Illness in returned travelers.


TO THE EDITOR: Dhalla and colleagues’ (1) retrospective observational cohort study among older adults comparing chlorthalidone recipients with hydrochlorothiazide (HCTZ) recipients departs methodologically from other studies of antihypertensive drugs and health outcomes. First, there was no standardization in diagnosing cardiovascular events (CVEs). Second, the median follow-up for chlorthalidone recipients was only 255 days (8.4 months). The difference in CVEs between the 2 drugs does not manifest until about 9 months (Figure 1), implying that one half of the effect of chlorthalidone is not reflected in the hazard ratio (HR). Third, the analysis incorporated total mortality into the primary outcome, something not generally done because these medications have no effect on noncardiovascular deaths. These problems bias the HR toward 1.00 (that is, toward finding no difference in health outcomes between the 2 medications). Despite these factors, the HR from Dhalla and associates’ article is 0.93, not different statistically from the HR of 0.79 (95% CI, 0.68 to 0.92) from another retrospective observational cohort study that avoids these methodological problems (2). Pooling these 2 HRs gives an HR of 0.87 (CI, 0.78 to 0.96; P 0.005), an underestimate of the true benefit of chlorthalidone relative to HCTZ. Among chlorthalidone recipients and HCTZ recipients in Dhalla and coworkers’ study, what are the HRs (95% CIs) for hospitalization for CVEs in those who became hypokalemic versus those with sustained normokalemia? An analysis of ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial), the largest hypertension trial available with approximately 9000 chlorthalidone recipients, concludes, “Thus, for most patients, concerns about potassium levels should not influence clinician’s decision about initiating hypertension treatment with low-moderate doses of thiazide diuretics (12.5–25.0 mg of chlorthalidone)” (3). Dhalla and colleagues state incorrectly that our peer-reviewed network analysis (4) is “conflicting” with the network analysis presented by Psaty and colleagues (5) in their letter to the editor and that the latter analysis “compared chlorthalidone and hydrochlorothiazide.” Per the title of their letter—“Meta-analysis of Health Outcomes of Chlorthalidone-Based vs Nonchlorthalidone-Based Low-Dose Diuretic Therapies”—Psaty and associates compared chlorthalidone-based diuretics with non–chlorthalidone-based diuretics and used just 3 trials for the nonchlorthalidone side of the network: indapamide, HCTZ plus amiloride, and HCTZ plus triamterene. Also, Psaty and coworkers did not include ALLHAT, the ACCOMPLISH (Avoiding Cardiovascular Events Through Combination Therapy in Patients Living With Systolic Hypertension) trial, ANBP2 (Second Australian National Blood Pressure Study), and the HDFP (Hypertension Detection and Follow-up Program) study, 4 large trials strongly favoring chlorthalidone over HCTZ in network analysis (4).

DOI: 10.7326/0003-4819-158-12-201306180-00020

Cite this paper

@article{Blanc2013IllnessIR, title={Illness in returned travelers.}, author={Paul David Blanc}, journal={Annals of internal medicine}, year={2013}, volume={158 12}, pages={924} }