João Pedro Ferreira1,2,3, David Fitchett4, Anne Pernille Ofstad5, Bettina Johanna Kraus6,7, Christoph Wanner7, Isabella Zwiener8, Bernard Zinman9, Sabine Lauer8, Jyothis T George10, Patrick Rossignol1,2,3, Faiez Zannad1,2,3. 1. Université de Lorraine, Centre d'Investigations Cliniques Plurithématique Inserm 1433, Nancy, France. 2. CHRU de Nancy, Inserm U1116, Nancy, France. 3. FCRIN INI-CRCT, Nancy, France. 4. Division of Cardiology, St Michael's Hospital, University of Toronto, Toronto, Ontario, Canada. 5. Boehringer Ingelheim Norway KS, Asker, Norway. 6. Comprehensive Heart Failure Center, University of Würzburg, Würzburg, Germany. 7. Department of Internal Medicine I, University Hospital Würzburg, Würzburg, Germany. 8. Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany. 9. Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada. 10. Boehringer Ingelheim International GmbH, Ingelheim, Germany.
Abstract
BACKGROUND: Type 2 diabetes (T2D) and resistant hypertension often coexist, greatly increasing risk of target-organ damage and death. We explored the effects of empagliflozin in patients with and without presumed resistant hypertension (prHT) in a post hoc analysis of EMPA-REG OUTCOME (NCT01131676). METHODS: Overall, 7,020 patients received empagliflozin 10, 25 mg, or placebo with median follow-up of 3.1 years. We defined baseline prHT as ≥3 classes of antihypertensive drugs including a diuretic and uncontrolled blood pressure (BP; systolic blood pressure (SBP) ≥140and/or diastolic blood pressure ≥90 mm Hg) or ≥4 classes of antihypertensive, including a diuretic, and controlled BP. We explored the effect of empagliflozin on cardiovascular (CV) death, heart failure (HF) hospitalization, 3-point major adverse cardiac events, all-cause death, and incident/worsening nephropathy by Cox regression and BP over time by a mixed-repeated-measures-model analysis. RESULTS: 1,579 (22.5%) patients had prHT. The mean difference in change in SBP from baseline to week 12 vs. placebo was -4.5 (95% confidence interval, -5.9 to -3.1) mm Hg (P < 0.001) in prHT and -3.7 (-4.5, -2.9) mm Hg (P < 0.001) in patients without prHT. SBP was more frequently controlled (<130/80 mm Hg) with empagliflozin than with placebo. Patients with prHT had 1.5- to 2-fold greater risk of HF hospitalization, incident/worsening nephropathy, and CV death compared with those without prHT. Empagliflozin improved all outcomes in patients with and without prHT (interaction P > 0.1 for all outcomes). CONCLUSIONS:Empagliflozin induced a clinically relevant reduction in SBP and consistently improved all outcomes regardless of prHT status. Due to these dual effects, empagliflozin should be considered for patients with hypertension and T2D.
RCT Entities:
BACKGROUND:Type 2 diabetes (T2D) and resistant hypertension often coexist, greatly increasing risk of target-organ damage and death. We explored the effects of empagliflozin in patients with and without presumed resistant hypertension (prHT) in a post hoc analysis of EMPA-REG OUTCOME (NCT01131676). METHODS: Overall, 7,020 patients received empagliflozin 10, 25 mg, or placebo with median follow-up of 3.1 years. We defined baseline prHT as ≥3 classes of antihypertensive drugs including a diuretic and uncontrolled blood pressure (BP; systolic blood pressure (SBP) ≥140 and/or diastolic blood pressure ≥90 mm Hg) or ≥4 classes of antihypertensive, including a diuretic, and controlled BP. We explored the effect of empagliflozin on cardiovascular (CV) death, heart failure (HF) hospitalization, 3-point major adverse cardiac events, all-cause death, and incident/worsening nephropathy by Cox regression and BP over time by a mixed-repeated-measures-model analysis. RESULTS: 1,579 (22.5%) patients had prHT. The mean difference in change in SBP from baseline to week 12 vs. placebo was -4.5 (95% confidence interval, -5.9 to -3.1) mm Hg (P < 0.001) in prHT and -3.7 (-4.5, -2.9) mm Hg (P < 0.001) in patients without prHT. SBP was more frequently controlled (<130/80 mm Hg) with empagliflozin than with placebo. Patients with prHT had 1.5- to 2-fold greater risk of HF hospitalization, incident/worsening nephropathy, and CV death compared with those without prHT. Empagliflozin improved all outcomes in patients with and without prHT (interaction P > 0.1 for all outcomes). CONCLUSIONS:Empagliflozin induced a clinically relevant reduction in SBP and consistently improved all outcomes regardless of prHT status. Due to these dual effects, empagliflozin should be considered for patients with hypertension and T2D.
Authors: João Pedro Ferreira; Subodh Verma; David Fitchett; Anne Pernille Ofstad; Sabine Lauer; Isabella Zwiener; Jyothis George; Christoph Wanner; Bernard Zinman; Silvio E Inzucchi Journal: Cardiovasc Diabetol Date: 2020-11-26 Impact factor: 9.951