Cardiology

Question 1

Aspirin and heparin in acute unstable angina trial

Journal and year of publication

Answer 1

NEJM, 1988

Question 2

Aspirin and heparin in acute unstable angina trial

Trial Design

Answer 2

Double-blind, randomized, placebo-controlled trial

Question 3

Aspirin and heparin in acute unstable angina trial

Population

Answer 3

Key inclusion criteria: Patients with unstable angina based on symptoms and ECG changes
Key exclusion criteria: Unclear from manuscrip

Question 4

Aspirin and heparin in acute unstable angina trial

Intervention
Studied

Answer 4

Intervention Studied: Aspirin (325 mg twice daily), heparin (1000 units per hour by intravenous infusion), and a combination of the two
Control: Placebo

Question 5

Aspirin and heparin in acute unstable angina trial

Outcomes

Answer 5

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).

Question 6

Aspirin and heparin in acute unstable angina trial

Conclusion

Answer 6

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.”

Question 7

CURE trial

Journal and year of publication

Answer 7

NEJM, 2001

Question 8

CURE trial

Trial Design

Answer 8

Double-blind, randomized, placebo-controlled trial

Question 9

CURE trial

Population

Answer 9

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

Question 10

CURE trial

Intervention Studied

Answer 10

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

Question 11

CURE trial

Outcomes

Answer 11

– 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

Question 12

CURE trial

Conclusion

Answer 12

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.

Question 13

CLARITY-TIMI 28 trial

Journal and year of publication

Answer 13

NEJM, 2005

Question 14

CLARITY-TIMI 28 trial

Trial Design

Answer 14

Double-blind, randomized, placebo-controlled trial

Question 15

CLARITY-TIMI 28 trial

Population

Answer 15

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

Question 16

CLARITY-TIMI 28 trial

Intervention Studied

Answer 16

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

Question 17

CLARITY-TIMI 28 trial

Outcomes:

Answer 17

– 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

Question 18

CLARITY-TIMI 28 trial

Conclusion

Answer 18

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.

Question 19

GUSTO trial

Journal and year of publication

Answer 19

NEJM, 1993

Question 20

GUSTO trial

Trial Design

Answer 20

Randomized controlled trial

Question 21

GUSTO trial

Population

Answer 21

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).

Question 22

GUSTO trial

Intervention Studied:

Answer 22

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

Question 23

GUSTO trial

Outcomes

Answer 23

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)

Question 24

GUSTO trial

Conclusion

Answer 24

Accelerated t-PA given with intravenous heparin provides a survival benefit over previous standard thrombolytic regimens.

Question 25

# TRITON-TIMI 38 trial Journal and year of publication

Answer 25

NEJM, 2007

Question 26

# TRITON-TIMI 38 trial Trial Design

Answer 26

Double-blind, randomized trial

Question 27

# TRITON-TIMI 38 trial Population

Answer 27

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

Question 28

# TRITON-TIMI 38 trial Intervention Studied

Answer 28

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

Question 29

# TRITON-TIMI 38 trial Outcomes

Answer 29

– 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

Question 30

# TRITON-TIMI 38 trial Conclusion

Answer 30

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.

Question 31

# PLATO trial Journal and year of publication

Answer 31

NEJM, 2009

Question 32

# PLATO trial Trial Design

Answer 32

Double-blind, randomized trial

Question 33

# PLATO trial Population

Answer 33

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

Question 34

# PLATO trial Intervention Studied

Answer 34

I: Ticagrelor (180-mg loading dose, 90 mg twice daily thereafter) C: Clopidogrel (300 to 600 mg loading dose, 75 mg daily thereafter)

Question 35

# PLATO trial Outcomes

Answer 35

– 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

Question 36

# PLATO trial Conclusion

Answer 36

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

Question 37

# DANAMI-2 trial Journal and year of publication

Answer 37

NEJM, 2003

Question 38

# DANAMI-2 trial Trial Design

Answer 38

Randomized clinical trial

Question 39

# DANAMI-2 trial Population

Answer 39

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

Question 40

# DANAMI-2 trial Intervention Studied

Answer 40

I: Treatment with angioplasty (including those needing transfer) C: Accelerated treatment with intravenous alteplase

Question 41

# DANAMI-2 trial Outcomes

Answer 41

– 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

Question 42

# DANAMI-2 trial Conclusion

Answer 42

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

Question 43

# COMMIT trial Journal and year of publication

Answer 43

The Lancet, 2005

Question 44

# COMMIT trial Trial Design

Answer 44

Randomized, placebo-controlled clinical trial

Question 45

# COMMIT trial Population

Answer 45

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

Question 46

# COMMIT trial Intervention Studied

Answer 46

I: Metoprolol (up to 15 mg intravenous then 200 mg oral daily) C: Matching placebo

Question 47

# COMMIT trial Outcomes

Answer 47

– 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)

Question 48

# COMMIT trial Conclusion

Answer 48

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

Question 49

# BASKET-PROVE trial Journal and year of publication

Answer 49

NEJM, 2010

Question 50

# BASKET-PROVE trial Trial Design

Answer 50

Randomized clinical trial

Question 51

# BASKET-PROVE trial Population

Answer 51

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

Question 52

# BASKET-PROVE trial Intervention Studied

Answer 52

I: Sirolimus-eluting, everolimus-eluting stents C: Bare-metal stents

Question 53

# BASKET-PROVE trial Outcomes

Answer 53

– 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)

Question 54

# BASKET-PROVE trial Conclusion

Answer 54

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

Question 55

# TIMI score study Journal and year of publication

Answer 55

JAMA, 2000

Question 56

# TIMI score study Trial Design

Answer 56

Validation of scoring system in patients from 2 RCTs (TIMI & ESSENCE)

Question 57

# TIMI score study Population

Answer 57

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

Question 58

# TIMI score study Intervention Studied

Answer 58

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

Question 59

# TIMI score study Outcomes

Answer 59

– 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)

Question 60

# TIMI score study Conclusion

Answer 60

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.”

Question 61

# TIMACS trial Journal and year of publication

Answer 61

NEJM, 2009

Question 62

# TIMACS trial Trial Design

Answer 62

Randomized clinical trial

Question 63

# TIMACS trial Population

Answer 63

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

Question 64

# TIMACS trial Intervention Studied

Answer 64

I: routine early intervention (coronary angiography ≤24 hours after randomization) C: Delayed intervention (coronary angiography ≥36 hours after randomization)

Question 65

# TIMACS trial Outcomes

Answer 65

– 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)

Question 66

# TIMACS trial Conclusion

Answer 66

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

Question 67

# COURAGE trial Journal and year of publication

Answer 67

NEJM, 2007

Question 68

# COURAGE trial Trial Design

Answer 68

Randomized controlled clinical trial

Question 69

# COURAGE trial Population

Answer 69

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

Question 70

# COURAGE trial Intervention Studied

Answer 70

I: PCI with optimal medical therapy C: optimal medical therapy alone

Question 71

# COURAGE trial Outcomes

Answer 71

– 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

Question 72

# COURAGE trial Conclusions

Answer 72

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.

Question 73

# SYNTAX trial Journal and year of publication

Answer 73

NEJM, 2009

Question 74

# SYNTAX trial Trial Design

Answer 74

Randomized controlled clinical trial

Question 75

# SYNTAX trial Population

Answer 75

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

Question 76

# SYNTAX trial Intervention Studied

Answer 76

I: Percutaneous coronary intervention (PCI) C: oronary-artery bypass grafting (CABG)

Question 77

# SYNTAX trial Outcomes

Answer 77

– 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)

Question 78

# SYNTAX trial Conclusion

Answer 78

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

Question 79

# FREEDOM trial Journal and year of publication

Answer 79

NEJM, 2012

Question 80

# FREEDOM trial Trial Design

Answer 80

Randomized controlled clinical trial

Question 81

# FREEDOM trial Population

Answer 81

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

Question 82

# FREEDOM trial Intervention Studied

Answer 82

Intervention Studied: Percutaneous coronary intervention (PCI) with DES Control: Coronary-artery bypass grafting (CABG)

Question 83

# FREEDOM trial Outcomes

Answer 83

– 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)

Question 84

# FREEDOM trial Conclusion

Answer 84

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

Question 85

# PROVE-IT TIMI 22 trial Journal and year of publication

Answer 85

NEJM, 2004

Question 86

# PROVE-IT TIMI 22 trial Trial Design

Answer 86

Randomized, double-blinded controlled clinical trial

Question 87

# PROVE-IT TIMI 22 trial Population

Answer 87

4,162 patients with ACS Key inclusion criteria: – Hospitalized for an acute coronary syndrome – Have a total cholesterol level of 240 mg/dL (6.21 mmol/L) or less Key exclusion criteria: – On any statin at a dose of 80 mg per day at the time of the index event or lipid-lowering therapy with fibric acid derivatives or niacin that could not be discontinued before randomization – Had obstructive hepatobiliary disease or other serious hepatic diseases – Had an unexplained elevation in the creatine kinase level that was more than three times the upper limit of normal

Question 88

# PROVE-IT TIMI 22 trial Intervention Studied

Answer 88

Intervention Studied: 80 mg of atorvastatin daily (intensive therapy) Control: 40 mg of pravastatin daily (standard therapy)

Question 89

# PROVE-IT TIMI 22 trial Outcomes

Answer 89

– Primary end point at two years (a composite of death from any cause, MI, documented unstable angina requiring rehospitalization, revascularization (performed at least 30 days after randomization), and stroke): 26.3% in the pravastatin group vs 22.4% in the atorvastatin group, resulting in a 16% reduction in the HR in favor of atorvastatin (P=0.005; 95% CI 5-26%) – Median LDL levels achieved during treatment: 95 mg per deciliter with pravastatin, 62 mg per deciliter with atorvastatin (P<0.001)

Question 90

# PROVE-IT TIMI 22 trial Conclusion

Answer 90

Intensive lipid-lowering statin regimen provides greater protection against death or major cardiovascular, in patients who have recently had an acute coronary syndrome, compared to a standard regimen. These findings indicate that such patients benefit from early and continued lowering of LDL cholesterol to levels substantially below current target levels.

Question 91

# HOPE trial Journal and year of publication

Answer 91

NEJM, 2000

Question 92

# HOPE trial Trial Design

Answer 92

Randomized, double-blinded, placebo-controlled clinical trial

Question 93

# HOPE trial Population

Answer 93

9,297 high CV risk patients Key inclusion criteria: – At least 55 years old – History of CAD, stroke, peripheral vascular disease, OR diabetes plus at least one other cardiovascular risk factor (hypertension, elevated total cholesterol levels, low HDL cholesterol levels, cigarette smoking, or documented microalbuminuria) Key exclusion criteria: – Heart failure known to have a low ejection fraction (<40%). – Had uncontrolled hypertension or overt nephropathy. – Had an MI or stroke within four weeks before the study began

Question 94

# HOPE trial Intervention Studied

Answer 94

Intervention Studied: Ramipril (10 mg once per day orally) for a mean of five years Control: A matching placebo for a mean of five years

Question 95

# HOPE trial Outcomes

Answer 95

– Primary endpoint (composite of myocardial infarction, stroke, or death from cardiovascular causes): 14% in the ramipril group vs 17.8% in the placebo group (relative risk, 0.78; 95% CI 0.70-0.86; P<0.001) – Treatment with ramipril also reduced rates of death from any cause, revascularization procedures, cardiac arrest, heart failure, and diabetes complications

Question 96

# HOPE trial Conclusion

Answer 96

Ramipril significantly reduces the rates of death, myocardial infarction, and stroke in a broad range of high-risk patients who are not known to have a low ejection fraction or heart failure.

Question 97

# PIONEER AF-PCI trial Journal and year of publication

Answer 97

NEJM, 2016

Question 98

# PIONEER AF-PCI trial Trial Design

Answer 98

Randomized controlled clinical trial

Question 99

# PIONEER AF-PCI trial Population

Answer 99

2,124 patients with nonvalvular Afib + PCI Key inclusion criteria: – Undergone a PCI (with stent placement) for primary atherosclerotic disease – Have documented medical history of non-valvular atrial fibrillation Key exclusion criteria: – Contraindication to anticoagulation – Calculated CrCl <30 mL/min at screening or pre-randomization – Known significant liver disease – Planned CABG

Question 100

# PIONEER AF-PCI trial Intervention Studied

Answer 100

Group 1: low-dose rivaroxaban (15 mg once daily) plus a P2Y12 inhibitor for 12 months Group 2: Very-low-dose rivaroxaban (2.5 mg twice daily) plus DAPT for 1, 6, or 12 months Group 3: standard therapy with a dose-adjusted vitamin K antagonist (once daily) plus DAPT for 1, 6, or 12 month

Question 101

# PIONEER AF-PCI trial Outcomes

Answer 101

– Primary endpoint (rates of clinically significant bleeding) was lower in the two groups receiving rivaroxaban: Group 1 was 16.8%, Group 2 was 18.0%, and Group 3 was 26.7% (HR for group 1 vs. group 3 was 0.59; 95% CI 0.47-0.76; P<0.001; and HR for group 2 vs. group 3 was 0.63; 95% CI 0.50-0.80; P<0.001) – The rates of death from cardiovascular causes, myocardial infarction, or stroke were similar in the three groups– Primary endpoint (rates of clinically significant bleeding) was lower in the two groups receiving rivaroxaban: Group 1 was 16.8%, Group 2 was 18.0%, and Group 3 was 26.7% (HR for group 1 vs. group 3 was 0.59; 95% CI 0.47-0.76; P<0.001; and HR for group 2 vs. group 3 was 0.63; 95% CI 0.50-0.80; P<0.001) – The rates of death from cardiovascular causes, myocardial infarction, or stroke were similar in the three groups

Question 102

# PIONEER AF-PCI trial Conclusion

Answer 102

In participants with atrial fibrillation undergoing PCI with placement of stents, the administration of either low-dose rivaroxaban plus a P2Y12 inhibitor for 12 months or very-low-dose rivaroxaban plus DAPT for 1, 6, or 12 months was associated with a lower rate of clinically significant bleeding than was standard therapy with a vitamin K antagonist plus DAPT for 1, 6, or 12 months. The three groups had similar efficacy rates, although the observed broad confidence intervals diminish the surety of any conclusions regarding efficacy

Question 103

# AUGUSTUS trial Journal and year of publication

Answer 103

NEJM, 2019

Question 104

# AUGUSTUS trial Trial Design

Answer 104

Randomized controlled clinical trial

Question 105

# AUGUSTUS trial Population

Answer 105

4,614 patients with nonvalvular Afib + ACS/PCI Key inclusion criteria: – History of atrial fibrillation and planned long-term use of an oral anticoagulant. – Recent acute coronary syndrome or PCI. – Planned use of a P2Y12 inhibitor for at least 6 months Key exclusion criteria: – Patients who were using anticoagulation for other conditions (e.g., prosthetic valves, venous thromboembolism, and mitral stenosis). – Severe renal insufficiency. – History of intracranial hemorrhage. – Recent or planned coronary-artery bypass graft surgery.

Question 106

# AUGUSTUS trial Intervention Studied

Answer 106

Intervention Studied: Intervention 1: Apixaban (5 mg twice daily or to take 2.5 mg twice daily if they met reduced dose criteria) Intervention 2: Aspirin (81 mg daily) Control: Control 1: Vitamin K antagonist to target INR of 2.0 – 3.0 Control 2: Matching placebo

Question 107

# AUGUSTUS trial Outcomes

Answer 107

– Primary endpoint (major or clinically relevant nonmajor bleeding): 10.5% in the apixaban group vs 14.7% in the vitamin K antagonist group (HR 0.69; 95% CI 0.58-0.81; P<0.001 for both noninferiority and superiority) and 16.1% of the patients receiving aspirin vs 9.0% of those receiving placebo (HR 1.89; 95% CI 1.59-2.24, P<0.001) – Patients in the apixaban group lower incidence of death or hospitalization than the VKA group, and both had similar incidences of ischemic events

Question 108

# AUGUSTUS trial Conclusion

Answer 108

In patients with atrial fibrillation and a recent acute coronary syndrome or PCI treated with a P2Y12 inhibitor, an antithrombotic regimen that included apixaban, without aspirin, resulted in less bleeding and fewer hospitalizations without significant differences in the incidence of ischemic events than regimens that included a vitamin K antagonist, aspirin, or both

Question 109

# AIM-HIGH trial Journal and year of publication

Answer 109

NEJM, 2011

Question 110

# AIM-HIGH trial Trial Design

Answer 110

Randomized controlled clinical trial

Question 111

# AIM-HIGH trial Population

Answer 111

3,414 patients Key inclusion criteria: – Low baseline levels of HDL cholesterol (<40 mg/dL for men; <50 mg/dL for women) – 45 years and older with established vascular disease and atherogenic dyslipidemia – Discontinued lipid-modifying drugs, except for statins or ezetimibe Key exclusion criteria: – Had a stroke within the preceding 8 weeks – Fasting glucose >180 mg/dL or HbA1C >9.0% – Patients with left main coronary disease ≥50% and no prior CABG

Question 112

# AIM-HIGH trial Intervention Studied

Answer 112

Intervention Studied: Extended-release niacin 1500 to 2000 mg/day (+/- Simvastatin 40 to 80 mg/day, ezetimibe 10 mg/day, to maintain an LDL cholesterol level of 40 to 80 mg/dL) Control: Placebo (+/- Simvastatin 40 to 80 mg/day, ezetimibe 10 mg/day, to maintain an LDL cholesterol level of 40 to 80 mg/dL)

Question 113

# AIM-HIGH trial Outcomes

Answer 113

At 2 years, Niacin group had the following changes in their lipid panel results: – Median HDL cholesterol level: Increased from 35 to 42 mg/dL (P<0.001) – Triglyceride level: Lowered from 164 to 122 mg/dL – LDL cholesterol level: Lowered from 74 to 62 mg/dL Primary end point occurrence (first event of the composite of death from coronary heart disease, nonfatal MI, ischemic stroke, hospitalization for an ACS, or symptom-driven coronary or cerebral revascularization): – Niacin group: 282 patients (16.4%) vs Placebo group: 274 patients (16.2%); HR:1.02 (95% CI: 0.87 to 1.21) (P=0.79)

Question 114

# AIM-HIGH trial Conclusion

Answer 114

Among patients with atherosclerotic cardiovascular disease and LDL cholesterol levels of less than 70 mg per deciliter (1.81 mmol per liter), there was no incremental clinical benefit from the addition of niacin to statin therapy during a 36-month follow-up period, despite significant improvements in HDL cholesterol and triglyceride levels.