Increasing complexity: which drug class to choose for treatment of hypertension in the elderly?

Figures & data

Figure 1 Model of the current problems of antihypertensive therapy in the elderly and very elderly.

Table 1 Comparison of recommended target blood pressure goals and substance classes in the elderly

	ACCF/AHA 2011	ESH/ESC 2013	CHEP 2013	NICE 2011
Recommended substances	• Thiazides • Chlorthalidon • Bendrofluazide	• Diuretics • BBs • CCBs • ACEIs • ARBs	ISH • Thiazide diuretics • ARBs or • Non-dihydropyridine CCBs	• Diuretics • CCBs ISH • Combination of diuretics/CCBs or diutetics/ACEIs (ARBs)
Recommended BP goals	General goal: SBP <140 mmHg Unclear if the same BP goal should be applied for patients older/younger than 80 years	Goal for patients ≥80 years: If BP initially >160 mmHg: SBP goal 140–150 mmHg Goal for patients <80 years: If BP initially >140 mmHg: BP goal <140 mmHg	Goal for patients ≥80 years: SBP goal <150 mmHg Goal for patients <80 years: SBP >140 mmHg ISH: SBP <140 mmHg	General goal: BP <150/90 mmHg ISH: <140/90 mmHg
Recommendation for application	• Start low and titrate • Add second class if primary drug’s full dose is reached • E stablish initial dual-drug therapy if BP exceeds >20/10 mmHg above goal	• Start low and titrate	• Start low and titrate • Add additional drugs if target BP levels are not achieved with standard-dose monotherapy • Add second class if primary drug’s full dose is reached • E stablish initial dual-drug therapy if BP exceeds >20/10 mmHg above goal • Caution in patients with risk for substantial fall in BP	• CCBs as preferred add-on substances
Additional comments	• BBs do not show convincing benefit; however, good fit for patients with hypertension and coronary artery disease, heart failure, arrythmias, migraine, and senile tremor • CCBs should be considered if there is evidence for arterial stiffness and decreased vascular compliance, diastolic dysfunction, angina and supraventricular arrythmias	• Diuretics and CCBs should be considered in patients with ISH	• Hypokalemia must be avoided in patients treated with thiazide diuretic monotherapy • Alpha-blockers are not recommended as first-line agents for uncomplicated hypertension • BBs are not recommended as first-line therapy for uncomplicated hypertension in patients 60 years of age and older • Caution when combining a non-dihydropyridine CCB and a BB, as well as an ACEI and an ARB	• Use same antihypertensive drugs for patients ≥80 years as in patients 55–80 years • Be aware of comorbidities

Notes: ACCF/AHA 2011 Expert Consensus Document on Hypertension in the Elderly; 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); CHEP 2013. The 2012–2013 Canadian Hypertension Education Program (CHEP) guidelines for pharmacists: An update; NICE (National Institutes for Health and Clinical Excellence) 2011. Clinical management of primary hypertension in adults.

Abbreviations: ACCF/AHA, American College of Cardiology Foundation/American Heart Association; ACEIs, angiotensin-converting enzyme inhibitors; ARBs, angiotensin receptor blockers; BBs, beta-blockers; BP, blood pressure; CCBs, calcium channel blockers; ISH, isolated systolic hypertension; SBP, systolic BP.

Table 2 Comparison of latest divergent guideline-recommendations of ASH/ISH 2013 and JNC8 2014

	ASH/ISH 2013	JNC8 2014
Recommended substances	• Thiazides • ARBs/ACEIs • CCBs	• Thiazides • ARBs/ACEIs • CCBs
Recommended BP goals	Goal for patients ≥80 years: • SBP <140/90 mmHg for patients older than 80 years • <150/80 mmHg for some of the patients that are even older • If older patients (>80 years) have chronic kidney disease or diabetes melitus, BP should be lowered below 140/90 mmHg	Goal for patients ≥60 years: • <150/90 mmHg, • no benefit to lower SBP <140 mmHg • If treatment is well tolerated and SBP is lowered <140 mmHg, no upwards adjustment is necessary
Recommendation for application	• First step: CCBs or thiazide diuretics as first drug choice • Second step: ARBs, ACEI (or CCB or thiazide if ACEI or ARB used first) as second drug • Third step: combination of CCB + ACEI or ARB + thiazide diuretic	• Initiate thiazide-type diuretic or CCB, alone or in combination in black patients • Initiate thiazide-type diuretic or ACEI or ARB or CCB, alone or in combination in non-black patients
Additional comments	• Consideration of ethnicity and race • Long-acting drugs should be preferred • Availability (government and other agencies) and affordability influences drug-choice	• Different possible drug-strategies including a) Maximizing first medication before adding second, b) Add second medication before reaching maximum dose of first medication c) Start with two medication classes seperately or as fixed-dose combination

Notes: ASH/ISH 2013 Clinical Practice Guidelines for the Management of Hypertension in the Community, A Statement by the American Society of Hypertension and the International Society of Hypertension, 2014 Evidence-Based Guideline for the Management of High Blood Pressure on Adults, Report From the Panel Members Appointed to the Eighth Joint National Committee (JNC8).

Abbreviations: CCBs, calcium channel blockers; ACEIs, angiotensin-converting enzyme inhibitors; ARBs, angiotensin receptor blockers; BP, blood pressure; SBP, systolic blood pressure ASH/ISH, American Society of Hypertension and the International Society of Hypertension.

Table 3 Most common drug-related side-effects of the main substance classes

Drug class	Adverse effects
Thiazide and loop diuretics	• Hypokalemia, hyponatremia, hypomagnesemia
	• Volume-depletion and orthostatic hypotension
	• Renal impairment, hyperuricemia, gout, lipid alterations, hyperglycemia, insulin resistance
	• NSAIDs reduce thiazide potency
	• Erectile dysfunction and possibly impotence
	• Reduction of lithium excretion and precipitate lithium toxicity
	• Potential to increase fatigue and lethargy
	• Pro-diabetogenic potential in combination with BBs
	• Increase of urinary frequency, leg cramps
	• Decrease of renal blood flow, creatinine clearance, GFR
Potassium-sparing diuretics	• Hyperkalemia, hypotension
BBs	• Sinus bradycardia, fatigue, AV-nodal heart block bronchospasm, aggravation of acute heart failure
	• Intermittent claudication, confusion, hyperglycemia
	• Diabetes mellitus
	• Drowsiness, lethargy, sleep disturbance, visual hallucinations, depression, blurring of vision, nightmares
	• Pulmonary side-effects (increased airway resistance in asthmatics)
	• Peripheral vascular side-effects (cold extremities, Raynaud’s phenomenon)
	• Erectile dysfunction
ACEIs	• Cough, hyperkalemia
	• Angioneurotic edema
	• Rash, altered taste sensation, renal impairment
ARBs	• Hyperkalemia, renal impairment
CCBs (non-dihydropyridines)	• Rash, sinus bradycardia, heart block, heart failure, constipation (verapamil), gingival hyperplasia
	• Ankle edema, headache and postural hypotension
CCBs (dihydropyridines)	• Peripheral edema, heart failure, tachycardia
	• Aggravation of angina pectoris (short-acting agents)
Direct vasodilators	• Tachycardia, fluid retention
	• Angina pectoris
Alpha1-adrenergic antagonists	• Hypotension
Alpha-beta adrenergic blockers (vasodilator-beta adrenergic blockers)	• Hypotension, heart block, sinus bradycardia, bronchospasm
Central-acting substances	• Sedation, constipation, dry mouth
Direct renin inhibitors	• Mild diarrhea

Abbreviations: ACEIs, angiotensin-converting enzyme inhibitors; ARBs, angiotensin receptor blockers; BBs, beta-blockers; CCBs, calcium channel blockers; NSAIDs, non-steroidal anti-inflammatory drugs; GFR, glomerular filtration rate; eGFR, estimated glomerular filtration rate; AV, atrioventricular.

Table 4 Comparison of recommended substance classes in special situations in hypertension management

Condition/factor	Recommended drug ESH/ESC 2013	Recommended drug ACCF/AHA 2011
Asymptomatic atherosclerosis/coronary artery disease risk	CCBs, ACEIs	Diuretics, BBs, ACEIs, CCBs, mineralocorticoid receptor antagonists
Recurrent stroke protection	Any drug reducing BP	Diuretics, ACEIs
Recurrent AMI protection	BBs, ACEIs, ARBs	BBs, ACEIs, mineralocorticoid receptor antagonists
End stage renal disease/proteinuria/chronic kidney disease	ACEIs, ARBs	ACEIs, ARBs
Diabetes mellitus	ACEIs, ARBs	Diuretics, BBs, ACEIs, ARBs, CCBs, mineralocorticoid receptor antagonists
Heart failure	Diuretics, BBs, ACEIs, ARBs, mineralocorticoid receptor antagonists	–
Black patients	Diuretics, CCBs	–
Other factors not mentioned in guideline recommendations applicable to the elderly/very elderly
Adherence	CCBs, ARBs
Costs savings	Diuretics, BBs, costs/adherence: ARBs
Dementia	ACEIs, CCBs

Notes: ACCF/AHA 2011 Expert Consensus Document on Hypertension in the Elderly: A Report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents developed in collaboration with the American Academy of Neurology, American Geriatrics Society, American Society for Preventive Cardiology, American Society of Hypertension, American Society of Nephrology, Association of Black Cardiologists, and European Society of Hypertension;⁴ 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).

Abbreviations: ACCF/AHA, American College of Cardiology Foundation/American Heart Association; ACEI, angiotensin-converting enzyme inhibitors; AMI, acute myocardial infarction; ARBs, angiotensin receptor blockers; BBs, beta-blockers; CCBs, calcium channel blockers.

AronowWSFlegJLPepineCJACCF/AHA 2011 expert consensus document on hypertension in the elderly: a report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents developed in collaboration with the American Academy of Neurology, American Geriatrics Society, American Society for Preventive Cardiology, American Society of Hypertension, American Society of Nephrology, Association of Black Cardiologists, and European Society of HypertensionJ Am Soc Hypertens20115425935221771565

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