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QT prolongation refers to a delay in ventricular repolarisation, visible as an extended QT interval on an electrocardiogram (ECG). This condition can predispose patients to a rare but potentially fatal arrhythmia known as torsade de pointes (TdP), which may progress to sudden cardiac death if not promptly recognised and managed [1].
Diuretics can inadvertently increase this risk through their effect on serum electrolytes. This article explores the mechanisms, risks, and considerations for healthcare professionals when prescribing diuretics in patients at risk of QT prolongation.
What Are Diuretics?
Diuretics are medications that promote the excretion of sodium and water from the body by increasing urine output [2]. They are typically used in the management of conditions such as hypertension, congestive heart failure, cirrhosis, and nephrotic syndrome. The three main classes of diuretics include:
- Loop diuretics (e.g. furosemide, bumetanide): Act on the thick ascending limb of the loop of Henle and are potent diuretics often used in acute settings such as pulmonary oedema.
- Thiazide diuretics (e.g. hydrochlorothiazide, indapamide): Act on the distal convoluted tubule and are commonly used for long-term hypertension control.
- Potassium-sparing diuretics (e.g. spironolactone, amiloride): Work in the collecting ducts and help conserve potassium.
Each class of diuretic carries a different risk profile with respect to electrolyte imbalances that may predispose a patient to QT prolongation.
How Diuretics Affect the QT Interval
The principal mechanism through which diuretics can lead to QT prolongation is by causing disturbances in electrolytes essential for cardiac repolarisation [3][4]. The most relevant abnormalities include:
- Hypokalaemia: Low potassium levels reduce the repolarising potassium current, prolonging the action potential duration.
- Hypomagnesaemia: Magnesium acts as a co-factor for potassium uptake; its deficiency may exacerbate hypokalaemia and promote early afterdepolarisations.
- Hypocalcaemia: Although less commonly affected by diuretics, reduced calcium can influence cardiac excitability.
An analysis of a pharmacovigilance database listed furosemide among the top 40 most common drugs associated with QT interval prolongation, with 350 cases reported from 2004 to 2022. This finding underscores the need for close monitoring to prevent serious adverse events, especially in patients on chronic diuretic therapy [3].
Additional Risk Factors for QT Prolongation
Diuretics may not be the sole contributor to QT prolongation. Other patient-specific and pharmacological factors can synergistically increase risk:
- Bradycardia, which prolongs the repolarisation phase [4].
- Congenital long QT syndrome, a genetic predisposition to prolonged repolarisation [4].
- Structural or functional heart disease, including myocardial infarction and cardiomyopathy [4].
- Concomitant use of QT-prolonging drugs such as macrolides (e.g. azithromycin), fluoroquinolones (e.g. ciprofloxacin), antipsychotics (e.g. haloperidol), and antiarrhythmics (e.g. amiodarone) [3].
When combined with electrolyte disturbances, these factors significantly heighten the likelihood of TdP [4].
Clinical Consequences of Using Diuretics in At-Risk Populations
Patients with pre-existing cardiovascular disease, elderly individuals, and those with renal impairment are particularly vulnerable [5]. Clinical consequences include:
- Torsade de pointes, which can degenerate into ventricular fibrillation.
- Sudden cardiac death, particularly in outpatient or poorly monitored settings.
- Exacerbation of existing medical conditions (e.g. congenital long QT syndrome, heart failure) where electrolyte shifts can further increase arrhythmic risk.
These serious adverse outcomes not only compromise patient safety but also increase healthcare utilisation and cost.
How Clinical Decision Solutions Enhances Safety
MIMS Clinical Decision Solutions (CDS) offers prescribers robust safety nets in the form of:
Drug Interaction Alert Module
This tool flags clinically significant interactions between diuretics and QT-prolonging agents. It provides context-sensitive recommendations such as:
- Avoiding high-risk combinations
- Monitoring ECG intervals
- Recommendations for electrolyte corrections
Drug Health Alert Module
This module identifies patient-specific risk factors (e.g. electrolyte abnormalities, bradycardia, renal impairment) and correlates them with the prescribed drug regimen. Key features include recommendations such as:
- Monitoring ECG intervals
- Monitoring and correcting serum electrolytes (e.g. potassium, magnesium, calcium)
- Avoiding certain medications in at-risk patient groups
When used together, these modules empower clinicians to make evidence-informed, patient-specific prescribing decisions, reducing preventable harm.
Conclusion
Diuretics remain a cornerstone in the management of cardiovascular and renal conditions. However, when used in high-risk patients or in combination with other QT-prolonging agents, they require cautious prescribing and monitoring.
MIMS CDS supports prescribers in delivering safer, smarter prescribing through integrated alerts that address both drug interactions and individual patient risk factors—bridging the gap between best practice and practical implementation at the point of care.
References
- Cohagan B, Brandis D. Torsade de Pointes. [Updated 2023 Aug 8]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan. See more
- Arumugham VB, Shahin MH. Therapeutic Uses of Diuretic Agents. [Updated 2023 May 29]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan. See more
- Tan H, Yan X, Chen Y et al. A real-world pharmacovigilance study of drug-induced QT interval prolongation: analysis of spontaneous reports submitted to FAERS. Front Cardiovasc Med. 2024 May 13;11:1363382. See more
- Trinkley KE, Page RL 2nd, Lien H et al. QT interval prolongation and the risk of torsades de pointes: essentials for clinicians. Curr Med Res Opin. 2013 Dec;29(12):1719-26. See more
- Tisdale JE. Drug-induced QT interval prolongation and torsades de pointes: Role of the pharmacist in risk assessment, prevention and management. Can Pharm J (Ott). 2016 May;149(3):139-52. See more