HYPERTENSION: UPDATE 2018

Transcription

1 HYPERTENSION: UPDATE 2018 From the Cardiologist point of view Richard C Padgett, MD

2 I have no disclosures

3 HYPERTENSION ALWAYS THE ELEPHANT IN THE EXAM ROOM

4 BUT SOMETIMES IT CHARGES

5 HTN IN US ~78 million adults (33% of population) By 2030 ~41.4% NHANES % aware 74.9% current treatment 52.5% controlled 47.5% not controlled ~75% have visits at least 2x/y Heart disease and stroke statistics 2014 update: AHA. Circulation 14;129:e28-e292 Vital signs: awareness and treatment of uncontrolled HTN among adults MMWR MorbMortal WklyRep. 12;61:703-9

6 HYPERTENSION Most common modifiable CVD risk factor Contributes to >50% of adverse CVD outcomes JAMAD 16;17: edit. Morbidity/mortality correlates with BP > 115/75 BP control Reduces HF 50%; CVA 40%; MI 25% Presence of other CV risk factors multiplicative increase in risk for CV events Circulation 15;131:e435-e70

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8 JNC 7 GUIDELINES 2003

9 TREATING BP TO GOAL STUDIES African American Study of Kidney Disease and Hypertension (AASK) trial SBP <140 vs <130 No decrease in progression of CKD or mortality NEJM 10;363: Action to Control Cardiovascular Risk in Diabetes(ACCORD) trial SBP <140 vs <120 No decrease in composite of CV events CVA reduced 0.32% vs. 0.53% (HR 0.59, p=0.01) Serious ADEs 3.3% vs 1.3% (p<0.001) NEJM 10;362:

10 RELAXED TREATMENT TARGETS JNC 8 BP target of 140/90 mmhg People <60 years of age Diabetes Chronic Kidney Disease BP target of 150/90 mmhg People >60 years of age Without Diabetes or Chronic Kidney Disease

11 CONCERN FOR JNC 8 TREATMENT TARGETS Multiple groups expressed concern around the new treatment targets Five members of the JNC 8 committee published a letter expressing concern regarding the relaxation of the treatment guidelines Drs Jackson Wright (University Hospitals Case Medical Center, Cleveland, OH) Lawrence Fine (National Heart, Lung, and Blood Institute (Bethesda, MD) Daniel Lackland (Medical University of South Carolina, Charleston) Gbenga Ogedegbe (New York University School of Medicine, New York) Cheryl Dennison Himmelfarb (Johns Hopkins University School of Nursing, Baltimore, MD) A series of letters and articles were published in the Major Journals including the Annals of Internal Med and JAMA

12 SPECIFIC CONCERNS TO JNC 8 Increasing the systolic BP target in those 60 years or older will have the effect of reducing the intensity of antihypertensive treatment among patients already being treated, among them a large population with established CVD or at high risk for CVD (including African Americans and patients with multiple CVD risk factors other than chronic kidney disease) The evidence supporting upping the target from 140 mm Hg to 150 mm Hg in people 60 or older was insufficient and inconsistent

13 SPECIFIC CONCERNS TO JNC 8 Evidence from trials and observational studies that the panel did not use as part of its review supports the lower goal, especially in high-risk patients Raising the target may have the unintended effect of reversing decades of declining CVD rates, especially stroke mortality

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15 Background High BP very common High SBP leading risk factor for mortality and disability-adjusted life years Worldwide, >1 billion adults have hypertension Observational studies identify strong association between BP and risk of CVD, with no evidence of threshold for the relationship Clinical trials demonstrate antihypertensive drug therapy reduces risk of CVD However, optimal target for SBP lowering uncertain

16 SPRINT Research Question Examine effect of more intensive high blood pressure treatment than is currently recommended Randomized Controlled Trial Target Systolic BP Intensive Treatment Goal SBP < 120 mm Hg Standard Treatment Goal SBP < 140 mm Hg SPRINT design details available at: ClinicalTrials.gov (NCT ) Ambrosius WT et al. Clin. Trials. 2014;11:

17 Major Inclusion Criteria 50 years old Systolic blood pressure : mm Hg (treated or untreated) Additional cardiovascular disease (CVD) risk Clinical or subclinical CVD (excluding stroke) Chronic kidney disease (CKD), defined as egfr 20 <60 ml/min/1.73m 2 Framingham Risk Score for 10-year CVD risk 15% At least one Age 75 years

18 Major Exclusion Criteria Stroke Diabetes mellitus Polycystic kidney disease Congestive heart failure (symptoms or EF < 35%) Proteinuria >1g/d CKD with egfr < 20 ml/min/1.73m 2 (MDRD) Adherence concerns

19 Location of 102 SPRINT Clinical Centers Clinical Center Networks -Ohio -Southeast -Utah -UAB -VA Central Laboratory MRI Reading Center Project Office, NIH Coordinating Center Wake Forest School of Medicine ECG Reading Center Drug Distribution Center

20 SPRINT: Enrollment and Follow-up Experience Screened (N=14,692) Randomized (N=9,361) Intensive Treatment (N=4,678) Standard Treatment (N=4,683) Consent withdrawn Discontinued intervention Lost to follow-up Analyzed 4,678 4,683 (Intention to treat) (Vital status assessment: entire cohort)

21 Primary Outcome and Primary Hypothesis Primary outcome CVD composite: first occurrence of Myocardial infarction (MI) Acute coronary syndrome (non-mi ACS) Stroke Acute decompensated heart failure (HF) Cardiovascular disease death Primary hypothesis* CVD composite event rate lower in intensive compared to standard treatment *Estimated power of 88.7% to detect a 20% difference - based on recruitment of 9,250 participants, 4-6 years of follow-up and loss to follow-up of 2%/year.

22 BP Intervention BP monitored monthly for 3 months and every 3 months thereafter (additional visits could be scheduled) Antihypertensive medication titration decisions based on mean BP (3 readings at each visit), using a structured stepped-care approach Agents from all major antihypertensive drug classes available free of charge Periodic assessment for orthostatic hypotension and related symptoms

23 Systolic BP During Follow-up Year 1 Mean SBP mm Hg Standard Average SBP (During Follow-up) Standard: mm Hg Mean SBP mm Hg Intensive Intensive: mm Hg Average number of antihypertensive medications Number of participants

24 SPRINT Primary Outcome Cumulative Hazard Hazard Ratio = 0.75 (95% CI: 0.64 to 0.89) Standard (319 events) Intensive (243 events) During Trial (median follow-up = 3.26 years) Number Needed to Treat (NNT) to prevent a primary outcome = 61 Number of Participants

25 Primary Outcome Experience in the Six Pre-specified Subgroups of Interest *Treatment by subgroup interaction

26 SPRINT Primary Outcome and its Components Event Rates and Hazard Ratios Intensive Standard No. of Events Rate, %/year No. of Events Rate, %/year HR (95% CI) P value Primary Outcome (0.64, 0.89) <0.001 All MI (0.64, 1.09) 0.19 Non-MI ACS (0.64, 1.55) 0.99 All Stroke (0.63, 1.25) 0.50 All HF (0.45, 0.84) CVD Death (0.38, 0.85) 0.005

27 Serious Adverse Events* (SAE) During Follow-up All SAE reports Number (%) of Participants Intensive Standard HR (P Value) 1793 (38.3) 1736 (37.1) 1.04 (0.25) SAEs associated with Specific Conditions of Interest Hypotension 110 (2.4) 66 (1.4) 1.67 (0.001) Syncope 107 (2.3) 80 (1.7) 1.33 (0.05) Injurious fall 105 (2.2) 110 (2.3) 0.95 (0.71) Bradycardia 87 (1.9) 73 (1.6) 1.19 (0.28) Electrolyte abnormality 144 (3.1) 107 (2.3) 1.35 (0.020) Acute kidney injury or acute renal failure 193 (4.1) 117 (2.5) 1.66 (<0.001) *Fatal or life threatening event, resulting in significant or persistent disability, requiring or prolonging hospitalization, or judged important medical event.

28 Decision to Stop BP Intervention On August 20 th, 2015, NHLBI Director accepted DSMB recommendation to inform SPRINT investigators and participants of CVD results Concurrently, decision made to stop BP intervention This presentation based on adjudicated events that occurred through August 20 th, 2015 Median follow-up = 3.26 years Data for some secondary non-cvd outcomes (e.g. dementia and cognitive impairment) being collected at final close-out visit and this process will be completed in 2016

29 Summary and Conclusions SPRINT examined effects of more intensive antihypertensive therapy than currently recommended Participants were US adults 50 years with hypertension and additional risk for CVD Rapid and sustained difference in SBP achieved between the two treatment arms Trial stopped early, due to benefit, after median follow-up of 3.26 years Incidence of primary outcome (composite of CVD events) 25% lower in Intensive compared to Standard Group and all-cause mortality reduced by 27%. Treatment effect similar in all six pre-specified groups of interest. The number needed to treat to prevent primary outcome event or death 61 and 90, respectively

30 Summary and Conclusions In participants with CKD at baseline, no differences in renal outcomes In participants without CKD at baseline, incidence of egfr reduction 30% more common in Intensive Group No overall difference in serious adverse events (SAEs) between treatment groups SAEs associated with hypotension, syncope, electrolyte abnormalities, and hospital discharge reports of acute kidney injury or acute renal failure more common in Intensive Group Overall, benefits of more intensive BP lowering exceeded the potential for harm

31 MAYBE WE CAN FINALLY SEE THE ELEPHANT FOR WHAT HE IS

32 WELL NOT SO FAST..

33 CONCERN WITH SPRINT TRIAL

34 A SCIENTIFIC POLL OF CARDIOLOGISTS European Society of Cardiology

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36 DEFINING THE PROBLEM OLD VS NEW JNC 7/8 ACC/AHA 2017 Stage 2 - Hypertension >160/100 Stage 1 - Hypertension Pre-Hypertension Stage 2 - Hypertension / />80 Stage 1 - Hypertension /<80 Elevated BP Normal <120/<80 Normal 32% of US pop 46% of US pop

37 GRAPHICAL 2017 GUIDELINES

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39 ASCVD RISK ESTIMATOR

40 ASCVD RISK ESTIMATOR

41 ASCVD RISK ESTIMATOR

42 ASCVD RISK ESTIMATOR

43 ASCVD RISK REDUCTION SCENARIOS

44 UPDATES IN CLASSIFYING HYPERTENSION Diet/Lifestyle Medications CAD ASCVD >10%

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