Cardiology Flashcards
Aspirin and heparin in acute unstable angina trial
Journal and year of publication
NEJM, 1988
Aspirin and heparin in acute unstable angina trial
Trial Design
Double-blind, randomized, placebo-controlled trial
Aspirin and heparin in acute unstable angina trial
Population
Key inclusion criteria: Patients with unstable angina based on symptoms and ECG changes
Key exclusion criteria: Unclear from manuscrip
Aspirin and heparin in acute unstable angina trial
Intervention
Studied
Intervention Studied: Aspirin (325 mg twice daily), heparin (1000 units per hour by intravenous infusion), and a combination of the two
Control: Placebo
Aspirin and heparin in acute unstable angina trial
Outcomes
Incidence of myocardial infarction was significantly reduced in the groups receiving aspirin (3 percent; P = 0.01), heparin (0.8 percent; P<0.001), and aspirin plus heparin (1.6 percent, P = 0.003).
Aspirin and heparin in acute unstable angina trial
Conclusion
The authors concluded that “In the acute phase of unstable angina, either aspirin or heparin treatment is associated with a reduced incidence of myocardial infarction.”
CURE trial
Journal and year of publication
NEJM, 2001
CURE trial
Trial Design
Double-blind, randomized, placebo-controlled trial
CURE trial
Population
12,562 patients with NSTEMI
Key inclusion criteria:
– Patients hospitalized within 24 hours after the onset of symptoms and did not have ST-segment elevation
Key exclusion criteria:
– Patients with contraindications to antithrombotic or antiplatelet therapy
– Patients who were at high risk for bleeding or severe heart failure
– Patients who were taking oral anticoagulants
– Patients who had undergone coronary revascularization in the previous three months
– Patients who had received intravenous glycoprotein IIb/IIIa receptor inhibitors in the previous three days
CURE trial
Intervention Studied
Intervention: Clopidogrel (300 mg immediately, followed by 75 mg once daily) + Aspirin for 3 to 12 months
Control: Placebo + Aspirin for 3 to 12 months
CURE trial
Outcomes
– First primary outcome: a composite of death from cardiovascular causes, nonfatal myocardial infarction, or stroke. Relative risk with clopidogrel as compared with placebo, 0.80; 95 percent confidence interval, 0.72 to 0.90; P<0.001
– The percentages of patients with in-hospital refractory or severe ischemia, heart failure, and revascularization procedures were also significantly lower with clopidogrel.
– Major bleeding: Relative risk with clopidogrel as compared with placebo,1.38; P=0.001). No significantly more patients with episodes of life-threatening bleeding (2.1 percent vs. 1.8 percent, P=0.13) or hemorrhagic strokes between groups
CURE trial
Conclusion
Clopidogrel has beneficial effects in patients with acute coronary syndromes without ST-segment elevation. However, the risk of major bleeding is increased among patients treated with clopidogrel.
CLARITY-TIMI 28 trial
Journal and year of publication
NEJM, 2005
CLARITY-TIMI 28 trial
Trial Design
Double-blind, randomized, placebo-controlled trial
CLARITY-TIMI 28 trial
Population
3,491 patients with STEMI
Key inclusion criteria:
– Patients between 18 to 75 years of age with ischemic symptoms and ST-segment elevation of at least 0.1 mV in at least two contiguous limb leads, ST-segment elevation of at least 0.2 mV in at least two contiguous precordial leads, or left bundle-branch block that was not known to be old
– And who were scheduled to receive a fibrinolytic agent, an anticoagulant (if a fibrin-specific lytic agent was prescribed), and aspirin
Key exclusion criteria:
– Treatment with clopidogrel within 7 days before enrollment or planned treatment with clopidogrel or a glycoprotein IIb/IIIa inhibitor before angiography
– Contraindications to fibrinolytic therapy (including documented stroke, intracranial hemorrhage, and intracranial neoplasm)
– A plan to perform angiography within 48 hours in the absence of a new clinical indication
– Cardiogenic shock
– Prior coronary artery bypass grafting
CLARITY-TIMI 28 trial
Intervention Studied
I: Clopidogrel (300-mg loading dose, followed by 75 mg once daily) + Aspirin, fibrinolytic, and heparin when appropriate
C: Placebo + Aspirin, fibrinolytic, and heparin when appropriate
CLARITY-TIMI 28 trial
Outcomes:
– The primary outcome was a composite of an occluded infarct-related artery on angiography or death or recurrent myocardial infarction before angiography
– Absolute reduction of 6.7% in the rate and a 36% reduction in the odds of the endpoint with clopidogrel therapy (95% CI, 24-47%; P<0.001)
– Rates of major bleeding and intracranial hemorrhage were similar in the two groups
CLARITY-TIMI 28 trial
Conclusion
In patients 75 years of age or younger who have myocardial infarction with ST-segment elevation and who receive aspirin and a standard fibrinolytic regimen, the addition of clopidogrel improves the patency rate of the infarct-related artery and reduces ischemic complications.
GUSTO trial
Journal and year of publication
NEJM, 1993
GUSTO trial
Trial Design
Randomized controlled trial
GUSTO trial
Population
41,021 patients with STEMI
Key inclusion criteria:
– Presenting to a participating hospital less than 6 hours after the onset of symptoms.
– Chest pain lasting at least 20 minutes
– ECG signs of ≥ 0.1 mV of ST-segment elevation in two or more limb leads or ≥ 0.2 mV in two or more contiguous precordial leads
Key exclusion criteria:
– Previous stroke.
– Active bleeding.
– Previous treatment with streptokinase or anistreplase.
– Recent trauma or major surgery.
– Relative contraindication to enrollment: Patients with severe, uncontrolled hypertension (systolic blood pressure ≥ 180 mm Hg, unresponsive to therapy).
GUSTO trial
Intervention Studied:
I: 1) Streptokinase and subcutaneous heparin
2) Streptokinase and intravenous heparin
3) Accelerated tissue plasminogen activator (t-PA) and intravenous heparin*
4) Combination of streptokinase plus t-PA with intravenous heparin
GUSTO trial
Outcomes
Mortality rates in the four treatment groups were as follows:
– – Streptokinase and subcutaneous heparin: 7.2%.
– – Streptokinase and intravenous heparin: 7.4%.
– – Accelerated t-PA and intravenous heparin: 6.3%.
– – Combination of both thrombolytic agents with intravenous heparin: 7.0%.
*14% reduction (95% CI, 5.9 to 21.3%) in mortality for accelerated t-PA as compared with the two streptokinase-only strategies (P= 0.001).
A combined end point of death or disabling stroke:
– – Significantly lower in the accelerated-t-PA group than in the streptokinase-only groups (6.9 percent vs. 7.8 percent, P = 0.006)
GUSTO trial
Conclusion
Accelerated t-PA given with intravenous heparin provides a survival benefit over previous standard thrombolytic regimens.
TRITON-TIMI 38 trial
Journal and year of publication
NEJM, 2007
TRITON-TIMI 38 trial
Trial Design
Double-blind, randomized trial
TRITON-TIMI 38 trial
Population
3,608 patients with acute coronary syndromes with scheduled PCI
Key inclusion criteria:
– For patients with NSTEMI: either ST-segment deviation of 1 mm or more or elevated cardiac biomarkers of necrosis and TIMI risk score of 3 or more,
– For patients with STEMI: within 12 hours after the onset of symptoms if primary PCI was planned, or within 14 days after receiving medical treatment for ST-elevation myocardial infarction
Key exclusion criteria:
– Cardiogenic shock
– Fibrinolytic therapy within 24 hours
– Intracranial neoplasm or history of hemorrhagic stroke
– Clinical findings, in the judgment of the investigator, associated
with an increased risk of bleeding
TRITON-TIMI 38 trial
Intervention Studied
I: Prasugrel (60 mg loading dose, 10 mg daily dose) for 6 to 15 months
C: Clopidogrel (300 mg loading dose, 75 mg daily dose) for 6 to 15 months
TRITON-TIMI 38 trial
Outcomes
– The primary efficacy endpoint: (rate of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke): occurred in 9.9% of patients receiving prasugrel and 12.1% of patients receiving clopidogrel – HR for prasugrel vs. clopidogrel, 0.81; 95% CI 0.73 – 0.90; P<0.001)
– Others: Lower rates of myocardial infarction, urgent target-vessel revascularization, and stent thrombosis in the prasugrel group
– Major bleeding: higher in the prasugrel group including life-threatening as well as fatal bleeding
TRITON-TIMI 38 trial
Conclusion
In patients with ACS with scheduled PCI, prasugrel therapy was associated with significantly reduced rates of ischemic events, including stent thrombosis, but with an increased risk of major bleeding, including fatal bleeding. Overall mortality did not differ significantly between treatment groups.
PLATO trial
Journal and year of publication
NEJM, 2009
PLATO trial
Trial Design
Double-blind, randomized trial
PLATO trial
Population
18,624 patients with ACS
Key inclusion criteria:
– Patients hospitalized for an acute coronary syndrome, with or without ST-segment elevation, with an onset of symptoms during the previous 24 hours
Key exclusion criteria:
– Contraindication to the use of clopidogrel or fibrinolytic therapy within 24 hours before randomization
– A need for oral anticoagulation therapy
– Increased risk of bradycardia
– Concomitant therapy with a strong CYP-450 3A inhibitor or inducer
PLATO trial
Intervention Studied
I: Ticagrelor (180-mg loading dose, 90 mg twice daily thereafter)
C: Clopidogrel (300 to 600 mg loading dose, 75 mg daily thereafter)
PLATO trial
Outcomes
– At 12 months, the primary endpoint (a composite of death from vascular causes, myocardial infarction, or stroke): lower in the ticagrelor group (HR 0.84; 95% CI 0.77 – 0.92; P<0.001)
– Bleeding: No significant difference in the rates of major bleeding was found between the ticagrelor and clopidogrel groups, but ticagrelor was associated with a higher rate of major bleeding not related to CABG
PLATO trial
Conclusion
In patients who have an ACS with or without ST-segment elevation, treatment with ticagrelor as compared with clopidogrel significantly reduced the rate of death from vascular causes, myocardial infarction, or stroke without an increase in the rate of overall major bleeding but with an increase in the rate of non–procedure-related bleeding
DANAMI-2 trial
Journal and year of publication
NEJM, 2003
DANAMI-2 trial
Trial Design
Randomized clinical trial
DANAMI-2 trial
Population
1572 patients with acute MI
Key inclusion criteria:
– The presence of symptoms for at least 30 minutes but less than 12 hours
– Cumulative ST-segment elevation of at least 4 mm in at least two contiguous leads
Key exclusion criteria:
– Contraindication to fibrinolysis
– LBBB
– Acute myocardial infarction and fibrinolytic treatment within the past 30 days
– Prior CABG
– Creatinine > 2.83 mg/dL
– Diabetics treated with metformin
DANAMI-2 trial
Intervention Studied
I: Treatment with angioplasty (including those needing transfer)
C: Accelerated treatment with intravenous alteplase
DANAMI-2 trial
Outcomes
– Primary study endpoint: a composite of death, clinical evidence of reinfarction, or disabling stroke at 30 days
– At invasive treatment centers: 6.7 percent of the patients in the angioplasty group reached the primary endpoint, as compared with 12.3 percent in the fibrinolysis group (P=0.05)
– From referral hospitals: the primary endpoint was reached in 8.5 percent of the patients in the angioplasty group, as compared with 14.2 percent of those in the fibrinolysis group (P=0.002)
– Lower rates of re-infarction in the angioplasty group, but no differences in the rates of death or strokes between the two groups
DANAMI-2 trial
Conclusion
A strategy for reperfusion involving the transfer of patients to an invasive-treatment center for primary angioplasty is superior to on-site fibrinolysis, provided that the transfer takes two hours or less
COMMIT trial
Journal and year of publication
The Lancet, 2005
COMMIT trial
Trial Design
Randomized, placebo-controlled clinical trial
COMMIT trial
Population
45,852 patients with acute MI
Key inclusion criteria:
– Patients who presented with ST-elevation, left-bundle branch block, or ST depression within 24 h of the onset of the symptoms
Key exclusion criteria:
– Bradycardia (HR < 50 bpm)
– Hypotension (SBP < 100 mmHg)
– Patients with planned PCI
– Heart block
– Cardiogenic shock
COMMIT trial
Intervention Studied
I: Metoprolol (up to 15 mg intravenous then 200 mg oral daily)
C: Matching placebo
COMMIT trial
Outcomes
– Primary study endpoint (Death, reinfarction, or cardiac arrest): 9·4% of patients allocated to metoprolol had at least one such event compared with 9·9% allocated to placebo (OR 0·96, 95% CI 0·90–1·01; p=0·1)
– Reinfarction: 2.0% in the metoprolol group vs 2.5% in the placebo group (OR 0·82, 0·72–0·92; p=0·001)
– Ventricular fibrillation: 2.5% in the metoprolol group vs 3.0% in the placebo group (OR 0·83, 0·75–0·93; p=0·001)
– Cardiogenic shock: 5.0% in the metoprolol group vs 3.9% in the placebo group (OR 1·30, 1·19–1·41; p<0·00001)
COMMIT trial
Conclusion
he use of early β-blocker therapy in acute MI reduces the risks of reinfarction and ventricular fibrillation, but increases the risk of cardiogenic shock, especially during the first day or so after admission. Consequently, it might generally be prudent to consider starting β-blocker therapy in hospital only when the haemodynamic condition after MI has stabilised
BASKET-PROVE trial
Journal and year of publication
NEJM, 2010
BASKET-PROVE trial
Trial Design
Randomized clinical trial
BASKET-PROVE trial
Population
2314 patients undergoing stenting
Key inclusion criteria:
– Those who presented with chronic or acute coronary disease
– Undergoing angioplasty with stenting and who required only stents that were 3.0 mm or more in diameter
Key exclusion criteria:
– In-stent restenosis or thrombosis of stents placed before the study
– Unprotected left main coronary artery (i.e., with no functioning bypass graft) or substantial stenosis in a bypass graft
– Patients on oral anticoagulation
– Plans for any surgery within 12 months
BASKET-PROVE trial
Intervention Studied
I: Sirolimus-eluting, everolimus-eluting stents
C: Bare-metal stents
BASKET-PROVE trial
Outcomes
– Primary endpoint (death from cardiac causes or nonfatal MI at 2 years): 2.6% in the sirolimus-eluting stents group, 3.2% in the everolimus-eluting stents group, and 4.8% in the bare-metal stents (no significant differences between groups)
– Rates of target-vessel revascularization for reasons unrelated to myocardial infarction: 3.7% in the sirolimus-eluting stents, 3.1% in the everolimus-eluting stents, and 8.9% in the bare-metal stents (p <0.001)
BASKET-PROVE trial
Conclusion
In patients requiring stenting of large coronary arteries, no significant differences were found among sirolimus-eluting, everolimus-eluting, and bare-metal stents with respect to the rate of death or myocardial infarction. With the two drug-eluting stents, similar reductions in rates of target-vessel revascularization were seen
TIMI score study
Journal and year of publication
JAMA, 2000
TIMI score study
Trial Design
Validation of scoring system in patients from 2 RCTs (TIMI & ESSENCE)
TIMI score study
Population
Key inclusion criteria:
– All patients (n = 3910 in TIMI 11B and n = 3171 in ESSENCE) presented within 24 hours of an episode of UA/NSTEMI at rest.
– At least 1 of the following: ST-segment deviation on the qualifying ECG, documented history of coronary artery disease, or elevated serum cardiac markers.
Key exclusion criteria:
– Planned revascularization in 24 hours or less
– A correctable cause of angina
TIMI score study
Intervention Studied
To develop a simple risk score that has broad applicability, is easily calculated at patient presentation, does not require a computer, and identifies patients with different responses to treatments for UA/NSTEMI
TIMI score study
Outcomes
– Event rates increased significantly as the TIMI risk score increased in the test cohort in TIMI 11B (P<.001 by χ2 for trend):
— 4.7% for a score of 0/1
— 8.3% for 2
— 13.2% for 3
— 19.9% for 4
— 26.2% for 5
— 40.9% for 6/7
– Significant interaction between TIMI risk score and treatment (P = .02)
TIMI score study
Conclusion
In patients with UA/NSTEMI, the TIMI risk score is a simple prognostication scheme that categorizes a patient’s risk of death and ischemic events and provides a basis for therapeutic decision making.”
TIMACS trial
Journal and year of publication
NEJM, 2009
TIMACS trial
Trial Design
Randomized clinical trial
TIMACS trial
Population
3031 patients with ACS
Key inclusion criteria:
– Patients presenting with unstable angina or NSTEMI within 24 hours of symptoms onset
Key exclusion criteria:
– Patients not suitable candidates for revascularization
– Severe renal insufficiency (creatinine >3 g/dL)
– Hemorrhagic stroke within the past 12 months
TIMACS trial
Intervention Studied
I: routine early intervention (coronary angiography ≤24 hours after randomization)
C: Delayed intervention (coronary angiography ≥36 hours after randomization)
TIMACS trial
Outcomes
– Primary outcome (a composite of death, MI, or stroke at 6 months): 9.6% of patients in the early-intervention group, as compared with 11.3% in the delayed-intervention group (HR in the early-intervention group, 0.85; 95% CI 0.68 – 1.06; P=0.15)
– Early intervention improved the primary outcome in the third of patients who were at the highest risk (hazard ratio, 0.65; 95% CI, 0.48 to 0.89)
– Secondary outcome ( death, MI, or refractory ischemia at 6 months): 9.5 % in the early-intervention group as compared to 12.9% in the delayed-intervention group (HR 0.72; 95% CI 0.58 – 0.89; P=0.003)
TIMACS trial
Conclusion
Early intervention did not differ greatly from delayed intervention in preventing the primary outcome, but it did reduce the rate of the composite secondary outcome of death, myocardial infarction, or refractory ischemia and was superior to delayed intervention in high-risk patients
COURAGE trial
Journal and year of publication
NEJM, 2007
COURAGE trial
Trial Design
Randomized controlled clinical trial
COURAGE trial
Population
2,287 patients with stable CAD
Key inclusion criteria:
– Stenosis of at least 70% in at least one proximal epicardial coronary artery AND objective evidence of myocardial ischemia
Key exclusion criteria:
– Unstable angina and symptoms refractory to maximal oral and intravenous medical therapy
– Coronary angiographic exclusions such as patients with no prior CABG and left main coronary disease >50%, patients with nonsignificant CAD in whom PCI would not be considered appropriate or indicated, and patients with restenosis of a lesion previously treated with PCI and no other target lesion
– EF <30% (<35% if patient has 3-vessel disease including >70% LAD proximal stenosis)
– CABG or PCI within the last 6 months
– Concomitant valvular heart disease likely to require surgery or affect prognosis during follow-up
COURAGE trial
Intervention Studied
I: PCI with optimal medical therapy
C: optimal medical therapy alone
COURAGE trial
Outcomes
– Primary outcome (death from any cause and nonfatal myocardial infarction during a follow-up period): were 19.0% in the PCI group and 18.5% in the medical therapy group (HR for the PCI group, 1.05. 95% CI 0.87-1.27; P=0.62)
– No significant differences in hospitalization either
COURAGE trial
Conclusions
As an initial management strategy in patients with stable coronary artery disease, PCI did not reduce the risk of death, myocardial infarction, or other major cardiovascular events when added to optimal medical therapy.
SYNTAX trial
Journal and year of publication
NEJM, 2009
SYNTAX trial
Trial Design
Randomized controlled clinical trial
SYNTAX trial
Population
1,800 patients with 3-vessel and/or left main CAD
Key inclusion criteria:
– ≥50% stenosis in at least 3 coronary arteries and/or left main CAD
Key exclusion criteria:
– Previous PCI or CABG
– Acute MI
– Need for concomitant cardiac surgery
SYNTAX trial
Intervention Studied
I: Percutaneous coronary intervention (PCI)
C: oronary-artery bypass grafting (CABG)
SYNTAX trial
Outcomes
– Primary outcome: rates of major adverse cardiac or cerebrovascular events at 12 months: Significantly higher in the PCI group (17.8%, vs. 12.4% for CABG; P=0.002), in large part because of an increased rate of repeat revascularization
– Rates of death were similar between the two groups
– Stroke was significantly more likely to occur with CABG (2.2%, vs. 0.6% with PCI; P=0.003)
SYNTAX trial
Conclusion
CABG remains the standard of care for patients with three-vessel or left main coronary artery disease, since the use of CABG, as compared with PCI, resulted in lower rates of the combined end point of major adverse cardiac or cerebrovascular events at 1 year
FREEDOM trial
Journal and year of publication
NEJM, 2012
FREEDOM trial
Trial Design
Randomized controlled clinical trial
FREEDOM trial
Population
1,900 patients with DM and CAD
Key inclusion criteria:
– DM type 1 or 2
– Angiographically confirmed multivessel CAD (critical [≥70%] lesions in ≥2 major epicardial vessels) amenable to either PCI or CABG
– Indications for revascularization present
Key exclusion criteria:
– Previous CABG or cardiac valve surgery
– Left main CAD stenosis (>50%)
– Acute ST-elevation
– Planned simultaneous cardiac surgery
FREEDOM trial
Intervention Studied
Intervention Studied: Percutaneous coronary intervention (PCI) with DES
Control: Coronary-artery bypass grafting (CABG)
FREEDOM trial
Outcomes
– Primary outcome (composite of death from any cause, nonfatal myocardial infarction, or nonfatal stroke): 5-year rates of 26.6% in the PCI group and 18.7% in the CABG group (P=0.005)
– Stroke: 5-year rates of 2.4% in the PCI group and 5.2% in the CABG group (P=0.03)
FREEDOM trial
Conclusion
For patients with diabetes and advanced coronary artery disease, CABG was superior to PCI in that it significantly reduced rates of death and myocardial infarction, with a higher rate of stroke
PROVE-IT TIMI 22 trial
Journal and year of publication
NEJM, 2004
PROVE-IT TIMI 22 trial
Trial Design
Randomized, double-blinded controlled clinical trial
