Effects of Bariatric Surgery in Obese Patients with Hypertension The - - PowerPoint PPT Presentation

Carlos Aurelio Schiavon, MD, FACS On behalf of the GATEWAY Executive Committee and Investigators

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

DISCLOSURE Study Funding: Ethicon Inc. Speaker Bureau and Honoraria: Johnson & Johnson Medical Brasil

BACKGROUND

THE PROBLEM ~40% of the American adults are Obese (~20% - Brazil). 60-70% 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.

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 2016. 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

Concealed Randomization 1:1

Medical Therapy

(Lifestyle intervention with visits to cardiologist, nutritionist and psychologist) 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.

Gastric Bypass Plus Medical Therapy

m I T T

49 PATIENTS WERE INCLUDED

1 PATIENT LOST TO FOLLOW-UP

47 PATIENTS WERE INCLUDED

2 PATIENTS LOST TO FOLLOW-UP 1 PATIENT WITHDREW CONSENT m I T T

GATEWAY design details available at: ClinicalTrials.gov (NCT1784848) Schiavon et al. BMJ Open. 2014;4:e005702.

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.

MEDICAL THERAPY

⦿ 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.

BP Target: SBP<140 and DBP<90

BASELINE

Characteristics Gastric Bypass (n=50) Medical Therapy (n=50) Age - yr 43.1 ± 9.2 44.6 ± 9.2 Female – no.(%) 36 (72) 34 (68) Race, Caucasian – no.(%) 31 (62) 34 (68) Afro-Brazilian – no.(%) 19 (38) 16 (32) BMI – Kg/m2 37.4 ± 2.4 36.4 ± 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 ± 0.1 0.8 ± 0.2 Office SBP – mm Hg 123.0 ± 11.6 122.8 ± 12.9 Office DBP – mm Hg 77.6 ± 7.0 78.0 ± 9.3 Number of antihypertensive drugs Median (IQR) 3 (2 to 3) 3 (3 to 3) Number of antihypertensive drugs 2.8 ± 0.6 3.1 ± 0.7

(41/49)

83.7% Gastric bypass

(25/49)

51%

Rate ratio, 6.6; 95% CI, 3.1 to 14.0; P value <0.001

(6/47)

12.8% Medical therapy

25 50 75 100

≥30% reduction in no. of antihypertensive medications while maintaining controlled blood pressure (%)

PRIMARY END POINT

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.

SPRINT TARGET

Reduction of at least 30% of the total antihypertensive medications, maintaining a SBP<120 mm Hg

Rate ratio, 3.8; 95% CI, 1.4 to 10.6; P value 0.005

25 50 75 100

≥30% reduction in no. of antihypertensive medications while maintaining systolic blood pressure <120mmHg (%)

(16/49)

32.7% Gastric bypass

(4/47)

8.5% Medical therapy

(11/49)

22.4%

22.4% (11/49) Patients showed a remission of hypertension maintaining a SBP<120 mm Hg

WEIGHT LOSS

• 12
• 8
• 4

3 6 9 12 Change in BMI from Baseline (kg/m2) Medical therapy Gastric bypass

Month Gastric bypass 37.4 30.4 28.2 26.8 Medical therapy 36.4 35.9 36.0 36.3

P<0.001

PRIMARY END POINT HAPPENED BEFORE WEIGHT CHANGE

0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0

• 50
• 40
• 30
• 20
• 10

0.0 1 2 3 4 5 6 7 8 9 10 11 12

Month The proportion of patients Change in Body weight from baseline (%)

Group

Gastric bypass Medical therapy

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) <0.001 10-year Framingham risk score -% 4.5±4.0 (n=46) 6.8±5.3 (n=39) 0.04

SECONDARY END POINTS

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 ± 1.0 3 ± 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

75% è 1 or less 50% è 3 or more

ADVERSE EVENTS

Event, no./total no. (%) Gastric Bypass P Value

Base 12 m

Nutritional deficiencies

13/50 (26) 23/46 (50) 0.012

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

ADVERSE EVENTS

Event, no./total no. (%) Gastric Bypass Medical Therapy P Value Deaths 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

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.

⦿ 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.

THANK YOU

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