Baris Gencer1, Nicholas A Marston1, KyungAh Im1, Christopher P Cannon2, Peter Sever3, Anthony Keech4, Eugene Braunwald1, Robert P Giugliano1, Marc S Sabatine5. 1. TIMI Study Group, Division of Cardiovascular Medicine, Harvard Medical School, Boston, MA, USA. 2. Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. 3. National Heart and Lung Institute, Imperial College London, London, UK. 4. National Health and Medical Research Council Clinical Trials Centre, Sydney Medical School, University of Sydney, Sydney, NSW, Australia. 5. TIMI Study Group, Division of Cardiovascular Medicine, Harvard Medical School, Boston, MA, USA. Electronic address: msabatine@bwh.harvard.edu.
Abstract
BACKGROUND: The clinical benefit of LDL cholesterol lowering treatment in older patients remains debated. We aimed to summarise the evidence of LDL cholesterol lowering therapies in older patients. METHODS: In this systematic review and meta-analysis, we searched MEDLINE and Embase for articles published between March 1, 2015, and Aug 14, 2020, without any language restrictions. We included randomised controlled trials of cardiovascular outcomes of an LDL cholesterol-lowering drug recommended by the 2018 American College of Cardiology and American Heart Association guidelines, with a median follow-up of at least 2 years and data on older patients (aged ≥75 years). We excluded trials that exclusively enrolled participants with heart failure or on dialysis because guidelines do not recommend lipid-lowering therapy in such patients who do not have another indication. We extracted data for older patients using a standardised data form for aggregated study-level data. We meta-analysed the risk ratio (RR) for major vascular events (a composite of cardiovascular death, myocardial infarction or other acute coronary syndrome, stroke, or coronary revascularisation) per 1 mmol/L reduction in LDL cholesterol. FINDINGS: Data from six articles were included in the systematic review and meta-analysis, which included 24 trials from the Cholesterol Treatment Trialists' Collaboration meta-analysis plus five individual trials. Among 244 090 patients from 29 trials, 21 492 (8·8%) were aged at least 75 years, of whom 11 750 (54·7%) were from statin trials, 6209 (28·9%) from ezetimibe trials, and 3533 (16·4%) from PCSK9 inhibitor trials. Median follow-up ranged from 2·2 years to 6·0 years. LDL cholesterol lowering significantly reduced the risk of major vascular events (n=3519) in older patients by 26% per 1 mmol/L reduction in LDL cholesterol (RR 0·74 [95% CI 0·61-0·89]; p=0·0019), with no statistically significant difference with the risk reduction in patients younger than 75 years (0·85 [0·78-0·92]; pinteraction=0·37). Among older patients, RRs were not statistically different for statin (0·82 [0·73-0·91]) and non-statin treatment (0·67 [0·47-0·95]; pinteraction=0·64). The benefit of LDL cholesterol lowering in older patients was observed for each component of the composite, including cardiovascular death (0·85 [0·74-0·98]), myocardial infarction (0·80 [0·71-0·90]), stroke (0·73 [0·61-0·87]), and coronary revascularisation (0·80 [0·66-0·96]). INTERPRETATION: In patients aged 75 years and older, lipid lowering was as effective in reducing cardiovascular events as it was in patients younger than 75 years. These results should strengthen guideline recommendations for the use of lipid-lowering therapies, including non-statin treatment, in older patients. FUNDING: None.
BACKGROUND: The clinical benefit of LDL cholesterol lowering treatment in older patients remains debated. We aimed to summarise the evidence of LDL cholesterol lowering therapies in older patients. METHODS: In this systematic review and meta-analysis, we searched MEDLINE and Embase for articles published between March 1, 2015, and Aug 14, 2020, without any language restrictions. We included randomised controlled trials of cardiovascular outcomes of an LDL cholesterol-lowering drug recommended by the 2018 American College of Cardiology and American Heart Association guidelines, with a median follow-up of at least 2 years and data on older patients (aged ≥75 years). We excluded trials that exclusively enrolled participants with heart failure or on dialysis because guidelines do not recommend lipid-lowering therapy in such patients who do not have another indication. We extracted data for older patients using a standardised data form for aggregated study-level data. We meta-analysed the risk ratio (RR) for major vascular events (a composite of cardiovascular death, myocardial infarction or other acute coronary syndrome, stroke, or coronary revascularisation) per 1 mmol/L reduction in LDL cholesterol. FINDINGS: Data from six articles were included in the systematic review and meta-analysis, which included 24 trials from the Cholesterol Treatment Trialists' Collaboration meta-analysis plus five individual trials. Among 244 090 patients from 29 trials, 21 492 (8·8%) were aged at least 75 years, of whom 11 750 (54·7%) were from statin trials, 6209 (28·9%) from ezetimibe trials, and 3533 (16·4%) from PCSK9 inhibitor trials. Median follow-up ranged from 2·2 years to 6·0 years. LDL cholesterol lowering significantly reduced the risk of major vascular events (n=3519) in older patients by 26% per 1 mmol/L reduction in LDL cholesterol (RR 0·74 [95% CI 0·61-0·89]; p=0·0019), with no statistically significant difference with the risk reduction in patients younger than 75 years (0·85 [0·78-0·92]; pinteraction=0·37). Among older patients, RRs were not statistically different for statin (0·82 [0·73-0·91]) and non-statin treatment (0·67 [0·47-0·95]; pinteraction=0·64). The benefit of LDL cholesterol lowering in older patients was observed for each component of the composite, including cardiovascular death (0·85 [0·74-0·98]), myocardial infarction (0·80 [0·71-0·90]), stroke (0·73 [0·61-0·87]), and coronary revascularisation (0·80 [0·66-0·96]). INTERPRETATION: In patients aged 75 years and older, lipid lowering was as effective in reducing cardiovascular events as it was in patients younger than 75 years. These results should strengthen guideline recommendations for the use of lipid-lowering therapies, including non-statin treatment, in older patients. FUNDING: None.
Authors: Ariela R Orkaby; Jane A Driver; Yuk-Lam Ho; Bing Lu; Lauren Costa; Jacqueline Honerlaw; Ashley Galloway; Jason L Vassy; Daniel E Forman; J Michael Gaziano; David R Gagnon; Peter W F Wilson; Kelly Cho; Luc Djousse Journal: JAMA Date: 2020-07-07 Impact factor: 56.272
Authors: Richard G Bach; Christopher P Cannon; Robert P Giugliano; Jennifer A White; Yuliya Lokhnygina; Erin A Bohula; Robert M Califf; Eugene Braunwald; Michael A Blazing Journal: JAMA Cardiol Date: 2019-09-01 Impact factor: 14.676
Authors: Marc S Sabatine; Stephen D Wiviott; KyungAh Im; Sabina A Murphy; Robert P Giugliano Journal: JAMA Cardiol Date: 2018-09-01 Impact factor: 14.676
Authors: Rory Collins; Christina Reith; Jonathan Emberson; Jane Armitage; Colin Baigent; Lisa Blackwell; Roger Blumenthal; John Danesh; George Davey Smith; David DeMets; Stephen Evans; Malcolm Law; Stephen MacMahon; Seth Martin; Bruce Neal; Neil Poulter; David Preiss; Paul Ridker; Ian Roberts; Anthony Rodgers; Peter Sandercock; Kenneth Schulz; Peter Sever; John Simes; Liam Smeeth; Nicholas Wald; Salim Yusuf; Richard Peto Journal: Lancet Date: 2016-09-08 Impact factor: 79.321
Authors: Brian A Ference; Deepak L Bhatt; Alberico L Catapano; Chris J Packard; Ian Graham; Stephen Kaptoge; Thatcher B Ference; Qi Guo; Ulrich Laufs; Christian T Ruff; Arjen Cupido; G Kees Hovingh; John Danesh; Michael V Holmes; George Davey Smith; Kausik K Ray; Stephen J Nicholls; Marc S Sabatine Journal: JAMA Date: 2019-10-08 Impact factor: 56.272
Authors: Brian A Ference; Christopher P Cannon; Ulf Landmesser; Thomas F Lüscher; Alberico L Catapano; Kausik K Ray Journal: Eur Heart J Date: 2018-07-14 Impact factor: 29.983
Authors: Maciej Banach; Paweł Burchardt; Krzysztof Chlebus; Piotr Dobrowolski; Dariusz Dudek; Krzysztof Dyrbuś; Mariusz Gąsior; Piotr Jankowski; Jacek Jóźwiak; Longina Kłosiewicz-Latoszek; Irina Kowalska; Maciej Małecki; Aleksander Prejbisz; Michał Rakowski; Jacek Rysz; Bogdan Solnica; Dariusz Sitkiewicz; Grażyna Sygitowicz; Grażyna Sypniewska; Tomasz Tomasik; Adam Windak; Dorota Zozulińska-Ziółkiewicz; Barbara Cybulska Journal: Arch Med Sci Date: 2021-11-08 Impact factor: 3.318
Authors: Boris Draznin; Vanita R Aroda; George Bakris; Gretchen Benson; Florence M Brown; RaShaye Freeman; Jennifer Green; Elbert Huang; Diana Isaacs; Scott Kahan; Jose Leon; Sarah K Lyons; Anne L Peters; Priya Prahalad; Jane E B Reusch; Deborah Young-Hyman Journal: Diabetes Care Date: 2022-01-01 Impact factor: 19.112
Authors: Leandro Barbagelata; Walter Masson; Emiliano Rossi; Martin Lee; Juan Lagoria; Manuel Vilas; Rodolfo Pizarro; Guillermo Rosa Diez Journal: High Blood Press Cardiovasc Prev Date: 2022-06-25
Authors: Greg B Mills; Hanna Ratcovich; Jennifer Adams-Hall; Benjamin Beska; Emma Kirkup; Daniell E Raharjo; Murugapathy Veerasamy; Chris Wilkinson; Vijay Kunadian Journal: Eur Heart J Open Date: 2021-12-17