Good News and Bad for High-Intensity Statin Use in ASCVD

Two new studies published this week highlight the successes, as well as the disappointments, in the battle to get patients to take a high-intensity statin for secondary prevention.

In the “good news” report, researchers showed that the percentage of adults taking a high-intensity statin following a myocardial infarction increased substantially over a recent period. In this post-MI setting, the percentage of patients prescribed high-intensity statin therapy increased from 30.7% in 2011 to 78.6% in 2019.

For the second study, which included a broader cohort of patients with atherosclerotic cardiovascular disease (ASCVD), the results were not as encouraging, with just one in five taking a high-intensity statin in 2019. Women, older patients, and those with peripheral artery disease were even less likely to be taking one of the more-potent lipid-lowering therapies.

“We see a lot of evidence in clinical practice where we have a plethora of data supporting agents with proven efficacy yet translating those findings to clinical practice and to our patients remains problematic,” Adam Nelson, MBBS, PhD (Duke Clinical Research Institute, Durham, NC), lead investigator of the ASCVD analysis, told TCTMD.

From a population-health-strategy perspective, statins are cheap, they’re available, and we have really good data. Adam Nelson

Senior investigator Christopher Granger, MD (Duke Clinical Research Institute), called the results quite shocking, stating they should serve as a wake-up call for clinicians treating patients with atherosclerosis.

“Statins for patients with vascular disease are highly effective at preventing death, [they’re] inexpensive, safe, and well tolerated,” he said in an email. “The fact that only 22% of patients in a commercially insured population are on high-intensity statins underscores the poor job we are doing in healthcare in the care of our patients. This really is a call to action. “

Both studies were published May 2, 2022, in the Journal of the American College of Cardiology.

Crawling Before Walking

In the 2018 American College of Cardiology/American Heart Association (ACC/AHA) cholesterol guidelines, statins are the cornerstone of therapy. In established ASCVD, it’s recommended that patients reduce LDL-cholesterol levels by 50% or more with a high-intensity statin (atorvastatin 40 to 80 mg and rosuvastatin 20 to 40 mg), or the maximally tolerated statin dose (class I indication).

“There’s been a lot of interest around newer [lipid-lowering] agents—more potent but also more expensive—and those therapies build on the foundation of statin therapy,” said Nelson. “The vast majority of this evidence is based around patients who are already on statins, and those studies do show incremental gains. But we need to crawl before we can walk, and the use of statins remains particularly important as an opportunity to springboard into these newer therapies.”

In their study, Nelson and colleagues evaluated the patterns and predictors of statin use among 601,934 patients (mean age 67.5 years; 41.7% female) with established ASCVD, which included CAD, PAD, and cerebrovascular disease. Statin use on the index date of January 31, 2019, was evaluated, as was the 12-month rate of adherence and discontinuation.    

Overall, 22.5% of patients were on a high-intensity statin, 27.5% were treated with another type of statin, and 49.9% were not taking any statin at all. Stratified by sex, just 15.8% of women were prescribed a high-intensity statin compared with 27.3% of men. High-intensity statin use was highest among those aged 45 to 74 years (26.1%), followed by those 75 years and older (16.6%) and those younger than 45 years (12.7%). Only 16.7% of PAD patients were prescribed high-intensity statins, compared with 22.0% of those with cerebrovascular disease and 27.4% of those with CAD.

Patients seen by a cardiologist in the past year were more likely to be prescribed one of the more-potent LDL cholesterol-lowering agents. Overall, 82.8% of those prescribed high-intensity statins adhered to the medication as indicated by the proportion of days covered (PDC ≥ 75%). During the 12-month period, 19.2% of patients had a change in statin therapy, with almost half of these patients being switched to a lower dose or stopping it altogether.

The issue of clinical inertia is real, and results in failure to start therapies and intensify those in follow-up visits. Fatima Rodriguez

In terms of the results, “we were surprised to see there were no gains [in high-intensity statin use], and perhaps even some ground lost,” said Nelson, adding that the study should serve as a call to arms, particularly for some of the subgroups, like women, who remain undertreated. 

Fatima Rodriguez, MD (Stanford University School of Medicine, CA), who wasn’t involved in the study, said high-intensity statin underuse and underprescribing, which results in failure to achieve LDL-cholesterol goals, reflects barriers at the patient, clinician, and system level.

“We know that misinformation about statins and perceived side effects, including the disutility of taking a daily medication, can have huge effects on patients' adherence to these medications,” she told TCTMD. “From a clinician standpoint, there are so many changing guidelines and targets that it may be hard to keep up. The issue of clinical inertia is real, and results in failure to start therapies and intensify those in follow-up visits.”

Nonetheless, the lesson from years of clinical trials on lowering cholesterol in secondary prevention is clear, she stressed. “The lower the LDL cholesterol, the better the outcomes,” said Rodriguez.  

Encouraging Data in the Post-MI Setting

In the second study, Lisandro Colantonio, MD, PhD (University of Alabama at Birmingham), and colleagues turned to Medicare data to analyze trends in high-intensity statin use among post-MI patients. In total, 522,039 MI hospitalizations were included in the analysis.

The overall increase in high-intensity statin use from 2011 to 2019 was also seen in those starting statins for the first time as well as among those currently on a low- or moderate-intensity statin. For statin-naive patients, 28.1% of post-MI patients were started on a high-intensity agent in 2011 compared with 82.3% in 2019. Among those on a low- or moderate-dose statin before their MI, 18.1% left hospital on a high-intensity statin in 2011 compared with 63.8% in 2019. 

The increased use was seen among non-Hispanic white (26.7% to 75.1%), non-Hispanic Black (28.8% to 74.7%), Hispanic (26.8% to 74.5%), and Asian (27.6% to 73.2%) patients. In post-MI men, use of the more-potent drugs increased from 33.5% in 2011 to 80.1% in 2019, whereas use increased from 26.5% to 72.0% in women. High-intensity statins were less frequently used in older patients.  

We have to be doctors. Robert Rosenson

“These data were quite encouraging,” senior investigator Robert Rosenson, MD (Icahn School of Medicine at Mount Sinai, New York, NY), told TCTMD. In past studies, the uptake of high-intensity statin therapy wasn’t nearly as good. Also, previous studies, including one from the GOULD registry, had shown that physicians infrequently intensify LDL-cholesterol medications, he said. 

As for why the post-MI patients fared better than ASCVD patients, Rosenson said it likely comes down to the different populations, noting that ASCVD is a broad umbrella that includes patients who might not fall under the care of cardiologists. Also, the evidence for statin use, while very strong for patients with stable ASCVD, is even stronger for those with acute coronary syndromes. The ACC/AHA cholesterol guidelines even make a strong recommendation for prescribing a high-intensity statin to ACS patients before they leave hospital, said Rosenson.  

Guidelines Emphasize High-Intensity Statins

Statin intolerance and patient perceptions about the drug class contribute to the low uptake of high-intensity statin therapy, but there has been excellent research in the past several years showing that most patients can tolerate statins to some extent, said Nelson. While they may report muscle aches and pains, which they attribute to statins, placebo-controlled data shows the percentage attributable to the drug is quite small. Reengaging patients with statin intolerance can be a lengthy process, though studies have shown it can be effective, he said.   

Rosenson also stressed the need for physicians to be reengage statin-intolerant patients and to sort out real side effects from either the nocebo effect or symptoms unrelated to the drug. A few years back, Rosenson developed the Statin-Associated Muscle Symptom Clinical Index (SAMS-CI) to determine if muscle symptoms were truly caused by or worsened by the drug.

“We have to be doctors,” he said. “It requires the clinician to discuss with the patient which muscle aches and pains are consistent with the statin versus those that aren’t.”

While there are new drugs commercially available, including PCSK9 inhibitors, bempedoic acid (Nexletol; Esperion), and inclisiran (Leqvio; Novartis), statins should not be overlooked, according to experts who spoke with TCTMD. “The whole field of prevention is in a Renaissance and we all have an eye on that, but the other view is that from a population-health strategy perspective, statins are cheap, they’re available, and we have really good data,” said Nelson.

The emergence of new drugs is exciting and will help physicians bring patients to goal, Rosenson said, though he emphasized that statins should remain the bedrock of lipid-lowering therapy, highlighting the vast evidence supporting their safety and efficacy.

In an editorial, Salim Virani, MD, PhD (Michael E. DeBakey Veterans Affairs Medical, Houston, TX), Christie Ballantyne, MD (Baylor College of Medicine, Houston), and Laura Petersen, MD (Michael E. DeBakey Veterans Affairs Medical), point out there’s more than 30 years of evidence supporting statins, particularly high-intensity statins, for the safe reduction of major adverse cardiovascular events.

Like others, the editorialists believe the reason for the low use of guideline-directed therapy in ASCVD patients is multifactorial, blaming it not only on clinician inertia and SAMS, but also widespread media and internet sources that have cast statins in a bad light. To counter this underutilization, they recommend improving guideline dissemination, leveraging team-based care approaches, applying of smart clinical-decision support tools, and helping patients identify trust sources of information.