Spironolactone Versus Clonidine as a Fourth-Drug Therapy for Resistant Hypertension: The ReHOT Randomized Study (Resistant Hypertension Optimal Treatment)

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Krieger, Eduardo M.
Drager, Luciano F.
Giorgi, Dante M. A.
Pereira, Alexandre C.
Soares Barreto-Filho, Jose Augusto
Nogueira, Armando R.
Mill, Jose Geraldo
Lotufo, Paulo A.
Amodeo, Celso
Batista, Marcelo C.

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Lippincott Williams & Wilkins


The aim of this study is to compare spironolactone versus clonidine as the fourth drug in patients with resistant hypertension in a multicenter, randomized trial. Medical therapy adherence was checked by pill counting. Patients with resistant hypertension (no office and ambulatory blood pressure [BP] monitoring control, despite treatment with 3 drugs, including a diuretic, for 12 weeks) were randomized to an additional 12-week treatment with spironolactone (12.5-50 mg QD) or clonidine (0.1-0.3 mg BID). The primary end point was BP control during office (<140/90 mmHg) and 24-h ambulatory (<130/80 mmHg) BP monitoring. Secondary end points included BP control from each method and absolute BP reduction. From 1597 patients recruited, 11.7% (187 patients) fulfilled the resistant hypertension criteria. Compared with the spironolactone group (n=95), the clonidine group (n=92) presented similar rates of achieving the primary end point (20.5% versus 20.8%, respectively; relative risk, 1.01 [0.55-1.88]; P=1.00). Secondary end point analysis showed similar office BP (33.3% versus 29.3%) and ambulatory BP monitoring (44% versus 46.2%) control for spironolactone and clonidine, respectively. However, spironolactone promoted greater decrease in 24-h systolic and diastolic BP and diastolic daytime ambulatory BP than clonidine. Per-protocol analysis (limited to patients with 80% adherence to spironolactone/clonidine treatment) showed similar results regarding the primary end point. In conclusion, clonidine was not superior to spironolactone in true resistant hypertensive patients, but the overall BP control was low (approximate to 21%). Considering easier posology and greater decrease in secondary end points, spironolactone is preferable for the fourth-drug therapy. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT01643434.



blood pressure, clinical trial, humans, hypertension, risk, therapeutics

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Hypertension. Philadelphia: Lippincott Williams & Wilkins, v. 71, n. 4, p. 681-690, 2018.