By Michael H. Crawford, MD, Editor
The following is an overview of important cardiology research presented Aug. 25 through Aug. 28 in Amsterdam and online during the ESC Congress 2023.
PACMAN-AMI
SYNOPSIS: In a study of serial coronary artery plaque composition imaging in the year after an acute myocardial infarction, aggressive low-density lipoprotein cholesterol-lowering with alirocumab helped significantly more patients achieve triple component plaque regression than those on placebo. This magnitude of plaque regression was associated with fewer adverse cardiovascular events.
SOURCE: Biccirè FG, et al. Concomitant coronary atheroma regression and stabilization in response to lipid-lowering therapy. J Am Coll Cardiol 2023; Aug 20: S0735-1097(23)06468-9. doi: 10.1016/j.jacc.2023.08.019. [Online ahead of print].
The frequency, characteristics, and outcomes of acute myocardial infarction (AMI) patients subsequently demonstrating plaque regression on lipid-lowering therapy are unknown. In an analysis of the PACMAN-AMI trial (Räber L, et al. JAMA 2022;327:1771-1781), Biccirè et al assessed the frequency of triple plaque regression — atheroma volume reduction, lipid content reduction, and increased fibrous cap thickness — by serial intravascular ultrasound, near-infrared spectroscopy, and optical coherence tomography in patients with AMI subsequently treated with high-intensity lipid-lowering therapy. Researchers also determined the characteristics of the triple regression patients and their one-year outcomes. Of 263 patients enrolled in PACMAN-AMI, 84 exhibited triple regression (41% in the alirocumab group and 23% in the placebo group; P = 0.002).
As expected, low-density lipoprotein cholesterol (LDL) levels were lower in patients with triple regression vs. those without triple regression (between-group difference: -27 mg/dL; P < 0.001). In addition to alirocumab therapy, triple regression was independently predicted by higher plaque lipid content (OR, 1.03; 95% CI, 1.01-1.06; P = 0.013). The composite endpoint of death, MI, or ischemia-driven revascularization was lower in patients with triple regression (8.3% vs. 18.2%; P = 0.04). The authors concluded that in post-AMI patients, subsequent triple plaque regression was associated with high-intensity lipid-lowering therapy (alirocumab), higher baseline plaque lipid content, and fewer adverse cardiovascular events.
COMMENTARY
Since alirocumab is a potent LDL-reducing agent, it is not surprising that it is associated with fewer major adverse cardiovascular events and improved plaque characteristics. What is surprising is that fewer than half the patients on alirocumab showed triple regression, and almost one-quarter of those on placebo showed triple regression. Clearly, other factors are involved. Many of those on placebo may have adopted a healthy lifestyle, while many on alirocumab may not have. These results strengthen physicians’ recommendation to adopt a healthy lifestyle and lower cholesterol levels after an AMI.
DAPA-RESIST
SYNOPSIS: In patients with acute decompensated heart failure complicated by diuretic resistance, dapagliflozin was not more effective than metolazone in improving fluid overload.
SOURCE: Yeoh SE, et al. Dapagliflozin vs. metolazone in heart failure resistant to loop diuretics. Eur Heart J 2023;44:2966-2977.
DAPA-RESIST was a multicenter, open-label, randomized trial of dapagliflozin 10 mg/day vs. metolazone 5 mg/day or 10 mg/day for three days in patients with acute decompensated heart failure resistant to loop diuretics. Diuretic resistance was defined as less than 1 kg decrease in weight or less than 1 L net negative fluid balance over 24 hours despite IV furosemide 160 mg or more per day and persistent signs of congestion. Patients with an estimated glomerular filtration rate less than 20 mL/min/1.73 m² were excluded. Investigators enrolled 61 patients (median age = 79 years; 54% women; ejection fraction less than 40% in 44% of patients).
The primary endpoint of mean change in weight at 96 hours was -3 kg vs. -3.6 kg (P = 0.11). Rates of increased serum creatinine, hypokalemia, hypotension, or death were not significantly different between the two groups. The authors concluded there was no improvement in decongestion with dapagliflozin compared to metolazone in diuretic-resistant patients with acute decompensated heart failure.
COMMENTARY
Loop diuretic resistance in acute heart failure patients is a challenging condition that often leads to the cardio-renal syndrome. This randomized comparison of dapagliflozin vs. metolazone revealed similar outcomes between the two treatment arms, although the trial was not powered for noninferiority. The adverse effects also were similar in the two groups, despite higher doses of furosemide for participants in the dapagliflozin group after their randomization (mean = 977 mg vs. 704 mg).
Sodium-glucose cotransporter 2 agents are recommended as first-line therapy for heart failure. (Monzo L, et al. Eur Heart J Suppl 2023;25:C309-C315.) The results of DAPA-RESIST support their use very early in the course of acute heart failure with reduced or normal ejection fraction.
HEART-FID
SYNOPSIS: A randomized trial of IV ferric carboxymaltose vs. placebo in patients with chronic systolic heart failure with mild anemia and iron deficiency revealed a modest improvement in cardiovascular outcomes.
SOURCE: Mentz RJ, et al. Ferric carboxymaltose in heart failure with iron deficiency. N Engl J Med 2023; Aug 26. doi: 10.1056/NEJMoa2304968. [Online ahead of print].
The value of iron supplementation in patients with systolic heart failure, anemia, and iron deficiency has been controversial. The authors of guidelines published in 2017 labeled such supplementation as a class IIB recommendation. (Yancy CW, et al. J Am Coll Cardiol 2017;70:776-803.) HEART-FID was a randomized, parallel group, double-blind, placebo-controlled study. The authors enrolled 3,065 ambulatory patients with an ejection fraction 40% or less, a hemoglobin level lower than 15 g/dL in men and lower than 13.5 g/dL in women (but higher than 9 g/dL in all), a ferritin level lower than 100 ng/mL or 100 ng/mL to 300 ng/mL with a transferrin saturation less than 20%, and either a heart failure hospitalization within the past 12 months or an elevated natriuretic peptide level (mean age = 69 years; 33% were women).
The primary outcome was death, hospitalization for heart failure, and six-minute walk distance, which was marginally significant after a median follow-up of two years (HR, 1.1; 95% CI, 0.99-1.23; P = 0.019). All-cause mortality was 8.6% with IV ferric carboxymaltose (IVFC) vs. 10.3% with placebo. Heart failure hospitalizations were 13% with IVFC vs. 15% with placebo. The change in six-minute walk distance was 8 m with IVFC vs. 4 m with placebo. Adverse events were similar in the two groups (27% vs. 26%). The authors concluded IVFC was safe, but marginally effective, at preventing adverse cardiovascular outcomes in mildly anemic patients with systolic heart failure.
COMMENTARY
Unfortunately, this study is unlikely to resolve the controversy surrounding treating chronic heart failure ambulatory patients with IVFC. Although a P value of 0.019 seems significant, the authors set less than 0.01 as a significant difference. However, the actual numbers of events do favor IVFC, and it was safe. This is a select group of patients because no one recorded a hemoglobin level < 9 g/dL,. Thus, it looks like it will be up to the physician to decide which of their patients diagnosed with mild anemia to treat.
The following is an overview of important cardiology research presented Aug. 25 through Aug. 28 in Amsterdam and online during the ESC Congress 2023.
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