ABSTRACT
ABSTRACT: 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.
Subject(s)
Spironolactone , Clonidine , Drug Therapy , HypertensionABSTRACT
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.
Subject(s)
Blood Pressure/drug effects , Clonidine , Hypertension , Spironolactone , Adult , Aged , Antihypertensive Agents/administration & dosage , Antihypertensive Agents/adverse effects , Antihypertensive Agents/classification , Blood Pressure Monitoring, Ambulatory/methods , Clonidine/administration & dosage , Clonidine/adverse effects , Drug Monitoring/methods , Drug Resistance , Drug Therapy, Combination/methods , Female , Humans , Hypertension/diagnosis , Hypertension/drug therapy , Hypertension/physiopathology , Male , Medication Adherence , Middle Aged , Spironolactone/administration & dosage , Spironolactone/adverse effects , Treatment OutcomeABSTRACT
INTRODUCTION AND OBJECTIVES: Chagas disease is a prevalent cause of heart failure in Latin America, and its prognosis is worse than other etiologies. The Heart Failure Survival Score has been used to assess prognosis in patients with heart failure; however, this score has not yet been studied in patients with Chagas cardiopathy. METHODS: The Heart Failure Survival Score was calculated in 55 patients with severe left ventricular systolic dysfunction due to Chagas disease. Correlations were assessed between the Heart Failure Survival Score and variables obtained from, cardiopulmonary exercise tests, quality-of-life measures, and 6-minute walking tests. RESULTS: Patients were distributed among New York Heart Association classes II-IV; 89% were taking angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, 62% were taking beta-blockers, 86% were taking diuretics, and 74% were taking aldosterone receptor blockers. The mean Heart Failure Survival Score was 8.75 (0.80). The score correlated well with cardiopulmonary test variables such as peak oxygen uptake (0.662; P<.01), oxygen uptake at the anaerobic threshold (0.644; P<.01), ventilation carbon dioxide efficiency slope (-0.417; P<.01), oxygen pulse (0.375; P<.01), oxygen uptake efficiency slope (0.626; P<.01), 6-minute walking test (0.370; P<.01), left ventricle ejection fraction (0.650; P=.01), and left atrium diameter (-0.377; P<.01). There was also a borderline significant correlation between the Heart Failure Survival Score and quality of life (-0.283; P<.05). CONCLUSIONS: In heart failure patients with Chagas disease, the Heart Failure Survival Score correlated well with the main prognostic functional test variables.
Subject(s)
Chagas Cardiomyopathy/mortality , Heart Failure/mortality , Ventricular Dysfunction, Left/mortality , Adrenergic beta-Antagonists/therapeutic use , Adult , Aged , Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Chagas Cardiomyopathy/complications , Chagas Cardiomyopathy/physiopathology , Echocardiography , Exercise Test/methods , Female , Heart Failure/drug therapy , Heart Failure/etiology , Heart Failure/physiopathology , Humans , Male , Middle Aged , Quality of Life , Survival Analysis , Ventricular Dysfunction, Left/drug therapy , Ventricular Dysfunction, Left/etiology , Ventricular Dysfunction, Left/physiopathology , Young AdultABSTRACT
OBJECTIVE: To evaluate early effects of bone marrow cell transplantation to the myocardium of patients with heart failure (CHF) due to Chagas disease. METHODS: We studied 28 patients (mean age 52.2 +/- 9.9), of whom 24 were male. Despite optimized treatment, 25 patients were in NYHA class III and three patients, in NYHA class IV. The procedure consisted of aspiration of 50 mL of bone marrow, separation of the mononuclear fraction, and intracoronary injection. Effects on left ventricle ejection fraction (LVEF), distance walked in the six-minute walking test, quality-of-life, NYHA class, arrhythmogenic and biochemical parameters, were all evaluated. RESULTS: There were no complications directly related to the procedure. Baseline left ventricular ejection fraction was 20.1 +/- 6.8%, and 60 days after transplantation it increased to 23.0 +/- 9.0%, p = 0.02. Significant improvements were observed in the NYHA class (3.1 +/- 0.3 to 1.8 +/- 0.5; p < 0.0001); quality-of-life (50.9 +/- 11.7 to 21.8 +/- 13.4; p < 0.0001); and distance walked in six minutes (355 +/- 136 m to 443 +/- 110 m; p = 0,003). The number of ventricular premature beats in 24 hours tended to increase (5,322 +/- 4,977 to 7,441 +/- 7,955; p = 0,062), but without increase in ventricular tachycardia episodes (61 +/- 127 to 54 +/- 127; p = 0.27). CONCLUSION: Our data demonstrate for the first time that intracoronary injection of bone marrow mononuclear cells is feasible and suggest that it may be potentially safe and effective in patients with CHF due to Chagas disease.
Subject(s)
Bone Marrow Transplantation/standards , Cardiac Output, Low/surgery , Chagas Cardiomyopathy/surgery , Adult , Aged , Cardiac Output, Low/etiology , Chagas Cardiomyopathy/complications , Chronic Disease , Female , Follow-Up Studies , Humans , Male , Middle Aged , Sodium/analysis , Stem Cell Transplantation/standards , Stem Cells/cytology , Treatment OutcomeABSTRACT
OBJETIVO: Avaliar efeitos precoces do transplante de células de medula óssea para o miocárdio de pacientes com insuficiência cardíaca (IC) de etiologia chagásica. MÉTODOS: A amostra consistiu de 28 pacientes, idade média 52,2±9,9 anos, 24 masculinos, 25 em classe NYHA III e 3 em NYHA IV, apesar de tratamento otimizado. O procedimento consistiu na aspiração de 50ml de medula óssea, separação da fração mononuclear e injeção intracoronariana. Foram avaliados os efeitos sobre a fração de ejeção ventricular esquerda (FEVE), distância no teste de 6 minutos, qualidade de vida, classe NYHA, efeitos arritmogênicos e bioquímicos. RESULTADOS: Não houve complicações relacionadas diretamente ao procedimento. A fração de ejeção ventricular esquerda em repouso antes do transplante era 20,1±6,8 por cento e, após 60 dias, aumentou para 23,0±9,0 por cento, p = 0,02. Houve melhora da classe NYHA (3,1±0,3 para 1,8±0,5; p<0.0001); qualidade de vida (50,9±11,7 para 21,8±13,4; p<0.0001); distância caminhada (355±136 m para 443±110 m; p = 0,003). O número de extrassístoles ventriculares em 24h apresentou tendência à elevação (5.322±4.977 para 7.441±7.955; p = 0,062), porém sem incremento dos episódios de taquicardia ventricular (61±127 para 54±127; p = 0,27). CONCLUSÃO: Nossos dados demonstram que a injeção intracoro¡nariana de células mononucleares da medula óssea é exeqüível e sugere ser potencialmente segura e eficaz em pacientes com IC de etiologia chagásica.
