RISE, FALL AND RESURRECTION OF RENAL DENERVATION. Michael A. Weber, MD State University of New York Downstate College of Medicine

Transcription

1 RISE, FALL AND RESURRECTION OF RENAL DENERVATION Michael A. Weber, MD State University of New York Downstate College of Medicine

2 Michael Weber, Disclosures Research/Trial Commitments and Consulting: Boston Scientific; Medtronics; ReCor; Ablative Solutions, Sanofi Consulting: Novartis; Arbor; Takeda; Boehringer Ingelheim; Astellas; Johnson & Johnson

3 Renal Nerves EFFERENT AND AFFERENT FIBERS INFLUENCE MULTIPLE ORGAN SYSTEMS Vasoconstriction atherosclerosis Hypertrophy Arrhythmia Oxygen consumption Insulin resistance Sleep disturbances Renal afferent nerves (affect brain/systemic SNS) Renal efferent Nerves (Govern Renal BP Effects) Renin release RAAS activation Sodium retention Renal blood flow

4 CARDIOVASCULAR CONTINUUM: START THERAPY EARLIER IN HIGH-RISK PATIENTS, SMALL RELATIVE RISK REDUCTIONS TRANSLATE INTO LARGE ABSOLUTE BENEFITS 5% 10% 7.5 CV risk % in 10 years 15 20% % 37.5 Treatment Benefit: 25% Risk reduction 40% Death 50% Cardiovascular (CV) continuum: A sequence of events beginning with risk factors, leading to subclinical (asymptomatic) organ damage Untreated, results in clinical (symptomatic) disease and CV events (stroke, MI, HF) and death Approximate risk is shown as % CV events expected in 10 years. Risk can be reduced depending on when treatment is initiated Treatment benefit is calculated to be approximately 25% reduction of initial risk 1 Zanchetti A. Nat Rev Cardiol. 2010;7: Law MR, et al. BMJ. 2009; 338,

5 SYMPATHETIC ACTIVITY IN DIFFERENT HYPERTENSIVE POPULATIONS 400 Rate of spillover of noradrenaline from the kidneys to plasma (ng/min) Isolated systolic ** hypertension is the predominant hypertensive * phenotype 100 in elderly patients 0 Normal BP Essential Hypertension years Esler M, J Hypertension. 1990

6 Change in Office BP in Treatment Resistant Hypertension: Symplicity 2 (Controlled, open-label trial) BP change (mmhg) SBP mmhg DBP mmhg -45 P<0.01 for from BL for all time points 1 mo (n=143) 3 mo (n=148) 6 mo (n=144) 12 mo (n=132) 24 mo (n=105) 30 mo (n=44) 36 mo (n=34)* Schlaich M, TCT 2012 Reported as mean with 95% confidence intervals *Number of patients represents data available at time of data-lock

7 Office SBP (mm Hg) Symplicity 3: RDN vs. Sham in Treatment Resistant HTN Δ = (95% CI, to 2.12) P=0.26* 200 Δ = -14.1±23.9 P<0.001 Δ = -11.7±25.9 P< mm Hg 166 mm Hg 180 mm Hg 168 mm Hg 100 Baseline 6 Months 50 0 (N=364) (N=353) Denervation (N=171) Sham (N=171) *P value for superiority with a 5 mm Hg margin; bars denote standard deviations

8 Lessons Learned Cannot get reliable results when an inconsistent technique is applied to an ill-defined clinical condition Solution Optimize catheter designs to ensure full circumferential effects Establish rigorous standards of procedural technique: should we go beyond main renal artery? Study carefully defined hypertensive populations Use trial designs that effectively measure the effects of treatment on high blood pressure

9 Caution: The Symplicity Renal Denervation System is an Investigational Device. Limited by U.S. law to investigational use. Trademarks may be registered and are the property of their respective owners. For OMA distribution only Medtronic, Inc. All rights reserved DOC_1A 3/2014

10 Systolic Blood Pressure Change (mm Hg) 24h Ambulatory BP Change Symplicity FLEX Symplicity SPYRAL 0 3Mo 6Mo 1Yr 2Yr 3Yr 3Mo 6Mo 1Yr 2Yr 3Yr n=965 n=966 n=880 n=580 n=353 n=125 n=122 n=104 n= P < vs. Baseline Baseline ABPM 154 ± 18 mmhg P < vs. Baseline Baseline ABPM 157 ± 18 mmhg

11 SBP Change from Baseline to 6 Months (mm Hg) DENER HTN: The First Successful Controlled Trial of Renal Denervation in Treatment Resistant Hypertension* 0 : 5.9 mm Hg (95% CI: 11.3 to 0.5) p = : 6.3 mm Hg (95% CI: 12.0 to 0.6) p = Denervation Control 20 Daytime ABPM Nighttime ABPM Primary endpoint *It required 1416 referred resistant patients to yield 106 eligible for the trial (1:13) Azizi M et al. The Lancet Jan

12 DENER HTN: Compliance with Drug Therapy Azizi et al. Circulation 2016; 134:

13 NON ADHERENCE TO ANTIHYPRTENSIVE DRUG THERAPY IS WIDESPREAD, DYNAMIC AND DIFFICULT TO DETECT Proportion of poor or nonadherence according to drug monitoring in different cohorts of patients with apparently resistant hypertension Berra E, et al. Hypertension. 2016;68:

14 NON ADHERENCE TO ANTIHYPERTENSIVE MEDICATION IS ASSOCIATED WITH INCREASED MORBIDITY AND MORTALITY Meta Analysis of 44 studies N=1,978,919 Only 60% of participants with hypertension had good adherence (>80%) Poor adherence to antihypertensive medications increased cardiovascular disease events by 19% Poor adherence to antihypertensive medications increased mortality events by 29% Chowdhury R, et al. European Heart Journal (2013) 34,

15 SPYRAL HTN OFF MED BLOOD PRESSURE CHANGE FROM BASELINE TO 3 MONTHS: OFFICE BP Townsend RR, et al. Lancet Aug 25. pii: S (17)32281-X. doi: /S (17)32281-X.

16 Relative Risk Reduction (%) RELATIVE RISK REDUCTION FOR A 10 MMHG FALL IN OFFICE BLOOD PRESSURE Meta analysis of 123 studies N= 613,815 patients Placebo adjusted pressure reductions Independent of baseline pressure and co-morbidity Major CVD CHD Stroke HF Mortality Source: Ettehad D et al, Lancet. 2016,387:

17 What do we know, and what can we say, about renal denervation..in the future. Given that this procedure reduces blood pressure in hypertensive patients when used alone or in combination with other therapies, we can propose that: --- This procedure can be combined with antihypertensive drugs in hypertensive patients whose blood pressures are not adequately reduced despite systematic prescription of drugs alone --- This procedure can be used in hypertensive patients intolerant of antihypertensive drugs

18 What do we know, and what can we say, about renal denervation.in the future. Part 2 It will be critical to explore the value of this procedure in important subgroups of hypertension not fully addressed in initial pivotal trials, including: ---- Patients with isolated or predominant systolic hypertension ---- As a core therapy, the young -- primarily adults aged < 40

19 Hypertension Guidelines Just Announced Hypertension is the new egalitarian medical condition we can all share --- it includes just about everyone!!

20 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/ APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults American College of Cardiology Foundation and American Heart Association

21 Categories of BP in Adults* BP Category SBP DBP Normal <120 mm Hg and <80 mm Hg Elevated Hypertension mm Hg and <80 mm Hg Stage mm or mm Hg Hg Stage mm Hg or 90 mm Hg *Individuals with SBP and DBP in 2 categories should be designated to the higher BP category. BP indicates blood pressure (based on an average of 2 careful readings obtained on 2 occasions, as detailed in DBP, diastolic blood pressure; and SBP systolic blood pressure.

22 Blood Pressure Summary (1) Threshold for diagnosis of hypertension is generally >140/90 mmhg BUT, it is >130/80 mmhg if: Previous CV/stroke event or procedure Ischemic heart disease Diabetes Chronic kidney disease Age >65 10% 10 year risk of a CV event Question: Will 130/80 mmhg soon become the standard threshold for everyone?

23 Blood Pressure Summary (2) The treatment target is < 130/80 mmhg in ALL patients