1/28/2020 Hypertension 2020 Chris Rembold MD Preventive Cardiology Cardiovascular Division Hypertension 1
1/28/2020 Ischemic heart death is predicted by AGE > BP, total cholesterol, and HDL 61 trials with 900,000 patients; Lancet 360:1903, 2002 & 370:1829, 2007 Systolic BP Total Cholesterol HDL 4.5 is 174 8 is 310 1 is 39 2 is 77 Stroke is predicted by AGE > BP, not by total cholesterol or HDL 61 trials with 900,000 patients; Lancet 360:1903, 2002 & 370:1829, 2007 Systolic BP Total Cholesterol HDL 2
1/28/2020 The Pathophysiology of Hypertension How Low should we treat BP ? Observational data 130-139/ 85- 89 120-129/ 80- 84 <120/<80 mmHg 3
1/28/2020 SPRINT NEJM (2015) • 9361 people SBP >130 no diabetes for 3.3 y • Randomized SBP goal 120 vs 140 • Achieved 121/69 vs 136/76 on 2.8 vs 1.8 meds • Primary: MI, ACS, CVA, CHF, CV death • Surprisingly, no effect on stroke, reduced mortality Parachute Trial BMJ 2018; 363:k5094 • Do clinical trials always show the correct result? • 92 people randomized to jumping from an airplane with a parachute or an empty backpack • Parachute use did not significantly reduce death or major injury (0% for parachute or 0% for empty backpack, p>0.9) • This is the first and only trial testing benefit of a parachute, there was no benefit. • Go back and read the methods 4
1/28/2020 SPRINT NEJM (2015) • Lets go back and read the methods • Nothing helpful in main paper, keep looking • The previously published methods paper reveals that BP was measured with an automated BP machine that measured and averaged BP when there was no clinician in the room • This automated BP machine finds SBP values 5-13 points lower than cuff BP • So Sprint aggressive rx 121/69 is cuff SBP 126-134 • & Sprint less aggressive 136/76 is cuff SBP 141-149 • Prior trials suggest goal ~130 with cuff, so Sprint actually adds little to prior knowledge SPRINT PP (Krishnaswami, AJM 131:1220. 2018) • Serious adverse events (hypotension, syncope, electrolyte anomaly, acute kidney injury, and injurious falls) sorted by pulse pressure • Higher pulse pressure and more aggressive BP Rx associated with more adverse events 5
1/28/2020 SPRINT DBP (Lee, AJM 131:1228, 2018) • On treatment DBP < 56 at any visit was associated with higher MI, ACS, CVA, CHF, or death • Occurred in both aggressive and regular BP treatment groups INVEST AIM 144:884, 2006 • 22576 patients with CAD and HBP • Rx atenolol ± HCTz vs. verapamil ± trandolapril • No difference in outcomes between Rx groups • DBP <70 associated with more MI – Blood flow to heart occurs during diastole 6
1/28/2020 SPRINT & ACCORD Resistant HBP (Smith, AJM 131:1463, 2018) • Combined Sprint and Accord data • Resistant HBP is use 4+ meds or BP >130/80 on 3 meds • Most benefit in Resistant Hypertension How to decide who needs more and less BP treatment ? • Resistant needs more BP control • Use pulse pressure ? • Get more data (fundoscopy, albumin creatinine ratio, 24 hour BP monitor) – Normal BP (low office, low home) – White Coat (high office, low home) – Hypertension (high office, high home) – Masked (low office, high home) 7
1/28/2020 Masked HT or Sustained HT worse than White coat HBP or normal BP • 7295 people with ISH (DBP < 90) followed 10.6 years, 655 CV events • Sustained HT = cuff >140, amb>135 Masked = cuff <140, amb>135 White coat HT = cuff >140, amb<135 Normal BP = cuff <140, amb<135 • Hypertension 59:564, 2012 BP dipping (BP fall at night) Cuspidi et al. J Clin HBP 19:713, 2017 • 2900 dippers (nocturnal fall 10-20%) – Low risk • 2712 nondippers (nocturnal fall 0-10%) – Intermediate risk • 696 reverse dipper (nocturnal BP rise) Day 121/75 Night 108/68 – Highest risk • Extreme dipper Nonfatal and fatal CV events (nocturnal fall >20%) – Also low risk 8
1/28/2020 Hansen Nocturnal BP Hypertension 57:2, 2011 • 9,641 people in 8 studies • Mortality and CV events (CV death, MI, revasc, CHF, CVA) adjusted for sex, age, BMI, smoking, TC, HxCVD, DM, BP meds • Nighttime BP & not dipping more associated w mortality more c IDACO JAMA 322:4019 2019 • 11135 people followed 13.8 y (Europe, Asia, SA) • BP Office 132/80, automated office 135/82 • 24 h 123/73, Day 130/79, Night 113/64, Dip 13% • Nighttime BP predicted mortality, D&N predict CVAs 9
1/28/2020 HYGIA EurHeartJ 2019 • 19084 hypertensive Galicians (Spain) for 6.3 y • Age 61, 56% female, 23% DM, 15% smoker, 10% CAD, creatinine 1.06, albumin creatinine ratio 6 • HBP is SBP >135/85 awake or >120/70 asleep • BP Office 149/86, Wake 136/81, Sleep 123/70 • Average 1.8 meds: – Monotherapy ARBorACEI 69% CCB (amlodipine) 13% – Dual ARBorACEI/HCTz 43% ARBorACEI/CCB 26% – Triple ARBorACEI/HCTz/CCB 69% – ARB 53% HCTz 43% CCB 34% ACEI 24% BB 22% HYGIA EurHeartJ 2019 #2 • 19084 hypertensive Galicia (Spain) for 6.3 y • Randomized: all BP meds Awakening vs. Bedtime – If GLACOMA, excluded, NO BEDTIME BP MEDs • Awakening Bedtime • Number meds 1.8 1.7 * • Office BP 143/82 140/81 * • Waking BP 130/77 129/76 NS • Asleep BP 118/66 115/65 * • Dipping 13% 15% * • Creatinine 1.16 1.06 * 10
1/28/2020 HYGIA EurHeartJ 2019 #3 • Raw numbers not in paper, but to get OR 0.55, Bed n=643 vs AM n=1109, p = 2E-30 (p of p >99.99%) HYGIA #4 EurHeartJ 2019 • Bedtime dosing of BP meds clearly better than AM dosing • Benefit more if no prior BP rx and no prior CV event (right) • No difference in adverse events • IF GLACOMA, NO BEDTIME BP MEDs 11
1/28/2020 24 hour BP monitoring #1 • 73 M on Benicar 40 Metoprolol 100 Office 164/86 • Mean Day 127/65 Night 115/59 with White Coat • No further Rx needed 24 hour BP monitoring #2 • 59 F on no BP meds Office BP 152/90 • Mean Day 130/89 Night 128/81 (no dipping) • White coat (high office) but Nocturnal HBP, Rx 12
1/28/2020 24 hour BP monitoring #3 • 57 F on no meds Office BP 146/86 • Mean Day 156/96 Night 157/94 – mild office HBP but Masked severe HBP with reverse dipping – Rx 24 hour BP monitoring #4 • 55 M DMx20y A1c 12 on Lisinopril 2.5 Office BP 98/66 sitting 72/50 standing with presyncope • Mean Day 99/67 night 116/80 – Rx orthostasis 13
1/28/2020 Which BP agent ? • 50+ trials in mostly in moderate-severe HBP • Thiazides better than placebo (MRC, SHEP, lots) • Thiazides better than β blockers (MRC) • ARB better than β blockers (LIFE) • ACEI better dihydropyridine (StopHBP2, Insight) • In DM, ACEI better dihydropyridine (ABCD, FACET) • In CRI, ACEI orARB better than no (many, Renaal, Idnt) • In CRI, ACEI better than dihydropyridine or βB (AASK) • In mild hypertension, thiazides = ACEI = amlodipine and all three better than α blockers • In moderate hypertension, thiazides = ACEI/ARB >other Beta blocker inferior to ACEI, ARB, CCB, and diuretics • Ettehad Lancet 387:957, 2015 14
1/28/2020 LEGEND Lancet 2019 (Suchard) • 4,893,591 patients with new onset of and new single agent treatment for hypertension • From OHDSI global network of 6 claim and 3 EMR databases with data from 1996-2018 • Corrected for treatment bias (eg ACEI in DM) • Thiazides (mostly HCTz) 861k 17% • ACEI (mostly lisinopril) 2373k 48% • ARB (mostly losartan) 752k 16% • dCCB (mostly amlodipine) 799k 15% • ndCCB (mostly diltiazem) 139k 3% LEGEND Lancet 2019 (Suchard) • ARB vs Thiazide: ARB more hyperkalemia, Thiazide more hypokalemia and hyponatremia – overall SIMILAR 15
1/28/2020 LEGEND Lancet 2019 (Suchard) • ACEi vs Thiazide: ACEi had more mortality, diarrhea, GI bleed, AKI, high K, hypotension, angioedema cough LEGEND Lancet 2019 (Suchard) • Dihydropyridine vs Thiazide: DHP more mortality, dementia, CRI, ESRD, high K, neutropenia, low platelets thrombocytopenia 16
1/28/2020 LEGEND Lancet 2019 (Suchard) • Diltiazem/Verapamil vs Thiazide: more mortality, low HR, TIA, dementia, GI bleed, AKI, ESRD, high K, hypotension Summary of BP treatment • Best agents are THIAZIDEs and ARBs – Second agents ACEi or dihydropyridine • Bedtime dosing (except GLACOMA) • Consider 24 hour monitoring to Rx Nocturnal BP (goal <120/70) • β blockers and α blockers clearly inferior • Do not use ACEI and ARB (ONTARGET) – combination no benefit & more adverse effects • Dihydropridines ok as 3 rd line, less effective on outcomes if DM or CRI 17
Recommend
More recommend
