Dyslipidemia trials (IPFC 3)

Nurses’ Health Study

P: 1*, healthy women

I: healthy habits (no smoking, exercise, healthy diet, healthy weight, mod alcohol intake)

C: fewer healthy lifestyle habits

O: more healthy lifestyle factors = lower CVD risk (RRR 50%), increased life expectancy (mortality RRR 35%), smoking 1 cigarette/day sig increase MI risk (50%)

ASCOT trial

P: 1*, >40y, multiple CV risk factors, elevated LDL

I: mod intensity statin

C: placebo

O: reduced composite CV outcomes

take home: mod intensity statins work for high risk 1* prevention

USPSTF Evidence review

P: 1*, 40+

I: statins

C: placebo/no statin

O: reduced CV events

take home: strong evidence supporting statins for 1* prevention

JUPITER trial

P: 1*, elevated CRP >2, no established ASCVD

I: high intensity rosuvastatin

C: placebo

O: reduced major CV events, increased incidence DM, trial stopped early due to benefit

take home: high intensity statins benefit some 1* pts but slightly increases DM

JAMA Treat to Target Trial

P: 2*, established ASCVD

I: treat to target LDL

C: fixed high intensity statin

O: non inferior outcome

take home: treat to target performed similar to routine high intensity

Helsinki Heart Study

P: 1*, high non HDL cholesterol

I: gemfibrozil

C: placebo

O: reduced CV events, no reduction in all cause mortality, many GI AEs

take home: gemfibrozil has evidence as monotherapy in 1* but benefits limited

FIELD trial

P: T2DM

I: fenofibrate

C: placebo

O: reduced non fatal MI and coronary revascularization, no reduction in fatal CV events

take home: limited benefit, fibrates not added to statins

LRC-CPPT trial

P: 1*, very high total cholesterol

I: cholestyramine

C: placebo

O: reduced CHD, no reduction in overall mortality, significant GI AEs

take home: older pre statin evidence supports cholestyramine for 1* prevention

IMPROVE-IT trial

P: 2*, recent ACS

O: simvastatin + ezetimibe

C: simvastatin only

O: reduced CV events, no reduction in all cause mortality

take home: ezetimibe works as add on therapy, no evidence as monotherapy

FOURIER trial

P: 2* prevention, ASCVD + max tolerated statin

I: evolocumab

C: placebo

O: reduced MI, stroke and composite CV events

take home: PCSK9i improve outcomes only as add on therapy to statins

ODYSSEY outcomes trial

P: 2*, recent ACS, already on statin

I: alirocumab

C: placebo

O: reduced CV events and composite CV outcome

take home: PCSK9i + statin good

ORION 10/11 phase 3 trials

P: 2*, high risk with ASCVD

I: inclisiran

C: placebo

O: large LDL reduction (50%), no complete CV outcomes yet

take home: strong LDL lowering but clinical outcome evidence still developing

ORION 4 trial

P: 2*, ACSVD

I: inclisiran

C: placebo

O: ongoing CV outcomes trial

ELIPSE HoFH trial

P: 2*, HoFH

I: ANGPTL3i

C: standard therapy

O: significant LDL reduction, no clinical outcome evidence

take home: surrogate LDL benefit only

REDUCE-IT (VASCEPA) trial

P: 70% 2*, 30% 1* with DM, elevated TG despite maximal statin (TG 1.52-5.63)

I: icosapent ethyl

C: placebo

O: reduced CV events, no reduction in all cause mortality

take home: use only in high risk pts with TG 1.5-5.6 already on maximally tolerated statins

Lomitapide Phase III study

P: 2*, HoFH

I: lomitapide

C: standard therapy

O: reduced LDL, limited clinical outcome data, liver toxicity concern

take home: LDL lowering only, monitor liver fx

AIM-HIGH trial

P: 2*

I: simvastatin + ER niacin

C: simvastatin only

O: no CV benefit, trial stopped early, possible increase in ischemic stroke

take home: niacin does not improve outcomes when added to statins

HPS2 THRIVE trial

P: 2*

I: simvastatin + ER niacin + laropiprant

C: simvastatin only

O: no CV benefit, more AEs, possible increase in mortality

take home: niacin not rec (harms > benefit)

ACCELERATE trial

P: 2*, included DM

I: evacetrapib

C: placebo

O: LDL decreased, HDL increased, no reduction in CV events

take home: improving surrogates does not equal clinical outcomes

CLEAR outcomes trial

P: 1* or 2* prevention, statin intolerant (or low dose statin)

I: bempedoic acid

C: placebo

O: reduced CV events and clinical outcomes in both 1* and 2*

take home: only non statin med with evidence for monotherapy in statin intolerant