In adults with AMI who are at risk for HF, empagliflozin did not reduce a composite of first HF hospitalization or all-cause death at 18 mo.

SOURCE CITATION: Butler J, Jones WS, Udell JA, et al. Empagliflozin after acute myocardial infarction. N Engl J Med. 2024;390:1455-1466. 38587237.

In noncardiac thoracic surgery, low-dose colchicine did not reduce AF or myocardial injury after noncardiac surgery at 14 d.

SOURCE CITATION: Conen D, Ke Wang M, Popova E, et al; COP-AF Investigators. Effect of colchicine on perioperative atrial fibrillation and myocardial injury after non-cardiac surgery in patients undergoing major thoracic surgery (COP-AF): an international randomised trial. Lancet. 2023;402:1627-1635. 37640035.

Reduced dietary sodium did not reduce clinical events in heart failure.

SOURCE CITATION: Ezekowitz JA, Colin-Ramirez E, Ross H, et al. Reduction of dietary sodium to less than 100 mmol in heart failure (SODIUM-HF): an international, open-label, randomised, controlled trial. Lancet. 2022;399:1391-400. 35381194.

In patients with MI or high-risk coronary disease, influenza vaccination reduced CV events at 12 mo.

SOURCE CITATION: Fröbert O, Götberg M, Erlinge D, et al. Influenza vaccination after myocardial infarction: a randomized, double-blind, placebo-controlled, multicenter trial. Circulation. 2021;144:1476-84. 34459211.

In patients with stable CVD receiving statins, evolocumab reduced acute arterial events across all vascular territories.

SOURCE CITATION: Oyama K, Giugliano RP, Tang M, et al. Effect of evolocumab on acute arterial events across all vascular territories: results from the FOURIER trial. Eur Heart J. 2021;42:4821-9. 34537830.

After PCI and short-term DAPT, P2Y12 inhibitors alone vs. ongoing DAPT reduce major bleeding; CV events do not differ.

SOURCE CITATION: Malik AH, Yandrapalli S, Shetty SS, et al. Meta-analysis of dual antiplatelet therapy versus monotherapy with P2Y12 inhibitors in patients after percutaneous coronary intervention. Am J Cardiol. 2020;127:25-9. 32389351.

Hypothesis: Paroxetine, a G Protein-Coupled Receptor Kinase 2 (GRK2) Inhibitor Reduces Morbidity and Mortality in Patients With Heart Failure.

The hypothesis that paroxetine decreases morbidity and mortality in patients with heart failure (HF) is plausible but unproven. Basic research demonstrates that inhibition of G protein-coupled receptor kinase 2 (GRK2) both in vitro and in vivo in the myocardium may be beneficial. G protein-coupled receptor kinase 2 antagonism is purported to exert cardioprotective effects immediately following myocardial injury by blunting toxic overstimulation on a recently injured heart. In addition, chronic overexpression of GRK2 inhibits catecholamine induction of vital positive chronotropic and ionotropic effects required to preserve cardiac output leading to worsening of congestive HF. In cardiac-specific GRK2 conditional knockout mice, there is significant improvement in left ventricular wall thickness, left ventricular end-diastolic diameter (LVEDD), and ejection fraction (EF) compared to controls. Paroxetine is a selective serotonin reuptake inhibitor which was recently shown to have the ability to directly inhibit GRK2 both in vitro and in vivo. At physiologic temperatures, paroxetine inhibits GRK2-dependent phosphorylation of an activated G-protein-coupled receptor with a half maximal inhibitory concentration of 35 micromoles, a substantially greater affinity than for other G protein-coupled receptor kinases. In a randomized trial in mice with systolic HF and depressed EF postmyocardial infarction, those treated with paroxetine had a 30% increase in EF, improved contractility, and LVEDD and wall thickness compared to those treated with medical therapy alone. While further basic research may continue to elucidate plausible mechanisms of benefit and observational studies will contribute important relevant information, large scale randomized trials designed a priori to do so are necessary to test the hypothesis.

Non-critical care telemetry and in-hospital cardiac arrest outcomes.

BACKGROUND: Telemetry is increasingly used to monitor hospitalized patients with lower intensities of care, but its effect on in-hospital cardiac arrest (IHCA) outcomes in non-critical care patients is unknown. HYPOTHESIS: Telemetry utilization in non-critical care patients does not affect IHCA outcomes. METHODS: A retrospective cohort analysis of all patients in non-critical care beds that experienced a cardiac arrest in a university-affiliated teaching hospital during calendar years 2011 and 2012 was performed. Data were collected as part of AHA Get With the Guidelines protocol. The independent variable and exposure studied were whether patients were on telemetry or not. Telemetry was monitored from a central location. The primary endpoint was return of spontaneous circulation (ROSC) and the secondary end point was survival to discharge. RESULTS: Of 123 IHCA patients, the mean age was 75±15 and 74 (61%) were male. 80 (65%) patients were on telemetry. Baseline demographics were similar except for age; patients on telemetry were younger with mean age of 70.3 vs. 76.8 in the non-telemetry group (p=0.024). 72 patients (60%) achieved ROSC and 46 (37%) achieved survival to discharge. By univariate analysis, there was no difference between patients that had been on telemetry vs. no telemetry in ROSC (OR=1.13, p=0.76) or survival to discharge (OR=1.18, p=0.67). Similar findings were obtained with multivariate analysis for ROSC (0.91, p=0.85) and survival to discharge (OR=0.92, p=0.87). CONCLUSIONS: The use of cardiac telemetry in non-critical care beds, when monitored remotely in a central location, is not associated with improved IHCA outcomes.

Cardiovascular risks of cyclooxygenase-2 inhibitors and traditional anti-inflammatory drugs: necessary but not sufficient for clinical decision making.

Cyclooxygenase-2 inhibitors were initially developed, then received regulatory approval and were subsequently widely marketed to achieve effective pain relief in patients with inflammatory conditions while decreasing gastrointestinal complications. Gastrointestinal symptoms as well as signs had been a major concern with the use of traditional non-steroidal anti-inflammatory drugs. Individual clinical judgements about the prescription of cyclooxygenase-2 inhibitors and non-steroidal anti-inflammatory drugs for relief of pain from inflammatory arthritis should not be limited to risks of cardiovascular disease but should also consider gastrointestinal complications, symptoms as well as signs, and other benefits which include, but are not limited to improvements in quality of life resulting from decreases in pain or impairment from musculoskeletal pain syndromes.

Aspirin increases nitric oxide formation in chronic stable coronary disease.

INTRODUCTION: There are no published randomized data on secondary prevention in humans about whether aspirin affects nitric oxide (NO) formation. In patients with chronic stable coronary disease, we tested whether aspirin at clinically relevant doses increases NO formation. MATERIALS AND METHODS: In a randomized, double-blind trial, 37 patients from 2 cardiology office practices were assigned to daily doses of 81, 162.5, 325, 650, or 1300 aspirin for 12 weeks. Primary prespecified outcome measures were changes in heme oxygenase (HO-1), a downstream target of NO formation, and asymmetrical dimethyl arginine (ADMA), a competitive inhibitor of NO synthase. RESULTS: There were no significant differences for HO-1 or ADMA between any of the clinically relevant doses of aspirin tested, so all were combined. For HO-1, there was a significant increase (10.29 ± 2.44, P < .001) from baseline (15.37 ± 1.85) to week 12 (25.66 ± 1.57). The mean ratio (MR) of week 12 to baseline for HO-1 was significantly higher than 1.0 (1.67, confidence interval [CI] from 1.60 to 1.74, P < .001). For ADMA, there was a significant decrease (-0.24 ± 0.11, P < .001) from baseline (0.78 ± 0.08) to week 12 (0.54 ± 0.07). The MR of week 12 to baseline for ADMA was significantly lower than 1.0 (0.69, CI from 0.66 to 0.73, P < .001). CONCLUSIONS: In patients with chronic stable coronary disease, all clinically relevant daily doses of aspirin tested, from 81 to 1300 mg, produce similar and statistically significant increases in HO-1 and decreases in ADMA. These are the first randomized data on secondary prevention patients. These data support the hypothesis that aspirin has additional beneficial effects mediated through NO formation. Further research, including direct randomized comparisons on atherosclerosis using noninvasive techniques as well as on occlusive vascular disease events, is necessary.

Enhanced sensitivity to drug-induced QT interval lengthening in patients with heart failure due to left ventricular systolic dysfunction.

Patients with heart failure (HF) are at increased risk for drug-induced torsades de pointes (TdP) due to unknown mechanisms. Our objective was to determine if sensitivity to drug-induced QT interval lengthening is enhanced in patients with HF. In this multicenter, prospective study, 15 patients with atrial fibrillation or flutter requiring conversion to sinus rhythm were enrolled: 6 patients with New York Heart Association class II to III HF (mean ejection fraction [EF], 30% ± 9%), and 9 controls (mean EF, 53% ± 6%). Patients received ibutilide 1 mg intravenously. Blood samples and 12-lead electrocardiograms were obtained prior to and during 48 hours postinfusion. Serum ibutilide concentrations at 50% maximum effect on Fridericia-corrected QT (QT(F)) intervals (EC(50)) were determined, and areas under the effect (QT(F) interval vs time) curves (AUECs) were calculated. Ibutilide concentration-QT(F) relationships were best described by a sigmoidal E(max) model with a hypothetical effect compartment. Median [interquartile range] AUEC from 0 to 4 hours was larger in the HF group than in controls (1.86 [1.86-1.93] vs 1.82 [1.81-1.84] s·h; P = .04). Median EC(50) was lower in the HF group (0.48 [0.46-0.49] vs 1.85 [1.10-3.23] µg/L; P = .008). Sensitivity to drug-induced QT interval lengthening is enhanced in patients with systolic HF, which may contribute to the increased risk of drug-induced TdP.

Do Statins Reduce Atrial Fibrillation After Coronary Artery Bypass Grafting?

Background: Atrial Fibrillation (AF) is a common postoperative complication after coronary artery bypass grafting. There is contradictory evidence as to whether pre-operative statin use lowers the incidence of postoperative AF. This study aimed to assess whether pre operative statin therapy prevents the post-operative AF. Methods: In this retrospective cohort study we used a propensity score-matching analysis to evaluate the effect of preoperative treatment with statins on postoperative atrial fibrillation. There were 427 matched pairs of patients. Primary outcome was the incidence of postoperative AF. Secondary outcomes were 30 day mortality, stroke, myocardial infarction and length of hospital stay. Results: The incidence of postoperative AF was not different in the statin users compared with the nonusers (123, 28.1%, versus 127, 29.7%, respectively; p = 0.764). The 30 day mortality (6, 1.4%, versus 8, 1.9%; p = 0.590), stroke (10, 2.3%, versus 8, 1.9%; p = 0.634), myocardial infarction (2, 0.5%, versus 0, 0.0%; p = 0.499) and length of hospital stay in days (11.8 ± 9.0, versus 11.9 ± 9.3; p = 0.544) did not differ significantly between the two groups. Conclusions: In a propensity-matched cohort of patients undergoing coronary bypass surgery, we could not demonstrate that preoperative statins were protective for the development of post operative atrial fibrillation.