Effect of a Multicomponent Home-Based Physical Therapy Intervention on Ambulation After Hip Fracture in Older Adults: The CAP Randomized Clinical Trial.

Importance: Disability persists after hip fracture in older persons. Current rehabilitation may not be sufficient to restore ability to walk in the community. Objective: To compare a multicomponent home-based physical therapy intervention (training) with an active control on ability to walk in the community. Design, Setting, and Participants: Parallel, 2-group randomized clinical trial conducted at 3 US clinical centers (Arcadia University, University of Connecticut Health Center, and University of Maryland, Baltimore). Randomization began on September 16, 2013, and ended on June 20, 2017; follow-up ended on October 17, 2017. Patients aged 60 years and older were enrolled after nonpathologic, minimal trauma hip fracture, if they were living in the community and walking without human assistance before the fracture, were assessed within 26 weeks of hospitalization, and were not able to walk during daily activities at the time of enrollment. A total of 210 participants were randomized and reassessed 16 and 40 weeks later. Interventions: The training intervention (active treatment) (n = 105) included aerobic, strength, balance, and functional training. The active control group (n = 105) received transcutaneous electrical nerve stimulation and active range-of-motion exercises. Both groups received 2 to 3 home visits from a physical therapist weekly for 16 weeks; nutritional counseling; and daily vitamin D (2000 IU), calcium (600 mg), and multivitamins. Main Outcomes and Measures: The primary outcome (community ambulation) was defined as walking 300 m or more in 6 minutes at 16 weeks after randomization. The study was designed to test a 1-sided hypothesis of superiority of training compared with active control. Results: Among 210 randomized participants (mean age, 80.8 years; 161 women [76.7%]), 197 (93.8%) completed the trial (187 [89.0%] by completing the 6-minute walk test at 16 weeks and 10 [4.8%] by adjudication of the primary outcome). Among these, 22 of 96 training participants (22.9%) and 18 of 101 active control participants (17.8%) (difference, 5.1% [1-sided 97.5% CI, -∞ to 16.3%]; 1-sided P = .19) became community ambulators. Seventeen training participants (16.2%) and 15 control participants (14.3%) had 1 or more reportable adverse events during the intervention period. The most common reportable adverse events reported were falls (training: 6 [5.7%], control: 4 [3.8%]), femur/hip fracture (2 in each group), pneumonia (training: 2, control: 0), urinary tract infection (training: 2, control: 0), dehydration (training: 0, control: 2), and dyspnea (training: 0, control: 2). Conclusions and Relevance: Among older adults with a hip fracture, a multicomponent home-based physical therapy intervention compared with an active control that included transcutaneous electrical nerve stimulation and active range-of-motion exercises did not result in a statistically significant improvement in the ability to walk 300 m or more in 6 minutes after 16 weeks. Trial Registration: ClinicalTrials.gov Identifier: NCT01783704.

Impact of percutaneous coronary intervention on biomarker levels in patients in the subacute phase following myocardial infarction: the Occluded Artery Trial (OAT) biomarker ancillary study.

BACKGROUND: The purpose of the Occluded Artery Trial (OAT) Biomarker substudy was to evaluate the impact of infarct related artery (IRA) revascularization on serial levels of N-terminal prohormone of brain natriuretic peptide (NT-proBNP) and dynamics of other biomarkers related to left ventricular remodeling, fibrosis and angiogenesis. METHODS: Patients were eligible for OAT-Biomarker based on the main OAT criteria. Of 70 patients (age 60.8 ± 8.8, 25% women) enrolled in the substudy, 37 were randomized to percutaneous coronary intervention (PCI) and 33 to optimal medical therapy alone. Baseline serum samples were obtained prior to OAT randomization with follow up samples taken at one year. The primary outcome was percent change of NT-proBNP from baseline to 1 year. The secondary outcomes were respective changes of matrix metalloproteinases (MMP) 2 and 9, tissue inhibitor of matrix metalloproteinase 2 (TIMP-2), Vascular Endothelial Growth Factor (VEGF), and Galectin-3. RESULTS: Paired (baseline and one-year) serum samples were obtained in 62 subjects. Baseline median NT-proBNP level was 944.8 (455.3, 1533) ng/L and decreased by 69% during follow-up (p < 0.0001). Baseline MMP-2 and TIMP-2 levels increased significantly from baseline to follow-up (p = 0.034, and p = 0.027 respectively), while MMP-9 level decreased from baseline (p = 0.038). Levels of VEGF and Galectin-3 remained stable at one year (p = NS for both). No impact of IRA revascularization on any biomarker dynamics were noted. CONCLUSIONS: There were significant changes in measured biomarkers related to LV remodeling, stress, and fibrosis following MI between 0 and 12 month. Establishing infarct vessel patency utilizing stenting 24 hours-28 days post MI did not however influence the biomarkers' release.

Percutaneous revascularization and long term clinical outcomes of diabetic patients randomized in the Occluded Artery Trial (OAT).

BACKGROUND: Percutaneous coronary intervention (PCI) of a persistently totally occluded infarct-related artery (IRA) in stable high-risk patients >24h after myocardial infarction (MI) does not reduce the occurrence of death, re-infarction, or heart failure. Diabetic patients are at higher risk for cardiovascular events; we examined their outcomes overall with PCI and optimal medical therapy alone (MED). METHODS: The long-term (7-year) outcomes of 454 diabetic patients (20.6%) randomized to PCI or MED in the Occluded Artery Trial (OAT) were assessed for the composite primary endpoint of death, re-MI, or New York Heart Association class IV heart failure. Diabetics and non-diabetics were compared and outcomes assessed by treatment strategy. RESULTS: The 7-year cumulative primary event rate for diabetic patients was 35.0% vs. 19.4% in the non-diabetic cohort (p<0.001). Multivariable analyses revealed diabetes to be an independent predictor (p<0.01) for the primary outcome, fatal or nonfatal recurrent MI, Class IV Heart Failure (HF), and death. The 7-year cumulative primary event rates were 35.3% in the PCI group vs. 34.5% in the medical therapy group in diabetic patients (p=0.19) and 19.3% in the PCI group vs. 19.5% in the medical therapy group in patients without diabetes (p=0.60). CONCLUSIONS: Despite the higher overall risk conferred by the presence of diabetes, PCI did not improve clinical outcomes in this subpopulation, and is not indicated in otherwise stable patients with a totally occluded infarct-related artery in the sub-acute phase after MI.

Infarct artery distribution and clinical outcomes in occluded artery trial subjects presenting with non-ST-segment elevation myocardial infarction (from the long-term follow-up of Occluded Artery Trial [OAT]).

We hypothesized that the insensitivity of the electrocardiogram in identifying acute circumflex occlusion would result in differences in the distribution of the infarct-related artery (IRA) between patients with non-ST-segment elevation myocardial infarction (NSTEMI) and STEMI enrolled in the Occluded Artery Trial. We also sought to evaluate the effect of percutaneous coronary intervention to the IRA on the clinical outcomes for patients with NSTEMI. Overall, those with NSTEMI constituted 13% (n = 283) of the trial population. The circumflex IRA was overrepresented in the NSTEMI group compared to the STEMI group (42.5 vs 11.2%; p <0.0001). The 7-year clinical outcomes for the patients with NSTEMI randomized to percutaneous coronary intervention and optimal medical therapy versus optimal medical therapy alone were similar for the primary composite of death, myocardial infarction, and class IV congestive heart failure (22.3% vs 20.2%, hazard ratio 1.20, 99% confidence interval 0.60 to 2.40; p = 0.51) and the individual end points of death (13.8% vs 17.0%, hazard ratio 0.82, 99% confidence interval 0.37 to 1.84; p = 0.53), myocardial infarction (6.1 vs 5.1%, hazard ratio 1.11, 99% confidence interval 0.28 to 4.41; p = 0.84), and class IV congestive heart failure (6.7% vs 6.0%, hazard ratio 1.50, 99% confidence interval 0.37 to 6.02; p = 0.45). No interaction was seen between the electrocardiographically determined myocardial infarction type and treatment effect (p = NS). In conclusion, the occluded circumflex IRA is overrepresented in the NSTEMI population. Consistent with the overall trial results, stable patients with NSTEMI and a totally occluded IRA did not benefit from randomization to percutaneous coronary intervention.

Heart failure in post-MI patients with persistent IRA occlusion: prevalence, risk factors, and the long-term effect of PCI in the Occluded Artery Trial (OAT).

BACKGROUND: The incidence and predictors of heart failure (HF) after myocardial infarction (MI) with modern post-MI treatment have not been well characterized. METHODS AND RESULTS: A total of 2,201 stable patients with persistent infarct-related artery occlusion >24 hours after MI with left ventricular ejection fraction <50% and/or proximal coronary artery occlusion were randomized to percutaneous intervention plus optimal medical therapy (PCI) or optimal medical therapy (MED) alone. Centrally adjudicated HF hospitalizations for New York Heart Association (NYHA) III/IV HF and mortality were determined in patients with and without baseline HF, defined as a history of HF, Killip Class >I at index MI, rales, S3 gallop, NYHA II at randomization, or NYHA >I before index MI. Long-term follow-up data were used to determine 7-year life-table estimated event rates and hazard ratios. There were 150 adjudicated HF hospitalizations during a mean follow-up of 6 years with no difference between the randomized groups (7.4% PCI vs. 7.5% MED, P = .97). Adjudicated HF hospitalization was associated with subsequent death (44.0% vs. 13.1%, HR 3.31, 99% CI 2.21-4.92, P < .001). Baseline HF (present in 32% of patients) increased the risk of adjudicated HF hospitalization (13.6% vs. 4.7%, HR 3.43, 99% CI 2.23-5.26, P < .001) and death (24.7% vs. 10.8%, HR 2.31, 99% CI 1.71-3.10, P < .001). CONCLUSIONS: In the overall Occluded Artery Trial (OAT) population, adjudicated HF hospitalizations occurred in 7.5% of subjects and were associated with increased risk of subsequent death. Baseline or prior HF was common in the OAT population and was associated with increased risk of hospitalization and death.

Long-term outcomes after a strategy of percutaneous coronary intervention of the infarct-related artery with drug-eluting stents or bare metal stents vs medical therapy alone in the Occluded Artery Trial (OAT).

BACKGROUND: The OAT, a randomized study of routine percutaneous coronary intervention or optimal medical therapy (MED) alone for the treatment of a totally occluded infarct-related artery in the subacute phase after myocardial infarction, showed similar rates of death, reinfarction and congestive heart failure (CHF) between study groups. Although most percutaneous coronary intervention patients were treated with bare metal stents (BMS), drug-eluting stents (DES) were also implanted in the latter part of the study. The aim of the study was to conduct an exploratory analysis of long-term outcomes for DES vs. BMS deployment vs. MED in the OAT. METHODS: Patients enrolled after February 2003 (when first DES was implanted) were followed (DES n = 79, BMS n = 393, MED n = 552) up to a maximum of 6 years (mean survivor follow-up 5.1 years). RESULTS: The 6-year occurrence of the composite end point of death, reinfarction and class IV CHF was similar [20.4% of DES, 18.9% of BMS and 18.4% of MED (P = .66)] as were the rates of the components of the primary end point. During the follow-up period, 33.4% of DES, 44.4% of BMS and 48.1% of MED patients, developed angina (P = .037). The rate of revascularization during follow up was 11.3%, 20.5% and 22.5% among these groups, respectively (P = .045). CONCLUSIONS: There is no suggestion of reduced long-term risk of death, reinfarction or class IV CHF with DES usage compared to BMS or medical treatment alone. An association between DES use and freedom from angina and revascularization relative to medical therapy is suggested.

Effect of late revascularization of a totally occluded coronary artery after myocardial infarction on mortality rates in patients with renal impairment.

Renal dysfunction is an independent predictor of cardiovascular events and a negative prognostic indicator after myocardial infarction (MI). Randomized data comparing percutaneous coronary intervention to medical therapy in patients with MI with renal insufficiency are needed. The Occluded Artery Trial (OAT) compared optimal medical therapy alone to percutaneous coronary intervention with optimal medical therapy in 2,201 high-risk patients with occluded infarct arteries >24 hours after MI with serum creatinine levels ≤2.5 mg/dl. The primary end point was a composite of death, MI, and class IV heart failure (HF). Analyses were carried out using estimated glomerular filtration rate (eGFR) as a continuous variable and by eGFR categories. Long-term follow-up data (maximum 9 years) were used for this analysis. Lower eGFR was associated with development of the primary outcome (6-year life-table rates of 16.9% for eGFR >90 ml/min/1.73 m(2), 19.2% for eGFR 60 to 89 ml/min/1.73 m(2), and 34.9% for eGFR <60 ml/min/1.73 m(2); p <0.0001), death, and class IV HF, with no difference in rates of reinfarction. On multivariate analysis, eGFR was an independent predictor of death and HF. There was no effect of treatment assignment on the primary end point regardless of eGFR, and there was no significant interaction between eGFR and treatment assignment on any outcome. In conclusion, lower eGFR at enrollment was independently associated with death and HF in OAT participants. Despite this increased risk, the lack of benefit from percutaneous coronary intervention in the overall trial was also seen in patients with renal dysfunction and persistent occlusion of the infarct artery in the subacute phase after MI.

Relationship of female sex to outcomes after myocardial infarction with persistent total occlusion of the infarct artery: analysis of the Occluded Artery Trial (OAT).

BACKGROUND: Long-term follow-up (up to 9 years) from the OAT allows for the examination of sex differences in outcomes and the effect of percutaneous coronary intervention (PCI) in a relatively homogeneous cohort of myocardial infarction (MI) survivors. METHODS: The OAT randomized 484 (22%) women and 1717 men to PCI of the occluded infarct-related artery vs medical therapy alone >24 hours post-MI. There was no benefit of PCI on the composite of death, MI, and class IV heart failure. We analyzed outcomes by sex and investigated for sex-based trial selection bias using a concurrent registry. RESULTS: Women were older and more likely to have left anterior descending infarct-related artery, diabetes and hypertension, history of heart failure, and rales at randomization but were less likely to smoke. The proportion and characteristics of women enrolled in the trial and the registry were similar, including left ventricular ejection fraction and extent of disease. Women had higher rates of the primary composite (hazard ratio [HR] 1.48, P = .0002), death (HR 1.50, P = .001), and heart failure (HR 2.53, P < .0001) but not reinfarction (HR 1.12, P = .57). Female sex was not independently associated with the primary end point or death on multivariate analysis. There was a trend toward independent association of female sex with heart failure (HR 1.66, P = .02). CONCLUSION: Women in OAT had a higher primary end point event rate than did men, mainly driven by heart failure. Female sex was not independently associated with death or MI in this well-defined cohort with comparable extent of coronary artery disease, similar medical therapy, and equivalent left ventricular ejection fraction by sex.

Comparison of late results of percutaneous coronary intervention among stable patients ≤65 versus >65 years of age with an occluded infarct related artery (from the Occluded Artery Trial).

Although opening an occluded infarct-related artery >24 hours after myocardial infarction in stable patients in the Occluded Artery Trial (OAT) did not reduce events over 7 years, there was a suggestion that the effect of treatment might differ by patient age. Baseline characteristics and outcomes by treatment with percutaneous coronary intervention (PCI) versus optimal medical therapy alone were compared by prespecified stratification at age 65 years. A p value <0.01 was prespecified as significant for OAT secondary analyses. The primary outcome was death, myocardial infarction, or New York Heart Association class IV heart failure. Patients aged >65 years (n = 641) were more likely to be female, to be nonsmokers, and to have hypertension, lower estimated glomerular filtration rates, and multivessel disease compared to younger patients (aged ≤65 years, n = 1,560) (p <0.001). There was no significant observed interaction between treatment assignment and age for the primary outcome after adjustment (p = 0.10), and there was no difference between PCI and optimal medical therapy observed in either age group. At 7-year follow-up, younger patients tended to have angina more often compared to the older group (hazard ratio 1.21, 99% confidence interval 1.00 to 1.46, p = 0.01). The 7-year composite primary outcome was more common in older patients (p <0.001), and age remained significant after covariate adjustment (hazard ratio 1.42, 99% confidence interval 1.09 to 1.84). The rate of early PCI complications was low in the 2 age groups. The trend toward a differential effect of PCI in the young versus the old for the primary outcome was likely driven by measured and unmeasured confounders and by chance. PCI reduces angina to a similar degree in the young and old. In conclusion, there is no indication for routine PCI to open a persistently occluded infarct-related artery in stable patients after myocardial infarction, regardless of age.

Long-term effects of percutaneous coronary intervention of the totally occluded infarct-related artery in the subacute phase after myocardial infarction.

BACKGROUND: Despite observations suggesting a benefit for late opening of totally occluded infarct-related arteries after myocardial infarction, the Occluded Artery Trial (OAT) demonstrated no reduction in the composite of death, reinfarction, and class IV heart failure over a 2.9-year mean follow-up. Follow-up was extended to determine whether late trends would favor either treatment group. METHODS AND RESULTS: OAT randomized 2201 stable patients with infarct-related artery total occlusion >24 hours (calendar days 3-28) after myocardial infarction. Patients with severe inducible ischemia, rest angina, class III-IV heart failure, and 3-vessel/left main disease were excluded. We conducted extended follow-up of enrolled patients for an additional 3 years for the primary end point and angina (6-year median survivor follow-up; longest, 9 years; 12 234 patient-years). Rates of the primary end point (hazard ratio, 1.06; 95% confidence interval, 0.88-1.28), fatal and nonfatal myocardial infarction (hazard ratio, 1.25; 95% confidence interval, 0.89-1.75), death, and class IV heart failure were similar for the percutaneous coronary intervention (PCI) and medical therapy alone groups. No interactions between baseline characteristics and treatment group on outcomes were observed. The vast majority of patients at each follow-up visit did not report angina. There was less angina in the PCI group through early in follow-up; by 3 years, the between group difference was consistently <4 patients per 100 treated and not significantly different, although there was a trend toward less angina in the PCI group at 3 and 5 years. The 7-year rate of PCI of the infarct-related artery during follow-up was 11.1% for the PCI group compared with 14.7% for the medical therapy alone group (hazard ratio, 0.79; 95% confidence interval, 0.61-1.01; P=0.06). CONCLUSIONS: Extended follow-up of the OAT cohort provides robust evidence for no reduction of long-term rates of clinical events after routine PCI in stable patients with a totally occluded infarct-related artery and without severe inducible ischemia in the subacute phase after myocardial infarction.

The Occluded Artery Trial (OAT) Viability Ancillary Study (OAT-NUC): influence of infarct zone viability on left ventricular remodeling after percutaneous coronary intervention versus optimal medical therapy alone.

BACKGROUND: The Occluded Artery Trial (OAT) showed no difference in outcomes between percutaneous coronary intervention (PCI) versus optimal medical therapy (MED) in patients with persistent total occlusion of the infarct-related artery 3 to 28 days post-myocardial infarction. Whether PCI may benefit a subset of patients with preservation of infarct zone (IZ) viability is unknown. METHODS AND RESULTS: The OAT nuclear ancillary study hypothesized that (1) IZ viability influences left ventricular (LV) remodeling and that (2) PCI as compared with MED attenuates adverse remodeling in post-myocardial infarction patients with preserved viability. Enrolled were 124 OAT patients who underwent resting nitroglycerin-enhanced technetium-99m sestamibi single-photon emission computed tomography (SPECT) before OAT randomization, with repeat imaging at 1 year. All images were quantitatively analyzed for infarct size, IZ viability, LV volumes, and function in a core laboratory. At baseline, mean infarct size was 26% ± 18 of the LV, mean IZ viability was 43% ± 8 of peak uptake, and most patients (70%) had at least moderately retained IZ viability. There were no significant differences in 1-year end-diastolic or end-systolic volume change between those with severely reduced versus moderately retained IZ viability, or when compared by treatment assignment PCI versus MED. In multivariable models, increasing baseline viability independently predicted improvement in ejection fraction (P = .005). There was no interaction between IZ viability and treatment assignment for any measure of LV remodeling. CONCLUSIONS: In the contemporary era of MED, PCI of the infarct-related artery compared with MED alone does not impact LV remodeling irrespective of IZ viability.

Loss of short-term symptomatic benefit in patients with an occluded infarct artery is unrelated to non-protocol revascularization: results from the Occluded Artery Trial (OAT).

BACKGROUND: the OAT found that routine late (3-28 days post-myocardial infarction) percutaneous coronary intervention (PCI) of an occluded infarct-related artery did not reduce death, reinfarction, or heart failure relative to medical treatment (MED). Angina rates were lower in PCI early, but the advantage over MED was lost by 3 years. METHODS: angina and revascularization status were collected at 4 months, then annually. We assessed whether non-protocol revascularization procedures in MED accounted for loss of the early symptomatic advantage of PCI. RESULTS: seven per 100 more PCI patients were angina-free at 4 months (P < .001) and 5 per 100 at 12 months (P = .005) with the difference narrowing to 1 per 100 at 3 years (P = .34). Non-protocol revascularization was more frequent in MED (5-year rate 22% vs 19% PCI, P = .05). Indications for revascularization included acute coronary syndromes (39% PCI vs 38% MED), stable angina/inducible ischemia (39% in each group), and physician preference (17% PCI vs 15% MED). Revascularization rates among patients with angina at any time during follow-up (35% of cohort) did not differ by treatment group (5-year rates 26% PCI vs 28% MED). Most symptomatic patients were treated without revascularization during follow-up (77%). CONCLUSIONS: in a large randomized clinical trial of stable post-myocardial infarction patients, the modest benefit on angina from PCI of an occluded infarct-related artery was lost by 3 years. Revascularization was slightly more common in MED during follow-up but was not driven by acute ischemia, and almost 1 in 5 procedures were attributed to physician preference alone.

Impact of collateral flow to the occluded infarct-related artery on clinical outcomes in patients with recent myocardial infarction: a report from the randomized occluded artery trial.

BACKGROUND: Collateral flow to the infarct artery territory after acute myocardial infarction may be associated with improved clinical outcomes and may also impact the benefit of subsequent recanalization of an occluded infarct-related artery. METHODS AND RESULTS: To understand the association between baseline collateral flow to the infarct territory on clinical outcomes and its interaction with percutaneous coronary intervention of an occluded infarct artery, long-term outcomes in 2173 patients with total occlusion of the infarct artery 3 to 28 days after myocardial infarction from the randomized Occluded Artery Trial were analyzed according to angiographic collaterals documented at study entry. There were important differences in baseline clinical and angiographic characteristics as a function of collateral grade, with generally lower-risk characteristics associated with higher collateral grade. Higher collateral grade was associated with lower rates of death (P=0.009), class III and IV heart failure (P<0.0001) or either (P=0.0002) but had no association with the risk of reinfarction. However, by multivariate analysis, collateral flow was neither an independent predictor of death nor of the primary end point of the trial (composite of death, reinfarction, or class IV heart failure). There was no interaction between angiographic collateral grade and the results of randomized treatment assignment (percutaneous coronary intervention or medical therapy alone) on clinical outcomes. CONCLUSIONS: In recent myocardial infarction, angiographic collaterals to the occluded infarct artery are correlates but not independent predictors of major clinical outcomes. Late recanalization of the infarct artery in addition to medical therapy shows no benefit compared with medical therapy alone, regardless of the presence or absence of collaterals. Therefore, revascularization decisions in patients with recent myocardial infarction should not be based on the presence or grade of angiographic collaterals. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00004562.

Impact of left ventricular ejection fraction on clinical outcomes over five years after infarct-related coronary artery recanalization (from the Occluded Artery Trial [OAT]).

In the Occluded Artery Trial (OAT), percutaneous coronary intervention (PCI) of an infarct-related artery on days 3 to 28 after acute myocardial infarction was of no benefit compared to medical therapy alone. The present analysis was conducted to determine whether PCI might provide benefit to the subgroup of higher risk patients with a depressed ejection fraction (EF). Of 2,185 analyzed patients (age 58.6 +/- 11.0 years) with infarct-related artery occlusion on days 3 to 28 after acute myocardial infarction in the Occluded Artery Trial, 1,094 were assigned to PCI and 1,091 to medical therapy. The primary end point was a composite of death, reinfarction, and New York Heart Association class IV heart failure. The outcomes were analyzed by EF (first tertile, EF < or =44%, vs second and third tertiles combined, EF >44%). Interaction of the treatment effect with EF on the study outcomes were examined using the Cox survival model. The 5-year rates of the primary end point (death, reinfarction, or New York Heart Association class IV heart failure) were not different in either subgroup (PCI vs medical therapy, hazard ratio 1.25, 99% confidence interval 0.83 to 1.88, for EF < or =44%; hazard ratio 0.98, 99% confidence interval 0.64 to 1.50, for EF >44%). However, in patients with an EF >44%, PCI reduced the rate of subsequent revascularization (p = 0.004, interaction p = 0.05). In conclusion, optimal medical therapy remains the overall treatment of choice for stable patients with a persistent total occlusion of the infarct-related artery after acute myocardial infarction, irrespective of the baseline EF. In patients with normal or moderately impaired left ventricular contractility, PCI reduced the need for subsequent revascularization but did not otherwise improve outcomes.

Percutaneous coronary intervention in the Occluded Artery Trial: procedural success, hazard, and outcomes over 5 years.

BACKGROUND: The Occluded Artery Trial (OAT) was a 2,201-patient randomized clinical trial comparing routine stent-based percutaneous coronary intervention (PCI) versus optimal medical therapy alone in stable myocardial infarction (MI) survivors with persistent infarct-related artery occlusion identified day 3 to 28 post MI. Intent-to-treat analysis showed no difference between strategies with respect to the incidence of new class IV congestive heart failure, MI, or death. The influence of PCI failure, procedural hazard, and crossover on trial results has not been reported. METHODS: Study angiograms were analyzed and adjudicated centrally. Factors associated with PCI failure were examined. Time-to-event analysis using the OAT primary outcome was performed by PCI success status. Landmark analysis (up to and beyond 30 days) partitioned early hazard versus late outcome according to treatment received. RESULTS: Percutaneous coronary intervention was adjudicated successful in >87%. Percutaneous coronary intervention failure rates were similar in US and non-US sites, and did not significantly influence outcome at 60 months (hazard ratio for success vs fail 0.79, 99% CI 0.45-1.40, P = .29). Partitioning of early procedural hazard revealed no late benefit for PCI (hazard ratio for PCI success vs medical therapy alone 1.06, 99% CI 0.75-1.50, P = .66). CONCLUSIONS: Percutaneous coronary intervention failure and complication rates in the OAT were low. Neither PCI failure nor early procedural hazard substantively influenced the primary trial results.

Impact of stress testing before percutaneous coronary intervention or medical management on outcomes of patients with persistent total occlusion after myocardial infarction: analysis from the occluded artery trial.

BACKGROUND: In the Occluded Artery Trial (OAT), 2,201 stable patients with an occluded infarct-related artery (IRA) were randomized to percutaneous coronary intervention (PCI) or optimal medical treatment alone (MED). There was no difference in the primary end point of death, reinfarction, or congestive heart failure (CHF). We examined the prognostic impact of prerandomization stress testing. METHODS: Stress testing was required by protocol except for patients with single-vessel disease and akinesis/dyskinesis of the infarct zone. The presence of severe inducible ischemia was an exclusion criterion for OAT. We compared outcomes based on performance and results of stress testing. RESULTS: Five hundred ninety-eight (27%) patients (297 PCI, 301 MED) underwent stress testing. Radionuclide imaging or stress echocardiography was performed in 40%. Patients who had stress testing were younger (57 vs 59 years); had higher ejection fractions (49% vs 47%); and had lower rates of death (7.8% vs 13.2%), class IV CHF (2.4% vs 5.5%), and the primary end point (13.9% vs 18.9%) than patients without stress testing (all P < .01). Mild-moderate ischemia was observed in 40% of patients with stress testing and was not related to outcomes. Among patients with inducible ischemia, outcomes were similar for PCI and MED (all P > .10). CONCLUSIONS: In OAT, patients who underwent stress testing had better outcomes than patients who did not, likely related to differences in baseline characteristics. In patients managed with optimal medical therapy or PCI, mild-moderate inducible ischemia was not related to outcomes. The lack of benefit for PCI compared to MED alone was consistent regardless of whether stress testing was performed or inducible ischemia was present.

Late coronary intervention for totally occluded left anterior descending coronary arteries in stable patients after myocardial infarction: Results from the Occluded Artery Trial (OAT).

BACKGROUND: We analyzed a prespecified hypothesis of the Occluded Artery Trial (OAT) that late percutaneous coronary intervention (PCI) of the infarct-related artery (IRA) would be most beneficial for patients with anterior myocardial infarction (MI). METHODS: Two thousand two hundred one stable, high-risk patients with total occlusion of the IRA (793 left anterior descending [LAD]) on days 3 to 28 (minimum of 24 hours) after MI were randomized to PCI and stenting with optimal medical therapy (1,101 patients) or to optimal medical therapy alone (1,100 patients). The primary end point was a composite of death, recurrent MI, or hospitalization for class IV heart failure. RESULTS: The 5-year cumulative primary end point rate was more frequent in the LAD group (19.5%) than in the non-LAD group (16.4%) (HR 1.34, 99% CI 1.00-1.81, P = .01). Within the LAD group, the HR for the primary end point in the PCI group (22.7%) compared with the medical therapy group (16.4%) was 1.35 (99% CI 0.86-2.13, P = .09), whereas in the non-LAD group the HR for the primary end point in PCI (16.9%) compared with medical therapy (15.8%) was 1.03 (99% CI 0.70-1.52, P = .83) (interaction P = .24). The results were similar when the effect of PCI was assessed in patients with proximal LAD occlusion. CONCLUSIONS: In stable patients, persistent total occlusion of the LAD post MI is associated with a worse prognosis compared with occlusion of the other IRAs. A strategy of PCI of occluded LAD IRA >24 hours post MI in stable patients is not beneficial and may increase risk of adverse events in comparison to optimal medical treatment alone.

Angiographic and clinical outcomes of drug-eluting versus bare metal stent deployment in the Occluded Artery Trial.

BACKGROUND: The majority of patients randomized to percutaneous coronary intervention (PCI) in the Occluded Artery Trial (OAT) and its angiographic substudy, the Total Occlusion Study of Canada 2 (TOSCA-2) were treated with bare metal stents (BMS). We aimed to determine if stenting of the target occlusion in OAT with drug-eluting stents (DES) was associated with more favorable angiographic results and clinical outcome when compared with treatment with BMS. METHODS: TOSCA-2 DES was a prospective nonrandomized substudy that provided 1-year angiographic comparison of late loss and reocclusion in 25 patients treated with DES and in 128 treated with BMS. In addition, all PCI-assigned patients enrolled from the time when DES were first utilized were similarly categorized (DES n = 77, and BMS n = 386) and compared using the 3-year cumulative OAT primary combined endpoint of death, myocardial infarction, or Class-IV heart failure, as well as angina. RESULTS: In-segment late loss was 0.14 +/- 0.45 mm for DES and 0.75 +/- 0.86 mm for BMS (P < 0.001). Corresponding binary restenosis rates were 13.0% and 44.3% (P = 0.005). Occlusion at 1 year was observed in 4.0 and 12.1%, respectively (P = 0.23). The 3-year cumulative primary event rate was 13.8% with DES and 12.5% with BMS (hazard ratio 1.08, 99% confidence intervals 0.44, 2.64; P = 0.83). Angina over time occurred less frequently in the DES group (P = 0.01). CONCLUSIONS: Although the reduction of late loss and trend to reduction in reocclusion with the use of DES for PCI of persistently occluded IRA 3-28 days post myocardial infarction did not translate into a signal for reduction in death, reinfarction, or Class IV heart failure, DES use was associated with less angina over time. Further follow-up is warranted.

Electrophysiological effects of late percutaneous coronary intervention for infarct-related coronary artery occlusion: the Occluded Artery Trial-Electrophysiological Mechanisms (OAT-EP).

BACKGROUND: The Occluded Artery Trial-Electrophysiological Mechanisms (OAT-EP) tested the hypothesis that opening a persistently occluded infarct-related artery by percutaneous coronary intervention and stenting (PCI) after the acute phase of myocardial infarction compared with optimal medical therapy alone reduces markers of vulnerability to ventricular arrhythmias. METHODS AND RESULTS: Between April 2003 and December 2005, 300 patients with an occluded native infarct-related artery 3 to 28 days (median, 12 days) after myocardial infarction were randomized to PCI or optimal medical therapy. Ten-minute digital Holter recordings were obtained before randomization, at 30 days, and at 1 year. The primary end point was the change in alpha1, a nonlinear heart rate variability parameter, between baseline and 1 year. Major secondary end points were the changes in the filtered QRS duration on the signal-averaged ECG and variability in T-wave morphology (T-wave variability) between baseline and 1 year. There were no significant differences in the changes in alpha1 (-0.04; 95% CI, -0.12 to 0.04), filtered QRS (2.2 ms; 95% CI, -1.4 to 5.9 ms), or T-wave variability (3.0 microV; 95% CI, -4.8 to 10.7 microV) between the PCI and medical therapy groups (medical therapy change minus PCI change). Multivariable analysis revealed that the results were unchanged after adjustment for baseline clinical variables and medication treatments during the Holter recordings. CONCLUSIONS: PCI with stenting of a persistently occluded infarct-related artery during the subacute phase after myocardial infarction compared with medical therapy alone had no significant effect on changes in heart rate variability, the time-domain signal-averaged ECG, or T-wave variability during the first year after myocardial infarction. These findings are consistent with the lack of clinical benefit, including no reduction in sudden death, with PCI for stable patients with persistently occluded infarct-related arteries after myocardial infarction in the main OAT.

Lack of benefit from percutaneous intervention of persistently occluded infarct arteries after the acute phase of myocardial infarction is time independent: insights from Occluded Artery Trial.

AIMS: The Occluded Artery Trial (OAT) (n = 2201) showed no benefit for routine percutaneous intervention (PCI) (n = 1101) over medical therapy (MED) (n = 1100) on the combined endpoint of death, myocardial infarction (MI), and class IV heart failure (congestive heart failure) in stable post-MI patients with late occluded infarct-related arteries (IRAs). We evaluated the potential for selective benefit with PCI over MED for patients enrolled early in OAT. METHODS AND RESULTS: We explored outcomes with PCI over MED in patients randomized to the