VIENNA, Austria—Patients who undergo surgical valve replacement for aortic stenosis appear to derive a substantial clinical benefit if they’re treated with statins after the procedure, according to new results from a large Swedish study. This is especially true when intermediate or high intensity statins are used.

After more than 5 years of follow-up, the relative risk of MACE—a composite of all-cause mortality, stroke, or MI—was significantly lower in SAVR patients with ongoing statin treatment compared with untreated patients (HR 0.76; 95% CI 0.71-0.82), and this benefit was driven by a significant reduction in all-cause mortality (HR 0.69; 95% CI 0.64-0.75).

Emily Pan MD, PhD (Turku University, Finland, and Brigham and Women’s Hospital, Boston, MA), who presented the results of the study at the European Association for Cardio-Thoracic Surgery (EACTS) annual meeting, said that while there are data showing statins reduce the risk of cardiovascular events in TAVI-treated patients, there is limited information in the surgical realm.

“And because of this, currently both European and American guidelines have no specific recommendations regarding medications after SAVR, apart from treating other comorbidities,” said Pan.

Senior investigator Anders Jeppsson, MD, PhD (Sahlgrenska University Hospital, Gothenburg, Sweden), said the European Society of Cardiology (ESC)/EACTS task force will make update their guidelines soon. He suspects these new data will have to considered.

“The best evidence would be a randomized trial, but I doubt that will ever be done,” he told TCTMD. “Statins are inexpensive and the patents are [expired]. So, the pharmaceutical industry won’t likely start a trial that it’s going to need to last many years and include thousands of patients. We will have to rely on observational data.” 

What’s Driving Mortality Benefit?

The study, presented today at EACTS 2023 during the “President’s Choice” kickoff session, included patients enrolled in the Swedish Cardiac Surgery Registry, which is part of the larger SWEDEHEART registry. Data were linked to the national patient register, which includes information on all ICD codes, and two other registries tracking cause of death and drug prescriptions.

In total, the analysis included 11,893 patients who underwent SAVR between 2006 and 2020. Of these, 50.5% were prescribed statins at baseline, which was defined as within 6 months of hospital discharge. More than one-quarter were prescribed a high-intensity statin, 68.4% were prescribed an intermediate-intensity statin, and 3.5% were prescribed a low-intensity drug.

After a median follow-up of 5.4 years, the 24% relative reduction in MACE, as noted, was the result of a statistically significant reduction in all-cause mortality. MI was not significantly reduced in the Cox regression model nor in the propensity-score matched model, but the risk of stroke was significantly lower in the latter. Cardiovascular mortality, a secondary endpoint, was 26% lower in the statin-treated patients, but there was no effect on the endpoints of peripheral artery disease or new aortic valve intervention.

Patients treated with statins were significantly older at baseline, were more often male, had higher body mass index, and had more comorbidities than those who weren’t on treatment, but Jeppsson said the analysis adjusted for differences in baseline characteristics and time-updated data on medications.

The benefit was seen across all investigated subgroups, including men and women, young and old, those with different comorbidities, and in those with biological and mechanical valves. Overall, the treatment effect appeared stronger in patients with hypertension and hyperlipidemia at baseline. When stratified by statin intensity and adjusted for confounders, the reduction in MACE was statistically significant in those treated with intermediate- intensity statins (HR 0.74; 95% CI 0.68-0.80) and high-intensity statins (HR 0.86; 95% CI 0.77-0.97), but not in those prescribed weaker agents (HR 0.83; 95% CI 0.65-1.05). 

Session moderator Patrick Myers, MD (Lausanne University Hospital, Switzerland), EACTS secretary general, said these new data will help better treat patients with medical therapy after SAVR. Still, he questioned just how statins exerted their beneficial effect, noting that while there was a reduction in mortality, there was no effect on MI or repeat interventions on the aortic valve.

Pan said it was a question they asked themselves, too, but he suggested it might be the result of statins’ known pleiotropic effects, which include reduced inflammation and oxidative stress, among other systemic benefits.

Speaking with TCTMD, Cristian Baeza, MD (University Hospitals, Cleveland, OH), who wasn’t involved in the study, said that if you subtract the aortic valve replacement from the equation, it’s no surprise that patients treated with statins fared significantly better given the drugs’ demonstrated track record in secondary prevention. As a surgeon who also performs TAVIs, Baeza said that one major question left unanswered by the presentation is whether statin therapy prolonged valve durability, something that can’t be addressed in the current analysis.  

Cardiac surgeon Tom Nguyen, MD (University of California, San Francisco), who spoke during the session, questioned if it’s possible to rule out the impact of other “socioeconomic compliance” factors on the results. He noted that patients who take a statin could also be more compliant with other medications, such as aspirin, clopidogrel, or anticoagulation regimens, whereas not taking statins might reflect an inability or unwillingness to take these secondary prevention treatments.

To TCTMD, Pan pointed out that follow-up after surgery for aortic stenosis starts with cardiology, followed by primary care. “So, a lot of the secondary prevention medications will be started by those doctors,” she said. Generally speaking, patients on more medications would likely have more visits with their physicians, which could have impacted the quality of care they received, but Pan doesn’t think socioeconomic factors had an impact on compliance and outcomes. Access to healthcare and socioeconomic disparities are less pronounced in Sweden and other Scandinavian countries than in other regions, she said.