The main goal of treatment is to decrease the risk of mortality and of cardiovascular and renal morbidity.[4]Hansson L, Zanchetti A, Carruthers SG, et al. Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial. Lancet. 1998 Jun 13;351(9118):1755-62.
http://www.ncbi.nlm.nih.gov/pubmed/9635947?tool=bestpractice.com
[60]Musini VM, Tejani AM, Bassett K, et al. Pharmacotherapy for hypertension in adults 60 years or older. Cochrane Database Syst Rev. 2019 Jun 5;(6):CD000028.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD000028.pub3/full
http://www.ncbi.nlm.nih.gov/pubmed/31167038?tool=bestpractice.com
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How does pharmacotherapy affect outcomes in people aged 60 years or older with hypertension?/cca.html?targetUrl=https://www.cochranelibrary.com/cca/doi/10.1002/cca.2634/fullShow me the answer The following recommendations are based on the Eighth Joint National Committee (JNC 8) guidelines. JNC 8 states that blood pressure (BP) goal should be <140/90 mmHg for adults ages 18-59 years, including those with diabetes or chronic kidney disease, and <150/90 mmHg in the general population beginning at age 60 years.[3]James PA, Oparil S, Carter BL, et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2014 Feb 5;311(5):507-20.
https://jamanetwork.com/journals/jama/fullarticle/1791497
http://www.ncbi.nlm.nih.gov/pubmed/24352797?tool=bestpractice.com
In contrast, the American College of Cardiology/American Heart Association (ACC/AHA) guidelines recommend a BP target of <130/80 mmHg for adults, regardless of age, with confirmed hypertension and known cardiovascular disease (CVD), or a 10-year atherosclerotic CVD risk (using the atherosclerotic CVD [ASCVD] risk estimator) of 10% or more.[5]Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2018 May 15;71(19):e127-248.
https://www.jacc.org/doi/full/10.1016/j.jacc.2017.11.006
http://www.ncbi.nlm.nih.gov/pubmed/29146535?tool=bestpractice.com
American College of Cardiology: ASCVD risk estimator plus
external link opens in a new window For adults with confirmed hypertension without additional markers of increased CVD risk, a BP target of <130/80 mmHg may be reasonable.
In the general population ages ≥60 years, the JNC 8 guideline recommends pharmacologic therapy to lower blood pressure when BP ≥150/90 mmHg.[3]James PA, Oparil S, Carter BL, et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2014 Feb 5;311(5):507-20.
https://jamanetwork.com/journals/jama/fullarticle/1791497
http://www.ncbi.nlm.nih.gov/pubmed/24352797?tool=bestpractice.com
However, some panel members recommended retaining the JNC 7 systolic BP goal of <140 mmHg, concluding that there was insufficient evidence to implement the less intensive target in high-risk groups, including black people, those with cardiovascular disease, and those with multiple risk factors.[61]Wright Jr JT, Fine LJ, Lackland DT, et al. Evidence supporting a systolic blood pressure goal of less than 150 mmHg in patients aged 60 years or older: the minority view. Ann Intern Med. 2014 Apr 1;160(7):499-503.
https://www.acpjournals.org/doi/10.7326/M13-2981?articleid=1813288
http://www.ncbi.nlm.nih.gov/pubmed/24424788?tool=bestpractice.com
The American College of Physicians and American Academy of Family Physicians joint guideline recommends that treatment is initiated in adults ages ≥60 years with systolic BP persistently ≥150 mmHg to achieve a target systolic blood pressure of <150 mmHg to reduce the risk for mortality, stroke, and cardiac events.[62]Qaseem A, Wilt TJ, Rich R, et al. Pharmacologic treatment of hypertension in adults aged 60 years or older to higher versus lower blood pressure targets: a clinical practice guideline from the American College of Physicians and the American Academy of Family Physicians. Ann Intern Med. 2017 Mar 21;166(6):430-7.
https://www.acpjournals.org/doi/10.7326/M16-1785
http://www.ncbi.nlm.nih.gov/pubmed/28135725?tool=bestpractice.com
The joint guideline recommends considering treating adults ≥60 years old with a history of stroke or transient ischemic attack, or at high cardiovascular risk, to achieve a target systolic blood pressure of <140 mmHg.[62]Qaseem A, Wilt TJ, Rich R, et al. Pharmacologic treatment of hypertension in adults aged 60 years or older to higher versus lower blood pressure targets: a clinical practice guideline from the American College of Physicians and the American Academy of Family Physicians. Ann Intern Med. 2017 Mar 21;166(6):430-7.
https://www.acpjournals.org/doi/10.7326/M16-1785
http://www.ncbi.nlm.nih.gov/pubmed/28135725?tool=bestpractice.com
The European Society of Cardiology/European Society of Hypertension guidelines recommend a desired target systolic BP of 130-139 mmHg for adults aged >65 years.[2]Williams B, Mancia G, Spiering W, et al. 2018 ESC/ESH guidelines for the management of arterial hypertension. Eur Heart J. 2018 Sep 1;39(33):3021-104.
https://academic.oup.com/eurheartj/article/39/33/3021/5079119
http://www.ncbi.nlm.nih.gov/pubmed/30165516?tool=bestpractice.com
US and European guidelines - classification and management
external link opens in a new window
Evolving treatment goals
Blood pressure goals are evolving as more studies are being carried out.[63]Xie X, Atkins E, Lv J, et al. Effects of intensive blood pressure lowering on cardiovascular and renal outcomes: updated systematic review and meta-analysis. Lancet. 2016 Jan 30;387(10017):435-43.
http://www.ncbi.nlm.nih.gov/pubmed/26559744?tool=bestpractice.com
The SPRINT trial (Systolic Blood Pressure Intervention Trial) ended early as it found that a lower systolic target of 120 mmHg (as measured by automated office blood pressure [AOBP]) reduced cardiovascular complications and deaths in people ages over 50 years with high blood pressure and at least one additional risk factor for heart disease.[6]The SPRINT Study Research Group. Systolic Blood Pressure Intervention Trial. 2016 [internet publication].
https://www.sprinttrial.org/public/dspHome.cfm
[64]Wright JT Jr, Williamson JD, Whelton PK, et al; SPRINT Research Group. A randomized trial of intensive versus standard blood-pressure control. N Engl J Med. 2015 Nov 26;373(22):2103-16.
https://www.nejm.org/doi/full/10.1056/NEJMoa1511939
http://www.ncbi.nlm.nih.gov/pubmed/26551272?tool=bestpractice.com
[65]Vaduganathan M, Claggett BL, Juraschek SP, et al. Assessment of long-term benefit of intensive blood pressure control on residual life span: secondary analysis of the Systolic Blood Pressure Intervention Trial (SPRINT). JAMA Cardiol. 2020 May 1;5(5):576-81.
http://www.ncbi.nlm.nih.gov/pubmed/32101262?tool=bestpractice.com
Patients with diabetes or stroke were excluded from the trial. However, in the HOPE-3 trial, intermediate-risk people without cardiovascular disease did not benefit from BP lowering unless in the highest tertile of starting BP (>143.5 mmHg) (as opposed to higher-risk patients in SPRINT).[66]Lonn EM, Bosch J, López-Jaramillo P, et al; HOPE-3 Investigators. Blood-pressure lowering in intermediate-risk persons without cardiovascular disease. N Engl J Med. 2016 May 26;374(21):2009-20.
http://www.ncbi.nlm.nih.gov/pubmed/27041480?tool=bestpractice.com
Because of differences in the general health of older patients, the decision to treat should be on an individual basis, and BP lowering should be gradual and carefully monitored by the physician.[2]Williams B, Mancia G, Spiering W, et al. 2018 ESC/ESH guidelines for the management of arterial hypertension. Eur Heart J. 2018 Sep 1;39(33):3021-104.
https://academic.oup.com/eurheartj/article/39/33/3021/5079119
http://www.ncbi.nlm.nih.gov/pubmed/30165516?tool=bestpractice.com
[67]Beckett NS, Peters R, Fletcher AE, et al; HYVET Study Group. Treatment of hypertension in patients 80 years of age or older. N Engl J Med. 2008 May 1;358(18):1887-98.
https://www.nejm.org/doi/full/10.1056/NEJMoa0801369
http://www.ncbi.nlm.nih.gov/pubmed/18378519?tool=bestpractice.com
The SPRINT trial results showed equal benefit in people ages >75 years, regardless of frailty or walking speed.[68]Williamson JD, Supiano MA, Applegate WB, et al; SPRINT Research Group. Intensive vs standard blood pressure control and cardiovascular disease outcomes in adults aged ≥75 years: a randomized clinical trial. JAMA. 2016 Jun 28;315(24):2673-82.
https://jamanetwork.com/journals/jama/fullarticle/2524266
http://www.ncbi.nlm.nih.gov/pubmed/27195814?tool=bestpractice.com
Patients with orthostasis at enrollment, patients with dementia, and those resident in a nursing home were excluded from the trial. One systematic review found insufficient evidence regarding the benefits of hypertension treatment for frail people >80 years of age taking multiple medications, concluding that treatment should be individualized.[69]Benetos A, Rossignol P, Cherubini A, et al. Polypharmacy in the aging patient: management of hypertension in octogenarians. JAMA. 2015 Jul 14;314(2):170-80.
http://www.ncbi.nlm.nih.gov/pubmed/26172896?tool=bestpractice.com
Older patients >80 years should not be denied treatment or have treatment withdrawn solely on the basis of age.[2]Williams B, Mancia G, Spiering W, et al. 2018 ESC/ESH guidelines for the management of arterial hypertension. Eur Heart J. 2018 Sep 1;39(33):3021-104.
https://academic.oup.com/eurheartj/article/39/33/3021/5079119
http://www.ncbi.nlm.nih.gov/pubmed/30165516?tool=bestpractice.com
Regarding patients with concomitant diabetes mellitus, there is good-quality evidence from the ACCORD trial that very intensive BP lowering (targeting a systolic pressure <120 mmHg, as compared with targeting <140 mmHg) does not lessen risk (composite outcome: nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular cause) and may increase risk of adverse events.[70]Cushman WC, Evans GW, Byington RP, et al; ACCORD Study Group. Effects of intensive blood-pressure control in type 2 diabetes mellitus. N Engl J Med. 2010 Apr 29;362(17):1575-85.
https://www.nejm.org/doi/full/10.1056/NEJMoa1001286
http://www.ncbi.nlm.nih.gov/pubmed/20228401?tool=bestpractice.com
The American Diabetes Association recommends that blood pressure targets in people with diabetes and hypertension are individualized by assessing cardiovascular risk, potential adverse effects, and patient preference.[71]American Diabetes Association. Standards of medical care in diabetes - 2020. Diabetes Care. 2020 Jan;43(Suppl 1):S1-212.
https://care.diabetesjournals.org/content/43/Supplement_1
Targets for people with diabetes range from <130/80 mmHg for those at higher risk and <140/90 mmHg for those at lower risk; for pregnant patients with diabetes, the recommended target is ≤135/85 mmHg.[71]American Diabetes Association. Standards of medical care in diabetes - 2020. Diabetes Care. 2020 Jan;43(Suppl 1):S1-212.
https://care.diabetesjournals.org/content/43/Supplement_1
Lower systolic and diastolic blood pressure targets, such as 130/80 mmHg, may be appropriate for individuals at high risk of cardiovascular disease if they can be achieved without undue treatment burden. The ACC/AHA recommend a blood pressure goal of <130/80 mmHg for patients with diabetes.[5]Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2018 May 15;71(19):e127-248.
https://www.jacc.org/doi/full/10.1016/j.jacc.2017.11.006
http://www.ncbi.nlm.nih.gov/pubmed/29146535?tool=bestpractice.com
Lifestyle modification
The initial approach to a newly diagnosed patient should include a thorough explanation of the risks associated with hypertension and the need for adequate control and adherence to therapy. Initial therapeutic measure should be lifelong lifestyle modification including:[2]Williams B, Mancia G, Spiering W, et al. 2018 ESC/ESH guidelines for the management of arterial hypertension. Eur Heart J. 2018 Sep 1;39(33):3021-104.
https://academic.oup.com/eurheartj/article/39/33/3021/5079119
http://www.ncbi.nlm.nih.gov/pubmed/30165516?tool=bestpractice.com
[5]Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2018 May 15;71(19):e127-248.
https://www.jacc.org/doi/full/10.1016/j.jacc.2017.11.006
http://www.ncbi.nlm.nih.gov/pubmed/29146535?tool=bestpractice.com
[36]Sacks FM, Svetkey LP, Vollmer WM, et al. Effects on blood pressure of reduced dietary sodium and the Dietary Approaches to Stop Hypertension (DASH) diet. DASH-Sodium Collaborative Research Group. N Engl J Med. 2001 Jan 4;344(1):3-10.
https://www.nejm.org/doi/full/10.1056/NEJM200101043440101
http://www.ncbi.nlm.nih.gov/pubmed/11136953?tool=bestpractice.com
[72]Geleijinse JM, Kork FJ, Grobbee DE. Blood pressure response to changes in sodium and potassium intake: a meta-regression analysis of randomized trials. J Hum Hypertens. 2003 Jul;17(7):471-80.
http://www.ncbi.nlm.nih.gov/pubmed/12821954?tool=bestpractice.com
[73]Whelton SP, Chin A, Xin X, et al. Effect of aerobic exercise on blood pressure: a meta-analysis of randomized, controlled trials. Ann Intern Med. 2002 Apr 2;136(7):493-503.
http://www.ncbi.nlm.nih.gov/pubmed/11926784?tool=bestpractice.com
[74]Hartley TR, Lovallo WR, Whisett TL, et al. Cardiovascular effects of caffeine in men and women. Am J Cardiol. 2004 Apr 15;93(8):1022-6.
http://www.ncbi.nlm.nih.gov/pubmed/15081447?tool=bestpractice.com
Sodium reduction (optimal goal ≤1.5 g/day)
Potassium supplementation (3.5 to 5.0 g/day): preferably by consumption of a potassium-rich diet unless contraindicated in the presence of chronic kidney disease or use of medication that reduces potassium excretion
Dietary Approaches to Stop Hypertension (DASH) diet (8-10 servings of fruit and vegetables daily, whole grains, low sodium, low-fat proteins)
Waist circumference <40 inches (<102 cm) for men and <35 inches (<88 cm) for women; weight loss to a BMI of about 25 kg/m²
Increased physical activity: at least 30 minutes of moderate-intensity, dynamic aerobic exercise (walking, jogging, cycling, or swimming) 5 days per week to total 150 minutes per week, as tolerated or recommended by physician
Limited alcohol consumption: ≤2 standard drinks (<20-30 g alcohol) per day in hypertensive men; ≤1 standard drink (<10-20 g alcohol) per day in hypertensive women. Total weekly alcohol consumption should not exceed 140 g for men and 80 g for women.
Advice about lifestyle modification should be given upon diagnosis and should continue concurrently with all other therapeutic measures. Prior to initiation of an exercise program, patients should discuss a plan with their healthcare provider.
Smoking cessation should always be encouraged as well, to promote general vascular health, though smoking cessation has not been associated with decreased BP.
A 3-month trial is recommended in adherent patients willing to make therapeutic lifestyle changes, prior to determining that pharmacologic therapy is necessary. Most patients will require drug therapy to achieve target BP control.
Antihypertensive drugs
The main classes of antihypertensives include:[2]Williams B, Mancia G, Spiering W, et al. 2018 ESC/ESH guidelines for the management of arterial hypertension. Eur Heart J. 2018 Sep 1;39(33):3021-104.
https://academic.oup.com/eurheartj/article/39/33/3021/5079119
http://www.ncbi.nlm.nih.gov/pubmed/30165516?tool=bestpractice.com
[5]Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2018 May 15;71(19):e127-248.
https://www.jacc.org/doi/full/10.1016/j.jacc.2017.11.006
http://www.ncbi.nlm.nih.gov/pubmed/29146535?tool=bestpractice.com
Diuretics:
ACE inhibitors: lisinopril, enalapril, captopril
Angiotensin-II receptor antagonists: candesartan, irbesartan, losartan, valsartan
Calcium-channel blockers: amlodipine, diltiazem
Beta-blockers: metoprolol, bisoprolol, carvedilol.
Beta-blockers are not recommended for first-line treatment of hypertension except in the presence of coronary artery disease, heart failure, or atrial fibrillation.[5]Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2018 May 15;71(19):e127-248.
https://www.jacc.org/doi/full/10.1016/j.jacc.2017.11.006
http://www.ncbi.nlm.nih.gov/pubmed/29146535?tool=bestpractice.com
The examples of antihypertensive drugs listed are common examples of drugs in each class only; other drugs are available. Some of these drugs are available in fixed-dose combination formulations. These single pill formulations simplify dosing regimens and improve adherence.[2]Williams B, Mancia G, Spiering W, et al. 2018 ESC/ESH guidelines for the management of arterial hypertension. Eur Heart J. 2018 Sep 1;39(33):3021-104.
https://academic.oup.com/eurheartj/article/39/33/3021/5079119
http://www.ncbi.nlm.nih.gov/pubmed/30165516?tool=bestpractice.com
[75]Gradman AH, Basile JN, Carter BL, et al; American Society of Hypertension Writing Group. Combination therapy in hypertension. J Am Soc Hypertens. 2010 Jan-Feb;4(1):42-50.
http://www.ncbi.nlm.nih.gov/pubmed/20374950?tool=bestpractice.com
Calcium-channel blockers may cause peripheral edema that can lead to a diuretic being prescribed; however, diuretics are generally not indicated in this situation.[76]Savage RD, Visentin JD, Bronskill SE, et al. Evaluation of a common prescribing cascade of calcium channel blockers and diuretics in older adults with hypertension. JAMA Intern Med. 2020 May 1;180(5):643-51.
http://www.ncbi.nlm.nih.gov/pubmed/32091538?tool=bestpractice.com
Drug therapy for stage 1
The ACC/AHA guidelines define stage 1 hypertension as BP 130-139/80-89 mmHg.[5]Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2018 May 15;71(19):e127-248.
https://www.jacc.org/doi/full/10.1016/j.jacc.2017.11.006
http://www.ncbi.nlm.nih.gov/pubmed/29146535?tool=bestpractice.com
The European Society of Cardiology/European Society of Hypertension guidelines define this category of BP as high-normal BP.[2]Williams B, Mancia G, Spiering W, et al. 2018 ESC/ESH guidelines for the management of arterial hypertension. Eur Heart J. 2018 Sep 1;39(33):3021-104.
https://academic.oup.com/eurheartj/article/39/33/3021/5079119
http://www.ncbi.nlm.nih.gov/pubmed/30165516?tool=bestpractice.com
For stage 1 hypertension, combination therapy or monotherapy where appropriate can be initiated.[2]Williams B, Mancia G, Spiering W, et al. 2018 ESC/ESH guidelines for the management of arterial hypertension. Eur Heart J. 2018 Sep 1;39(33):3021-104.
https://academic.oup.com/eurheartj/article/39/33/3021/5079119
http://www.ncbi.nlm.nih.gov/pubmed/30165516?tool=bestpractice.com
[77]Salam A, Kanukula R, Atkins E, et al. Efficacy and safety of dual combination therapy of blood pressure-lowering drugs as initial treatment for hypertension: a systematic review and meta-analysis of randomized controlled trials. J Hypertens. 2019 Sep;37(9):1768-74.
http://www.ncbi.nlm.nih.gov/pubmed/30986788?tool=bestpractice.com
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How does first‐line combination therapy compare with first‐line monotherapy in people with primary hypertension?/cca.html?targetUrl=https://www.cochranelibrary.com/cca/doi/10.1002/cca.3009/fullShow me the answer The choice of antihypertensive agent is driven by efficacy, adverse-effect profile, and cost. The ACC/AHA guidelines recommend initiating a single antihypertensive agent for patients with a 10-year atherosclerotic CVD risk ≥10% or known cardiovascular disease, diabetes, or chronic kidney disease.[5]Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2018 May 15;71(19):e127-248.
https://www.jacc.org/doi/full/10.1016/j.jacc.2017.11.006
http://www.ncbi.nlm.nih.gov/pubmed/29146535?tool=bestpractice.com
American College of Cardiology: ASCVD risk estimator plus
external link opens in a new window European guidelines recommend initiating antihypertensive treatment with a two-drug combination, preferably a single pill combination, with the exception of patients with high-normal BP and a high cardiovascular risk or in frail older patients in whom initiating treatment with monotherapy may be appropriate.[2]Williams B, Mancia G, Spiering W, et al. 2018 ESC/ESH guidelines for the management of arterial hypertension. Eur Heart J. 2018 Sep 1;39(33):3021-104.
https://academic.oup.com/eurheartj/article/39/33/3021/5079119
http://www.ncbi.nlm.nih.gov/pubmed/30165516?tool=bestpractice.com
In patients with high-normal BP and a high cardiovascular risk only a small reduction in BP may be required to achieve the BP target and in frail older patients baroreflex sensitivity is frequently impaired and the risk of hypotension is greater.[2]Williams B, Mancia G, Spiering W, et al. 2018 ESC/ESH guidelines for the management of arterial hypertension. Eur Heart J. 2018 Sep 1;39(33):3021-104.
https://academic.oup.com/eurheartj/article/39/33/3021/5079119
http://www.ncbi.nlm.nih.gov/pubmed/30165516?tool=bestpractice.com
Many people with stage 1 hypertension have a constellation of other cardiovascular risk factors such as smoking or mild dyslipidemia that increase the importance of BP lowering.
If BP cannot be controlled with a single agent, a drug from a different class of antihypertensives is added.
Generally, when an ACE inhibitor would usually be chosen but is not tolerated, an angiotensin-II receptor antagonist can be substituted.
Stage 1 hypertension: without CVD-related comorbidity or chronic renal disease, or with diabetes
A choice among four preferred classes of drugs is recommended for initial therapy.[2]Williams B, Mancia G, Spiering W, et al. 2018 ESC/ESH guidelines for the management of arterial hypertension. Eur Heart J. 2018 Sep 1;39(33):3021-104.
https://academic.oup.com/eurheartj/article/39/33/3021/5079119
http://www.ncbi.nlm.nih.gov/pubmed/30165516?tool=bestpractice.com
[5]Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2018 May 15;71(19):e127-248.
https://www.jacc.org/doi/full/10.1016/j.jacc.2017.11.006
http://www.ncbi.nlm.nih.gov/pubmed/29146535?tool=bestpractice.com
[78]Bangalore S, Fakheri R, Toklu B, et al. Diabetes mellitus as a compelling indication for use of renin angiotensin system blockers: systematic review and meta-analysis of randomized trials. BMJ. 2016 Feb 11;352:i438.
https://www.bmj.com/content/352/bmj.i438.long
http://www.ncbi.nlm.nih.gov/pubmed/26868137?tool=bestpractice.com
[79]Suchard MA, Schuemie MJ, Krumholz HM, et al. Comprehensive comparative effectiveness and safety of first-line antihypertensive drug classes: a systematic, multinational, large-scale analysis. Lancet. 2019 Nov 16;394(10211):1816-26.
http://www.ncbi.nlm.nih.gov/pubmed/31668726?tool=bestpractice.com
Thiazide (or thiazide-like) diuretics have been shown to be safe and efficacious first-line therapy.[80]Wright JM, Musini VM, Gill R. First-line drugs for hypertension. Cochrane Database Syst Rev. 2018 Apr 18;(4):CD001841.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD001841.pub3/full
http://www.ncbi.nlm.nih.gov/pubmed/29667175?tool=bestpractice.com
They also decrease renal calcium excretion, so may be a good choice for women with osteoporosis. As with all antihypertensive medications, the initial dose should be the lowest possible, and then titrated for a therapeutic effect, while observing for potential adverse effects.
Alternative first-line choices include ACE inhibitors, angiotensin-II receptor antagonists, or calcium-channel blockers, or a combination of two different drugs from these classes (excluding the combination of ACE inhibitors and angiotensin-II receptor antagonists).
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How do renin‐angiotensin system inhibitors compare with other first‐line antihypertensive drugs in people with hypertension?/cca.html?targetUrl=https://www.cochranelibrary.com/cca/doi/10.1002/cca.2375/fullShow me the answer Aliskiren, a direct renin inhibitor, is also available; however, its place in the treatment pathway is not yet clear due to concerns about risks in combination with ACE inhibitors or angiotensin-II receptor antagonists, and in the settings of diabetes or renal impairment, and it is not considered to be a preferred option.[6]The SPRINT Study Research Group. Systolic Blood Pressure Intervention Trial. 2016 [internet publication].
https://www.sprinttrial.org/public/dspHome.cfm
In the general black population, including those with diabetes, a thiazide (or thiazide-like) diuretic or a calcium-channel blocker is recommended as initial pharmacologic therapy.[2]Williams B, Mancia G, Spiering W, et al. 2018 ESC/ESH guidelines for the management of arterial hypertension. Eur Heart J. 2018 Sep 1;39(33):3021-104.
https://academic.oup.com/eurheartj/article/39/33/3021/5079119
http://www.ncbi.nlm.nih.gov/pubmed/30165516?tool=bestpractice.com
[5]Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2018 May 15;71(19):e127-248.
https://www.jacc.org/doi/full/10.1016/j.jacc.2017.11.006
http://www.ncbi.nlm.nih.gov/pubmed/29146535?tool=bestpractice.com
The recommendation is derived from a prespecified subgroup analysis of black patients, 46% of whom had diabetes, in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) trial.[81]The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs. diuretic: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA. 2002 Dec 18;288(23):2981-97.
https://jamanetwork.com/journals/jama/fullarticle/195626
http://www.ncbi.nlm.nih.gov/pubmed/12479763?tool=bestpractice.com
[82]Leenen FH, Nwachuku CE, Black HR, et al. Clinical events in high-risk hypertensive patients randomly assigned to calcium channel blocker versus angiotensin-converting enzyme inhibitor in the antihypertensive and lipid-lowering treatment to prevent heart attack trial. Hypertension. 2006 Sep;48(3):374-84.
https://www.ahajournals.org/doi/full/10.1161/01.hyp.0000231662.77359.de
http://www.ncbi.nlm.nih.gov/pubmed/16864749?tool=bestpractice.com
In patients with diabetes who have increased albumin excretion, ACE inhibitors or angiotensin-II receptor antagonists are recommended. The ALLHAT study showed that chlorthalidone, amlodipine, or lisinopril were co-equal for mild hypertension in type 2 diabetes.[81]The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs. diuretic: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA. 2002 Dec 18;288(23):2981-97.
https://jamanetwork.com/journals/jama/fullarticle/195626
http://www.ncbi.nlm.nih.gov/pubmed/12479763?tool=bestpractice.com
ACE inhibitors are renoprotective, decreasing the progression of proteinuria in patients with diabetes.[83]Thurman JM, Schrier RW. Comparative effects of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers on blood pressure and the kidney. Am J Med. 2003 May;114(7):588-98.
http://www.ncbi.nlm.nih.gov/pubmed/12753883?tool=bestpractice.com
Sleep-time BP is the most significant independent prognostic marker of cardiovascular events in diabetes.
Comorbid coronary artery disease
Beta-blockers are first-line. Beta-blockers have proven beneficial in patients with chronic stable angina, post-myocardial infarction, or congestive heart failure (CHF), in patients with coronary artery disease (CAD) undergoing surgery, or in patients with hypertrophic obstructive cardiomyopathy.[84]Beta Blocker Heart Attack Trial. A randomized trial of propranolol in patients with acute myocardial infarction. I. Mortality results. JAMA. 1982 Mar 26;247(12):1707-14.
http://www.ncbi.nlm.nih.gov/pubmed/7038157?tool=bestpractice.com
[85]Pfeffer MA, Braunwald E, Moye LA, et al. Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction: results of the Survival and Ventricular Enlargement Trial. N Engl J Med. 1992 Sep 3;327(10):669-77.
http://www.ncbi.nlm.nih.gov/pubmed/1386652?tool=bestpractice.com
[86]Tepper D. Frontiers in congestive heart failure: effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomized Intervention Trial in Congestive Heart Failure (MERIT-HF). Congest Heart Fail. 1999 Jul-Aug;5(4):184-5.
http://www.ncbi.nlm.nih.gov/pubmed/12189311?tool=bestpractice.com
[87]Packer M, Coats AJ, Fowler MB, et al. Effect of carvedilol on survival in severe chronic heart failure. N Engl J Med. 2001 May 31;344(22):1651-8.
https://www.nejm.org/doi/full/10.1056/NEJM200105313442201
http://www.ncbi.nlm.nih.gov/pubmed/11386263?tool=bestpractice.com
[88]Lindenauer PK, Fitzgerald J, Hoople N, et al. The potential preventability of postoperative myocardial infarction: underuse of perioperative beta-adrenergic blockade. Arch Intern Med. 2004 Apr 12;164(7):762-6.
https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/216902
http://www.ncbi.nlm.nih.gov/pubmed/15078646?tool=bestpractice.com
ACE inhibitors have been shown in some trials to decrease cardiovascular events, while other studies have not demonstrated a benefit for ACE inhibitors in the setting of stable CAD with normal left ventricular function.[89]Yusuf S, Sleight P, Pogue J, et al; Heart Outcomes Prevention Evaluation Study Investigators. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. N Engl J Med. 2000 Jan 20;342(3):145-53.
https://www.nejm.org/doi/full/10.1056/NEJM200001203420301
http://www.ncbi.nlm.nih.gov/pubmed/10639539?tool=bestpractice.com
[90]The European Trial on Reduction of Cardiac Events with Perindopril in Stable Coronary Artery Disease Investigators. Efficacy of perindopril in reduction of cardiovascular events among patients with stable coronary artery disease: randomised, double-blind, placebo-controlled, multicentre trial (the EUROPA study). Lancet. 2003 Sep 6;362(9386):782-8.
http://www.ncbi.nlm.nih.gov/pubmed/13678872?tool=bestpractice.com
[91]Braunwald E, Domanski MJ, Fowler SE, et al; PEACE Trial Investigators. Angiotensin-converting-enzyme inhibition in stable coronary artery disease. N Engl J Med. 2004 Nov 11;351(20):2058-68.
https://www.nejm.org/doi/full/10.1056/NEJMoa042739
http://www.ncbi.nlm.nih.gov/pubmed/15531767?tool=bestpractice.com
Beta-blockers, ACE inhibitors, or angiotensin-II receptor antagonists can be used as first-line for compelling indications (e.g., previous myocardial infarction, stable angina).[2]Williams B, Mancia G, Spiering W, et al. 2018 ESC/ESH guidelines for the management of arterial hypertension. Eur Heart J. 2018 Sep 1;39(33):3021-104.
https://academic.oup.com/eurheartj/article/39/33/3021/5079119
http://www.ncbi.nlm.nih.gov/pubmed/30165516?tool=bestpractice.com
[5]Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2018 May 15;71(19):e127-248.
https://www.jacc.org/doi/full/10.1016/j.jacc.2017.11.006
http://www.ncbi.nlm.nih.gov/pubmed/29146535?tool=bestpractice.com
Other drugs such as dihydropyridine calcium-channel blockers, thiazide diuretics, and/or mineralocorticoid receptor antagonists are added as required to further control hypertension.
Many patients with CAD also take nitrates, which act as exogenous nitric oxide donor. Modest reductions in systolic BP can be observed, but the Food and Drug Administration has not approved the use of nitrates solely as antihypertensive therapy.[13]Saad MF, Rewers M, Selby J, et al. Insulin resistance and hypertension: the Insulin Resistance Atherosclerosis Study. Hypertension. 2004 Jun;43(6):1324-31.
https://www.ahajournals.org/doi/full/10.1161/01.hyp.0000128019.19363.f9
http://www.ncbi.nlm.nih.gov/pubmed/15123571?tool=bestpractice.com
Comorbid heart failure with reduced ejection fraction
In patients with comorbid heart failure with reduced ejection fraction (<40%), an ACE inhibitor (or an angiotensin-II receptor antagonist if not tolerated) plus a beta-blocker with or without an aldosterone antagonist is used.
ACE inhibition has been shown to convey a survival advantage in patients with CHF.[85]Pfeffer MA, Braunwald E, Moye LA, et al. Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction: results of the Survival and Ventricular Enlargement Trial. N Engl J Med. 1992 Sep 3;327(10):669-77.
http://www.ncbi.nlm.nih.gov/pubmed/1386652?tool=bestpractice.com
[92]The CONSENSUS Trial Study Group. Effects of enalapril on mortality in severe congestive heart failure: results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS). N Engl J Med. 1987 Jun 4;316(23):1429-35.
http://www.ncbi.nlm.nih.gov/pubmed/2883575?tool=bestpractice.com
Angiotensin-II receptor antagonists also decrease morbidity and mortality.[93]Dickstein K, Kjekshus J. Effects of losartan and captopril on mortality and morbidity in high-risk patients after acute myocardial infarction: the OPTIMAAL randomised trial. Lancet. 2002 Sep 7;360(9335):752-60.
http://www.ncbi.nlm.nih.gov/pubmed/12241832?tool=bestpractice.com
[94]McMurray J, Östergren J, Pfeffer M, et al. Clinical features and contemporary management of patients with low and preserved ejection fraction heart failure: baseline characteristics of patients in the Candesartan in Heart failure-Assessment of Reduction in Mortality and morbidity (CHARM) programme. Eur J Heart Fail. 2003 Jun;5(3):261-70.
https://onlinelibrary.wiley.com/doi/full/10.1016/S1388-9842%2803%2900052-7
http://www.ncbi.nlm.nih.gov/pubmed/12798823?tool=bestpractice.com
Compared with ACE inhibitors, angiotensin-II receptor antagonists were equivalent, but not superior, in the treatment of patients with CHF.[95]Black HR, Sollins JS, Garofalo JL. The addition of doxazosin to the therapeutic regimen of hypertensive patients inadequately controlled with other antihypertensive medications: a randomized, placebo-controlled study. Am J Hypertens. 2000 May;13(5 Pt 1):468-74.
http://www.ncbi.nlm.nih.gov/pubmed/10826396?tool=bestpractice.com
[96]Velasquez EJ, Pfeffer MA, McMurray JV, et al; VALIANT Investigators. VALsartan In Acute myocardial iNfarcTion (VALIANT) trial: baseline characteristics in context. Eur J Heart Fail. 2003 Aug;5(4):537-44.
https://onlinelibrary.wiley.com/doi/full/10.1016/S1388-9842%2803%2900112-0
http://www.ncbi.nlm.nih.gov/pubmed/12921816?tool=bestpractice.com
Beta-blockers have proven mortality benefits in patients with chronic CHF.[86]Tepper D. Frontiers in congestive heart failure: effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomized Intervention Trial in Congestive Heart Failure (MERIT-HF). Congest Heart Fail. 1999 Jul-Aug;5(4):184-5.
http://www.ncbi.nlm.nih.gov/pubmed/12189311?tool=bestpractice.com
[87]Packer M, Coats AJ, Fowler MB, et al. Effect of carvedilol on survival in severe chronic heart failure. N Engl J Med. 2001 May 31;344(22):1651-8.
https://www.nejm.org/doi/full/10.1056/NEJM200105313442201
http://www.ncbi.nlm.nih.gov/pubmed/11386263?tool=bestpractice.com
Aldosterone antagonists should be given to patients with heart failure and ejection fraction under 35% who are taking optimized ACE inhibitor or angiotensin-II receptor antagonist plus beta-blocker treatment, who still require antihypertensive therapy. Blockade of aldosterone has been associated with decreased end-organ fibrosis.[97]Pitt B, Zannad F, Remme WJ, et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure: Randomized Aldactone Evaluation Study Investigators. N Engl J Med. 1999 Sep 2;341(10):709-17.
https://www.nejm.org/doi/full/10.1056/NEJM199909023411001
http://www.ncbi.nlm.nih.gov/pubmed/10471456?tool=bestpractice.com
Diuretics (nonaldosterone) confer no mortality benefit for patients with CHF. However, they are frequently used to relieve symptoms of fluid overload.
The combination of hydralazine and a nitrate (e.g., isosorbide dinitrate/hydralazine) has been shown to be of benefit for self-defined African Americans already taking ACE inhibitors, beta-blockers, and aldosterone antagonists, as well as in all patients with CHF who are intolerant of both ACE inhibitors and angiotensin-II receptor antagonists.[98]Cohn JN, Archibald DG, Ziesche S, et al. Effect of vasodilator therapy on mortality in chronic congestive heart failure: results of a Veterans Administration Cooperative Study. N Engl J Med. 1986 Jun 12;314(24):1547-52.
http://www.ncbi.nlm.nih.gov/pubmed/3520315?tool=bestpractice.com
[99]Taylor AL, Ziesche S, Yancy C, et al; African-American Heart Failure Trial Investigators. Combination of isosorbide dinitrate and hydralazine in blacks with heart failure. N Engl J Med. 2004 Nov 11;351(20):2049-57.
https://www.nejm.org/doi/full/10.1056/NEJMoa042934
http://www.ncbi.nlm.nih.gov/pubmed/15533851?tool=bestpractice.com
Nondihydropyridine calcium-channel blockers are not recommended for the treatment of hypertension in adults with heart failure with reduced ejection fraction.[5]Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2018 May 15;71(19):e127-248.
https://www.jacc.org/doi/full/10.1016/j.jacc.2017.11.006
http://www.ncbi.nlm.nih.gov/pubmed/29146535?tool=bestpractice.com
Sacubitril/valsartan and ivabradine are newer drugs also used for chronic heart failure.
Comorbid heart failure with preserved ejection fraction
Diuretics should be used to control hypertension in patients with comorbid heart failure with preserved ejection fraction (>45%) who present with symptoms of volume overload.[5]Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2018 May 15;71(19):e127-248.
https://www.jacc.org/doi/full/10.1016/j.jacc.2017.11.006
http://www.ncbi.nlm.nih.gov/pubmed/29146535?tool=bestpractice.com
If hypertension persists after the management of volume overload, ACE inhibitors or angiotensin-II receptor antagonists and beta-blockers should be used and titrated to achieve the target BP goal.
Comorbid left ventricular hypertrophy
ACE inhibition has proven beneficial across a myriad of cardiovascular disease states including CHF and left ventricular hypertrophy (LVH).[89]Yusuf S, Sleight P, Pogue J, et al; Heart Outcomes Prevention Evaluation Study Investigators. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. N Engl J Med. 2000 Jan 20;342(3):145-53.
https://www.nejm.org/doi/full/10.1056/NEJM200001203420301
http://www.ncbi.nlm.nih.gov/pubmed/10639539?tool=bestpractice.com
[90]The European Trial on Reduction of Cardiac Events with Perindopril in Stable Coronary Artery Disease Investigators. Efficacy of perindopril in reduction of cardiovascular events among patients with stable coronary artery disease: randomised, double-blind, placebo-controlled, multicentre trial (the EUROPA study). Lancet. 2003 Sep 6;362(9386):782-8.
http://www.ncbi.nlm.nih.gov/pubmed/13678872?tool=bestpractice.com
An angiotensin-II receptor antagonist is first choice for comorbid LVH. Angiotensin-II receptor antagonists have been shown to decrease morbidity and mortality in patients with hypertension and LVH.[93]Dickstein K, Kjekshus J. Effects of losartan and captopril on mortality and morbidity in high-risk patients after acute myocardial infarction: the OPTIMAAL randomised trial. Lancet. 2002 Sep 7;360(9335):752-60.
http://www.ncbi.nlm.nih.gov/pubmed/12241832?tool=bestpractice.com
Comorbid renal disease
An ACE inhibitor is first choice for comorbid renal disease (chronic kidney disease stage 3 or higher or stage 1 or 2 with albuminuria [≥300 mg/day or ≥300 mg/g albumin-to-creatinine ratio or equivalent in the first morning void]).[5]Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2018 May 15;71(19):e127-248.
https://www.jacc.org/doi/full/10.1016/j.jacc.2017.11.006
http://www.ncbi.nlm.nih.gov/pubmed/29146535?tool=bestpractice.com
If an ACE inhibitor is not tolerated, an angiotensin-II receptor antagonist can be used.
Continuing ACE inhibitor or angiotensin-II receptor antagonist therapy may be associated with cardiovascular benefit as kidney function declines.[100]Qiao Y, Shin JI, Chen TK, et al. Association between renin-angiotensin system blockade discontinuation and all-cause mortality among persons with low estimated glomerular filtration rate. JAMA Intern Med. 2020 May 1;180(5):718-26.
http://www.ncbi.nlm.nih.gov/pubmed/32150237?tool=bestpractice.com
Second-choice options are a calcium-channel blocker or thiazide diuretic. A non-dihydropyridine calcium-channel blocker (i.e., diltiazem, verapamil) may be indicated if there is proteinuria.[101]Bakris GL, Weir MR, Secic M, et al. Differential effects of calcium antagonist subclasses on markers of nephropathy progression. Kidney Int. 2004 Jun;65(6):1991-2002.
https://www.kidney-international.org/article/S0085-2538(15)49945-4/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/15149313?tool=bestpractice.com
Spironolactone may further reduce proteinuria when added to an ACE inhibitor or angiotensin-II receptor antagonist, but also raises the risk of hyperkalemia.[102]Navaneethan SD, Nigwekar SU, Sehgal AR, et al. Aldosterone antagonists for preventing the progression of chronic kidney disease: a systematic review and meta-analysis. Clin J Am Soc Nephrol. 2009 Mar;4(3):542-51.
https://cjasn.asnjournals.org/content/4/3/542
http://www.ncbi.nlm.nih.gov/pubmed/19261819?tool=bestpractice.com
[103]Alexandrou ME, Papagianni A, Tsapas A, et al. Effects of mineralocorticoid receptor antagonists in proteinuric kidney disease: a systematic review and meta-analysis of randomized controlled trials. J Hypertens. 2019 Dec;37(12):2307-24.
http://www.ncbi.nlm.nih.gov/pubmed/31688290?tool=bestpractice.com
Comorbid atrial fibrillation
First choice is a beta-blocker. Second choice is a nondihydropyridine calcium-channel blocker.
Evidence from post-hoc analyses suggest that angiotensin-II receptor antagonists and ACE inhibitors do not prevent the occurrence or the recurrence of atrial fibrillation.[104]Yusuf S, Diener HC, Sacco RL, et al; PRoFESS Study Group. Telmisartan to prevent recurrent stroke and cardiovascular events. N Engl J Med. 2008 Sep 18;359(12):1225-37.
https://www.nejm.org/doi/full/10.1056/NEJMoa0804593
http://www.ncbi.nlm.nih.gov/pubmed/18753639?tool=bestpractice.com
[105]Yusuf S, Teo K, Anderson C, et al; Telmisartan Randomised AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease (TRANSCEND) Investigators. Effects of the angiotensin-receptor blocker telmisartan on cardiovascular events in high-risk patients intolerant to angiotensin-converting enzyme inhibitors: a randomised controlled trial. Lancet. 2008 Sep 27;372(9644):1174-83.
http://www.ncbi.nlm.nih.gov/pubmed/18757085?tool=bestpractice.com
[106]Tveit A, Grundvold I, Olufsen M, et al. Candesartan in the prevention of relapsing atrial fibrillation. Int J Cardiol. 2007 Aug 9;120(1):85-91.
http://www.ncbi.nlm.nih.gov/pubmed/17113170?tool=bestpractice.com
[107]Disertori M, Latini R, Barlera S, et al; GISSI-AF Investigators. Valsartan for prevention of recurrent atrial fibrillation. N Engl J Med. 2009 Apr 16;360(16):1606-17. [Erratum in: N Engl J Med. 2009 May 28;360(22):2379.]
https://www.nejm.org/doi/full/10.1056/NEJMoa0805710
http://www.ncbi.nlm.nih.gov/pubmed/19369667?tool=bestpractice.com
However, more recent guidelines note that use of ACE inhibitors and angiotensin-II receptor antagonists may be effective in the prevention of atrial fibrillation.[5]Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2018 May 15;71(19):e127-248.
https://www.jacc.org/doi/full/10.1016/j.jacc.2017.11.006
http://www.ncbi.nlm.nih.gov/pubmed/29146535?tool=bestpractice.com
[108]January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol. 2014 Dec 2;64(21):e1-76.
https://www.jacc.org/doi/full/10.1016/j.jacc.2014.03.022
http://www.ncbi.nlm.nih.gov/pubmed/24685669?tool=bestpractice.com
More investigation is needed.
Comorbid benign prostatic hypertrophy
The ALLHAT study conclusively demonstrated that alpha-blockers should not be a first-line antihypertensive therapy for patients with symptomatic benign prostatic hypertrophy (BPH). In these patients, the preferred first-line antihypertensive options are the same as for most other groups (i.e., thiazide-like diuretics, ACE inhibitors, angiotensin-II receptor antagonists, and calcium-channel blockers), and the alpha-blocker indication is simply to treat the BPH symptoms.
Comorbid Raynaud disease, peripheral vascular disease, or coronary artery spasm
Calcium-channel blockers are first choice. In addition to vascular disease, calcium-channel blockers are also useful for persistent angina or stroke prevention.[109]Angeli F, Verdecchia P, Reboldi GP, et al. Calcium channel blockade to prevent stroke in hypertension: a meta-analysis of 13 studies with 103,793 subjects. Am J Hypertens. 2004 Sep;17(9):817-22.
https://academic.oup.com/ajh/article/17/9/817/322548
http://www.ncbi.nlm.nih.gov/pubmed/15363825?tool=bestpractice.com
[110]Poole-Wilson PA, Lubsen J, Kirwan BA, et al. Effect of long-acting nifedipine on mortality and cardiovascular morbidity in patients with stable angina requiring treatment (ACTION trial): randomized control trial. Lancet. 2004 Sep 4-10;364(9437):849-57.
http://www.ncbi.nlm.nih.gov/pubmed/15351192?tool=bestpractice.com
Stage 2 hypertension
The ACC/AHA guidelines define stage 2 hypertension as BP ≥140/90 mmHg.[5]Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2018 May 15;71(19):e127-248.
https://www.jacc.org/doi/full/10.1016/j.jacc.2017.11.006
http://www.ncbi.nlm.nih.gov/pubmed/29146535?tool=bestpractice.com
The European Society of Cardiology guidelines define this category of BP in three grades:[2]Williams B, Mancia G, Spiering W, et al. 2018 ESC/ESH guidelines for the management of arterial hypertension. Eur Heart J. 2018 Sep 1;39(33):3021-104.
https://academic.oup.com/eurheartj/article/39/33/3021/5079119
http://www.ncbi.nlm.nih.gov/pubmed/30165516?tool=bestpractice.com
Grade 1 hypertension BP 140-159/90-99 mmHg
Grade 2 hypertension 160-179/100-109 mmHg
Grade 3 hypertension ≥180 mmHg/110 mmHg.
Patients presenting with stage 2 hypertension will require more than one drug for BP control. Therefore, the initiation of two concurrent antihypertensives of different classes is recommended.
The combination of a nondihydropyridine calcium-channel blocker with a beta-blocker should be avoided, because of an increased risk of high-degree atrioventricular block.
Recalcitrant (resistant) hypertension
Recalcitrant (resistant) hypertension is defined as above-goal elevated BP in a patient taking three antihypertensive agents (commonly including a long-acting calcium-channel blocker, an ACE inhibitor or angiotensin-II receptor antagonist, and a diuretic) at maximally tolerated doses.[59]Carey RM, Calhoun DA, Bakris GL, et al. Resistant hypertension: detection, evaluation, and management: a scientific statement from the American Heart Association. Hypertension. 2018 Nov;72(5):e53-90.
https://www.ahajournals.org/doi/10.1161/HYP.0000000000000084
http://www.ncbi.nlm.nih.gov/pubmed/30354828?tool=bestpractice.com
Managing recalcitrant hypertension requires expertise. Frequently requiring multiple antihypertensive agents, patients must be observed and counseled regarding adverse effects, medication adherence, potential drug-drug interactions, and metabolic abnormalities. Infrequently, patients will require a screen for secondary causes of hypertension.
Representative agents of the main treatment class options, including ACE inhibitors, angiotensin-II receptor antagonists, and calcium-channel blockers, should be maximized. An optimally dosed thiazide-like diuretic, such as chlorthalidone or indapamide, should be used over hydrochlorothiazide.[59]Carey RM, Calhoun DA, Bakris GL, et al. Resistant hypertension: detection, evaluation, and management: a scientific statement from the American Heart Association. Hypertension. 2018 Nov;72(5):e53-90.
https://www.ahajournals.org/doi/10.1161/HYP.0000000000000084
http://www.ncbi.nlm.nih.gov/pubmed/30354828?tool=bestpractice.com
ACE inhibitors, angiotensin-II receptor antagonists, and/or direct renin inhibitors should not be used together due to the risk of acute renal failure.
The fourth-line drug option is generally spironolactone. Eplerenone can be used as an alternative. Spironolactone and eplerenone are contraindicated in patients with hyperkalemia. Caution should be used in patients with renal impairment; either a dose adjustment may be required, or the drug may be contraindicated depending on the severity of renal impairment, indication for use (i.e., hypertension versus heart failure), and local guidance. Concomitant administration with potassium-sparing diuretics is contraindicated.
Otherwise, a safe fourth- or fifth-line option is a peripheral adrenergic blocker. Hydralazine is a less-preferred option due its twice-daily dose requirement and increased risk of edema with simultaneous calcium-channel blocker treatment. Minoxidil is rarely required in patients with advanced chronic kidney disease and its use requires some expertise in anticipating and managing side-effects of fluid retention. Combined alpha- and beta-blockers (e.g., carvedilol, labetalol) are considerations. Additionally, physicians with expertise in managing difficult-to-control hypertension have had niche success using a combination of a dihydropyridine calcium-channel blocker plus a nondihydropyridine calcium-channel blocker (e.g., amlodipine plus diltiazem). Clonidine is generally avoided because of its side-effect profile.
The most important principles for managing challenging hypertension are:
Promotion of medication adherence using the principle of pill reduction (i.e., use of single pill, fixed-dose combination formulations or avoidance of twice-daily dose regimens when possible)
Maximizing the dose of the diuretic (thiazide or thiazide-like)
Use of spironolactone or eplerenone as a fourth drug when possible.[111]Williams B, MacDonald TM, Morant S, et al; British Hypertension Society's PATHWAY Studies Group. Spironolactone versus placebo, bisoprolol, and doxazosin to determine the optimal treatment for drug-resistant hypertension (PATHWAY-2): a randomised, double-blind, crossover trial. Lancet. 2015 Nov 21;386(10008):2059-68.
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(15)00257-3/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/26414968?tool=bestpractice.com
It is also important to question the patient's alcohol use and offer lifestyle counseling.
Referral to a specialist in hypertension should be considered.
Older adults
In the oldest adult patients, many physicians are reluctant to treat hypertension in accordance with usual BP goals, for a number of reasons, including concerns about fall risk, drug interactions, adverse effects, and lack of benefit in mortality reduction. Previous literature reviews and meta-analysis demonstrated reductions in stroke, heart failure, and cardiovascular events in much older adults without reaching mortality benefit.[112]Charpentier MM, Bundeff A. Treating hypertension in the very elderly. Ann Pharmacother. 2011 Sep;45(9):1138-43.
http://www.ncbi.nlm.nih.gov/pubmed/21852597?tool=bestpractice.com
[113]Schall P, Wehling M. Treatment of arterial hypertension in the very elderly: a meta-analysis of clinical trials. Arzneimittelforschung. 2011;61(4):221-8.
http://www.ncbi.nlm.nih.gov/pubmed/21650080?tool=bestpractice.com
However, the SPRINT trial found that treating ambulatory adults ages 75 years or older to a systolic BP target of <120 mmHg (as measured by AOBP) resulted in significantly lower rates of fatal and nonfatal major cardiovascular events and death from any cause, compared with a systolic BP target of <140 mmHg.[68]Williamson JD, Supiano MA, Applegate WB, et al; SPRINT Research Group. Intensive vs standard blood pressure control and cardiovascular disease outcomes in adults aged ≥75 years: a randomized clinical trial. JAMA. 2016 Jun 28;315(24):2673-82.
https://jamanetwork.com/journals/jama/fullarticle/2524266
http://www.ncbi.nlm.nih.gov/pubmed/27195814?tool=bestpractice.com
The SPRINT trial also found that intensive BP control did not result in any adverse effects on cognition: the risk of mild cognitive impairment and the combined rate of mild cognitive impairment or probable dementia was reduced in patients treated to a systolic BP target of <120 mmHg; however, the incidence of probable dementia was not reduced.[114]Williamson JD, Pajewski NM, Auchus AP, et al; SPRINT MIND Investigators for the SPRINT Research Group. Effect of intensive vs standard blood pressure control on probable dementia: a randomized clinical trial. JAMA. 2019 Feb 12;321(6):553-61.
https://jamanetwork.com/journals/jama/fullarticle/2723256
http://www.ncbi.nlm.nih.gov/pubmed/30688979?tool=bestpractice.com
Patients with orthostasis at enrollment, patients with dementia, and those resident in a nursing home were excluded from the trial.
The 2017 ACC/AHA guidelines recommend a systolic BP goal of <130 mmHg for noninstitutionalized ambulatory community-dwelling adults. For older adults ≥65 years of age with hypertension and a high burden of comorbidity and limited life expectancy, clinical judgment, patient preference, and a team-based approach to assess risk/benefit is reasonable for decisions regarding intensity of BP lowering and choice of antihypertensive drugs.[5]Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2018 May 15;71(19):e127-248.
https://www.jacc.org/doi/full/10.1016/j.jacc.2017.11.006
http://www.ncbi.nlm.nih.gov/pubmed/29146535?tool=bestpractice.com
European guidelines recommend a BP target of <140/90 mmHg in all patients including independent older patients and, if treatment is tolerated, a BP target of ≤130/80 mmHg in most patients.[2]Williams B, Mancia G, Spiering W, et al. 2018 ESC/ESH guidelines for the management of arterial hypertension. Eur Heart J. 2018 Sep 1;39(33):3021-104.
https://academic.oup.com/eurheartj/article/39/33/3021/5079119
http://www.ncbi.nlm.nih.gov/pubmed/30165516?tool=bestpractice.com
The JNC 8 guideline recommends initiating pharmacologic therapy for patients aged ≥60 years at systolic BP ≥150 mmHg or diastolic BP ≥90 mmHg, and to treat to a systolic BP goal of <150 mmHg and a diastolic BP goal of <90 mmHg.[3]James PA, Oparil S, Carter BL, et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2014 Feb 5;311(5):507-20.
https://jamanetwork.com/journals/jama/fullarticle/1791497
http://www.ncbi.nlm.nih.gov/pubmed/24352797?tool=bestpractice.com
Pregnancy
Treatment described in this topic is for nonpregnant patients. Management in pregnancy should be referred to an obstetrician specializing in high-risk patients.
For more information, please see our topic on Gestational hypertension.
Implementation success
High levels of hypertension control in large multi-ethnic populations has been demonstrated using basic principles of implementation science.[115]Jaffe MG, Lee GA, Young JD, et al. Improved blood pressure control associated with a large-scale hypertension program. JAMA. 2013 Aug 21;310(7):699-705.
https://jamanetwork.com/journals/jama/fullarticle/1730511
http://www.ncbi.nlm.nih.gov/pubmed/23989679?tool=bestpractice.com
[116]Sim JJ, Handler J, Jacobsen SJ, et al. Systematic implementation strategies to improve hypertension: the Kaiser Permanente southern California experience. Can J Cardiol. 2014 May;30(5):544-52.
http://www.ncbi.nlm.nih.gov/pubmed/24786445?tool=bestpractice.com
[117]Shaw KM, Handler J, Wall HK, et al. Improving blood pressure control in a large multiethnic California population through changes in health care delivery 2004-2012. Prev Chronic Dis. 2014 Oct 30;11:E191.
https://www.cdc.gov/pcd/issues/2014/14_0173.htm
http://www.ncbi.nlm.nih.gov/pubmed/25357259?tool=bestpractice.com
Core principles include:
A comprehensive hypertension registry
An evidence-based hypertension treatment algorithm based on single pill combination therapy
Free medical assistant visits for blood pressure measurement with follow-up triage, and
Team-based performance reporting.
The use of 2-drug combination therapy, including single pill combinations, for patients with newly diagnosed hypertension with and without comorbidities is consistent with the evidence-based JNC 8 guideline as well as the 2017 ACC/AHA guidelines and the European guidelines.[2]Williams B, Mancia G, Spiering W, et al. 2018 ESC/ESH guidelines for the management of arterial hypertension. Eur Heart J. 2018 Sep 1;39(33):3021-104.
https://academic.oup.com/eurheartj/article/39/33/3021/5079119
http://www.ncbi.nlm.nih.gov/pubmed/30165516?tool=bestpractice.com
[5]Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2018 May 15;71(19):e127-248.
https://www.jacc.org/doi/full/10.1016/j.jacc.2017.11.006
http://www.ncbi.nlm.nih.gov/pubmed/29146535?tool=bestpractice.com
Given the large number of patients with hypertension and the use of protocol-based hypertension care delivery, team-based care incorporating nurses and clinical pharmacists is a key success factor.[118]Proia KK, Thota AB, Njie GJ, et al. Team-based care and improved blood pressure control: a community guide systematic review. Am J Prev Med. 2014 Jul;47(1):86-99.
http://www.ncbi.nlm.nih.gov/pubmed/24933494?tool=bestpractice.com
[119]Carter BL, Bosworth HB, Green BB. The hypertension team: the role of the pharmacist, nurse, and teamwork in hypertension therapy. J Clin Hypertens (Greenwich). 2012 Jan;14(1):51-65.
https://onlinelibrary.wiley.com/doi/10.1111/j.1751-7176.2011.00542.x
http://www.ncbi.nlm.nih.gov/pubmed/22235824?tool=bestpractice.com
In team-based care collaboration, generally the role of the clinical pharmacist involves medication choice and delivery, and the role of the nurse is patient education. One randomized controlled trial demonstrated the efficacy of a low cost nurse-led email reminder program across a spectrum of cardiovascular risk factors, including lipid improvement and blood pressure reduction.[120]Cicolini G, Simonetti V, Comparcini D, et al. Efficacy of a nurse-led email reminder program for cardiovascular prevention risk reduction in hypertensive patients: a randomized controlled trial. Int J Nurs Stud. 2014 Jun;51(6):833-43.
http://www.ncbi.nlm.nih.gov/pubmed/24225325?tool=bestpractice.com
The patient should be considered a hypertension team member. The TASMINH4 trial has shown that self-monitoring, with or without telemonitoring, used by general practitioners to titrate antihypertensive medication in patients with poorly controlled blood pressure, leads to significantly lower blood pressure compared with titration guided by clinic readings.[121]McManus RJ, Mant J, Franssen M, et al. Efficacy of self-monitored blood pressure, with or without telemonitoring, for titration of antihypertensive medication (TASMINH4): an unmasked randomised controlled trial. Lancet. 2018 Mar 10;391(10124):949-59.
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(18)30309-X/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/29499873?tool=bestpractice.com
An important goal is to continue to make efforts to improve disparities in blood pressure control among people of different ancestries.[122]Ayanian JZ, Landon BE, Newhouse JP, et al. Racial and ethnic disparities among enrollees in Medicare Advantage plans. N Engl J Med. 2014 Dec 11;371(24):2288-97.
https://www.nejm.org/doi/10.1056/NEJMsa1407273
http://www.ncbi.nlm.nih.gov/pubmed/25494268?tool=bestpractice.com