Cardiovascular drugs are the most frequently prescribed medicines for older people. However, it can be difficult to find a regimen that does more good than harm, especially if the patient is frail.
Prescribers should determine the goals of treatment, understand the limitations of the evidence and be vigilant for the adverse effects of cardiovascular drugs.
Regimens for common cardiovascular diseases, such as hypertension, chronic heart failure and chronic atrial fibrillation, need to be tailored to the individual patient, taking into account factors such as comorbidity and life expectancy.
The prevalence of diseases such as hypertension, coronary heart disease, chronic heart failure and chronic atrial fibrillation increases with age, so cardiovascular drugs are the most frequently prescribed treatments for older people. These drugs are also responsible for a large proportion of the adverse drug reactions suffered by older people.
Important considerations when prescribing
There are some general principles to apply when prescribing cardiovascular drugs to older people (Box). It is important to tailor a regimen for each individual patient.
Determine the goals of treatment
Prescribers should ask themselves, 'What outcome do I hope to achieve for this patient?' The prescriber should also consider what their patient hopes to achieve by following the treatment regimen. In general, cardiovascular drugs are helpful for symptom control, prevention of cardiovascular events or life extension. In a healthy 80-year-old person all three goals may be applicable. In contrast, symptom control may be the only goal for an 80-year-old with severe dementia.
In frail older people with multiple comorbidities and functional limitations, it is important to prioritise the goals of treatment. These priorities should guide prescribing. A common dilemma faced by clinicians is the combination of supine hypertension and symptomatic postural hypotension in a frail older person. In this situation, if the hypotension results in falls, dizziness and impairment of everyday function then avoiding postural hypotension should be the priority even at the expense of less than ideal control of blood pressure. High blood pressure may have to be accepted as long as it is not causing symptoms. The consequences of a fractured hip as a result of a fall due to postural hypotension can be more devastating than the vascular events one was aiming to prevent by lowering blood pressure.
Table 1 gives examples of how priorities may differ between a well older person and a frail older person for the treatment of specific cardiovascular diseases. Avoiding adverse effects is important in both groups, but the risk of harm is greater in frail older people. In addition, mortality benefits are less likely to be seen in frail older people.
Be aware of the limited evidence
Older people are poorly represented in clinical trials,1 so there are limited data about the benefit and harm of giving cardiovascular drugs to frail older patients. Clinical guidelines for cardiovascular diseases rarely provide any details on how they should apply to older frail people with multiple comorbidities. Given these limitations, prescribers should choose a regimen which is appropriate for the individual patient and minimises the risk of harm. Prescribing purely on evidence from younger patients or disease-specific guidelines leads to polypharmacy, pill burden and often harm. However, the lack of direct evidence should not be a reason to deny older people treatments that have the potential to improve their quality of life. For example, treatment to minimise the breathlessness of heart failure can have a big impact on the everyday function and overall quality of life of an older person.
Be vigilant for adverse effects
Over the past 20 years there has been an increase in hospital admissions due to adverse drug reactions particularly in people over 80 years old.2 Cardiovascular drugs are responsible for about 20% of these reactions in this age group. Adverse drug reactions can occur even at recommended adult doses. As people become frailer and acquire new diseases a previously safe and tolerated regimen may result in harm. Age-related changes in drug receptors, impairments in homeostatic mechanisms and postural autonomic function are just some of the reasons why older people are more sensitive to the hypotensive effects of many cardiovascular drugs.
Older people are likely to have diseases that result in disease–drug interactions. For example, people with dementia may become more confused if they are prescribed drugs that can cause confusion such as beta blockers. Frail older people with Parkinson's disease often have orthostatic hypotension due to disease-related autonomic dysfunction. They are therefore more likely to come to harm from hypotension when prescribed cardiovascular drugs which lower blood pressure. This problem can be exacerbated by the blood pressure lowering effects of drugs for Parkinson's disease.
In addition, older people on many different drugs (polypharmacy) are at increased risk of adverse events, in part because of the increased likelihood of drug–drug interactions.
To minimise the possibility of adverse drug reactions it is a good idea to take a 'start low, go slow' approach when prescribing. If possible, start only one new drug at a time, at the lowest dose possible and increase the dose slowly while being vigilant for possible adverse effects.
It is important to question and examine older people for possible adverse drug reactions. Often the symptoms can be non-specific such as falls, tiredness or confusion. An adverse drug reaction such as postural hypotension can easily be missed if not looked for. It is important to be aware of the common problems that could be the adverse effects of cardiovascular drugs (see Table 2). Ask specifically about, and look for, these adverse effects. Be particularly aware of drugs that have a narrow therapeutic window or a long half-life such as digoxin and warfarin.
The drug regimen should be easy to follow and, with the help of pharmacists, have packaging, labels and dose administration aids that are easy to use. A general practitioner can order a home medicine review for people living in the community. A similar scheme is funded to encourage a medication management review for patients in residential aged-care facilities.
The Hypertension in the Very Elderly Trial (HYVET) found that treating hypertension (systolic blood pressure above 160 mmHg) in patients over 80 years old is beneficial in terms of all-cause mortality, episodes of heart failure and deaths from strokes.3 However, it is important to be aware that participants were screened carefully for comorbidity including postural hypotension (systolic blood pressure less than 140 mmHg after two minutes of standing was an exclusion criteria). Although patients in the trial were healthier than the general population of the same age, antihypertensive therapy should be considered in this age group if their life expectancy is more than one or two years. However, there will be a proportion of patients, particularly the frail, who will not tolerate treatment or in whom a decision will be made not to treat after weighing up the harms and benefits.
The current National Heart Foundation hypertension guidelines4 recommend treating patients with grade 2 and 3 hypertension (systolic >160 mmHg or diastolic >100 mmHg). For patients aged 80 and over, the results from HYVET would support this recommendation. However, it is not clear if antihypertensive therapy should be prescribed to patients with grade 1 hypertension (systolic 140–159 mmHg or diastolic 90–99 mmHg). There is no direct clinical trial evidence in people aged 80 and over showing a benefit for treating this range of blood pressure.
The guidelines also recommend antihypertensive treatment regardless of blood pressure in patients with associated conditions such as diabetes, strokes and chronic kidney disease, or evidence of end-organ damage such as proteinuria from chronic kidney disease. It may be reasonable to follow this recommendation, but it is based on extrapolating the evidence from trials in much younger patients. Clinical judgement and common sense are required. For example, most patients over 80 years old will not live long enough for proteinuria to ever progress to clinically significant renal failure.
The National Heart Foundation correctly says that all patients aged 75 years and over can be assumed to have a high absolute cardiovascular risk (more than 15% probability of a cardiovascular event within the next five years) without needing to use a cardiovascular risk calculator. This could be interpreted as a recommendation that all patients aged over 75 years should be prescribed antihypertensives, but there is no direct evidence to support treatment regardless of blood pressure. There is also little evidence that treating hypertension in old age prevents dementia or slows progression in patients with dementia.
Target blood pressure
HYVET had a target blood pressure of 150/80 mmHg. The National Heart Foundation recommends less than 140/90 mmHg and less than 130/80 mmHg in patients with associated conditions or end-organ damage. 'Lower is better' may not apply to blood pressure in the very old. There is evidence from epidemiological studies in older people that low blood pressure is associated with poorer survival. These studies suggest there is a threshold blood pressure, which varied by study, below which mortality increases.
Choice of drug
Coexisting conditions, tolerability and the potential for adverse effects should guide the choice of antihypertensive drug. In many patients other conditions such as ischaemic heart disease or chronic heart failure will determine what is prescribed. Avoiding the adverse effects of high doses of a single drug is a reasonable rationale for adding a second drug. However, there is no evidence that combination antihypertensive drugs are more effective or safer in older people.
Chronic heart failure
A study in the USA suggests that many older patients would have been excluded from clinical trials in heart failure.5 Only 18%, 13% and 25% of more than 20 000 patients aged over 65 years from a heart failure cohort would have met the enrolment criteria of three major trials in heart failure – SOLVD (ACE inhibitor),6 MERIT-HF (beta blocker)7 and RALES (aldosterone antagonist).8 For example, impaired systolic function was an entry criterion for these trials. However, a large proportion of older people have heart failure with preserved systolic function for which there is little evidence that 'standard' treatments are of benefit.
Choice of drug
In a robust older person with systolic heart failure it is reasonable to try to achieve optimal doses of ACE inhibitors and beta blockers, but start at low doses and watch for adverse effects. In frail patients with systolic heart failure the best approach is to try one drug at a time, starting at a low dose, and observe closely for benefit and harm. In many cases, the recommended doses will not be achievable and measured renal function may decline. If the patient's function and health improves, the uncertainty about whether there are mortality benefits at lower doses is less important. In addition, the decline in measured renal function may not be clinically significant.
In patients with preserved left systolic function, the regimen should focus on minimising the symptoms and signs of heart failure. Diuretics are the mainstay of treatment for relieving symptoms of fluid retention. Age-related decreases in renal function may reduce the efficacy of conventional doses of diuretics so careful upward titration of the dose may be needed. This needs to be balanced with the fact that older people are more at risk of electrolyte disturbances and volume depletion from diuretics. Older people and their carers can sometimes learn to self-adjust the dose of diuretic using weight as a guideline.
Atrial flutter or fibrillation can occur in older people as the result of a transient condition such as an infection. This is important to recognise, as a long-term antiarrhythmic drug may not be required. Chronic atrial fibrillation usually, but not always, requires rate control. Symptomatic improvement should be the goal rather than a specific heart rate. Digoxin and beta blockers are commonly used for rate control in atrial fibrillation.
Digoxin has a narrow therapeutic window. Reduced renal function and a lower lean body mass increase serum digoxin concentrations. A number of commonly used drugs, such as verapamil, amiodarone and diltiazem, can also increase serum digoxin. Electrolyte abnormalities such as hypokalaemia, hypomagnesaemia, hypercalcaemia as well as conditions such as hypothyroidism and myocardial ischaemia can aggravate digoxin toxicity. Health professionals need to be aware that symptoms of digoxin toxicity can occur in the target range. The prescriber should therefore be vigilant in checking for adverse effects such as anorexia, nausea, vomiting, visual disturbances, depression and confusion.
In patients with renal impairment, use beta blockers with predominantly hepatic elimination (for example metoprolol). For patients with hepatic impairment, use beta blockers with predominantly renal elimination (for example atenolol). Even if liver function tests are normal, there is an age-related decrease in liver blood flow. So if adverse effects such as confusion are thought to be possibly due to a predominantly hepatically eliminated beta blocker, it may be worth a trial of changing to a renally eliminated beta blocker. Less lipid soluble beta blockers (atenolol and bisoprolol) may be less likely to enter the brain so may cause fewer sleep disturbances and nightmares.
In carefully selected older patients with non-valvular atrial fibrillation, there is good evidence that oral anticoagulation is better than antiplatelet therapy in reducing the risk of stroke. The clinical dilemma is that older people are at a higher risk of bleeding during anticoagulation. The decision on anticoagulation versus antiplatelet therapy is best made by a doctor who has a comprehensive understanding of the whole patient and is able to take into account factors such as falls risk, bleeding history, potential drug interactions and likely compliance with dose adjustments and INR monitoring. There are a number of bleeding risk scoring systems,9 but they are not used much in everyday practice. There is no evidence that a lower target INR (<2) is effective or has a lower risk of bleeding than a target of 2–3.
The newer oral anticoagulants, such as dabigatran, may seem to be an attractive alternative to warfarin in older people as regular blood tests are not required. However, there is no antidote or reversal drug if bleeding occurs. In addition, severe renal impairment is a contraindication and any decrease in renal function can increase the risk of bleeding.
Appropriate and safe prescribing of cardiovascular drugs for older people can be challenging. There are many things to take into account when prescribing for older people, especially if they are frail. Tailoring treatment to the individual patient with the aim of doing more good than harm, should be the guiding principle when prescribing cardiovascular drugs to older people.
Conflict of interest: none declared
The following statements are either true or false.
1. An INR below 2.0 is effective in preventing stroke in an elderly patient being anticoagulated for atrial fibrillation.
2. Diuretics should not be prescribed for patients over 80 years old with fluid retention due to heart failure.
Answers to self-test questions
- Nair BR. Evidence based medicine for older people: available, accessible, acceptable, adaptable? Australas J Ageing 2002;21:58-60.
- Burgess CL, Holman CD, Satti AG. Adverse drug reactions in older Australians, 1981-2002. Med J Aust 2005;182:267-70.
- Beckett NS, Peters R, Fletcher AE, Staessen JA, Liu L, Dumitrascu D, et al. Treatment of hypertension in patients 80 years of age or older. N Engl J Med 2008;358:1887-98.
- National Heart Foundation of Australia (National Blood Pressure and Vascular Disease Advisory Committee). Guide to management of hypertension 2008. Updated December 2010. National Heart Foundation; 2010.
- Masoudi FA, Havranek EP, Wolfe P, Gross CP, Rathore SS, Steiner JF, et al. Most hospitalized older persons do not meet the enrollment criteria for clinical trials in heart failure. Am Heart J 2003;146:250-7.
- SOLVD Investigators. Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. N Engl J Med 1991;325:293-302.
- MERIT-HF Investigators. Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF). Lancet 1999;353:2001-7.
- Pitt B, Zannad F, Remme WJ, Cody R, Castaigne A, Perez A, et al; Randomized Aldactone Evaluation Study Investigators. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. N Engl J Med 1999;341:709-17.
- NPS MedicineWise. Good anticoagulant practice. Medicinewise News 2013 Feb 4. www.nps.org.au/publications/health-professional/medicinewise-news/2013/good-anticoagulant-practice [cited 2013 Nov 7]