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Hypertension Mohammad Garakyaraghi,MD Cardiologist Associate Professor 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 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 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 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 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, CKDrelated mortality) A – Strong evidence B – Moderate evidence C – Weak evidence D – Against E – Expert Opinion N – No recommendation JNC8: Strength of Recommendation Grade Strength of Recommendation A Strong: High certainty net benefit is substantial Moderate B • Moderate certainty net benefit is moderate to substantial, or • High certainty that net benefit is moderate C E Weak: At least moderate certainty of small net benefit Expert Opinion • Insufficient evidence, or • Evidence is unclear or conflicting • Further research is recommended in this area 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? Age > 60 yo ◦ Systolic: Threshold > 150 mmHg Goal < 150 mmHg LOE: Grade A ◦ Diastolic: Threshold > 90 mmHg Goal < 90 mmHg LOE: Grade A 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 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 Nonblack, including DM ◦ Thiazide diuretic, CCB, ACEI, ARB LOE: Grade B Black, including DM ◦ Thiazide diuretic, CCB LOE: Grade B (Grade C for diabetics) 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 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 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 Comparison of Recent Guideline Statements JNC 8 ESH/ESC AHA/ACC ASH/ISH >140/90 Threshold >140/90 < 60 yr Eldery SBP >160 for Drug Rx >150/90 >60 yr Consider SBP >140/90 <80 yr >140/90 >150/90 >80 yr 140-150 if <80 yr B-blocker First line Rx No Yes No No Initiate Therapy >160/100 "Markedly >160/100 >160/100 Goal BP Group General BP Goal (mm Hg) DM* CKD** JNC 8: <60 yr: <140/90 >60 yr: <150/90 < 140/90 < 140/90 ESH/ESC: < 140/90 < 140/85 < 140/90 Elderly 140-150/90 (<80 yr: SBP<140) ASH/ISH < 140/90 >80 yr: <150/90 AHA/ACC < 140/90 *ADA: < 140/80 or lower (SBP < 130 if proteinuria) < 140/90 < 140/90 (Consider < 130/80 if proteinuria) < 140/90 < 140/90 **KDIGO: <140/90 w/o albuminuria <130/80 if >30 mg/24hr Comparison of JNC Guidelines JNC7 JNC8 • Nonsystematic literature review and expert opinion • Range of study designs • No grading system for recommendations • Recommendations: • Systematic review • Randomized, controlled trials (RCT) only • Graded recommendations • Recommendations: – – – – Lifestyle modifications Initial therapy for HTN Compelling indications Addressed secondary HTN and resistant HTN – No specific lifestyle recommendations – Initial therapy for HTN – Racial, CKD, and diabetic subgroups addressed – Addressed three key questions 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 Recommendations for General Population Age < 60 Years JNC 7 • BP Goal < 140/90 mmHg Evidence for JNC8 • HDFP Trial • Hypertension-Stroke JNC8 • SBP Goal < 140 mmHg – Grade E • DBP Goal < 90 mmHg – Ages 30-59 years (Grade A) – Ages 18-29 years (Grade E) Cooperative Trial • MRC Trial • ANBP Trial • VA Cooperative Trial 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 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 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 <130/80 for patients with proteinuria (>3g/24 hours) • REIN-2 Trial • No trials showed goal <130/80 mmHg significantly lowered kidney or CV end points compared to 140/90 Recommendations for General Population Age ≥ 18 with DM JNC 7 Evidence for JNC8 • Goal BP: < 130/80 mmHg • ACCORD-BP Trial • No difference in outcomes with SBP < 140 vs. SBP < 120 JNC8 • No good or fair quality trials • Goal BP: < 140/90 mmHg – Grade E to support DBP < 80 2013 ESH/ESC Guidelines for the management of arterial hypertension Blood pressure goals in hypertensive patients 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 SBP, systolic blood pressure; CV, cardiovascular; TIA, transient ischaemic attack; CHD, coronary heart disease; CKD, chronic kidney disease; DBP, diastolic blood pressure. 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 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 Hypertension treatment for people with diabetes Recommendations Additonal 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 • Avoid in patients with diabetes Coadministration of RAS blockers not recommended SBP, systolic blood pressure; DBP, diastolic blood pressure; RAS, renin–angiotensin system. 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 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 Hypertension treatment for people with nephropathy Recommendations Additonal considerations Consider lowering SBP to <140 mmHg Consider SBP <130 mmHg with overt proteinuria • Monitor 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 blockers • Not recommended Aldosterone antagonist not recommended in CKD • Especially in combination with a RAS blocker • Risk of excessive reduction in renal function, hyperkalemia SBP, systolic blood pressure; CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate; RAS, renin–angiotensin system. 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 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 Lifestyle changes for hypertensive patients Recommendations to reduce BP and/or CV risk factors Salt intake Restrict 5-6 g/day Moderate alcohol intake Limit to 20-30 g/day men, 10-20 g/day women Increase vegetable, fruit, low-fat dairy intake 25 kg/m2 BMI goal Waist circumference goal Men: <102 cm (40 in.)* Women: <88 cm (34 in.)* ≥30 min/day, 5-7 days/week (moderate, dynamic exercise) Exercise goals Quit smoking * Unless contraindicated. BMI, body mass index. 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 Medical Education & Information – for all Media, all Disciplines, from all over the World Powered by 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 Thank You For Your Attention