Intended for healthcare professionals

Practice Rapid Recommendations

PCSK9 inhibitors and ezetimibe for the reduction of cardiovascular events: a clinical practice guideline with risk-stratified recommendations

BMJ 2022; 377 doi: https://doi.org/10.1136/bmj-2021-069066 (Published 04 May 2022) Cite this as: BMJ 2022;377:e069066
Visual summary of recommendation
Population This recommendation applies only to people with these characteristics: Adults with elevated low-density lipoprotein (LDL) cholesterol Over 70 mg/dL Over 1.8 mmol/L Using high dose statins or intolerant to statins Wanting to reduce the risk of major cardiovascular events People using high dose statins Recommendation Risk of experiencinga major adversecardiovascular eventwithin 5 years People intolerant to statins MACE Low <5% 1 Recommendation 5 Recommendation Moderate 5-15% 2 Recommendation 6 Recommendation High 15-20% 3 Recommendation 7 Recommendation Very high >20% 4 Recommendation 8
Interventions compared Statins alone Ezetimibeplus statins Ezetimibe plusPCSK9 inhibitorsplus statins PCSK9 inhibitorsplus statins People receiving high dose statins No lipid- lowering drug Ezetimibealone Ezetimibe plusPCSK9 inhibitors PCSK9 inhibitorsalone People intolerant to statins
Recommendation 1Adults considering cardiovascular risk reduction |Receiving high dose statins | Low cardiovascular risk
Statins aloneAdding a second lipid-loweringdrugorPeople consideringcardiovascular risk reductionWe recommend against adding a secondlipid-lowering drugStrongAll or nearly all informed people would likelywant the intervention to the left. Benefitswould outweigh harms for almost everyoneWeakMost people would likely want the interventionto the left. Benefits would outweigh harms forthe majority, but not for everyoneWeakMost people would likely want the interventionto the right. Benefits would outweigh harmsfor the majority, but not for everyoneStrongAll or nearly all informed people would likelywant the intervention to the right. Benefitswould outweigh harms for almost everyone
Recommendation 2Adults considering cardiovascular risk reduction |Receiving high dose statins | Moderatecardiovascular risk
Statins aloneAdding a second lipid-loweringdrugorPeople consideringcardiovascular risk reductionWe suggest not adding a second lipid-lowering drugStrongAll or nearly all informed people would likelywant the intervention to the left. Benefitswould outweigh harms for almost everyoneWeakMost people would likely want the interventionto the left. Benefits would outweigh harms forthe majority, but not for everyoneWeakMost people would likely want the interventionto the right. Benefits would outweigh harmsfor the majority, but not for everyoneStrongAll or nearly all informed people would likelywant the intervention to the right. Benefitswould outweigh harms for almost everyone
Ezetimibe plus statinsPCSK9 inhibitors plus statinsorPeople adding a secondlipid-lowering drugWe suggest adding ezetimibe firstStrongAll or nearly all informed people would likelywant the intervention to the left. Benefitswould outweigh harms for almost everyoneWeakMost people would likely want the interventionto the left. Benefits would outweigh harms forthe majority, but not for everyoneWeakMost people would likely want the interventionto the right. Benefits would outweigh harmsfor the majority, but not for everyoneStrongAll or nearly all informed people would likelywant the intervention to the right. Benefitswould outweigh harms for almost everyone
Ezetimibe plus statinsEzetimibe plus PCSK9inhibitors plus statinsorPeople considering furthercardiovascular risk reductionWe recommend not adding a PCSK9 inhibitor toezetimibe plus statinsStrongAll or nearly all informed people would likelywant the intervention to the left. Benefitswould outweigh harms for almost everyoneWeakMost people would likely want the interventionto the left. Benefits would outweigh harms forthe majority, but not for everyoneWeakMost people would likely want the interventionto the right. Benefits would outweigh harmsfor the majority, but not for everyoneStrongAll or nearly all informed people would likelywant the intervention to the right. Benefitswould outweigh harms for almost everyone
Recommendation 3Adults considering cardiovascular risk reduction |Receiving high dose statins | High cardiovascular risk
Statins aloneAdding a second lipid-loweringdrugorPeople consideringcardiovascular risk reductionWe suggest adding a second lipid-lowering drugStrongAll or nearly all informed people would likelywant the intervention to the left. Benefitswould outweigh harms for almost everyoneWeakMost people would likely want the interventionto the left. Benefits would outweigh harms forthe majority, but not for everyoneWeakMost people would likely want the interventionto the right. Benefits would outweigh harmsfor the majority, but not for everyoneStrongAll or nearly all informed people would likelywant the intervention to the right. Benefitswould outweigh harms for almost everyone
Ezetimibe plus statinsPCSK9 inhibitors plus statinsorPeople adding a secondlipid-lowering drugWe suggest adding ezetimibe firstStrongAll or nearly all informed people would likelywant the intervention to the left. Benefitswould outweigh harms for almost everyoneWeakMost people would likely want the interventionto the left. Benefits would outweigh harms forthe majority, but not for everyoneWeakMost people would likely want the interventionto the right. Benefits would outweigh harmsfor the majority, but not for everyoneStrongAll or nearly all informed people would likelywant the intervention to the right. Benefitswould outweigh harms for almost everyone
Ezetimibe plus statinsEzetimibe plus PCSK9inhibitors plus statinsorPeople considering furthercardiovascular risk reductionWe suggest not adding a PCSK9 inhibitor toezetimibe plus statinsStrongAll or nearly all informed people would likelywant the intervention to the left. Benefitswould outweigh harms for almost everyoneWeakMost people would likely want the interventionto the left. Benefits would outweigh harms forthe majority, but not for everyoneWeakMost people would likely want the interventionto the right. Benefits would outweigh harmsfor the majority, but not for everyoneStrongAll or nearly all informed people would likelywant the intervention to the right. Benefitswould outweigh harms for almost everyone
Recommendation 4Adults considering cardiovascular risk reduction |Receiving high dose statins | Very highcardiovascular risk
Statins aloneAdding a second lipid-loweringdrugorPeople consideringcardiovascular risk reductionWe suggest adding a second lipid-lowering drugStrongAll or nearly all informed people would likelywant the intervention to the left. Benefitswould outweigh harms for almost everyoneWeakMost people would likely want the interventionto the left. Benefits would outweigh harms forthe majority, but not for everyoneWeakMost people would likely want the interventionto the right. Benefits would outweigh harmsfor the majority, but not for everyoneStrongAll or nearly all informed people would likelywant the intervention to the right. Benefitswould outweigh harms for almost everyone
Ezetimibe plus statinsPCSK9 inhibitors plus statinsorPeople adding a secondlipid-lowering drugWe suggest adding ezetimibe firstStrongAll or nearly all informed people would likelywant the intervention to the left. Benefitswould outweigh harms for almost everyoneWeakMost people would likely want the interventionto the left. Benefits would outweigh harms forthe majority, but not for everyoneWeakMost people would likely want the interventionto the right. Benefits would outweigh harmsfor the majority, but not for everyoneStrongAll or nearly all informed people would likelywant the intervention to the right. Benefitswould outweigh harms for almost everyone
Ezetimibe plus statinsEzetimibe plus PCSK9inhibitors plus statinsorPeople considering furthercardiovascular risk reductionWe suggest adding a PCSK9 inhibitor to ezetimibeplus statinsStrongAll or nearly all informed people would likelywant the intervention to the left. Benefitswould outweigh harms for almost everyoneWeakMost people would likely want the interventionto the left. Benefits would outweigh harms forthe majority, but not for everyoneWeakMost people would likely want the interventionto the right. Benefits would outweigh harmsfor the majority, but not for everyoneStrongAll or nearly all informed people would likelywant the intervention to the right. Benefitswould outweigh harms for almost everyone
Recommendation 5Adults considering cardiovascular risk reduction |Intolerant to statins | Low cardiovascular risk
No lipid-lowering drugEzetimibe or PCSK9 inhibitorsorPeople consideringcardiovascular risk reductionWe recommend against using a lipid-lowering drugStrongAll or nearly all informed people would likelywant the intervention to the left. Benefitswould outweigh harms for almost everyoneWeakMost people would likely want the interventionto the left. Benefits would outweigh harms forthe majority, but not for everyoneWeakMost people would likely want the interventionto the right. Benefits would outweigh harmsfor the majority, but not for everyoneStrongAll or nearly all informed people would likelywant the intervention to the right. Benefitswould outweigh harms for almost everyone
Recommendation 6Adults considering cardiovascular risk reduction |Intolerant to statins | Moderate cardiovascular risk
No lipid-lowering drugEzetimibe or PCSK9 inhibitorsorPeople consideringcardiovascular risk reductionWe suggest not using a lipid-lowering drugStrongAll or nearly all informed people would likelywant the intervention to the left. Benefitswould outweigh harms for almost everyoneWeakMost people would likely want the interventionto the left. Benefits would outweigh harms forthe majority, but not for everyoneWeakMost people would likely want the interventionto the right. Benefits would outweigh harmsfor the majority, but not for everyoneStrongAll or nearly all informed people would likelywant the intervention to the right. Benefitswould outweigh harms for almost everyone
EzetimibePCSK9 inhibitorsorPeople starting alipid-lowering drugWe suggest adding ezetimibe firstStrongAll or nearly all informed people would likelywant the intervention to the left. Benefitswould outweigh harms for almost everyoneWeakMost people would likely want the interventionto the left. Benefits would outweigh harms forthe majority, but not for everyoneWeakMost people would likely want the interventionto the right. Benefits would outweigh harmsfor the majority, but not for everyoneStrongAll or nearly all informed people would likelywant the intervention to the right. Benefitswould outweigh harms for almost everyone
EzetimibeEzetimibe plus PCSK9inhibitorsorPeople considering furthercardiovascular risk reductionWe suggest not adding a PCSK9 inhibitor toezetimibeStrongAll or nearly all informed people would likelywant the intervention to the left. Benefitswould outweigh harms for almost everyoneWeakMost people would likely want the interventionto the left. Benefits would outweigh harms forthe majority, but not for everyoneWeakMost people would likely want the interventionto the right. Benefits would outweigh harmsfor the majority, but not for everyoneStrongAll or nearly all informed people would likelywant the intervention to the right. Benefitswould outweigh harms for almost everyone
Recommendation 7Adults considering cardiovascular risk reduction |Intolerant to statins | High cardiovascular risk
No lipid-lowering drugEzetimibe or PCSK9 inhibitorsorPeople consideringcardiovascular risk reductionWe recommend using a lipid-lowering drugStrongAll or nearly all informed people would likelywant the intervention to the left. Benefitswould outweigh harms for almost everyoneWeakMost people would likely want the interventionto the left. Benefits would outweigh harms forthe majority, but not for everyoneWeakMost people would likely want the interventionto the right. Benefits would outweigh harmsfor the majority, but not for everyoneStrongAll or nearly all informed people would likelywant the intervention to the right. Benefitswould outweigh harms for almost everyone