Cardiovascular Drugs in Older People

VOLUME 36 : NUMBER 6 : DECEMBER 2013

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Cardiovascular drugs in older people

Vasi Naganathan symptomatic postural hypotension in a frail older Associate professor SUMMARY person. In this situation, if the hypotension results in Centre for Education and falls, dizziness and impairment of everyday function Research on Ageing Cardiovascular drugs are the most frequently then avoiding postural hypotension should be the Sydney Medical School prescribed medicines for older people. priority even at the expense of less than ideal control University of Sydney However, it can be difficult to find a regimen of blood pressure. High blood pressure may have to Consultant geriatrician that does more good than harm, especially if be accepted as long as it is not causing symptoms. Concord Hospital the patient is frail. Sydney The consequences of a fractured hip as a result Prescribers should determine the goals of of a fall due to postural hypotension can be more treatment, understand the limitations of the devastating than the vascular events one was aiming Key words evidence and be vigilant for the adverse to prevent by lowering blood pressure. aged 80 and over, atrial fibrillation, heart failure, effects of cardiovascular drugs. Table 1 gives examples of how priorities may differ hypertension Regimens for common cardiovascular between a well older person and a frail older person diseases, such as hypertension, chronic heart for the treatment of specific cardiovascular diseases. Aust Prescr 2013;36:190–4 failure and chronic atrial fibrillation, need to Avoiding adverse effects is important in both groups, be tailored to the individual patient, taking but the risk of harm is greater in frail older people. In into account factors such as comorbidity and addition, mortality benefits are less likely to be seen in life expectancy. frail older people. Be aware of the limited evidence Introduction Older people are poorly represented in clinical trials,1 The prevalence of diseases such as hypertension, so there are limited data about the benefit and harm coronary heart disease, chronic heart failure and chronic atrial fibrillation increases with age, so cardiovascular drugs are the most frequently Box Guidelines for prescribing prescribed treatments for older people. These drugs cardiovascular drugs to older people are also responsible for a large proportion of the adverse drug reactions suffered by older people. 1. Take into account all the information obtained from a Important considerations when comprehensive assessment (e.g. postural hypotension, prescribing cognitive status, life expectancy) 2. Set goals of treatment – symptom control vs life There are some general principles to apply when prolongation prescribing cardiovascular drugs to older people 3. Understand and apply the evidence appropriately (Box). It is important to tailor a regimen for each 4. Avoid under-prescribing drugs that are likely to have individual patient. symptomatic and functional benefits (e.g. diuretics for Determine the goals of treatment chronic heart failure) 5. Be vigilant for adverse effects (see Table 2) Prescribers should ask themselves, ‘What outcome do I hope to achieve for this patient?’ The prescriber 6. Specifically look for drug–drug and drug–disease interactions should also consider what their patient hopes to 7. Discuss the potential benefits and harms with patient, achieve by following the treatment regimen. In general, family and carers cardiovascular drugs are helpful for symptom control, 8. Choose drugs wisely, start at a low dose and then prevention of cardiovascular events or life extension. increase the dose slowly In a healthy 80-year-old person all three goals may be 9. Try to avoid starting several drugs simultaneously applicable. In contrast, symptom control may be the 10. Conduct regular drug reviews only goal for an 80-year-old with severe dementia. 11. Stop drugs that are unlikely to be of benefit or are In frail older people with multiple comorbidities and likely to result in more harm than good functional limitations, it is important to prioritise the 12. Take a multidisciplinary approach to achieving optimal goals of treatment. These priorities should guide regimens (e.g. pharmacists can advise on simplifying prescribing. A common dilemma faced by clinicians the regimen and the best delivery system) is the combination of supine hypertension and

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Table 1 Priorities of treatment for cardiovascular diseases in healthy and frail older people

Disease Healthy older person Frail older person

Hypertension Decrease risk of vascular events Avoid symptoms of hypertension and hypotension Decrease mortality

Chronic heart failure Symptomatic relief Symptomatic relief Decrease admissions to hospital for decompensated Decrease admissions to hospital for decompensated acute heart failure acute heart failure Potential mortality benefit Avoid symptomatic hypotension and other adverse effects

Anticoagulation for chronic Harm–benefit ratio usually favours anticoagulation Harm–benefit ratio may favour antiplatelet drug over atrial fibrillation anticoagulant

Dyslipidaemia Decrease risk of vascular events Maintaining nutrition and treating malnutrition takes priority over dyslipidaemia

of giving cardiovascular drugs to frail older patients. are therefore more likely to come to harm from Clinical guidelines for cardiovascular diseases rarely hypotension when prescribed cardiovascular drugs provide any details on how they should apply to older which lower blood pressure. This problem can be frail people with multiple comorbidities. Given these exacerbated by the blood pressure lowering effects of limitations, prescribers should choose a regimen drugs for Parkinson’s disease. which is appropriate for the individual patient and In addition, older people on many different drugs minimises the risk of harm. Prescribing purely on (polypharmacy) are at increased risk of adverse evidence from younger patients or disease-specific events, in part because of the increased likelihood of guidelines leads to polypharmacy, pill burden and drug–drug interactions. often harm. However, the lack of direct evidence To minimise the possibility of adverse drug reactions it should not be a reason to deny older people is a good idea to take a ‘start low, go slow’ approach treatments that have the potential to improve their when prescribing. If possible, start only one new drug quality of life. For example, treatment to minimise the at a time, at the lowest dose possible and increase the breathlessness of heart failure can have a big impact dose slowly while being vigilant for possible adverse on the everyday function and overall quality of life of effects. an older person. It is important to question and examine older people Be vigilant for adverse effects for possible adverse drug reactions. Often the Over the past 20 years there has been an increase symptoms can be non-specific such as falls, tiredness in hospital admissions due to adverse drug or confusion. An adverse drug reaction such as postural reactions particularly in people over 80 years old.2 hypotension can easily be missed if not looked for. It is Cardiovascular drugs are responsible for about important to be aware of the common problems that 20% of these reactions in this age group. Adverse could be the adverse effects of cardiovascular drugs drug reactions can occur even at recommended (see Table 2). Ask specifically about, and look for, these adult doses. As people become frailer and acquire adverse effects. Be particularly aware of drugs that new diseases a previously safe and tolerated have a narrow therapeutic window or a long half-life regimen may result in harm. Age-related changes such as digoxin and warfarin. in drug receptors, impairments in homeostatic The drug regimen should be easy to follow and, mechanisms and postural autonomic function are with the help of pharmacists, have packaging, labels just some of the reasons why older people are and dose administration aids that are easy to use. more sensitive to the hypotensive effects of many A general practitioner can order a home medicine cardiovascular drugs. review for people living in the community. A similar Older people are likely to have diseases that result scheme is funded to encourage a medication in disease–drug interactions. For example, people management review for patients in residential aged- with dementia may become more confused if they care facilities. are prescribed drugs that can cause confusion such as beta blockers. Frail older people with Parkinson’s Hypertension disease often have orthostatic hypotension due The Hypertension in the Very Elderly Trial (HYVET) to disease-related autonomic dysfunction. They found that treating hypertension (systolic blood

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ARTICLE Cardiovascular drugs in older people

pressure above 160 mmHg) in patients over 80 be made not to treat after weighing up the harms years old is beneficial in terms of all-cause mortality, and benefits. episodes of heart failure and deaths from strokes.3 The current National Heart Foundation hypertension However, it is important to be aware that participants guidelines4 recommend treating patients with were screened carefully for comorbidity including grade 2 and 3 hypertension (systolic >160 mmHg postural hypotension (systolic blood pressure less or diastolic >100 mmHg). For patients aged 80 than 140 mmHg after two minutes of standing was and over, the results from HYVET would support an exclusion criteria). Although patients in the trial this recommendation. However, it is not clear if were healthier than the general population of the antihypertensive therapy should be prescribed to same age, antihypertensive therapy should be patients with grade 1 hypertension (systolic 140–159 considered in this age group if their life expectancy is mmHg or diastolic 90–99 mmHg). There is no direct clinical trial evidence in people aged 80 and over more than one or two years. However, there will be showing a benefit for treating this range of blood a proportion of patients, particularly the frail, who pressure. will not tolerate treatment or in whom a decision will The guidelines also recommend antihypertensive treatment regardless of blood pressure in patients with associated conditions such as diabetes, strokes Table 2 Problems with cardiovascular drugs and chronic kidney disease, or evidence of end- Problem Drug organ damage such as proteinuria from chronic

Confusion beta blockers kidney disease. It may be reasonable to follow this recommendation, but it is based on extrapolating digoxin the evidence from trials in much younger patients. HMGCoA reductase inhibitors (statins)* Clinical judgement and common sense are required. Cough ACE inhibitors For example, most patients over 80 years old will not less common with angiotensin receptor antagonists live long enough for proteinuria to ever progress to clinically significant renal failure. Gout thiazide diuretics loop diuretics The National Heart Foundation correctly says that all patients aged 75 years and over can be Headache/flushing calcium channel blockers assumed to have a high absolute cardiovascular Hyperkalaemia ACE inhibitors risk (more than 15% probability of a cardiovascular angiotensin receptor antagonists event within the next five years) without needing aldosterone antagonists to use a cardiovascular risk calculator. This could be interpreted as a recommendation that all Hypokalaemia thiazide diuretics patients aged over 75 years should be prescribed loop diuretics antihypertensives, but there is no direct evidence Hyponatraemia ACE inhibitors to support treatment regardless of blood pressure. thiazide diuretics There is also little evidence that treating hypertension loop diuretics in old age prevents dementia or slows progression in patients with dementia. Lethargy beta blockers

Oedema calcium channel blockers Target blood pressure HYVET had a target blood pressure of 150/80 mmHg. Postural hypotension antihypertensive drugs The National Heart Foundation recommends less diuretics than 140/90 mmHg and less than 130/80 mmHg in nitrates patients with associated conditions or end-organ Bleeding antiplatelet drugs e.g. aspirin, clopidogrel damage. ‘Lower is better’ may not apply to blood anticoagulants e.g. warfarin, dabigatran and rivaroxaban pressure in the very old. There is evidence from epidemiological studies in older people that low blood Renal failure diuretics pressure is associated with poorer survival. These ACE inhibitors studies suggest there is a threshold blood pressure, angiotensin receptor antagonists which varied by study, below which mortality Myalgia and myopathy statins increases. Constipation calcium channel blockers Choice of drug

* based on case reports Coexisting conditions, tolerability and the potential for adverse effects should guide the choice of

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ARTICLE antihypertensive drug. In many patients other atrial fibrillation usually, but not always, requires rate conditions such as ischaemic heart disease or chronic control. Symptomatic improvement should be the heart failure will determine what is prescribed. goal rather than a specific heart rate. Digoxin and Avoiding the adverse effects of high doses of a single beta blockers are commonly used for rate control in drug is a reasonable rationale for adding a second atrial fibrillation. drug. However, there is no evidence that combination antihypertensive drugs are more effective or safer in Digoxin older people. Digoxin has a narrow therapeutic window. Reduced renal function and a lower lean body mass increase Chronic heart failure serum digoxin concentrations. A number of A study in the USA suggests that many older patients commonly used drugs, such as verapamil, would have been excluded from clinical trials in heart amiodarone and diltiazem, can also increase 5 failure. Only 18%, 13% and 25% of more than 20 000 serum digoxin. Electrolyte abnormalities such as patients aged over 65 years from a heart failure hypokalaemia, hypomagnesaemia, hypercalcaemia cohort would have met the enrolment criteria of three as well as conditions such as hypothyroidism and 6 major trials in heart failure – SOLVD (ACE inhibitor), myocardial ischaemia can aggravate digoxin toxicity. MERIT-HF (beta blocker)7 and RALES (aldosterone Health professionals need to be aware that antagonist).8 For example, impaired systolic function symptoms of digoxin toxicity can occur in the target was an entry criterion for these trials. However, a large range. The prescriber should therefore be vigilant proportion of older people have heart failure with in checking for adverse effects such as anorexia, preserved systolic function for which there is little nausea, vomiting, visual disturbances, depression evidence that ‘standard’ treatments are of benefit. and confusion. Choice of drug Beta blockers In a robust older person with systolic heart failure In patients with renal impairment, use beta blockers it is reasonable to try to achieve optimal doses of with predominantly hepatic elimination (for example ACE inhibitors and beta blockers, but start at low metoprolol). For patients with hepatic impairment, doses and watch for adverse effects. In frail patients use beta blockers with predominantly renal with systolic heart failure the best approach is to elimination (for example atenolol). Even if liver try one drug at a time, starting at a low dose, and function tests are normal, there is an age-related observe closely for benefit and harm. In many cases, the recommended doses will not be achievable and decrease in liver blood flow. So if adverse effects measured renal function may decline. If the patient’s such as confusion are thought to be possibly due to function and health improves, the uncertainty about a predominantly hepatically eliminated beta blocker, whether there are mortality benefits at lower doses it may be worth a trial of changing to a renally is less important. In addition, the decline in measured eliminated beta blocker. Less lipid soluble beta renal function may not be clinically significant. blockers (atenolol and bisoprolol) may be less likely to enter the brain so may cause fewer sleep disturbances In patients with preserved left systolic function, the and nightmares. regimen should focus on minimising the symptoms and signs of heart failure. Diuretics are the mainstay Anticoagulation of treatment for relieving symptoms of fluid retention. In carefully selected older patients with non-valvular Age-related decreases in renal function may reduce atrial fibrillation, there is good evidence that oral the efficacy of conventional doses of diuretics so anticoagulation is better than antiplatelet therapy in careful upward titration of the dose may be needed. reducing the risk of stroke. The clinical dilemma is This needs to be balanced with the fact that older that older people are at a higher risk of people are more at risk of electrolyte disturbances bleeding during anticoagulation. The decision and volume depletion from diuretics. Older people on anticoagulation versus antiplatelet therapy is and their carers can sometimes learn to self-adjust the best made by a doctor who has a comprehensive dose of diuretic using weight as a guideline. understanding of the whole patient and is able to Atrial fibrillation take into account factors such as falls risk, Atrial flutter or fibrillation can occur in older people as bleeding history, potential drug interactions and the result of a transient condition such as an infection. likely compliance with dose adjustments and INR This is important to recognise, as a long-term monitoring. There are a number of bleeding risk antiarrhythmic drug may not be required. Chronic scoring systems,9 but they are not used much in

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everyday practice. There is no evidence that a lower Conclusion target INR (<2) is effective or has a lower risk of bleeding than a target of 2–3. Appropriate and safe prescribing of cardiovascular SELF-TEST The newer oral anticoagulants, such as dabigatran, QUESTIONS drugs for older people can be challenging. There are may seem to be an attractive alternative to warfarin in many things to take into account when prescribing True or false? older people as regular blood tests are not required. for older people, especially if they are frail. Tailoring 3. An INR below However, there is no antidote or reversal drug if 2.0 is effective in treatment to the individual patient with the aim of preventing stroke in an bleeding occurs. In addition, severe renal impairment doing more good than harm, should be the guiding elderly patient being is a contraindication and any decrease in renal principle when prescribing cardiovascular drugs to anticoagulated for atrial fibrillation. function can increase the risk of bleeding. older people. 4. Diuretics should Conflict of interest: none declared not be prescribed for patients over 80 years old with fluid retention REFERENCES due to heart failure. 1. Nair BR. Evidence based medicine for older people: available, 6. SOLVD Investigators. Effect of enalapril on survival in Answers on page 219 accessible, acceptable, adaptable? Australas J Ageing patients with reduced left ventricular ejection fractions and 2002;21:58-60. congestive heart failure. N Engl J Med 1991;325:293-302. 2. Burgess CL, Holman CD, Satti AG. Adverse drug reactions in 7. MERIT-HF Investigators. Effect of metoprolol CR/XL in older Australians, 1981-2002. Med J Aust 2005;182:267-70. chronic heart failure: Metoprolol CR/XL Randomised 3. Beckett NS, Peters R, Fletcher AE, Staessen JA, Liu L, Intervention Trial in Congestive Heart Failure (MERIT-HF). Dumitrascu D, et al. Treatment of hypertension in patients Lancet 1999;353:2001-7. 80 years of age or older. N Engl J Med 2008;358:1887-98. 8. Pitt B, Zannad F, Remme WJ, Cody R, Castaigne A, 4. National Heart Foundation of Australia (National Blood Perez A, et al; Randomized Aldactone Evaluation Study Pressure and Vascular Disease Advisory Committee). Guide Investigators. The effect of spironolactone on morbidity and to management of hypertension 2008. Updated December mortality in patients with severe heart failure. N Engl J Med 2010. National Heart Foundation; 2010. 1999;341:709-17. 5. Masoudi FA, Havranek EP, Wolfe P, Gross CP, Rathore SS, 9. NPS MedicineWise. Good anticoagulant practice. Steiner JF, et al. Most hospitalized older persons do not Medicinewise News 2013 Feb 4. meet the enrollment criteria for clinical trials in heart failure. www.nps.org.au/publications/health-professional/ Am Heart J 2003;146:250-7. medicinewise-news/2013/good-anticoagulant-practice [cited 2013 Nov 7]