1. Powered by Infomedica Infomedica Conference Coverage* of 26 th European Meeting on Hypertension and Cardiovascular Protection Paris (France), June 10-13, 2016 * Infomedica is an independent medical education provider that produces medical information to healthcare professionals through conference coverage and online educational programs and activities. 26 th European Meeting on Hypertension and Cardiovascular Protection Paris (France), June 10-13, 2016 HARMONY: Similar Results with Morning and Evening Dosing of Antihypertensive Therapy From ESH 2016 | LB 1: Neil R. Poulter, MD Imperial College London, United Kingdom

2. 26 th European Meeting on Hypertension and Cardiovascular Protection Paris (France), June 10-13, 2016 Powered by Infomedica Overview  Morning or evening administration of antihypertensive medication had no effect on blood pressure levels measured by 24-hour ambulatory blood pressure monitoring (ABPM) or on quality of life in the HARMONY study  Optimal timing of administering antihypertensive medications to reduce major adverse cardiovascular events (MACE) is subject of research  Some nighttime dosing has been suggested to be beneficial by some research

3. 26 th European Meeting on Hypertension and Cardiovascular Protection Paris (France), June 10-13, 2016 Powered by Infomedica HARMONY Design  Women and men aged 18-80 years with well- controlled blood pressure (≤150 mmHg systolic and ≤90 mmHg diastolic) for ≥3 months on ≥1 antihypertensive medication were randomized to taking their medication in the morning (between 6 and 11 am) or in the evening (between 6 and 11 pm); at 12 weeks, without a washout period, patients were crossed over to the other time period  All patients took their usual antihypertensive therapy  Primary endpoint: mean 24-hour systolic blood pressure (SBP) measured by ABPM

4. 26 th European Meeting on Hypertension and Cardiovascular Protection Paris (France), June 10-13, 2016 Powered by Infomedica Overview: Baseline Characteristics in Patients in HARMONY VariableEvening/MorningMorning/Evening N 5251 Age, mean (SD) 61.8 (9.7)61.8 (11.0) Female, N (%) 21 (40)24 (47) BMI, mean (SD) 29.1 (5.6)29.1 (4.7) Heart rate, mean (SD) 72.8 (10.3)72.7 (9.6) Systolic BP, mean (SD) 127.1 (8.7)129.0 (8.8) Diastolic BP, mean (SD) 76.6 (6.1)76.3 (6.2) Current smoker, N (%) 4 (8)8 (16) Alcohol units per week, mean (SD) 16.7 (17.2)11.8 (11.9) Fasting plasma glucose, mean (SD) 5.6 (0.9)5.5 (1.0) Non-HDL cholesterol, mean (SD) 3.4 (1.0)3.5 (1.0) BP, blood pressure; DBP, diastolic blood pressure; QOL, quality of life; SBP, systolic blood pressure.

5. 26 th European Meeting on Hypertension and Cardiovascular Protection Paris (France), June 10-13, 2016 Powered by Infomedica Overview: Achieved Blood Pressures by Doing Time for Primary and Secondary Endpoints Outcome mmHg (N=95) Baseline Drug taken Observed difference (Evening - Morning) Adjusted difference (95% CI) MorningEvening 24h Systolic BP128.64129.65129.750.100.11 (-3.20, 3.42) 24h Diastolic BP76.9277.2477.990.750.77 (-1.38, 2.91) Day time SBP131.16132.24132.770.530.54 (-2.82, 3.89) Day time DBP79.1479.2780.551.281.30 (-0.96, 3.56) Night time SBP120.89122.76121.08-1.68-1.62 (-5.38, 2.15) Night time DBP69.8370.9270.57-0.35-0.32 (-2.81, 2.17) Clinic SBP128.07129.37129.810.440.39 (-2.91, 3.69) Clinic DBP76.5477.2677.410.150.14 (-2.03, 2.32) QOL score82.8084.1484.04-0.10-0.12 (-3.12, 2.89) BP, blood pressure; DBP, diastolic blood pressure; QOL, quality of life; SBP, systolic blood pressure.

6. 26 th European Meeting on Hypertension and Cardiovascular Protection Paris (France), June 10-13, 2016 Powered by Infomedica Results  No difference observed for the primary endpoint or any prespecified secondary endpoints in relation to timing of therapy  Largest between-group difference seen for nighttime systolic blood pressure, although not significant, could be important at population level in relation to reducing CV events  No impact on quality of life in relation to timing of therapy

7. 26 th European Meeting on Hypertension and Cardiovascular Protection Paris (France), June 10-13, 2016 Powered by Infomedica Results  Definitive evidence on a benefit of nighttime doing for MACE prevention will come from the ongoing Treatment in Morning versus Evening (TIME) trial with 10,200 patients followed for 5 years

8. Powered by Infomedica Infomedica Conference Coverage* of 26 th European Meeting on Hypertension and Cardiovascular Protection Paris (France), June 10-13, 2016 * Infomedica is an independent medical education provider that produces medical information to healthcare professionals through conference coverage and online educational programs and activities. 26 th European Meeting on Hypertension and Cardiovascular Protection Paris (France), June 10-13, 2016 HARMONY: Similar Results with Morning and Evening Dosing of Antihypertensive Therapy From ESH 2016 | LB 1: Neil R. Poulter, MD Imperial College London, United Kingdom