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Low-dose chlorthalidone is significantly better at reducing blood pressure over a 24-hour period than is the most commonly prescribed formulation of hydrochlorothiazide for essential hypertension, findings from a randomized, controlled trial published Jan. 25 suggest.
Standard HCTZ at 12.5 mg was seen reducing blood pressure during daytime or office hours, resulting in undetected or masked hypertension during nighttime and early-morning hours, investigators found.
However, both 6.25 mg chlorthalidone and an extended-release preparation of 12.5 mg HCTZ were shown to be effective at sustaining a smooth, 24-hour control as measured by ambulatory blood pressure monitoring.
For their research, Dr. Anil K. Pareek of Ipca Laboratories in Mumbai, India, and his colleagues randomized 54 patients aged 65 years and younger with stage 1 hypertension and no comorbidities to chlorthalidone, 6.25 mg (16 patients); HCTZ 12.5 mg (18); or HCTZ-controlled release 12.5 mg (20) for 12 weeks.
For the cohort as a whole, patients’ mean in-office blood pressure was 149/93 mm Hg. At both 4 and 12 weeks, all three study arms saw significant reductions in office BP (P less than .01).
However, only patients treated with chlorthalidone or HCTZ-CR saw statistically significant reductions in ambulatory diastolic and systolic blood pressure at both time points, while the standard HCTZ group did not see statistically significant changes. At 12 weeks, patients treated with chlorthalidone or HCTZ-CR achieved reductions of 11.1/7.8 mm Hg, and 10.3/8.2 mm Hg, respectively, while those in the standard HCTZ arm saw drops of 6.0/4.2 mm Hg (J Am Coll Cardiol. 2016 Jan 25;67:379-89).
Also at 12 weeks, the chlorthalidone and HCTZ-CR groups had mean nocturnal systolic pressure decreases of 10.2 and 12.7 mm/Hg, respectively, while those receiving standard HCTZ saw nighttime SBP reduced by mean 4.9 mm Hg.
Low potassium was seen in 10% (n = 2) of patients taking HCTZ-CR, 5.6% of patients on standard HCTZ, and 6.3% (n = 1) of patients on chlorthalidone.
Dr. Pareek and his colleagues noted that chlorthalidone possesses a distinct pharmacokinetic profile from HCTZ, with a higher potency that allows it to be used as monotherapy in smaller doses and has “a wider volume of distribution, with partitioning into red blood cells” that may be responsible for its longer duration of action.
Dr. Pareek and his colleagues wrote that previous studies have shown an overestimation of the response to standard HCTZ, based on office blood pressure measurements alone.
“Assessing the antihypertensive efficacy of HCTZ by [office] BP measurements only is deceptive and prone to lull physicians and patients into a false sense of security,” the researchers wrote. “With HCTZ therapy, sustained hypertension merely will be converted into masked hypertension.”
Low-dose chlorthalidone can be used as monotherapy in treating essential hypertension, Dr. Pareek and his colleagues concluded, whereas standard low-dose HCTZ should no longer be considered an acceptable option.
The investigators noted as a limitation of their study its small size.
Ipca Laboratories, a manufacturer of chlorthalidone, sponsored the study, whose lead author and two coauthors are also employees of Ipca.
Despite the overwhelming cardiovascular outcome data and established 24-hour efficacy of chlorthalidone in hypertension, prescription patterns are unchanged, with HCTZ remaining the diuretic of choice due to concerns regarding hypokalemia and greater likelihood of new-onset diabetes associated with chlorthalidone. Ambulatory blood pressure monitoring data have shown that chlorthalidone has antihypertensive effects beyond 24 hours, whereas HCTZ has antihypertensive effects for roughly 12-14 hours.
It could be argued that the superiority of chlorthalidone in cardiovascular outcome trials is not attributable to its potency, but rather its duration of action, given its extended effects on nocturnal blood pressure. As such, controlled-release HCTZ was also able to achieve comparable antihypertensive effects in terms of blood pressure reduction and duration of effect. These long-acting preparations are crucial to blood pressure control during the early morning, when one is most vulnerable to CV events.
Although this trial may appear to reflect a lower rate of side effects, specifically the absence of hyponatremia, the trial duration was short, the study was underpowered to detect this outcome, and those at highest risk, that is, people older than 65 years of age, were excluded. Only one-third of those screened were enrolled, suggesting that just a fraction of the patients seen on a daily basis would fit the focused study criteria, namely those without comorbidities and younger than 65 years. Additionally, because the study was conducted in a Southeast Asian country, it remains unclear whether the results can be extrapolated to those on Western diets or of other ethnicities.
Dr. Hillel Z. Sternlicht and Dr. George Bakris of the ASH Comprehensive Hypertension Center, University of Chicago Medicine, made these comments in an accompanying editorial (J Am Coll Cardiol. 2016 Jan 25. doi: 10.1016/j.jacc.2015.11.025). Dr. Sternlicht has reported that he has no relationships relevant to this paper. Dr. Bakris disclosed financial relationships with AbbVie, Janssen, AstraZeneca, Bayer, Takeda, NxStage, and Daiichi-Sankyo.
Despite the overwhelming cardiovascular outcome data and established 24-hour efficacy of chlorthalidone in hypertension, prescription patterns are unchanged, with HCTZ remaining the diuretic of choice due to concerns regarding hypokalemia and greater likelihood of new-onset diabetes associated with chlorthalidone. Ambulatory blood pressure monitoring data have shown that chlorthalidone has antihypertensive effects beyond 24 hours, whereas HCTZ has antihypertensive effects for roughly 12-14 hours.
It could be argued that the superiority of chlorthalidone in cardiovascular outcome trials is not attributable to its potency, but rather its duration of action, given its extended effects on nocturnal blood pressure. As such, controlled-release HCTZ was also able to achieve comparable antihypertensive effects in terms of blood pressure reduction and duration of effect. These long-acting preparations are crucial to blood pressure control during the early morning, when one is most vulnerable to CV events.
Although this trial may appear to reflect a lower rate of side effects, specifically the absence of hyponatremia, the trial duration was short, the study was underpowered to detect this outcome, and those at highest risk, that is, people older than 65 years of age, were excluded. Only one-third of those screened were enrolled, suggesting that just a fraction of the patients seen on a daily basis would fit the focused study criteria, namely those without comorbidities and younger than 65 years. Additionally, because the study was conducted in a Southeast Asian country, it remains unclear whether the results can be extrapolated to those on Western diets or of other ethnicities.
Dr. Hillel Z. Sternlicht and Dr. George Bakris of the ASH Comprehensive Hypertension Center, University of Chicago Medicine, made these comments in an accompanying editorial (J Am Coll Cardiol. 2016 Jan 25. doi: 10.1016/j.jacc.2015.11.025). Dr. Sternlicht has reported that he has no relationships relevant to this paper. Dr. Bakris disclosed financial relationships with AbbVie, Janssen, AstraZeneca, Bayer, Takeda, NxStage, and Daiichi-Sankyo.
Despite the overwhelming cardiovascular outcome data and established 24-hour efficacy of chlorthalidone in hypertension, prescription patterns are unchanged, with HCTZ remaining the diuretic of choice due to concerns regarding hypokalemia and greater likelihood of new-onset diabetes associated with chlorthalidone. Ambulatory blood pressure monitoring data have shown that chlorthalidone has antihypertensive effects beyond 24 hours, whereas HCTZ has antihypertensive effects for roughly 12-14 hours.
It could be argued that the superiority of chlorthalidone in cardiovascular outcome trials is not attributable to its potency, but rather its duration of action, given its extended effects on nocturnal blood pressure. As such, controlled-release HCTZ was also able to achieve comparable antihypertensive effects in terms of blood pressure reduction and duration of effect. These long-acting preparations are crucial to blood pressure control during the early morning, when one is most vulnerable to CV events.
Although this trial may appear to reflect a lower rate of side effects, specifically the absence of hyponatremia, the trial duration was short, the study was underpowered to detect this outcome, and those at highest risk, that is, people older than 65 years of age, were excluded. Only one-third of those screened were enrolled, suggesting that just a fraction of the patients seen on a daily basis would fit the focused study criteria, namely those without comorbidities and younger than 65 years. Additionally, because the study was conducted in a Southeast Asian country, it remains unclear whether the results can be extrapolated to those on Western diets or of other ethnicities.
Dr. Hillel Z. Sternlicht and Dr. George Bakris of the ASH Comprehensive Hypertension Center, University of Chicago Medicine, made these comments in an accompanying editorial (J Am Coll Cardiol. 2016 Jan 25. doi: 10.1016/j.jacc.2015.11.025). Dr. Sternlicht has reported that he has no relationships relevant to this paper. Dr. Bakris disclosed financial relationships with AbbVie, Janssen, AstraZeneca, Bayer, Takeda, NxStage, and Daiichi-Sankyo.
Low-dose chlorthalidone is significantly better at reducing blood pressure over a 24-hour period than is the most commonly prescribed formulation of hydrochlorothiazide for essential hypertension, findings from a randomized, controlled trial published Jan. 25 suggest.
Standard HCTZ at 12.5 mg was seen reducing blood pressure during daytime or office hours, resulting in undetected or masked hypertension during nighttime and early-morning hours, investigators found.
However, both 6.25 mg chlorthalidone and an extended-release preparation of 12.5 mg HCTZ were shown to be effective at sustaining a smooth, 24-hour control as measured by ambulatory blood pressure monitoring.
For their research, Dr. Anil K. Pareek of Ipca Laboratories in Mumbai, India, and his colleagues randomized 54 patients aged 65 years and younger with stage 1 hypertension and no comorbidities to chlorthalidone, 6.25 mg (16 patients); HCTZ 12.5 mg (18); or HCTZ-controlled release 12.5 mg (20) for 12 weeks.
For the cohort as a whole, patients’ mean in-office blood pressure was 149/93 mm Hg. At both 4 and 12 weeks, all three study arms saw significant reductions in office BP (P less than .01).
However, only patients treated with chlorthalidone or HCTZ-CR saw statistically significant reductions in ambulatory diastolic and systolic blood pressure at both time points, while the standard HCTZ group did not see statistically significant changes. At 12 weeks, patients treated with chlorthalidone or HCTZ-CR achieved reductions of 11.1/7.8 mm Hg, and 10.3/8.2 mm Hg, respectively, while those in the standard HCTZ arm saw drops of 6.0/4.2 mm Hg (J Am Coll Cardiol. 2016 Jan 25;67:379-89).
Also at 12 weeks, the chlorthalidone and HCTZ-CR groups had mean nocturnal systolic pressure decreases of 10.2 and 12.7 mm/Hg, respectively, while those receiving standard HCTZ saw nighttime SBP reduced by mean 4.9 mm Hg.
Low potassium was seen in 10% (n = 2) of patients taking HCTZ-CR, 5.6% of patients on standard HCTZ, and 6.3% (n = 1) of patients on chlorthalidone.
Dr. Pareek and his colleagues noted that chlorthalidone possesses a distinct pharmacokinetic profile from HCTZ, with a higher potency that allows it to be used as monotherapy in smaller doses and has “a wider volume of distribution, with partitioning into red blood cells” that may be responsible for its longer duration of action.
Dr. Pareek and his colleagues wrote that previous studies have shown an overestimation of the response to standard HCTZ, based on office blood pressure measurements alone.
“Assessing the antihypertensive efficacy of HCTZ by [office] BP measurements only is deceptive and prone to lull physicians and patients into a false sense of security,” the researchers wrote. “With HCTZ therapy, sustained hypertension merely will be converted into masked hypertension.”
Low-dose chlorthalidone can be used as monotherapy in treating essential hypertension, Dr. Pareek and his colleagues concluded, whereas standard low-dose HCTZ should no longer be considered an acceptable option.
The investigators noted as a limitation of their study its small size.
Ipca Laboratories, a manufacturer of chlorthalidone, sponsored the study, whose lead author and two coauthors are also employees of Ipca.
Low-dose chlorthalidone is significantly better at reducing blood pressure over a 24-hour period than is the most commonly prescribed formulation of hydrochlorothiazide for essential hypertension, findings from a randomized, controlled trial published Jan. 25 suggest.
Standard HCTZ at 12.5 mg was seen reducing blood pressure during daytime or office hours, resulting in undetected or masked hypertension during nighttime and early-morning hours, investigators found.
However, both 6.25 mg chlorthalidone and an extended-release preparation of 12.5 mg HCTZ were shown to be effective at sustaining a smooth, 24-hour control as measured by ambulatory blood pressure monitoring.
For their research, Dr. Anil K. Pareek of Ipca Laboratories in Mumbai, India, and his colleagues randomized 54 patients aged 65 years and younger with stage 1 hypertension and no comorbidities to chlorthalidone, 6.25 mg (16 patients); HCTZ 12.5 mg (18); or HCTZ-controlled release 12.5 mg (20) for 12 weeks.
For the cohort as a whole, patients’ mean in-office blood pressure was 149/93 mm Hg. At both 4 and 12 weeks, all three study arms saw significant reductions in office BP (P less than .01).
However, only patients treated with chlorthalidone or HCTZ-CR saw statistically significant reductions in ambulatory diastolic and systolic blood pressure at both time points, while the standard HCTZ group did not see statistically significant changes. At 12 weeks, patients treated with chlorthalidone or HCTZ-CR achieved reductions of 11.1/7.8 mm Hg, and 10.3/8.2 mm Hg, respectively, while those in the standard HCTZ arm saw drops of 6.0/4.2 mm Hg (J Am Coll Cardiol. 2016 Jan 25;67:379-89).
Also at 12 weeks, the chlorthalidone and HCTZ-CR groups had mean nocturnal systolic pressure decreases of 10.2 and 12.7 mm/Hg, respectively, while those receiving standard HCTZ saw nighttime SBP reduced by mean 4.9 mm Hg.
Low potassium was seen in 10% (n = 2) of patients taking HCTZ-CR, 5.6% of patients on standard HCTZ, and 6.3% (n = 1) of patients on chlorthalidone.
Dr. Pareek and his colleagues noted that chlorthalidone possesses a distinct pharmacokinetic profile from HCTZ, with a higher potency that allows it to be used as monotherapy in smaller doses and has “a wider volume of distribution, with partitioning into red blood cells” that may be responsible for its longer duration of action.
Dr. Pareek and his colleagues wrote that previous studies have shown an overestimation of the response to standard HCTZ, based on office blood pressure measurements alone.
“Assessing the antihypertensive efficacy of HCTZ by [office] BP measurements only is deceptive and prone to lull physicians and patients into a false sense of security,” the researchers wrote. “With HCTZ therapy, sustained hypertension merely will be converted into masked hypertension.”
Low-dose chlorthalidone can be used as monotherapy in treating essential hypertension, Dr. Pareek and his colleagues concluded, whereas standard low-dose HCTZ should no longer be considered an acceptable option.
The investigators noted as a limitation of their study its small size.
Ipca Laboratories, a manufacturer of chlorthalidone, sponsored the study, whose lead author and two coauthors are also employees of Ipca.
FROM JACC
Key clinical point: Standard HCTZ 12.5 mg did not significantly lower blood pressure over 24 hours, while 6.25 mg chlorthalidone and 12.5 mg controlled-release HCTZ did.
Major finding: At 12 weeks, patients treated with chlorthalidone or HCTZ-CR achieved reductions of 11.1/7.8 mm Hg and 10.3/8.2 mm Hg (P less than .01 for both), respectively, while those in the standard HCTZ arm saw drops of 6.0/4.2 mm Hg.
Data source: A randomized, double-blind, comparative study enrolling 54 patients with stage 1 hypertension. Patients were randomized to receive chlorthalidone 6.25 mg, HCTZ-CR 12.5 mg, or conventional HCTZ 12.5 mg and were followed up at 4 and 12 weeks with ambulatory and in-office BP monitoring.
Disclosures: The study was sponsored by a manufacturer of chlorthalidone, with lead author and two coauthors who are company employees.
