Stopping Statins Ups CVD and Mortality Risks in Pill-Burdened Seniors

Older patients taking a bevy of drugs for multiple conditions who stop taking their statins are at a higher risk of adverse cardiovascular events and all-cause death than patients who keep statins in their multidrug regimen, according to a new observational study.

The risks of stopping statins weren’t trivial either, say investigators, noting that statin discontinuation was associated with a 12% higher relative risk of all-cause hospital admissions and a 24% higher risk of heart failure.

“On the other hand, the simplification of the polypharmacy burden in these patients did not generate a significant reduction in access to the emergency department for neurological causes, considered a proxy for the onset of episodes of delirium,” write lead investigator Federico Rea, PhD (University of Milano-Bicocca, Milan, Italy), and colleagues online June 14, 2021, in JAMA Network Open.

The new study addresses one of the more-pressing aspects of clinical care—how to care for aging patients treated with multiple guideline-directed medical therapies for various conditions. Both the exposure to various chronic diseases and extensive polypharmacy may have negative clinical consequences, including the possibility of cognitive impairment and adverse drug-drug interactions, according to the researchers. Statins, on the other hand, play a pivotal role in the primary and secondary prevention of CVD.

It’s a common complaint I hear from my patients. They think they’re on too many medications. Ann Marie Navar

Ann Marie Navar, MD, PhD (UT Southwestern Medical Center, Dallas, TX), who wasn’t involved in the study, said polypharmacy is one of the unintended downsides to advances in medicine.

“If somebody has a not-uncommon set of conditions—diabetes, heart failure, and coronary disease—they could be on two or three medications to lower their cholesterol, two medications to prevent blood clots, a couple of medications to lower blood pressure, two or three medications for their diabetes, and another one or two medications for heart failure,” Navar told TCTMD. “They’re all recommended by the guidelines and they all work. They all lower the risk of hospitalization, but it ends up being a lot of pills.”

There is evidence showing that adherence to medical therapy is correlated with the number of pills the patient is taking, with higher counts associated with worse adherence. Combination therapies, such as those available for treating hypertension and high cholesterol, are available and would lower the patient’s pill count, but these agents can be challenging for physicians because it is more difficult to adjust dosages with them, said Navar. Even when they are used, combination therapies might only save the patient from taking one or two pills.

“It’s a common complaint I hear from my patients,” said Navar. “They think they’re on too many medications.”

Dropping Statins Not Good For Outcomes

The present study was intended to address the clinical implications of stopping statin therapy in individuals with multiple comorbidities receiving polypharmacy.

The study included 29,047 patients (mean age 76.5 years; 62.9% men) taking statins, blood pressure-lowering medication, pharmacotherapy for diabetes, and antiplatelet agents who were part of a healthcare utilization database in Lombardy, Italy. Of these, 20% had a history of ischemic heart disease, 7.9% had previous cerebrovascular disease, 7.9% had prior heart failure, and 8.1% had respiratory disease. Based on a multisource comorbidity score, which includes cardiovascular and noncardiovascular conditions, 11.7% were considered to have a “severe” clinical profile.

After approximately 2.4 years of follow-up per patient, 9,204 patients (31.7%) discontinued statins, including 5,819 patients who stopped statins before discontinuing other drug therapies. Focusing on the patients that stopped statins but stuck with the other drug classes, the researchers matched 4,010 patients who stopped the statin alone with 4,010 patients who maintained adherence to all four drug classes.

After a median follow-up of 10 months, those who stopped taking statin therapy had a significantly higher risk of hospitalization for any cardiovascular outcome (HR 1.14; 95% CI 1.03-1.26), hospitalization for heart failure (HR 1.24; 95% CI 1.07-1.43), deaths from any cause (HR 1.15; 95% CI 1.02-1.30), and emergency admissions for any cause (HR 1.12; 95% CI 1.05-1.19).

The researchers acknowledge there are limitations to the analysis, noting that it is not known why the patients stopped taking statins. Physicians might have opted to deprescribe, but if this were true, those who discontinued statin therapy would likely have a lower-risk profile at baseline and a lower overall risk of CVD and mortality, which was not observed, according to the researchers. It’s also possible the drugs were stopped because of the onset of adverse effects, but the high rate of discontinuation is unlikely to be explained fully by side effects.

Additionally, the researchers point out that patients who continued statin therapy might be more likely to engage in healthier behavior, the “so-called healthier user effect.”

To TCTMD, Navar also cautioned interpreting the data, noting, like the researchers, that medication adherence can be a surrogate for overall health-seeking behavior. While the increased risk of CVD events and hospitalizations may be attributed to the loss of statins, those who stopped statin therapy might be less engaged with their healthcare overall.

Fear of Side Effects

In the Patient and Provider Assessment of Lipid Management (PALM) registry, the perception and fear of side effects was the number one reason for stopping statin therapy, said Navar. In practice, it can be difficult to rechallenge patients with another statin if they stopped “because the side effect feels very real to the patient even if it isn’t caused by the molecule itself,” she said. Recently, the SAMSON trial showed that the vast majority of “statin-related” side effects were also reported by patients taking a placebo.

A conversation about the potential nocebo effect, as well as to debunk some of the myths around statins, can help with adherence to statins, “but it does take a lot of time and a lot providers don’t have the time to go through an informed process around statin side effects,” said Navar.   

While deprescribing has been raised as a potential solution to older patients burdened with multiple medications, drugs such as statins, sodium-glucose cotransporter 2 (SGLT2) inhibitors, or antihypertensive medications are difficult to deprescribe because they have a real clinical benefit, said Navar. Further talks can help when patients ask how long they need to be a certain medication, she said.

“I have found that if I explain to patients what each of the medications does, and how each of those medications is helping, they are much more willing to be on therapy,” said Navar. “A lot of people . . . haven’t had a conversation with their doctor to understand the reasons for each of the medications that they’re currently on. So it feels like a lot. Once they have a conversation and learn that each of the medicines has its own benefit, they feel better about taking it.”

Navar noted that a lot of patients complicate their pill burden by taking over-the counter vitamins or supplements. Subtracting these, which are often paid for out of pocket, can help patients feel like they’re taking less medication overall. “At least deprescribing things they don’t need, including over-the-counter vitamins, can be pretty helpful,” she said.