BP, cholesterol interventions yield ‘legacy’ benefit in ASCOT trial follow-up

MUNICH — Sixteen years of follow-up in the ASCOT Legacy trial show that antihypertensive treatment with a calcium channel blocker-based regimen and lipid lowering with a statin demonstrated long-term beneficial effects on mortality.

Patients on amlodipine-based treatment had fewer stroke deaths and patients on atorvastatin had fewer CV deaths more than a decade after the trial was stopped.

“This study is the first to report that both blood pressure and lipid-lowering treatments confer long-term cardiovascular mortality benefits,” Ajay K. Gupta, MD, of the William Harvey Research Institute, Queen Mary University London, told Cardiology Today.

Gupta reported 16-year follow-up data from ASCOT Legacy at the European Society of Cardiology Congress. ASCOT was a multicenter, randomized trial with a 2x2 factorial design. Patients in the U.K. with hypertension were followed for all-cause and CV mortality for a median of 15.7 years (interquartile range, 9.7-16.4).

The overall ASCOT trial included 19,000 patients, but Gupta presented findings from 8,580 U.K. patients who were initially assigned to a BP-lowering arm, to compare amlodipine-based treatment, with perindopril added as needed (n = 4,305), and atenolol-based treatment, with bendroflumethazide added as needed (n = 4,275). Patients with hyperlipidemia (total cholesterol 6.5 mmol/L) and no history of lipid treatment were included in a lipid-lowering arm, to compare atorvastatin treatment (n = 2,317) and placebo treatment (n = 2,288); the remaining 3,975 patients were included in a non-lipid-lowering arm.

Overall, 38% of patients died during follow-up. In the BP arm, 38.4% of patients assigned atenolol-based treatment died vs. 38.1% of those assigned amlodipine-based treatment. In the lipid-lowering arm, 39.5% of patients assigned placebo died vs. 37.3% of those assigned atorvastatin. According to the researchers, 36.9% of all deaths were related to CV causes.

In the BP-lowering arm, there was no difference in all-cause mortality between atenolol- or amlodipine-based treatment (adjusted HR = 0.9; 95% CI, 0.81-1.01). However, patients assigned amlodipine-based treatment had a significant 29% reduction in stroke death (aHR = 0.71; 95% CI, 0.53-0.97), and numerically fewer CV deaths during the 16-year follow-up, Gupta said during a presentation.

In the lipid-lowering arm, patients assigned atorvastatin had a significant 15% reduction in CV death (HR = 0.85; 95% CI, 0.72-0.99). The researchers also observed fewer all-cause and CHD deaths in the atorvastatin group, but the differences were not significant.

In the non-lipid-lowering arm, fewer CV deaths occurred among those assigned amlodipine-based treatment vs. atenolol-based treatment (aHR = 0.79; 95% CI, 0.67-0.93).

“Findings from the higher baseline risk group — the non-lipid-lowering arm subgroup — confirm the long-term benefits of blood pressure-lowering therapies in such patients,” Gupta said.

The researchers noted in The Lancet that “the long-term benefits associated with the amlodipine-based regimen could not be attributed to earlier differences in blood pressures during the trial.”

In the ASCOT trial, the BP-lowering arm was stopped early after 5.5 years of treatment and the lipid-lowering arm after 3.3 years, due to reductions in major outcomes.

Diederick E. Grobbee, MD, PhD, FESC, professor of epidemiology at The Julius Center for Health Sciences and Primary Care at University Medical Center Utrecht, Netherlands, discussed the findings at ESC Congress.

“I think [these are] important data, but I don’t think the implication should be short-term aggressive LDL-C lowering starting early in life,” Grobbee said.

Rather, he said, it is important to inform patients of long-term benefits and to discuss the long-term benefits of medication to improve adherence and uptake.

“Our study gives a good argument ... that patients with hypertension should be on a calcium channel blocker or ACE inhibitor or angiotensin receptor blocker and also a statin. ... I think that’s the most important message from a physician point of view,” Gupta told Cardiology Today. “For the patient point of view, we are giving them hope that not only today is important, but tomorrow is also important,” in terms of treatment. – by Katie Kalvaitis

References:

Gupta AK, et al. Clinical Trial Updates. Presented at: European Society of Cardiology Congress; Aug. 25-29, 2018; Munich.

Gupta A, et al. Lancet. 2018;doi:10.1016/S0140-6736(18)31776-8.

Disclosures: The study was funded by Pfizer. Gupta reports he received support from the Foundation for Circulatory Health during the conduct of the study and nonfinancial support from Servier outside the submitted work. Please see the full study for a list of the other authors’ relevant financial disclosures. Grobbee reports no relevant financial disclosures.