Acute coronary syndrome in elderly and frail patients

Keywords

acute coronary syndrome, elderly patients, follow-up, frailty, interventions, percutaneous coronary

Abbreviations list

ACS                  acute coronary syndrome

DAPT               double antiplatelet therapy

EF                    ejection fraction

EKG                 electrocardiogram

PCI                   percutaneous coronary intervention

Take-home messages

1. Patients over 75 years of age are underrepresented in randomised controlled trials, and they have a mortality rate twice as high as younger patients. It is necessary to carefully evaluate individual patient frailty with regard to comorbidities, quality of life, estimated risk/benefit balance of the invasive strategy, as well as patient preference.
2. There are no specific guidelines and/or integrated care pathways available for elderly patients with ACS. The identification of different discharge pathways based on the individual risk profiles and degree of family support is important to improving the quality of care and life of these patients.
3. The availability of specialised facilities dedicated professional figures (i.e., cardiogeriatrics), and caregivers is essential to ensure adequate clinical monitoring that encourages control of cardiovascular risk factors and adherence to pharmacological therapy, as well as planning and implementing personalised clinical and procedural follow-ups.

Patient-oriented messages

• Age is not per se a contraindication to the use of the most up-to-date treatment strategies for acute coronary syndrome. The best pharmacological and invasive approach should be selected according to the individual risk profile and prognosis.
• Comorbidities such as diabetes, chronic kidney disease, peripheral arterial disease, chronic obstructive pulmonary disease, active cancer, and left ventricle ejection fraction are the most important elements for the choice of a tailored therapy.
• The presence of caregivers and a structured follow-up program including rehabilitation and physical activity are of paramount importance to improve or at least restore the level of autonomy present before hospitalisation.

Impact on practice statement

Guideline-directed strategies should be offered to elderly patients with acute coronary syndrome and tailored to the specific clinical presentation and risk profile.

The hazard-benefit ratio between thrombotic and bleeding risk factors should guide the choice between invasive and/or medical management and the choice of specific post-PCI pharmacological drug regimens and duration.

Establishing the patient long-term prognosis is critical and should guide therapeutic decisions to avoid futility.  The geriatrician should be the key professional who coordinates the other physicians taking care of elderly patients and offers the best treatment and follow-up strategies.

Family support is a key for therapy and follow-up adherence of the elderly patient.

Every effort should be made to preserve the elderly patient’s daily life, as well as to maintain their cognitive and psychological status.

Introduction

The increase in life expectancy is leading to a progressively aging population in Western countries. Approximately one-third of patients hospitalised for acute coronary syndrome (ACS) are over 75 years of age, but only 10–20% of patients enrolled in clinical trials are elderly patients [1]. Notably, these patients have a mortality rate twice as high as younger patients. Advancing age is indeed associated with a progressive increase in both thrombotic and haemorrhagic risk [2].

The definition of “elderly” is also evolving. Previously, a patient aged >75 years was defined as elderly, but nowadays with the increasing age of the general population, this cut-off is less defined [3]. Moreover, the percentage of very elderly people has increased, and they are a population that is even less represented in the trial cohorts. Given the small proportion of elderly patients in randomised controlled trials, it becomes necessary to carefully evaluate the individual patient, with regards to their comorbidities, quality of life, estimated risk/benefit balance of the invasive or conservative strategy, and patient preference [4]. Indeed, for the management of ACS in elderly patients (Figure 1), it may be useful to specify a general methodological clinical approach: chronological age should not constitute a sufficient reason to influence any clinical choice. On the contrary, a patient’s biological age and general condition (comorbidities, cognitive and functional status, and frailty) should be considered. In particular, it is important to estimate the patient’s frailty.

Frailty is a syndrome characterised by reduced biological reserve, leading to a failure of homeostatic mechanisms following stressor events, including ACS [5]. Different scores for frailty assessment can be useful in the evaluation of patient risk. It can be simplified by identifying the presence of ≥3 of the following 5 criteria: unintentional weight loss, self-reported physical exhaustion, reduced physical strength, slow walking/apraxic gait, poor physical activity [6].

Figure 1. Elderly patients with acute coronary syndrome: challenging steps.

Clinical management

Invasive strategy

The elderly population has double the mortality rate as compared to the younger population; however, a progressive reduction in mortality, due to improved use of evidence-based therapies, including primary PCI, has been observed over the years. The in-hospital and 1-year mortality of ST-segment elevation myocardial infarction (STEMI) patients is approximately 4-12% and 10%, respectively [4].

Primary PCI is more effective and safer compared to fibrinolytic therapy and has drastically improved outcomes for all ages, with a more pronounced benefit in patients at greater risk. Fibrinolysis may be reasonable only when primary PCI is not feasible in a timely manner, however, the associated risk in elderly patients is often high [7]. Non- ST-segment elevation myocardial infarction (NSTEMI) patients present a lower in-hospital mortality, but a medium/long-term mortality comparable to that of STEMI patients, a consequence of the greater number of comorbidities [4].

Elderly patients with NSTEMI less frequently receive pharmacotherapies and invasive assessment, present more complex coronary disease, have longer hospital stays, and are at higher risk of death. Indeed, as demonstrated in the ICON1 study, frail patients are reported to have a higher rate of a composite of all-cause mortality, MI, stroke, unplanned revascularisation, and major bleeding [1].

Frailty and multimorbidity may impact the degree of benefit derived from an invasive approach, and invasive management appears to be associated with only modest improvements in quality of life at 1 year follow-up in these patients. Furthermore, the presence of multimorbidities confers an increased risk of long-term adverse cardiovascular events, mainly driven by a higher risk of all-cause mortality [9]. Therefore, an individualised approach must be taken for these patients and a careful evaluation of the risk versus benefit balance is needed. To aid in decision-making in these patients, routine assessment of frailty (e.g. with the Rockwood Frailty Scale) and comorbidity (e.g. with the Charlson Comorbidity Index) is recommended [4]. This careful assessment allows frail patients at high risk of cardiovascular events and low risk of complications to undergo invasive strategy and/or optimal medical therapy, preferring optimal medical therapy alone for those patients at lower risk of future cardiovascular events, but with a high risk of developing procedural complications. For those patients for whom any form of treatment is deemed futile, a palliative end-of-life care approach should be adopted [4].

Pharmacotherapy

In general, the same medical treatment strategies are recommended in older and younger ACS patients, but due to the exclusion of “very old” patients from major RCTs, caution is requested when applying trial results to this patient population [4]. Pharmacotherapy should be adapted to renal function, comorbidities, comedications, frailty, and specific contraindications. Some strategies can be applied to reduce bleeding events: i.e., shortening of double antiplatelet therapy (DAPT) duration (<12 months) and de-escalation of intensity treatment. Six-month DAPT after DES implantation in a cohort of elderly ACS patients is safe with regard to ischaemic events [10].  A reduction in bleeding risk with no increase of ischaemic events with 1-month as compared to 6-month DAPT has been demonstrated in a cohort of patients at high bleeding risk (HBR); the most used P2Y12 receptor inhibitor was clopidogrel [10]. Regarding prasugrel, a dose reduction from 10 mg to 5 mg per day is currently recommended in patients ≥75 years. However, prasugrel 5 mg per day as compared to clopidogrel increases the bleeding risk in ACS-PCI patients, with no reduction in ischaemic endpoints [10].

The overall safety of ticagrelor as compared with clopidogrel was not found to be age-dependent [11], but it has been associated with a higher risk of bleeding and death than clopidogrel [12]. In non-ST-elevation (NSTE)-ACS patients older than 70 years, DAPT with clopidogrel led to fewer major and minor bleedings and a trend towards a reduced rate of the combined net clinical endpoint as compared with DAPT with a potent P2Y12 receptor inhibitor [13]. Finally, in ACS-PCI patients with atrial fibrillation the recommended therapeutic strategy is a short period (generally up to 1 week, or up to 1 month in patients at high ischaemic risk) of triple antithrombotic therapy (TAT) with direct oral anticoagulant (DOAC) and DAPT (with aspirin and clopidogrel) followed by dual antithrombotic therapy (DAT) with DOAC at the recommended dose for stroke prevention and a single antiplatelet (preferably clopidogrel) for up to 12 months [4]. In older HBR patients, DAT should be shortened to ≤6 months according to clinical judgment, by withdrawing the antiplatelet.

In ACS patients managed medically, i.e., for presentation beyond 12 hours or for those who cannot undergo reperfusion treatment, available data from RCTs support DAT over TAT, with a single antiplatelet agent (most commonly clopidogrel) for at least 6 months.

Gender differences

Several studies have examined age-stratified sex differences in care and outcomes of ACS patients and have shown that disparities may differ according to age. Worse outcomes in women have been attributed to older age and a greater burden of comorbidities, but also to a lower revascularisation rate. An analysis of elderly patients treated with PCI, found significantly higher mortality among women with STEMI, as compared with men [14]. No current data support a different management of ACS based on sex, but women with ACS are often managed differently than men. They often go to the emergency room late after the onset of symptoms and are less likely to receive coronary angiography, timely revascularisation or secondary prevention medications [4]. Of note, several studies have reported that a disproportionately low proportion of women are recruited to RCTs. Increased representation of female patients with ACS in future clinical trials is desirable to collect more information about their optimal management [4].

Prognostic stratification

Clinical presentation

Elderly patients with ACS present with atypical symptoms in 8.4% of cases (dyspnoea, diaphoresis, nausea, and syncope or pre-syncope) with frequent delays to first ECG. Furthermore, the initial ECGs are less likely to diagnose ACS. On the other hand, symptoms are often underreported, due to difficulties in expression, and to cognitive impairment in elderly patients. They are less likely to call emergency services or to go to hospital on their own, and the occurrence of in-hospital ACS (during hospitalisation for non-cardiac reasons) is more frequent.

Comorbidities

Diabetes

In general, 20% of the elderly population has diabetes, and a similar proportion have undiagnosed diabetes. Complications and management in the elderly vary according to hyperglycaemia duration, personal background, and comorbidities. Usually, glycaemic targets are less stringent, due to difficulties in achieving optimal glycaemic control in this subgroup of patients. Approximately 60% of diabetic patients develop cardiovascular disease and diabetic patients have a worse outcome both at 30 days and at 1 year follow-up.

Chronic kidney disease

A series of studies documented the prognostic importance of chronic renal failure in ACS. In particular, patients with a glomerular filtration rate (GFR) <30 ml/min have a worse hospital prognosis compared to those with GFR between 30-60 ml/min or with normal GFR (mortality rate 12.2%, 5.5%, 1.4%, respectively).

Peripheral arterial disease

The coexistence of peripheral arterial disease (PAD) with ACS leads to a worse clinical course and prognosis. Moreover, PAD has a higher incidence in diabetic patients.

Chronic obstructive pulmonary disease

In stable chronic obstructive pulmonary disease (COPD), the risk of ACS is 2-3 times higher than in non-COPD patients and is up to 5 times higher in a flare-up phase. Special attention is required for elderly patients with both ACS and COPD, both in the acute phase (adequate and prompt care of O2/CO2 balance in order to limit additional myocardial damage due to discrepancy, antibiotic and anti-inflammatory therapy) and thereafter (favouring betablockers as bisoprolol, for example, and monitoring the right heart function and pulmonary pressures, adding, if needed, right heart catheterisation especially in elderly women with coexistent rheumatologic disease). Vaccination programs are warranted. 

Active cancer

Cancer itself enhances both bleeding and thrombotic risk. These patients represent a challenge both for the clinical cardiologist, who should select those who may or may not undergo reperfusion according to prognosis and vital status including patient’s choice, and for the interventionalist, who should adapt intraprocedural antithrombotic drugs to the bleeding risk and choose the best interventional strategy. This may include limiting the number of stents, selecting special stents [10], or using drug-eluting balloons when possible to limit the thrombotic risk.

Left ventricle ejection fraction

Haemodynamic instability and cardiogenic shock are more frequent in elderly hospitalised patients. The percentage of patients with an ejection fraction (EF) <40% after an ACS is about 20% and the 12-year survival rates in patients with EF >50%, EF between 35-49% and EF <35% are 73%, 54% and 21%, respectively [15]. Moreover, another important aspect to take into consideration is the early onset of post-MI heart failure which represents the most important predictor of long-term mortality [15]. When indicated, age per se, is not a contraindication for an intracardiac defibrillator (ICD) or cardiac resynchronisation devices in a situation of unrestricted economic resources. Of course, these should be implanted when life expectancy is more than one year and take into consideration the cognitive, clinical, and vital status of the patient. In particular, the implantation of an ICD in post-ACS patients ≥80 years old with residual left ventricle EF <30% (as assessed at least 40 days after ACS or revascularisation) should be evaluated on an individual basis. 

Hospital discharge and follow-up strategies

Hospital discharge

Currently, no specific guidelines and/or integrated care pathways are available for the management of elderly ACS patients at discharge. It is essential to select the best post-discharge path based on the clinical and functional risk, taking into consideration patient comorbidities, length of hospital stay, EF at discharge, mental status and availability of caregivers (Figure 2).

Figure 2. Hospital discharge of elderly patients with acute coronary syndromes.

In our Cardiology Department, we examined the case histories of ACS patients over the last year (Figure 3), from 31 January 2023 to 31 January 2024. Over these 12 months, 135 patients ³75 years old were admitted with an ACS diagnosis. Of those, 131 were offered invasive therapy (122 underwent PCI, 9 had coronary angiography, 1 patient died before arriving in the cath lab), and 3 patients were treated with medical therapy. The in-hospital mortality rate was 5% (7 patients: 5 PCI patients, 1 on medical therapy and the one who died before coronary angiography). Of these 7, 1 patient died due to cardiac rupture, 1 patient for pulseless electrical activity during PM implantation, 3 patients died of cardiogenic shock and 2 of sepsis.

Of the remaining 128 patients, 118 (92.1%) were discharged home (108 after PCI, 9 after coronary angiography, 1 treated medically), 6 patients (4.7%) were transferred to long-term care facilities (all after PCI) and 3 (2.4%) were transferred to rehabilitation (2 after PCI, 1 was medically treated). Only one patient returned to the referral hospital after PCI to complete his non-cardiological therapeutic course (worsening of kidney function occurred during hospitalisation). With regards to medical history and risk profile of these patients, those sent to long-term care had a reduced EF and/or had senile involution, while those transferred to rehabilitation mostly had reduced EF and long hospital stays (mean hospitalisation: 34 days). Patients with EF ≥40%, few comorbidities, a short in-hospital stay and good family care network were discharged home with follow-up programs. Therefore, based on the patient's prognostic stratification, tailored follow-up management strategies should be envisaged for elderly ACS patients.

Figure 3. Discharge paths of elderly ACS patients at Mauriziano hospital.

ACS: acute coronary syndromes; EF: ejection fraction

As for all ACS patients, post-discharge management should prioritise lifestyle changes, which, in synergy with pharmacological therapy, aim to reduce the risk of new cardiovascular events. This can be difficult in older patients, due to possible limitations in mobility and in self-care.

With these limitations in mind, specialised facilities and dedicated professional figures are needed to ensure adequate clinical patient monitoring, to encourage pharmacological therapy adherence, as well as to implement optimal control of cardiovascular risk factors and plan personalised clinical and instrumental follow-ups. Regular check-ups should be shared between the primary physician and the hospital/outpatient cardiologist. The former should evaluate symptoms, patient therapeutic adherence and the achievement of targets for heart rate, blood pressure and lipid profile. The cardiologist, in addition to the clinical evaluation, must indicate the timing for more thorough exams, including those to detect inducible ischaemia and coronary angiography if needed, as well as any change in pharmacological therapy, while always paying attention to the thrombotic and bleeding risks.

Given the comorbidities of these patients, the polypharmacy, the risk of falls, and the particular complexity of specific situations in which socio-economic, cognitive, emotional and ethical factors play an important role, it would be very useful to include a geriatrician who can manage these patients with a holistic and integrated approach [16]. But an equally important figure is the caregiver, who should be identified at the time of discharge and educated about drug therapy, lifestyle changes, medical visits and the symptoms to watch out for. In last years, a new follow-up management method has been developed and implemented: telemedicine [17]. Telemedicine helps the optimisation of economic and human resources by reducing the frequency of hospital or clinical visits. Telemedicine can be used to evaluate a patient’s symptoms, adherence to therapy and any side effects, and to establish timing and need of in-person follow-up. This opportunity is certainly advantageous for elderly patients with a high number of comorbidities and can also influence their autonomy and their need for a caregiver.

Follow-up management

General lifestyle changes are important at any age and include:

Physical activity

Older adults are generally underrepresented in secondary prevention exercise programs, due to low physician referral because of low functional capacities and multiple comorbidities. However, if activities are individually tailored, frail patients may also find physical, cognitive, and psychological benefits. The exercise recommendations from the World Health Organization include both aerobic and strength training as well as balance exercises to reduce the risk of falls. If older adults cannot follow the guidelines because of chronic conditions, they should be as active as their ability and conditions allow. It is important to note that the recommended amount of physical activity is in addition to routine activities of daily living [18]. Therefore, physiotherapy in older patients should aim at improving, or at least restoring, their level of autonomy before hospitalisation, while continuing to preserve the activities of daily life.

Smoking

Prevalence of smoking in elderly patients is still too high. As for younger patients, the cessation of smoking is essential.

Nutrition and body weight

Dietary habits influence cardiovascular risk by affecting risk factors such as hypercholesterolemia, hypertension, obesity and diabetes; malnutrition and cachectic states must be carefully monitored. Weight loss goals should be inferior or equal to 5% of body mass in the elderly population because significant weight loss increases the risk of morbidity and mortality due to undernutrition. A body mass index (BMI) between 25 and 35 kg/m2 may be optimal in the older population since older individuals with BMI values <25 and >35 kg/m2 have a higher risk of decreased functional capacity, balance, walking, mobilisation disorders, fall risk, reduction in muscle strength, and malnutrition [19].

Follow-up strategies

Currently, there are no structured follow-up algorithms for elderly patients with ACS, but reference can be made to three optimal follow-up strategies [20] which have been suggested for patients treated with PCI according to the patient's risk profile: Strategy A, for high-risk patients (PCI during ACS and EF £ 45%; PCI in patient with symptoms and signs of heart failure); Strategy B, for intermediate-risk patients (PCI during ACS and preserved EF, PCI in left main disease or in proximal descendent anterior artery disease or multivessel coronary artery disease, patient with incomplete and/or suboptimal revascularisation, diabetic patient); Strategy C, for low-risk patients (patient without relevant comorbidities, with preserved EF and complete revascularisation).

Conclusion

With an aging population, approximately one-third of hospitalised patients with an ACS are over 75 years of age and their mortality rate is double compared to younger patients. This population is underrepresented in RCTs, and guidelines do not provide clear indications. Thus, their management in the acute phase and during follow-up should be tailored according to the individualised risk profile. The selection of interventional and pharmacological therapies should be in accordance with the patient’s specific ischaemic and bleeding risk, the presence of comorbidities, frailty, cognitive dysfunction and comedications. It is also important to identify different discharge paths based on the specific risk profiles and presence of family support. An integrated management approach including several people (cardiologist, geriatrician, primary physician, and caregiver) is warranted for a more efficient use of resources, time-effective interventions, and hopefully, a reduction of morbidity and mortality.