Effect of adrenergic agonist oral decongestants on blood pressure.

Abstract

Background: Adrenergic agonist oral decongestants are commonly taken daily over long periods of time to relieve sinus and nasal congestion. The mechanism of action of decongestants potentially increases blood pressure, and these effects may be acute or chronic. However, no systematic reviews to date have comprehensively assessed the chronic blood pressure effects of adrenergic agonist oral decongestants as a drug class, despite their widespread non-prescription availability.

Objectives: Primary objective To assess the effects of adrenergic agonist oral decongestants on systolic and diastolic blood pressure compared to placebo. Secondary objective To assess the effects of adrenergic agonist oral decongestants on heart rate and withdrawals due to adverse effects.

Search methods: The Cochrane Hypertension Information Specialist searched the following databases for randomized controlled trials (RCT) up to July 2024: Cochrane Hypertension Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL) via Cochrane Register of Studies, Ovid MEDLINE, Ovid Embase, and ClinicalTrials.gov. There were no language, publication year, or publication status restrictions.

Selection criteria: We included RCTs of at least seven days' duration with parallel groups (intervention and placebo) comparing adrenergic agonist oral decongestants versus placebo on blood pressure in people aged over six years.

Data collection and analysis: Two review authors (JJC and MC) independently assessed the trials for inclusion, extracted the data, and assessed the risk of bias from the included trials. In cases where there were disagreements, the third review author (JMW) adjudicated. For any missing or unclear information in the studies, we contacted the study author to request the missing information or seek clarification. The primary outcomes were systolic blood pressure and diastolic blood pressure. Secondary outcomes were heart rate and withdrawal due to adverse effects. We used a fixed-effect model to combine the effect sizes from all studies. We assessed the certainty of the evidence using GRADE.

Main results: Five RCTs randomizing 882 participants met the inclusion criteria. The shortest study duration was one week, and the longest study duration was 24 weeks. These studies measured blood pressure and heart rate after one to seven weeks of taking oral decongestants. The largest study included 568 people, and the smallest study included 18 people. The mean age of participants was 20.0 years, with 326 males and 591 females. The studies were conducted in the USA and Europe; most were set in the USA. Pharmaceutical companies funded three of the five included studies. The findings are relevant to all people using adrenergic agonist oral decongestants for seven days or longer regardless of comorbidities or pre-existing conditions. The adrenergic agonist oral decongestants included were ephedrine (one RCT), pseudoephedrine (one RCT), and phenylpropanolamine (three RCTs). Compared to placebo, adrenergic agonist oral decongestants may have little to no effect on systolic blood pressure, but the evidence is very uncertain (mean difference [MD] 0.91 mmHg, 95% confidence interval [CI] -0.57 to 2.38; 4 RCTs, 784 participants; I² = 54%; very low-certainty evidence). Adrenergic agonist oral decongestants may have little to no effect on diastolic blood pressure (MD 0.44 mmHg, 95% CI -0.59 to 1.48; 5 RCTs, 882 participants; I² = 30%; low-certainty evidence). Adrenergic agonist oral decongestants may have little to no effect on heart rate, but the evidence is very uncertain (MD 1.92 beats per minute, 95% CI -0.62 to 4.47; 2 RCTs, 190 participants; I² = 79%; very low-certainty evidence). Adrenergic agonist oral decongestants may have little to no effect on the number of withdrawals due to adverse effects (risk ratio [RR] 1.20, 95% CI 0.37 to 3.88; 4 RCTs, 806 participants; low-certainty evidence; note 1 study reported withdrawals due to adverse effects but recorded 0 events in both groups. Thus, the RR and CIs were calculated from 3 studies rather than 4). Four studies were at overall high risk of bias, and one study was at overall low risk of bias.

Authors' conclusions: In this systematic review, chronic daily intake of adrenergic agonist oral decongestants had little to no effect on blood pressure, heart rate, and withdrawals due to adverse effects. People making decisions about using these medicines should consider the very low certainty of evidence and the theoretical risk of increased blood pressure. Independent trials free from biases that are designed to answer this question are required. The evidence was limited due to the small number of studies, and the blood pressure and heart rate not being measured at the optimal time after drug ingestion.