Risk stratification in elderly ACS patient is difficult because supporting evidence is scarce. One critical point, especially in the very old, is the prediction of the cause of death in the short-medium term, since this information may help in decision-making for invasive procedures. Among the general elderly population, the Italian administrative data drawn from the National Institute of Statistics have shown that cardiovascular disease is reported as the cause of death (CoD) in 41 % of men and 49 % of women [15], much greater than the 30 % reported in the United States by the Centers for Disease Control and Prevention [16], but similar to the 40 % cardiovascular CoD reported among male Medicare beneficiaries >67 years hospitalised and followed up for 2 years in the United States [17]. Among elderly patients hospitalised for noncardiovascular illness, cardiovascular deaths contributed to total mortality in about 40–50 % of the cases [18, 19]. Even among patients with cardiovascular diseases other than an ACS, such as those with nonvalvular atrial fibrillation [20] or aortic stenosis [21], CV death accounts for 40 % of overall mortality at follow-up. However, when an elderly patient becomes hospitalised for an ACS, cardiovascular events will represent more than 70 % of the causes of death at follow-up. This has been recently shown in the Italian Elderly ACS study, where the contribution of cardiovascular deaths to overall mortality in the following year was as great as 80 %, and most of these deaths were of ischaemic origin [22]. This finding was surprisingly similar to those reported in a population of US veterans hospitalised for an ACS [23]. Also very similar data came from the subanalysis of the elderly population enrolled in the PLATelet inhibition and patient Outcomes (PLATO) [24] and TRILOGY [7] trials. For these reasons, risk stratification with regard to overall mortality, but also for CV death, may be extremely important in order to select treatment strategies and, specifically, for the high-risk and high-cost procedures, also for an estimate of “futility”.

The independent predictors of total and cardiovascular death among elderly patients with NSTEACS have been investigated in the Italian Elderly ACS study, using the full database of the randomised clinical trial and registry [22]. As shown in Fig. 13.3, lower values of ejection fraction, estimated glomerular filtration rate (eGFR) and blood haemoglobin and older age were independent predictors of CV death, although three of these four predictors were also predictors of non-CV death. Starting from the same database, a simple risk prediction score for 1-year mortality was developed from the randomised trial (313 patients) by using logistic regression analysis and validated in the registry cohort of the study patients (332 patients) [25]. The risk score included five statistically significant covariates: previous vascular event, haemoglobin level, estimated glomerular filtration rate, ischaemic electrocardiographic changes and elevated troponin level. The model allowed a maximum score of 6. The score demonstrated a good discriminating power (c statistic 0.739) and calibration, even among subgroups defined by gender and age. When validated in the registry cohort, the scoring system confirmed a strong association with the risk for all-cause death. Moreover, a score >3 (the highest baseline risk group) identified a subset of patients with NSTEACS most likely to benefit from an invasive approach.

A frailty parameter (which, unfortunately, was not collected in the study) would have probably resulted as an independent predictor on non-CV and overall mortality [26–28].

Primary angioplasty (pPCI) has emerged as the most effective and safe reperfusion strategy in elderly patients with STEMI. The TRatamiento del Infarto Agudo de miocardio eN Ancianos (TRIANA) trial was started in 2005 to compare the efficacy and safety of pPCI and fibrinolysis in very old STEMI patients [5]. This study, planned to enrol 570 patients, was interrupted after the enrolment of 266 patients over 33 months and showed a trend towards a reduction in the primary endpoint of 30-day death, re-MI or disabling stroke with pPCI (18.9 % vs. 25.4 %; odds ratio [OR], 0.69; 95 % confidence interval [95 % CI] 0.38–1.23). The incidence of each of the components of the primary endpoint was directionally lower with pPCI. A pooled analysis of this and two previous RCTs comparing pPCI with lytic therapy, published in the same paper, showed a trend towards mortality reduction and a significant reduction in death, re-MI and stroke at 30 days. The relevance of this RCT data for clinical practice finds confirmation from the analysis of the prospective, multicentre registry of the Reseau de Cardiologie de Franche Comte, comparing two periods of time in 2001 and 2006 [29]. From 2001 to 2006, pPCI became the preferential modality of reperfusion therapy over fibrinolysis [adjusted OR 6.9, 95 % CI 3.1–15], and this change in strategy was associated with a significantly lower 30-day mortality in 2006 (9.2 % vs. 23.3 %, p < 0.001).

A recent meta-analysis including 6,298 patients who underwent pPCI and stent implantation included in the drug-eluting stent in primary angioplasty (DESERT) cooperation database [11] confirmed that, despite the expected higher rate of death at long-term follow-up in elderly as compared to younger patients (HR 2.17 95 % CI 1.97–2.39, p <0.0001), no impact of age was observed on the risk of re-MI, stent thrombosis and target vessel revascularisation.

A favourable outcome was described with regard to 199 patients aged >80 years treated within the Minneapolis regional STEMI system [30]: the median length of hospital stay was 4 days, in-hospital mortality was 11.6 % and 1-year mortality was 25.6 %. Of the 166 patients with age >80 who lived independently or in assisted living before hospital admission and survived, 150 (90 %) were discharged to a similar living situation or projected to such a living situation after temporary nursing home care.

In recent Italian ACS registries, patients aged >75 years represent approximately 40 % of those with NSTEACS [1]. Over the last few years, inferential analyses from registries [31] and subgroup analyses of RCTs [8, 10] have suggested that an early invasive approach is associated with better outcome in elderly patients as compared to conservative treatment.

Among patients aged >75 years enrolled in the Treat Angina with Aggrastat and Determine Cost of Therapy with an Invasive or Conservative Strategy–Thrombolysis in Myocardial Infarction (TACTICS–TIMI) 18 trial [8], the early invasive strategy conferred an absolute reduction of 10.8 percentage points (10.8 % vs. 21.6 %; p = 0.016) and a relative reduction of 56 % in death or MI at 6 months, a much higher benefit as compared to that observed in younger age groups (Fig. 13.4). In this study, thrombolysis in myocardial infarction (TIMI) major bleeding rates were almost prohibitive with the early aggressive strategy in patients >75 years of age (16.6 % vs. 6.5 %; p = 0.009), most likely due to the systematic upstream therapy with tirofiban and unfractionated heparin and the universal use of the femoral approach to catheterisation.

A collaborative analysis of individual data from the FRISC II–ICTUS–RITA-3 (FIR) trials [10], all comparing routine-versus-selective invasive strategy in NSTEACS, assessed outcomes up to 5 years after index admission. The composite of cardiovascular death or MI was significantly lower with the routine invasive strategy in patients aged 65–74 years (HR 0.72, 95 % CI 0.58–0.90) and in those aged >75 years (HR 0.71, 95 % CI 0.55–0.91), but not in those aged <65 years (HR 1.11, 95 % CI 0.90–1.38; p < 0.001 for interaction between treatment strategy and age). The interaction was driven by an excess of early MI in patients <65 years of age, whereas there was no heterogeneity between age groups concerning cardiovascular death. The benefits were smaller for women than for men (p < 0.009 for interaction).

The Italian Elderly ACS study [6] was the first RCT to enrol exclusively patients with NSTEACS and an age >75 years: patients were randomised to an early invasive (coronary angiography and, when indicated, revascularisation within 72 h) or an initially conservative (angiography and revascularisation only for recurrent ischaemia). The study was initially planned to enrol 504 patients with a primary endpoint set at 6-month follow-up but was subsequently modified to a 12-month primary endpoint with the sample size set at 313 patients; further 332 patients excluded from the trial for any reason were enrolled in a parallel registry. The mean age of the study population was 82 years, and 50 % were women. The primary endpoint (a net clinical benefit of all-cause mortality, MI, disabling stroke and repeat hospital stay for cardiovascular causes or severe bleeding) was significantly reduced by an early invasive approach in patients with elevated troponin levels on admission (61 % of the cases) (Fig. 13.5), though the benefit was not significant in the whole study population (27.9 % vs. 34.6 %; HR: 0.80; 95 % CI: 0.53–1.19), with a significant treatment per troponin status interaction (p = 0.03). All of the components of the primary endpoint trended towards benefit with the early invasive strategy. In this contemporary study only, one adjudicated case (0.6 %) of major bleeding was recorded during index admission, and three subsequent hospital admissions were due to severe bleeding (1.9 %). This remarkable safety may be due to a high rate (75 %) of radial approach to percutaneous coronary intervention (PCI) and a limited (20 % in patients undergoing PCI) use of GPIIb/GPIIIa inhibitors.

Finally in a recent metaregression analysis including all of the RCTs comparing treatment strategies in NSTEACS, a routine early invasive strategy has been confirmed to reduce the composite endpoint of death and MI (p for interaction = 0.044), as well as repeat hospitalisation (p for interaction <0.0001), to a greater extent in elderly than in younger individuals, without significant differences between men and women [32].

Elderly patients with cardiogenic shock and those resuscitated from an out-of-hospital cardiac arrest have traditionally been considered off-limits as candidates to PCI in the ACS scenario. A subgroup analysis of the SHOCK trial had shown a non-significant trend towards increased 30-day mortality (75 % vs. 53 %) when a total of 56 elderly patients with acute MI and cardiogenic shock had received emergency revascularisation compared with initial medical stabilisation [33]. A recent meta-analysis of nonrandomised studies [34] has considered a total of 1935 patients with MI and cardiogenic shock aged >75 years, of which 468 had been treated by emergency revascularisation and 1467 with initial medical stabilisation. Despite a lower rate of successful revascularisation in elderly patients compared with their younger counterparts (n = 7 studies; 88 % vs. 95 %, p < 0.0001), patients who received emergency revascularisation experienced lower short-term (55 % vs. 72 %; OR = 0.48, 95 % CI = 0.33–0.69) and intermediate-term (60 % vs. 80 %; OR = 0.47, 95 % CI = 0.27–0.83) mortality. However, this kind of analysis does not allow to conclude whether the better outcome is attributable to patient selection or to the positive effect of emergency revascularisation.