Trials

Question 1

What did the CURE trial demonstrate?

Answer 1

• Clopidogrel in Unstable angina to prevent Recurrent Events (CURE)
• Clinical question –>
  
  • in patients with UA/NSTEMI does the addition of clopidogrel reduce CV mortality, MI, or stroke?
• Bottom line –>
  
  • DAPT with clopidogrel and ASA reduced CV mortality, non-fatal MI, or stroke largely due to reduction in MI
  • but increase the rate of major bleeding

Question 2

What did the WOEST trial show?

Answer 2

• Clinical question –>
  
  • In patients on oral anticoagulation undergoing PCI, does using clopidogrel alone reduce the risk of bleeding compared with clopidogrel plus aspiring?
• Bottom line –>
  
  • in patients on OAC undergoing PCI, use of clopidogrel alone (double therapy) was associated with a significant reduction in bleeding complications compared to patients receiving clopidogrel with aspirin (triple therapy)

Question 3

What did the PIONEER AF-PCI trial show?

Answer 3

• “Prevention of bleeding in patients with AF undergoing PCI”
• Clinical Question –>
  
  • Among patients with nonvalvular AF undergoing PCI with stent placement,
  • Reduce risk of bleeding:
    
    • low-dose rivaroxaban +DAPT
    • Rivaroxaban + P2Y12 inhibitor
    • Warfarain + DAPT
• Bottom line –>
  
  • Among patients with nonvalvular AF undergoing PCI with stent placement:
    
    • use of low dose rivaroxaban plus either single or DAPT reduces the risk of bleeding when compared to warfarin plus DAPT at 1 year.
    • No difference in CV mortality, MI or storke at 1 year

Question 4

What did the RALES trial show?

Answer 4

• “The effect of spironolactone on mobidity and mortality in patients with severe heart failure”
• Clinical Question –>
  
  • In patients with HFrEF and NYHA class III-IV symptoms, does spironolactone reduce mortality?
• Bottom Line –>
  
  • In patients with HFrEF (EF < 35%) and NYHA III-IV symptoms, spironolactone led to a 30% reduction in all-cause mortality

Question 5

What did the EPHESUS trial show?

Answer 5

• Clinical Question –>
  
  • In patients with acute MI complicated by LV dysfunction and HF symptoms, does eplerenone reduce mortality?
• Bottom line –>
  
  • Eplerenone reduced the rate of mortality among patients with acute MI complicated by LV dysfunction and HF symptoms.

Question 6

What did the PARTNER B (2010) study show?

Answer 6

• TAVI for AS in patients who cannot undergo surgery
• Clinical Question –>
  
  • In patients with severe AS who are poor surgical candidates,
  • does TAVI compared to standard care (balloon valvuloplasty) reduce:
    
    • all-cause mortality
    • rehospitalization rates
• Bottom Line –>
  
  • reduces
    
    • all-cause mortality
    • rates of rehospitalization
  • Increased risk of strokes

Question 7

Describe the PARTNER B trial?

Answer 7

• Prospective, multicenter, randomized, open-labe, comparative trial
• 358 patients:
  
  • severe AS
  • poor surgical candidates
• Randomized:
  
  • TAVI
  • medical management (balloon angioplasty - class III recommendation)
• Major points:
  
  • 2% lower all-cause mortality at 1 year
  • lower major bleeding and A-fib
  • lower ICU and hospital stay
  • increased stroke and vascular complications at 1 year

Question 8

What did the PARTNER A trial show?

Answer 8

• Clinical Question –>
  
  • In patients with symptomatic severe AS who are high-risk surgical candidates (expected periprocedural mortality ~ 15%), is transcatheter aortic valve implantation (TAVI) noninferior to surgical aortic valve replacement (AVR) with regard to all-cause mortality?
• Bottom Line –>
  
  • In patients with symptomatic severe AS who are high-risk surgical candidates (expected periprocedural mortality ~ 15%); TAVI was associated with similar all-cause mortality to surgical AVR at 1 year

Question 9

Describe the PARTNER A (2011) trial?

Answer 9

• Prospective, multicenter, randomized, open-labe, comparative trial
• 699 patients:
  
  • severe, symptomatic AS
  • high-risk surgical candidates
    
    • (expected periprocedural mortality ~ 15%)
• Randomized:
  
  • TAVI
  • Surgical AVR
• Major points:
  
  • lower all-cause mortality at 1 year
• confirmed at 5 year follow up
• increased stroke at 1 year
• increased major bleeding at 1 year

Question 10

What did SCD-HeFT (2005) demonstrate?

Answer 10

• “Amiodarone or an ICD for CHF”
• Clinical question
  
  • In patients with HFrEF and NYHA II-III symptoms, how does amiodarone or ICD implantation compare to placebo in reducing all-cause mortality
• Bottom Line
  
  • SCD-HeFT demonstrated that ICD’s reduce mortality compared to conventional therapy or amiodarone among patients with HFrEF

Question 11

What Guidelines were adapted as a result of the SCD-HeFT trial (2005)?

Answer 11

• ICD if nonischemic dilated cardiomyopathy or ICM > 40 days post MI with LVEF < 35% and NYHA class II or III symptoms on OMT with expected survival > 1 year
• ICD for ICM > 40 days post MI with LVEF < 30%, NYHA class I symptoms on OMT with expected survival > 1 year

Question 12

Describe the SCD-HeFT trial

Answer 12

• Multicenter, double-blinded, parallel-group, randomized, placebo-controlled trial
• 2,521 patients
  
  • Amiodarone
  • Shock-only
  • Placebo
• Single-lead, shock-only ICD therapy reduces mortality by 23% compared to conventional therapy or amiodarone in stable NYhA class II or III HF with EF < 35%
• Amiodarone conferred no survival benefit compared to placebo

Question 13

What did the MADIT-II trial (2002) show?

Answer 13

• “Prophylactic Implantation of a Defibrillator in Patients with MI and Reduced EF”
  
  • Multicenter Automatic Defibrillator Implantation Trial II
• Clinical Question
  
  • In patients with ischemic cardiomyopathy, does prophylactic ICD placement improve survival?
• Bottom Line
  
  • In post-MI patients with systolic dysfunction (EF < 30%), prophylactic ICD reduced all-cause mortality compared to standar medical therapy

Question 14

Describe the MADIT-II (2002) trial

Answer 14

• Multicenter, non-blinded, parallel group, randomized controlled trial
• 1,232 patients with previous MI and LVEF < 30%
  
  • ICD
  • Conventional medical therapy
• Did not require EP testing for inducible VT prior to enrollment
• Trial terminated early (mean ~ 20 months) because prophylactic ICD reduced all-cause mortality
  
  • attributed to reduction in SCD

Question 15

What did the MADIT-I trial (1996) show?

Answer 15

• “Multicenter Automatic Defibrillator Implantation Trial (MADIT)
• Clinical Question
  
  • In patients with ICM, prior MI, LVEF < 35%, NYHA I-III, NSVT with EPS inducible arrhythmia does ICD reduce mortality
    
    • conventional medical therapy
    • CMT + ICD
• Bottom Line
  
  • Use of ICDs resulted in a 54% reduction in the risk of all-cause mortality rate in the defibrillator group as compared to the CMT group.