Bempedoic Acid for Statin- Intolerant Patients at High Cardiovascular Risk
The CLEAR Outcomes Trial, presented by Steven Nissen, MD, was designed to test the effects of bempedoic
acid—a first-in-class, orally administered ATP citrate lyase (ACL) inhibitor that reduces LDL-C—on
cardiovascular morbidity and mortality in 13,970 patients with statin in- tolerance who were at high risk
for cardiovascular disease. Participants were randomized 1:1 to bempedoic acid 180 mg/day or matching
placebo. The primary endpoint was a four-component composite of MACE, defined as non-fatal myocardial
infarction (MI), non-fatal stroke, coronary revascularisation, or cardiovascular death. After 6 months,
LDL-C reduction was greater with bempedoic acid than with placebo by 29.2 mg/dL, with an observed difference
of 21.1%(-21.7% vs -0.6%). The incidence of a primary endpoint event was significantly lower with bempedoic
acid compared with placebo. The primary endpoint was met by 819 (11.7%) and 927 (13.3%) patients,
respectively (HR, 0.87; 95% CI, 0.79–0.96; P=0.004). Notably, the HR in women was the same: 0.86. The
overall absolute risk reduction was 1.6% (number needed to treat: 63). “The CLEAR Outcomes trial provides
a sound rationale for the use of bempedoic acid to reduce major adverse cardiovascular outcomes in
patients who are intolerant to statins,” said Dr. Nissen.
Sleeping Well Tied to Better Life Expectancy
Researchers analyzed the association of low-risk sleep patterns with mortality and life expectancy, using
a nationally representative sample of 172,321 US adults who participated in the National Health Interview
Survey between 2013 and 2018. The authors devised a low-risk sleep score using five sleep-related factors.
Life expectancy at age 30 by sleep score was estimated. During a median follow-up of 4.3 years, 8,681
participants died, including 2,610 from cardiovascular disease and 2,052 from cancer. Young people with
more beneficial sleep habits were incrementally less likely to die early. The authors estimated that 7.9%
(5.5% to 10.4%) of the population-attributable risk from all-cause mortality in this cohort was due to
suboptimal sleep patterns. Among individuals who reported all five low-risk sleep factors, life expectancy
at 30 was 4.7 years greater for men (52.2 vs 47.5 years) and 2.4 years greater for women (56.7 vs 54.3 years)
compared with people with one or fewer of these factors.
Baxdrostat for Uncontrolled Hypertension
The results of a phase 2 study were highly anticipated, with no new agents to treat uncontrolled
hypertension in well over a decade, said Deepak Bhat, MD, MPH. Baxdrostat is a highly selective
aldosterone synthase inhibitor. Its efficacy and safety were evaluated in the randomized, double-blind,
placebo-controlled, multicenter, phase 2 HALO trial. Participants had to be on a stable regimen of an
angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB), an ACEi/ARB plus a
thiazide diuretic, or an ACEi/ARB plus a calcium channel blocker, and have a mean seated SBP of 140 mmHg
or greater. The primary endpoint was change from baseline in mean seated SBP after8 weeks of treatment.
A total of 249 patients were randomized 1:1:1:1 to baxdrostat 0.5 mg,1 mg, 2 mg, or placebo; 227
completed the trial. The primary endpoint was not met with any baxdrostat dose. SBP changes were -16.6
mmHg in the placebo group, and -17.0, -16.0, and -19.8 mmHg in the 0.5 mg, 1 mg, and 2 mg groups,
respectively. Changes in place-bo-corrected systolic BP for the 0.5, 1, and 2 mg groups were -0.5 mmHg,
0.6 mmHg, and -3.2 mmHg. Similarly, none of the baxdrostat doses were associated with a significant
difference in placebo-corrected diastolic blood pressure (DBP), which was a secondary endpoint. Change in
DBP at 8 weeks did not significantly differ, either, nor did the percentage of patients achieving a
seated SBP response of less than 130 mmHg at 8 weeks. Baxdrostat significantly reduced serum aldosterone
levels at all doses. The treatment was well tolerated.
Inflammation Stronger Predictor of MACE than Cholesterol Levels
Paul Ridker, MD, MPH, explained that he and colleagues aimed to determine the relative importance of
high-sensitivity C-reactive protein (hsCRP) and LDL-C as determinants of risk for MACE, CV death, and
all-cause death among patients receiving statins, hoping to resolve the question of whether to add a
second LDL-low-ering agent or anti-inflammatory to a statin. Dr. Ridker and colleagues performed a
collaborative analysis of 31,245 patients with, or at high risk for, atherosclerotic disease receiving
contemporary statins who participated in the PROMINENT, REDUCE-IT, or STRENGTH trials. Assessed were
quartiles of increasing baseline hsCRP and increasing baseline LDL-C. Comparing the highest (4th)
quartile with the first (referent) quartile, residual inflammatory risk measured by hsCRP was significantly
associated with incident MACE (HR, 1.31), CV mortality (HR, 2.68), and all-cause mortality (HR, 2.42).
Residual cholesterol risk was not associated with MACE (HR, 1.07). It was associated with CV death and
all-cause death, but HRs were much lower: 1.27 and 1.16, respectively. In all three trials, patients with
elevated hsCRP were at high CV risk irrespective of their LDL-C levels, Dr. Ridker concluded. “We believe
the combined use of aggressive LDL-lowering and inflammation-inhibiting therapies will become standard of
care for almost all [patients with atherosclerosis],” he said.
Multifaceted Strategy Improves Prescription of Therapies for T2D & ASCVD
The COORDINATE-Diabetes study evaluated the effect of a clinic-level intervention that incorporated
assessment, education, and feedback on the prescription of high-intensity statins, ACE inhibitors or ARBs,
and SGLT2i and/or glucagon-like peptide 1 receptor agonists (GLP1RAs). Neha Pagidipati, MD, MPH, explained
that clinics in the intervention group collaborated to develop a multifaceted intervention, which
entailed:
1. Assessment of local practices and barriers to prescribing recommended therapies
2. Developing strategies to overcome these barriers
3. Audit and feedback on quality metrics The study enrolled 1,049 patients, 459 of whom were treated in
clinics (intervention group) and 590 of whom received usual care. The primary outcome—proportion of
patients prescribed all three groups of therapies at 6-12 months after enrollment—was reached by 37.9% in
the intervention group and 14.5% in the control group, an absolute difference of 23.4%. Dr. Pagidipati
said this difference was primarily driven by a large increase in prescriptions for SGLT2i and GLP1RAs.
