Hypertension and Diabetes Will Controversies Help Our Patients? Insights of JNC Report Jorge De Jesús MD FACE

Transcription

1 Hypertension and Diabetes Will Controversies Help Our Patients? Insights of JNC Report Jorge De Jesús MD FACE

2 Disclosures Dr Jorge De Jesús has received honorariums as speaker for the following pharmaceutical companies: Novo-Nordisk ; Merck; Eli-Lilly; Boehringer- Ingelheim- Janssen Dr Jorge De Jesús has no conflicts of interests with any entity for the information included in this presentation Jorge De Jesus MD FACE

3 Objectives Audience will be able to define what is the target blood pressure for the diabetic patient* Participants will be able to select ideal agents to achieve target blood pressure* Special considerations in the hypertensive resistant patient Renal sympathetic denervation in resistant hypertension * guideline of preference to be used

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5 75 million adults suffer from hypertension in USA JNC7: 30% unaware of high BP, AHA Of those treated 60% not in target

6 Needs Assessment Hypertension is one of the most common chronic diseases seen in ambulatory medicine and leads to myocardial infarction, stroke; renal failure and death if not detected and treated appropriately. The last report of JNC 7 was published in 2003 Since then, an extensive body of evidence brings new perspectives based on multiple clinical trials that could change the approach and targets for BP control in this population at risk Our focus in this discussion will be the diabetic patient complicated with hypertension

7 Case presentation 49 y/o female 49- year old woman Controlled Diabetes Mellitus A1c=6.9 to 7% for the past 4 years Recently with hypertension Albumin creatinine ratio 200 mg /g DM2 with nephropathy; hypertension and proteinuria

8 Only relying on manual office pressures misses out on white coat and masked hypertension Ambulatory BP mmhg Masked Hypertension Hypertension Normotension White Coat Hypertension Manual Office BP mmhg From Pickering et al. Hypertension 2002;40:

9 Hypertension in the diabetic Autonomic neuropathy Loss of nocturnal dipping (50%) Isolated systolic BP elevation Higher heart rates

10 Renin Angiotensin-Aldosterone System activated in the diabetic patient Hyperinsulinemia increases sympathetic drive Hyperglucemia excitatory on RAAS Remember escape phenomenom

11 Increased sympathetic stimulation contributes to renin release

12 Figure 2 The circulating, tissue and intracellular RASs Intracellular RAS myocytes, fibroblasts, brain, kidney,among others Cell to cell ( paracrine) intra-cell ( autocrine) Implicted in the regulation of target organ damage Clinical Science (2012) 123, Rajesh Kumar, Candice M. Thomas and others.

13 Hyperglycemia increases intracellular Angiotensin II in cardiomyocytes

14 Intracellular ANG II in adult mouse cardiac myocytes. ANG II Yellow Candesartan no effect in ANG II = intracellular synthesis of Angio II in hyperglycemia ANG II YELLOW Kumar R et al. Am J Physiol Regul Integr Comp Physiol 2012;302:R510-R by American Physiological Society

15 Hyperglycemia upregulates pro-renin receptors in renal mesangial cells Increases tumor growth factor ᵝ Implicated in diabetic nephropathy Rat Kidney mesangial cell : for purpose of illustration only CHEN H 2011; Huan J 2010

16 Impact of health behaviors on blood pressure Intervention Systolic BP (mmhg) Diastolic BP (mmhg) Diet and weight control Reduced salt/sodium intake Reduced alcohol intake (heavy drinkers) DASH diet Physical activity Relaxation therapies Multiple interventions Clinical Guideline : Methods, evidence and recommendations National Institute for Health and Clinical Excellence (NICE) May 2011 Adapted from CHEP 2014

17 Treating the ABCs Reduces Diabetic Complications Strategy Complication Reduction of Complication Blood glucose control Myocardial infarction 37% 1 Blood pressure control Lipid control Cardiovascular disease Heart failure Stroke Diabetes-related deaths Coronary heart disease mortality Major coronary heart disease event Any atherosclerotic event Cerebrovascular disease event 51% 2 56% 3 44% 3 32% 3 35% 4 55% 5 37% 5 53% 4 1 UKPDS Study Group (UKPDS 33). Lancet. 1998;352: Grover SA, et al. Circulation. 2000;102: Hansson L, et al. Lancet. 1998;351: Pyŏrälä K, et al. Diabetes Care. 1997;20: UKPDS Study Group (UKPDS 38). BMJ. 1998;317:

18 JNC7 NORMAL: <120/ <80 PRE-HYPERTENSION: /80-89 STAGE1: / STAGE2: >160 / >100 ESSENTIAL : 90-95% OF CASES SECONDARY: 2-10% OF CASES ADAPTED BY JDJ FOR THIS PESENTATION

19 PRE-HYPERTENSION AND RISK OF STROKE 19 prospective cohort studies: 762,393 patients Pre hypertension ( / 80-89) was associated with 66% increased risk of stroke ( compared with individuals with optimal BP of <120/80) /85-89 (high range of pre-hypertension, had a 95% increased risk of stroke compared with those in the low range of pre-hypertension ( /80-84) HUANG Y, PREHYPERTENSION AND RISK OF STROKE MAR NEUROLOGY

20 CARDIA CAC of 100 HU Coronary Artery Risk in Young Adults followed for 25 years Close monitoring of young adults with hypertension are more likely to have calcification of their arteries in middle age. Blacks, Smokers,Had Worse Early Age Profiles Norrina B Allen, PhD JAMA Feb,

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23 JNC8 Panel Recommendation Recommends less aggressive target blood pressures and treatment initiation thresholds than the JNC7 for the elderly patients, and in patients younger than 60 years with diabetes and kidney disease. In the general population age 60: Initiate pharmacologic treatment SBP 150 mm HG; DBP 90 mm Hg No longer recommends just thiazide-type diuretics as initial therapy in most patients TREAT TO 150/ 90 IN PTS OVER /90 goal for everybody else JAMES PA, et al. JAMA,2014;

24 The most common condition in the primary care setting leading to: Myocardial infarction Stroke JNC7 2003* Renal failure NICE 2011 Death ESH/ESC 2013 If not detected early and JNC8panel 2013 treated appropriately ASH/ISH 2013 *James PA,et al. JAMA, 2014;31:

25 JNC-8 states there is not enough data to claim that over age 60 a target of < 140 SBP is better that < 150 ASH/ ISH Claim that there is enough evidence in ALLHAT, ACCOMPLISH,VALUE that included many pts which use the <140/90 as target for treatment. HYVET gives enough evidence that SBP < 150 should be used for age 80 and over

26 The HYpertension in the Very Elderly Trial N. Beckett, R. Peters, A. Fletcher, C. Bulpitt on behalf of the HYVET committees and investigators ClinicalTrials.gov: NCT

27 The Trial: International, multi-centre, randomised double-blind placebo controlled Inclusion Criteria: Exclusion Criteria: Aged 80 or more, Standing SBP < 140mmHg Systolic BP; mmHg Stroke in last 6 months + diastolic BP; <110 mmhg, Dementia Informed consent Need daily nursing care Primary Endpoint: All strokes (fatal and non-fatal) + Perindopril 2 mg Indapamide SR 1.5 mg + Perindopril 4 mg Placebo Placebo Target blood pressure 150/80 mmhg + Placebo + Placebo M-2 M-1 M0 M3 M6 M9 M12 M18 M24 M60

28 JNC8 include the following: In patients 60 or older, initiate therapy in those whose systolic BP levels at 150 mm Hg or greater ( 150 mm Hg) Or whose diastolic BP levels are 90 mm Hg or greater,( 90 mm Hg) Treat to below those thresholds. In patients younger than 60 as well as those older than 18 years with either CKD or diabetes, the BP treatment initiation and goals should be 140/90. In non-black hypertensive patients begin Rx with either a thiazide diuretic, CCB; ACE inh; or ARB, In hypertensive black patients, initiate with thiazide-type diuretic; or CCB. In patients 18 years and older with CKD, regardless of race or diabetic status, initial or add on therapy should consist of an ACE inh or ARB Do not use ACEinh+ARB in the same patient If BP goal not reached in one month optimize dose or add another agent of the recommended drug classes, if 2 drugs are not effective add a third agent Consider a hypertension specialist if target not achieved with multiple drug combinations adapted fron JNC8 by JDJ

29 Management of Diabetes and Hypertension JNC8: For diabetic individuals 18 years or older : initiate treatment at a systolic of 140 ; or diastolic of 90. Set a goal of <140/<90 JNC7 and ADA 2011 recommend blood pressure to be controlled to 130/80 or lower BUT:. This notion has been challenged by data of ACCORD trial, which showed that in patients with type 2 diabetes targeting SBP to less than 120, compared to less than 140 mm Hg did not reduce the composite outcome of fatal or nonfatal cardiovascular events.

30 ADVANCE & ACCORD In Context UKPDS Incidence of myocardial infarction and microvascular end points by mean systolic BP, adjusted for age, sex, and ethnic group expressed for white men aged 5054 years at diagnosis, with mean 50 duration of diabetes of 10 yrs ACCORD ADVANCE UKPDS 40 <120 (140) (144/82) (154/87) Myocardial Infarction Incidence per 1000 Patient-yrs (%) Microvascular Endpoints 37% non fatal 41% total Stroke improved Microalbuminuria improved BUT More SAE s and Multiple Meds Mean systolic BP (mmhg) 170 Alder Al et al. BMJ Aug 12;321(7258):412-9.

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35 The rationale for caution in lowering BP < 60 mmhg in CAD 2014

36 Improving the $tar Rating!! Controlling Blood Pressure: Comprehensive Diabetes Care Members years of age with hypertension are in adequate control ( <140/90) (this is an example just to show how a guideline could have implications in : the way our clinical interventions are evaluated and possibly in the way physicians are reimbursed ) This is an example for the purpose of presentation only

37 CPT II codes Data Collection for Performance Systolic <130 = 3074 F = 3075 F > 140 = 3077 F Diastolic <80= 3078 F 80-89= 3079 F >90= 3080 F In Patients over 60 initiate pharmacologic therapy if SBP>150 Or a diastolic blood pressure 90 or more ( JNC-8?)

38 RAAS BLOCKADE IN THE DIABETIC PATIENT Several studies have provided evidence that RAAS blockade in the diabetic patient is beneficial beyond the effect on BP control. ( HOPE; INNOVATION; AMADEO; ETC) ACE inh AND ARB S: comparable cardiovascular protection; ACE inh: decreases progression from micro to macroalbuminuria in DM1 ACE and ARB decrease micro to macro albuminuria in DM2 ONTARGET: ACE and ARB similar in cardiovascular outcomes ONTARGET:Telmisartan better than Ramipril in urinary albumin excretion rate. Telmisartan plus ramipril : hypotension; syncope ; renal dysfunction ; hyperkalemia

39 Hypertension and Diabetes In general, patients with type 1 or type 2 diabetes and hypertension have shown clinical improvement with diuretics, ACE inhibitors, beta blockers,arb s and CCB. Most studies have shown the superiority of ACE inhibitors or ARB,s Except for the ACCOMPLISH Trial in which the combination of benazepril with amlodipine ( ACE +CCB) was superior than benazepril with HCT in patients at high risk of cardiovascular events. (60% of cohort were diabetics) Two or more drugs at maximal doses should be used to achieve optimalbp targets ( either ACE or ARB) should be included. Thiazide diuretics if GFR > 30 mlmin1.73mm. Use loop diuretics if GF<30. Kidney function and potassium levels should be monitored. Accomplish Trial: high risk older pts (mean age 68) a dihydropyridine CCB agent preferred as an addition to ACE/ARB when CVD complications exist

40 Compelling Indications for Individual Drug Classes Compelling Indication Recommended Drugs Diuretic BB ACEI ARB CCB Aldo ANT Clinical Trial Basis Heart failure Post-myocardial infarction High coronary disease risk ACC/AHA Heart Failure Guideline, MERIT-HF, COPERNICUS, CIBIS, SOLVD, AIRE, TRACE, ValHEFT, RALES, CHARM ACC/AHA Post-MI Guideline, BHAT, SAVE, Capricorn, EPHESUS ALLHAT, HOPE, ANBP2, LIFE, CONVINCE, EUROPA, INVEST Diabetes NKF-ADA Guideline, UKPDS, ALLHAT Chronic kidney disease NKF Guideline, Captopril Trial, RENAAL, IDNT, REIN, AASK Recurrent stroke prevention PROGRESS Chobanian AV et al. Hypertension. 2003;42: Aldo ANT = aldosterone antagonist

41 New onset DM according to agent used

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44 Medscape: Disciplined Apprach

45 Hypertension never sleeps Medscape Education: disciplined apprach

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47 Persistent albuminuria vs micro or macro albuminuria

48 EMA EUROPEAN MEDICINE AGENCY See also NEJM 11/2013 EUROPEAN MEDICINE AGENCY MARCH 2014

49 Resistant Hypertension (or resistant to take antihypertensive medications?) Defined as A BP higher than 140/90 mm Hg despite Rx with 3 or more agents ( including a thiazide diuretic) Look for secondary causes or endocrine etiology ( in a series, 20% pts with resistant hypertension found with primary aldosteronism) 20-25% of cases admitted non adherence (V15.81) Addition of small dose of spirinolactone may be of benefit: be aware of side effects Renal Sympathetic Denervation still under investigation

50 Sympathetic Stimulation : Role in Hypertension

51 Renal Sympathetic Denervation Simplicity Medtronics

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54 Economic Burden of Hypertension Medical cost of treating uncontrolled BP Medical cost of not treating high BP: Stroke MI Renal Failure Quality of life Premature Death Disability

55 New JNC8 published guidelines Clarity is desired Confusion is pervasive Practitioners are in general terms hesitant to adopt new guidelines Lack of concensus and implementation issues

56 Summary Hypertension and Assess global risk factors Diabetes Patient centered approach : Home BP + Office BP Motivation ; Education ; Diet; Exercise; Reduction of stress SBP <140 mm Hg; 130; DBP < 90; 80 ACE inh / or ARB s first line CCB next ( unless compelling indication for other agents) Thiazide diuretics ( low dose thiazide-like ) Beta Blockers : not as first line agents ; use mainly if compelling indications present and if BP target not obtained JDJ interpretation

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