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Randomized Controlled Trial
. 2017 Apr;130(4):439-448.e9.
doi: 10.1016/j.amjmed.2016.10.002. Epub 2016 Oct 27.

Treatment-Resistant Hypertension and Outcomes Based on Randomized Treatment Group in ALLHAT

Affiliations
Randomized Controlled Trial

Treatment-Resistant Hypertension and Outcomes Based on Randomized Treatment Group in ALLHAT

Sripal Bangalore et al. Am J Med. 2017 Apr.

Abstract

Background: Although hypertension guidelines define treatment-resistant hypertension as blood pressure uncontrolled by ≥3 antihypertensive medications, including a diuretic, it is unknown whether patient prognosis differs when a diuretic is included.

Methods: Participants in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) were randomly assigned to first-step therapy with chlorthalidone, amlodipine, or lisinopril. At a Year 2 follow-up visit, those with average blood pressure ≥140 mm Hg systolic or ≥90 mm Hg diastolic on ≥3 antihypertensive medications, or blood pressure <140/90 mm Hg on ≥4 antihypertensive medications were identified as having apparent treatment-resistant hypertension. The prevalence of treatment-resistant hypertension and its association with ALLHAT primary (combined fatal coronary heart disease or nonfatal myocardial infarction) and secondary (all-cause mortality, stroke, heart failure, combined coronary heart disease, and combined cardiovascular disease) outcomes were identified for each treatment group.

Results: Of participants assigned to chlorthalidone, amlodipine, or lisinopril, 9.6%, 11.4%, and 19.7%, respectively, had treatment-resistant hypertension. During mean follow-up of 2.9 years, primary outcome incidence was similar for those assigned to chlorthalidone compared with amlodipine or lisinopril (amlodipine- vs chlorthalidone-adjusted hazard ratio [HR] 0.86; 95% confidence interval [CI], 0.53-1.39; P = .53; lisinopril- vs chlorthalidone-adjusted HR = 1.06; 95% CI, 0.70-1.60; P = .78). Secondary outcome risks were similar for most comparisons except coronary revascularization, which was higher with amlodipine than with chlorthalidone (HR 1.86; 95% CI, 1.11-3.11; P = .02). An as-treated analysis based on diuretic use produced similar results.

Conclusions: In this study, which titrated medications to a goal, participants assigned to chlorthalidone were less likely to develop treatment-resistant hypertension. However, prognoses in those with treatment-resistant hypertension were similar across treatment groups.

Keywords: Angiotensin-converting enzyme inhibitor; Calcium channel blocker; Diuretics; Hypertension; Resistance.

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Conflict of interest statement

The other authors report no conflicts.

Figures

Figure 1
Figure 1
Patient flow.
Figure 2
Figure 2
Cumulative incidence of primary outcome (combined fatal coronary heart disease or nonfatal myocardial infarction) by treatment group in those with treatment resistant hypertension.

References

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