From the Hypertension Unit, Heart Institute–InCor (E.M.K., L.F.D., D.M.A.G.), Hypertension Unit, Renal Division (L.F.D., D.M.), and Laboratory of Genetics and Molecular Medicine, Heart Institute–InCor (A.C.P., J.E.K.), University of Sao Paulo Medical School, Brazil; Division of Cardiology, Federal University of Sergipe, Brazil (J.A.S.B.-F.); Department of Clinical Research, Hospital Universitario Clementino Fraga Filho, Brazil (A.R.N.); Department of Physiological Sciences, Federal University of Espírito Santo, Brazil (J.G.M.); Division of Internal Medicine, Center for Clinical and Epidemiological Research, University Hospital (P.A.L.) and Ribeirao Preto Medical School (F.N.), University of Sao Paulo, Brazil; Department of Hypertension and Nephrology, Dante Pazzanese Institute of Cardiology, Sao Paulo, Brazil (C.A.); Division of Nephrology, Department of Medicine (M.C.B.) and Department of Cardiology (A.C.C.C.), Universidade Federal de São Paulo, Brazil; Pontificia Universidade Catolica do Rio Grande do Sul, Porto Alegre, Brazil (L.C.B.); Institute of Cardiology, University Cardiology Foundation, Porto Alegre, Brazil (I.C.); Department of Clinical Medicine, Federal University of Pernambuco, Recife, Brazil (H.C.); Department of Cardiology, Universidade Federal do Para, Belem, Brazil (E.A.S.C.); Escola Bahiana de Medicina e Saude Pública, Salvador, Brazil (G.S.F.); Division of Nephrology, Department of Internal Medicine, Botucatu Medical School, Sao Paulo State University, Brazil (R.J.S.F.); Division of Cardiology, Hospital de Clinicas de Porto Alegre, Federal University of Rio Grande do Sul, Brazil (F.D.F.); Federal University of Bahia, Salvador, Brazil (A.C.G.); Faculty of Medicine, Federal University of Goias, Goiânia, Brazil (P.C.J.); Department of Cardiology, School of Medicine, Federal University of Sao Paulo, Brazil (C.A.M.); Serviço de Cardiologia do Hospital Universitario Pedro Ernesto da Universidade do Estado do Rio de Janeiro, Brazil (M.E.M.); Department of Medicine, Ouro Preto Federal University, Brazil (R.M.N.); Hospital Universitario Antonio Pedro, Universidade Federal Fluminense, Rio de Janeiro, Brazil (A.C.N.); Department of Internal Medicine, Federal University of Minas Gerais, Belo Horizonte, Brazil (A.L.P.R.); Department of Cardiology, Federal University of Ceara, Fortaleza, Brazil (C.R.-S.); Discipline of Clinical and Experimental Pathophysiology, Rio de Janeiro State University, Brazil (A.F.S.); and Universidade Estadual de Ciencias da Saude de Alagoas, Maceio, Brazil (M.d.C.B.T.).Universidade Federal de Pernambuco
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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 mm Hg) and 24-h ambulatory (<130/80 mm Hg) 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 (≈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.