2. Hypertension Mohammad Garakyaraghi,MD Cardiologist Associate Professor

3.  Hypertension is the most common condition in primary care.  1 in 3 patients have hypertension according to NHLBI  Risk factor for MI, CVA, ARF, death

4.  National Institute for Health and Clinical Excellence (NICE), 2011  Kidney Disease: Improving Global Outcome (KDIGO), 2012  European Society of Hypertension/European Society of Cardiology, (ESH/ESC), 2013  American Diabetes Association (ADA), 2014  American Society of Hypertension and the International Society of Hypertension (ASH/ISH), 2014  Eighth Joint National Committee (JNC8), 2013

5.  Limited to RCT’s ◦ Hypertensive adults > 18 years old ◦ Sample size > 100 ◦ Follow-up > 1 year ◦ Reported effect of treatment on important health outcomes (mortality, MI, HF, CVA, ESRD)  January 1966 to December 2009 ◦ Separate criteria used of RCT’s published after December 2009

6.  RCT’s December 2009 – August 2013 1.Major study in hypertension  ACCORD, NEJM 2010 2.> 2,000 participants 3.Multicentered 4.Met all other inclusion/exclusion criteria

7.  Excluded sample size < 100 and f/up period < 1 year  Only included randomized, controlled trials rated as good or fair  Only included studies reporting effects of interventions on: ◦ MI ◦ Stroke ◦ ESRD, doubling of Scr, or halving of GFR ◦ Heart failure (HF) or hospitalization for HF ◦ Coronary revascularization or other revascularization ◦ Mortality (Overall mortality, CVD-related mortality, CKD- related mortality)

8. A – Strong evidence B – Moderate evidence C – Weak evidence D – Against E – Expert Opinion N – No recommendation

9. JNC8: Strength of Recommendation GradeStrength of Recommendation A Strong: High certainty net benefit is substantial B Moderate Moderate certainty net benefit is moderate to substantial, or High certainty that net benefit is moderate C Weak: At least moderate certainty of small net benefit E Expert Opinion Insufficient evidence, or Evidence is unclear or conflicting Further research is recommended in this area

10.  In adults with HTN, does initiating antihypertensive pharmacologic therapy at specific BP thresholds improve health outcomes?  In adults with HTN, does treatment with antihypertensive pharmacologic therapy to a specified BP goal lead to improvements in health outcomes?  In adults with HTN, do various antihypertensive drugs or drug classes differ in comparative benefits and harms on specific health outcomes?

11.  Age > 60 yo ◦ Systolic:  Threshold > 150 mmHg  Goal < 150 mmHg  LOE: Grade A ◦ Diastolic:  Threshold > 90 mmHg  Goal < 90 mmHg  LOE: Grade A

12.  Age < 60 yo ◦ Systolic:  Threshold > 140 mmHg  Goal < 140 mmHg  LOE: Grade E ◦ Diastolic:  Threshold > 90 mmHg  Goal < 90 mmHg  LOE: Grade A for ages 40-59; Grade E for ages 18-39

13.  Age > 18 yo with CKD or DM ◦ JNC 7: < 130/80 (MDRD NEJM 1994) ◦ Systolic:  Threshold > 140 mmHg  Goal < 140 mmHg  LOE: Grade E ◦ Diastolic:  Threshold > 90 mmHg  Goal < 90 mmHg  LOE: Grade E

14.  Nonblack, including DM ◦ Thiazide diuretic, CCB, ACEI, ARB  LOE: Grade B  Black, including DM ◦ Thiazide diuretic, CCB  LOE: Grade B (Grade C for diabetics)

15.  Age > 18 yo with CKD and HTN (regardless of race or diabetes) ◦ Initial (or add-on) therapy should include an ACEI or ARB to improve kidney outcomes  LOE: Grade B ◦ Blacks w/ or w/o proteinuria  ACEI or ARB as initial therapy (LOE: Grade E) ◦ No evidence for RAS-blockers > 75 yo  Diuretic is an option for initial therapy

16.  If goal BP not met after 1 month of treatment: ◦ Increase dose of initial drug, or ◦ Add a second drug (Thiazide, CCB, ACEi, or ARB)  If goal BP not met with 2 medications: ◦ Add and titrate a third medication (Thiazide, CCB, ACEi, or ARB) ◦ Do not use ACE and ARB together  Other classes may be used in the following scenarios: ◦ Goal BP not met with 3 medications ◦ Contraindication to thiazide, ACE/ARB, or CCB

17.  Titrate to max dose, then add a second drug  Add a second drug before achieving max dose of the initial drug  Start with 2 drugs at the same time ◦ If SBP ≥ 160mmHg and/or DBP ≥ 100 mmHg ◦ If SBP ≥ 20mmHg above goal and/or DBP ≥ 10mmHg above goal ***Consider scheduling follow-up with the Enhanced Care Clinic for titration of BP Meds

19. Comparison of Recent Guideline Statements JNC 8ESH/ESCAHA/ACCASH/ISH >140/90 Threshold>140/90 < 60 yrEldery SBP >160>140/90 <80 yr for Drug Rx>150/90 >60 yrConsider SBP>140/90>150/90 >80 yr 140-150 if <80 yr B-blockerNoYesNo First line Rx Initiate Therapy>160/100"Markedly>160/100 w/ 2 drugselevated BP"

20. Goal BP GroupBP Goal (mm Hg) GeneralDM*CKD** JNC 8:<60 yr: <140/90< 140/90 >60 yr: <150/90 ESH/ESC:< 140/90< 140/85< 140/90 Elderly140-150/90(SBP < 130 if proteinuria) (<80 yr: SBP<140) ASH/ISH< 140/90 >80 yr: <150/90(Consider < 130/80 if proteinuria) AHA/ACC< 140/90 *ADA: < 140/80 or lower **KDIGO: <140/90 w/o albuminuria 30 mg/24hr

22. Comparison of JNC Guidelines JNC7 Nonsystematic literature review and expert opinion Range of study designs No grading system for recommendations Recommendations: – Lifestyle modifications – Initial therapy for HTN – Compelling indications – Addressed secondary HTN and resistant HTN JNC8 Systematic review Randomized, controlled trials (RCT) only Graded recommendations Recommendations: – No specific lifestyle recommendations – Initial therapy for HTN – Racial, CKD, and diabetic subgroups addressed – Addressed three key questions

23. Recommendations for General Population Age ≥ 60 Years JNC 7 BP Goal < 140/90 mmHg (No age recommendations) JNC8 BP Goal < 150/90 mmHg – Rated Grade A Evidence for JNC8 HYVET Trial SHEP Trial JATOS Trial VALISH Trial

24. Recommendations for General Population Age < 60 Years JNC 7 BP Goal < 140/90 mmHg JNC8 SBP Goal < 140 mmHg – Grade E DBP Goal < 90 mmHg – Ages 30-59 years (Grade A) – Ages 18-29 years (Grade E) Evidence for JNC8 HDFP Trial Hypertension-Stroke Cooperative Trial MRC Trial ANBP Trial VA Cooperative Trial

25. Recommendations for General Non-black Population (Including DM) JNC 7 First-line: Thiazide diuretics (no racial distinction made) JNC8 First-line – Thiazide diuretics – CCB – ACE inhibitor – ARB Grade B Evidence for JNC8 ALLHAT Trial BP control more important than medication used Alpha blockers not recommended first-line LIFE Study Beta-blockers not recommended first-line Insufficient evidence to recommend other classes

26. Recommendations for General Black Population (Including DM) JNC 7 First-line: Thiazide diuretics (no racial distinction made) JNC8 Initial treatment for black population (Grade B) with DM (Grade C) – Thiazide diuretics – CCB ALLHAT Trial Pre-specified subgroup analysis Thiazide more effective in improving CV outcomes compared to ACEi in black patient subgroup 51% higher rate of stroke (RR 1.51; 95% CI 1.22-1.86) with use of ACEi as initial therapy in black patients (compared to CCB) 46% of patients in subgroup analysis had DM

27. Recommendations for General Population Age ≥ 18 with CKD JNC 7 Goal BP: < 130/80 mmHg First-line agent: ACEi or ARB JNC8 Goal BP: < 140/90 mmHg – Grade E Initial or add-on treatment: ACEi or ARB – Grade B – Regardless of race or DM status Evidence for JNC8 AASK Trial MDRD Trial Potential benefit of goal 3g/24 hours) REIN-2 Trial No trials showed goal <130/80 mmHg significantly lowered kidney or CV end points compared to 140/90

28. Recommendations for General Population Age ≥ 18 with DM JNC 7 Goal BP: < 130/80 mmHg JNC8 Goal BP: < 140/90 mmHg – Grade E Evidence for JNC8 ACCORD-BP Trial No difference in outcomes with SBP < 140 vs. SBP < 120 No good or fair quality trials to support DBP < 80

30. Medical Education & Information – for all Media, all Disciplines, from all over the World Powered by 2013 ESH/ESC Guidelines for the management of arterial hypertension The Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC) - J Hypertension 2013;31:1281-1357 Blood pressure goals in hypertensive patients SBP, systolic blood pressure; CV, cardiovascular; TIA, transient ischaemic attack; CHD, coronary heart disease; CKD, chronic kidney disease; DBP, diastolic blood pressure. Recommendations SBP goal for “most” Patients at low–moderate CV risk Patients with diabetes Consider with previous stroke or TIA Consider with CHD Consider with diabetic or non-diabetic CKD <140 mmHg SBP goal for elderly Ages <80 years Initial SBP ≥160 mmHg 140-150 mmHg SBP goal for fit elderly Aged <80 years <140 mmHg SBP goal for elderly >80 years with SBP ≥160 mmHg 140-150 mmHg DBP goal for “most”<90 mmHg DB goal for patients with diabetes<85 mmHg

31. Medical Education & Information – for all Media, all Disciplines, from all over the World Powered by 2013 ESH/ESC Guidelines for the management of arterial hypertension The Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC) - J Hypertension 2013;31:1281-1357 RecommendationsAdditonal considerations Mandatory: initiate drug treatment in patients with SBP ≥160 mmHg Strongly recommended: start drug treatment when SBP ≥140 mmHg SBP goals for patients with diabetes: <140 mmHg DBP goals for patients with diabetes: <85 mmHg All hypertension treatment agents are recommended and may be used in patients with diabetes RAS blockers may be preferred Especially in presence of preoteinuria or microalbuminuria Choice of hypertension treatment must take comorbidities into account Coadministration of RAS blockers not recommended Avoid in patients with diabetes Hypertension treatment for people with diabetes SBP, systolic blood pressure; DBP, diastolic blood pressure; RAS, renin–angiotensin system.

32. Medical Education & Information – for all Media, all Disciplines, from all over the World Powered by 2013 ESH/ESC Guidelines for the management of arterial hypertension The Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC) - J Hypertension 2013;31:1281-1357 RecommendationsAdditonal considerations Consider lowering SBP to <140 mmHg Consider SBP <130 mmHg with overt proteinuriaMonitor changes in eGFR RAS blockers more effective to reduce albuminuria than other agents Indicated in presence of microalbuminuria or overt proteinuria Combination therapy usually required to reach BP goals Combine RAS blockers with other agents Combination of two RAS blockersNot recommended Aldosterone antagonist not recommended in CKDEspecially in combination with a RAS blocker Risk of excessive reduction in renal function, hyperkalemia Hypertension treatment for people with nephropathy SBP, systolic blood pressure; CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate; RAS, renin–angiotensin system.

33. Medical Education & Information – for all Media, all Disciplines, from all over the World Powered by 2013 ESH/ESC Guidelines for the management of arterial hypertension The Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC) - J Hypertension 2013;31:1281-1357 Lifestyle changes for hypertensive patients * Unless contraindicated. BMI, body mass index. Recommendations to reduce BP and/or CV risk factors Salt intakeRestrict 5-6 g/day Moderate alcohol intakeLimit to 20-30 g/day men, 10-20 g/day women Increase vegetable, fruit, low-fat dairy intake BMI goal25 kg/m 2 Waist circumference goalMen: <102 cm (40 in.)* Women: <88 cm (34 in.)* Exercise goals≥30 min/day, 5-7 days/week (moderate, dynamic exercise) Quit smoking

34.  Goal BP for patients with DM ◦ Less than 140/80 mmHg  ACCORD-BP trial  HOT Trial  Showed 51% reduction in major CV events in patients with DM  Post-hoc analysis of small subgroup of the study (not pre-specified)  Evidence graded as low quality by JNC8  Preferred Agents ◦ ACEi or ARB  HOPE Study  Included non-hypertensive patients  Decreased risk of stroke with ACEi ◦ Despite conflicting evidence, continue to recommend ACE/ARB first-line  Cite high CVD risk and high prevalence of undiagnosed CVD in patients with DM

35. Thank You For Your Attention