There has been a limited representation of patients ≥75 years of age in the early clinical trials for non ST segment elevation acute coronary syndrome (NSTE ACS) ranging from 17 to 22 % (pooled data from GUSTO IIb, Paragon A, Paragon B, PURSUIT, GUSTO-IV ACS) and for ST segment elevation ACS (STE ACS) ranging from 12 to 18 % (pooled data from GUSTO I, GUSTO IIb, GUSTO III, ASSENT-2, ASSENT-3, HERO-2). Furthermore, there was only 2 % representation for patients age ≥85 years for both NSTE and STE ACS [1, 2]. TACTICS-TIMI 18 provided the initial evidence of a reduction in death or myocardial infarction (MI) at 6 months with an early invasive (EI) strategy compared to initial conservative (IC) management for high risk NSTE ACS in patients with age ≥75 years (21.6 vs 10.8, OR 0.44, total n = 278) [3]. With an accepted societal threshold of $50,000/death or MI prevented, cost effectiveness analysis (CEA) suggested that the incremental cost effectiveness ratio (ICER) for death or MI prevented was $25,478 with an EI approach, and therefore cost effective [4]. However, CEA was not stratified based on age. Due to this under representation and limited evidence, the 2007 AHA scientific statement for the management of NSTE ACS patients of age ≥75 years underscored the need for prospective randomized outcomes data in elderly patients for definite treatment recommendations [1]. Since the writing of these statement guideline, a contemporary randomized control trial of 313 patients (age ≥75 years, mean age 82) comparing the EI approach (88 % angiography, 55 % revascularization) to IC therapy for patients presenting with NSTE ACS (29 % angiography, 23 % revascularization) demonstrated comparable rates of mortality and MI between the two strategies at 1 year [5]. However, the primary endpoint (composite of death, MI, stroke, rehospitalization or severe bleeding at 1 year) was significantly lower in patients managed with an EI approach who presented with elevated troponin (HR 0.43, 95 % CI: 0.23–0.80) but not with normal troponin (HR 1.67, 95 % CI: 0.75–3.17) [5].

For elderly patients with STE ACS, primary PCI (PPCI) was demonstrated to be superior compared to fibrinolysis (FL) in the earlier trials. The senior PAMI trial (n = 481, age >70 years) demonstrated a 55 % reduction in death, non-fatal stroke or reinfarction in the PPCI group compared to FL (11.6 % vs 18 %, p = 0.05) at 30-days but it was not significant for patients >80 years of age [6]. In a pooled analysis of 11 randomized clinical trials of PPCI versus FL therapy for STE ACS conducted between 1989 and 1996 (n = 2635), PPCI lowered 30-day mortality compared to FL (13.3 vs 23.6, p < 0.05) for elderly patients (age ≥70 years, n = 641) [7]. Balloon angioplasty was the PPCI modality among these earlier clinical trials. As such, the 2007 AHA statement for the management of STE ACS indicated superior efficacy of PPCI in STE ACS in elderly patients but underscored the need for additional evidence in elderly patients with age >80 years of age [2].

Again, since the writing of the AHA statement, a contemporary meta-analysis of 22 randomized trials (n = 6763) compared 30-day mortality, MI and stoke between FL and PPCI across various age groups (<50, 50–60, 60–70, 70–80, >80 years) [8]. Mortality increased with age but the treatment effect demonstrated mortality reduction with PPCI compared to FL in all age groups except age <50 (overall OR 0.65, 95 % CI: 0.52–0.79) [8]. Further, mortality benefit of PCI persists in elderly patients presenting with acute MI complicated by cardiogenic shock at 1-year [9].

Trends in PCI volume over the last 25 years demonstrate that the proportion of patients undergoing PCI in the age range between 75 and 84 years has doubled and has increased by 5 fold for patients with age >85 years [10]. The angiographic success rates and clinical benefits are not different in the elderly patients compared to younger patients [11] In a prospective randomized trial of 800 octogenarian patients (age >80 years), drug eluting stent use (DES-Xience) was compared to bare metal stent use (BMS-Vision) for the 1-year composite of death, MI, stroke, target vessel revascularization (TVR) and major hemorrhage [12]. Rate of dual antiplatelet therapy at 1-year for the BMS group was 32 % and for the DES group was 94 % [12]. There was a trend towards a lower primary endpoint for DES compared to BMS (14.3 % vs 18.7 %, p = 0.09) with comparable 1-year rates of mortality, major hemorrhage and stroke [12]. TVR (2 % vs 7 %, p = 0.001) and MI (4.3 % vs 8.7 %, p = 0.01) were significantly lower in the DES group compared to BMS at 1-year [12]. Therefore, the available evidence suggests that elderly patients requiring PCI benefit from PCI with use of DES, similar to younger populations. The 2011 ACCF/AHA/SCAI PCI guidelines do not consider age as a prohibitive factor but warrant careful consideration of risk compared to benefit due to the increased risk of bleeding complications and stroke in elderly patients undergoing PCI [13–15].

The prevalence of aortic stenosis is 12.4 % and severe aortic stenosis is 3.4 % among elderly patients (age >75 years) [16]. Among patients with severe aortic stenosis, approximately 75 % are symptomatic and 40 % do not receive aortic valve surgery [16]. Patients with severe aortic stenosis and prohibitive operative mortality (inoperable) or high operative risk utilize tremendous amounts of medical resources. Clinical and economic outcomes analysis of medically managed patients with severe aortic stenosis demonstrated approximately 88 % mortality over 5-years with 1.8 years of mean survival [17]. During a 5-year follow up period, an average patient experienced 4–5 hospitalization, with a total 5-year health care cost of $63,844/patient and annual follow up cost of $29,278/year alive [17]. The estimated cost of providing care to medically managed patients with severe aortic stenosis among the Medicare population is $1.3 billion/year [17]. TAVR is an attractive treatment strategy for such patients.

Efficacy and safety of TAVR was compared to standard therapy for patients with prohibitively higher operative mortality in the PARTNER trial (Inoperable-cohort B, mean age 83 years, total n = 358) [18]. Compared to standard therapy, TAVR resulted in a 20 % reduction in mortality, improved functional status and reduced hospitalization rates at 1 year [18]. Long term outcomes up to 5 years have demonstrated significantly lower all cause mortality (71.8 % vs 93.6 %, p < 0.0001) and lower re-hospitalization (47.6 % vs 87.3 %, p < 0.0001) with TAVR compared to the standard therapy [19]. The total cost of care at 12-months was higher in the TAVR group compared to standard therapy driven mainly by the cost of the initial procedure and longer length of rehabilitation and skilled nursing [20]. The cost effectiveness analysis, accounting for improved survival and quality of life, demonstrated TAVR to be superior than standard therapy for inoperable severe aortic stenosis patients [20]. TAVR for patients with inoperable severe aortic stenosis appears to be either comparable or favorable to many other advanced procedures frequently performed in the elderly patients such as use of defibrillators in the primary prevention of sudden cardiac death, PCI, atrial fibrillation ablation, hemodialysis and destination left ventricular assist devices [20].

The PARTNER trial (cohort A) compared TAVR (mean age 84 years, total n = 699) in patients considered high, but not prohibitive, risk for perioperative mortality, with surgical aortic valve replacement (SAVR) [21]. One-year and subsequently reported 2-year outcomes demonstrated comparable rates of mortality and stroke [21]. Quality of life with TAVR was comparable to SAVR at 1-year [22]. TAVR can be performed via transfemoral (TF-TAV) or transapical (TA-TAVR) approaches for high risk severe aortic stenosis patients [21]. TA-TAVR is performed in patients who do not have favorable femoral artery anatomy [21]. Cost effectiveness analysis suggested that, compared to SAVR, TF-TAVR and not the TA-TAVR remains an economically attractive strategy due to reduced ICU stay and reduced length of hospitalization [22].

In summary, for elderly patients with severe aortic stenosis, available evidence suggests that TAVR is superior compared to standard therapy for inoperable patients. For high-risk patients, TAVR performed via the transfemoral route remains non-inferior and cost effective compared to SAVR.

Among patients with symptomatic severe mitral regurgitation (SMR), functional disease (74 %) from dilation of the left ventricle and primary degenerative disease (21 %) represent the predominant mechanisms [23]. Approximately, 64 % of patients with functional and 16 % of patients with degenerative SMR do not undergo surgery due to increased operative risk [23]. Among unoperated patients, 1 and 5-year mortality remain high at 20 % and 50 %, respectively, and among survivors, heart failure admissions increase from 41 % at 1 year to 90 % at 5-years [23]. Percutaneous catheter based edge-to-edge mitral valve repair with the MitraClip system has emerged as a potential option for patients with prohibitive operative risk for degenerative SMR. The EVEREST II trial evaluated safety and efficacy of TMVR (MitraClip) in 121 patients with degenerative SMR and prohibitive operative risk with a median follow up of 1.47 years [24]. Mean age was 82 years and 87 % of the population had New York Heart Association (NYHA) class III/IV symptoms. Thirty-day mortality was 6.3 %, MI was 0.8 % and stroke was 2.4 %. One-year mortality was 23.6 % [24]. Among patients alive at 1-year; 83 % had MR ≤ 2+; 87 % had NYHA class I or II symptoms, heart failure rehospitalization were significantly reduced and there was significant improvement in quality of life (measured by SF-36 quality of life scores) [24]. Although the mean age in this study was 82 years and suggested meaningful improvements on multiple levels for this age group, larger studies would be required to evaluate the impact of TMVR on mortality and its cost effectiveness compared to standard therapy before it can be widely recommended for elderly patients. MitraClip currently remains investigational for patients with functional SMR.