Revascularization Versus Medical Therapy in Patients Aged 80 Years and Older With Acute Myocardial Infarction

Derek Q. Phan, MD; Ara H. Rostomian, MD, MBA, MPH; Franz Schweis, MD; Joanie Chung, MPH; Bryan Lin, MS; Ray Zadegan, MD; Ming-Sum Lee, MD, PhD

Disclosures

J Am Geriatr Soc. 2020;68(11):2525-2533. 

In This Article

Discussion

There are limited data on the benefits of invasive therapies for older patients (aged ≥80 years) with ACS. This large retrospective observational study utilizing IPTW shows revascularization (with either PCI or CABG) is superior to medical therapy in reducing all-cause mortality and nonfatal MI in patients aged 80 years or older undergoing ICA for AMI. Both PCI and CABG separately were associated with favorable outcomes compared with medical therapy. The benefit was seen in all subgroups, except in Black patients and those with prior CABG.

Older patients are underrepresented in randomized clinical trials for ACS.[10–12] Trials focusing on older patients have been few, small in sample size, and showed mixed results. In 2012, Savonitto et al enrolled 313 adults aged 75 years or older with NSTEMI and randomly assigned them to either undergo initial ICA with subsequent PCI or CABG if indicated or conservative strategy.[18] They found no difference between groups for the combined primary outcome of death, MI, disabling stroke, and repeated hospitalization for cardiovascular causes or severe bleeding. Sanchis et al, in 2016, found similar results with no significant benefit with an invasive over a conservative strategy in adults aged 70 years or older with significant comorbidities presenting with NSTEMI (n = 106).[17] In contrast, the After Eighty Study, which was a larger randomized trial (n = 457) of patients aged 80 years or older in Norway with NSTEMI or unstable angina, found an invasive strategy to be superior to a conservative strategy with regard to the combined primary outcome of MI, urgent revascularization, stroke, and death (HR = 0.53; 95% CI = 0.41–0.69; P = .001).[19] Differences in results between studies could be explained by limited sample size among studies and different age groups that were included. Some studies have suggested older patients may actually derive a greater absolute benefit from invasive revascularization compared with their younger counterparts.[16] With the After Eighty Study enrolling a larger number of older and hence higher-risk patients, this may have allowed them to identify a difference in outcomes between the two treatment strategies.

Community- and registry-based observational studies also showed mixed results. In 2004, two observational studies showed conflicting findings. A registry in Italy of patients admitted to the Coronary Care Units with NSTEMI reported patients aged 75 years or older (n = 564, with 221 undergoing invasive strategy) had a higher risk for a composite outcome of death, AMI, and stroke at 30 days if treated with a conservative strategy (odds ratio (OR) = 2.31; 95% CI = 1.2–4.48).[23] Within the same year, a subgroup analysis from the CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation of the ACC/AHA Guidelines) quality improvement initiative in patients aged 75 years or older (N = 5,794) showed a lack of benefit of an early invasive strategy with regard to in-hospital mortality.[6] Observational studies following these were more consistent in showing benefit with revascularization. In 2008, data from the GRACE (Global Registry of Acute Coronary Events) registry reported revascularization led to a reduced 6-month mortality (OR = 0.68; 95% CI = 0.49–0.95) in patients older than 80 years (n = 3,029, of which 620 patients underwent PCI/CABG) presenting with high-risk NSTEMI.[15] Similarly, in 2018, data from the LONGEVO-SCA registry (n = 531) showed a lower 6-month rate of all-cause mortality (9.2% vs 22.9%; P = .001) with an invasive strategy compared with a conservative approach in patients aged 80 years or older with NSTEMI.[22] However, the benefit was attenuated in those who were frail. Lastly, a large population-based study from the 2003 to 2010 Nationwide Inpatient Sample database showed patients aged 80 years or older presenting with unstable angina/NSTEMI (N = 968,542) had lower in-hospital mortality (OR = 0.76; 95% CI = 0.75–0.78) with an early invasive approach compared with an initial conservative strategy, although results on follow-up after discharge were limited.[24]

Overall, conflicting results between randomized trials and observational studies with regard to revascularization in older patients with NSTEMI underscore the need for additional data. Real-world data show older patients are actually less likely to receive revascularization due to high risk-benefit ratio, despite them possibly benefiting the most from invasive treatment.[2–6,14,15]

Our current large retrospective study of patients aged 80 years or older with AMI contributes to the current literature, providing additional real-world data on the benefits of invasive revascularization in older patients. The strengths of our study being large sample size (N = 1,433, with 890 patients undergoing PCI or CABG) and long-term follow-up (median follow-up = 2.6 years (IQR = 1–4.8 years)). In addition, we further delineated the benefits by stratifying by revascularization strategy (PCI or CABG) compared with medical therapy; prior studies evaluated invasive revascularization as a combined group. As with all retrospective, observational studies, there is potential bias, especially confounding by indication. We note in our study that patients treated with medical therapy had more extensive comorbidities, more prior medication usage, extensive CAD (≥1 CTO in any vessel), and lower LVEF. To minimize these biases and potential confounding factors, we performed IPTW adjustment and successfully balanced baseline comorbidities and risk factors between the groups before analysis.

Our results are consistent with prior observational studies and larger randomized trials, further supporting an invasive revascularization approach in older patients. Overall, revascularization (with either PCI or CABG) led to a 34% reduction in all-cause mortality and a 32% reduction in nonfatal MI. Both revascularization strategies were associated with benefit (PCI: 30% reduction in all-cause mortality and 29% reduction in nonfatal MI; CABG: 42% reduction in all-cause mortality and 49% reduction in nonfatal MI). These benefits were seen in all subgroups, except in Black patients and those with prior CABG. We found a stronger benefit in the subgroup of patients aged 90 years or older, which may suggest that the highest-risk patients derive the most absolute benefit from revascularization. However, sample size was significantly diminished in this subgroup (n = 91), hence necessitating further studies before any conclusion can being made. However, this highlights that age alone should not preclude patients presenting with AMI from invasive revascularization.

We found no differences in all-cause mortality between revascularization strategy (PCI vs CABG), although PCI was associated with increased nonfatal MI and need for repeated revascularization. With regard to rationale for medical therapy, we found over one-third of patients did not receive revascularization due to high risk-benefit ratio, as deemed by the treating physician at the time. This is consistent with real-world data showing older patients are less likely to receive invasive therapies due to being high risk.[6,14,15] Over one-third of patients were not candidates for PCI or CABG; this an area that could potentially be studied further to help expand treatment options available for this particular subgroup. Medication regimen after ICA was not evaluated in the current study and is a potential area for additional research to determine if optimal medical treatment and compliance (especially with dual-antiplatelet therapy) has any effect on long-term outcomes in this unique population. Further study is needed in racial/ethnic groups (especially Black patients) to evaluate reason for disparity in outcomes.

Limitations

There are several limitations that need to be acknowledged. This is a retrospective observational study with inherent biases and confounders. Despite maximum effort to reduce confounding with successful balancing of groups with IPTW adjustment and multivariate Cox regression models, residual bias may remain. We do not have cause-specific mortality data (i.e., cardiac cause vs noncardiac cause of death), which may be important given multiple competing risks in the older patient population where the likelihood of death from a noncardiac illness is high. Determination of treatment (PCI vs CABG vs medical therapy) was at discretion of the treating physician at the time, and hence despite IPTW adjustment, confounding by indication may remain. However, we note that only 4.4% of patients had a history of dementia, suggesting a selection bias toward a potential candidacy for PCI or CABG may also be occurring before ICA, such that those not likely candidates for invasive revascularization to not be referred for ICA. Medical history was identified using ICD codes, and occasional errors in coding is a possibility. Patients included were from the southern California region with at least 1 year of enrollment in the insurance plan, thus limiting the generalizability of results to other geographical locations or economic status. Frailty was not available and hence could not be accounted for to determine its effects on the outcomes. Bleeding outcomes were also not available. Regardless of these limitations, sample size is robust with long-term follow-up compared with other observational studies that may be large in size but limited in follow-up (i.e., in-hospital mortality or 6-month follow-up only available).

Comments

3090D553-9492-4563-8681-AD288FA52ACE

processing....