Hypertension guidelines

ACRONYMS AND DEFINITIONS

AAFP - American Academy of Family Physicians

AAP - American Academy of Pediatrics

ACC - American College of Cardiology

ACP - American College of Physicians

ADA - American Diabetes Association

AHA - American Heart Association

BP - Blood pressure

CAD - Coronary artery disease

CKD - Chronic kidney disease

CVD - Cardiovascular disease

DBP - Diastolic blood pressure

DM - Diabetes mellitus

HFpEF - Heart failure with preserved ejection fraction (diastolic heart failure)

HFrEF - Heart failure with reduced ejection fraction

HTN - Hypertension

JNC 8 - Eighth Joint National Committee

KDIGO - Kidney Disease: Improving Global Outcomes

RCT - Randomized controlled trial

SBP - Systolic blood pressure

AHA/ACC 2017 HYPERTENSION GUIDELINES

^✝Hypertension is present if either SBP or DBP meet criteria
AHA/ACC Blood Pressure Categories
Category	SBP (mmHg)	DBP (mmHg)
Normal	< 120	< 80
Elevated	120 - 129	< 80
Stage 1 hypertension^✝	130 - 139	80 - 89
Stage 2 hypertension^✝	≥ 140	≥ 90

AHA/ACC BP Treatment Recommendations
Patients with any of the following: CVD, HFrEF, CKD, DM, 10-year risk of CVD ≥ 10% Treat with medications if average SBP ≥ 130 mmHg Treat with medications if average DBP ≥ 80 mmHg Use ACC/AHA risk estimator to estimate 10-year risk
Patients with HFpEF Treat with medication if average SBP ≥ 130 mmHg
All other patients Treat with medication if average SBP ≥ 140 mmHg Treat with medication if average DBP ≥ 90 mmHg

Reference [7]
AHA/ACC Medication Recommendations
Nonblack patients without comorbidities Use one of the first-line therapies below Two first-line agents are recommended in stage 2 hypertension for patients with an average BP ≥ 20/10 mmHg above their BP target First-line therapy includes the following: Thiazide diuretics ACE inhibitors Angiotensin receptor blockers (ARB) Calcium channel blockers
Black patients without comorbidities Thiazide diuretic or calcium channel blocker is preferred A randomized controlled trial published in 2019 found that amlodipine was superior to an ACE inhibitor and HCTZ for lowering blood pressure in black patients. See amlodipine study below.
Diabetes Patients without albuminuria: Any first-line agent Patients with albuminuria: ACE inhibitor or ARB
Chronic kidney disease (CKD) Treatment with an ACE inhibitor is reasonable to slow kidney disease progression ARB may be used if ACE inhibitor is not tolerated
Heart failure preserved ejection fraction (HFpEF) Diuretics should be used first-line in patients with volume overload ACE inhibitor / ARB and beta blockers can be used for further blood pressure lowering
Atrial fibrillation ARBs may help prevent recurrence of A fib
Patients with thoracic aortic disease (e.g. aneurysms) Beta blockers are preferred
Women who are pregnant or planning to become pregnant Use methyldopa, nifedipine, and/or labetalol

JNC 8 GUIDELINES

JNC 8 Blood Pressure Goals
Adults without diabetes or chronic kidney disease Adults < 60 years old Systolic blood pressure goal < 140 mmHg Diastolic blood pressure goal < 90 mmHg Adults ≥ 60 years old Systolic blood pressure goal < 150 mmHg Diastolic blood pressure goal < 90 mmHg
Adults with diabetes or chronic kidney disease Systolic blood pressure goal < 140 mmHg Diastolic blood pressure goal < 90 mmHg

JNC 8 Medication Recommendations
Adults without chronic kidney disease Nonblack patients Initiate therapy with one of the following: Thiazide diuretic ACE inhibitor Angiotensin receptor blocker Calcium channel blocker For patients with higher initial blood pressures (SBP > 160, DBP > 100), therapy may be initiated with 2 drugs Therapy should be titrated to achieve goal Dose of one drug may be maximized before adding another medication, or another medication may be added before previous drug is maximized DO NOT combine ACE inhibitors and Angiotensin Receptor Blockers If goal is not achieved with medications in the initial therapy group, then other medications may be added (ex. beta blockers, aldosterone antagonists, etc.) Black patients Initiate therapy with one of the following: Thiazide diuretic Calcium channel blocker A randomized controlled trial published in 2019 found that amlodipine was superior to an ACE inhibitor and HCTZ for lowering blood pressure in black patients. See amlodipine study below. For patients with higher initial blood pressures (SBP > 160, DBP > 100), therapy may be initiated with 2 drugs Therapy should be titrated to achieve goal Dose of one drug may be maximized before adding another medication, or another medication may be added before previous drug is maximized DO NOT combine ACE inhibitors and Angiotensin Receptor Blockers If goal is not achieved with one medication in the initial therapy group, then other medications may be added (ex. beta blockers, aldosterone antagonists, ACE inhibitors, etc.)
Adults with chronic kidney disease (diabetic or other) Initiate therapy with one of the following: ACE inhibitor Angiotensin receptor blocker For patients with higher initial blood pressures (SBP > 160, DBP > 100), therapy may be initiated with 2 drugs Therapy should be titrated to achieve goal Dose of one drug may be maximized before adding another medication, or another medication may be added before previous drug is maximized DO NOT combine ACE inhibitors and Angiotensin Receptor Blockers If goal is not achieved with one of the medications in the initial therapy group, then other medications may be added (ex. thiazide diuretic, calcium channel blocker beta blockers, aldosterone antagonists, etc.)

JNC 8 Medication Recommendations

Adults without chronic kidney disease

Nonblack patients

Initiate therapy with one of the following:

For patients with higher initial blood pressures (SBP > 160, DBP > 100), therapy may be initiated with 2 drugs
Therapy should be titrated to achieve goal
Dose of one drug may be maximized before adding another medication, or another medication may be added before previous drug is maximized
DO NOT combine ACE inhibitors and Angiotensin Receptor Blockers
If goal is not achieved with medications in the initial therapy group, then other medications may be added (ex. beta blockers, aldosterone antagonists, etc.)

Black patients

Initiate therapy with one of the following:

Thiazide diuretic
Calcium channel blocker
A randomized controlled trial published in 2019 found that amlodipine was superior to an ACE inhibitor and HCTZ for lowering blood pressure in black patients. See amlodipine study below.

For patients with higher initial blood pressures (SBP > 160, DBP > 100), therapy may be initiated with 2 drugs
Therapy should be titrated to achieve goal
Dose of one drug may be maximized before adding another medication, or another medication may be added before previous drug is maximized
DO NOT combine ACE inhibitors and Angiotensin Receptor Blockers
If goal is not achieved with one medication in the initial therapy group, then other medications may be added (ex. beta blockers, aldosterone antagonists, ACE inhibitors, etc.)

Adults with chronic kidney disease (diabetic or other)

Initiate therapy with one of the following:

For patients with higher initial blood pressures (SBP > 160, DBP > 100), therapy may be initiated with 2 drugs
Therapy should be titrated to achieve goal
Dose of one drug may be maximized before adding another medication, or another medication may be added before previous drug is maximized
DO NOT combine ACE inhibitors and Angiotensin Receptor Blockers
If goal is not achieved with one of the medications in the initial therapy group, then other medications may be added (ex. thiazide diuretic, calcium channel blocker beta blockers, aldosterone antagonists, etc.)

ACP/AAFP 2017 RECOMMENDATIONS FOR ADULTS ≥ 60 YEARS OLD

Reference [3]
ACP/AAFP Recommendations for adults ≥ 60 years old
Adults ≥ 60 years with a history of stroke or TIA, or who are at high risk for CVD disease Systolic blood pressure goal < 140 mmHg High risk for cardiovascular disease was generally defined as any of the following: Persons with known vascular disease Most patients with diabetes Older persons with chronic kidney disease (GFR < 45 ml/min) Metabolic syndrome (abdominal obesity, hypertension, diabetes, and dyslipidemia) Older persons
All other adults ≥ 60 years old Systolic blood pressure goal < 150 mmHg
Other Guidelines state there is insufficient evidence to make recommendations based on diastolic blood pressure Accurate blood pressure measurement (home and clinic) is important before initiating treatment

Reference [8]
2021 KDIGO blood pressure recommendations for CKD patients not on dialysis
Blood pressure measurement Office blood pressure measurement should follow a standardized procedure (see proper BP measurement) Out-of-office BP measurements with ambulatory BP monitoring or home BP monitoring may be used to complement standardized office BP readings for the management of high BP
Lifestyle interventions for lowering BP Target sodium intake should be < 2 g of sodium per day (or < 90 mmol of sodium per day, or < 5 g of sodium chloride per day) in patients with high BP and CKD. See sodium and hypertension. Moderate-intensity physical activity for a cumulative duration of at least 150 minutes per week, or to a level compatible with the patient's cardiovascular and physical tolerance is recommended
BP goals Target SBP: < 120 mmHg when tolerated
Medication choice Nondiabetics An ACE inhibitor or ARB is recommended in people with high BP, CKD, and severely increased albuminuria (CKD stage G1–G4 \| albuminuria category A3) An ACE inhibitor or ARB is suggested in people with high BP, CKD, and moderately increased albuminuria (CKD stage G1–G4 \| albuminuria category A2) Diabetics An ACE inhibitor or ARB is recommended in people with high BP, CKD, and moderately-to-severely increased albuminuria (CKD stage G1–G4 \| albuminuria category A2 and A3) See CKD stages and albuminuria categories in CKD for category definitions Medication management Use highest dose of ACE inhibitor or ARB that is tolerated Changes in BP, serum creatinine, and serum potassium should be checked within 2–4 weeks of initiation or increase in the dose of ACE inhibitor/ARB, depending on the current GFR and serum potassium Hyperkalemia associated with use of an ACE inhibitor or ARB can often be managed by measures to reduce the serum potassium levels rather than decreasing the dose or stopping the drug. See managing RAAS inhibitor-induced hyperkalemia and treating and preventing hyperkalemia in CKD. Continue ACE inhibitor or ARB therapy unless serum creatinine rises by more than 30% within 4 weeks following initiation of treatment or an increase in dose Consider reducing the dose or discontinuing ACE inhibitor or ARB in the setting of either symptomatic hypotension or uncontrolled hyperkalemia despite medical treatment, or to reduce uremic symptoms while treating kidney failure Aldosterone antagonists (spironolactone, eplerenone) are effective for management of refractory hypertension but may cause hyperkalemia or a reversible decline in kidney function, particularly among patients with low eGFR Do not combine ACE inhibitors, ARBS, or renin inhibitors
Kidney transplant recipients BP goals Target SBP: < 130 mmHg Target DBP: < 80 mmHg Medications A dihydropyridine calcium channel blocker or an ARB should be used as the first-line antihypertensive agent in adult kidney transplant recipients
Children with CKD BP goals 24-h mean arterial pressure by ambulatory BP monitoring should be lowered to ≤ 50th percentile for age, sex, and height When ambulatory BP monitoring is not available, manual auscultatory office BP obtained in a protocol-driven standardized setting targeting achieved SBP < 90th percentile for age, sex, and height of normal children is a reasonable approach Medications Use an ACE inhibitor or ARB as first-line therapy for high BP in children with CKD. These drugs lower proteinuria and are usually well tolerated, but they carry risk for hyperkalemia and have adverse fetal risks for pregnant women

AAP PEDIATRIC RECOMMENDATIONS

Screening

Screen all children and adolescents ≥ 3 years old annually
Screen children and adolescents ≥ 3 years at every health encounter if they have obesity, renal disease, history of aortic arch obstruction or coarctation, diabetes, or are taking medications known to increase blood pressure

Diagnosis

AAP definitions for blood pressure categories are defined in the table below. The second table is a quick reference guide for upper limits of normal values by age.
In order to make a diagnosis of hypertension, auscultatory-confirmed blood pressure readings ≥ 95th percentile must be performed at 3 different visits
Ambulatory blood pressure monitoring should be performed for confirmation of HTN in children and adolescents with office blood pressure measurements in the elevated blood pressure category for ≥ 1 year, stage 1 HTN over three clinic visits, and/or suspected white coat hypertension [6]

*See table below for upper limits of normal blood pressure readings by age

Reference [6]
AAP BLOOD PRESSURE CATEGORIES
Children aged 1 - 13 years
Normal BP	< 90th percentile
Elevated BP	≥90th percentile to < 95th percentile OR 120/80 mmHg to < 95th percentile (whichever is lower)
Stage 1 HTN	≥ 95th percentile to < 95th percentile + 12 mmHg, OR 130/80 to 139/89 mmHg (whichever is lower)
Stage 2 HTN	≥ 95th percentile + 12 mmHg, OR ≥ 140/90 mmHg (whichever is lower)
Children aged ≥ 13 years
Normal BP	<120/< 80 mmHg
Elevated BP	120/<80 to 129/<80 mmHg
Stage 1 HTN	130/80 to 139/89 mmHg
Stage 2 HTN	≥140/90 mmHg

Blood pressure readings above these values are considered high

Reference [6]
Upper limits of blood pressure by age
AGE (years)	Boys (SBP/DBP)	Girls (SBP/DBP)
1	98 / 52	98 / 54
2	100 / 55	101 / 58
3	101 / 58	102 / 60
4	102 / 60	103 / 62
5	103 / 63	104 / 64
6	105 / 66	105 / 67
7	106 / 68	106 / 68
8	107 / 69	107 / 69
9	107 / 70	108 / 71
10	108 / 72	109 / 72
11	110 / 74	111 / 74
12	113 / 75	114 / 75
≥ 13	120 / 80	120 / 80

Workup

All patients diagnosed with hypertension should have the following studies:

Urinalysis
Basic metabolic profile (BMP)
Lipid panel
Renal ultrasonography in those < 6 years of age or those with abnormal urinalysis or renal function

Secondary hypertension

Providers should look for signs and symptoms of secondary hypertension (see table below)
Patients ≥ 6 years of age do not require an extensive evaluation for secondary causes of hypertension if they have a positive family history of hypertension, are overweight or obese, and/or do not have history or physical examination findings suggestive of secondary hypertension

Reference [6]
SELECT CAUSES OF SECONDARY HYPERTENSION
Condition	Comments
Renal disease	Most common cause of secondary hypertension in children, particularly those < 6 years old
Coarctation of the aorta	Right arm SBP that is ≥ 20 mmHg more than the lower extremity SBP Hypertension is common even after successful repair (up to 77% of patients) Masked hypertension is common and ambulatory blood pressure monitoring should be performed
Obstructive sleep apnea	Snoring Adenotonsillar hypertrophy
Medications / Supplements	Oral contraceptives Corticosteroids and anabolic steroids Herbal and nutritional supplements Diet products
Congenital adrenal hyperplasia	Low potassium Acne, hirsutism, and virilization in girls Pseudoprecocious puberty in boys
Hyperaldosteronism	Low potassium May be familial
Cushing syndrome	Central obesity and enlarged fat pad on upper back (buffalo hump) Hirsutism and acne Moon facies Absent or irregular menses
Hyperthyroidism	Tachycardia, anxiety, sweating, heat intolerance
Environmental exposures	Lead, cadmium, mercury, phthalates
Neurofibromatosis	Cafe-au-lait macules Neurofibromas Lisch nodules of the iris Axillary freckling

Treatment

Treatment goals

SBP and DBP < 90th percentile or < 130/80 mmHg, whichever is lower (see pediatric BP values above)

Medications

Initiate therapy with one of the following:

Other

Children and adolescents with hypertension may participate in competitive sports once hypertensive target organ effects and cardiovascular risk have been assessed

STUDIES | BP GOALS

Overview

Two very large trials have now been published that compared outcomes between lower and higher blood pressure targets. The SPRINT trial, which took place in the U.S. and was published in 2015, treated patients to a target SBP of <120 or <140 over a median of 3.26 years. The STEP trial, which took place in China and was published in 2021, treated patients to a target SBP of <130 or <150 over a median of 3.34 years. Because a previous trial had found no advantage of lower BP targets in diabetics (ACCORD), the SPRINT trial excluded diabetics, but the STEP trial did not. Both trials are detailed below.

SPRINT trial - Intensive (SBP < 120) vs Standard (SBP < 140) Blood Pressure Control for CVD Outcomes, NEJM (2015) [PubMed abstract]

The SPRINT trial enrolled 9361 patients with a SBP ≥ 130 mmHg who were at increased risk of cardiovascular disease

Main inclusion criteria

Age ≥ 50 years
SBP 130 - 180 mmHg
Increased cardiovascular risk defined as ≥ 1 of the following: clinical or subclinical cardiovascular disease (except stroke), chronic kidney disease (CrCl 20 - < 60 ml/min), 10-year heart attack risk of ≥ 15% (Framingham risk calculator), age ≥ 75 years

Main exclusion criteria

Diabetes
History of stroke
Symptomatic heart failure within the past 6 months or EF < 35%

Baseline characteristics

Average age 68 years
Chronic kidney disease - 28%
Average SBP - 140 mmHg
Average DBP - 78 mmHg
Average Framingham 10-year risk - 20%

Randomized treatment groups

Group 1 (4678 patients) - Target SBP < 120 mmHg (Intensive)
Group 2 (4683 patients) - Target SBP < 140 mmHg (Standard)
There was no set treatment algorithm; patients could receive any blood pressure medication(s). Certain medications were encouraged in the study protocol - thiazides as first-line agents, loop diuretics for chronic kidney disease, beta blockers for CAD. Chlorthalidone was recommended as the primary thiazide diuretic. Amlodipine was the recommended calcium channel blocker.

Primary outcome: Composite of myocardial infarction, acute coronary syndrome not resulting in myocardial infarction, stroke, acute decompensated heart failure, or death from cardiovascular causes

Results

Outcome	Intensive	Standard	Comparisons
Duration: After a median of 3.26 years, the study was stopped early because the intensive group was superior
Average SBP during follow-up	121.5	134.6	N/A
Average number of BP meds	2.8	1.8	N/A
Primary outcome	5.2%	6.8%	HR 0.75, 95%CI [0.64 - 0.89], p<0.001
Myocardial infarction	2.1%	2.5%	HR 0.83, 95%CI [0.64 - 1.09], p=0.19
Acute coronary syndrome	0.9%	0.9%	HR 1.0, 95%CI [0.64 - 1.55], p=0.99
Stroke	1.3%	1.5%	HR 0.89, 95%CI [0.63 - 1.25], p=0.50
Heart failure	1.3%	2.1%	HR 0.62, 95%CI [0.45 - 0.84], p=0.002
Death from cardiovascular cause	0.8%	1.4%	HR 0.57, 95%CI [0.38 - 0.85], p=0.005
Death from any cause	3.3%	4.5%	HR 0.73, 95%CI [0.60 - 0.90], p=0.003
Hypotension	3.4%	2.0%	p<0.001
Syncope	3.5%	2.4%	p=0.003
Electrolyte abnormality	3.8%	2.8%	p=0.006
Acute kidney injury/failure	4.4%	2.6%	p<0.001
Medication types: ACE or ARB: Intensive - 77%, Standard - 55% \| Beta blocker: Intensive - 41%, Standard - 31% \| Diuretic: Intensive - 67%, Standard - 43%

Findings: Among patients at high risk for cardiovascular events but without diabetes, targeting a systolic blood pressure of less than 120 mm Hg, as compared with less than 140 mm Hg, resulted in lower rates of fatal and nonfatal major cardiovascular events and death from any cause, although significantly higher rates of some adverse events were observed in the intensive-treatment group.

SPRINT Subgroup Analysis of Participants ≥ 75 Years Old at Randomization, JAMA (2016) [PubMed abstract]

A subgroup analysis of the SPRINT trial looked at the 2636 patients who were ≥ 75 years old at randomization

Outcome	Intensive	Standard	Comparisons
Duration: After a median follow-up of 3.14 years, the study was stopped early because the intensive group was better
Average BP during follow-up	123/62	135/67	N/A
Average number of BP meds	2.6	1.8	N/A
Primary outcome	7.7%	11.2%	HR 0.66, 95%CI [0.51 - 0.85], p=0.001
Myocardial infarction	2.8%	4.0%	HR 0.69, 95%CI [0.45 - 1.05], p=0.09
Acute coronary syndrome	1.3%	1.3%	HR 1.03, 95%CI [0.52 - 2.04], p=0.94
Stroke	2.1%	2.6%	HR 0.72, 95%CI [0.43 - 1.21], p=0.22
Heart failure	2.7%	4.2%	HR 0.62, 95%CI [0.40 - 0.95], p=0.03
Death from cardiovascular cause	1.4%	2.2%	HR 0.60, 95%CI [0.33 - 1.09], p=0.09
Death from any cause	5.5%	8.1%	HR 0.67, 95%CI [0.49 - 0.91], p=0.009
Hypotension event	3.3%	2.0%	HR 1.66, 95%CI [1.03 - 2.73], p=0.039
Syncope	4.3%	3.3%	HR 1.28, 95%CI [0.85 - 1.92], p=0.240
Electrolyte abnormality	4.6%	3.3%	HR 1.44, 95%CI [0.97 - 2.16], p=0.067
Fall with injury	11.6%	14.1%	HR 0.80, 95%CI [0.64 - 0.99], p=0.040
Kidney injury/failure	5.5%	4.2%	HR 1.39, 95%CI [0.97 - 1.99], p=0.072
Medication types: ACE or ARB: Intensive - 71%, Standard - 52% \| Beta blocker: Intensive - 43%, Standard - 34% \| Diuretic: Intensive - 62%, Standard - 42%

Findings: Among ambulatory adults aged 75 years or older, treating to an SBP target of less than 120 mm Hg compared with an SBP target of less than 140 mm Hg resulted in significantly lower rates of fatal and nonfatal major cardiovascular events and death from any cause.

STEP study - Intensive (SBP < 130) vs Standard (SBP < 150) Blood Pressure Control in Older Patients with Hypertension, NEJM (2021) [PubMed abstract]

The STEP study enrolled 8511 Chinese patients 60 - 80 years old with hypertension

Main inclusion criteria

60 - 80 years of age
SBP 140 - 190 mmHg or taking BP meds
Han ethnicity

Main exclusion criteria

History of ischemic or hemorrhagic stroke
MI within 6 months
PCI or CABG within 12 months
NYHA class III - IV heart failure
HgA1C > 8%

Baseline characteristics

Average age 66 years
Average BMI - 26
Average BP - 146/82
Diabetes - 19%
History of CVD - 6.3%
Current smoker - 16%

Randomized treatment groups

Group 1 (4243 patients): SBP target of 110 to <130 mmHg (Intensive group)
Group 2 (4268 patients): SBP target of 130 to <150 mmHg (Standard group)
Treatment was standardized with an algorithm that included olmesartan, amlodipine, and HCTZ
Patients were seen every 3 months, and all were given home BP machines that uploaded readings to a data center. Patients were required to measure their home BP at least once a week.

Primary outcome: Composite of stroke (ischemic or hemorrhagic), acute coronary syndrome (acute myocardial infarction and hospitalization for unstable angina), acute decompensated heart failure, coronary revascularization, atrial fibrillation, or death from cardiovascular causes

Results

Outcome	Intensive	Standard	Comparisons
Duration: Median of 3.34 years
Average BP during follow-up	127/76	136/79	N/A
Average number of BP meds	1.9	1.5	N/A
Primary outcome	3.5%	4.6%	HR 0.74 95%CI [0.60 - 0.92], p=0.007
Stroke	1.1%	1.7%	HR 0.67 95%CI [0.47 - 0.97]
Acute coronary syndrome	1.3%	1.9%	HR 0.67 95%CI [0.47 - 0.94]
Acute heart failure	0.1%	0.3%	HR 0.27 95%CI [0.08 - 0.98]
Coronary revascularization	0.5%	0.7%	HR 0.69 95%CI [0.40 - 1.18]
Atrial fib	0.6%	0.6%	HR 0.96 95%CI [0.55 - 1.68]
Death from CV cause	0.4%	0.6%	HR 0.72 95%CI [0.39 - 1.32]
Overall mortality	1.6%	1.5%	HR 1.11 95%CI [0.78 - 1.56]
Hypotension	3.4%	2.6%	HR 1.31 95%CI [1.02 - 1.68], p=0.03
Medication types at 42 months: CCB only: Intensive - 10.8%, Standard - 20.5% \| ARB only: Intensive - 7.1%, Standard - 12.7% \| CCB + ARB: Intensive - 41.9%, Standard - 30.4% \| ARB+CCB+HCTZ: Intensive - 9.3%, Standard - 3.4% \| Other drugs: Intensive - 27.4%, Standard - 29.3%

Findings: In older patients with hypertension, intensive treatment with a systolic blood pressure target of 110 to less than 130 mmHg resulted in a lower incidence of cardiovascular events than standard treatment with a target of 130 to less than 150 mmHg

Summary

The SPRINT trial showed that a SBP target of <120 mmHg (compared to <140 mmHg) reduced the absolute risk of a composite CV outcome by 1.6%. Overall mortality was also significantly better with the lower target by 1.2%. The subgroup analysis that looked at patients ≥ 75 years also confirmed a benefit. Adverse events related to antihypertensives were more common in the lower target group. One weakness of the study is that treatment was not standardized, and patients in the intensive therapy group were more likely to be taking medications that have proven beneficial in heart failure, a significant component of the primary outcome (ACEIs/ARBs - 77% vs 55% | beta blockers 41% vs 31% | diuretics 67% vs 43%). While the study excluded patients with overt heart failure (EF < 35%), it's conceivable that a fair number of patients had subclinical or undiagnosed heart failure at randomization or developed it during the trial, and drug classes in the intensive regimen were more effective for this comorbidity.
The STEP study showed that a SBP target of <130 mmHg (compared to <150 mmHg) reduced the absolute risk of a composite CV outcome by 1.1%; overall mortality was not significantly better with the lower target. Adverse events were similar between groups except for a slightly higher incidence of hypotension in the intensive group. Unlike the SPRINT trial, treatment regimens were standardized so that the distribution of drug classes between groups remained similar. The study only enrolled Chinese patients, so it is unknown how its results would translate to other populations.
In conclusion, targeting a SBP in the range of 120 - 130 mmHg improves CV outcomes when compared to a target of 130 - 140 mmHg. In practice, many patients are intolerant of lower blood pressure targets, but for those without issues, a benefit may be seen.

STUDIES | MORNING VS EVENING DOSING

Overview

In most people, blood pressure tends to run higher in the morning when cortisol levels rise. Cardiovascular events are also more common during this time. Most blood pressure medications are taken once daily, meaning trough levels occur about 24 hours after dosing. Morning dosing of blood pressure medications causes the highest window of CV risk to coincide with the lowest levels of drugs. Taking medications at bedtime so that levels are higher in the morning could theoretically reduce the risk of CV events.
The two large trials detailed below compared CV events between people assigned to take their blood pressure medications in the morning versus the evening

STUDY
Bedtime vs Awakening Dosing of Blood Pressure Medications , European Heart Journal (2019) [PubMed abstract]

Design: Randomized controlled trial (N=19,084 | length = median 6.3 years) in patients with hypertension being treated with ≥ 1 antihypertensive medication(s)
Treatment: Take all BP medications at bedtime vs Take all BP meds upon awakening
Primary outcome: Composite of myocardial infarction, coronary revascularization, heart failure, ischaemic stroke, haemorrhagic stroke, and CVD death
Results:

Primary outcome: Bedtime to awakening hazard ratio 0.55 (95%CI [0.50–0.61]), p <0.001

Findings: Routine ingestion by hypertensive patients of ≥ 1 prescribed BP-lowering medications at bedtime, as opposed to upon waking, results in improved ambulatory BP control (significantly enhanced decrease in asleep BP and increased sleeptime relative BP decline, i.e. BP dipping) and, most importantly, markedly diminished occurrence of major CVD events.

STUDY
TIME study - Morning vs Evening Dosing of Blood Pressure Medications, Lancet (2022) [PubMed abstract]

Design: Randomized controlled trial (N=21,104 | length = median 5.2 years) in adults with hypertension taking at least one antihypertensive
Treatment: Take all BP meds in the morning (0600 - 1000 h) vs Take all BP meds in the evening (2000 - 0000 h)
Primary outcome: Composite of vascular death or hospitalization for non-fatal myocardial infarction or non-fatal stroke
Results:

Primary outcome: Morning - 3.7%, Evening - 3.4% (p=0.53)

Findings: Evening dosing of usual antihypertensive medication was not different from morning dosing in terms of major cardiovascular outcomes. Patients can be advised that they can take their regular antihypertensive medications at a convenient time that minimizes any undesirable effects.

Summary

The two trials above had conflicting results, with one finding a benefit with evening dosing and the other finding no effect. Both studies were very large and similar in design, so it's difficult to favor one over the other. Additional trials evaluating the morning versus evening effect are currently underway. Given the current evidence, patients should be advised to take their medications at whatever time optimizes their compliance.

STUDIES | BLACKS

STUDY
Amlodipine + Perindopril or HCTZ vs Perindopril + HCTZ for HTN in Blacks, NEJM (2019) [PubMed abstract]

Design: Randomized controlled trial (N=621 | length = 6 months) in black patients with uncontrolled hypertension
Treatment: Amlodipine 10 mg/HCTZ 25 mg vs Amlodipine 10 mg/Perindopril 8 mg vs Perindopril 8 mg/HCTZ 25 mg
Primary outcome: Change in the 24-hour ambulatory systolic blood pressure between baseline and 6 months
Results:

Primary outcome: Amlodipine/HCTZ was 3.14 mmHg lower than Perindopril/HCTZ (p=0.03). Amlodipine/Perindopril was 3.00 mmHg lower than Perindopril/HCTZ (p=0.04). There was no significant difference between Amlodipine/HCTZ and Amlodipine/Perindopril (p=0.92)

Findings: These findings suggest that in black patients in sub-Saharan Africa, amlodipine plus either hydrochlorothiazide or perindopril was more effective than perindopril plus hydrochlorothiazide at lowering blood pressure at 6 months.

BIBLIOGRAPHY

1 - PMID 24352797
2 - PMID 25829340
3 - PMID 28135725 - 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, Annals of Internal Medicine (2017)
4 - ADA Standards of Medical Care in Diabetes 2016
5 - PMID 27979887 - ADA Standards of Medical Care in Diabetes - 2017: Summary of Revisions
6 - PMID 28827377 - Clinical Practice Guideline for Screening and Management of High Blood Pressure in Children and Adolescents, Pediatrics (2017)
6 - PMID 29133356 - 2017 ACC/AHA 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. Hypertension (2017)
7 - ADA 2019 Standards of Medical Care in Diabetes
8 - PMID 34152826 - Management of Blood Pressure in Patients With Chronic Kidney Disease Not Receiving Dialysis: Synopsis of the 2021 KDIGO Clinical Practice Guideline, Ann Intern Med (2021)

HYPERTENSION GUIDELINES