Chronic hypertension medical therapy

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2017 ACC/AHA Hypertension Guidelines

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [5]; Associate Editor(s)-In-Chief: Yazan Daaboul; Serge Korjian

Overview

There has been a recent shift away from the administration of thiazide-type diuretics as first line therapy for patients with isolated essential hypertension to the use of any anti-hypertensive agent for isolated essential hypertension. Nonetheless, the administration of specific classes of drugs is indicated in particular patient populations with particular comorbid disease states.

Medical Therapy

Blood Pressure Targets of Therapy

JNC 8 recommendations for BP goals:[1]

  • Strong evidence for BP goal less than 150/90 mm Hg for patients above age 60.
  • Strong evidence exists for a diastolic goal of less than 90 mm Hg for hypertensive patients between ages 30 - 59.
  • There is insufficient evidence for patients below age 60 for a systolic goal, or in those below age 30 for a diastolic goal, so the panel recommended a BP of less than 140/90 mm Hg for those groups based on expert opinion.

Newer trials have identified conflicting benefits to more intensive therapy.

  • In the SPRINT randomized control trial, patients at high risk for CVD but who do not have a history of stroke or diabetes, intensive BP control (target SBP <120 mm Hg) improved CV outcomes and overall survival compared to standard therapy, while modestly increasing the risk of some serious adverse events[2].
  • In the HOPE-3 randomized controlled trial, patients with intermediate risk who did not have cardiovascular disease did not benefit from lowering blood pressure below 138.1/81.9 mm Hg was not beneficial. [3]
  • In patients with diabetes, the ACCORD (Action to Control Cardiovascular Risk in Diabetes) randomized controlled trial patients did not benefit from targeting a systolic blood pressure of less than 120 mm Hg, as compared with less than 140 mm Hg.[4]

Debate exists on how low should physicians target blood pressure in their patients especially in light of studies that have shown a J or U-shaped curve phenomenon associated with hypertension treatment where low and very high blood pressure values are associated with increased risk of cardiovascular events.[5] Along those lines, a new trend has recently surfaced advocating a less strict target in diabetic and elderly patients seen in the new ADA and ESH/ESC 2013 guidelines respectively. This rationale is supported by the fact that lower SBP targets in diabetic patients have not been shown to generate better outcomes.[6] Similarly, treatment of stage 1 hypertension in elderly patients and targeting SBP values to <140 mmHg have not been well substantiated and may sometimes carry more risk than benefit.[7]

Approach to Medical Therapy

Pharmacologic therapy is normally initiated based on the cardiovascular risk. Failure to achieve BP goals in patients with low and moderate cardiovascular risk after three to six months of non-pharmacologic measures necessitates the initiation of pharmacologic therapy. Medical management should be reserved to patients with BP>140/90 mmHg (except in certain cases discussed below). A lot of debate exists on the optimal approach to the medical management of hypertension. With the multitude of classes and agents that can be used, several questions arise about the single best agent, the optimal combination of agents, and the best step-wise approach to medical management. Although JNC7 tried to address these issues, almost a decade has passed since the release of their recommendations, with a myriad of studies and trials presenting newer compelling evidence to update the current recommendations. The 2013 ESH/ESC guidelines for the management of hypertension have dwelled into these issues and have outlined the rationale behind adopting a new approach. Below are the algorithms for the approach to the medical therapy of hypertension presented by ESH/ESC and JNC8 in 2013.


ESH/ESC 2013 Guidelines. Approach to medical therapy of hypertension.
ESH/ESC 2013 Guidelines. Approach to medical therapy of hypertension.
ESH/ESC 2013 Guidelines. Approach to medical therapy of hypertension.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Adult aged ≥18 years
with hypertension
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Implement lifestyle interventions
(continue throughout management)
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Set blood pressure goal
Inititate BP lowering-medication
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
General population
(no diabetes or CKD)
 
 
 
 
 
 
 
 
 
Diabetes
or CKD present
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Age ≥60 years
 
 
 
Age <60 years
 
 
 
All ages
Diabetes present
No CKD
 
 
 
All ages
CKD present with
or without diabetes
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Blood pressure goal
SBP <150 mm Hg
DBP <90 mm Hg
 
 
 
Blood pressure goal
SBP <140 mm Hg
DBP <90 mm Hg
 
 
 
Blood pressure goal
SBP <140 mm Hg
DBP <90 mm Hg
 
 
 
Blood pressure goal
SBP <140 mm Hg
DBP <90 mm Hg
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Nonblack
 
 
 
Black
 
 
 
 
 
 
All races
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Initiate thiazide-type diuretic
or ACEI or ARB or CCB,
alone or in combination
 
 
 
Initiate thiazide-type diuretic
or CCB, alone or in combination
 
 
 
 
 
 
Initiate ACEI or ARB, alone or in combination with other drug class.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Select a drug treatment titration strategy
A. Maximize 1st medication before adding 2nd
OR
B. Add 2nd medication before reaching maximum dose of 1st medication
OR
C. Start with 2 medication classes separately or as fixed-dose combination
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
At goal blood pressure?
 
 
 
 
 
 
Yes
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
No
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Reinforce medication and lifestyle adherence.
For strategies A and B:
Add and titrate thiazide-type diuretic or ACEI or ARB or CCB (use medication class not previously selected and avoid combined use of ACEI & ARB).
For strategy C:
Titrate doses of initial medications to maximum.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
At goal blood pressure?
 
 
 
 
 
 
Yes
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
No
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Reinforce medication and lifestyle adherence.
Add and titrate thiazide-type diuretic or ACEI or ARB or CCB (use medication class not previously selected and avoid combined use of ACEI & ARB).
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
At goal blood pressure?
 
 
 
 
 
 
Yes
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
No
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Reinforce medication and lifestyle adherence.
Add additional medication class (eg, β-blocker, aldosterone antagonist, or others) and/or refer to physician with expertise in HTN management.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
No
 
At goal blood pressure?
 
 
 
 
 
 
Yes
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Continue current treatment
and monitoring.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Antihypertensive Agents & Indications

Common Antihypertensive Agents

Several classes of medications are used in the treatment of hypertension namely diuretics, ACE inhibitors, angiotensin receptor blockers, beta-blockers, alpha-blockers, and direct vasodilators. Below is a list of common oral agents used in the treatment of hypertension.

JNC8: Common oral antihypertensive agents[8]
Class Drug Usual Dose Range (mg/day)
Thiazide Diuretics Chlorothiazide 125-500
Chlorthalidone 12.5-25
Hydrochlorothiazide 12.5-50
Polythiazide 2-4
Indapamide 1.25-2.5
Metolazone 0.5-5
Loop Diuretics Bumetanide 0.5-2
Furosemide 20-80
Torsemide 2.5-10
Potassium-sparing Diuretics Amiloride 5-10
Triamterene 50-100
Aldosterone Receptor Diuretics Spironolactone 25-50
Eplerenone 50-100
Beta-Blockers Atenolol 25-100
Betaxolol 5-20
Bisoprolol 2.5-10
Metoprolol 50-100
Metoprolol extended release 50-100
Nadolol 40-120
Propranolol 40-160
Propranolol long-acting 60-180
Timolol 20-40
Beta-Blockers with intrinsic sympathomimetic activity Acebutolol 200-800
Penbutolol 10-40
Pindolol 10-40
Combined Alpha- and Beta-Blockers Carvedilol 12.5-50
Labetalol 200-800
ACE Inhibitors Benazepril 10-40
Captopril 25-100
Enalapril 5-40
Fosinopril 10-40
Lisinopril 10-40
Moexipril 7.5-30
Perindopril 4-8
Quinapril 10-80
Ramipril 2.5-20
Trandolapril 1-4
Angiotensin Receptor Blockers Candesartan 8-32
Eprosartan 400-800
Irbesartan 150-300
Losartan 25-100
Olmesartan 20-40
Telmisartan 20-80
Valsartan 80-320
Nondihydropyridine Calcium Channel Blockers Diltiazem extended release 120-540
Verapamil immediate release 80-320
Verapamil long acting 120-480
Verapamil 120-360
Dihydropyridine Calcium Channel Blockers Amlodipine 2.5-10
Felodipine 2.5-10
Isradipine 2.5-10
Nicardipine sustained release 60-120
Nifedipine long-acting 30-60
Nisoldipine 10-40
Alpha-1 Blockers Doxazosin 1-16
Prazosin 2-20
Terazosin 1-20
Centrally Acting Drugs Clonidine 0.1-0.8
Methyldopa 250-1000
Reserpine 0.1-0.25
Guanfacine 0.5-2
Direct Vasodilators Hydralazine 25-100
Minoxidil 2.5-80

Choice of Initial Agent

There is currently a remarkable shift from JNC7 [8] (2004) and WHO/International Society of Hypertension[9] (2003) recommendations of starting thiazide-type diuretics as initial pharmacologic agents for isolated essential hypertension. Although several trials and observational studies found additional benefits in specific classes of anti-hypertensive medications, the consensus of starting any pharmacologic therapy as initial choice for isolated essential hypertension still holds today. According to the 2013 ESH/ESC Guidelines[10], pharmacologic therapy for the management of isolated hypertension may include any of beta-blockers, calcium channel blockers, ACE-inhibitors, ARBs, or thiazide diuretics. Ranking of different antihypertensive agents to specific lines of therapy is not evidence based. The guidelines explain that given the main goal of therapy (lowering blood pressure), the almost similar effects of different agents on outcome, and given the benefits and risks of each individual agent, ranking would not be of additional benefit.[10] However, compelling indications for various classes of anti-hypertensive medications are well-established and are still recommended according to patient profiles and medical history. Detailed indications are shown below.

JNC7: Compelling Indications and Choice of Antihypertensive Agents[8]

Clinical trials and basis for compelling indications for individual drug classes
Compelling Indication Recommended Drugs Clinical Trial Basis
Heart failure Diuretics, Beta blockers, ACEIs, ARBs, Aldosterone antagonist ACC/AHA Heart Failure Guideline [11]; MERIT-HF [12];COPERNICUS [13]; CIBIS [14]; SOLVD [15]; AIRE [16]; TRACE [17]; ValHEFT [18]; RALES [19]
Post-Myocardial infarction Beta blockers, ACEIs, Aldosterone antagonist ACC/AHA Post-MI Guideline [20]; BHAT [21]; SAVE [22]; CAPRICORN [23]; EPHESUS [24]
High coronary disease risk Diuretics, Beta blockers, ACEIs, CCBs, ALLHAT [25]; HOPE[26]; ANBP2 [27]; LIFE [28]; CONVINCE [29]
Diabetes Diuretics, Beta blockers, ACEIs, ARBs, CCBs NKF-ADA Guideline [30][31];UKPDS [32]; ALLHAT [25]
Chronic kidney disease ACEIs, ARBs NFK Guideline [31]; Captopril Trial [33]; RENAAL [34]; IDNT [35]; REIN [36]; AASK [37]
Recurrent stroke prevention Diuretics, ACEIs PROGRESS [38]



Contraindicated medications

Chronic hypertension is considered an absolute contraindication to the use of the following medications:


Severe uncontrolled arterial hypertension is considered an absolute contraindication to the use of the following medications:

ESH/ESC 2013 Guidelines: Drugs to be Preferred in Specific Conditions [10]

Patient Characteristic Drug
Asymptomatic organ damage
Left Ventricular Hypertrophy ACE inhibitor, calcium antagonist, ARB
Asymptomatic atherosclerosis Calcium antagonist, ACE inhibitor
Microalbuminuria ACE inhibitor, ARB
Renal dysfunction ACE inhibitor, ARB
Clinical CV event
Previous stroke Any agent effectively lowering BP
Previous myocardial infarction BB, ACE inhibitor, ARB
Angina pectoris BB, calcium antagonist
Heart failure Diuretic, BB, ACE inhibitor, ARB, mineralocorticoid receptor antagonists
Aortic aneurysm BB
Atrial fibrillation, prevention Consider ARB, ACE inhibitor, BB or mineralocorticoid receptor antagonist
Atrial fibrillation, ventricular rate control BB, non-dihydropyridine calcium antagonist
ESRD/proteinuria ACE inhibitor, ARB
Peripheral artery disease ACE inhibitor, calcium antagonist
Other
ISH (elderly) Diuretic, calcium antagonist
Metabolic syndrome ACE inhibitor, ARB, calcium antagonist
Diabetes mellitus ACE inhibitor, ARB
Pregnancy Methyldopa, BB, calcium antagonist
Blacks Diuretic, calcium antagonist

Management of Hypertension in Special Populations

Ethnic groups

  • African Americans: Enforcement of DASH diet due to its association with greater reduction of BP than other ethnicities.[39] According to the ALLHAT trial that included 15,000 Blacks, diuretics were more effective for African Americans than other classes of anti-hypertensive agents.[40]
  • Mexican Americans, other Hispanic Americans, Native Americans, and Asian/Pacific Islanders have been recruited in insufficient numbers in research trials to adequately identify special considerations.[41]

Diabetic Patients

  • According to the American Diabetes Association, BP goal for diabetic patients must be < 140/80 mmHg to reduce the progression of target organ damage but that lower systolic blood pressure targets <130 mmHg can be targeted in younger patients.[6] The recent shift in the approach to hypertension in diabetics proposed by the 2013 ADA guidelines as well as the 2013 ESH/ESC guidelines is supported by the fact that no major trials have consistently achieved a blood pressure level below 130/80 mmHg in diabetics nor have the smaller trials shown any major benefit from intensive treatment to reach that threshold. In parallel to the ADA, the 2013 ESH/ESC guidelines only support a lower DBP goal set at 80-85 mmHg.[10]
  • According to the American Diabetes Association, ACEI and ARBs are considered superior agents in diabetic patients for their renal protective effects (delay in both GFR decrease and albuminuria worsening).[42] Although RAAS blockers such as ACEI and ARBs are beneficial their combination can sometimes have significant effects on renal function especially in high risk patients.[43]
  • Thiazide-type diuretics were shown to be beneficial in reducing heart disease in diabetic patients.[40] Despite their side effects of worsening hyperglycemia, thiazide-type diuretics were associated with stable target organ damage compared to other anti-hypertensive agents.[44]
  • According to the LIFE study, beta-blockers are especially beneficial in diabetic patients with ischemic heart disease despite their controversial role as monotherapy.[45] Even though decreased insulin sensitivity is a side effect, beta-blockers are not absolutely contraindicated in diabetes.[41]
  • In the management of hypertension, CCBs are unquestionably useful in the reduction of BP values. However, their role in preventing target organ damage in diabetic patients is inferior to other agents. The ALLHAT study demonstrated that amlodipine, a DHP CCB, was less effective than thiazides in reducing heart failure.[40] Similarly, the ABCD Trial also showed that nisoldipine, a dihydropyridine CCB was less effective than enalapril, an ACEI, in reducing ischemic heart disease.[46]

Chronic Kidney Disease Patients

  • Based mostly on the results from meta-analyses of patients with proteinuria showing slower rate of CKD progression when SBP was targeted to <130 mmHg, JNC7 and the National Kidney Foundation recommended a set BP goal below 130/80 mmHg for all CKD patients and the use of more than a single agent for therapy. The recommended treatment regimen usually includes an ACEI or ARB in combination with a loop diuretic. [8]
  • In 2012, the KDIGO Clinical Practice Guideline for the Management of Blood Pressure in Chronic Kidney Disease recommended that diabetic and non-diabetic patients with CKD without proteinuria or microalbuminuria should be treated if their BP measurements are consistently above 140/90 mmHg. Target of treatment in this group is to maintain blood pressure below 140/90 mmHg. In patients with CKD and microalbuminuria or proteinuria, initiation of therapy should be at BP values >130/80 mmHg with target below 130/80 mmHg. The guidelines also advocated the use ACEIs and ARBs in patients with microalbuminuria or proteinuria. Lifestyle modifications proposed included lowering salt intake to <2g per day of sodium, exercise for at least 30 minutes 5 times per week.
  • In contrast, the 2013 ESH/ESC guidelines updated their old recommendations, changing the blood pressure target to <140/90 mmHg, no different than the general population. They based their recommendations on three trials[47][48][49] conducted in patients with chronic kidney disease without diabetes, that showed no difference in ESRD progression and all-cause mortality between patients randomized to low BP targets (<130 mmHg) to those randomized to a higher target (<140 mmHg). To note, observational follow-up data from 2 of these studies showed a tendency to lower adverse events in the lower target group especially in patients with proteinuria.[7]

Patients with Metabolic Syndrome

  • Metabolic syndrome as a clinical concept is largely debatable, mostly since studies have shown little added benefit of the definition on the predictive power of each of the constitutive individual factors, making recommendations about hypertension treatment in this subpopulation limited.[10]
  • Lifestyle modification plays the most important role in anti-hypertensive therapy in patients with metabolic syndrome.
  • Persistence of high BP > 140/90 mmHg still warrants pharmacologic therapy.
  • Management of dyslipidemia, glucose intolerance, and other concomitant comorbidities is essential for reduction of BP in patients with metabolic syndrome.[41]

Elderly Patients

  • There is particular advantage in weight loss and reduced sodium intake in elderly subjects. Trial of Non-pharmacologic Interventions in the Elderly (TONE) showed that sodium intake of less than 80 mmol per day (2 g of sodium per day or 5 grams of sodium chloride salt) could allow the discontinuation of anti-hypertensive agents in 40% of elderly.[50]
  • The 2013 ESH/ESC guidelines modified the approach adopted in 2007 to treat hypertension regardless of age. The new guidelines advocate holding medical therapy for elderly patients with stage 1 hypertension and initiating treatment only in those with stage 2 hypertension or greater. It is also recommended to target a SBP below 150 mmHg rather than 140mmHg. This rationale follows several studies involving elderly patients not achieving blood pressure measurements below 140mmHg. In patients below 80 years of age, treatment can be targeted below 140 mmHg if goal can be tolerated.[10]
  • The HYpertension in the Very Elderly Trial (HYVET) showed that in patients older than 80 years-old with SBP >160mmHg, a significant reduction in major CV events and all-cause mortality can be seen by aiming at SBP values <150mmHg. [51]
  • The JNC7 guidelines concluded in 2004 that antihypertensive therapy should not be withheld in patients with stage 1 hypertension based on age, even though no RCTs had shown benefits from treatment in this population at the time.

Pregnant Women

  • Distinguishing gestational from pre-gestational hypertension in pregnant women is essential. Hypertension is not considered to be caused by pregnancy when it develops before 20 weeks of gestation.[41]
  • Hypertensive women who plan to become pregnant should be instructed to use safe anti-hypertensive medications, such as methyldopa preferentially because long-term follow up studies are available. [52] Labetolol and nifedipine are also other treatment options that can be considered in pregnancy.[10]
  • Pregnant women with stage 1 hypertension present with low cardiovascular risk and anticipated physiological lowering of blood pressure during pregnancy. Thus healthcare providers might advise mere lifestyle modification as therapy during pregnancy and breast feeding, with caution on excessive weight reduction and with possible restriction of aerobic physical activity.[41]
  • The 2013 ESH/ESC guidelines recommend drug treatment of severe hypertension in pregnancy defined as SBP >160 mmHg or DBP >110 mmHg. They also advocate considering treatment in pregnant women with persistant hypertension ≥150/95 mmHg and in symptomatic patients or patients with target organ damage with BP ≥140/90 mmHg.[10]

Patients with Hypertensive Emergency or Urgency

  • Hypertensive emergency is defined as high blood pressure causing acute target organ damage. Usually BP exceed 180/20 mmHg, but can sometimes occur at even lower values in patients who do not usually have high blood pressure.
  • Hypertensive urgency is defined as a BP > 180/120 mmHg without target organ damage. Hypertensive urgency may or may not be symptomatic.
  • Triage to differentiate between hypertensive emergency and urgency is crucial for appropriate management. While hypertensive emergencies require intensive care unit (ICU) admission for close monitoring and aggressive parenteral agents, hypertensive urgencies can be managed in the emergency department with outpatient follow-up for optimization of therapy.[41]
  • Treatment is based on titrated intravenous medications that act rapidly but safely especially in avoiding severe hypotension and ischemic organ damage. Nicardipine, sodium nitroprusside, labetalol, furosemide and nitrates are some of the agents used. In certain cases of volume overload-associated hypertensive emergency where diuresis is insufficient, dialysis and ultrafiltration may be of benefit.[10]
  • Generally, JNC 7 outlines the acute management of hypertensive emergencies as reduction of a maximum of 25% of mean arterial BP within the first hour followed by decrease of BP to 160/100 within the next 2 to 6 hours. Normalization of blood pressure should occur at a span of 24-48 hours. Rapid decrease in BP might precipitate ischemia caused by target organ damage.[41]
  • The 2013 ESH/ESC guidelines do not dwell much into the treatment of hypertensive emergencies due to the lack of evidence considering the small number of cases but recommend that treatment be individualized by the physician.[10]
  • Specific clinical situations are considered exceptions to the abovementioned management plan:[41]
    • Ischemic stroke will not require immediate BP lowering to maintain cerebral perfusion.
    • Aortic dissection requires SBP to be lowered immediately to < 100 mmHg if tolerated followed by rapid specific management.

2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults JNC 8 (DO NOT EDIT)[53]

Recommendations for the Management of Hypertension

"1. In the general population aged ≥60 years, initiate pharmacologic treatment to lower blood pressure (BP) at systolic blood pressure (SBP) ≥150 mm Hg or diastolic blood pressure (DBP) ≥90 mm Hg and treat to a goal SBP <150 mm Hg and goal DBP <90 mm Hg. (Strong Recommendation: Grade A)"
"2. In the general population for ages 30-59 years, initiate pharmacologic treatment to lower BP at DBP ≥90 mm Hg and treat to a goal DBP <90 mm Hg. (Strong Recommendation: Grade A)"
"1. In the general population aged ≥60 years, if pharmacologic treatment for high BP results in lower achieved SBP (eg, <140 mm Hg) and treatment is well tolerated and without adverse effects on health or quality of life, treatment does not need to be adjusted. (Expert Opinion: Grade E)"
"2. In the general population for ages 18-29 years, initiate pharmacologic treatment to lower BP at DBP ≥90 mm Hg and treat to a goal DBP <90 mm Hg. (Expert Opinion: Grade E)"
"3. In the general population <60 years, initiate pharmacologic treatment to lower BP at SBP ≥140 mm Hg and treat to a goal SBP <140 mm Hg. (Expert Opinion: Grade E)"
"4. In the population aged ≥18 years with chronic kidney disease (CKD), initiate pharmacologic treatment to lower BP at SBP ≥140 mm Hg or DBP ≥90 mm Hg and treat to goal SBP <140 mm Hg and goal DBP <90 mm Hg. (Expert Opinion: Grade E)"
"5. In the population aged ≥18 years with diabetes, initiate pharmacologic treatment to lower BP at SBP ≥140 mm Hg or DBP ≥90 mm Hg and treat to a goal SBP <140 mm Hg and goal DBP <90 mm Hg. (Expert Opinion: Grade E)"
"6. In the general non-black population, including those with diabetes, initial antihypertensive treatment should include a thiazide-type diuretic, calcium channel blocker (CCB), angiotensin-converting enzyme inhibitor (ACEI), or angiotensin receptor blocker (ARB). (Moderate Recommendation: Grade B)"
"7. In the general black population, initial antihypertensive treatment should include a thiazide-type diuretic or CCB. (Moderate Recommendation: Grade B)"
"8. In the general black population with diabetes, initial antihypertensive treatment should include a thiazide-type diuretic or CCB. (Weak Recommendation: Grade C)"
"9. In the population aged ≥18 years with CKD, initial (or add-on) antihypertensive treatment should include an ACEI or ARB to improve kidney outcomes. This applies to all CKD patients with hypertension regardless of race or diabetes status. (Moderate Recommendation: Grade B)"
"10. The main objective of hypertension treatment is to attain and maintain goal BP. If goal BP is not reached within a month of treatment, increase the dose of the initial drug or add a second drug from one of the classes in recommendation 6 (thiazide-type diuretic, CCB, ACEI, or ARB). The clinician should continue to assess BP and adjust the treatment regimen until goal BP is reached. If goal BP cannot be reached with 2 drugs, add and titrate a third drug from the list provided. Do not use an ACEI and an ARB together in the same patient. If goal BP cannot be reached using only the drugs in recommendation 6 because of a contraindication or the need to use more than 3 drugs to reach goal BP, antihypertensive drugs from other classes can be used. Referral to a hypertension specialist may be indicated for patients in whom goal BP cannot be attained using the above strategy or for the management of complicated patients for whom additional clinical consultation is needed. (Expert Opinion: Grade E)"

2013 ESH/ESC Guidelines For The Management of Arterial Hypertension (DO NOT EDIT)[54]

Summary of Recommendations on Initiation of Antihypertensive Drug Treatment (DO NOT EDIT)[54]

Class I
"1. Prompt initiation of drug treatment is recommended in individuals with grade 2 and 3 hypertension with any level of CV risk, a few weeks after or simultaneously with initiation of lifestyle changes. (Level of Evidence: A)"
"3. In elderly hypertensive patients drug treatment is recommended when SBP is ≥160 mmHg.(Level of Evidence: A)"
"2. Lowering BP with drugs is also recommended when total CV risk is high because of OD, diabetes, CVD or CKD, even when hypertension is in the grade 1 range.(Level of Evidence: B)"
Class IIa
"1. Initiation of antihypertensive drug treatment should also be considered in grade 1 hypertensive patients at low to moderate risk, when BP is within this range at several repeated visits or elevated by ambulatory BP criteria, and remains within this range despite a reasonable period of time with lifestyle measures. (Level of Evidence: B)"
Class IIb
"1. Antihypertensive drug treatment may also be considered in the elderly (at least when younger than 80 years) when SBP is in the 140–159 mmHg range, provided that antihypertensive treatment is well tolerated.(Level of Evidence: C)"
Class III
"1. Unless the necessary evidence is obtained it is not recommended to initiate antihypertensive drug therapy at high normal BP. (Level of Evidence: A)"
"2. Lack of evidence does also not allow recommending to initiate antihypertensive drug therapy in young individuals with isolated elevation of brachial SBP, but these individuals should be followed closely with lifestyle recommendations. (Level of Evidence: A)"

Summary of Recommendations on Blood pressure Goals in Hypertensive Patients(DO NOT EDIT)[54]

Class I
"1. A SBP goal <140 mmHg:
a) is recommended in patients at low–moderate CV risk. (Level of Evidence: B)
b) is recommended in patients with diabetes. (Level of Evidence: A)"
"2. In elderly hypertensives less than 80 years old with SBP ≥160 mmHg there is solid evidence to recommend reducing SBP to between 150 and 140 mmHg.(Level of Evidence: A)"
"3. In individuals older than 80 years and with initial SBP ≥160 mmHg, it is recommended to reduce SBP to between 150 and 140 mmHg provided they are in good physical and mental conditions.(Level of Evidence: B)"
"3. A DBP target of <90 mmHg is always recommended, except in patients with diabetes, in whom values <85 mmHg are recommended. It should nevertheless be considered that DBP values between 80 and 85 mmHg are safe and well tolerated.(Level of Evidence: A)"
Class IIa
"1. A SBP goal <140 mmHg:
a) should be considered in patients with previous stroke or TIA. (Level of Evidence: B)
b) should be considered in patients with CHD. (Level of Evidence: B)
c) should be considered in patients with diabetic or non-diabetic CKD. (Level of Evidence: B)"
Class IIb
"1. In fit elderly patients less than 80 years old SBP values <140 mmHg may be considered, whereas in the fragile elderly population SBP goals should be adapted to individual tolerability.(Level of Evidence: C)"

Summary of Recommendations on Treatment Strategies and Choice of Drugs (DO NOT EDIT)[54]

Class I
"1. Diuretics (thiazides, chlorthalidone and indapamide), beta-blockers, calcium antagonists, ACE inhibitors, and angiotensin receptor blockers are all suitable and recommended for the initiation and maintenance of antihypertensive treatment, either as monotherapy or in some combinations with each other.(Level of Evidence: A)"
Class IIa
"1. Some agents should be considered as the preferential choice in specific conditions because used in trials in those conditions or because of greater effectiveness in specific types of OD. (Level of Evidence: C)"
"2. Other drug combinations should be considered and probably are beneficial in proportion to the extent of BP reduction. However, combinations that have been successfully used in trials may be preferable. (Level of Evidence: C)"
Class IIb
"1. Initiation of antihypertensive therapy with a two-drug combination may be considered in patients with markedly high baseline BP or at high CV risk.(Level of Evidence: C)"
"1. Combinations of two antihypertensive drugs at fixed doses in a single tablet may be recommended and favoured, because reducing the number of daily pills improves adherence, which is low in patients with hypertension.(Level of Evidence: B)"
Class III
"1. The combination of two antagonists of the RAS is not recommended and should be discouraged. (Level of Evidence: A)"

References

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  2. ↑ SPRINT Research Group. Wright JT, Williamson JD, Whelton PK, Snyder JK, Sink KM; et al. (2015). "A Randomized Trial of Intensive versus Standard Blood-Pressure Control". N Engl J Med. 373 (22): 2103–16. doi:10.1056/NEJMoa1511939. PMC 4689591. PMID 26551272.
  3. ↑ Yusuf S, Lonn E, Pais P, Bosch J, López-Jaramillo P, Zhu J; et al. (2016). "Blood-Pressure and Cholesterol Lowering in Persons without Cardiovascular Disease". N Engl J Med. 374 (21): 2032–43. doi:10.1056/NEJMoa1600177. PMID 27039945.
  4. ↑ ACCORD Study Group. Cushman WC, Evans GW, Byington RP, Goff DC, Grimm RH; et al. (2010). "Effects of intensive blood-pressure control in type 2 diabetes mellitus". N Engl J Med. 362 (17): 1575–85. doi:10.1056/NEJMoa1001286. PMC 4123215. PMID 20228401. Review in: Evid Based Med. 2010 Oct;15(5):142-3 Review in: Ann Intern Med. 2010 Jul 20;153(2):JC1-4, JC1-5
  5. ↑ Bangalore S, Messerli FH, Wun CC, Zuckerman AL, DeMicco D, Kostis JB; et al. (2010). "J-curve revisited: An analysis of blood pressure and cardiovascular events in the Treating to New Targets (TNT) Trial". Eur Heart J. 31 (23): 2897–908. doi:10.1093/eurheartj/ehq328. PMID 20846991.
  6. ↑ 6.0 6.1 "Summary of revisions for the 2013 clinical practice recommendations". Diabetes Care. 36 Suppl 1: S3. 2013. doi:10.2337/dc13-S003. PMC 3537268. PMID 23264423.
  7. ↑ 7.0 7.1 Mancia G, Fagard R, Narkiewicz K, Redán J, Zanchetti A, Böhm M; et al. (2013). "2013 Practice guidelines for the management of arterial hypertension of the European Society of Hypertension (ESH) and the European Society of Cardiology (ESC): ESH/ESC Task Force for the Management of Arterial Hypertension". J Hypertens. 31 (10): 1925–38. doi:10.1097/HJH.0b013e328364ca4c. PMID 24107724.
  8. ↑ 8.0 8.1 8.2 8.3 Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL; et al. (2003). "Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure". Hypertension. 42 (6): 1206–52. doi:10.1161/01.HYP.0000107251.49515.c2. PMID 14656957.
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  20. ↑ Braunwald E, Antman EM, Beasley JW, Califf RM, Cheitlin MD, Hochman JS et al. (2002)ACC/AHA 2002 guideline update for the management of patients with unstable angina and non-ST-segment elevation myocardial infarction--summary article: a report of the American College of Cardiology/American Heart Association task force on practice guidelines (Committee on the Management of Patients With Unstable Angina). J Am Coll Cardiol 40 (7):1366-74. PMID: 12383588
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  22. ↑ Hager WD, Davis BR, Riba A, Moye LA, Wun CC, Rouleau JL et al. (1998) Absence of a deleterious effect of calcium channel blockers in patients with left ventricular dysfunction after myocardial infarction: The SAVE Study Experience. SAVE Investigators. Survival and Ventricular Enlargement. Am Heart J 135 (3):406-13. PMID: 9506325
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  24. ↑ Pitt B, Remme W, Zannad F, Neaton J, Martinez F, Roniker B et al. (2003)Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med 348 (14):1309-21. [1] PMID: 12668699
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  26. ↑ Yusuf S, Sleight P, Pogue J, Bosch J, Davies R, Dagenais G (2000) Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med 342 (3):145-53. [2] PMID: 10639539
  27. ↑ Wing LM, Reid CM, Ryan P, Beilin LJ, Brown MA, Jennings GL et al. (2003) A comparison of outcomes with angiotensin-converting--enzyme inhibitors and diuretics for hypertension in the elderly. N Engl J Med 348 (7):583-92.DOI:10.1056/NEJMoa021716 PMID: 12584366
  28. ↑ Dahlöf B, Devereux RB, Kjeldsen SE, Julius S, Beevers G, de Faire U et al. (2002) Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet 359 (9311):995-1003. DOI:10.1016/S0140-6736(02)08089-3 PMID: 11937178
  29. ↑ Black HR, Elliott WJ, Grandits G, Grambsch P, Lucente T, White WB et al. (2003) Principal results of the Controlled Onset Verapamil Investigation of Cardiovascular End Points (CONVINCE) trial. JAMA 289 (16):2073-82.DOI:10.1001/jama.289.16.2073 PMID: 12709465
  30. ↑ Arauz-Pacheco C, Parrott MA, Raskin P, American Diabetes Association (2003)Treatment of hypertension in adults with diabetes.Diabetes Care 26 Suppl 1 ():S80-2. PMID: 12502624
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  35. ↑ Lewis EJ, Hunsicker LG, Clarke WR, Berl T, Pohl MA, Lewis JB et al. (2001) Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med 345 (12):851-60. [4] PMID: 11565517
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  39. ↑ Sacks FM, Svetkey LP, Vollmer WM, Appel LJ, Bray GA, Harsha D; et al. (2001). "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. 344 (1): 3–10. doi:10.1056/NEJM200101043440101. PMID 11136953.
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  42. ↑ "Executive summary: Standards of medical care in diabetes--2013". Diabetes Care. 36 Suppl 1: S4–10. 2013. doi:10.2337/dc13-S004. PMC 3537272. PMID 23264424.
  43. ↑ ONTARGET Investigators. Yusuf S, Teo KK, Pogue J, Dyal L, Copland I; et al. (2008). "Telmisartan, ramipril, or both in patients at high risk for vascular events". N Engl J Med. 358 (15): 1547–59. doi:10.1056/NEJMoa0801317. PMID 18378520. Review in: J Fam Pract. 2009 Jan;58(1):24-7 Review in: Evid Based Med. 2008 Oct;13(5):147
  44. ↑ Weinberger MH (1985). "Blood pressure and metabolic responses to hydrochlorothiazide, captopril, and the combination in black and white mild-to-moderate hypertensive patients". J Cardiovasc Pharmacol. 7 Suppl 1: S52–5. PMID 2580177.
  45. ↑ Sica DA (2002). "Cardiovascular morbidity and mortality in patients with diabetes in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol". Curr Hypertens Rep. 4 (4): 321–3. PMID 12117460.
  46. ↑ Schrier RW, Estacio RO, Esler A, Mehler P (2002). "Effects of aggressive blood pressure control in normotensive type 2 diabetic patients on albuminuria, retinopathy and strokes". Kidney Int. 61 (3): 1086–97. doi:10.1046/j.1523-1755.2002.00213.x. PMID 11849464.
  47. ↑ Wright JT, Bakris G, Greene T, Agodoa LY, Appel LJ, Charleston J; et al. (2002). "Effect of blood pressure lowering and antihypertensive drug class on progression of hypertensive kidney disease: results from the AASK trial". JAMA. 288 (19): 2421–31. PMID 12435255.
  48. ↑ Klahr S, Levey AS, Beck GJ, Caggiula AW, Hunsicker L, Kusek JW; et al. (1994). "The effects of dietary protein restriction and blood-pressure control on the progression of chronic renal disease. Modification of Diet in Renal Disease Study Group". N Engl J Med. 330 (13): 877–84. doi:10.1056/NEJM199403313301301. PMID 8114857.
  49. ↑ Ruggenenti P, Perna A, Loriga G, Ganeva M, Ene-Iordache B, Turturro M; et al. (2005). "Blood-pressure control for renoprotection in patients with non-diabetic chronic renal disease (REIN-2): multicentre, randomised controlled trial". Lancet. 365 (9463): 939–46. doi:10.1016/S0140-6736(05)71082-5. PMID 15766995.
  50. ↑ Appel LJ, Espeland MA, Easter L, Wilson AC, Folmar S, Lacy CR (2001). "Effects of reduced sodium intake on hypertension control in older individuals: results from the Trial of Nonpharmacologic Interventions in the Elderly (TONE)". Arch Intern Med. 161 (5): 685–93. PMID 11231700.
  51. ↑ Bulpitt CJ, Beckett NS, Peters R, Leonetti G, Gergova V, Fagard R; et al. (2012). "Blood pressure control in the Hypertension in the Very Elderly Trial (HYVET)". J Hum Hypertens. 26 (3): 157–63. doi:10.1038/jhh.2011.10. PMID 21390056.
  52. ↑ ACOG Committee on Practice Bulletins--Obstetrics (2002). "ACOG practice bulletin. Diagnosis and management of preeclampsia and eclampsia. Number 33, January 2002". Obstet Gynecol. 99 (1): 159–67. PMID 16175681.
  53. ↑ James, Paul A.; Oparil, Suzanne; Carter, Barry L.; Cushman, William C.; Dennison-Himmelfarb, Cheryl; Handler, Joel; Lackland, Daniel T.; LeFevre, Michael L.; MacKenzie, Thomas D.; Ogedegbe, Olugbenga; Smith, Sidney C.; Svetkey, Laura P.; Taler, Sandra J.; Townsend, Raymond R.; Wright, Jackson T.; Narva, Andrew S.; Ortiz, Eduardo (2013). "2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults". JAMA. doi:10.1001/jama.2013.284427. ISSN 0098-7484.
  54. ↑ 54.0 54.1 54.2 54.3 Authors/Task Force Members. Mancia G, Fagard R, Narkiewicz K, Redon J, Zanchetti A; et al. (2013). "2013 ESH/ESC Guidelines for the management of arterial hypertension: The Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC)". Eur Heart J. 34 (28): 2159–219. doi:10.1093/eurheartj/eht151. PMID 23771844.

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