Acute coronary syndrome (ACS) is a group of clinical syndromes based on the pathology of coronary atherosclerotic plaque rupture secondary to complete or incomplete occlusive thrombosis, including unstable angina (UA) , non-ST-segment elevation myocardial infarction (NSTEMI), and ST-segment elevation myocardial infarction (STEMI). Of these, UA and NSTEMI are collectively referred to as non-ST-segment elevation acute coronary syndrome (NSTE-ACS).
The condition of elderly patients with ACS is often complex. On the one hand, the reduced sensitivity to pain response and the frequent combination of other multisystem diseases (e.g., diabetes, renal insufficiency, cerebrovascular disease, peripheral vascular disease, etc.) make some elderly ACS patients’ symptoms atypical [1], and the diagnostic value of ECG is lower than that of younger patients, leading to increased diagnostic difficulty in elderly ACS; on the other hand, comorbidities and combined medications, age and disease-related physiological changes, all of which adversely affect the clinical management and prognosis of ACS [2]. In clinical practice, the acceptance rate of guideline-oriented formal treatment for elderly ACS patients is generally low, and “advanced age and safety” are often used as shields. In fact, pharmacological, interventional, and cardiac rehabilitation therapies are equally effective and even more beneficial in older patients than in younger ACS patients [1, 3].
In the last decade, percutaneous coronary intervention (PCI) has become increasingly common in elderly patients with coronary artery disease. Approximately half of the elderly patients undergoing PCI are NSTE-ACS, and approximately 32% to 40% of NSTE-ACS patients have undergone PCI. Early angiography and revascularization significantly reduce recurrent unstable angina, rehospitalization, MI, and death in patients with ACS [2]. In this paper, we intend to present the current status and relevant advances in the management of coronary interventions in elderly patients with ACS.
I. Management strategy of elderly ACS
The current management strategy for patients with STEMI is largely noncontroversial, but opinions are not unanimous on the issue of the best management plan for patients with UA and NSTEMI. The most common problem is that clinicians often overestimate the risk of bleeding and other complications in elderly patients, leading to less use of interventions (especially early intervention strategies) in clinical practice [4]. In fact, numerous lines of evidence suggest that older patients with ACS benefit equally, if not more, from interventional strategies than younger patients [5].
At the 2012 Transcatheter Interventional Therapy Conference (TCT), a report was presented retrospectively analyzing 1001 patients with ACS (555 NSTEMI, 213 STEMI) with a mean age of 81 ± 5 years, 776 treated with intervention and 224 treated conservatively. These patients had a combination of chronic obstructive pulmonary disease (COPD), prior PCI, prior coronary artery bypass grafting (CABG), peripheral vascular disease, stroke, renal insufficiency, diabetes, hypertension, hyperlipidemia, and obesity, and both groups were risk stratified according to the GRACE score. The results showed that mortality during hospitalization was significantly lower in the interventional group (3.5%) than in the conservative group (15.6%) (P < 0.001), while total complications did not differ between the two groups. Cumulative mortality was found to be better in both STEMI and NSTEMI than in the conservative treatment group using bivariate regression analysis, and GRACE score, renal insufficiency, Killip classification >2, diabetes, previous PCI, age, obesity, COPD, and previous stroke were found to be predictors of long-term mortality using univariate analysis. Therefore, in patients with ACS of advanced age (>75 years) given a direct PCI strategy after assessment of the above risk factors, age is not a determinant of the decision to proceed to conservative or invasive treatment. in the ACSIS registry study published in 2013 [6], patients with ACS over 80 years of age who underwent early coronary angiography had significantly lower 30-day and 1-year mortality than those who did not undergo coronary angiography. A 5-year follow-up analysis of the FRISC-II and RITA-3 studies showed that early invasive strategies significantly reduced mortality and myocardial infarction rates in patients ≥75 years of age, while the <65-year-old population failed to benefit equally [5]. In recent years, interventions in advanced age, even in ultra-advanced patients over 90 years of age, have become increasingly common, with procedural success rates similar to those of younger patients and a significant reduction in complications such as major bleeding.
Advanced age is a risk factor for surgical coronary artery bypass grafting (CABG), with a mortality rate of 5% -8% (11% for emergency surgery) for CABG in patients ≥80 years of age with NSTE-ACS, rising to 13% for those ≥90 years of age . However, CABG reduces cardiovascular events and rehospitalization rates more than PCI in elderly NSTE-ACS with combined diabetes or triple vascular disease (e.g., SYNTAX score >22). In addition, the ACS management strategy should be patient-centered, taking into account the patient’s wishes, comorbidities, functional and cognitive status, and life expectancy in addition to the condition [2].
II. Timing of ACS interventions in the elderly
The timing of intervention in STEMI patients is not controversial, but whether early PCI is routinely performed in NSTEMl patients has been the focus of debate in the medical community. Some scholars believe that ACS patients should undergo PCI 1 to several days after the onset of the disease, with the aim of allowing time for plaque stabilization and reducing thrombus formation at the PCI site. Others believe that PCI should be performed as early as possible in patients with ACS in order to reduce the risk of myocardial infarction from ACS and to minimize the length of hospital stay.
The results of clinical trials such as FRISC II, TACTICS and ISAR-COOL showed that: early intervention in high-risk ACS has a good procedural risk/benefit ratio; early intervention in general ACS patients with indications has better near-term and long-term results than conservative treatment, and its overall costs are comparable; the application of Platelet glycoprotein IIb/IIIa receptor antagonists can significantly reduce the incidence of perioperative thrombosis and no-flow phenomenon in both low- and high-risk ACS patients. In clinical practice, NSTE-ACS treatment strategies can be divided into three categories according to the urgency of the risk of cardiovascular events and the severity of the associated complications: urgent invasive strategies, early invasive interventional strategies, and conservative treatment strategies.
1.Emergency interventional strategy Emergency invasive strategy should be adopted (as soon as possible) if the following characteristics are met: (1) refractory angina; (2) recurrence of chest pain with S T-segment downward shift >2 mm or deep T-wave inversion even after intensive anti-anginal therapy; (3) clinical symptoms of heart failure or hemodynamic instability (shock); (4) presence of life-threatening arrhythmia (ventricular fibrillation or ventricular tachycardia).
2. Early interventional strategy An early invasive strategy should be adopted for patients who meet the following characteristics: (i) elevated troponin levels; (ii) presence of dynamic S T-segment changes (>0.5 mm) or T-wave changes (symptomatic or asymptomatic); (iii) diabetes mellitus; (iv) reduced renal function (GFR <60 ml/min); (v) reduced left ventricular ejection fraction (<40%); (vi) early post-infarction angina; (vii) percutaneous coronary Within 6 months after percutaneous coronary intervention; ⑧ Previous coronary artery bypass grafting; ⑨ Patients assessed as medium to high risk according to the risk score. The exact timing of cardiac catheterization can be determined by local hospital conditions, but should be completed within 72 hours.
Early interventional strategies are not recommended for patients with severe comorbidities (e.g., liver, renal, or pulmonary failure and malignancy), when the risk of comorbidity from hemodynamic reconstruction may outweigh the benefit. Early diagnostic coronary angiography and revascularization are also not recommended in patients with acute chest pain but negative troponin, low likelihood of NSTE-ACS, and who do not agree to revascularization.
3. Conservative treatment strategy Patients who meet the following criteria can be considered as low-risk patients and generally do not receive early invasive evaluation unless new clinical conditions arise: (i) no recurrent chest pain; (ii) no signs of heart failure; (iii) normal initial ECG and 6-12 h after ECG; and (iv) normal troponin levels at presentation and 6-12 h after presentation. A conservative treatment strategy is also supported for patients determined to be at low risk by risk score.
Current guidelines recommend conservative management of low-risk patients, with only interventions for those with spontaneous or exertional ischemia. However, this management strategy often results in only delaying the implementation of interventional therapy; it does not really reduce the number of interventions. In some low-risk patients who start with a conservative treatment strategy, the patient should be closely observed for recurrence of chest pain, signs of ischemia, repeated electrocardiograms, monitoring of ST-segment changes, and serial myocardial marker tests (CK-MB, troponin). Even in the absence of these manifestations, the patient may still be a patient with severe coronary artery disease, so a stress test must be done before discharge to clarify whether the patient is in a stable state and whether there is significant coronary artery obstruction. It should be emphasized. Although the recent prognosis of NSTEMI is good, some studies have shown that its long-term prognosis is worse. The recurrence rate of angina in the conservative treatment group is high, and 64.0% of the patients eventually need intervention, therefore, for this group of patients also need to focus on strengthening the secondary prevention of coronary heart disease, such as recurrent angina, then should go to the hospital with interventional conditions for interventional PCI treatment.
III. Technical aspects of interventional treatment of ACS in the elderly
The clinical situation of elderly patients with ACS, especially those aged ≥80 years, is complex, and the coexistence of multiple diseases often leads to treatment conflicts and affects clinical decision-making. Elderly patients with coronary artery disease have tortuous, angular, calcified coronary arteries, heavy lesions, many diffuse lesions, often multi-branch and multi-site complex lesions, and left main lesions and chronic occlusive lesions are common, making interventional procedures more difficult and risky, and the incidence of intraoperative complications is high. In addition, the heart and kidney function of the elderly are less tolerant to coronary interventions than those of younger patients, and changes in the condition during PCI are often unpredictable. The operator’s rich clinical experience, ability to improvise and high level of interventional operation are essential to improve the success rate of the procedure. The special characteristics of elderly patients with coronary artery disease should be highly valued, and a comprehensive assessment of the patient’s clinical condition and careful selection of the patient’s treatment strategy should be performed before PCI.
Since about 30% to 60% of patients with ACS have multi-vessel lesions, the proportion of patients with multi-vessel lesions is significantly higher in patients with NSTEMI. The current prevailing opinion is that intervention of non-offender vessels (non-infarct-related vessels) is not advocated during direct PCI for STEMI [7]. The rationale is that non-offender vessel intervention leads to hemodynamic hazards and vascular-related complications (entrapment, no recurrent flow) induced by balloon dilation; multi-vessel PCI causes prolonged intervention time and contrast dosing, which can trigger patient irritability and other adverse events. However, a recent Meta-analysis [8] showed that in STEMI patients, multi-vessel PCI (complete revascularization) improved immediate and long-term patient survival and reduced repeat PCI compared with single-branch PCI. another study [9] also showed that prophylactic PCI to non-offender vessels at the time of direct PCI in STEMI patients provides further benefit, so there are now a few scholars suggest extending PCI to non-offender lesions.
In patients with NSTE-ACS, simultaneous PCI of the target lesion and multiple vessels is not associated with increased MACE events and reduces the rate of revascularization [10]. 2014 AHA/ACC guidelines recommend that it is reasonable to perform multiple PCI in patients with NSTE-ACS (Class IIb evidence, Level of Evidence B). However, elderly patients with ACS have reduced systemic tolerance and often complex coronary lesions, and complete revascularization should not be deliberately pursued during PCI to avoid excessive use of contrast agents or procedural complications. In elderly ACS patients with multiple vascular lesions, the safety of the procedure should be fully considered. The clinical and prognostic significance of the lesions should be carefully understood, and staged, elective PCI can be chosen, and a single surgical intervention for multiple branches and multiple vascular lesions should not be forced. Most elderly patients with ACS can maintain a good quality of life even with incomplete revascularization if they are treated with aggressive medication.
For incomplete revascularization, offender vessel judgment is a basic skill of interventional treatment. The judgment methods include electrocardiography (dynamic changes of ST-T wave in the corresponding leads; poor incremental left bundle branch conduction block and new left bundle branch block suggesting anterior descending branch pathology; slow arrhythmia suggesting right coronary artery pathology, etc.), echocardiography (segmental ventricular wall motion abnormalities), coronary angiography (occlusion with contrast retention, slowing of blood flow after high stenosis, thrombus shadow, plaque rupture niche shadow, etc.), intravascular ultrasound (unstable plaque, plaque rupture phenomenon, entrapment, thrombus, etc.), optical coherence tomography (identification of unstable plaque, evaluation of thrombus and nature of thrombus), flow reserve fraction (FFR <0.75 is indicative of functional myocardial ischemia), etc.
IV. Drug therapy in the peri-interventional period of ACS
1. Antiplatelet agents The 2014 AHA/ACC guidelines [2] state that all patients with NSTE-ACS without contraindications should be given P2Y12 inhibitors (clopidogrel or tigretol) combined with aspirin for 12 months, regardless of whether they receive early interventional therapy. Patients treated with coronary PCI should be treated with a P2Y12 inhibitor (clopidogrel, prasugrel, or tigretol) for at least 12 months. For all patients with NSTE-ACS, it is reasonable to prioritize tegretol over clopidogrel for P2Y12 inhibitors. For patients with NSTE-ACS undergoing PCI who are not at high risk for bleeding, it is reasonable to prioritize prasugrel (initiated during PCI) over clopidogrel for the selection of P2Y12 inhibitors [2]. Glycoprotein IIb/IIIa receptor inhibitors (e.g., tirofiban) may be used prior to emergency/early intervention for ACS.
2. anticoagulation Regardless of the initial treatment strategy, anticoagulation combined with antiplatelet therapy should be recommended for all patients with NSTE-ACS. However, it should be emphasized that anticoagulation should be discontinued after PCI unless there is a compelling reason to continue the therapy. Anticoagulants are generally treated with low-molecular heparin or sodium fondaparinux.
Heparin remains the current standard anticoagulant for PCI, with the addition of a glycoprotein IIb/IIIa receptor inhibitor for patients with ACS with a high thrombotic load, typically maintained for 24-48 hours. A meta-analysis that included six RCT studies showed that no age adjustment was required for IIb/IIIa inhibitor therapy in ACS patients, but adverse events were significantly higher in older women. the ACUITY study showed that bivalirudin at PCI in older ACS patients had similar efficacy to glycoprotein IIb/IIIa inhibitor + heparin, but with fewer bleeding complications. For patients with NSTE-ACS who receive at least two subcutaneous doses (1 mg/kg) or a final dose of enoxaparin 8-12 hours prior to PCI, a further 0.3 mg/kg enoxaparin should be given intravenously at the time of PCI (class I/B). If the patient is receiving sodium fondaparinux at the time of PCI, a further 85 IU/kg UFH should be given intravenously prior to PCI to prevent catheter thrombosis.
Bleeding complications are a major complication of antithrombotic therapy in elderly ACS. the CRUSADE study showed that 15% of major bleeding was caused by overdose of heparin, low molecular heparin, and glycoprotein IIb/IIIa inhibitors. Aspirin should be maintained at 75-100 mg/day, and prasugrel therapy is not recommended in patients with ACS ≥75 years of age or weight <60 kg. The risk of bleeding is significantly increased with triple therapy (dual antiplatelet + warfarin) in elderly ACS combined with atrial fibrillation. the WOEST study showed that clopidogrel alone (not combined with aspirin) significantly reduced bleeding complications without increasing thrombotic events during PCI in patients on oral anticoagulants. However, due to limited strength of evidence, it has not been widely adopted and promoted in clinical practice.
3. Prevention of contrast nephropathy Contrast nephropathy is the most common complication after intervention in elderly ACS patients, up to 10%. Careful assessment of renal function, adequate hydration therapy, selection of isotonic contrast agents and minimization of contrast agent dosage before PCI are important for the prevention of contrast nephropathy.
4. Other drug therapy There is no special principle about other drug therapy for ACS in the elderly, which also emphasizes the standard application of statins, beta-blockers, angiotensin-converting enzyme inhibitors and other drugs based on improving lifestyle. However, medication should be administered taking into account the presence of age-related changes in pharmacokinetics/pharmacokinetics, volume of distribution, comorbidities, drug interactions and drug sensitivity in elderly patients, and drug therapy should be individualized, with dose adjustment based on body weight or creatinine clearance to reduce adverse drug reactions [2].