ABSTRACT
Importance: Prior trials of invasive vs conservative management of chronic coronary disease (CCD) have not enrolled patients with severe chronic kidney disease (CKD). As such, outcomes across kidney function are not well characterized. Objectives: To evaluate clinical and quality-of-life (QoL) outcomes across the spectrum of CKD following conservative and invasive treatment strategies. Design, Setting, and Participants: Participants from the International Study of Comparative Health Effectiveness With Medical and Invasive Approaches (ISCHEMIA) and ISCHEMIA-Chronic Kidney Disease (CKD) trials were categorized by CKD stage: stage 1 (estimated glomerular filtration rate [eGFR] 90 mL/min/1.73m2 or greater), stage 2 (eGFR 60-89 mL/min/1.73m2), stage 3 (eGFR 30-59 mL/min/1.73m2), stage 4 (eGFR 15-29 mL/min/1.73m2), or stage 5 (eGFR less than 15 mL/min/1.73m2 or receiving dialysis). Enrollment took place from July 26, 2012, through January 31, 2018, with a median follow-up of 3.1 years. Data were analyzed from January 2020 to May 2021. Interventions: Initial invasive management of coronary angiography and revascularization with guideline-directed medical therapy (GDMT) vs initial conservative management of GDMT alone. Main Outcomes and Measures: The primary clinical outcome was a composite of death or nonfatal myocardial infarction (MI). The primary QoL outcome was the Seattle Angina Questionnaire (SAQ) summary score. Results: Among the 5956 participants included in this analysis (mean [SD] age, 64 [10] years; 1410 [24%] female and 4546 [76%] male), 1889 (32%), 2551 (43%), 738 (12%), 311 (5%), and 467 (8%) were in CKD stages 1, 2, 3, 4, and 5, respectively. By self-report, 18 participants (<1%) were American Indian or Alaska Native; 1676 (29%), Asian; 267 (5%), Black; 861 (16%), Hispanic or Latino; 18 (<1%), Native Hawaiian or Other Pacific Islander; 3884 (66%), White; and 13 (<1%), multiple races or ethnicities. There was a monotonic increase in risk of the primary composite end point (3-year rates, 9.52%, 10.72%, 18.42%, 34.21%, and 38.01% respectively), death, cardiovascular death, MI, and stroke in individuals with higher CKD stages. Invasive management was associated with an increase in stroke (3-year event rate difference, 1%; 95% CI, 0.3 to 1.7) and procedural MI (1.6%; 95% CI, 0.9 to 2.3) and a decrease in spontaneous MI (-2.5%; 95% CI, -3.9 to -1.1) with no difference in other outcomes; the effect was similar across CKD stages. There was heterogeneity of treatment effect for QoL outcomes such that invasive management was associated with an improvement in angina-related QoL in individuals with CKD stages 1 to 3 and not in those with CKD stages 4 to 5. Conclusions and Relevance: Among participants with CCD, event rates were inversely proportional to kidney function. Invasive management was associated with an increase in stroke and procedural MI and a reduced risk in spontaneous MI, and the effect was similar across CKD stages with no difference in other outcomes, including death. The benefit for QoL with invasive management was not observed in individuals with poorer kidney function.
Subject(s)
Coronary Disease , Myocardial Infarction , Renal Insufficiency, Chronic , Stroke , Chronic Disease , Conservative Treatment , Coronary Disease/complications , Female , Humans , Kidney , Male , Middle Aged , Myocardial Infarction/complications , Quality of Life , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/epidemiology , Renal Insufficiency, Chronic/therapy , Stroke/complicationsABSTRACT
BACKGROUND: Prior trials comparing a strategy of optimal medical therapy with or without revascularization have not shown that revascularization reduces cardiovascular events in patients with stable ischemic heart disease (SIHD). However, those trials only included participants in whom coronary anatomy was known prior to randomization and did not include sufficient numbers of participants with significant ischemia. It remains unknown whether a routine invasive approach offers incremental value over a conservative approach with catheterization reserved for failure of medical therapy in patients with moderate or severe ischemia. METHODS: The ISCHEMIA trial is a National Heart, Lung, and Blood Institute supported trial, designed to compare an initial invasive or conservative treatment strategy for managing SIHD patients with moderate or severe ischemia on stress testing. Five thousand one-hundred seventy-nine participants have been randomized. Key exclusion criteria included estimated glomerular filtration rate (eGFR) <30 mL/min, recent myocardial infarction (MI), left ventricular ejection fraction <35%, left main stenosis >50%, or unacceptable angina at baseline. Most enrolled participants with normal renal function first underwent blinded coronary computed tomography angiography (CCTA) to exclude those with left main coronary artery disease (CAD) and without obstructive CAD. All randomized participants receive secondary prevention that includes lifestyle advice and pharmacologic interventions referred to as optimal medical therapy (OMT). Participants randomized to the invasive strategy underwent routine cardiac catheterization followed by revascularization with percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) surgery, when feasible, as selected by the local Heart Team to achieve optimal revascularization. Participants randomized to the conservative strategy undergo cardiac catheterization only for failure of OMT. The primary endpoint is a composite of cardiovascular (CV) death, nonfatal myocardial infarction (MI), hospitalization for unstable angina, hospitalization for heart failure, or resuscitated cardiac arrest. Assuming the primary endpoint will occur in 16% of the conservative group within 4 years, estimated power exceeds 80% to detect an 18.5% reduction in the primary endpoint. Major secondary endpoints include the composite of CV death and nonfatal MI, net clinical benefit (primary and secondary endpoints combined with stroke), angina-related symptoms and disease-specific quality of life, as well as a cost-effectiveness assessment in North American participants. Ancillary studies of patients with advanced chronic kidney disease and those with documented ischemia and non-obstructive coronary artery disease are being conducted concurrently. CONCLUSIONS: ISCHEMIA will provide new scientific evidence regarding whether an invasive management strategy improves clinical outcomes when added to optimal medical therapy in patients with SIHD and moderate or severe ischemia.
Subject(s)
Myocardial Ischemia/therapy , Myocardial Revascularization/methods , Outcome Assessment, Health Care , Randomized Controlled Trials as Topic/methods , Thrombolytic Therapy/methods , HumansSubject(s)
Clinical Decision-Making , Coronary Occlusion/surgery , Patient Selection , Percutaneous Coronary Intervention , Chronic Disease , Coronary Occlusion/diagnostic imaging , Coronary Occlusion/mortality , Coronary Occlusion/physiopathology , Humans , Percutaneous Coronary Intervention/adverse effects , Percutaneous Coronary Intervention/mortality , Risk Assessment , Risk Factors , Treatment OutcomeSubject(s)
Biomedical Research/trends , Cardiac Catheterization/trends , Cardiology/trends , Coronary Disease/therapy , Heart Valve Diseases/therapy , Heart Valve Prosthesis Implantation/trends , Percutaneous Coronary Intervention/trends , Animals , Cardiac Catheterization/adverse effects , Coronary Disease/diagnosis , Diffusion of Innovation , Forecasting , Heart Valve Diseases/diagnosis , Heart Valve Prosthesis/trends , Heart Valve Prosthesis Implantation/adverse effects , Heart Valve Prosthesis Implantation/instrumentation , Humans , Percutaneous Coronary Intervention/adverse effects , Percutaneous Coronary Intervention/instrumentation , Prosthesis Design , Stents/trends , Treatment OutcomeABSTRACT
All patients with stable ischemic heart disease (SIHD) should be managed with guideline-directed medical therapy (GDMT), which reduces progression of atherosclerosis and prevents coronary thrombosis. Revascularization is also indicated in patients with SIHD and progressive or refractory symptoms, despite medical management. Whether a strategy of routine revascularization (with percutaneous coronary intervention or coronary artery bypass graft surgery as appropriate) plus GDMT reduces rates of death or myocardial infarction, or improves quality of life compared to an initial approach of GDMT alone in patients with substantial ischemia is uncertain. Opinions run strongly on both sides, and evidence may be used to support either approach. Careful review of the data demonstrates the limitations of our current knowledge, resulting in a state of community equipoise. The ongoing ISCHEMIA trial (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) is being performed to determine the optimal approach to managing patients with SIHD, moderate-to-severe ischemia, and symptoms that can be controlled medically. (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches [ISCHEMIA]; NCT01471522).
Subject(s)
Myocardial Ischemia/therapy , Myocardial Revascularization , Cardiovascular Agents/therapeutic use , Humans , Myocardial Ischemia/mortality , Percutaneous Coronary Intervention , Quality of Life , StentsABSTRACT
BACKGROUND: Long-term data on outcomes after percutaneous coronary intervention (PCI) with drug-eluting stent (DES) and bare-metal stent (BMS) across racial groups are limited, and minorities are under-represented in existing clinical trials. Whether DES has better long-term clinical outcomes compared to BMS across racial groups remains to be established. Accordingly, we assessed whether longer-term clinical outcomes are better with DES compared to BMS across racial groups. METHODS: Using the multicenter National Heart, Lung, and Blood Institute (NHLBI)-sponsored Dynamic Registry, 2-year safety (death, MI) and efficacy (repeat revascularization) outcomes of 3326 patients who underwent PCI with DES versus BMS were evaluated. RESULTS: With propensity-score adjusted analysis, the use of DES, compared to BMS, was associated with a lower risk for death or MI at 2 years for both blacks (adjusted Hazard Ratio (aHR)=0.41, 95% CI 0.25-0.69, p<0.001) and whites (aHR=0.67, 95% CI 0.51-0.90, p=0.007). DES use was associated with a significant 24% lower risk of repeat revascularization in whites (aHR=0.76, 95% CI 0.60-0.97, p=0.03) and with nominal 34% lower risk in blacks (aHR=0.66, 95% CI 0.39-1.13, p=0.13). CONCLUSION: The use of DES in PCI was associated with better long-term safety outcomes across racial groups. Compared to BMS, DES was more effective in reducing repeat revascularization in whites and blacks, but this benefit was attenuated after statistical adjustment in blacks. These findings indicate that DES is superior to BMS in all patients regardless of race. Further studies are needed to determine long-term outcomes across racial groups with newer generation stents.
Subject(s)
Black People/ethnology , Drug-Eluting Stents/trends , National Heart, Lung, and Blood Institute (U.S.)/trends , Percutaneous Coronary Intervention/trends , Registries , White People/ethnology , Aged , Cohort Studies , Drug-Eluting Stents/adverse effects , Female , Follow-Up Studies , Humans , Male , Metals/adverse effects , Middle Aged , Racial Groups/ethnology , Stents/adverse effects , Stents/trends , Time Factors , Treatment Outcome , United States/ethnologySubject(s)
Cardiac Catheterization/trends , Coronary Artery Disease/therapy , Heart Diseases/therapy , Thoracic Surgery/trends , Angioplasty, Balloon, Coronary , Cardiac Catheterization/methods , Coronary Artery Bypass , Humans , Percutaneous Coronary Intervention , Thoracic Surgery/methods , Treatment OutcomeABSTRACT
Several factors contribute to the risk of percutaneous coronary intervention-related major entry site (MES) complications. We sought to examine the trends in MES among unselected patients during the stent era. Data from the Dynamic Registry including 5 distinct recruitment waves from 1997 to 2006 (n = 10,932) were used to assess baseline characteristics and MES among consecutive patients undergoing percutaneous coronary intervention. MES was defined as bleeding requiring transfusion, pseudoaneurysm, arterial thrombosis or dissection, vascular complication requiring surgery, or retroperitoneal bleed. Uncomplicated hematomas were not included. Several trends were observed in baseline characteristics including an increase from wave 1 to wave 5 in body mass index >30 kg/m(2) (30.2% to 40.4%), renal disease (3.5% to 9.1%), diabetes (28.0% to 34.1%), and hypertension (59.4% to 78%; ptrend <0.001 for all). The use of a thienopyridine increased significantly from wave 1 (49.7%) to wave 5 (84%), whereas glycoprotein IIb/IIIa inhibitor use peaked in wave 3 (53.1%) and then decreased (p <0.001). Access site was predominately femoral, but radial access increased over time (0.3% wave 1, 6.6% wave 5, p ≤0.0001). The rates of MES (2.8% to 2.2%, ptrend = 0.01) and MES requiring transfusion (2.0% to 0.74%, ptrend <0.001) were low and decreased with time. The trend in less risk for MES in later time periods remained after adjustment. In conclusion, MES has decreased over time; however, opportunity for bleeding avoidance strategies still exists.
Subject(s)
Angioplasty, Balloon, Coronary/adverse effects , Coronary Aneurysm/etiology , Hemorrhage/etiology , Myocardial Infarction/surgery , Thrombosis/etiology , Aged , Female , Humans , Male , Middle Aged , Prospective Studies , RegistriesABSTRACT
OBJECTIVES: This study sought to evaluate the safety and effectiveness of drug-eluting stents (DES) compared to bare-metal stents (BMS) for patients with large coronary vessels. BACKGROUND: Randomized trials have demonstrated that DES reduce the risk of target vessel revascularization (TVR) compared to BMS. This benefit is less pronounced as artery diameter increases. Whether DES are superior to BMS for larger coronary arteries in the setting of routine clinical practice is unknown. METHODS: We analyzed data from 869 patients undergoing de novo lesion PCI with reference vessel diameter greater than or equal to 3.5 mm in the NHLBI Dynamic Registry according to whether they were treated with DES or BMS. Patients were followed for 3 years for the occurrence of cardiovascular events. RESULTS: At 3-year follow-up, rates of TVR at 3 years were similar and low in both groups (4.4% vs. 3.7%, P = 0.62). After adjustment for differences in baseline characteristics, the adjusted hazard ratio for 3-year MI for DES was 1.85 (95% CI 0.93-3.7, P = 0.08), for TVR at 3 years 1.14 (95% CI 0.52-2.49, P = 0.75) and for mortality 0.89 (95%CI 0.49-1.62, P = 0.71). CONCLUSIONS: In our study of the unrestricted use of DES for patients with lesions in larger diameter coronary arteries, first generation DES did not reduce 3-year risk of TVR. Our findings do not support the preferred use of DES over BMS for patients with lesions located in arteries >3.5 mm. It is unknown whether secondary generation DES can offer better outcome compared to BMS in large coronary vessels. Further study on this issue is warranted.
Subject(s)
Coronary Artery Disease/surgery , Coronary Vessels/surgery , Drug-Eluting Stents , National Heart, Lung, and Blood Institute (U.S.)/statistics & numerical data , Percutaneous Coronary Intervention/methods , Registries , Coronary Angiography , Coronary Artery Disease/diagnostic imaging , Female , Follow-Up Studies , Humans , Male , Middle Aged , Prosthesis Design , Retrospective Studies , Risk Factors , Treatment Outcome , United StatesABSTRACT
BACKGROUND: Prior trials suggest it is safe to defer transfusion at hemoglobin levels above 7 to 8 g/dL in most patients. Patients with acute coronary syndrome may benefit from higher hemoglobin levels. METHODS: We performed a pilot trial in 110 patients with acute coronary syndrome or stable angina undergoing cardiac catheterization and a hemoglobin <10 g/dL. Patients in the liberal transfusion strategy received one or more units of blood to raise the hemoglobin level ≥10 g/dL. Patients in the restrictive transfusion strategy were permitted to receive blood for symptoms from anemia or for a hemoglobin <8 g/dL. The predefined primary outcome was the composite of death, myocardial infarction, or unscheduled revascularization 30 days post randomization. RESULTS: Baseline characteristics were similar between groups except age (liberal, 67.3; restrictive, 74.3). The mean number of units transfused was 1.6 in the liberal group and 0.6 in the restrictive group. The primary outcome occurred in 6 patients (10.9%) in the liberal group and 14 (25.5%) in the restrictive group (risk difference = 15.0%; 95% confidence interval of difference 0.7% to 29.3%; P = .054 and adjusted for age P = .076). Death at 30 days was less frequent in liberal group (n = 1, 1.8%) compared to restrictive group (n = 7, 13.0%; P = .032). CONCLUSIONS: The liberal transfusion strategy was associated with a trend for fewer major cardiac events and deaths than a more restrictive strategy. These results support the feasibility of and the need for a definitive trial.