Putting Evidence Based JNC 8 Guideline into Primary Care Practice

The global hypertension prevalence is estimated to increase from 40% to 50% in the year 2025, with a significant upsurge in future morbidity and mortality due to heart disease and strokes [1-3]. In the Kingdom of Bahrain, hypertension control has been achieved in only 1 out of 6 treated patients [4], which suggests that there is a major shortcoming either in clinician inertia or failure to take appropriate action to drive blood pressures ("BPs") down to guidelinerecommended levels [5].


Introduction
The global hypertension prevalence is estimated to increase from 40% to 50% in the year 2025, with a significant upsurge in future morbidity and mortality due to heart disease and strokes [1][2][3]. In the Kingdom of Bahrain, hypertension control has been achieved in only 1 out of 6 treated patients [4], which suggests that there is a major shortcoming either in clinician inertia or failure to take appropriate action to drive blood pressures ("BPs") down to guidelinerecommended levels [5].
We suggest that clinicians and the Ministry of Health ought to select one of the current guidelines and follow its recommendations. The Joint National Committee for Hypertension Detection and Management updated the JNC 8 guideline (2013), which if followed correctly, will achieve enhanced patient management and improve outcome indicators [6]. The JNC 8 panel has a different, focused and more simplified treatment approach than other expert panels, with a single BP recommendation (140/90 mm Hg) for both the pharmacologic treatment threshold and treatment goal for patients between the ages of 18 to 60 years old with/without diabetes ("DM") or chronic kidney disease ("CKD") [7] (Table 1) [8]. Furthermore, the JNC 8 relies solely on critical assessment of randomized controlled trials and reduces the number of first-line drugs from five to four [9][10][11][12].
Nonetheless, guidelines are not a substitute for clinical judgment, and clinicians must consider each patient's circumstances and clinical condition when making decisions about medical care [7].

Objectives
To initiate antihypertensive pharmacologic therapy at specific BP thresholds and to a specified BP goal improves health outcomes.
To start various antihypertensive drugs or drug classes differ in their comparative benefits and harms on specific health outcomes.  [8].

Strength of Recommendation
The patient's son inquired about the specific BP threshold to initiate antihypertensive pharmacologic therapy and specific level BP goal needed to be reached by the father. ( Table 2). The JNC 8 recommendation for the management of hypertension patients aged 60 years and older confirms beginning treatment for BP with 150 mm Hg systolic or 90 mm Hg diastolic or greater, and keep treating until the BP falls below those thresholds (strong recommendation-Grade A) [13][14]. However, if the patient tolerates a lower BP (e.g. ≤ 140 mm Hg systolic), then it is recommended not to adjust treatment to raise BP closer to 150 mm Hg (expert opinion-Grade E). Setting a goal systolic blood pressure ("SBP") of ≤ 140 mm Hg; in this age group provides no additional benefit in comparison with a higher SBP goals of 140 to 160 mm Hg or 140 to 149 mm Hg [15][16].
If a patient does not respond to ACEI, the alternative drug preferences specific for geriatric are calcium channel blocker ("CCB") and thiazide-type diuretics. The thiazide diuretics which include, chlorthalidone and indapamide; it does not include loop or potassiumsparing diuretics.
The patient was very well controlled on thiazide diuretics and CCB tablet.

Case 2: Hypertension in a young age patient < 65 years.
A 38 years old female Bahraini presented with uncontrolled diastolic hypertension (which ranged between = 100 -120) for the past 6 months. She was on Hydralazine 25 mg and Tenormin 100 mg, despite patient following strict life style modification. She was a symptomatic and questioning the benefits of her long-life treatment.
In the general population younger than 60 years old, JNC 8 recommends initiation of pharmacologic treatment, if diastolic blood pressure ("DBP") remains at 90 mm Hg or above (strong recommendation -Grade A) [17][18]. The guideline's goal is to lower the DBP lower than 90 mm Hg, which in turn reduces cerebrovascular events, heart failure and overall mortality [19].
The panel did not recommend β-blockers for the initial treatment of hypertension due to a higher rate of the primary composite outcome of cardiovascular death, myocardial infarction or stroke when compared to the use of an ARB [20].
There were no randomized controlled trials ("RCTs") of good or fair quality focusing on the following drug classes: dual α1-+ β-blocking agents (e.g. Carvedilol); vasodilating β-blockers (e.g. Nebivolol); central α2-adrenergic agonists (e.g. Clonidine); direct vasodilators (eg. Hydralazine); aldosterone receptor antagonists (e.g. Spironolactone), adrenergic neuronal depleting agents (e.g. Reserpine), and loop diuretics (e.g. Furosemide). The drugs of choice in younger age group are one of the followings: use of either ARB or ACEI and/or calcium channel blocker and/or medium potency diuretic (Figure 1). The patient was very well controlled on Indapamide diuretics and ACE inhibitor tablet [21].

Case 3: Hypertension in a black patient
A 52 years old Ethiopian black male presented with uncontrolled resistant hypertension for the past 5 years. He was on calcium channel blocker with thiazide diuretic prescribed from his country and strict life style modification. He was enquiring about the maximum dose.
For black patients, initial therapy should be a thiazide diuretic or calcium channel blocker. Thiazide diuretics were more effective in black patients for improving cerebrovascular, heart failure and combined cardiovascular outcomes. Additionally, a calcium channel blocker reduced rate of stroke to a greater degree than an ACE inhibitor in black population (moderate recommendation -Grade B) [22].
In non-black patients with hypertension, the initial treatment can be selected from the 4 drug classes recommended by the panel {a thiazide diuretic, calcium channel blocker ("CCB"), angiotensinconverting enzyme ("ACE") inhibitor or angiotensin receptor blocker ("ARB")} which effects on overall mortality, cardiovascular, cerebrovascular, and kidney outcomes, with one exception; heart failure. Therefore, our personal preference is that to initiate a thiazide-type diuretic is more effective than a CCB; but the panel did not reach this conclusion in its recommendation [22]. The patient has responded well to maximum drug dose (

Case 4: Hypertension in a chronic kidney disease (CKD) patient
A 55 years old Bahraini female presented with hypertensive for the past 10 years and recent micro-albuminuria. The BP was very well controlled on calcium channel blocker ("CCB"); the patient queried about micro-albuminuria treatment and the recommended dose.
In patients with CKD, initial or add-on therapy should be an ACE inhibitor or ARB, regardless of race or diabetes status (moderate recommendation-Grade B) since it improves kidney outcomes for patients with CKD. This recommendation applies to CKD patients with or without proteinuria, as studies using ACEIs or ARBs presented evidence of improved kidney outcomes in both groups -the patient's BP and proteinuria were very well controlled on ACEI + CCB [23] ( Tables 4 and 5).

Case 5: Hypertension in a diabetic patient
A 45 years old Bahraini female presented with hypertensive for the past 10 years and recent diabetes mellitus. She asked about her treatment of ARB and the recommended dose.
In the general non-black population, together with those with diabetes, primary antihypertensive treatment should include any one from the 4 anti-hypertensive class {thiazide-type diuretic, calcium channel blocker (CCB), angiotensin-converting enzyme inhibitor (ACEI), or angiotensin receptor blocker (ARB)} (moderate recommendation -Grade B) [16].
In the general black population, together with those with diabetes, early antihypertensive treatment should include a thiazide-type diuretic or CCB (weak recommendation -Grade C) [22].
The patient was advised to continue on her maximum dose of her ARB, she was doing well (Tables 4 and 5).

Case 6: Hypertension patient on thiazide treatment
A 50 years old foreigner patient with controlled hypertensive on thiazide-type diuretic was told previously that his BP was uncontrolled (systolic blood pressure ranged between 135 -140; while diastolic blood pressure ranged between 85 -90).

Case 7: Hypertensive with compelling indication
A 58 years old Bahraini male presented with uncontrolled hypertension, diabetes, hyperlipidemia, moderate obesity and hyperuracemia for 10 years duration, on ARB; Thiazide; Oral Hypoglycaemic; Statin and Zyloric.
Primary care physicians should regularly assess BP, encourage evidence-based lifestyle modification, adherence interventions, and then adjust treatment until goal BP is attained and maintained. In most cases, adjusting treatment means intensifying therapy by increasing the drug dose or by adding additional drugs to the regimen. JNC 7 recommends specific drug types for "compelling indications", including coronary heart disease, stroke, left ventricular dysfunction, heart failure, diabetes, gout and chronic kidney disease ("CKD") [6]. JNC 8 recommends specific drug classes for patients based on only four subtypes namely: age, race, diabetes, and CKD. These subtypes were the only ones with evidence randomized controlled trials studies [7]. Other recent guidelines incorporate these three subpopulations with age as a determinant of drug selection [9,12].
Most current guidelines approve of ACE inhibitors or ARBs for patients with diabetes and CKD, and thiazides or calcium channel blockers for black patients [7,9,12]. British and ASH/ISH guidelines prefer thiazides or calcium channel blockers as initial therapy for patients over ages of 55 or 60 years, respectively [9,12]. Both older age and black race are linked to low plasma renin levels, rendering drugs that inhibit the renin-angiotensin-aldosterone system ("RAAS") less effective if used solely (

Case 8: Hypertension with combined Renin Aldosterone Angiotensin Blockage System (RAAS) treatment
A 68 years old Bahraini male with hypertension with multiple comorbid diseases (diabetes and CKD) on combined RAAS treatment (ACEI and ARB) and other multiple drugs, with frequent episodic symptomatic attacks of hypotension, enquired about the cause of hypotension attacks. Neither JNC 7 nor JNC 8 addresses the combined use of drugs that block the RAAS, especially in patients with CKD [28,29]. There were three published randomized controlled trials that pointed out the threats of the Hypotension, acute renal failure and hyperkalemia [30][31][32]. The danger increases with the use of RAAS combined with a direct renin inhibitor such as aliskiren [30,31].

Conclusion
JNC 8 is a simpler guideline than other recent guidelines, with a single BP recommendation (140/90 mm Hg) for both the pharmacologic treatment threshold and treatment goal for patients between the ages of 18 and 60 years and patients with diabetes or CKD. JNC 8 also reduces the number of first-line drugs from five to four while recommending specific drug preferences for only three subpopulations: black patients, patients with diabetes, and patients with CKD.
The JNC 8 guideline is very helpful for primary care clinicians to better manage patients with hypertension. Primary care physicians can easily apply the evidence based JNC 8 guideline into their practice, however, the guideline is not a substitute for clinical judgment, and decisions about care must be carefully individualized.