Effects of Bariatric Surgery in Obese Patients with Hypertension The GATEWAY Randomized Trial

Transcription

1 Effects of Bariatric Surgery in Obese Patients with Hypertension The GATEWAY Randomized Trial Carlos Aurelio Schiavon, MD, FACS On behalf of the GATEWAY Executive Committee and Investigators DISCLOSURE Study Funding: Ethicon Inc. Speaker Bureau and Honoraria: Johnson & Johnson Medical Brasil

2 BACKGROUND THE PROBLEM ~40% of the American adults are Obese (~20% - Brazil) % of hypertension in adults is attributable to adiposity. THE EVIDENCE Observational and randomized trials (mainly focused in T2DM) showed reduction or discontinuation of antihypertensive medications and overall reduction in CV events after Bariatric Surgery. However, RCT s in a broad population of hypertensive obese patients had not been conducted. A PROMISING SOLUTION Bariatric Surgery can provide a safe and effective auxiliary tool to BLOOD PRESSURE control in obese hypertensive patients. Reduction in antihypertensive medications can help in adherence to treatment.

3 GATEWAY TRIAL Design: Single center, open-label, randomized clinical trial to evaluate the efficacy of Gastric Bypass in reducing the prescription of antihypertensive drugs and its effect on hypertension and other cardiovascular risk factors. Prevention of Bias: concealed allocation (central web-based randomization) + intention-to-treat analysis. Trial Size: 100 patients recruited between may 2013 and June This sample provides 90% power to detect an increase in the probability of the primary end point from 10% in the medical therapy group to 40% in the gastric bypass group, assuming a two-sided alpha of 5%. Quality Control: e-crf + data management

4 100 Patients with hypertension, aged 18 to 65 years, BMI between 30.0 and 39.9 Kg/m2, treated with at least two antihypertensive drugs at maximum doses or more than two at moderate doses. Key exclusion criteria: Uncontrolled blood pressure; Active Cardiovascular diseases; Severe psychiatric disorders; Secondary hypertension, except due to OSA; T1DM or T2DM with HbA1c > 7.0%; Current smokers. Concealed Randomization 1:1 Gastric Bypass Plus Medical Therapy Medical Therapy (Lifestyle intervention with visits to cardiologist, nutritionist and psychologist) mitt 1 PATIENT LOST TO FOLLOW-UP 2 PATIENTS LOST TO FOLLOW-UP 1 PATIENT WITHDREW CONSENT mitt 49 PATIENTS WERE INCLUDED 47 PATIENTS WERE INCLUDED GATEWAY design details available at: ClinicalTrials.gov (NCT ) Schiavon et al. BMJ Open. 2014;4:e

5 GATEWAY TRIAL Primary Endpoint: Reduction of at least 30% of the total antihypertensive drugs, maintaining BP < 140/90 mm Hg, at 12 months. Secondary Endpoints: Remission of hypertension (BP < 140/90 mmhg without medications); SPRINT Target (SBP<120 mmhg) Number of Antihypertensive drugs; SBP and DBP (office and 24h-ABPM); Weight, waist circumference and BMI; HOMA-IR, Lipid profile, High-sensitivity C-reactive protein levels; 10-year Framingham risk score; Adverse events.

6 MEDICAL THERAPY BP Target: SBP<140 and DBP<90 if at target, patient current regimen was maintained; if above target, patient current regimen was adapted to: ACE inhibitors or ARB plus Calcium channel blocker; As needed a Thiazide diuretic; As needed Spironolactone or Clonidine. Dose and/or number of antihypertensive drugs were reduced if: SBP<110 mm Hg and/or DBP<70 mm Hg, or Symptoms of orthostatic hypotension and 110<SBP<130 or 70>DBP<80, and For Gastric Bypass Patients: Reintroduction of medication was checked on a daily basis in the post-op period.

7 BASELINE Characteristics Gastric Bypass (n=50) Medical Therapy (n=50) Age - yr 43.1 ± ± 9.2 Female no.(%) 36 (72) 34 (68) Race, Caucasian no.(%) 31 (62) 34 (68) Afro-Brazilian no.(%) 19 (38) 16 (32) BMI Kg/m ± ± 2.9 Dylipidemia no.(%) 20 (40) 16 (32) Diabetes no.(%) 4 (8) 4 (8) Framingham median (IQR) 4.5 (2.9 to 7.3) 5 (2.8 to 7.1) Creatinine mg/dl 0.7 ± ± 0.2 Office SBP mm Hg ± ± 12.9 Office DBP mm Hg 77.6 ± ± 9.3 Number of antihypertensive drugs Median (IQR) 3 (2 to 3) 3 (3 to 3) Number of antihypertensive drugs 2.8 ± ± 0.7

8 PRIMARY END POINT 30% reduction in no. of antihypertensive medications while maintaining controlled blood pressure (%) Rate ratio, 6.6; 95% CI, 3.1 to 14.0; P value < % (41/49) 51% (25/49) Gastric bypass 12.8% (6/47) Medical therapy 51% (25/49) Patients showed a remission of hypertension (Office) No Patient showed a remission of hypertension Consistent with these sensitivity analyses: complete-case analysis; per-protocol analysis, as-treated analysis, worst-case scenario, and multiple imputation analysis.

9 SPRINT TARGET Reduction of at least 30% of the total antihypertensive medications, maintaining a SBP<120 mm Hg 30% reduction in no. of antihypertensive medications while maintaining systolic blood pressure <120mmHg (%) Rate ratio, 3.8; 95% CI, 1.4 to 10.6; P value % (16/49) 22.4% (11/49) Gastric bypass 8.5% (4/47) Medical therapy 22.4% (11/49) Patients showed a remission of hypertension maintaining a SBP<120 mm Hg

10 WEIGHT LOSS 0 Change in BMI from Baseline (kg/m 2 ) -4-8 P<0.001 Gastric bypass Medical therapy -12 Month Gastric bypass Medical therapy

11 PRIMARY END POINT HAPPENED BEFORE WEIGHT CHANGE Group Gastric bypass Medical therapy The proportion of patients Change in Body weight from baseline (%) Month

12 SECONDARY END POINTS End Point Gastric Bypass Medical Therapy P Value Waist circumference - cm 86.9±8.5 (n=47) 109.8±9.6 (n=39) <0.001 Fasting Plasma Glucose, mg/dl 84.0±6.8 (n=46) 98.4±19.0 (n=40) <0.001 HOMA-IR 1.1 ± 0.9 (n=46) 4.8 ± 3.3 (n=40) <0.001 LDL-cholesterol - mg/dl 86.9±29.2 (n=46) 116.5±35.7 (n=40) <0.001 HDL-cholesterol - mg/dl 56.0±12.7 (n=46) 51.2±15.1 (n=40) 0.05 Triglycerides - mg/dl 85.7±46.2 (n=46) 130.0±55.0 (n=40) <0.001 High-sensitivity C-reactive protein - mg/l 3.1±10.4 (n=46) 8.1±9.3 (n=40) < year Framingham risk score -% 4.5±4.0 (n=46) 6.8±5.3 (n=39) 0.04

13 SECONDARY END POINTS 75% è 1 or less 50% è 3 or more Number of antihypertensive drugs Median (IQR) 0 (0 to 1) (n=49) 3 (2.5 to 4) (n=47) <0.001 Number of antihypertensive drugs 0.7 ± ± 0.9 SBP - mmhg 123.6±13.4 (n=49) 128.3±18.0 (n=47) 0.11 DBP - mmhg 77.0±9.4 (n=49) 80.6±12.2 (n=47) 0.07

14 ADVERSE EVENTS Event, no./total no. (%) Gastric Bypass P Value Base 12 m Nutritional deficiencies 13/50 (26) 23/46 (50) Anemia 3/50 (6) 9/46 (20) 0.01 High PTH 6/45 (13) 6/42 (14) 1 Hypovitaminosis B12 4/46 (9) 12/43 (28) 0.01 Hypoalbuminemia 1/46 (2) 0/43 (0) 1

15 ADVERSE EVENTS Event, no./total no. (%) Gastric Bypass Medical Therapy P Value Deaths 0 0 Rehospitalization 6/49 (12) 0/47(0) 0.03 Reoperation for abscess 1/49 (2) 0/47(0) 1.00 Vomiting and dehydratation 1/49 (2) 0/47(0) 1.00 Cholelithiasis requiring laparoscopy 4/49(8) 0/47(0) 0.12 Hypertensive crisis (ER visit) 0/49(0) 1/47(2) 0.49 Anemia 9/46 (20) 4/40 (10) 0.23

16 CONCLUSIONS Bariatric surgery represents an effective strategy in the treatment of obese patients with hypertension; These results have implications in minimizing non-adherence to therapy and its related consequences; Taken together with the improved metabolic and inflammatory profile, such effects have, in theory, the potential to reduce major cardiovascular events.

17 THANK YOU COORDINATING CENTER: RESEARCH INSTITUTE Heart Hospital (HCor), Sao Paulo, Brazil. Co-Chairs: Carlos Schiavon, Otavio Berwanger; Executive Committee: Carlos Schiavon, Luciano Drager, Luiz Bortolotto, Celso Amodeo, Otavio Berwanger; Project Office-Coordinating Center: Angela Bersch-Ferreira, Eliana Santucci, Camila Torreglosa, Dimas Ikeoka, Priscila Bueno; Statisticians: Lucas Damiani, Renato Nakagawa Santos. The Surgical and Multidisciplinary Team: Patrícia M. Noujaim, Hélio Halpern, Frederico L. J. Monteiro, Roberta Rambaldi, Juliana D. Oliveira, Julia C. Frahya. Ethicon Inc. that funded the study; 100 Volunteers who agreed to participate in GATEWAY. Published online today at: