Antihypertensives do not induce falls, but tied to serious adverse events

Antihypertensive treatment is not associated with falls or fractures but appears to result in mild (eg, hyperkalaemia, hypotension) and severe adverse events (eg, acute kidney injury, syncope), according to a systematic review and meta-analysis. Moreover, some effects are specific to the drug class used.

“In patients at high risk of drug harms because of previous adverse events or poor renal function, these data should be used to inform shared decision making between doctors and patients around initiation and continuation of antihypertensive treatment,” the researchers said.

The databases of Embase, Medline, Central, and the Science Citation Index were searched from inception until 14 April 2020 for randomized controlled trials of adults receiving antihypertensive drugs compared with placebo or no treatment, more vs fewer antihypertensives, or higher vs lower blood pressure targets. Studies were required to have at least 650 patient-years of follow-up.

The researchers assessed risk of bias using the Cochrane risk of bias tool and pooled rate ratios (RRs), odds ratios, and hazard ratios across studies using random effects meta-analysis.

A total of 15,023 articles were identified, of which 58 met the eligibility criteria, including 280,638 participants followed for a median of 3 years. Forty trials (69 percent) had a low risk of bias. In the seven trials reporting data for falls, no evidence was found for an association between antihypertensive treatment (summary RR, 1.05, 95 percent confidence interval (CI), 0.89–1.24; τ²=0.009). [BMJ 2021;372:n189]

However, antihypertensives were found to correlate with a higher risk of acute kidney injury (RR, 1.18, 95 percent CI, 1.01–1.39; τ²=0.037; n=15), hyperkalaemia (RR, 1.89, 95 percent CI, 1.56–2.30; τ²=0.122; n=26), hypotension (RR, 1.97, 95 percent CI, 1.67–2.32; τ²=0.132; n=35), and syncope (RR, 1.28, 95 percent CI, 1.03–1.59; τ²=0.050; n=16).

When focusing on drugs that affect the renin angiotensin-aldosterone system, the heterogeneity between studies that investigated acute kidney injury and hyperkalaemia decreased. Results were robust to sensitivity analyses focusing on adverse events leading to withdrawal from each trial.

Notably, antihypertensive treatment led to a reduction in the risks of all-cause mortality, cardiovascular death, and stroke, but not myocardial infarction.

A previous meta-analysis by Thomopoulos and colleagues examining the impact of permanent antihypertensive treatment discontinuation due to adverse events showed a nearly twofold risk of adverse events (standardized RR, 1.89, 95 percent CI, 1.52–2.39). [J Hypertens 2016;34:1921-1932;  J Hypertens 2016;34:1451-1463]

“This was similar to findings from our sensitivity analyses focusing on permanent withdrawal as a result of hyperkalaemia, hypotension, and syncope events,” the researchers said. “These associations were stronger than those observed in the primary analysis focusing on all adverse event reporting.”

Of note, the findings of the current study should be ideally combined with information about an individual’s absolute risk of each harm outcome to make informed, personalized treatment decisions. Such process requires real-time data, according to the researchers.

“Further work is needed to understand better the results of this meta-analysis in the context of individualized absolute risks so that treatment initiation and discontinuation can be targeted at those with the most to gain,” they said. “In the absence of such information, doctors should focus on patients who have experienced previous adverse events or have poor renal function.” [J Hypertens 2016;34:1451-1463; JAMA 2020;323:2039-2051; J Intern Med 2003;254:548-554]