Treating Hypertension in 2018: What Makes the Most Sense Today?

Transcription

1 Treating Hypertension in 2018: What Makes the Most Sense Today? Daniel Blanchard, MD Professor of Medicine UC San Diego Cardiovascular Center La Jolla, California 1

2 2 Speaker Disclosures Consultant and/or speaker for : Sanofi Pfizer Portola

3 The ACCORD Study Group Effects of Intensive BP control in Type 2 DM N Engl J Med Volume 362(17): April 29, 2010

4 Study Overview 4733 patients, mean age 62 yrs, with type 2 DM, at high risk for CV events received treatment aimed at a target systolic BP of <120 mm Hg or <140 mm Hg. Primary end point: nonfatal MI, nonfatal stroke, or CV death. Mean follow-up of 4.7 years.

5 Mean Systolic Blood-Pressure Levels Baseline SBP 139/76 for both groups At 1 y mean SBP 133 v 119 mmhg Number of meds: 3.4 vs. 2.1 The ACCORD Study Group. N Engl J Med 2010;362:

6 Kaplan-Meier Analyses Annual rate1.9% v 2.1%l The ACCORD Study Group. N Engl J Med 2010;362: Event rate in the standard therapy 50% less than expected

7 Primary and Secondary Outcomes The ACCORD Study Group. N Engl J Med 2010;362: Number of patients treated for 5 yrs. to prevent 1 stroke = 89

8 The ACCORD Study: Signals of adverse effects Elevation in Scr > 1.5 Scr > 1.3 Intensive Therapy 13 % 11 % Standard Therapy 8 % (p<0.001) 7 % (P<0.001) Potassium < % 1.1%(P=0.01) egfr < 30 ml/min 4.2% 2.2% (<0.001) Higher incidence of hypotension (0.7% vs. 0.04%, P<0.001) Decreased incidence of macroalbuminuria

9 ACCORD - Conclusions In patients with type 2 DM at high risk for CV events, targeting a systolic BP of <120 mm Hg, as compared with <140 mm Hg, did not reduce the rate of fatal and nonfatal major CV events but increased the likelihood of hypotension & adverse renal outcome.

10 10 Fast-Forward to JNC Controversial recommendations NHLBI disbanded the group before publication of recommendations

11 The JNC8 Process Strictly evidence-based Focus only on randomized controlled trials assessing important health outcomes (no use of surrogate measures, like Afib or LVH) Evidence statements graded for quality using prespecified criteria Separate grading strength of recommendations Initial set of recommendations focused on 3 key questions Guidelines were released before SPRINT results were published

12 Three Main Questions: 1. When should we start BP meds in adults? 2. What BP goals should we shoot for? 3. What are the best drugs to treat HTN?

13 Recommendation 1 In the general population 60 years of age, initiate pharmacologic treatment to lower BP at SBP 150 mm Hg or DBP 90 mm Hg and treat to a goal SBP <150 mm Hg and goal DBP <90 mm Hg. Strong Recommendation Grade A Question 1: Trials Considered: ANBP, 1980; EWPHE, 1985; HYVET, 2008; SHEP, 1991; Syst-Eur, 1997; HDFP Cooperative, 1979; Hypertension Stroke Cooperative, 1974; MRC, 1985; VA Cooperative, 1967; VA Cooperative, 1970 Question 2: Trials Considered DBP: HYVET, 2008; MRC, 1985; VA Cooperative, 1967; VA Cooperative, 1970 ; VA Cooperative, 1974; ANBP, 1980; HDFP Cooperative, 1979; Cardio-Sis, 2009; JATOS, 2008; VALISH, 2010; Syst-Eur, 1997; SHEP 1991

14 Recommendation 2 In the general population <60 years of age, initiate pharmacologic treatment to lower BP at DBP 90 mm Hg and treat to a goal DBP <90 mm Hg. For ages years, Strong Recommendation Grade A For ages years, Expert Opinion Grade E

15 Recommendation 3 In the general population <60 years of age, initiate pharmacologic treatment to lower BP at SBP 140 mm Hg and treat to a goal SBP <140 mm Hg. Expert Opinion Grade E Recommended first-line BP meds include: Amlodipine ACEI ARB Thiazide diuretic

16 The SPRINT Study A Randomized Trial of Intensive Versus Standard Blood-Pressure Control NEJM 2015;373:

17 SPRINT Research Question Examine effect of more intensive high blood pressure treatment than is currently recommended Randomized, Controlled, open labeled Trial Target: Systolic BP Intensive Treatment Goal SBP < 120 mm Hg Standard Treatment Goal SBP < 140 mm Hg N Engl J Med 373(22): November 26, 2015

18 SPRINT Study Overview 9361 patients, >50 yrs (mean age 68 years, 28% >75 yrs), with SBP >130 and <180 mmhg & at increased CV risk but no DM. Pts were assigned to intensive treatment with a target of SBP<120 mm Hg or standard treatment with a target of SBP<140 mm Hg.

19 SPRINT Study Primary end point : Composite of cardiac events including MI, HF or CV mortality. After a median of 3.3 years, the Data Safety Monitoring Committee ended the study early. 19

20 Systolic Blood Pressure in the Two Treatment Groups over the Course of the Trial. Mean # of BP medications 2.8 vs.1.8 Mean SBP at 1 year 136 vs.121 mmhg The SPRINT Research Group. N Engl J Med DOI: /NEJMoa

21 Primary Outcome and Death from Any Cause. CV Death ACS HF The SPRINT Research Group. N Engl J Med DOI: /NEJMoa

22 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) All MI (0.64, 1.09) Non-MI ACS (0.64, 1.55) All Stroke (0.63, 1.25) All HF (0.45, 0.84) CVD Death (0.38, 0.85) <

23 23 SPRINT Study The benefit in both primary end point and all cause mortality was greatest in the senior group (>75 yrs): 33% v. 25%: primary endpoint (CV death, ACS, heart failure) 34% v 27%: mortality. 37% reduction in acute HF: NNT 28 --(HF increased mortality rate 27-fold) --NNT to prevent a death: 41

24 SPRINT Study: Serious adverse events Intensive treatment Standard treatment Hazard ratio P value > 30% reduction in GFR 1.2 %/y 0.35 %/y 3.49 <0.001 Important? Hypotension 2.4 % 1.4 % Electrolyte abnormalities 3.1 % 2.3 % AKI 4.1 % 2.5 % 1.66 <0.001 Orthostatic hypotension 16.6 % 18.3 % 0.88 <0.001

25 Conclusions Among non diabetic patients at high risk for CV events, (including >60 yo), SBP goal of <120 mmhg, as compared with goal of <140 mmhg, resulted in lower rates of fatal and nonfatal major CV events and death from any cause.

26 Conclusions But, aggressive treatment was associated with higher rates of adverse events, including renal dysfunction, hypotension, and electrolyte abnormalities.

27 27 SPRINT vs. ACCORD: Why the Difference? ACCORD SPRINT Population Diabetes? Yes No Mean age Primary outcome 9 vs 10% 5 vs 7% Major CV event 10.6 vs 11.4% 2.9 vs 3.3% Three times the CV event rate in ACCORD vs. SPRINT: Does this overwhelm a mild benefit from BP lowering?

28 How do we apply the results of SPRINT to real world practice? BPs were measured with patients seated for 5 min in a quiet room without talking, as an average of 3 measurements with an automated device and without the observer being present. Is your practice setting like this??

29 How do we apply the results of SPRINT to real world practice? BP readings were probably ~10 mmhg lower than typical practice readings, suggesting a <130 mmhg rather than <120 mmhg target for systolic BP.

30 How to apply the results of SPRINT to real world practice? Although mean SBP in Intensive group was 121 mmhg it was >120 mmhg in > 50%. Despite the original intention to test <120 mmhg, these findings better support a target of <130 mmhg

31 SPRINT vs. the real world The excess of hypotension, syncope, AKI, and electrolyte disturbances in the intensive arm suggests caution in targeting systolic BP levels <120 mmhg in usual clinical practice.

32 AHA/ACC Guidelines, Nov

33 New Guidelines, 2017 Normal systolic BP remains below 120 mmhg Decrease in target BP from 140/90 to maximum of 130/80 mmhg Goal of <120 mmhg is most useful in clinics that use the SPRINT method to measure BP. In those that don t (the majority), 130/80 or less may be a better goal

34 New Guidelines Hypertension has been split into stage 1 (130/80 to 139/89 mm Hg) and stage 2 (140/90 mm Hg and higher) Goals for BP lowering in stage 1 are primarily nonpharmacologic, unless ACC/AHA ASCVD 10-year risk calculation is >10% Recommendations include: Weight loss, DASH diet, Alcohol moderation, Physical activity

35 ASCVD Plus Risk Estimator Plus Free App from American College of Cardiology Risk based on Age & Sex Racial background Blood pressure Total cholesterol & HDL History of diabetes History of smoking Use of antihypertensives, statins, & aspirin This is a novel concept in guiding HTN treatment

36 New Guidelines Stage 1 Hypertension with low CV risk (<10%): institute lifestyle changes, then f/u in 3-6 months Stage 1 HTN with elevated CV risk: lifestyle changes and one antihypertensive medication. Follow-up in a month. Stage 2 HTN: lifestyle changes and TWO antihypertensive medications, follow-up within a month.

37 New Guidelines Before beginning antihypertensive meds, it is reasonable to first measure home BPs and obtain ambulatory BP readings Patients with resistant HTN, sudden onset HTN, young age at onset, etc., should be screened for secondary HTN. Almost all patients over 75 have >10% 10-year ASCVD risk

38 Benefit vs. Harm SPRINT data by quartiles of ASCVD risk: Phillips, et al. JACC 2018;71:1601

39 Benefit vs. Harm But all quartiles had lower event rates with intensive treatment

40 New Guidelines Prevalence of HTN in Americans will increase from ~32% to ~40% of adults. Focus on home and ambulatory BP measurement to identify white-coat & masked HTN. NHLBI sponsored, with many organizations signed on but not the ADA, ACP, and ACFP

41 Kaiser Permanente Southern California Population Sim J, et al. JACC 2014;64:

42 Sim J, et al. JACC 2014;64:

43 Sim J, et al. JACC 2014;64:

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