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Adherence to lipid-management guidelines benefits patients with CLI
Patients undergoing revascularization for critical limb ischemia had better mortality and major adverse limb event outcomes if they adhered to the statin intensity recommended in the 2013 American College of Cardiology/American Heart Association lipid-management guidelines, researchers reported.
The researchers conducted a retrospective analysis of all patients who underwent first-time endovascular or surgical revascularization for CLI — also called chronic limb-threatening ischemia — at Beth Israel Deaconess Medical Center, Boston, between 2005 and 2014.
After exclusion of patients on hemodialysis, 931 patients with 1,019 affected limbs were included and were stratified by intensity of statin therapy: high, moderate, low or none. According to the study background, the 2013 ACC/AHA guidelines recommend high-intensity statins for patients with CLI aged 75 years or younger and moderate-intensity statins for patients with CLI older than 75 years.
The researchers calculated propensity scores for probability of receiving guideline-recommended intensity of statin therapy. The primary outcomes were death and major adverse limb events. Median follow-up was 380 days.
Compared with those who were not, patients discharged on guideline-recommended statin therapy had higher rates of statin use before their procedure, CAD, chronic kidney disease, stroke, atrial fibrillation, congestive HF and prior CABG, Thomas F.X. O’Donnell, MD, from the division of vascular and endovascular surgery at Beth Israel Deaconess Medical Center, and colleagues wrote.
The recommended statin dose was taken in 35% of patients: 55% of those older than 75 years and 20% of those aged 75 years or younger, according to the researchers.
Discharge on any statin was associated with lower risk for mortality (HR = 0.71; 95% CI, 0.6-0.9), whereas discharge on the recommended intensity of statin therapy was associated with lower risk for mortality (HR = 0.73; 95% CI, 0.6-0.99) and major adverse limb events (HR = 0.71; 95% CI, 0.51-0.97), and the benefit did not differ by age, O’Donnell and colleagues wrote.
In patients older than 75 years, moderate-intensity statin therapy was associated with lower rates of death and major adverse limb events vs. high-intensity statin therapy, but the difference was not statistically significant (HR for death = 0.79; 95% CI, 0.49-1.26; HR for major adverse limb events = 0.82; 95% CI, 0.41-1.64), according to the researchers.
“Although adherence is improving, 60% of eligible patients in our institution were not receiving recommended [statin] doses even in 2014, an appealing target for future quality improvement projects,” O’Donnell and colleagues wrote. – by Erik Swain
Disclosure : The researchers report no relevant financial disclosures.
Perspective
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Although the benefit of HMG-CoA reductase inhibitors has been well established in preventing major adverse cardiac events, these remain underutilized in all patients. In particular, it is interesting to note in the O’Donnell study that in patients younger than 75 years, statins were prescribed more commonly in patients with recognized CAD and risk factors, including diabetes, hypertension, chronic kidney disease and dyslipidemia, as well prior MI or surgical/endovascular coronary revascularization. However, PAD in and of itself was not sufficiently recognized as a coronary equivalent warranting aggressive lipid-lowering management, although these patients did receive similar rates of antiplatelet therapy. Clearly, the message needs to be better disseminated that in younger patients with PAD and chronic limb-threatening ischemia, there is a need to assure statin compliance rigorously. The goal is to extend life primarily, and save limbs secondarily.
The utilization of statins should be ubiquitous across all populations with PAD, regardless of comorbidities (with the exception of end-stage renal disease) and age. In addition, we as physicians have a bad habit of moderating the intensity of therapy to avoid perceptions of intolerance, particularly muscle aches, as well as to reduce the overall medication burden on patients. The O’Donnell study suggests that any statin therapy has a favorable effect on overall mortality, but only guideline-adherent therapy — presumably higher doses — also has limb-preservation properties. Almost always, moderate-to-high intensity statins can be tolerated with good counseling and careful monitoring, and this should be the goal. The data from the O’Donnell study extends the findings of REACH, VQI and Laird et al, all of which have supported statins as limb protective and potentially associated with less need for repeat limb revascularization after both surgical and endovascular therapy. However, the data regarding the magnitude of this benefit in nonrevascularized patients is less certain and needs additional study. Prior studies including 4S, CARE, WOSCOPS and LIPID have shown cardiac and mortality benefit in non-PAD populations, but are lacking in defining effects in patients with known PAD.
Certainly, the benefits of statins are related to both their lipid-lowering and pleiotropic effects. In addition to improving LDL, statins have been shown to reduce vascular inflammation and improve arterial reactivity. Almost all patients can tolerate some form of statins, if necessary given in every-other-day or weekly dosing, and I have successfully given patients renally excreted statins such as pravastatin when they claim intolerance. However, for those patients who are truly statin-intolerant, with elevated creatine phosphokinase levels or other rate-limiting toxicities including hepatoxicity, then other lipid-lowering therapies should be recommended. This includes dietary modification, and I generally recommend adherence to a Mediterranean diet model in this regard. Other medications include bile acid sequestrants and intestinal cholesterol absorption inhibitors. Newer classes of medications, including PSCK9 inhibitors, also demonstrate amazing early promise both for their LDL-lowering potency and evidence of peripheral plaque regression. These may eventually replace or substantially contribute to the benefits currently derived from statins. Finally, it is important to remember that patients with PAD and chronic limb-threatening ischemia routinely benefit from antiplatelet and ACE inhibitor therapy as well, and these medications are important additional adjuncts to therapy.