Hypertension Controversies: SPRINTing to New Goals

Transcription

1 Hypertension Controversies: SPRINTing to New Goals Diana Isaacs, PharmD, BCPS, BC-ADM, CDE Clinical Pharmacy Specialist Cleveland Clinic Lauren Wolfe, PharmD Primary Care Clinical Specialist Cleveland Clinic

2 Disclosures Lauren Wolfe and Diana Isaacs have nothing to disclose.

3 Objectives Compare and contrast published guidelines for the treatment of patients with hypertension. Evaluate the literature utilized to determine guideline recommendations. Discuss the implications of the SPRINT trial in establishing blood pressure goals for different patient populations. Design a patient centered therapy plan based on published guidelines and clinical trials.

4 Patient Case AL is a 65 year old African American male. AL s in-office BP today is 148/88mmHg and same on repeat. One month ago, AL s BP was 146/88mmHg. PMH: Sleep apnea, allergic rhinitis Meds: Loratadine 10mg po daily No known drug allergies/adr s Height: lbs, BMI=31.4 Family history: mother with type 2 diabetes Social history: non-smoker, frequently eats out at restaurants, adds salt to food

5 Questions to Think About What is AL s BP goal? How would you treat AL s BP? How would your treatment plan differ if AL had diabetes? CAD? Would the goal BP change if AL was over 80 years old?

6 Definition/Epidemiology HTN defined: BP 140/90mm Hg on repeated exam About 1/3 of adults have HTN Most common condition seen in primary care Close relationship with high BP and risk of MI, stroke, renal failure and death Events lowest at BP=115/75 mmhg CV and stroke events double for each increase of 20/10mmHg in SBP/DBP Weber MA, et al. J Clin Hypertens Jan;16(1): James PA, et al. JAMA. 2014;311(5):

7 Trends in Awareness, Treatment, and Control of HTN Egan BM, et al. Circulation 2014;130:

8 Prevalence of high blood pressure in adults 20 years of age by age and sex (National Health and Nutrition Examination Survey: ) Go A S et al. Circulation. 2014;129:e28-e292

9 Joint National Committee (JNC7) Guidelines -Published in 2003 We anxiously waited for JNC8, but the years kept passing And then all of a sudden!

10 A Flood of HTN Guidelines Kidney Disease: Improving Global Outcomes (KDIGO)-2012 European Society of Cardiology/European Society of Hypertension(ESC/ESH)-2013 American College of Cardiology/American Heart Association/Centers for Disease Control (ACC/AHA/CDC) Scientific Advisory Evidence-Based Guideline for the Management of High Blood Pressure in Adults-2013 ( JNC8 ) American Society of Hypertension/International Society of Hypertension (ASH/ISH)-2013 AHA/ACC/ASH Treatment of Hypertension and Coronary Artery Disease-2015 Canadian Hypertension Educational Program (CHEP)-2016 American Diabetes Association (ADA) Standards of Care-2017 American College of Physicians/American Association of Family Physicians (ACP/AAFP) Pharmacologic Treatment of Hypertension in Adults Aged 60 Ann Intern Med-2017

11 Blood Pressure through the Ages N Engl J Med 2016;375:

12 BP Goals: Guideline Comparison General HTN JNC ESH/ESC 2013 ASH/ISH 2013 JNC CHEP 2016 Disease Specific <140/90 <140/90 <140/90 <140/90 <140/90 SPRINT data: <120/80 is better Diabetes <130/80 <140/85 <140/90 <140/90 <130/80 ADA: <140/90 AACE: <130/80 CKD <130/80 <140/90 Proteinurea: <130/80 <140/90 Proteinurea: consider <130/80 <140/90 <140/90 KDIGO: <140/90 Proteinurea: <130/80 CAD <140/90 <140/90 <140/90 <140/90 <140/90 AHA: <140/90 Elderly <140/90 Age 80 <150/90 Age 80 <150/90 Age 60 <150/90 Age 80 <150/90 ACF/AAFP: Age 60 <150/90 Stroke/TIA<140/90 JNC: Joint National Committee ASH/ISH: American Society of Hypertension/International Society of Hypertension ESH/ESC: European Society of Cardiology/European Society of Hypertension CHEP: Canadian Hypertension Education Program ADA: American Diabetes Association KDIGO: Kidney Disease: Improving Global Outcomes Chobanioan AV et al. JAMA. 2003;289(19): Mancia G et al. J. Hypertension 2013;31: Weber MA et al. J Clin Hypertens Jan;16(1): James PA et al. JAMA. 2014;311(5): Diabetes Care (Suppl 1).Vol 38:. SS1-92 Kidney Intl Suppl 2012;2: CHEP Available at: Qaseem et al. Ann Intern Med. 2017;166(6):

13 Antihypertensive Agents First line: ACEI, ARB, CCB, thiazide diuretics Condition First Drug(s) Add On Diabetes Historically ACEI or ARB If no albuminurea, may use any 1 st line agent CCB or thiazide CKD ACEI or ARB CCB or thiazide Clinical CAD Beta blocker + ACEI or ARB CCB or thiazide Stroke ACEI or ARB CCB or thiazide Heart Failure ACEI or ARB + beta blocker + diuretic + spironolactone Dihydropyridine CCB Weber MA et al. J Clin Hypertens Jan;16(1):14-26

14 JNC8 vs. ASH/ISH ASH/ISH <140/90 for most <150/90 if age>80 JNC8 <140/90 for most <150/90 if age>60

15 JNC8: A Unanimous Consensus? Agreement on all but 1 recommendation SBP from 140 to 150 mm Hg in persons aged 60 years or older without DM or CKD The majority embraced the view that in the absence of definitive evidence, increasing the SBP goal was the optimum approach The minority concluded that the evidence for increasing a BP target in high-risk populations should be at least as strong as the evidence required to decrease the recommended BP target BP goal should be <140/90 in patients <80 and <150/90 in patients 80 Ann Intern Med, 2014;160:

16 Definition of Elderly Merriam-Webster: being past middle age Most countries have accepted the age of 65 years as the definition of 'elderly Lack of United Nations standard numerical criterion, however agreed cutoff is 60 years of age By 2050,1/5 people will be 60 years of age World Health Organization. Accessed 2017 April 4. Merriam-Webster. Accessed 2017 April 4.

17 Hypertension in the Elderly Systolic blood pressure (SBP) increases steadily with age Diastolic BP (DBP) increases until age 55, then declines Importance of BP as a cardiovascular risk has been demonstrated to shift from DBP to SBP with advancing age Isolated systolic hypertension Most common form by age 50 Increased risk of target organ damage and adverse health outcomes Treatment associated with reduced risk for dementia, stroke, MI, and CHF Circulation. 2011;124:e175.

18 How Low is Too Low? Consistent relationship between degree of BP elevation and risk of CVD and stroke Treating to lower target levels may not result in fewer CV events J-shaped association: CV risk at both low and high BP Overaggressive treatment can lead to organ hypoperfusion Excessive BP lowering may impair quality of life Orthostatic hypotension more common and associated with increased CV risk and fall risk In the U.S., almost 40% of people age 60 years and older take at least 5 medications Clinical Interventions in Aging 2013:8; Circulation. 2011;124:e175. Brocklehurst s Textbook of Geriatric Medicine. 2010:

19 Literature Behind JNC8 SHEP Syst-Eur JATOS VALISH HYVET CARDIO- SIS

20 SHEP (Systolic HTN in the Elderly Program) Primary Objective To assess the ability of antihypertensive therapy to reduce the risk of nonfatal and fatal stroke in isolated systolic hypertension Inclusion N=4736 Age 60 (mean 72 years) SBP , DBP<90mmHg Low CV risk Treatment SBP<160 or SBP by 20mmHg Chlorthalidone +/- atenolol +/-reserpine Mean follow-up: 4.5yrs Outcomes Non-fatal plus fatal stroke (primary): RR: 0.64, CI: , p= Non-fatal MI: RR: 0.67,CI: Symptomatic MI events: 63 (tx) vs 98 (placebo), p=0.005 CHD: RR:0.75,CI: Non-fatal MI or CHD deaths: RR: 0.73,CI: Fatal and non-fatal HF:RR: 0.51, CI: , p<0.001 JAMA. 1991;265(24):

21 Take Away Points: SHEP Results Average SBP: 143mmHg (treatment), 155mmHg (placebo) 36% decrease in stroke and 34% decrease in major CVD No difference in total or CV deaths Mean follow-up: 4.5yrs Limitations Reduction below <150mmHg was not evaluated Patients included had low CVD risk Did not determine differences in adverse events Conclusions Treatment to SBP <150mmHg may reduce risk of stroke and major CVD JAMA. 1991;265(24):

22 SYST- EUR (Systolic HTN in Europe) Primary Objective To assess the ability of antihypertensive therapy to reduce the risk of nonfatal and fatal stroke in isolated systolic hypertension Inclusion N=4695 Age 60 (mean age 70 years) SBP and DBP<95mmHg (Mean baseline SBP=173.8mmHg) Treatment Outcomes SBP goal<150 and SBP by 20mmHg Nitrendipine +/- enalapril +/- HCTZ Median follow- up: 2 yrs Mean in BP: 23/7(tx) vs 13/2 (placebo) mmhg fatal and non-fatal stroke (primary): HR: 0.59, CI: , P<0.01 fatal/non-fatal cardiac endpoints: HR: 0.71, CI: , P< % non-fatal stroke, p= % fatal MI, p= % non-fatal HF, p= 0.06 Lancet. 1997;350(9080):

23 Take Away Points: Syst-Eur Results Treatment mean SBP: 151mmHg Placebo mean SBP: 173mmHg 42% decrease in total stroke incidence (p=0.003) 26% decrease in fatal and nonfatal CV endpoints (p=0.03) Limitations Placebo group did not receive antihypertensive treatment Adverse events were not reported Further SBP reduction not evaluated Conclusions SBP <150mmHG had benefit in reduction of total stroke and nonfatal CV Lancet. 1997;350(9080):

24 HYVET (Hypertension in the Very Elderly) Primary Objective To determine the benefits/risks of antihypertensive treatment in patients 80 Inclusion N=3845 Age 80 SBP 160mmHg (Mean baseline SBP=173mmHg) Treatment Outcomes Treatment: indapamide ± perindopril to goal: <150/80 mmhg vs placebo Mean follow-up: 2.1 yrs Mean BP 15.0/6.1 mmhg lower tx group than placebo (SBP 144 vs. 159mmhg) fatal or non-fatal stroke (primary): HR 0.7, CI: , P=0.06 morality: HR=0.79, CI: , P=0.02 death from stroke: HR=0.661, CI: , P=0.046 fatal or non-fatal HF: HR=0.36, CI: , P<0.001 N Engl J Med. 2008;358(18):

25 Take Away Points: HYVET Results Mean BP 15.0/6.1 mmhg lower in the active-treatment group than in the placebo group (SBP 144 vs. 159mmhg) 30% reduction fatal or nonfatal stroke (95% CI: 1 to 51, p=0.06) 39% reduction rate of death from stroke (95% CI: 1 to 62, p=0.05) Limitations Short duration (1.8 years) Unable to assess effects of BP on dementia or cognitive dysfunction Benefits of further BP lowering unknown Conclusions Indapamide (sustained release, 1.5 mg), with or without 2 to 4 mg of perindopril, significantly reduces the risks of death from stroke and death from any cause in very elderly patients N Engl J Med. 2008;358(18):

26 JATOS and VALISH Trial Inclusion Treatment Outcomes JATOS (Japanese Trial to Assess Optimal systolic BP in Elderly Hypertensive Patients) VALISH (Valsartan in Elderly Isolated Systolic HTN) N=4418 Japanese patients Mean Age: 73.6 years Low CV risk N=3260 Japanese patients Mean Age: 76.1 years Low CV risk SBP<140 vs SBP <160mmHg Efonidipine +/- others Treatment mean BP 135.9/74.8mmHg Control mean BP: 145.6/78.1mmHg 2 years duration SBP<140 vs. SBP<150 mmhg Valsartan +/- others Treatment Mean BP: 136.6/74.8 mmhg Control Mean BP: 142/76.5 mmhg 2.8 years duration Primary endpoint: Events: 86 vs 86, p=0.99 Death from any cause: Events: 54 vs 42, p=0.22 Cerebrovascular disease: Events: 52 vs 49, p=0.77 Cardiac and vascular disease: Events: 26 vs 28, p=0.78 Composite of CV events (primary) Events: 52 vs. 47, p=0.564 All cause death: Events: 30 vs 24, p=0.362 Fatal and non-fatal MI: Events:4 vs. 5, p=0.761 Fatal and non-fatal stroke: Events: 23 vs. 16, p=0.237 Hypertens Res. 2008;31(12): Hypertension. 2010;56(2):

27 Take Away Points: JATOS and VALISH Limitations Short study durations Did not achieve power Lack of generalizability of patient population Conclusions Did not show a difference in primary endpoints including cerebrovascular disease, cardiac and vascular disease, or renal failure Hypertens Res. 2008;31(12): Hypertension. 2010;56(2):

28 Usual Versus Tight Control of SBP in Non-Diabetic Patients with Hypertension (Cardio-Sis) Primary Objective To determine if tight control vs. usual control would be beneficial in non-diabetic patients with hypertension Inclusion Treatment Outcomes 1,111 patients 55 years (Mean Age: 67 yrs) SBP 150 mm Hg or greater (Mean SBP mmhg) At least 1 risk factor for CVD Smoker TC 5 2 mmol/l, HDL <1 0 mmol/l, LDL l 3 4 mmol/l, Family hx CVD in 1 relative [<65 yr women and <55 yr men] TIA or stroke CAD or PAD Open-label treatment to SBP <130 (tight) or <140 mmhg (usual) Tight: more diuretic use (OR 1.36; ; p=0 009), 17% higher ARB use (OR 1.17, ; p=0.066) Use of BB, CCB, ACEI did not differ Mean in BP: 27.3 (tight) vs 23.5 (usual) mmhg 1 outcome: left ventricular hypertrophy: 17% (82/483) usual vs 11.4% (55/484) tight (OR 0.63, 95% CI ; p=0.013 ) Composite CV endpoint: 9.4% (52/483) usual vs 4.8% (27/484) tight (HR 0.5, 95% CI ; p=0.003) Lancet. 2009;374(9689):

29 Take Away Points: Cardio-Sis Results Tight Mean BP: 131.9/77.4mmHg Standard Mean BP: 135.6/75mmHg 37% decrease in left ventricular hypertrophy 50% decrease composite endpoint Limitations Open-label design 2 year duration Caucasian patients only Both groups reached BP <140/90 Conclusions Primary endpoint improvement with lower BP Lancet. 2009;374(9689):

30 Literature Not Referenced by JNC8 FEVER SPS3 INVEST SPRINT

31 Journal of Hypertension. 2005;23: Lancet. 2013;382(9891): J Am Coll Cardiol 2014;64: Literature Not Referenced by JNC8 Trial Patients Intervention Achieved SBP FEVER SPS3 INVEST 9,711 Chinese patients Age Mean Age: ,020 patients 30 Mean Age: 63 Recent, symptomatic, MRI-confirmed lacunar stroke 8,354 patients 60 with a baseline SBP 150mmHg Mean Age: 70.7 Randomized to felodipine 5mg/day or placebo Treatment to SBP target of mmHg or <130mmHg Randomized to verapamil- SR/trandolapril OR- atenolol/hctz Felodipine Mean BP mmhg Placebo Mean BP: mmhg Lower Target Mean SBP: 127mmHg Higher Target Mean SBP: 138mmHg SBP <140 (n=4787) SBP (n=1747) SBP 150 (n=1820) Outcomes Incidence of stroke and CV events reduced in felodipine group by 27% (p=0.001) Subgroup analysis: patients 65 44% reduction in all strokes (p<0.0010) Lower SBP target reduced subsequent strokes by 19% (p = 0.08) and hemorrhagic strokes by nearly 50% (p < 0.01) Lower rates primary outcome (all cause death, nonfatal MI, nonfatal stroke) SBP <140 vs. higher SBPs (9.36% vs % vs %; p<0.0001)

32 Randomized trial of intensive versus standard blood pressure control (SPRINT) Inclusion 9361 patients, age 50 years (mean age: 67.9 years) Risk (one or more of the following) Presence of clinical or subclinical CVD (not stroke) Chronic Kidney Disease (CKD), defined as egfr ml/min/1.73m 2 Framingham Risk Score for 10-year CVD risk 15% Not needed if eligible based on preexisting CVD or CKD Age 75 years Systolic blood pressure SBP: mm Hg on 0 or 1 medication SBP: mm Hg on up to 2 medications SBP: mm Hg on up to 3 medications SBP: mm Hg on up to 4 medications Intervention Open-label treatment to SBP <120 (intensive group) or <140 (standard group) Endpoints Primary composite: ACS, stroke, HF, or death from CV causes N Engl J Med. 2015;373:

33 Study Design: Patient Population Exclusion Criteria Stroke Diabetes Congestive heart failure (symptoms or EF < 35%) Proteinuria >1g/d CKD with egfr < 20 ml/min/1.73m 2 (MDRD) Adherence flags N Engl J Med. 2015;373:

34 Baseline Demographics: SPRINT Intensive (N=4678) Standard (N=4683) Baseline SBP (mmhg) (mean, SD) Distribution SBP (%) 132 mm Hg >132 to<145mmhg 145 mm Hg Age, yr (mean, SD) Age 75 yr no.(%) Women no.(%) Black Non-Hispanic black Hispanic Non-Hispanic white Other 139.7± (33.8) 1489 (31.8) 1606 (34.3) 67.9± (28.2) 1684 (36.0) 1454 (31.1) 1379 (29.5) 503 (10.8) 2698 (57.7) 98 (2.1) 139.7± (33.2) 1549 (33.1) 1581 (33.8) 67.9± (28.2) 1648 (35.2) 1493 (31.9) 1423 (30.4) 481 (10.3) 2701 (57.7) 78 (1.7) Estimated GFR ml/min/1.73 m2 Among all participants egfr 60 ml/min/1.73 m2 egfr <60 ml/min/1.73 m2 71.8± ± ± ± ± ±9.5 Statin use (%) 1978 (42.6) 2076 (44.7) Aspirin use (%) 2406 (51.6) 2350 (50.4) Body-mass index 29.9± ±5.7 Antihypertensive agents no./pt 1.8± ±1.0 No antihypertensive agents no. (%) 432 (9.2) 450 (9.6) N Engl J Med. 2015;373:

35 Intervention Groups Standard Intensify therapy if: SBP 160 mm g at 1 visit 140 mmhg at 2 consecutive visits Down-titration if: SBP <130 mmhg at 1 visit <135 mmhg at 2 consecutive visits Intensive Blood pressure medications are added and/or titrated at each study visit to achieve SBP <120 mm Hg Intervention goal is to create a minimum mean difference between randomized groups of at least 10 mm Hg N Engl J Med. 2015;373:

36 Primary Outcome: SPRINT N Engl J Med. 2015;373:

37 SPRINT Results: Intensive vs standard SBP N Engl J Med. 2015;373:

38 Take Away Points: SPRINT Results Mean SBP 121.5mmHg (intensive) vs mmHg (standard) at 3.26 years 25% decrease in primary outcomes in lower SBP group NNT to prevent one primary outcome event: 61; death any cause: 90 No difference: serious adverse event, injurious falls, bradycardia, orthostatic hypotension with dizziness in hypotension, syncope, electrolyte abnormality, AKI/ARF in intensive treatment group (NNH of 71, 91,100, and 56 respectively) Limitations Exclusion of patients with prior stroke and patients residing in nursing homes or assisted-living facilities Early cessation of trial Baseline use of statin 43%, aspirin 51% Open label Difficult to replicate BP monitoring techniques N Engl J Med. 2015;373:

39 Practical Application: SPRINT Treatment to SBP <140mmHg Only achieved in 50% of population Treatment to SBP <120mmHg Required ~1 additional medication Achieved in less than half of strict treatment group More demanding, time-consuming, and costly in practice SPRINT-MIND SPRINT-SENIOR

40 SPRINT-Senior Pre-specified subgroup for analysis Objective: evaluate effects of intensive vs standard SBP in patients 75 yr with HTN but without DM 815 participants (30.9%) were classified as frail and 1456 (55.2%) as less fit Exclusion criteria: dementia, expected survival <3 years, SBP <110mmHg after 1 min standing, unintentional weight loss >10% 6 months prior, nursing home residents Outcomes: Primary: composite of MI, ACS not resulting in MI, nonfatal stroke, nonfatal acute decompensated HF, death from CV causes JAMA. 2016;315(24):

41 Baseline Characteristics: SPRINT-Senior Characteristic Intensive (n=1317) Standard (n=1319) Age, mean (SD), y 79.8 (3.9) 79.9 (4.1) Female (%) White (%) Black (%) Seated BP mmhg (mean, SD) Systolic Diastolic 499 (37.9) 977 (74.2) 225 (17.1) (15.7) 71.5 (11) 501 (38) 987 (74.8) 226 (17.1) (15.8) 70.9 (11) Orthostatic Hypotension (%) 127 (9.6) 124 (9.6) Number of anti-htn meds (SD) 1.9 (1) 1.9 (1) History of CVD (%) 338 (25.7) 309 (23.4) Estimated GFR (mean (SD) <60 ml/min/1.73 m 2, % <45 ml/min/1.73 m 2, % 584 (44.3) 207 (15.7) 577 (43.7) 212 (16.1) Statin use (%) 682 (58.1) 697 (52.8) Aspirin use (%) 820 ( (58) JAMA. 2016;315(24):

42 Outcomes: SPRINT-Senior JAMA. 2016;315(24):

43 Take Away Points: SPRINT-Senior Results Mean SBP 123.4mmHg (intensive) vs mmHg (standard) NNT estimate for the primary outcome was 27 (95% CI, 19-61) and 41 (95% CI, ) for all-cause mortality at 3.14 years Intensive group required 1 more medication to reach the lower BP Safety Intensive group SAEs 48.4% vs 48.3% in the standard group (HR, 0.99 [95% CI, ]; P =.90). in hypotension, syncope, electrolyte abnormality, AKI/ARF in intensive treatment group Absolute rate of injurious falls was lower in the intensive treatment group (4.9% vs 5.5%; HR, 0.91 [95% CI, ]) JAMA. 2016;315(24):

44 SBP Goal Literature Support SBP<150 SHEP Syst-Eur SBP<140 Cardio-Sis FEVER SPS3 INVEST SPRINT

45 BP Goals in Diabetes

46 Guideline Comparison-Diabetes JNC8 <140/90 AACE <130/80 ASH/ISH <140/90 CHEP <130/80 ADA <140/90 ESH <140/85

47 Clinical Trials in Diabetes Trial Inclusion Treatment (tx) Outcomes ACCORD-BP (Action to Control Cardiovascular Risk in Diabetes) N= T2DM, A1c 7.5%, Age 40 SBP: mmHg Mean follow-up: 4.7 yrs SBP goal<140 vs <120mmHg Mean SBP=119.3 vs mmHg ACEI or ARB or BB or CCB or diuretic or combo Non-fatal stroke: HR: 0.63, CI: , p=0.03 Any stroke: HR: 0.59, CI: , p = 0.01 syncope and hyperkalemia in<120 group: (3.3% vs 1.3%, p=0.001) No statistical difference in composite of first occurrence of major CV event (primary), death, non-fatal MI, major coronary disease event, fatal or non-fatal HF, renal failure, ESRD UKPDS (UK Prospective Diabetes Study Group) N= T2DM Age BP 150/85 mmhg Mean follow-up: 8.4 yrs SBP goal<150/85 vs. <185/105mmHg Mean BP change: 15/12 vs. 12/7mmHg Captopril or atenolol Any DM related endpoint (primary): RR:0.76, CI: ,p= Stroke: RR:0.56,CI: ,p=0.013 HF:RR: 0.44,CI:0.20,-0.94, p= Death related to DM: RR:0.68,CI: ,p=0.019 No statistical different in all cause mortality, MI, sudden death, death from renal failure BMJ. 1998;317(7160): N Engl J Med. 2010;362(17):

48 Clinical Trials in Diabetes Trial Inclusion Treatment Outcomes HOT (Hypertension Optimal Treatment) N=18790 (1501 with DM) 1998 T2DM, age with DBP mmHg Mean followup: 3.8 yrs Compared DBP 80 vs 85 vs 90mmHg Mean BP not reported for DM subpopulation Felopidpine +/- ACE +/-BB +/- diuretic Major CV Events (Primary): 45( 90 ) vs. 22( 80), HR:2.06, CI: Total mortality: 90 vs 80: RR: 1.77, CI: No statistical difference in MI, stroke for 90 vs. 80. No statistical difference in any outcomes for 90 or 80 vs. 85 Lancet. 1998;351(9118): ,.

49 DM BP Goal: <140/90 vs <130/80 ACCORD-BP had similar outcomes for SBP=140 vs SBP=120 HOT Trial supports DBP<80 over DBP<90, but was considered low quality evidence Post hoc analysis of a small subgroup (8% of study population) UKPDS: BP=150/85 had better outcomes than 180/105 However, unable to determine if positive outcomes from SBP or DBP DM excluded in Sprint trial Are ACEI and ARB still preferred? Large HTN trials including patients with diabetes had similar outcomes comparing ACEI, ARB, thiazide, CCB ADA 2017 guidelines all 1 st line agents reasonable to use except in albuminuria/ckd (ACEI/ARB preferred) James PA, et al. JAMA. 2014;311(5): Diabetes Care 2017;40 (Suppl.1):s11-s24.

50 BP Goals in CAD Most guidelines recommend <140/90 with no separate category for CAD

51 SPRINT vs. ACCORD-BP ACCORD-BP N=4733, 34% with a previous CV event BP<120/80, lower stroke rate SPRINT Better outcomes with BP<120/80 vs <140/80 in high risk patients

52 CAD/BP Goal Comparisons Prospective, observational study (N=22,672) 45 countries represented Patients with Stable CAD + HN Median f/u: 5.0 years Primary Outcome: CV death, MI, stroke BP>140/80-worse outcomes SBP<120 = increased risk Adjusted HR 1.56, 95% CI DBP<70 DBP 60-69: adjusted HR % CI DBP <60: adjusted HR % CI Vidal Petiot E, et al. Lancet Aug 26..

53 2015 AHA/ACC/ASH Guidelines Rosendorff C et al. J Am Coll Cardiol 2015;65:

54 Back to the Case AL is a 65 year old African American male. AL s in-office BP today is 148/88mmHg and same on repeat. One month ago, AL s BP was 146/88mmHg. PMH: Sleep apnea, allergic rhinitis Meds: Loratadine 10mg po daily No known drug allergies/adr s Height: lbs, BMI=31.4 Family history: mother with type 2 diabetes Social history: non-smoker, frequently eats out at restaurants, adds salt to food

55 What is AL s BP Goal? A. <150/90 B. <140/90 C. <130/80 D. <120/80

56 AL is now 70 and he developed diabetes. Current BP is 136/80 and now he s on HCTZ 25mg daily and metformin 1000mg BID. Which of the following is the best plan? A1C=6.9%. CMP is wnl. Neg albuminurea A. Continue current therapy B. Add lisinopril 10mg daily C. Add amlodipine 5mg daily D. Add lisinopril 10mg daily and amlodipine 5mg daily

57 Two years later (age 72) he developed CAD and had an MI 3 months ago. Current meds: metoprolol succinate, furosemide, metformin, sitagliptin, lisinopril, ASA. Current BP is 132/74. What is the most appropriate BP goal? A. <150/90 B. <140/90 C. <130/80 D. <120/80 What should his BP goal be in 10 years? (Age=82?)

58 In Summary Guidelines differ on optimal BP goals but agree <140/90 is a good starting point for most Thiazides, CCB, ACE-inhibitors, ARB s are 1 st line agents SPRINT provides evidence that lower BP may benefit some patients Keep in mind SPRINT trial exclusion criteria and overall limitations Guidelines provide a general framework, but always consider the individual patient

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