ACC.19: 3 Studies in Cardioprotection

DECLARE-TIMI 58. This was a double-blind multinational RCT comprised of 17 160 patients with type 2 diabetes and established CVD or at high CV risk. It is the first diabetes cardiovascular outcomes trial to evaluate patients stratified by EF. Randomization was to the SGLT2 inhibitor dapagliflozin 10 mg daily or placebo added to standard therapy.  Primary outcome measure: composite of CV death/hospitalization for HF (HHF).
 

DAPA Lowers HHF/CV Death More in HFrEF. Primary outcome: Lower risk of HHF/CV death with DAPA vs placebo; risk found lower in patients with HFrEF (38% lower) vs those without HFrEF (12% lower risk).

Larger Decrease in Mortality in HFrEF. Results driven by significantly larger decrease in CV death and all-cause mortality only in HFrEF. Hospitalization for heart failure: difference not significant. CV death: significantly lower in patients with HFrEF (p=0.012). All-cause mortality: significantly lower with HFrEF (p=0.016)

DECLARE-TIMI 58 Conclusion/Implications. Among T2DM patients stratified by LVEF, dapagliflozin reduced HHF in patients with and without HFrEF, and reduced CV death and all-cause mortality in patients with HFrEF. Clinical implication: EF status may help identify T2DM patients who could benefit most from therapy with SGTL2 inhibitors.

REDUCE-IT-Reduction of Cardiovascular Events with EPA-intervention. Double blind multinational RCT comprised of 8179 patients with hypertriglyceridemia despite maximally-tolerated statin therapy; 71% with atherosclerosis, 29% with DM. Randomized to icosapent ethyl 4 g/day or placebo. Primary endpoint: total first pluCV Es subsequent ischemic events. Median follow-up: 4.9 years.

CV Events Reduced with Icosapent Ethyl Added to Statins. 30% relative risk reduction in total ischemic events with icosapent ethyl vs placebo. First event: 25% reduction; second event: 32% reduction; third event: 31% reduction; ≥4 events: 48% reduction.

REDUCE-IT Conclusion and Clinical Implication. “Among statin-treated patients with elevated triglycerides and cardiovascular disease or diabetes, multiple statistical models demonstrate that icosapent ethyl substantially reduces the burden of first, subsequent, and total ischemic events.” Clinical implications: Icosapent ethyl may further reduce total ischemic events in patients with inadequate response to statins.

CLEAR Wisdom Trial. RCT with 779 participants with ASCVD or FH and hyppercholesterolemia despite maximally tolerated statins; 30% with diabetes, 94% with ASCVD alone; 53% high intensity statin, 31% moderate intensity statin. Primary outcome: change in LDL-C from baseline. Follow-up: 52 weeks.
 

LDL -C Change from Baseline Significantly Lower. Change in LDL from baseline significantly lower with bempedoic acid vs placebo (-15.1%vs  2.4%). Many secondary outcomes significantly better with bempedoic acid vs placebo but no differences in clinical outcomes were observed.

CLEAR Wisdom Secondary Outcomes and Conclusions. “The results of this trial indicate that bempedoic acid is safe and effective in reducing LDL-C compared with placebo among patients with ASCVD or heterogeneous FH  on maximum-tolerated statin therapy. These are encouraging data, but outcomes data are needed prior to recommending this agent to patients.”