Clinical Trials Flashcards
What is the ISCHEMIA Trial? What were the major findings? How many patients were enrolled? Who is the first author? What are the weaknesses of the trial?
The ISCHEMIA trial randomized 5179 patients with stable CAD and moderate or severe ischemia on stress testing to an initial invasive strategy or initial conservative strategy with invasive strategy if medical management failed. Exclusion criteria were: patients with ACS, LM >50%, LVEF <35%, advanced CKD, recent PCI/CABG within the last year, NYHA 3-4 symptoms. In the invasive strategy 96% underwent angiography and in the conservative strategy 26% underwent angiography. At a median followup of 3.2 years, there was no difference between groups in the primary outcome, a composite of death from CV causes, MI, hospitalization for UA, CHF or resuscitated cardiac arrest. There was no difference in a composite of death from CV causes, MI or angina QoL. There was no difference in all cause mortality. There were more procedural MIs of unclear significance but less non-procedural MIs with the invasive strategy. The primary definition of MI is similar to the SCAI use and a secondary definition of MI yielded higher rates of MI using the 3rd universal definition of MI. 1/3rd of patients did not report anginal symptoms prior to enrollment in this trial.
The first author is David Maron
The weaknesses of the trial include reduced power and lower event rates than expected and a limited median follow-up of only 3.2 years
The trial showed that for patients with moderate to severe ischemia and stable CAD and normal LVs, an initial invasive strategy vs initial conservative strategy showed no difference in mortality or a composite outcome at 3.2 years. The invasive strategy was associated with an initial higher rate of procedural MI but a lower rate of spontaneous MI. The initial higher rate of total MI reversed itself by 2 years. The invasive strategy did provide a modest benefit in terms of relieving symptoms of angina particularly in patients reporting daily/weekly anginal symptoms.
What is the SYNTAX Trial?
What were the major findings?
Who was the first author?
What are the common criticisms?
Non inferiority trial for PCI (1st gen DES) vs CABG for 3VD and/or LMS disease
All lesions deemed amenable to either therapy
1800 patients
First author is Patrick Serruys
MACE or stroke @ 12 months significantly higher for PCI (RR 1.44; p=0.002)
-Largely due to increased rate of repeat revascularization (RR 2.29; p<0.001)
Death from cardiac causes higher for PCI (RR 1.75; p=0.05)
Reduced rate of stroke for PCI (RR 0.25; p=0.003) (2.2% stroke rate in CABG, 0.6% for PCI at 1 year)
Similar rates of death and MI
Criticisms include use of 1st gen DES instead of 2nd gen DES and lower rates of OMT in the CABG group
What is the STITCH Trial?
The STITCH Trial is an open label RCT that randomized 1212 patients with CAD amenable to CABG and an LVEF <35% to either medical therapy, medical therapy+CABG or medical therapy+CABG+SVR. Patients were categorized into one of 3 strata, those eligible for medical therapy + CABG only, those eligible for all three and those eligible for medical therapy+CABG or medical therapy+CABG+SVR. This was published in two studies, one which compared medical therapy to medical therapy+CABG and another one which compared medical therapy+CABG to medical therapy+CABG+SVR.
What were the findings of the STITCH CABG vs OMT study?
Median followup of 56 months
Ejection fraction of 35% or less & coronary disease:
- There was 17% crossover from medical therapy to CABG at a median of 142 days and there was a 9% crossover from CABG to medical therapy
CABG + medical therapy vs. medical therapy alone
- No significant difference to all-cause mortality (p=0.12, favouring CABG)
- Became significant when adjusting for baseline statistics (p=0.039)
- Significant difference in cardiovascular mortality (HR 0.81, p=0.05) and all cause death + hospitalization for heart failure (HR 0.84, p=0.03) all cause death + hospitalization for cardiovascular causes (HR 0.74, p=<0.001)
- Early risk of death as a result of the surgical intervention itself
- -Disappeared at 2 years
- Significant reduction in death from any cause or hospitalization for CV causes
N.B. An as-treated analysis showed significant mortality benefit (p<0.001)
What were the findings of the STITCH CABG vs CABG+SVR study?
Median followup of 48 months
Surgical ventricular reconstruction reduced the end-systolic volume index by 19%, as compared with a reduction of 6% with CABG alone.
Cardiac symptoms and exercise tolerance improved from baseline to a similar degree in the two study groups.
No significant difference was observed in the primary outcome (death or hospitalization for cardiac causes), which occurred in 292 patients (59%) who were assigned to undergo CABG alone and in 289 patients (58%) who were assigned to undergo CABG with surgical ventricular reconstruction (hazard ratio for the combined approach, 0.99; 95% confidence interval, 0.84 to 1.17; P=0.90).
Weaknesses of this study included the open label nature of the trial, a lower amount of reduction in SVI than in previous studies and the perceived conduct of the trial by surgeons who may not have been experienced in SVR.
What is the REDUCE-IT trial?
What is the EVAPORATE trial?
RCT of 8000 patients randomized to icosapentyl ethyl + statin vs statin + placebo
Inclusion criteria: secondary prevention cohort (>45 yrs) or primary prevention cohort (>50 yrs with diabetes and one other risk factor)
70% were secondary prevention, 30% primary prevention
Median triglycerides, 2.44
HDL, 1.03
Primary endpoint: CV death, nonfatal MI, nonfatal stroke, coronary revasc, hospitalization for unstable angina
Key outcome: CV death
Outcomes: 1% increase in a-fib/flutter and non-significant increase in bleeding (primary GI, not cerebral)
About 12.5-15% of patients with CAD met the REDUCE-IT criteria
The EVAPORATE trial is a small RCT of 80 patients following REDUCE-IT that looked at those patients comparing icosapentyl ethyl and compared it to placebo and followed by CTA. There was reduction in plaque as well as high risk plaque (low attenuation) at 9 months with increased reduction at 18 months.
What is the FOURIER trial?
Evolocumab reduced CV risk by 2% ARR in a secondary prevention population
What is the TIME study and its major findings?
Trial of Invasive versus Medical Therapy in Elderly Patients with Chronic Symptomatic Coronary Artery Disease. In elderly patients, there was no difference in symptoms, quality of life, death or non-fatal MI in patients treated with an initial medical invasive strategy (20 vs 17%). Medically treated patients had a higher risk of major clinical events (64 vs 26%) and had a 50% crossover rate to revascularization.
What is the MASS-II Study and its major findings?
The Medicine, Angioplasty, or Surgery study (MASS-II) randomized patients with multivessel disease among medical therapy, PCI and CABG. 10 year survival rates were 74.9% with CABG, 75.1% with PCI and 69% with MT. Re-intervention at 1 year was highest in PCI at 86.7%, 93.7% in MT and 99.5% in CABG patients.
What is the COURAGE trial and its major findings? What was the main criticism of the trial?
The COURAGE trial randomized 2287 patients with stable angina and objective evidence of ischemia to OMT or PCI and OMT. The trial found no difference between PCI and OMT for death, MI or MACCE. The primary criticism of the study was low rate of DES (3%)
What is the SHOCK trial and what were the major findings?
The SHOCK trial randomized patients to emergency revascularization versus initial medical stabilization in patients presenting with STEMI and cardiogenic shock. It found similar survival between CABG and PCI despite a higher rate of T2DM and complex coronary anatomy in the CABG cohort.
