ACC.16 American College of Cardiology Scientific Sessions Highlights

The 2016 American College of Cardiology (ACC) Expert Consensus Decision Pathway on the Role of Non-Statin Therapies for LDL-C Lowering in the Management of ASCVD Risk

By Carl Orringer, MD, FNLA

Following “LDL Think Tank” meeting convened by ACC in October 2015, a meeting attended by expert clinicians and multiple stakeholder organizations, the National Lipid Association was invited by the ACC to participate in a 9-person writing group, the purpose of which was to create a document that would answer three key questions: 1) In what patient populations should non-statin therapies be considered? 2) In what situations should non-statin therapies be considered, i.e., when is the amount of LDL-C lowering (percent LDL-C reduction or LDL-C range achieved on therapy) less than anticipated, less than desired, or inadequate, and which treatment options should be considered in patients who are truly statin intolerant? and 3) If non-statin therapies are to be added, which agents or therapies should be added and in what order? The answers to these questions are addressed in the 2016 American College of Cardiology Expert Consensus Decision Pathway on the Role of Non-Statin Therapies for LDL-C Lowering in the Management of ASCVD Risk, a document that was endorsed by the NLA Board of Directors and subsequently published online in the Journal of the American College of Cardiology on April 1, 2016. The NLA was the only external organization represented on the Writing Group.

The article examines multiple subsets of patients falling into the statin benefit groups defined by the 2013 ACC/AHA Blood Cholesterol Guideline and presents algorithms that help to define clinically appropriate recommendations for the use of non-statin adjunctive therapy in these patients. The Writing Group recognized that patients in the randomized controlled trials demonstrating safety and efficacy of LDL-C lowering therapy tended to achieve absolute LDL-C levels within a given range. Those individuals with LDL-C levels above that range might be candidates for additive non-statin therapy. Thus, the document provides levels of LDL-C, or thresholds, in terms of both percentage of LDL-C reduction and absolute on-treatment LDL-C measurement as factors that might affect the decision to consider the use of non-statin therapies. Additional lipid management recommendations are made for certain special populations, including those with: New York Heart Association class II and III heart failure due to ischemic heart disease; chronic kidney disease; and pregnancy.

The ACC Writing Group hopes that this document will serve as a clinically useful bridge until the next set of formal Guidelines are released. The NLA has been asked to be active participants in the process of creating the next set of Guidelines and looks forward to the opportunity to contribute to the creation of this important tool for the prevention of ASCVD. Click here to read the document.

Carl Orringer, MD, FNLA, was on the ACC Writing Group of the Consensus Paper, and is currently the NLA President.

HOPE-3 Trial

The Heart Outcomes Prevention Evaluation (HOPE) 3 trial is a 2X2 factorial design that compared low dose statin (rosuvastatin 10 mg) and antihypertensive therapy (candesartan HCTZ  16/12.5), either alone or together, compared to placebo. This “polypill” concept trial did prove that rosuvastatin alone in a primary prevention population of 50% women and 50% Asians reduced hard CVD events by 24% over 5.5 years, and combined with blood pressure treatment, reduced hard events by 30%. Unfortunately, the candesartan HCTZ arm did not reach statistical significance. Click here to read more.

GAUSS-3 Trial

The GAUSS-3 trial was a rigorous evaluation of statin-intolerant subjects, having a blinded, placebo-controlled crossover design to confirm true muscle symptoms before the subjects were randomized to ezetimibe or evolocumab 420 mg/month by injection. As expected, the LDL-C reduction was 55% with evolocumab, and the therapy was well tolerated. Click here to read more.

ACCELERATE Trial

The ACCELERATE trial with evacetrapib was presented, without simultaneous publication. This trial was stopped in the fall of 2015 for futility, and the HR for the primary endpoint at 36 months was 1.01. Evacetrapib at 130 mg/day, added to maximally-tolerated statin, increased HDL-C 130% (45 mg/dL at baseline to 104 mg/dL) and reduced LDL-C 37% (from 81 mg/dL baseline to 55 mg/dL). There were no significant adverse events. The authors had no answer as to why a reduction in LDL-C of 37% did not at least trend toward reduced CVD events, and remarked that one outcome trial still in progress, REVEAL with anacetrapib, is the last hope for the CETP class.