Thiazide-Induced Metabolic Adverse Events in Older Adults
Thiazide-Induced Metabolic Adverse Events in Older Adults
Objectives. To evaluate the risk and predictors of thiazide-induced adverse events (AEs) in multimorbid older adults in real-world clinical settings.
Design. Observational cohort study.
Setting. National Veterans Affairs data from 2007 to 2008.
Participants. Veterans aged 65 and older newly prescribed a thiazide (N = 1,060) compared with propensity-matched nonusers of antihypertensive medications (N = 1,060).
Measurements. The primary outcome was a composite of metabolic AEs defined as sodium less than 135 mEq/L, potassium less than 3.5 mEq/L, or a decrease in the estimated glomerular filtration rate (eGFR) of more than 25% from the baseline rate. Secondary outcomes included sev-ere AEs (sodium <130 mEq/L, potassium <3.0 mEq/L, or a decrease in eGFR of more than 50%).
Results. Over 9 months of follow-up, 14.3% of new thiazide users developed an AE, compared with 6.0% of nonusers (number needed to harm (NNH) 12, 95% confidence interval (CI) = 9–17, P < .001); 1.8% of new users developed a severe AE, compared with 0.6% of nonusers (NNH = 82, P = .008), and 3.8% of new users had an emergency department visit or hospitalization with an AE, compared with 2.0% of nonusers (NNH = 56, P = .02). Risk of AEs did not vary according to age, but having five or more comorbidities was associated with 3.0 times the odds (95% CI = 1.4–6.2) of developing an AE as having one comorbidity (hypertension). Low-normal and unmeasured baseline sodium and potassium values were among the strongest predictors of hyponatremia and hypokalemia, respectively. Only 42% of thiazide users had laboratory monitoring within 90 days after initiation.
Conclusion. Thiazide-induced AEs are common in older adults. Greater attention should be paid to potential complications in prescribing thiazides to older adults, including closer laboratory monitoring before and after initiation of thiazides.
The Seventh Report of the Joint National Committee recommends a thiazide diuretic as the preferred initial medication for the treatment of hypertension in older adults. Several randomized controlled trials with highly selected participants have shown thiazides to be relatively safe in this population, but little is known about the risk of thiazide-induced adverse events (AEs) in real-world clinical practice, where older adults who are treated may have greater comorbidity burden, complicated medical regimens, and poorer adherence to follow-up.
Hyponatremia, hypokalemia, and acute kidney injury are potential metabolic AEs due to thiazides that are associated with greater morbidity, mortality, and costs. An observational study of individuals prescribed a thiazide at one of two academic centers found that three in 10 developed hyponatremia over a 10-year interval, a 60% greater risk than with alternative antihypertensive therapy. Although this study highlights one important metabolic complication due to thiazides, a more-comprehensive metabolic risk assessment of thiazides is needed, especially for older adults, who are more likely to be at risk for medication-induced AEs.
Because other antihypertensive classes are as effective as thiazides at reducing cardiovascular events in older adults, a better understanding of the risk of thiazide-induced metabolic AEs in this population, including defining subgroups of individuals that may be at particularly high risk of complications, can help inform safer prescribing practices. However, a randomized controlled trial examining the metabolic risk of thiazides in this population is unlikely to be forthcoming. Therefore, national observational data using propensity scoring techniques were used to evaluate the risk of thiazide-induced metabolic AEs in older adults, predictors of this risk, and laboratory surveillance patterns after thiazide initiation.
Abstract and Introduction
Abstract
Objectives. To evaluate the risk and predictors of thiazide-induced adverse events (AEs) in multimorbid older adults in real-world clinical settings.
Design. Observational cohort study.
Setting. National Veterans Affairs data from 2007 to 2008.
Participants. Veterans aged 65 and older newly prescribed a thiazide (N = 1,060) compared with propensity-matched nonusers of antihypertensive medications (N = 1,060).
Measurements. The primary outcome was a composite of metabolic AEs defined as sodium less than 135 mEq/L, potassium less than 3.5 mEq/L, or a decrease in the estimated glomerular filtration rate (eGFR) of more than 25% from the baseline rate. Secondary outcomes included sev-ere AEs (sodium <130 mEq/L, potassium <3.0 mEq/L, or a decrease in eGFR of more than 50%).
Results. Over 9 months of follow-up, 14.3% of new thiazide users developed an AE, compared with 6.0% of nonusers (number needed to harm (NNH) 12, 95% confidence interval (CI) = 9–17, P < .001); 1.8% of new users developed a severe AE, compared with 0.6% of nonusers (NNH = 82, P = .008), and 3.8% of new users had an emergency department visit or hospitalization with an AE, compared with 2.0% of nonusers (NNH = 56, P = .02). Risk of AEs did not vary according to age, but having five or more comorbidities was associated with 3.0 times the odds (95% CI = 1.4–6.2) of developing an AE as having one comorbidity (hypertension). Low-normal and unmeasured baseline sodium and potassium values were among the strongest predictors of hyponatremia and hypokalemia, respectively. Only 42% of thiazide users had laboratory monitoring within 90 days after initiation.
Conclusion. Thiazide-induced AEs are common in older adults. Greater attention should be paid to potential complications in prescribing thiazides to older adults, including closer laboratory monitoring before and after initiation of thiazides.
Introduction
The Seventh Report of the Joint National Committee recommends a thiazide diuretic as the preferred initial medication for the treatment of hypertension in older adults. Several randomized controlled trials with highly selected participants have shown thiazides to be relatively safe in this population, but little is known about the risk of thiazide-induced adverse events (AEs) in real-world clinical practice, where older adults who are treated may have greater comorbidity burden, complicated medical regimens, and poorer adherence to follow-up.
Hyponatremia, hypokalemia, and acute kidney injury are potential metabolic AEs due to thiazides that are associated with greater morbidity, mortality, and costs. An observational study of individuals prescribed a thiazide at one of two academic centers found that three in 10 developed hyponatremia over a 10-year interval, a 60% greater risk than with alternative antihypertensive therapy. Although this study highlights one important metabolic complication due to thiazides, a more-comprehensive metabolic risk assessment of thiazides is needed, especially for older adults, who are more likely to be at risk for medication-induced AEs.
Because other antihypertensive classes are as effective as thiazides at reducing cardiovascular events in older adults, a better understanding of the risk of thiazide-induced metabolic AEs in this population, including defining subgroups of individuals that may be at particularly high risk of complications, can help inform safer prescribing practices. However, a randomized controlled trial examining the metabolic risk of thiazides in this population is unlikely to be forthcoming. Therefore, national observational data using propensity scoring techniques were used to evaluate the risk of thiazide-induced metabolic AEs in older adults, predictors of this risk, and laboratory surveillance patterns after thiazide initiation.
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