In a new strategy for preventing heart attacks and strokes, leading cardiologists are urging their fellow physicians to focus on reducing the LDL cholesterol of patients at greatest risk of suffering a cardiovascular crisis, and to use costly new drugs if necessary.
These prescription medications have been shown to slash patients’ levels of “bad” cholesterol by as much as 60% — an amount that can cut a population’s rate of serious cardiovascular events by almost half, according to an analysis of large clinical trials.
For healthy people whose risk of a heart attack or stroke is only somewhat elevated, doctors should continue to recommend healthier lifestyles and inexpensive statin drugs such as Zocor (simvastatin), Lipitor (atorvastatin) and Pravachol (pravastatin).
The new guidelines, released Saturday by the American Heart Assn. and the American College of Cardiology, put the focus back on lower targets for bad cholesterol. That marks a significant shift from controversial guidelines issued by the two organizations in 2013, which asked doctors to greatly expand the number of patients taking statins without fixating on specific cholesterol targets.
“The big news is that targets are back, and lower is better,” said Dr. Steven Nissen of the Cleveland Clinic, who was an outspoken critic of the 2013 guidelines and was not involved in the drafting of the new ones. “This is really a reversal of course, and I actually think they moved this in the right direction.”
When recommending the more aggressive treatment of those who are at highest risk of heart attacks and strokes, “it helps patients and providers when you give them numbers and targets,” Nissen said. “Because if you’re constantly checking, you keep patients staying focused on compliance, what it takes to stay healthy.”
Nearly 800,000 people die of heart attacks, strokes and other manifestations of cardiovascular disease in the United States each year, making it the country’s leading cause of death. But while 78 million Americans — close to 37% of the adult population — either take or should consider taking medication to lower their cholesterol, close to half don’t do so.
The new guidelines not only concentrate on lowering cholesterol in populations whose risk of heart attacks and strokes is highest; they ask physicians, within four to 12 weeks, to assess whether a patient’s new drug regimen is having the desired effect.
In a departure from 2013 guidelines, those released Saturday also recommend that adults under 40 and over 75 should be medicated if their cholesterol — or their heart attack and stroke risk — is very high. That includes younger patients with family histories of heart attack and older patients who’ve had diabetes for years.
To “intensify” therapy in patients with established heart disease and stubbornly high levels of LDL, doctors should first consider supplementing or replacing a statin with the drug ezetimibe (sold commercially as Zetia and paired with simvastatin in a drug called Vytorin), the new guidelines say. Compared to high-risk patients who received statins alone, those taking ezetimibe reduced their LDL cholesterol a further 20% to 25%, on average.
If that doesn’t bring high-risk patients’ LDL levels to between 50 and 70 mg/dL or lower, doctors and patients should consider trying a new class of injected medications that likely will.
These so-called PCSK9 inhibitors — known commercially as Praluent (alirocumab) and Repatha (evolocumab) — were approved by the Food and Drug Administration in 2015 and 2017, respectively. They have proved highly effective in driving LDL cholesterol numbers down in several groups of patients at high risk of having first or repeat heart attacks or strokes. And they worked to reduce the risk of such events in difficult-to-treat patients: those with familial high cholesterol (about 600,000 Americans), those for whom statins caused intolerable side effects such as extreme muscle aches or rises in blood sugar (between 5% and 20% of those who take them), and those for whom statins have had a marginal effect.
But there’s a catch. A prescription for either Praluent or Repatha originally came with a price tag of $14,000 per year. That was a turn-off for both patients and insurers. A 2016 study found that even when used in a narrow population, the drugs would only become cost-effective at one-third their starting price.
The makers of Praluent — Regeneron Pharmaceuticals and Sanofi — have since devised programs that reduce the cost to as low as $4,500 per year. In a bid to boost sales of Repatha, Amgen cut its list price to $5,850 a year. But both drugs are still expensive compared with statins and ezetimibe, which are all now available in inexpensive generic forms.
The new guidelines also recommend more extensive use of imaging scans that detect the presence and density of calcium deposits in the arteries leading to the heart.
The scans, which can cost patients between $100 and $400 and expose patients to some radiation, are not considered a good screening tool for the population at large. They should, however, be more widely used to identify patients already judged to be at elevated cardiovascular risk, and who may need more intensive treatment to lower their cholesterol. They would probably prove most valuable in sparing patients seemingly at high risk, but who are found to have no calcium deposits in their coronary vessels, the cost and bother of taking medications.
In patients whose risk for having a heart attack or stroke in the coming decade puts them on the bubble for starting medication, a coronary artery scan can serve as a “tiebreaker,” said Dr. Neil J. Stone of Northwestern University’s Feinberg School of Medicine, who helped draft the new guidelines.
Stone, who also worked on the 2013 recommendations, touted the new guidelines’ focus on “shared decision-making” between patients and their doctors, in which they jointly consider the pros and cons of cholesterol-lowering treatments.
He added that new “decision tools” — such as the coronary artery calcium scan, diabetes status and kidney function, and women’s histories of gestational diabetes or preeclampsia in pregnancy — will help refine physicians’ assessments of their patients’ individual risks and “ make it more clear whether taking a statin makes sense.”
Dr. Paul Thompson, chief of cardiology at Hartford Hospital, cheered the new guidelines’ focus on treating more patients with ezetemibe in a bid to drive down their cholesterol and heart disease risk. A veteran of many guidelines-drafting sessions (but not of these), he said he was encouraged to see that the new guidelines took into account a wide range of research, including a clinical trial of alirocumab that was published only this week.
Others saw improvements in the new guidelines, but cautioned that doctors — and patients — must be brought along.
“All in all, I do believe they represent significant positive steps in the way we treat cholesterol, and the way we will assess patients’ cardiovascular risk,” said the Mayo Clinic’s Dr. Francisco Lopez-Jimenez. He and others had criticized the earlier guidelines for drawing too many patients at relatively low risk of stroke and heart attack into medication regimens while failing to recognize or concentrate on patients at greatest risk.
The new guidelines address many of those concerns, Lopez-Jimenez said. They’re “more pragmatic,” he said, and do a better job of taking into account patients’ roles in making decisions about their treatment. But whether high-risk patients will heed the call to step up their medication regimens “is the elephant in the room,” he added.
Dr. Harlan Krumholz, a cardiologist and healthcare researcher at Yale University, said that by giving physicians more talking points as well as more tools for the management of high cholesterol, the new guidelines should help bring patients along.
“I think it’s more important to be having discussions with patients about what they want to achieve,” Krumholz said. “Guidelines can be important in telling people what experts’ ideas are. But it’s not coming down from the mountain.”