‘We have options’: New strategies for treating statin intolerance
Click Here to Manage Email Alerts
Key takeaways:
- There are many options for statin-intolerant patients, including alternative dosing schedules and nonstatin therapies.
- Clinicians should strive for a “lower for longer” LDL for patients.
Editor's Note: This is part 3 of a three-part Healio Exclusive series on developments and challenges in heart transplantation. Part 1 can be viewed here. Part 2 can be viewed here.
Experts agree that whether statin-associated adverse effects are real or not matters little if a patient cannot or will not take the statin because of the symptoms they describe.
Source: Allison Fellers, National Lipid Association. Printed with permission.
Statins are among the most highly investigated agents and studies show they reduce risk for MI, ischemic stroke, hospitalization for unstable angina, CV mortality and all-cause mortality. Despite the data, approximately 50% of patients stop taking their statin after 6 months and only 20% of high-risk patients are taking their statin after 5 years, Peter P. Toth, MD, PhD, FAHA, FESC, FACC, director of preventive cardiology at CGH Medical Center in Sterling, Illinois; professor of clinical family and community medicine at University of Illinois College of Medicine in Peoria; professor of medicine at Michigan State University College of Osteopathic Medicine in East Lansing, wrote in an editorial published in the Journal of the American College of Cardiology.
“The issue of statin intolerance warrants considerable further investigation, because it undermines standard of care for a very large number of patients worldwide and leaves them vulnerable to ASCVD-related events,” Toth wrote. “Aches and pains are a fact of life; just because a patient has them does not mean they should be attributed to their statin.”
For patients who are unable or unwilling to take a statin to reduce CV risk, clinicians must find a plan that works to reduce their LDL, according to Kevin C. Maki, PhD, CLS, FNLA, president and chief scientist of Midwest Biomedical Research, adjunct professor at Indiana University School of Public Health and immediate past president of the National Lipid Association.
“If a person thinks that the aches and pains are related to the statin, you are going to have a hard time keeping them on the statin,” Maki told Healio. “Clinicians must work closely with patients to educate them on the value of lowering LDL. We have very good evidence that lower for longer is better when it comes to LDL and reducing event risk. Then, it is a matter of working as a team to say, ‘If you have a side effect, we have options.’”
Alternative dosing regimens
Finding a regimen that is acceptable to the patient may require switching agents, changing dosages or using alternative regimens such dosing on alternate days.
“There are many statins,” Fatima Rodriguez, MD, MPH, FACC, FAHA, FASPC, associate professor in cardiovascular medicine at Stanford University, told Healio. “For example, someone may experience side effects or drug-drug interactions with simvastatin but may be able to tolerate rosuvastatin. You can also try intermittent dosing or very low dosing. A little bit of statin is better than no statin. Even if we need to add a second nonstatin medication to reduce the LDL or a nonstatin alternative altogether, lowering LDL is the ultimate goal.”
Healio | Cardiology Today Editorial Board Member Steven E. Nissen, MD, MACC, chief academic officer of the Sydell and Arnold Miller Family Heart, Vascular & Thoracic Institute and the Lewis and Patricia Dickey Chair in Cardiovascular Medicine at Cleveland Clinic, said he has some patients who take rosuvastatin 3 days per week, plus ezetimibe.
“One strategy that has worked very well for me is trying a low dose of a statin, 5 mg of rosuvastatin, and then adding ezetimibe,” Nissen told Healio. “If you add ezetimibe to 5 mg rosuvastatin, you get the equivalent LDL lowering to 40 mg of rosuvastatin.”
Healio | Cardiology Today Editorial Board Member Erin D. Michos, MD, MHS, FACC, FAHA, FASE, FASPC, associate professor of medicine and director of women’s cardiovascular health at Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease, said a clinician must consider a person’s risk category when deciding on an LDL-lowering regimen.
“If they are very high risk, if they have ASCVD and already had an MI, I am quickly moving to effective therapies to get their LDL down,” Michos told Healio. “But in primary prevention, you can give it a little more time. I may try a different statin, or intermittent dosing, like 5 mg three times a week of rosuvastatin. You would be surprised; you can see pretty significant LDL lowering with modest doses of a moderate-intensity statin.”
Michos said acknowledging a patient’s reported symptoms can also go a long way in building trust and confidence to try either a different statin or statin dose.
“The symptoms are real to the patient, and sometimes they feel they have been dismissed by other clinicians,” Michos said. “Like all of us, as humans, we want to feel our symptoms are validated. I listen to them and take them seriously. This is about building trust. I may start with 5 mg rosuvastatin once a week, just to get them used to the idea of taking a statin. Then we move to twice a week and then to three times a week. I escalate pretty quickly, I don’t wait.”
Nonstatin options
Nonstatin therapy may be required for patients who cannot reach therapeutic objectives with lifestyle and maximally tolerated statin therapy. The NLA guidance states that clinicians should favor nonstatin therapies with data from outcomes trials showing a reduction in adverse CV events.
In the CLEAR Outcomes trial, bempedoic acid (Nexletol, Esperion Therapeutics), which significantly lowered LDL compared with placebo, reduced risk for major adverse CV events (CV death, nonfatal MI, nonfatal stroke and coronary revascularization) by 13% vs. placebo, including a 23% lower risk for MI, among adults with a history of CVD or at high risk and deemed statin intolerant. To be enrolled in CLEAR Outcomes, prospective participants needed to sign a statin intolerance confirmation form, stating they were unable to tolerate statins even though they would reduce the person’s risk for MI, stroke or death, making it the first trial designed to exclusively enroll statin-intolerant patients.
“Bempedoic acid produces moderate LDL lowering but is now shown to reduce CV events,” Nissen said. “PCSK9 inhibitors are also very effective and well tolerated and tend not to induce statin-type adverse events. They are expensive, as is bempedoic acid, and some people do not want to self-inject medication every 2 weeks.”
Another alternative could be inclisiran (Leqvio, Novartis), a PCSK9 inhibitor administered infrequently, Nissen said. Long-term data from the ORION-3 study demonstrated that, in adults with ASCVD or a risk equivalent, twice-yearly inclisiran injections were associated with a 44% reduction in LDL that was sustained over 4 years, with no new safety signals observed.
“After the first two doses, it is once every 6 months,” Nissen said. “It is a really nice approach, and one that may gain additional traction in coming years.”
The right regimen: ‘Time matters’
Clinicians agree that the overarching message when it comes to LDL and ASCVD risk is “lower for longer.” However, achieving an LDL goal is more complicated when a provider is struggling to find a regimen that works for a patient who cannot or will not take a recommended statin.
For these patients, Maki said, clinicians must strike a careful balance: Finding a therapy regimen that works, without waiting too long to reduce LDL in a meaningful way. That approach could mean more intense follow-up for some patients, trying multiple statins or alternative therapies and moving on quickly if something does not work to avoid lost time, he said.
“I am not so concerned about how the LDL level is lowered,” Maki said. “But I do not like to see patients, especially those with ASCVD, left untreated or undertreated for a year while a provider is trying to figure out a regimen. Time matters. Lower [LDL] for longer is better, and getting there as fast as you can is ideal.”
We want to hear from you:
Healio wants to hear from you: How do you navigate statin intolerance with patients? Share your thoughts with Healio by emailing the author at rschaffer@healio.com or tweeting @CardiologyToday. We will contact you if we wish to publish any part of your story.
References:
- Cheeley MK, et al. J Clin Lipidol. 2022;doi:10.1016/j.jacl.2022.05.068.
- Nissen SE, et al. N Engl J Med. 2023;doi:10.1056/NEJMoa2215024.
- Ray KK, et al. Lancet. 2023;doi:10.1016/S0140-6736(22)00353-9.
- Toth PP. J Am Coll Cardiol. 2021;doi:10.1016/j.jacc.2021.07.025.
For more information:
Kevin C. Maki, PhD, CLD, FNLA, can be reached at kmaki@mbclinicalresearch.com.
Erin D. Michos, MD, MHS, FACC, FAHA, FASPC, can be reached at edonnell@jhmi.edu; X (Twitter): @erinmichos.
Steven E. Nissen, MD, MACC, can be reached at nissens@ccf.org.
Fatima Rodriguez, MD, MPH, FACC, FAHA, FASPC, can be reached at frodrigu@stanford.edu; X (Twitter): @farodriguezmd.
Collapse
Healio Interviews
Click Here to Manage Email Alerts