New guidelines, PCSK9s, fish oil, TAVR, MitraClip, and aspirin
Headline-making developments for 2018 included new guidelines and landmark trials. The following brief summaries highlight some of the notable cardiology stories covered by MedPage Today thus far in 2018.
Perhaps the most practice-changing development came recently, with the release of the American Heart Association/American College of Cardiology's lipid guidelines. The update featured an algorithm for when to reach for a PCSK9 inhibitor and revised risk assessment in primary prevention.
PCSK9 inhibitors were recommended as "reasonable" for very high-risk atherosclerotic cardiovascular disease patients with multiple prior major events or for those who have a single such event plus multiple high-risk conditions when their LDL is 70 mg/dL or higher, and they are on maximally tolerated statin and ezetimibe (Zetia) therapy.
Risk assessment for people without diabetes or known cardiovascular disease still uses the pooled cohort equations and calculator, but adds in factors to personalize the discussion on starting statins, such as comorbidities and history, the potential for adverse effects, accrued costs, and patient preferences and values. Coronary artery calcium (CAC) scans gained a 2a endorsement for intermediate-risk adults, 40 to 75 years of age who don't have diabetes and have a LDL in the 70 to 189 mg/dL range. These intermediate-rise adults have a 10-year atherosclerotic cardiovascular disease (ASCVD) risk of 7.5% to 19.9%, and the decision about statin therapy for them is still uncertain. Statins can be withheld or delayed for most such people with a CAC score of zero.
Another major development made this year with PCSK9 inhibitors include the landmark ODYSSEY Outcomes trial, which came through with a relative 15% reduction in the composite of coronary heart disease death, nonfatal myocardial infarction (MI), fatal or nonfatal ischemic stroke, and unstable angina requiring hospitalization with alirocumab (Praluent), compared with a placebo among patients who had recent acute coronary syndrome and elevated cholesterol levels.
The trial also scored a win with a nominally significant relative 15% reduction in all-cause mortality, whereas the FOURIER trial showed that both cardiovascular and all-cause mortality went slightly in the wrong direction with evolocumab (Repatha). The findings presented at the American College of Cardiology meeting were published in the New England Journal of Medicine just prior to the American Heart Association meeting, in which the new lipid guidelines (including ODYSSEY's data) were released.
Manufacturers also announced new efforts to ease the loggerhead with insurers that had stymied prescription rates. In March, Sanofi and Regeneron announced that they would cut the price of alirocumab for any insurer that would ease access barriers. And in May, such a deal was struck with the nation's largest pharmacy benefits manager, Express Scripts, for a simplified "attestation" by the physician to replace the burdensome requirements for laboratory results and detailed patient history. Then in October, Amgen announced a plan to cut the list price for evolocumab (Repatha) by 60% across the board, in order to address copay issues for Medicare patients in particular.
Two controversial agents for cardiovascular primary prevention -- aspirin and fish oil -- had a spate of mixed findings in large trials.
For aspirin, the ARRIVE trial reduced the composite of MI, stroke, transient ischemic attack, and death from non-intracranial hemorrhage vascular causes by a relative 12% but increased major bleeds by 29%, compared with a placebo in adults who had diabetes of any type. "There was no group in which the benefits clearly outweighed the risks," according to the lead author. The underpowered ASCEND trial, which aimed for a moderate-risk but nondiabetic middle age and older population showed no significant benefit of aspirin, but a roughly doubled bleeding risk.
In the ASPREE trial in patients 70 or older, aspirin didn't reduce cardiovascular disease or the combined endpoint of death, dementia, or persistent physical disability compared with a placebo, and there was an increased bleeding risk. Notably, cancer mortality was unexpectedly elevated.
For fish oil, the ASCEND trial of a lower-dose supplement for patients with diabetes didn't reduce the composite of non-fatal MI or stroke, transient ischemic attack, or cardiovascular death versus an olive-oil placebo. The same dose of a fish oil supplement failed to reduce major cardiovascular events in the VITAL trial too, although there was a signal for fewer MIs. But, the REDUCE-IT trial that included high-grade prescription fish oil, icosapent ethyl (Vascepa), cut the combined CV death, non-fatal MI, non-fatal stroke, coronary revascularization, and unstable angina rate by 25% when compared with a mineral oil placebo.
Guidelines from the American Heart Assocation/American Stroke Association expanded the treatment window for endovascular thrombectomy from 6 hours to 24 hours, after patients with acute ischemic stroke were last known to be well. The recommendation was class Ia for the period of 6 to 16 hours, as both the DAWN trial and the DEFUSE 3 trial, released the same day at the International Stroke Conference, confirmed better outcomes than with medical therapy alone; only DAWN addressed the window out to 24 hours, so the recommendation to that point was IIa.
The Centers for Medicare & Medicaid Services convened experts and industry to discuss revising the procedural volume requirements for reimbursement of transcatheter aortic valve replacement. However, the panel didn't come to many solid conclusions. Opinions were divided, and the average level of confidence in the evidence among the voting members hovered in the intermediate range for nearly all of the questions.
More decisive was the win for MitraClip in functional mitral regurgitation in the COAPT trial. For moderate-to-severe cases, symptomatic mitral regurgitation in heart failure patients who had exhausted pharmaceutical options cut heart failure hospitalizations nearly in half versus medical therapy alone, and substantially reduced all-cause mortality as well. While the study closely followed negative results with MitraClip in functional mitral regurgitation in the MITRA-FR trial, COAPT was larger, longer, and ultimately deemed more influential.
Read the original article on Medpage Today: Year in Review: Cardiology