RESUMEN
BACKGROUND: Prior unblinded studies have suggested that catheter-based renal-artery denervation reduces blood pressure in patients with resistant hypertension. METHODS: We designed a prospective, single-blind, randomized, sham-controlled trial. Patients with severe resistant hypertension were randomly assigned in a 2:1 ratio to undergo renal denervation or a sham procedure. Before randomization, patients were receiving a stable antihypertensive regimen involving maximally tolerated doses of at least three drugs, including a diuretic. The primary efficacy end point was the change in office systolic blood pressure at 6 months; a secondary efficacy end point was the change in mean 24-hour ambulatory systolic blood pressure. The primary safety end point was a composite of death, end-stage renal disease, embolic events resulting in end-organ damage, renovascular complications, or hypertensive crisis at 1 month or new renal-artery stenosis of more than 70% at 6 months. RESULTS: A total of 535 patients underwent randomization. The mean (±SD) change in systolic blood pressure at 6 months was -14.13±23.93 mm Hg in the denervation group as compared with -11.74±25.94 mm Hg in the sham-procedure group (P<0.001 for both comparisons of the change from baseline), for a difference of -2.39 mm Hg (95% confidence interval [CI], -6.89 to 2.12; P=0.26 for superiority with a margin of 5 mm Hg). The change in 24-hour ambulatory systolic blood pressure was -6.75±15.11 mm Hg in the denervation group and -4.79±17.25 mm Hg in the sham-procedure group, for a difference of -1.96 mm Hg (95% CI, -4.97 to 1.06; P=0.98 for superiority with a margin of 2 mm Hg). There were no significant differences in safety between the two groups. CONCLUSIONS: This blinded trial did not show a significant reduction of systolic blood pressure in patients with resistant hypertension 6 months after renal-artery denervation as compared with a sham control. (Funded by Medtronic; SYMPLICITY HTN-3 ClinicalTrials.gov number, NCT01418261.).
Asunto(s)
Desnervación , Hipertensión/cirugía , Arteria Renal/cirugía , Anciano , Presión Sanguínea , Femenino , Humanos , Análisis de Intención de Tratar , Masculino , Persona de Mediana Edad , Placebos , Radiografía , Arteria Renal/diagnóstico por imagen , Arteria Renal/inervación , Método Simple Ciego , Insuficiencia del TratamientoRESUMEN
IMPORTANCE: The current recommendation is for at least 12 months of dual antiplatelet therapy after implantation of a drug-eluting stent. However, the optimal duration of dual antiplatelet therapy with specific types of drug-eluting stents remains unknown. OBJECTIVE: To assess the clinical noninferiority of 3 months (short-term) vs 12 months (long-term) of dual antiplatelet therapy in patients undergoing percutaneous coronary intervention (PCI) with zotarolimus-eluting stents. DESIGN, SETTING, AND PATIENTS: The OPTIMIZE trial was an open-label, active-controlled, 1:1 randomized noninferiority study including 3119 patients in 33 sites in Brazil between April 2010 and March 2012. Clinical follow-up was performed at 1, 3, 6, and 12 months. Eligible patients were those with stable coronary artery disease or history of low-risk acute coronary syndrome (ACS) undergoing PCI with zotarolimus-eluting stents. INTERVENTIONS: After PCI with zotarolimus-eluting stents, patients were prescribed aspirin (100-200 mg daily) and clopidogrel (75 mg daily) for 3 months (n = 1563) or 12 months (n = 1556), unless contraindicated because of occurrence of an end point. MAIN OUTCOMES AND MEASURES: The primary end point was net adverse clinical and cerebral events (NACCE; a composite of all-cause death, myocardial infarction [MI], stroke, or major bleeding); the expected event rate at 1 year was 9%, with a noninferiority margin of 2.7%. Secondary end points were major adverse cardiac events (MACE; a composite of all-cause death, MI, emergent coronary artery bypass graft surgery, or target lesion revascularization) and Academic Research Consortium definite or probable stent thrombosis. RESULTS: NACCE occurred in 93 patients receiving short-term and 90 patients receiving long-term therapy (6.0% vs 5.8%, respectively; risk difference, 0.17 [95% CI, -1.52 to 1.86]; P = .002 for noninferiority). Kaplan-Meier estimates demonstrated MACE rates at 1 year of 8.3% (128) in the short-term group and 7.4% (114) in the long-term group (HR, 1.12 [95% CI, 0.87-1.45]). Between 91 and 360 days, no statistically significant association was observed for NACCE (39 [2.6%] vs 38 [2.6%] for the short- and long-term groups, respectively; HR, 1.03 [95% CI, 0.66-1.60]), MACE (78 [5.3%] vs 64 [4.3%]; HR, 1.22 [95% CI, 0.88-1.70]), or stent thrombosis (4 [0.3%] vs 1 [0.1%]; HR, 3.97 [95% CI, 0.44-35.49]). CONCLUSIONS AND RELEVANCE: In patients with stable coronary artery disease or low-risk ACS treated with zotarolimus-eluting stents, 3 months of dual antiplatelet therapy was noninferior to 12 months for NACCE, without significantly increasing the risk of stent thrombosis. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01113372.
Asunto(s)
Síndrome Coronario Agudo/terapia , Aspirina/administración & dosificación , Enfermedad de la Arteria Coronaria/terapia , Stents Liberadores de Fármacos , Inhibidores de Agregación Plaquetaria/administración & dosificación , Ticlopidina/análogos & derivados , Anciano , Aspirina/efectos adversos , Clopidogrel , Esquema de Medicación , Quimioterapia Combinada , Femenino , Hemorragia , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio , Inhibidores de Agregación Plaquetaria/efectos adversos , Riesgo , Sirolimus/administración & dosificación , Sirolimus/análogos & derivados , Accidente Cerebrovascular , Trombosis , Ticlopidina/administración & dosificación , Ticlopidina/efectos adversosRESUMEN
The current recommendation is for at least 12 months of dual antiplatelettherapy after implantation of a drug-eluting stent. However, the optimal duration of dualantiplatelet therapy with specific types of drug-eluting stents remains unknown.OBJECTIVE To assess the clinical noninferiority of 3 months (short-term) vs 12 months(long-term) of dual antiplatelet therapy in patients undergoing percutaneous coronaryintervention (PCI) with zotarolimus-eluting stents.DESIGN, SETTING, AND PATIENTS The OPTIMIZE trialwas an open-label, active-controlled, 1:1randomized noninferiority study including 3119 patients in 33 sites in Brazil between April2010 and March 2012. Clinical follow-up was performed at 1, 3, 6, and 12 months. Eligiblepatients were those with stable coronary artery disease or history of low-risk acute coronarysyndrome (ACS) undergoing PCI with zotarolimus-eluting stents.INTERVENTIONS After PCI with zotarolimus-eluting stents, patients were prescribed aspirin(100-200mg daily) and clopidogrel (75mg daily) for 3 months (n = 1563) or 12 months(n = 1556), unless contraindicated because of occurrence of an end point.MAIN OUTCOMES AND MEASURES The primary end pointwas net adverse clinical and cerebralevents (NACCE; a composite of all-cause death, myocardial infarction [MI], stroke, or majorbleeding); the expected event rate at 1 year was 9%, with a noninferiority margin of 2.7%.Secondary end points were major adverse cardiac events (MACE; a composite of all-causedeath, MI, emergent coronary artery bypass graft surgery, or target lesion revascularization)and Academic Research Consortium definite or probable stent thrombosis.RESULTS NACCE occurred in 93 patients receiving short-term and 90 patients receivinglong-term therapy...