Norm Campbell, MD, FRCPC, Departments of Medicine, Community Health Sciences, and Pharmacology and Therapeutics, University of Calgary, Calgary; Libin
Cardiovascular Institute, Calgary, AB.

Sailesh Mohan, MD, MPH, Departments of Medicine, Community Health Sciences, and Pharmacology and Therapeutics, University of Calgary, Calgary; Libin Cardiovascular Institute,
Calgary, AB.

Abstract:

As over 9 in 10 older adults will develop hypertension, it is important for clinicians to routinely assess blood pressure. It is as important to treat hypertension in older adults as it is in
younger people. In general, select a low-dose diuretic. Beta-blockers are not as effective at preventing stroke as other major antihypertensive drug classes. Specifi c indications for drug classes
are provided. Target the blood pressure levels to <140/90 mmHg in general, <130/80 mmHg in people with diabetes or chronic kidney disease, and focus on systolic blood pressure control. If blood
pressure control is not achieved using a moderate dose of your initial selection, add a second antihypertensive drug.

Key Words: hypertension, antihypertensive drugs, pharmacotherapy, cardiovascular disease, stroke.

Introduction

It is estimated that over 90% of normotensive people age 55-65 will eventually develop hypertension if they live an average lifespan.¹ Hypertension is not to be ignored as it is the
leading risk for death and disability in older people, and is both preventable and treatable.^2,3 Two-thirds of stroke and half of ischemic heart disease and heart failure are attributable
to elevated blood pressure, and the absolute risk from hypertension increases with age.⁴ Most older adults are or will become candidates for antihypertensive therapy.



Lifestyle changes can both prevent and treat hypertension. When used in combination with antihypertensive drugs, such changes can considerably reduce the number and doses of medication
required.⁵ Recent data indicate that few Canadians make lifestyle changes after a diagnosis of hypertension. In Canadians over age 60, there is only a 3.2% reduction in smoking after a
diagnosis of hypertension, and there is no change in body mass index, physical inactivity, or excess alcohol consumption.⁶ Lifestyle changes are thus markedly underutilized and this leads
to overreliance on pharmacotherapy.



As pharmacotherapy does offer important benefits, especially in light of the difficulty in promoting lifestyle changes that could result in lowered blood pressure, it is important to review the
principles of instituting antihypertensive therapy. This article aims to assist clinicians in selecting appropriate initial antihypertensive therapy.



Prior to prescribing antihypertensive drugs it is important to assess the person for white coat hypertension, secondary hypertension, and factors such as pain or stress that may temporarily increase
blood pressure. White coat hypertension and secondary hypertension are more common among older people. White coat hypertension can be easily detected and followed by home measurement of blood
pressure. Importantly the threshold for hypertension using home measurement of blood pressure is 135/85 mmHg or higher. Ambulatory blood pressure is recommended to be considered to confirm the
diagnosis of white coat hypertension.

Initiation of Therapy

There are a large number of specific antihypertensive drugs that both lower blood pressure and reduce death and disability for older people.⁷ The initial drug to be used is an important
choice. The blood pressure lowering to be expected by the use of one drug alone is about 9/5 mmHg; hence most people will require combinations of drugs to bring blood pressure down to recommended
levels for optimal cardiovascular protection (Table 1).⁸ Initial therapy using two antihypertensive drugs is a consideration if the pretreatment blood pressure is 160/100 mmHg or more (or
150/90 mmHg or more in people with diabetes).⁷

For older people, drug therapy generally should be initiated if the blood pressure averages above 140 mmHg systolic or 90 mmHg diastolic and in most people should be lowered to less than 140 mmHg
systolic and less than 90 mmHg diastolic.⁷ For people with diabetes or chronic kidney disease, treatment should be initiated if the blood pressure averages greater than 130 mmHg systolic
or 80 mmHg diastolic and should be lowered to less than these values.⁷ Systolic blood pressure is a more important cardiovascular risk than diastolic blood pressure in older adults, is
often less well controlled, and requires greater clinician attention.



In 2009, CHEP is emphasizing maintaining blood pressure below 130/80 mmHg in people with diabetes. Up to 80% of deaths in people with diabetes are due to cardiovascular disease and up to 75% of
specific cardiovascular complications in people with diabetes are attributable to high blood pressure.⁹ Controlling blood pressure in people with hypertension and diabetes results in very
large reductions in death and cardiovascular event rates, and reduces the progression of renal disease and retinopathy.^10,11 However, despite the strong clinical benefits of blood pressure
lowering, a recent Ontario survey found that two-thirds of individuals with diabetes and hypertension were not achieving blood pressure targets.¹² Both diabetes and hypertension commonly
coexist in older people, and hence clinicians need to be vigilant for the deadly duo and pay particular attention to blood pressure control.



There have been concerns that treatment may prevent stroke in the oldest old but increase other adverse events, including total mortality.¹³ However, in 2008, a large randomized controlled
trial demonstrated large reductions in cardiovascular events and total mortality by lowering blood pressure with a diuretic with or without a angiotensin-converting enzyme (ACE) inhibitor in people
over age 80.¹⁴ Most studies, including this latter trial, included predominantly healthy people. Caution should be exercised in lowering blood pressure in older adults who are frail or
have significant postural hypotension or have substantial comorbidity, in whom reduction in blood pressure would not be expected to improve quality or quantity of life.⁷

Uncomplicated Hypertension

Initial therapy should be selected from antihypertensive drugs that optimally reduce cardiovascular events. These include low-dose thiazide-type diuretics, ACE inhibitors, long-acting calcium channel
blockers and angiotensin receptor blockers.⁷ Beta-blockers are not as effective at preventing stroke as low-dose thiazide-type diuretics, long-acting calcium channel blockers, and
angiotensin receptor blockers in older adults and therefore should not be selected as initial therapy in those over age 60 unless there is a compelling indication (Table 2).^15-20
Currently, there are no clinical trials to assess whether direct renin inhibitors improve cardiovascular outcomes of hypertensive patients, hence prescription of the newly released class should only
be considered in patients where proven therapies are unable to control blood pressure.

Choosing between Possible First-Line Choices

Table 2 outlines the specific pharmacotherapeutic recommendations of CHEP (2009) in different clinical settings.⁷ There are often several different potential first-line therapies to choose
among. Some principals can be used to help guide the initial selection. In the absence of a specific indication for a drug class, in general, older people have a better hypotensive response to
monotherapy with a low-dose diuretic or long-acting calcium channel blocker.²¹ Thiazide-like diuretics are very inexpensive, are well tolerated, and have the same cardiovascular benefits
as other classes, and therefore, in the authors’ opinion, should be the default choice if there is no contraindication to diuretics or specific indication for a different drug class (Figure 1).
Persistence with diuretic therapy is slightly lower than other drug classes and erectile dysfunction related to diuretics occurs in about 2% of people. Active gout can be precipitated by diuretic
therapy and hence diuretics should be avoided as initial therapy in people who have gout unless they are already prescribed therapy to prevent gout (e.g., allopurinol). Diuretics can also cause a
slight increase in blood glucose and lipid levels. The outcomes of people with diabetes, impaired glucose tolerance, or normal glucose levels are improved to the same extent with diuretics as with an
ACE inhibitor or calcium channel blocker. Hence, these clinical situations are not a valid reason to avoid prescribing a diuretic.²² Initial starting drugs and doses include
hydrochlorothiazide 12.5-25 mg/day, indapamide 1.25-2.5 mg/day, and chlorthalidone 12.5-25 mg/day (1/4-1/2 tablet). If single-drug antihypertensive therapy is anticipated, using a combination
diuretic tablet (hydrochlorothizide 12.5-25 mg with spironolactone or amiloride) will reduce the risk of developing hypokalemia and dysglycemia.

In older people for whom initial use of a low-dose thiazide-like diuretic is not indicated, a long-acting calcium channel blocker will lower blood pressure to a similar extent or slightly greater
extent as a diuretic.²³ Edema is a more common problem with dihydropyridine (e.g., amlodipine, nifedipine) than nondihydropyridine calcium channel blockers (e.g., verapamil, diltiazam).
When using nondihydropyridine calcium channel blockers, be alert for potential drug interactions (nondihydropyridine calcium channel blockers are CYP 3A4 inhibitors), the contraindication in people
with systolic heart failure and the potential to cause heart block in people with atrio-ventricular (A-V) conduction defects or people who are using other drugs that reduce A-V conduction (e.g.,
beta-blocker). Typical initial choices of calcium channel blockers and their doses include amlodipine 2.5-5 mg/day, Adalat (nifedipine) XL 20-30 mg/day, diltiazam (in extended release form) 120-240
mg/day and verapamil (in extended release form) 240 mg/day. A recent randomized controlled trial has concluded that calcium channel blocker therapy paired with an ACE inhibitor is superior to a
diuretic paired to a ACE inhibitor.²⁴ However, methodological issues in the conduct of the trial may preclude the study affecting therapeutic recommendations.



Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers may be used as initial choices of antihypertensive drugs for older adults although, based on differing efficacy to lower
blood pressure, the National Institute of Clinical Evaluation suggests they be selected after considering a diuretic and calcium channel blocker first.^7,21 In general, the ACE inhibitors
and angiotensin receptor blockers are excellent to add to the initial choice if blood pressure targets are not achieved with single drug treatment.²¹ A large randomized controlled trial
using ACE inhibitors in isolated systolic hypertension has not been conducted, and hence CHEP does not recommend ACE inhibitors in that setting. Cough and angioedema are adverse effects of specific
concern with ACE inhibitors. Numerous ACE inhibitors and angiotensin receptor blockers with different starting doses are in common use.



Conclusion

Maximal blood pressure lowering effect from most antihypertensive drug classes requires about 4-6 weeks, and therefore titration of therapy in the absence of a medical urgency can occur at that
interval. About 80% of the blood pressure lowering of most drug classes is achieved at half of the maximum dose, while side effects are much more common in the higher half of the dose
range.⁸ Therefore, use a combination of two drugs if there is an inadequate response to the initial therapy at moderate dose. Notably, based on a new clinical trial in 2008, CHEP now
recommends the combination of an ACE inhibitor with a ARB only be considered in selected and closely monitored people with advanced heart failure or proteinuric nephropathy.



When prescribing the initial drug it is reasonable to advise the patient that good blood pressure control usually requires lifestyle changes plus two or more drugs. This helps avoid the potential
disappointment and concerns if the initial therapy does not control the blood pressure.

The unhealthy lifestyles that cause hypertension (especially nutrition) usually elevate other cardiovascular risks, and hence a comprehensive approach to identifying and managing cardiovascular risks
is required. In particular, carefully screening for dyslipidemia and diabetes is required as these diagnoses will have a major impact on cardiovascular outcomes and treatments. Age itself is the
greatest risk factor for cardiovascular disease,⁴ and therefore all older adults with hypertension should be considered for blood pressure-lowering pharmacotherapy. Nevertheless, care
needs to be taken that the person truly has hypertension by excluding white coat hypertension and acute hypertensive responses to physical or emotional stresses, performing an appropriate diagnostic
work-up, and assessing the person for increased risks of hypotensive complications.



Appropriate antihypertensive pharmacotherapy is an effective mechanism to reduce cardiovascular morbidity and mortality in older adults. Individualized, simplified, but rational regimes of relatively
inexpensive antihypertensive drugs can control the blood pressure of most people. More information on treatment of hypertension including patient handouts can be found at "http://www.hypertension.ca">www.hypertension.ca.

Dr. Mohan has no stated conflicts of interest. Dr. Campbell has given talks sponsored by Bayer, Sanofi Aventis, Biovail, Bristol Myers Squibb, Pfizer, Novartis and Merck-Frosst, and also has
been on advisory boards for Novartis, Pfizer, Servier, Boehringer Ingelheim and Schering-Plough.

KEY POINTS / CLINICAL PEARLS

Kenneth M. Madden, MSc, MD, FRCP, VITALITY (Vancouver Initiative to Add Life To Years) Group, Department of Medicine, University of British Columbia, Vancouver, BC.

Orthostatic hypotension (OH), while not itself a disease, is an important physical finding in the setting of unexplained syncope or falls. All antihypertensive medications directly interfere with the normal cardiovascular responses (increased venous return, tachycardia, and vasoconstriction) to orthostatic stress. Regular screening for this condition in older adults with hypertension, as well as careful titration of antihypertensive medications, can greatly improve both mortality and quality of life in this vulnerable population.
Keywords: orthostatic hypotension, postural vitals, antihypertensives, syncope, geriatric medicine.