Adherence to lipid-management guidelines benefits patients with CLI

John H. Rundback, MD, FAHA, FSVM, FSIR

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.