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BACKGROUND: ISCHEMIA (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) did not find an overall reduction in cardiovascular events with an initial invasive versus conservative management strategy in chronic coronary disease; however, there were conservative strategy participants who underwent invasive coronary angiography early postrandomization (within 6 months). Identifying factors associated with angiography in conservative strategy participants will inform clinical decision-making in patients with chronic coronary disease. METHODS: Factors independently associated with angiography performed within 6 months of randomization were identified using Fine and Gray proportional subdistribution hazard models, including demographics, region of randomization, medical history, risk factor control, symptoms, ischemia severity, coronary anatomy based on protocol-mandated coronary computed tomography angiography, and medication use. RESULTS: Among 2591 conservative strategy participants, angiography within 6 months of randomization occurred in 8.7% (4.7% for a suspected primary end point event, 1.6% for persistent symptoms, and 2.6% due to protocol nonadherence) and was associated with the following baseline characteristics: enrollment in Europe versus Asia (hazard ratio [HR], 1.81 [95% CI, 1.142.86]), daily and weekly versus no angina (HR, 5.97 [95% CI, 2.7812.86] and 2.63 [95% CI, 1.514.58], respectively), poor to fair versus good to excellent health status (HR, 2.02 [95% CI, 1.233.32]) assessed with Seattle Angina Questionnaire, and new/more frequent angina prerandomization (HR, 1.80 [95% CI, 1.342.40]). Baseline low-density lipoprotein cholesterol <70 mg/dL was associated with a lower risk of angiography (HR, 0.65 [95% CI, 0.460.91) but not baseline ischemia severity nor the presence of multivessel or proximal left anterior descending artery stenosis >70% on coronary computed tomography angiography. CONCLUSIONS: Among ISCHEMIA participants randomized to the conservative strategy, angiography within 6 months of randomization was performed in <10% of patients. It was associated with frequent or increasing baseline angina and poor quality of life but not with objective markers of disease severity. Well-controlled baseline low-density lipoprotein cholesterol was associated with a reduced likelihood of angiography. These findings point to the importance of a comprehensive assessment of symptoms and a review of guideline-directed medical therapy goals when deciding the initial treatment strategy for chronic coronary disease.
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BACKGROUND: Anatomic complete revascularization (ACR) and functional complete revascularization (FCR) have been associated with reduced death and myocardial infarction (MI) in some prior studies. The impact of complete revascularization (CR) in patients undergoing an invasive (INV) compared with a conservative (CON) management strategy has not been reported. OBJECTIVES: Among patients with chronic coronary disease without prior coronary artery bypass grafting randomized to INV vs CON management in the ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) trial, we examined the following: 1) the outcomes of ACR and FCR compared with incomplete revascularization; and 2) the potential impact of achieving CR in all INV patients compared with CON management. METHODS: ACR and FCR in the INV group were assessed at an independent core laboratory. Multivariable-adjusted outcomes of CR were examined in INV patients. Inverse probability weighted modeling was then performed to estimate the treatment effect had CR been achieved in all INV patients compared with CON management. RESULTS: ACR and FCR were achieved in 43.4% and 58.4% of 1,824 INV patients. ACR was associated with reduced 4-year rates of cardiovascular death or MI compared with incomplete revascularization. By inverse probability weighted modeling, ACR in all 2,296 INV patients compared with 2,498 CON patients was associated with a lower 4-year rate of cardiovascular death or MI (difference -3.5; 95% CI: -7.2% to 0.0%). In comparison, the event rate difference of cardiovascular death or MI for INV minus CON in the overall ISCHEMIA trial was -2.4%. Results were similar but less pronounced with FCR. CONCLUSIONS: The outcomes of an INV strategy may be improved if CR (especially ACR) is achieved. (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches [ISCHEMIA]; NCT01471522).
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Enfermedad de la Arteria CoronariaRESUMEN
BACKGROUND: Whether initial invasive management in older vs younger adults with chronic coronary disease and moderate or severe ischemia improves health status or clinical outcomes is unknown. OBJECTIVES: The goal of this study was to examine the impact of age on health status and clinical outcomes with invasive vs conservative management in the ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) trial. METHODS: One-year angina-specific health status was assessed with the 7-item Seattle Angina Questionnaire (SAQ) (score range 0-100; higher scores indicate better health status). Cox proportional hazards models estimated the treatment effect of invasive vs conservative management as a function of age on the composite clinical outcome of cardiovascular death, myocardial infarction, or hospitalization for resuscitated cardiac arrest, unstable angina, or heart failure. RESULTS: Among 4,617 participants, 2,239 (48.5%) were aged <65 years, 1,713 (37.1%) were aged 65 to 74 years, and 665 (14.4%) were aged ≥75 years. Baseline SAQ summary scores were lower in participants aged <65 years. Fully adjusted differences in 1-year SAQ summary scores (invasive minus conservative) were 4.90 (95% CI: 3.56-6.24) at age 55 years, 3.48 (95% CI: 2.40-4.57) at age 65 years, and 2.13 (95% CI: 0.75-3.51) at age 75 years (Pinteraction = 0.008). Improvement in SAQ Angina Frequency was less dependent on age (Pinteraction = 0.08). There were no age differences between invasive vs conservative management on the composite clinical outcome (Pinteraction = 0.29). CONCLUSIONS: Older patients with chronic coronary disease and moderate or severe ischemia had consistent improvement in angina frequency but less improvement in angina-related health status with invasive management compared with younger patients. Invasive management was not associated with improved clinical outcomes in older or younger patients. (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches [ISCHEMIA]; NCT01471522).
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Persona de Mediana Edad , Anciano , Calidad de Vida , Enfermedad de la Arteria CoronariaRESUMEN
BACKGROUND: The ISCHEMIA trial (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) postulated that patients with stable coronary artery disease (CAD) and moderate or severe ischemia would benefit from revascularization. We investigated the relationship between severity of CAD and ischemia and trial outcomes, overall and by management strategy. METHODS: In total, 5179 patients with moderate or severe ischemia were randomized to an initial invasive or conservative management strategy. Blinded, core laboratoryinterpreted coronary computed tomographic angiography was used to assess anatomic eligibility for randomization. Extent and severity of CAD were classified with the modified Duke Prognostic Index (n=2475, 48%). Ischemia severity was interpreted by independent core laboratories (nuclear, echocardiography, magnetic resonance imaging, exercise tolerance testing, n=5105, 99%). We compared 4-year event rates across subgroups defined by severity of ischemia and CAD. The primary end point for this analysis was all-cause mortality. Secondary end points were myocardial infarction (MI), cardiovascular death or MI, and the trial primary end point (cardiovascular death, MI, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest). RESULTS: Relative to mild/no ischemia, neither moderate ischemia nor severe ischemia was associated with increased mortality (moderate ischemia hazard ratio [HR], 0.89 [95% CI, 0.611.30]; severe ischemia HR, 0.83 [95% CI, 0.571.21]; P=0.33). Nonfatal MI rates increased with worsening ischemia severity (HR for moderate ischemia, 1.20 [95% CI, 0.861.69] versus mild/no ischemia; HR for severe ischemia, 1.37 [95% CI, 0.981.91]; P=0.04 for trend, P=NS after adjustment for CAD). Increasing CAD severity was associated with death (HR, 2.72 [95% CI, 1.066.98]) and MI (HR, 3.78 [95% CI, 1.638.78]) for the most versus least severe CAD subgroup. Ischemia severity did not identify a subgroup with treatment benefit on mortality, MI, the trial primary end point, or cardiovascular death or MI. In the most severe CAD subgroup (n=659), the 4-year rate of cardiovascular death or MI was lower in the invasive strategy group (difference, 6.3% [95% CI, 0.2%12.4%]), but 4-year all-cause mortality was similar. CONCLUSIONS: Ischemia severity was not associated with increased risk after adjustment for CAD severity. More severe CAD was associated with increased risk. Invasive management did not lower all-cause mortality at 4 years in any ischemia or CAD subgroup.
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Enfermedad de la Arteria Coronaria , Intervención Coronaria Percutánea , Isquemia , Revascularización Miocárdica , Puente de Arteria CoronariaRESUMEN
Background: It is unknown whether an initial invasive strategy in patients with stable ischemic heart disease and at least moderate ischemia improves outcomes in patients with a history of heart failure (HF) or left ventricular dysfunction (LVD) when EF >35%, but <45%. Methods: Among 5179 participants randomized into the International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA), all of whom had LVEF >35%, we compared cardiovascular outcomes by treatment strategy in those with a history of HF or LV dysfunction (HF/LVD) at baseline versus those without HF/LVD. Median follow up was 3.2 years. Results: There were 398 (7.7%) participants with HF/LVD at baseline of whom 177 had HF/LVEF>45%, 28 had HF/LVEF 35-45% and 193 had LVEF 35-45% but no prior history of HF. HF/LVD was associated with more comorbidities at baseline, particularly prior myocardial infarction (MI), stroke and hypertension. Compared to those without HF/LVD, those with HF/LVD were more likely to experience a primary outcome composite of cardiovascular death, nonfatal MI, or hospitalization for unstable angina, HF, or resuscitated cardiac arrest; four-year cumulative incidence rate (22.7% vs. 13.8%), cardiovascular death or MI (19.7% vs. 12.3%), and all-cause death or HF (15.0% vs. 6.9%). Those with HF/LVD randomized to the invasive versus conservative strategy had a lower rate of the primary outcome (17.2% vs. 29.3%, difference in 4- year event rate -12.1%; 95% CI: -22.6, -1.6%), whereas those without HF/LVD did not (13.0% vs. 14.6%, difference in 4-year event rate -1.6%; 95% CI: -3.8%, 0.7%; p-interaction = 0.055). A similar differential effect was seen for the primary outcome, all-cause mortality, and CV mortality when invasive versus conservative strategy associated outcomes were analyzed with LVEF as a continuous variable for those with and without prior HF. Conclusions: ISCHEMIA trial participants with stable ischemic heart disease and at least moderate ischemia with a history of HF or LVD were at increased risk for the primary outcome. In the small, high-risk subgroup with HF and LVEF 35-45%, an initial invasive approach was associated with a better event-free survival. This result should be considered hypothesis generating.
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Tratamiento Conservador , Insuficiencia Cardíaca , IsquemiaRESUMEN
BACKGROUND: Recent trials have reported similar clinical outcomes between on-pump and off-pump coronary artery bypass graft (CABG). However, long-term cost-effectiveness of these strategies is unknown. METHODS: A prespecified economic study was performed based on the MASS III trial. Costs were estimated for all patients based on observed healthcare resource usage over a 5-year follow-up. Health state utilities were evaluated with the SF-6D questionnaire. Cost-effectiveness was assessed as cost per quality-adjusted life-year (QALY) gained using a Markov model. Probabilistic sensitivity analysis with the Monte-Carlo simulation and cost-effectiveness acceptability curve were used to address uncertainty. RESULTS: Quality of life improved significantly in both groups during follow-up compared with baseline. At 5â¯years, when comparing on-pump and off-pump CABG groups, no differences were found in cumulative life-years (4.851 and 4.766â¯years, Pâ¯=â¯.319) and QALY gained (4.150 and 4.105 QALYs, Pâ¯=â¯.332). Mean cost in US dollars per patient during the trial did not differ significantly between the on-pump and off-pump groups ($5890.29 and $5674.75, respectively, Pâ¯=â¯.409). Over a lifetime horizon, the incremental cost-effectiveness ratio of on-pump versus off-pump CABG was $12,576 per QALY gained, which is above the suggested cost-effectiveness threshold range (from $3210 to 10,122). In the sensitivity analysis, the probability that on-pump CABG is cost-effective compared to off-pump surgery for a willingness-to-pay threshold of $3212 per QALY gained was <1%. For the $10,122 per QALY threshold, the same probability was 35%. CONCLUSION: This decision-analytic model suggests that on-pump CABG is not cost-effective when compared to off-pump CABG from a public health system perspective.
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Puente de Arteria Coronaria Off-Pump/economía , Puente de Arteria Coronaria/economía , Enfermedad de la Arteria Coronaria/economía , Enfermedad de la Arteria Coronaria/cirugía , Análisis Costo-Beneficio/métodos , Brasil/epidemiología , Puente de Arteria Coronaria/tendencias , Puente de Arteria Coronaria Off-Pump/tendencias , Enfermedad de la Arteria Coronaria/epidemiología , Análisis Costo-Beneficio/tendencias , Femenino , Estudios de Seguimiento , Humanos , Masculino , Cadenas de MarkovRESUMEN
OBJECTIVES: To determine whether sex-based differences exist in clinical effectiveness of percutaneous coronary intervention (PCI) when added to optimal medical therapy (OMT) in patients with stable coronary artery disease. BACKGROUND: A prior pre-specified unadjusted analysis from COURAGE showed that women randomized to PCI had a lower rate of death or myocardial infarction during a median 4.6-year follow-up with a trend for interaction with respect to sex. METHODS: We analyzed outcomes in 338 women (15%) and 1949 men (85%) randomized to PCI plus OMT versus OMT alone after adjustment for relevant baseline characteristics. RESULTS: There was no difference in treatment effect by sex for the primary end point (death or myocardial infarction; HR, 0.89; 95% CI, 0.77-1.03 for women and HR, 1.02, 95% CI 0.96-1.10 for men; P for interaction = .07). Although the event rate was low, a trend for interaction by sex was nonetheless noted for hospitalization for heart failure, with only women, but not men, assigned to PCI experiencing significantly fewer events as compared to their counterparts receiving OMT alone (HR, 0.59; 95% CI, 0.40-0.84, P < .001 for women and HR, 0.86; 95% CI, 0.74-1.01, P = .47 for men; P for interaction = .02). Both sexes randomized to PCI experienced significantly reduced need for subsequent revascularization (HR, 0.72; 95% CI, 0.62-0.83, P < .001 for women; HR, 0.84; 95% CI, 0.79-0.89, P < .001 for men; P for interaction = .02) with evidence of a sex-based differential treatment effect. CONCLUSION: In this adjusted analysis of the COURAGE trial, there were no significant differences in treatment effect on major outcomes between men and women. However, women assigned to PCI demonstrated a greater benefit as compared to men, with a reduction in heart failure hospitalization and need for future revascularization. These exploratory observations require further prospective study.