The incidence and predictors of heart failure (HF) post myocardial infarction (MI) with modern post-MI treatment have not been well characterized.
Methods and Results
2201 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 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 prior to 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=0.97). Adjudicated HF hospitalization was associated with subsequent death (44.0% vs. 13.1%, HR 3.31, 99% CI 2.21–4.92, p<0.001). 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<0.001) and death (24.7% vs. 10.8%, HR 2.31, 99% CI 1.71–3.10, p<0.001).
In the overall 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.
Heart Failure; Myocardial Infarction; Occlusion; Revascularization
Renal dysfunction is an independent predictor of cardiovascular events and a negative prognostic indicator after myocardial infarction (MI). Randomized data comparing percutaneous coronary intervention (PCI) to medical therapy in MI patients with renal insufficiency are needed. The Occluded Artery Trial (OAT) compared optimal medical therapy alone to PCI with optimal medical therapy in 2201 high risk patients with an occluded infarct artery >24 hours post-MI with serum creatinine ≤2.5 mg/dl. The primary endpoint was a composite of death, MI, and class IV heart failure (HF). Analyses were carried out utilizing estimated glomerular filtration rates (eGFR) as a continuous variable and by eGFR categories. Long term follow up data (maximum 9 years) were used for this analysis. Lower eGFR (ml/min/1.73m2) was associated with development of the primary outcome (6-year life-table rate 16.9% in eGFR>90; 19.2% in eGFR 60–89; 34.9% in eGFR<60; p-value <0.0001), death, and class IV HF, with no difference in rates of reinfarction. On multivariable analysis, eGFR was an independent predictor of death and HF. There was no effect of treatment assignment on the primary endpoint 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 PCI in the overall trial was also seen in patients with renal dysfunction and persistent occlusion of the infarct artery in the subacute phase post MI.
Myocardial Infarction; Stents and Kidney Disease
Despite the known benefits of regular exercise, the reasons why many coronary heart disease (CHD) patients engage in little physical activity are not well understood. This study identifies factors associated with low activity levels in individuals with chronic CHD participating in the STABILITY study, a global clinical outcomes trial evaluating the lipoprotein phospholipaseA2 inhibitor darapladib.
Methods and results
Prior to randomization, 15 486 (97.8%) participants from 39 countries completed a lifestyle questionnaire. Total physical activity was estimated from individual subject self-reports of hours spend each week on mild, moderate, and vigorous exercise, corresponding approximately to 2, 4, and 8 METS, respectively. Multivariate logistic regression evaluated clinical and demographic variables for the lowest compared with higher overall exercise levels, and for individuals who decreased rather than maintained or increased activity since diagnosis of CHD. The least active 5280 subjects (34%) reported exercise of ≤24MET.h/week. A total of 7191 subjects (46%) reported less exercise compared with before diagnosis of CHD. The majority of participants were either ‘not limited’ or ‘limited a little’ walking 100 m (84%), climbing one flight of stairs (82%), or walking 1 km/½ mile (68%), and <10% were limited ‘a lot’ by dyspnoea or angina. Variables independently associated with both low physical activity and decreasing exercise after diagnosis of CHD included more co-morbid conditions, poorer general health, fewer years of education, race, and country (P < 0.001 for all).
In this international study, low physical activity was only partly explained by cardiovascular symptoms. Potentially modifiable societal and health system factors are important determinants of physical inactivity in patients with chronic CHD.
Physical activity; Exercise; Coronary artery disease; Cardiac rehabilitation
The Occluded Artery Trial (OAT) was a large, randomized controlled trial published in 2006 that demonstrated no benefit to routine percutaneous coronary intervention (PCI) of persistently totally occluded infarct-related arteries (IRA) identified a minimum of 24 hours (on calendar days 3–28) after myocardial infarction (MI). The purpose of this study was to determine the impact of OAT results and consequent change in guideline recommendations for PCI for treatment of persistently occluded IRAs.
We identified all patients enrolled in the CathPCI Registry, from 2005 to 2008, undergoing catheterization more than 24 hours after MI with a totally occluded native coronary artery and no major OAT exclusion criteria. We examined trends in monthly rates of PCI for occlusions after OAT publication and after guideline revisions. Because reporting of diagnostic catheterizations was not mandatory, we examined trends among hospitals in the highest quartile for reporting of diagnostic procedures.
A total of 28 780 patient visits from 896 hospitals were included. Overall, we found no significant decline in the adjusted monthly rate of PCI of occlusions after publication of OAT (odds ratio [OR], 0.997; 95% confidence interval [CI], 0.989–1.006) or after guideline revisions (OR, 1.007; 95% CI, 0.992–1.022). Among hospitals consistently reporting diagnostic catheterizations, there was no significant decline after OAT publication (OR, 1.018; 95% CI, 0.995–1.042), and there was a trend toward decline after guideline revisions (OR, 0.963; 95% CI, 0.920–1.000).
These findings suggest that the results of OAT and consequent guideline revisions have not, to date, been fully incorporated into clinical practice in a large cross-section of hospitals in the United States.
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.
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).
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).
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.
Larger infarct size measured by creatine kinase (CK)-MB release is associated with higher mortality and has been used as an important surrogate endpoint in the evaluation of new treatments for ST-segment elevation myocardial infarction (STEMI). Traditional approaches to quantify infarct size include the observed CK-MB peak and calculated CK-MB area under the curve (AUC). We evaluated alternative approaches to quantifying infarct size using CK-MB values, and the relationship between infarct size and clinical outcomes.
Of 1,850 STEMI patients treated with reperfusion therapy in the COMplement inhibition in Myocardial infarction treated with Angioplasty (COMMA) (percutaneous coronary intervention (PCI)-treated) and the COMPlement inhibition in myocardial infarction treated with thromboLYtics (COMPLY) (fibrinolytic-treated) trials, 1,718 (92.9%) (COMMA, n = 868; COMPLY, n = 850) had at least five of nine protocol-required CK-MB measures. In addition to traditional methods, curve-fitting techniques were used to determine CK-MB AUC and estimated peak CK-MB. Cox proportional hazards modeling assessed the univariable associations between infarct size and mortality, and the composite of death, heart failure, shock and stroke at 90 days.
In COMPLY, CK-MB measures by all methods were significantly associated with higher mortality (hazard ratio range per 1,000 units increase: 1.09 to 1.13; hazard ratio range per 1 standard deviation increase: 1.41 to 1.62; P <0.01 for all analyses). In COMMA, the associations were similar but did not reach statistical significance. For the composite outcome of 90-day death, heart failure, shock and stroke, the associations with all CK-MB measures were statistically significant in both the COMMA and COMPLY trials.
Sophisticated curve modeling is an alternative to infarct-size quantification in STEMI patients, but it provides information similar to that of more traditional methods. Future studies will determine whether the same conclusion applies in circumstances other than STEMI, or to studies with different frequencies and patterns of CK-MB data collection.
Creatine kinase-MB; Infarct size; ST-segment elevation myocardial infarction; Clinical outcomes
There is no angiographically demonstrable obstructive coronary artery
disease (CAD) in a significant minority of patients with myocardial
infarction (MI), particularly women. We sought to determine mechanism(s) of
MI in this setting using multiple imaging techniques.
Methods and Results
Women with MI were enrolled prospectively, prior to angiography if
possible. Women with ≥50% angiographic stenosis or use of
vasospastic agents were excluded. Intravascular ultrasound (IVUS) was
performed during angiography and cardiac magnetic resonance imaging (CMR)
within one week. Fifty women (age 57±13 years) had median peak
troponin 1.60 ng/ml; 11 had ST elevation. Median diameter stenosis of the
worst lesion was 20% by angiography; 15 patients (30%) had
normal angiograms. Plaque disruption was observed in 16/42 patients
(38%) undergoing IVUS. There were abnormal myocardial CMR findings
in 26/44 patients (59%) undergoing CMR: late gadolinium enhancement
(LGE) in 17 and T2 signal hyperintensity indicating edema in 9 additional
patients. The most common LGE pattern was ischemic
(transmural/subendocardial). Non-ischemic LGE patterns
(midmyocardial/subepicardial) were also observed. LGE was infrequent with
plaque disruption but T2 signal hyperintensity was common with plaque
Plaque rupture and ulceration are common in women with MI without
angiographically demonstrable obstructive CAD. LGE is also common in this
cohort of women, with an ischemic pattern of injury most evident. Vasospasm
and embolism are possible mechanisms of ischemic LGE without plaque
disruption. IVUS and CMR provide complementary mechanistic insights in
female MI patients without obstructive CAD and may be useful in identifying
potential etiologies and therapies.
myocardial infarction; magnetic resonance imaging; coronary disease; imaging
While opening an occluded infarct-related artery (IRA) > 24 hours post myocardial infarction in stable patients in the Occluded Artery Trial (OAT) did not reduce events over 7 years, there was a suggestion that effect of treatment may differ by patient age. Baseline characteristics and outcomes by treatment with percutaneous coronary intervention (PCI) vs. optimal medical therapy (MED) alone were compared by pre-specified stratification at age 65. P<0.01 was pre-specified as significant for OAT secondary analyses. The primary outcome was death, myocardial infarction or Class IV heart failure. Patients > 65 years of age (n=641) were more likely to be female, non-smokers, and to have hypertension, lower estimated glomerular filtration rate and multivessel disease compared to younger patients (age ≤ 65, n=1560), p<0.001. There was no significant observed interaction between treatment assignment and age for the primary outcome after adjustment (p=0.1) and there was no difference between PCI and MED observed in either age group. At 7 year follow-up, younger patients tended to have angina more often compared to the older group (H.R. 1.21, 99% CI: 1.00–1.46, p=0.01). The 7-year composite primary outcome was more common in older patients (p<0.001), and age remained significant after co-variate adjustment (H.R. 1.42, 99% CI: 1.09–1.84). The rate of early PCI complications was low in both age groups. The trend toward a differential effect of PCI in the young vs. 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. There is no indication for routine PCI to open a persistently occluded IRA in stable patients post-MI regardless of age.
Elderly; PCI; Age; occlusion
Long-term follow-up (up to 9 years) from the Occluded Artery Trial (OAT) allows for examination of sex differences in outcomes and the effect of PCI in a relatively homogeneous cohort of MI survivors.
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.
Women were older and more likely to have LAD infarct-related artery, diabetes and hypertension, history of heart failure and rales at randomization, but less likely to smoke. The proportion and characteristics of women enrolled in the trial and the registry were similar, including LVEF and extent of disease. Women had higher rates of the primary composite [HR 1.48, p=0.0002], death [HR 1.50, p=0.001] and heart failure [HR 2.53, p<0.0001] but not reinfarction [HR 1.12, p=0.57]. Female sex was not independently associated with the primary endpoint or death on multivariate analysis. There was a trend toward independent association of female sex with heart failure [HR 1.66, p=0.02].
Women in OAT had a higher primary endpoint event rate than 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 LVEF by sex.
Despite observations suggesting a benefit for late opening of occluded infarct-related arteries (IRA) post-myocardial infarction (MI), the Occluded Artery Trial (OAT) demonstrated no reduction in the composite of death, reinfarction and class IV heart failure (HF) over 2.9-yearmean 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 IRA occlusion >24hours (calendar days3-28) after MI. Severe inducible ischemia, rest angina, class III-IV HF and 3-vessel/left main disease were excluded. We conducted extended followed up of enrolled patients for an additional 3 years for the primary endpoint and angina (6-year median survivor follow up, longest 9 years, 12,234 patient-years).Rates of the primary endpoint (HR 1.06, 95% CI 0.88-1.28), fatal and nonfatal MI (HR 1.25, 95% CI 0.89-1.75), death and class IV HF were similar for PCI vs. MED groups. No interaction 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 though there was a trend toward less angina in the PCI group at 3 and 5 years. The 7-year rate of PCI of the IRA during follow up was 11.1% for the PCI group compared to 14.7% for the MED group (HR 0.79, 95% CI 0.61-1.01. p=0.06).
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 an occluded IRA and without severe inducible ischemia in the subacute phase post-MI.
myocardial infarction; stents; trials
In patients with cardiogenic shock (CS) complicating an acute myocardial infarction, a strategy of emergency revascularization vs. initial medical stabilization improves survival. Intra-aortic balloon counterpulsation (IABC) provides hemodynamic support and facilitates coronary angiography and revascularization in CS patients.
Methods and Results
We evaluated 499 patients with record of systemic hypoperfusion status, as an early response to IABC from the SHOCK Trial (n=185) and Registry (n=314) to determine the association between rapid complete reversal of systemic hypoperfusion following 30 minutes of IABC(CRH)and 30-day and 1-year mortality. CRH was highly associated with lower 30-day mortality (45% vs. 78%, p<0.001) in all patients. In the SHOCK Trial, among patients assigned to ERV vs. IMS, 30-day mortality was 26% vs. 29% with CRH, and 61% vs. 81% respectively without CRH, after commencing IABC. The corresponding 1-year mortality rates were 35% vs. 52% for ERV and 69% vs. 87% for IMS (interaction p ≥ 0.25 at both time points). After adjusting for important correlates of outcome (LV ejection fraction, age, and randomization to ERV) a significant association remained between CRH and 30-day mortality (odds ratio 0.18; 95% CI 0.08–0.42, p<0.001) and 1-year mortality (odds ratio 0.28; 95% CI 0.12–0.67, p<0.001).
In CS patients, CRH after commencing IABC was independently associated with improved 30-day and 1-year survival regardless of emergency revascularization. In CS patients, CRH with IABC is an important early prognostic feature.
cardiogenic shock; intra-aortic balloon counterpulsation; systemic hypoperfusion; survival
The Occluded Artery Trial (OAT) showed no difference in outcomes between percutaneous coronary intervention (PCI) vs. optimal medical therapy (MED) in patients with persistent total occlusion of the infarct related artery (IRA) 3–28 days post-MI. 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 to MED attenuates adverse remodeling in post-MI patients with preserved viability. Enrolled were 124 OAT patients, who underwent resting nitroglycerin-enhanced 99mTc sestamibi SPECT prior to 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 lab. At baseline, mean infarct size was 26%±18 of the LV, mean IZ viability was 43%±8 of peak uptake, and the majority (70%) of patients had at least moderately retained IZ viability. There were no significant differences in 1-year EDV or ESV change between those with severely reduced vs. moderately retained IZ viability, or when compared by treatment assignment PCI vs. MED. In multivariable models, increasing baseline viability independently predicted improvement in EF (p=0.005). There was no interaction between IZ viability and treatment assignment for any measure of LV remodeling.
In the contemporary era of optimal medical therapy, PCI of the IRA compared to medical therapy alone does not impact LV remodeling irrespective of IZ viability.
Acute Coronary Syndrome; Total Occlusions; Percutaneous Coronary Intervention; Coronary Flow; Viability; Remodeling
The Occluded Artery Trial found that routine late (3–28d post-MI) percutaneous coronary intervention (PCI) of an occluded infarct-related artery (IRA) did not reduce death, re-infarction 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.
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.
Seven per 100 more PCI patients were angina-free at 4 months (p<0.001) 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-yr 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%).
In a large randomized clinical trial of stable post-MI patients, the modest benefit on angina from PCI of an occluded IRA was lost by 3 years. Revascularization was slightly more common in MED during follow up but was not driven by acute ischemia, and almost one in five procedures were attributed to physician preference alone.
Collateral flow to the infarct artery territory after acute myocardial infarction may be associated with improved clinical outcomes and may also influence 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 PCI 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 OAT randomized 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 endpoint 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 (PCI or medical therapy alone) on clinical outcomes.
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 to medical therapy alone, regardless of the presence or absence of collaterals. Therefore, revascularisation decisions in patients with recent myocardial infarction should not be based on the presence or grade of angiographic collaterals.
collaterals; heart failure; myocardial infarction; recanalization
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 ≤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 five-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 ≤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.
To study if impaired renal function is associated with increased risk of peri-infarct heart failure (HF) in patients with preserved ejection fraction (EF).
Patients with occluded infarct-related arteries (IRAs) between 1 to 28 d after myocardial infarction (MI) were grouped into chronic kidney disease (CKD) stages based on estimated glomerular filtration rate (eGFR). Rates of early post-MI HF were compared among eGFR groups. Logistic regression was used to explore independent predictors of HF.
Reduced eGFR was present in 71.1% of 2160 patients, with significant renal impairment (eGFR < 60 mL/min every 1.73 m2) in 14.8%. The prevalence of HF was higher with worsening renal function: 15.5%, 17.8% and 29.4% in patients with CKD stages 1, 2 and 3 or 4, respectively (P < 0.0001), despite a small absolute difference in mean EF across eGFR groups: 48.2 ± 10.0, 47.9 ± 11.3 and 46.2 ± 12.1, respectively (P = 0.02). The prevalence of HF was again higher with worsening renal function among patients with preserved EF: 10.1%, 13.6% and 23.6% (P < 0.0001), but this relationship was not significant among patients with depressed EF: 27.1%, 26.2% and 37.9% (P = 0.071). Moreover, eGFR was an independent correlate of HF in patients with preserved EF (P = 0.003) but not in patients with depressed EF (P = 0.181).
A significant proportion of post-MI patients with occluded IRAs have impaired renal function. Impaired renal function was associated with an increased rate of early post-MI HF, the association being strongest in patients with preserved EF. These findings have implications for management of peri-infarct HF.
Heart failure; Myocardial infarction; Kidney disease
As of April 2007 the early open artery hypothesis is alive and well, but the late open artery hypothesis is adrift. For the foreseeable future, stable patients with persistent occlusion of the infarct artery late after myocardial infarction, and without severe ischaemia or uncontrollable angina, should be managed initially with optimal medical treatment alone, and not with percutaneous coronary intervention. Efforts should focus on establishing reperfusion earlier, including reducing the time to patient presentation.
open artery hypothesis; Occluded Artery Trial
OAT randomised patients with an occluded infarct artery three to 28 days after myocardial infarction (MI). The study demonstrated that PCI did not reduce the occurrence of the primary composite endpoint of death, re-MI, and New York Heart Association class IV heart failure in comparison with patients assigned to optimal medical therapy alone (MED). In view of prior literature in similar cohorts showing fewer sudden cardiac deaths and less left ventricular (LV) remodelling, but excess re-MI with PCI, causes of death were analysed in more detail.
Methods and results
Stepwise Cox regression was used to examine baseline variables associated with causes of death. The immediate and primary cause of death did not differ between 1,101 PCI and 1,100 MED patients. One-year cardiovascular death rates were 3.8% for the PCI group, and 3.7% for the MED group, and 0.9% per year for the next four years in both groups. Five of six cases of cardiac rupture occurred in patients undergoing PCI.
In stable post-MI patients with occlusion of the infarct-related artery, PCI did not change the rate or cause of death. The observation that the majority of cardiac ruptures occurred in patients undergoing PCI deserves further investigation.
Myocardial infarction; causes of death; percutaneous coronary intervention; cardiac rupture
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.
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.
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).
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.
There is conflicting information about whether sex-differences modulate short-term mortality following acute coronary syndromes (ACS).
To investigate the relationship between sex and 30-day mortality in ACS, and determine whether this relationship is modified by clinical syndrome or coronary anatomy using a large database across the spectrum of ACS and adjusting for potentially confounding clinical covariates.
Design Setting and Participants
Data from 11 ACS trials from 1993 to 2006 were pooled. Of 136,247 patients, 38,048 (28%) were women; 102,004 (26% women) STEMI, 14,466 (29% women) NSTEMI and 19,777 (40% women) unstable angina (UA).
Main Outcome Measure
Thirty-day mortality following ACS.
Mortality at 30 days was 9.6% in women and 5.3% in men (odds ratio [OR] 1.91, 95% confidence interval [CI] 1.83–2.00). After multivariable adjustment, mortality was not significantly different between women and men (adjusted OR 1.06, 95% CI 0.99–1.15). Importantly, a significant sex by type of ACS interaction was demonstrated (P<0.001). In STEMI, 30-day mortality was higher among women (adjusted OR 1.15, 95% CI 1.06–1.24), whereas NSTEMI (adjusted OR 0.77, 95% CI 0.63–0.95), and UA mortality was lower among women (adjusted OR 0.55, 95% CI 0.43–0.70). In a cohort of 35,128 patients with angiographic data, women more often had non-obstructive (15% vs. 8%,) and less often had 2-vessel (25% vs. 28%) and 3-vessel (23% vs. 26%) coronary disease regardless of ACS type. After additional adjustment for angiographic disease severity, 30-day mortality among women was not significantly different than men, regardless of ACS type. The relationship between sex and 30-day mortality was similar across the levels of angiographic disease severity (p-value for interaction =0.70),
Sex-based differences exist in 30-day mortality among ACS patients and vary depending on clinical presentation. However, these differences are markedly attenuated following adjustment for clinical differences and angiographic data.
To assess the incidence and timing of atrial fibrillation (AF), describe antithrombotic therapy use, and evaluate the association of AF with 90 day mortality and other secondary clinical outcomes.
Methods and results
We studied 5745 ST-segment elevation myocardial infarction patients treated with primary percutaneous coronary intervention (PCI) in APEX-AMI. Approximately 11% had AF during hospitalization. Atrial fibrillation prevalence at baseline and at discharge was 4.8% [confidence interval (CI) 4.3–5.4%] and 2.5% (CI 2.1–2.9%), respectively. The proportion of 5466 patients without AF at baseline who developed new onset AF was 6.3% (CI 5.6–6.9%). This corresponded to 9.3 cases of new onset AF/1000 patient days at risk. New onset AF was independently associated with 90 day mortality [adjusted hazard ratio (HR) 1.81; 95% CI 1.06–3.09; P = 0.029] after accounting for baseline covariates and in-hospital procedures and complications. New onset AF was associated with shock (adjusted HR 3.81; 95% CI 1.88–7.70; P = 0.0002), congestive heart failure (adjusted HR 2.66; 95% CI 1.74–4.06; P < 0.0001), and stroke (adjusted HR 2.98; 95% CI 1.47–6.04; P = 0.0024) in models accounting for baseline covariates. Of AF patients, 55% did not receive oral anticoagulation therapy at discharge. Among patients with coronary stents, 5.1% were discharged on triple therapy. Patients at highest risk of stroke (CHADS2 score ≥2) were least likely to receive oral anticoagulation at discharge (39%). Warfarin use in patients with AF at discharge (43.4%) was associated with lower rates of 90 day mortality and stroke.
Atrial fibrillation prevalence at baseline and at discharge was 4.8 and 2.5%, respectively. The proportion of patients who developed new onset AF was 6.3%. New onset AF was independently associated with 90 day mortality and was a marker of adverse outcomes in patients undergoing primary PCI.
Atrial fibrillation; Myocardial infarction; Antithrombotic therapy; Outcomes
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.
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.
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).
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.
open artery hypothesis; percutaneous coronary intervention; drug-eluting stent; bare metal stent; angina
In the Occluded Artery Trial (OAT), 2201 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 endpoint of death, re-MI or heart failure (CHF). We examined the prognostic impact of pre-randomization stress testing.
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.
598 (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 endpoint (13.9% vs. 18.9%) than patients without stress testing (all p<0.01). 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>0.1).
In OAT, patients who underwent stress testing had better outcomes than patients who did not, likely related to differences in age and LV function. 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.
The open artery hypothesis postulates that late opening of an infarct-related artery after myocardial infarction (MI) will improve clinical outcomes. The quality of life (QOL) and economic outcomes associated with this strategy have not been described.
The Occluded Artery Trial (OAT) compared percutaneous coronary intervention (PCI) plus stenting with medical therapy alone in stable, high-risk patients who had a totally occluded infarct-related artery at 3 to 28 days post-MI. In 951 patients (44% of those eligible), QOL was assessed by a battery that included two principal outcome measures, the Duke Activity Status Index (DASI) reflecting cardiac-related physical functioning, and the Rand Short-Form 36 Mental Health Inventory 5 reflecting psychological well-being. Structured QOL interviews were performed at baseline, 4, 12, and 24 months. Costs were measured in 458 of 469 U.S. patients (98%) and 2-year cost effectiveness was estimated.
At 4 months, the medical therapy group showed a clinically marginal 3.4-point decline in DASI relative to the PCI group (p=0.007). At 1 and 2 years, the differences were smaller. No significant differences in psychological well-being were observed. In the 469 US OAT patients, cumulative 2-year costs were about $7,000 higher in the PCI group (p<0.0001) while quality-adjusted survival was marginally higher in the medical therapy group.
In this trial, PCI was associated with a marginal advantage in cardiac physical functioning at 4 months but not thereafter. At 2 years, medical therapy remained significantly less expensive than routine PCI and had higher quality-adjusted survival.
Percutaneous coronary intervention; quality of life; costs; coronary artery disease; myocardial infarction