Felix Mahfoud Saarland University Hospital, Homburg, Germany CRT 2017 What Are the Primary Endpoints for Controlling Hypertension? Unattended or Attended Office, Ambulatory or Home BP? Felix Mahfoud Saarland University Hospital, Homburg, Germany

Disclosure Statement of Financial Interest I have the following potential conflicts of interest to report: Research grants: Deutsche Hochdruckliga Deutsche Gesellschaft für Kardiologie Saarländisches Ministerium für Wissenschaft und Forschung Medtronic, St. Jude Consultant/Lecture fee:

Office attended non-automated BP Home BP Office automated unattended BP Office automated attended BP 24-h Ambulatory BP

SPRINT - Reduction in endpoints Intensive (121 mmHg) vs. standard treatment (135 mmHg) Cardiovascular death: - 43% Overall mortality: -27% Heart failure: -38%

Blood pressure measurements in SPRINT

Blood pressure measurements in SPRINT X

Blood pressure measurements in SPRINT

Blood pressure measurement in perspective SBP by automated office BP monitors is comparable to daytime ambulatory 10-15 mmHg lower compared to (attended) office BP Kjeldsen SE, Hypertension 2016

Blood pressure measurement in perspective SBP by automated office BP monitors is comparable to daytime ambulatory 10-15 mmHg lower compared to (attended) office BP Kjeldsen SE, Hypertension 2016

Data from 897 SPRINT patients at 27-month FU Intensive treatment, n=453 BP Unattended 120 mmHg Daytime 126 mmHg 24-hour 123 mmHg Drawz PE, Hypertension 2017

Data from 897 SPRINT patients at 27-month FU Intensive treatment, n=453 BP Unattended 120 mmHg Daytime 126 mmHg 24-hour 123 mmHg Standard treatment, n=444 BP Unattended 136 mmHg Daytime 139 mmHg 24-hour 134 mmHg Drawz PE, Hypertension 2017

Correlation between clinic and ABP in other hypertension trials 24-hour SBP (mmHg) 134 123 Clinic BP (mmHg) 132 152 Parati G, Hypertension 2017

ABP versus office BP Advantages of ABPM Provides more precise BP profiles Ability to determine BP during sleep Identification of the white-coat effect Detection of masked hypertension Improved reproducibility Can be easily blinded

ABP versus office BP Disadvantages of ABPM Costs Discomfort/reluctancy No real-time blood pressure assesment Lack of evidence-based recommendations for target BP based on ambulatory values

Correlation in ABPM and office BP reductions – data from drug trials Mancia G, J Hypertension 2004

Schmieder RE, Hypertension 2014

REDUCE-HTN: REINFORCE Study 24-hour ABP Daytime ABP REDUCE-HTN: REINFORCE Study 24-hour ABP 24-hour ABP 24-hour ABP

Clinical Consensus Conference on Device-based Therapies for Hypertension Part II As target BP in a clinical trial of device-based therapy in hypertension, the European Expert Group recommended an attended target seated office BP <140 mmHg using the conventional method and a validated device. Whichever method is used, it is critical that consistency is maintained in all centres and at all visits.

Clinical Consensus Conference on Device-based Therapies for Hypertension Part II Considering the less well established standardization of home compared with ABPM, the European Expert Group does not recommend using home BP measurement as a primary endpoint in clinical trials, while there is large agreement that it can be used as a secondary endpoint. Furthermore, in device trials home BP monitoring may conceivably influence adherence.

What needs to be discussed for future device-based hypertension trials? Inclusion criteria Office BP >140 mmHg? 24-hour BP >135 mmHg? Daytime BP >135 mmHg?

What needs to be discussed for future device-based hypertension trials? Inclusion criteria Office BP >140 mmHg? 24-hour BP >130 mmHg? Daytime BP >135 mmHg? Clinical meaningful BP reduction Office BP change >10 mmHg? 24-hour BP change >5 mmHg? Daytime BP change >5 mmHg?

Thank you! Felix Mahfoud, MD FESC Klinik für Innere Medizin III Kardiologie, Angiologie und Intern. Intensivmedizin Universitätsklinikum des Saarlandes Homburg/Saar felix.mahfoud@uks.eu