine

This meta-analysis found no evidence to suggest that antihypertensive treatment is associated with falls but found evidence of an association with mild (hyperkalaemia, hypotension) and severe adverse events (acute kidney injury, syncope). These data could be used to inform shared decision making between doctors and patients about initiation and continuation of antihypertensive treatment, especially in patients at high risk of harm because of previous adverse events or poor renal function.

Nephrology

Renal physicians should read this study which looks at the potential adverse outcomes of antihypertensive medication in large populations from RCTs, specifically in the context of risks of AKI and hyperkalaemia.

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