Shipra Arya1,2,3, Anjali Khakharia4, Zachary O Binney2, Randall R DeMartino5, Luke P Brewster4, Philip P Goodney6, Peter W F Wilson7,8. 1. Division of Vascular Surgery and Endovascular Therapy, Department of Surgery (S.A., A.K., L.P.B.) sarya1@stanford.edu. 2. Emory School of Medicine, and Department of Epidemiology, Rollins School of Public Health (S.A., Z.O.B.), Emory University, Atlanta, GA. 3. Surgical Service Line (S.A., L.P.B.). 4. Division of Vascular Surgery and Endovascular Therapy, Department of Surgery (S.A., A.K., L.P.B.). 5. Division of Vascular and Endovascular Surgery, Mayo Clinic, Rochester, MN (R.R.D.). 6. Section of Vascular Surgery, Dartmouth-Hitchcock Medical Center, Lebanon, NH (P.P.G.). 7. Division of Cardiology (P.W.F.W.). 8. Epidemiology and Genomic Medicine (P.W.F.W.), Atlanta VA Medical Center, Decatur, GA.
Abstract
BACKGROUND: Statin dose guidelines for patients with peripheral artery disease (PAD) are largely based on coronary artery disease and stroke data. The aim of this study is to determine the effect of statin intensity on PAD outcomes of amputation and mortality. METHODS: Using an observational cohort study design and a validated algorithm, we identified patients with incident PAD (2003-2014) in the national Veterans Affairs data. Highest statin intensity exposure (high-intensity versus low-to-moderate-intensity versus antiplatelet therapy but no statin use) was determined within 1 year of diagnosis of PAD. Outcomes of interest were lower extremity amputations and death. The association of statin intensity with incident amputation and mortality was assessed with Kaplan-Meier plots, Cox proportional hazards modeling, propensity score-matched analysis, and sensitivity and subgroup analyses, as well, to reduce confounding. RESULTS: In 155 647 patients with incident PAD, more than a quarter (28%) were not on statins. Use of high-intensity statins was lowest in patients with PAD only (6.4%) in comparison with comorbid coronary/carotid disease (18.4%). Incident amputation and mortality risk declined significantly with any statin use in comparison with the antiplatelet therapy-only group. In adjusted Cox models, the high-intensity statin users were associated with lower amputation risk and mortality in comparison with antiplatelet therapy-only users (hazard ratio, 0.67; 95% confidence interval, 0.61-0.74 and hazard ratio, 0.74; 95% confidence interval, 0.70-0.77, respectively). Low-to-moderate-intensity statins also had significant reductions in the risk of amputation and mortality (hazard ratio amputation, 0.81; 95% confidence interval, 0.75- 0.86; hazard ratio death, 0.83; 95% confidence interval, 0.81-0.86) in comparison with no statins (antiplatelet therapy only), but effect size was significantly weaker than the high-intensity statins (P<0.001). The association of high-intensity statins with lower amputation and death risk remained significant and robust in propensity score-matched, sensitivity, and subgroup analyses. CONCLUSIONS: Statins, especially high-intensity formulations, are underused in patients with PAD. This is the first population-based study to show that high-intensity statin use at the time of PAD diagnosis is associated with a significant reduction in limb loss and mortality in comparison with low-to-moderate-intensity statin users, and patients treated only with antiplatelet medications but not with statins, as well.
BACKGROUND: Statin dose guidelines for patients with peripheral artery disease (PAD) are largely based on coronary artery disease and stroke data. The aim of this study is to determine the effect of statin intensity on PAD outcomes of amputation and mortality. METHODS: Using an observational cohort study design and a validated algorithm, we identified patients with incident PAD (2003-2014) in the national Veterans Affairs data. Highest statin intensity exposure (high-intensity versus low-to-moderate-intensity versus antiplatelet therapy but no statin use) was determined within 1 year of diagnosis of PAD. Outcomes of interest were lower extremity amputations and death. The association of statin intensity with incident amputation and mortality was assessed with Kaplan-Meier plots, Cox proportional hazards modeling, propensity score-matched analysis, and sensitivity and subgroup analyses, as well, to reduce confounding. RESULTS: In 155 647 patients with incident PAD, more than a quarter (28%) were not on statins. Use of high-intensity statins was lowest in patients with PAD only (6.4%) in comparison with comorbid coronary/carotid disease (18.4%). Incident amputation and mortality risk declined significantly with any statin use in comparison with the antiplatelet therapy-only group. In adjusted Cox models, the high-intensity statin users were associated with lower amputation risk and mortality in comparison with antiplatelet therapy-only users (hazard ratio, 0.67; 95% confidence interval, 0.61-0.74 and hazard ratio, 0.74; 95% confidence interval, 0.70-0.77, respectively). Low-to-moderate-intensity statins also had significant reductions in the risk of amputation and mortality (hazard ratio amputation, 0.81; 95% confidence interval, 0.75- 0.86; hazard ratio death, 0.83; 95% confidence interval, 0.81-0.86) in comparison with no statins (antiplatelet therapy only), but effect size was significantly weaker than the high-intensity statins (P<0.001). The association of high-intensity statins with lower amputation and death risk remained significant and robust in propensity score-matched, sensitivity, and subgroup analyses. CONCLUSIONS: Statins, especially high-intensity formulations, are underused in patients with PAD. This is the first population-based study to show that high-intensity statin use at the time of PAD diagnosis is associated with a significant reduction in limb loss and mortality in comparison with low-to-moderate-intensity statin users, and patients treated only with antiplatelet medications but not with statins, as well.
Authors: Matthew A Allison; Elena Ho; Julie O Denenberg; Robert D Langer; Anne B Newman; Richard R Fabsitz; Michael H Criqui Journal: Am J Prev Med Date: 2007-04 Impact factor: 5.043
Authors: Alan T Hirsch; Timothy P Murphy; Marge B Lovell; Gwen Twillman; Diane Treat-Jacobson; Eileen M Harwood; Emile R Mohler; Mark A Creager; Robert W Hobson; Rose Marie Robertson; W James Howard; Paul Schroeder; Michael H Criqui Journal: Circulation Date: 2007-09-17 Impact factor: 29.690
Authors: Michael S Conte; Dennis F Bandyk; Alexander W Clowes; Gregory L Moneta; Hamid Namini; Lynn Seely Journal: J Vasc Surg Date: 2005-09 Impact factor: 4.268
Authors: Thomas F Rehring; Brian G Sandhoff; Ryan S Stolcpart; John A Merenich; H Whitton Hollis Journal: J Vasc Surg Date: 2005-05 Impact factor: 4.268
Authors: A T Hirsch; M H Criqui; D Treat-Jacobson; J G Regensteiner; M A Creager; J W Olin; S H Krook; D B Hunninghake; A J Comerota; M E Walsh; M M McDermott; W R Hiatt Journal: JAMA Date: 2001-09-19 Impact factor: 56.272
Authors: Dharam J Kumbhani; Ph Gabriel Steg; Christopher P Cannon; Kim A Eagle; Sidney C Smith; Shinya Goto; E Magnus Ohman; Yedid Elbez; Piyamitr Sritara; Iris Baumgartner; Subhash Banerjee; Mark A Creager; Deepak L Bhatt Journal: Eur Heart J Date: 2014-02-28 Impact factor: 29.983
Authors: Sanne van Wissen; Tineke J Smilde; Eric de Groot; Barbara A Hutten; John J P Kastelein; Anton F H Stalenhoef Journal: Eur J Cardiovasc Prev Rehabil Date: 2003-12
Authors: Sanne E Hoeks; Wilma J M Scholte op Reimer; Yvette R B M van Gestel; Olaf Schouten; Mattie J Lenzen; Willem-Jan Flu; Jan-Peter van Kuijk; Corine Latour; Jeroen J Bax; Hero van Urk; Don Poldermans Journal: Circ Cardiovasc Qual Outcomes Date: 2009-04-24
Authors: Aaron W Aday; Patrick R Lawler; Nancy R Cook; Paul M Ridker; Samia Mora; Aruna D Pradhan Journal: Circulation Date: 2018-11-20 Impact factor: 29.690
Authors: Adam J Nelson; Kevin Haynes; Sonali Shambhu; Zubin Eapen; Mark J Cziraky; Michael G Nanna; Sara B Calvert; Kerrin Gallagher; Neha J Pagidipati; Christopher B Granger Journal: J Am Coll Cardiol Date: 2022-05-10 Impact factor: 27.203
Authors: E Hope Weissler; Cassie B Ford; Manesh R Patel; Phil Goodney; Amy Clark; Chandler Long; W Schuyler Jones Journal: Am Heart J Date: 2021-08-08 Impact factor: 4.749