Race-Specific Comparisons of Antihypertensive and Metabolic Effects of Hydrochlorothiazide and Chlorthalidone

Pairwise comparison of hydrochlorothiazide and chlorthalidone responses among hypertensive patients

“…These paired data also suggest that while CTD is numerically better at BP lowering in both EA patients and AA patients, the relevance of this might be much less in AA patients as the majority of AA patients achieved a BP target of 140/90 mmHg with both drugs, whereas potassium risk is consistently higher with CTD. As in our larger unpaired analysis, 17 these data suggest TZD initiation with CTD in EA patients seems appropriate, regardless of BP target, whereas use of HCTZ as the first TZD in AA patients may be a safer approach if the BP target is <140/90 mmHg. Neither drug was highly effective at achieving a BP target <130/80 mmHg, thus the numerically greater BP lowering with CTD may make it the more appropriate choice in all patients with a lower BP target.…”

“…Considering that BP lowering and adverse safety profile are immediate drivers of therapy selection in HTN management in clinics, it is important to accurately compare the two drugs for their efficacy and safety without the confounding factors of race and interindividual variability. We have previously published race‐specific comparisons of HCTZ and CTD 17 from a large cohort suggesting that although CTD as preferred TZD is reasonable in EA patients, it may be less appropriate in AA patients, due to similar achievement of BP targets with the two drugs and greater adverse effects with CTD. However, population data mask the interpatient variability and, here, we report data on 50 patients who took both drugs, to provide additional guidance to clinicians on selection of TZD in individual patients.…”

“…Higher potency and its PK properties are also attributed to higher rate of adverse effects with CTD, although some argue that the effects are not clinically relevant at low doses. Considering the significant differences in the dose–response relationship 16 of the two drugs, and the confounding effect of interindividual differences in response to various antihypertensive drugs, 17 , 18 it is imperative to compare them at the commonly used equal milligram doses and in the same patients for an accurate estimate of the relative efficacy/safety of the two drugs. While the interindividual differences in response to different classes of antihypertensive drugs is well‐established, variation within a drug class is not well studied.…”

“…We compared the antihypertensive and metabolic responses of 50 patients with HTN from the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) clinical trial upon treatment with HCTZ and responses to CTD in the PEAR‐2 clinical trial. We separated the analysis by genetically defined ancestry into European American (EA) and African American (AA) patients using principal component analysis on the genomewide genotype data from the subjects, because our previous work 17 identified differences in the relative efficacies of the drugs between AA patients and EA patients.…”

Initial combination therapy for hypertension in patients of African ancestry: a systematic review and meta-analysis

“…CTD has been recommended over HCT because of presumed greater efficacy with fewer adverse outcomes [63,64], but no direct comparison is available [11][12][13][14][15] (Table S3.A, Supplemental Digital Content, http://links.lww.com/HJH/B829). Moreover, recent retrospective comparisons suggest that HCT is more effective and has less adverse effects than CTD [64,65]. The ongoing Veterans Affairs (VA) Diuretic Comparison Project is expected to provide more data [66].…”