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High-intensity statins reduce risk for death, amputation in PAD
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New data show that in patients with peripheral artery disease, the use of statins, particularly high-intensity statins, at the time of diagnosis was linked to reduced risks for death and limb loss.
The 2013 American Heart Association/American College of Cardiology guidelines recommend that patients with atherosclerotic CVD should start taking high-intensity statins, but they also note that the evidence for their use in PAD is low, according to the researchers.
“Given the lack of evidence supporting use of high-intensity statins in PAD patients, the objective of our study was to determine the effect of statin intensity (based on 2013 ACC/AHA guidelines) on PAD outcomes of amputation and mortality,” they wrote in Circulation.
For their study, the researchers evaluated data from the national Veterans Affairs database from 2003 to 2014. They determined the intensity of statin use — high-intensity, low-moderate-intensity or antiplatelet therapy but no statin use — within 1 year of PAD diagnosis and analyzed associations between statin intensity and the risks for amputation and mortality.
Of the 155,647 patients with incident PAD included in the study, 28% were not taking statins. The proportion of patients taking high-intensity statins was higher in patients with comorbid coronary or carotid disease, compared with PAD alone (6.4% vs. 18.4%).
Amputation, death risks
After adjustment, patients taking high-intensity statins had a 33% lower risk for amputation (HR = 0.67; 95% CI, 0.61-0.74) and a 26% lower risk for death (HR = 0.74; 95% CI, 0.7-0.77), compared with those taking antiplatelet medication only, according to the data.
Additionally, after adjustment, patients taking low-moderate-intensity statins had a 19% lower risk for amputation (HR = 0.81; 95% CI, 0.75-0.86) and a 17% lower risk for death (HR = 0.83; 95% CI, 0.81-0.86), compared with those taking antiplatelet medication only. The effect size was weaker, however, for those taking low-moderate-intensity statins vs. high-intensity statins, demonstrating a protective dose-response relationship (P < .001).
Similar results were seen in a propensity-score matched analysis, according to the researchers. High-intensity statins were again associated with significantly lower risks for amputation and mortality, as were low-moderate-intensity statins, albeit to a lesser degree.
The researchers also conducted subgroup analyses according to age, sex, diabetes status, comorbid CAD and race. Overall, the data were consistent with the main findings, but the researchers noted some differences. For instance, patients older than 75 years had an even lower risk for lower-limb loss than younger patients when taking high-intensity statins. The effect of high-intensity statins on mortality and amputation risk was also magnified in patients without diabetes, compared with those with diabetes.
Benefit of statins
“Our study shows an associated benefit between patients on high-intensity statins before or early upon diagnosis of PAD to have a lower lifetime risk of death and amputations,” the researchers wrote, noting that low-moderate-intensity statins also reduced these risks and may be beneficial for patients who cannot tolerate high-intensity statins.
“Further work is needed to quantify the risk-benefit with patient medication adherence, the effect of statin intensity on disease severity of PAD as well as implementation of strategies to increase statin use in PAD patients,” they wrote. – by Melissa Foster
Disclosures: The authors report no relevant financial disclosures.
Perspective
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Frank Pomposelli , MD
Major limb amputation and CV death are the most significant complications of PAD. It comes as no surprise from this well-done observational study that statins reduce the risk for both amputation and mortality in patients with PAD, given the positive benefits demonstrated with long-term statin use in patients undergoing invasive treatments for PAD. For example, one previous study demonstrated statins to be independently associated with a reduced mortality in patients undergoing lower-extremity bypass surgery for critical limb ischemia in follow-up at 1 year, in spite of no demonstrable improvement in graft patency, perioperative mortality and/or CV events. In retrospective studies, statins have also been demonstrated to improve patency, mortality and limb salvage and catheter-based interventions for PAD. In patients undergoing carotid endarterectomy, statins reduce the long-term risk for stroke and death but not the periprocedural risk, while conflicting evidence exists as to whether statins reduce the incidence of carotid restenosis.
Perhaps the most important message from this study is the dose-dependent effect of statins in reducing mortality with the largest impact demonstrated in those patients receiving high-dose statins and a less but significant benefit in those taking moderate or lower doses. No benefit was realized from antiplatelet therapy alone. Although the results of this study are based on a largely male population, the results provide strong evidence in support of routinely prescribing statins to all patients identified with PAD at the highest dose tolerable whether they are undergoing invasive treatment and add further evidence that antiplatelet therapy alone is not an effective preventative strategy.
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