FOURIER Trial design: Patients with established cardiovascular disease on statin therapy were randomized to evolocumab 140 mg subcutaneous every 2 weeks.

Slides:

Advertisements

Similar presentations

Slide Source: Lipids Online Slide Library Pravastatin or Atorvastatin Evaluation and Infection Therapy (PROVE IT): Design Cannon CP.

Advertisements

TNT: Study Design Treating to New Targets 2 5 years 10,001 Patients Clinically evident CHD LDL-C 130  250 mg/dL following up to 8-week washout and 8-week.

Cholesterol quintile (mg/dL)

VBWG IDEAL: The Incremental Decrease in End Points Through Aggressive Lipid Lowering Study.

Randomized, double-blind, multicenter, controlled trial.

VBWG HPS. Lancet. 2003;361: Gæde P et al. N Engl J Med. 2003;348: Recent statin trials: Reduction in primary outcome in patients with diabetes.

Laura Mucci, Pharm.D. Candidate Mercer University 2012 Preceptor: Dr. Rahimi February 2012.

WOSCOPS: West Of Scotland Coronary Prevention Study Purpose To determine whether pravastatin reduces combined incidence of nonfatal MI and death due to.

LIPID: Long-term Intervention with Pravastatin in Ischemic Disease Purpose To determine whether pravastatin will reduce coronary mortality and morbidity.

HOPE: Heart Outcomes Prevention Evaluation study Purpose To evaluate whether the long-acting ACE inhibitor ramipril and/or vitamin E reduce the incidence.

The Heart Outcomes Prevention Evaluation (HOPE) 2 Investigators. N Engl J Med 2006; available at: End pointActive therapy PlaceboRelative.

Rosuvastatin 10 mg n=2514 Placebo n= to 4 weeks Randomization 6weeks3 monthly Closing date 20 May 2007 Eligibility Optimal HF treatment instituted.

The JUPITER Trial Reference Ridker PM. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008;359:2195–2207.

Statins The AURORA Trial Reference Fellstrom BC. Rosuvastatin and cardiovascular events in patients undergoing hemodialysis. N Engl J Med. 2009;360. A.

ACCP Cardiology PRN Journal Club

FOURIER Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk

(p for noninferiority = 0.01)

Trial profile SAS denotes the Simvastatin in Aortic Stenosis Study

European Society of Cardiology 2017 Clinical Trial Update I

PRAGUE-18 Trial design: Patients with STEMI undergoing primary PCI were randomized to prasugrel (n = 634) versus ticagrelor (n = 596). Results (p = 0.94)

NORSTENT Trial design: Patients with obstructive coronary artery disease were randomized to a drug-eluting stent (DES) (n = 4,504) versus a bare-metal.

CORAL Trial design: Patients with renal artery stenosis and hypertension or chronic kidney disease were randomized to renal artery stenting (n = 467) vs.

APEX Trial design: Patients hospitalized with an acute medical illness were randomized to oral betrixaban for days (n = 3,759) versus subcutaneous.

HOPE: Heart Outcomes Prevention Evaluation study

SOCRATES Trial design: Patients with acute ischemic stroke were randomized in a 1:1 fashion to receive either ticagrelor 180 mg load + 90 mg BID or aspirin.

The IDEAL Study Reference

Reduction in Total Cardiovascular Events with the PCSK9 Inhibitor Evolocumab in Patients with Cardiovascular Disease in the FOURIER Trial Sabina A. Murphy,

CANTOS: The Canakinumab Anti-Inflammatory Thrombosis Outcomes Study

SPIRE Program: Studies of PCSK9 Inhibition and the Reduction of Vascular Events Unanticipated attenuation of LDL-c lowering response to humanized PCSK9.

TNT: Baseline and final LDL cholesterol levels

RE-CIRCUIT Trial design: Patients with atrial fibrillation undergoing catheter ablation were randomized to uninterrupted dabigatran 150 mg twice daily.

BENEFIT Trial design: Patients with positive serologic tests for T. Cruzi and cardiomyopathy were randomized to benznidazole 300 mg daily for days.

EUCLID Trial design: Patients with peripheral arterial disease (PAD) were randomized to ticagrelor 90 mg twice daily (n = 6,930) vs. clopidogrel 75 mg.

GLAGOV Trial design: Patients with CAD and elevated LDL cholesterol on statin therapy were randomized to subcutaneous evolocumab (n = 484) vs. subcutaneous.

LEVO-CTS Trial design: Patients undergoing cardiac surgery with the use of cardiopulmonary bypass were randomized to infusion of levosimendan 0.2 µg/kg/min.

EMPA-REG OUTCOME Trial design: Patients with type 2 diabetes mellitus (DM2) at high risk for CV events were randomized to receive in a 1:1:1 fashion either.

Figure 3 Ischaemic outcomes in the ST-segment elevation myocardial

EVITA Trial design: Smokers admitted with an acute coronary syndrome were randomized to varenicline 1 mg twice daily (n = 151) vs. placebo (n = 151). Study.

Compare-Acute Trial design: STEMI patients undergoing primary PCI were randomized to fractional flow reserve (FFR)-guided complete revascularization (n.

PRECISION Trial design: Patients with arthritis and increased cardiovascular risk were randomized to celecoxib 100 mg twice daily (n = 8,072) vs. ibuprofen.

ANTARCTIC Trial design: Patients with acute coronary syndrome undergoing stenting were randomized to tailored antiplatelet therapy (n = 435) versus conventional.

SIGNIFY Trial design: Participants with stable coronary artery disease without clinical heart failure and resting heart rate >70 bpm were randomized to.

SMILE Trial design: NSTEMI patients were randomized to complete revascularization during the index procedure (i.e., 1-stage revascularization; n = 264)

SUSTAIN-6 Trial design: Patients with DM2 at high risk for CV events were randomized in a 1:1:1:1 fashion to either semaglutide 0.5 mg, semaglutide 1 mg,

LATITUDE-TIMI 60 Trial design: Patients hospitalized with AMI on guideline-recommended therapy were randomized in a 1:1 fashion to either losmapimod 7.5.

After Eighty Study Trial design: Elderly patients with non–ST-elevation acute coronary syndrome (NSTE-ACS) were randomized to invasive therapy (n = 229)

TACTICS-HF Trial design: Patients with acute heart failure (reduced or preserved ejection fraction) were randomized to tolvaptan 30 mg at 0, 24, and 48.

Screening, Lipid Stabilization, and Placebo Run-in

(p = 0.32 for noninferiority)

(p < for noninferiority)

OSLER Trial design: Patients from five phase 2 trials and seven phase 3 trials with evolocumab were invited to participate in the OSLER extension program,

(p for noninferiority < 0.001)

(p = for noninferiority)

Potential mechanisms whereby statins may reduce the risk of stroke

ARISE Trial Aggressive Reduction of Inflammation Stops Events

HOPE-3 Trial design: Patients without known cardiovascular disease, and with an intermediate risk of cardiovascular events, were randomized in a 2 x 2.

Flow diagram for exclusions of trials identified RCT indicates randomized controlled trial Hulten E, et al. Arch Intern Med 2006;166:

RUTHERFORD-2 Trial design: Patients with heterogeneous familial hypercholesterolemia (HeFH) on statins were randomized in a 2:2:1:1 fashion to subcutaneous.

SOLID-TIMI 52 Trial design: Participants within 30 days of an acute coronary syndrome (ACS) were randomized to darapladib 160 mg daily (n = 6,504) versus.

Baseline Characteristics by hs-CRP

IVUS-XPL Trial design: Patients undergoing drug-eluting stent implantation for long coronary lesions were randomized to IVUS-guided PCI (n = 700) vs. angiography-guided.

(p for noninferiority = 0.01)

MATRIX: Radial vs. Femoral

SPIRE Program: Studies of PCSK9 Inhibition and the Reduction of Vascular Events Unanticipated attenuation of LDL-c lowering response to humanized PCSK9.

Additional benefit of PCSK9 inhibition in high risk patients after myocardial infarction A FOURIER subanalysis Primary endpoint: composite of CV death,

The benefit of evolocumab treatment is consistent regardless of inflammation level HR %CI ARR 1.6% 1.8%

Baseline characteristics of study population

CIRCUS Trial design: Patients with anterior STEMI were randomized to IV cyclosporine 2.5 mg/kg (n = 475) vs. placebo (n = 495) immediately before coronary.

Section C: Clinical trial update: Oral antiplatelet therapy

LDL is causal of atherosclerosis Evidence from meta-analyses of Mendelian randomization studies, prospective cohort studies, and randomized controlled.

Presentation transcript:

FOURIER Trial design: Patients with established cardiovascular disease on statin therapy were randomized to evolocumab 140 mg subcutaneous every 2 weeks or 420 mg monthly (n = 13,784) versus placebo every 2 weeks (n = 13,780). Results (p < 0.0001) Cardiovascular death, MI, stroke, hospitalization for unstable angina, or coronary revascularization: 12.6% of the evolocumab group versus 14.6% of the placebo group (p < 0.0001) Any serious adverse event: 24.8% with evolocumab versus 24.7% with placebo 14.6 % 12.6 Conclusions Among patients with elevated cardiovascular risk on statin therapy, evolocumab versus placebo was effective at reducing adverse cardiovascular events Serious adverse events were similar between treatment groups Evolocumab Placebo Sabatine MS, et al. N Engl J Med 2017;Mar 17:[Epub]