Hospitalization For Unstable Angina Research Articles

Safety of Linagliptin in Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis of Randomized Clinical Trials.

Linagliptin is an oral dipeptidyl peptidase DPP-4 inhibitor, which is indicated for the treatment of Type 2 diabetes mellitus (T2DM) as monotherapy or add-on to therapy with other hypoglycemic drugs. We aimed to summarize the evidence from randomized controlled trials (RCTs) to assess the safety of linagliptin focusing on cardiovascular risks among subjects with type 2 diabetes mellitus. We conducted a systematic search across the following databases: Medline, Embase, the Cochrane Central Register of Controlled Trials and ClinicalTrials.gov from inception to November 2021. Randomized controlled trials (RCTs) of linagliptin compared to placebo in patients with Type 2 diabetes were included. The primary safety points were cardiovascular (CV) adverse events including non-fatal stroke, non-fatal myocardial infarction (MI), CV death, MI, stroke, and hospitalization for unstable angina. While, secondary safety points included 17 reported adverse events such as infections, hypoglycemia and abdominal pain. Three reviewers independently screened and reviewed each study to extract relevant information. Any discrepancies were resolved by consensus. We conducted a meta-analysis using the random effects model. Pooled risk ratios (RRs) of targeted adverse events with linagliptin compared to placebo were estimated using the Mantel-Haenszel test. A total of 24 studies with 19,981 adult patients were included. There was no difference in the incidence of all CV adverse events or individual CV adverse events between linagliptin and the placebo arms. The pooled estimate of the risk of upper respiratory tract infection was reported in twelve trials with a 38% risk reduction among patients treated with the linagliptin group compared to the placebo group (RR = 0.62, 95% CI: 0.45-0.85, and I2 = 0%), while no difference was found in other infections. For gastrointestinal disorders, the risk of abdominal pain showed a 65% risk reduction among patients treated with the linagliptin group compared to the placebo group (RR = 0.35, 95% CI: 0.16-0.77, and I2 = 0%). Our study showed an overall acceptable safety profile of linagliptin in patients with T2DM. Moreover, our study showed a risk reduction of upper respiratory tract infection and abdominal pain when using linagliptin compared to placebo.

Risk of extended major adverse cardiovascular event endpoints with tofacitinib versus TNF inhibitors in patients with rheumatoid arthritis: a post hoc analysis of a phase 3b/4 randomised safety study

ObjectivesCompare the risk of extended major adverse cardiovascular (CV) event (MACE) composite outcomes and component events in patients with rheumatoid arthritis (RA) treated with tofacitinib versus tumour necrosis factor inhibitors...

Pemafibrate and other triglyceride-lowering therapies to reduce risk of cardiovascular and metabolic disease.

Although high triglycerides are consistently associated with elevated risk of cardiovascular disease (CVD), therapies that reduce triglyceride levels have inconsistently translated into reduced CVD risk. To date, three clinical trials have tested triglyceride-lowering therapies in patients with hypertriglyceridemia (HTG) and elevated risk of incident/recurrent CVD. In REDUCE-IT (Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial), assignment to IPE, a highly purified eicosapentanoic acid (EPA), resulted in a 25% reduction in nonfatal myocardial infarction), nonfatal stroke, cardiovascular death, coronary revascularization and hospitalization for unstable angina. By contrast, the combination of EPA and docosahexanoic acid (DHA) carboxylic fatty acids used in the STRENGTH trial (Statin Residual Risk With Epanova in High Cardiovascular Risk Patients With Hypertriglyceridemia) failed to reduce CVD risk. Most recently, PROMINENT (Pemafibrate to Reduce Cardiovascular Outcomes by Reducing Triglycerides in Patients with Diabetes) also failed to demonstrate reduction in CVD events despite use of a potent triglyceride-lowering, fibric-acid derivative. However, improvement in HTG-associated metabolic complications (e.g. nonalcoholic fatty liver disease) was observed with pemafibrate as well as with another potent triglyceride-lowering therapy (i.e. pegozafermin). Moreover, trials are underway evaluating whether the most fatal metabolic complication of HTG, pancreatitis, may be reduced with highly potent triglyceride-lowering therapies (e.g. apolipoprotein C3 inhibitors). Taken together, HTG is associated with increased risk of CVD and attendant adverse metabolic sequalae. To this end, a potentially promising and evidence-based landscape is emerging for treating a clinical phenotype that in the past has been insufficiently addressed.

Sex Differences in Revascularization, Treatment Goals, and Outcomes of Patients With Chronic Coronary Disease: Insights From the ISCHEMIA Trial.

Women with chronic coronary disease are generally older than men and have more comorbidities but less atherosclerosis. We explored sex differences in revascularization, guideline-directed medical therapy, and outcomes among patients with chronic coronary disease with ischemia on stress testing, with and without invasive management. The ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) trial randomized patients with moderate or severe ischemia to invasive management with angiography, revascularization, and guideline-directed medical therapy, or initial conservative management with guideline-directed medical therapy alone. We evaluated the primary outcome (cardiovascular death, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest) and other end points, by sex, in 1168 (22.6%) women and 4011 (77.4%) men. Invasive group catheterization rates were similar, with less revascularization among women (73.4% of invasive-assigned women revascularized versus 81.2% of invasive-assigned men; P<0.001). Women had less coronary artery disease: multivessel in 60.0% of invasive-assigned women and 74.8% of invasive-assigned men, and no ≥50% stenosis in 12.3% versus 4.5% (P<0.001). In the conservative group, 4-year catheterization rates were 26.3% of women versus 25.6% of men (P=0.72). Guideline-directed medical therapy use was lower among women with fewer risk factor goals attained. There were no sex differences in the primary outcome (adjusted hazard ratio [HR] for women versus men, 0.93 [95% CI, 0.77-1.13]; P=0.47) or the major secondary outcome of cardiovascular death/myocardial infarction (adjusted HR, 0.93 [95% CI, 0.76-1.14]; P=0.49), with no significant sex-by-treatment-group interactions. Women had less extensive coronary artery disease and, therefore, lower revascularization rates in the invasive group. Despite lower risk factor goal attainment, women with chronic coronary disease experienced similar risk-adjusted outcomes to men in the ISCHEMIA trial. URL: http://wwwclinicaltrials.gov. Unique identifier: NCT01471522.

A Practical Approach to the Management of Residual Cardiovascular Risk: United Arab Emirates Expert Consensus Panel on the Evidence for Icosapent Ethyl and Omega-3 Fatty Acids.

Patients with hyperlipidemia treated with statins remain at a residual cardiovascular (CV) risk. Omega-3 polyunsaturated fatty acids hold the potential to mitigate the residual CV risk in statin-treated patients, with persistently elevated triglyceride (TG) levels. We reviewed the current evidence on the use of icosapent ethyl (IPE), an omega-3 fatty acid yielding a pure form of eicosapentaenoic acid. REDUCE-IT reported a significant 25% reduction in CV events, including the need for coronary revascularization, the risk of fatal/nonfatal myocardial infarction, stroke, hospitalization for unstable angina, and CV death in patients on IPE, unseen with other omega-3 fatty acids treatments. IPE was effective in all patients regardless of baseline CV risk enhancers (TG levels, type-2 diabetes status, weight status, prior revascularization, or renal function). Adverse events (atrial fibrillation/flutter) related to IPE have occurred mostly in patients with prior atrial fibrillation. Yet, the net clinical benefit largely exceeded potential risks. The combination with other omega-3 polyunsaturated fatty acids, in particular DHA, eliminated the effect of EPA alone, as reported in the STRENGTH and OMEMI trials. Adding IPE to statin treatment seems to be cost-effective, especially in the context of secondary prevention of CVD, decreasing CV event frequency and subsequently the use of healthcare resources. Importantly, IPE has been endorsed by 20 international medical societies as a statin add-on treatment in patients with dyslipidemia and high CV risk. Robust medical evidence supports IPE as a pillar in the management of dyslipidemia.

Real-World Risk of Recurrent Cardiovascular Events in Atherosclerotic Cardiovascular Disease Patients with LDL-C Above Guideline-Recommended Threshold: A Retrospective Observational Study.

The 2021 Canadian Cardiovascular Society (CCS) guidelines recommend intensive low-density lipoprotein cholesterol (LDL-C) reduction for patients with atherosclerotic cardiovascular disease (ASCVD). For patients above LDL-C threshold on maximally tolerated statins, adding ezetimibe and/or a proprotein convertase subtilisin/kexin type9 inhibitor (PCSK9i) is recommended. This population-based, real-world study examined cardiovascular (CV) events in patients with ASCVD who are on statins and above current guideline threshold LDL-C levels. Using administrative health data in Alberta, Canada, we identified patients with myocardial infarction (MI), ischemic stroke (IS), or peripheral artery disease with LDL-C > 1.8mmol/L on statins between April 1, 2010 and March 31, 2016. Exploratory subgroups included very high-risk patients with ASCVD shown to derive the most benefit from PCSK9i intensification as identified by the CCS guidelines, including those with acute coronary syndrome (ACS) or recent MI. Frequencies and rates of individual and composite CV events (primary outcome: MI, IS, hospitalization for unstable angina, coronary revascularization, cardiovascular death; secondary outcome: MI, IS, CV death) were calculated over follow-up. The study included 32,984 patients with a mean (standard deviation) follow-up of 40.8 (21.0) months. Overall, 17.7% and 15.6% experienced a primary and secondary outcome, respectively, with rates of 5.58 and 4.83 per 100 patient-years, respectively. CV death and MI were the most common events. Subgroups with recurrent MI and comorbid diabetes exhibited higher CV event rates (23.6% and 22.2% had a primary outcome, respectively). Rates of CV events were notably high in patients with ACS or recent MI (49.4% and 54.0% had a primary outcome, respectively). This real-world study confirms that statin-treated high-risk patients with ASCVD and above-threshold LDL-C levels have substantial incidence of recurrent CV events. These findings reinforce the opportunity for lipid-lowering therapy intensification in high-risk patients to levels below guideline-recommended threshold in order to reduce CV risk.

Fully automated artificial intelligence-based coronary CT angiography image processing: efficiency, diagnostic capability, and risk stratification.

To prospectively investigate whether fully automated artificial intelligence (FAAI)-based coronary CT angiography (CCTA) image processing is non-inferior to semi-automated mode in efficiency, diagnostic ability, and risk stratification of coronary artery disease (CAD). Adults with indications for CCTA were prospectively and consecutively enrolled at two hospitals and randomly assigned to either FAAI-based or semi-automated image processing using equipment workstations. Outcome measures were workflow efficiency, diagnostic accuracy for obstructive CAD (≥ 50% stenosis), and cardiovascular events at 2-year follow-up. The endpoints included major adverse cardiovascular events, hospitalization for unstable angina, and recurrence of cardiac symptoms. The non-inferiority margin was 3 percentage difference in diagnostic accuracy and C-index. In total, 1801 subjects (62.7 ± 11.1 years) were included, of whom 893 and 908 were assigned to the FAAI-based and semi-automated modes, respectively. Image processing times were 121.0 ± 18.6 and 433.5 ± 68.4 s, respectively (p<0.001). Scan-to-report release times were 6.4 ± 2.7 and 10.5 ± 3.8 h, respectively (p< 0.001). Of all subjects, 152 and 159 in the FAAI-based and semi-automated modes, respectively, subsequently underwent invasive coronary angiography. The diagnostic accuracies for obstructive CAD were 94.7% (89.9-97.7%) and 94.3% (89.5-97.4%), respectively (difference 0.4%). Of all subjects, 779 and 784 in the FAAI-based and semi-automated modes were followed for 589 ± 182 days, respectively, and the C-statistic for cardiovascular events were 0.75 (0.67 to 0.83) and 0.74 (0.66 to 0.82) (difference 1%). FAAI-based CCTA image processing significantly improves workflow efficiency than semi-automated mode, and is non-inferior in diagnosing obstructive CAD and risk stratification for cardiovascular events. Conventional coronary CT angiography image processing is semi-automated. This observation shows that fully automated artificial intelligence-based image processing greatly improves efficiency, and maintains high diagnostic accuracy and the effectiveness in stratifying patients for cardiovascular events. • Coronary CT angiography (CCTA) relies heavily on high-quality and fast image processing. • Full-automation CCTA image processing is clinically non-inferior to the semi-automated mode. • Full automation can facilitate the application of CCTA in early detection of coronary artery disease.

Meta-analysis of risk of major adverse cardiovascular events in adults with type 2 diabetes treated with bexagliflozin.

To explore the risk of major adverse cardiovascular events (MACE) associated with exposure to bexagliflozin. The analysis included 4090 participants with type 2 diabetes (T2D) enrolled in nine phase 2 and 3 double-blind randomized controlled trials. All potential MACE were adjudicated by a blinded committee. The primary endpoint for the meta-analysis was the hazard ratio (HR) for the time to first occurrence of non-fatal stroke, non-fatal myocardial infarction (MI), cardiovascular (CV) death or hospitalization for unstable angina (MACE+), tested for non-inferiority to a ratio of 1.8. The secondary endpoints were time to first occurrence of (i) non-fatal stroke, non-fatal MI or CV death (MACE), tested for non-inferiority to a ratio of 1.3; and (ii) CV death or hospitalization for heart failure, tested for superiority. The HR for the primary endpoint of MACE+ was 0.80 (95% confidence interval [CI] 0.58, 1.09), which fulfilled the non-inferiority objective with a P value of less than 0.0001. Non-inferiority for the first key secondary endpoint of MACE was also shown (HR = 0.82; 95% CI 0.59, 1.13; P = 0.0023). Superiority for time to CV death or first hospitalization for heart failure was not shown. Bexagliflozin did not increase the risk of MACE in participants with T2D when compared with placebo or active control. Both the preapproval and postapproval thresholds for CV safety were met and bexagliflozin has been approved by the US Food and Drug Administration.

In-Hospital influenza vaccination to prevent cardiorespiratory events in the first 45 days after acute coronary syndrome: A prespecified analysis of the VIP-ACS trial

BackgroundInfluenza vaccination prevents major cardiovascular events in individuals presenting a recent acute coronary syndrome (ACS), however the early effect of an in-hospital double-dose vaccination strategy remains uncertain. MethodsThe VIP-ACS was a randomized, pragmatic, multicenter, open-label trial with a blinded-adjudication endpoint. Patients with ACS ≤ 7 days of hospitalization were randomized to an in-hospital double-dose quadrivalent inactivated influenza vaccine (double-dose) or a standard-dose influenza vaccine at 30 days post-randomization. The primary endpoint was a hierarchical composite of death, myocardial infarction, stroke, hospitalization for unstable angina, hospitalization for heart failure, urgent coronary revascularization, and hospitalization for respiratory infections, analyzed with the win ratio (WR) method in short-term follow-up (45-days after randomization). ResultsThe trial enrolled 1,801 patients (≥18 years old). Median participant age was 57 years, 70 % were male. There were no significant differences between groups on the primary hierarchical endpoint: there were 5.7 % wins in the double-dose in-hospital group and 5.5 % wins in the standard-dose delayed vaccination group (WR: 1.03; 95 % CI: 0.70–––1.53; P = 0.85). In a sensitivity analysis including COVID-19 infection in the hospitalizations for respiratory infections endpoint, overall results were maintained (WR: 1.03; 95 % CI 0.71–––1.51; P = 0.87). Results were consistent for major cardiovascular events only (WR: 0.82; 95 % CI: 0.48–––1.39; P = 0.46). No serious adverse events were observed. ConclusionIn patients with recent ACS, in-hospital double-dose influenza vaccination did not significantly reduce cardiorespiratory events at 45 days compared with standard-dose vaccination at 30 days post-randomization.

Prognostic implications of obstructive sleep apnea in patients with acute coronary syndrome stratified by homocysteine level: a prospective cohort study

BackgroundSporadic studies have examined the impact of OSA on ACS patients by homocysteine (Hcy) level. This study attempted to comprehensively evaluate the effects of the interaction between Hcy and OSA on long-term cardiovascular outcomes in ACS patients.MethodsIn this prospective, large-scale cohort study, 2160 patients admitted for ACS were recruited to undergo overnight sleep monitoring. OSA was diagnosed when apnea–hypopnea index ≥ 15 events/h. Patients with normohomocysteinemia (NHcy) were defined as having serum Hcy ≤ 15 μmol/L, and the others had hyperhomocysteinemia (HHcy). The primary endpoint was major adverse cerebrocardiovascular event (MACCE), a composite of cardiovascular death, myocardial infarction, stroke, ischemia-driven revascularization and hospitalization for unstable angina and heart failure.ResultsA total of 1553 eligible ACS patients (average age: 56.3 ± 10.5 years) were enrolled, among which 819 (52.7%) had OSA, and 988 (63.6%) were with NHcy. OSA did not significantly affect the level of Hcy. During a median follow-up of 2.9 (1.6, 3.5) years, after adjustment for clinical confounders, OSA was associated with increased risk for MACCE occurrence versus non-OSA ones in ACS patients with NHcy (adjusted hazard ratio [HR] = 1.36, 95% confidence interval [CI] 1.02–1.83, P = 0.039), but not in those with HHcy (adjusted HR = 0.92, 95%CI 0.62–1.36, P = 0.668). There was an absence of interaction between homocysteine level and OSA in relation to MACCE (interaction P = 0.106).ConclusionsOSA was independently associated with worse prognosis in ACS patients with NHcy. Our study emphasized the necessity to identify potential presence of OSA in such a population.Trial registration: ClinicalTrials.gov; Number: NCT03362385; URL: www.clinicaltrials.gov.

Lesion-specific pericoronary adipose tissue CT attenuation improves risk prediction of major adverse cardiovascular events in coronary artery disease.

To determine whether lesion-specific pericoronary adipose tissue CT attenuation (PCATa) is superior to PCATa around the proximal right coronary artery (PCATa-RCA) and left anterior descending artery (PCATa-LAD) for major adverse cardiovascular events (MACE) prediction in coronary artery disease (CAD). Six hundred and eight CAD patients who underwent coronary CTA from January 2014 to December 2018 were retrospectively included, with clinical risk factors, plaque features, lesion-specific PCATa, PCATa-RCA, and PCATa-LAD collected. MACE was defined as cardiovascular death, non-fatal myocardial infarction, unplanned revascularization, and hospitalization for unstable angina. Four models were established, encapsulating traditional factors (Model A), traditional factors and PCATa-RCA (Model B), traditional factors and PCATa-LAD (Model C), and traditional factors and lesion-specific PCATa (Model D). Prognostic performance was evaluated with C-statistic, area under receiver operator characteristic curve (AUC), and net reclassification index (NRI). Lesion-specific PCATa was an independent predictor for MACE (adjusted hazard ratio = 1.108, P < .001). The C-statistic increased from 0.750 for model A to 0.762 for model B (P = .078), 0.773 for model C (P = .046), and 0.791 for model D (P = .005). The AUC increased from 0.770 for model A to 0.793 for model B (P = .027), 0.793 for model C (P = .387), and 0.820 for model D (P = .019). Compared with model A, the NRIs for models B, C, and D were 0.243 (-0.323 to 0.792, P = .392), 0.428 (-0.012 to 0.835, P = .048), and 0.708 (0.152-1.016, P = .001), respectively. Lesion-specific PCATa improves risk prediction of MACE in CAD, which is better than PCATa-RCA and PCATa-LAD. Lesion-specific PCATa was superior to PCATa-RCA and PCATa-LAD for MACE prediction.

Safe Deferral of Coronary Computed Tomography Angiography for Patients With a Low Pretest Probability of Coronary Artery Disease in 2019 European Society of Cardiology Guidelines.

Coronary computed tomography angiography is increasingly used as the first-line test for suspected coronary artery disease. Its overuse in a low pretest probability (PTP) population may lead to low diagnostic yield without change in patient management. We evaluated the clinical consequences of the updated 2019 European Society of Cardiology (ESC) chronic coronary syndromes guidelines' PTP estimation and whether imaging could be safely deferred in patients with a low PTP. This retrospective cohort included all 1753 consecutive patients who underwent coronary computed tomography angiography for suspected coronary artery disease at Helsinki University Hospital between 2009 and 2017. PTP was calculated according to the 2013 and 2019 ESC guidelines. The overall mortality, cardiac deaths, myocardial infarctions, and hospitalizations for unstable angina were acquired from national registry data for 1 to 10 years of follow-up (median, 4 years). Updated 2019 ESC guidelines classified 72% of the patients as having low PTP, whose imaging could have been deferred. The revascularization rate (4.7%) and annual cardiac mortality (0.4%) were low in the 857 patients reclassified from the recommendation to test, according to the 2013 ESC guideline, to deferral of coronary computed tomography angiography, according to the new 2019 guideline. The updated 2019 ESC guideline PTP score aids clinicians in safely preventing the overuse of cardiac imaging in patients deemed at low PTP of coronary artery disease. Diagnostic yield, revascularization rate, and cardiac mortality are low in patients with low pretest risk.

Outcomes According to Coronary Revascularization Modality in the ISCHEMIA Trial

BackgroundIn the ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) trial, the risk of ischemic events was similar in patients with stable coronary artery disease treated with an invasive (INV) strategy of angiography and percutaneous coronary intervention (PCI) or surgical (coronary artery bypass grafting [CABG]) coronary revascularization and a conservative (CON) strategy of initial medical therapy. ObjectivesThe authors analyzed separately the outcomes of INV patients treated with PCI or CABG. MethodsPatients without preceding primary outcome events were categorized as INV-PCI or INV-CABG from the time of revascularization. The ISCHEMIA primary outcome (composite of cardiovascular death, protocol-defined myocardial infarction or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest) was used. ResultsAmong INV-CABG patients, primary outcome events occurred in 84 of 512 (16.4%) at a median follow-up of 2.85 years; 48 events (57.1%) occurred within 30 days after CABG, including 40 procedural MIs. Among INV-PCI patients, primary outcome events occurred in 147 of 1,500 (9.8%) at median follow-up of 2.94 years; 31 of which (21.1%) occurred within 30 days after PCI, including 24 procedural MIs. In comparison, 352 of 2,591 CON patients (13.6%) had primary outcome events at a median follow-up of 3.2 years, 22 of which (6.3%) occurred within 30 days of randomization. The adjusted primary outcome risks were higher after both CABG and PCI within 30 days (HR: 16.25 [95% CI: 11.44-23.07] and HR: 2.99 [95% CI: 1.97-4.53]) and lower thereafter (0.63 [95% CI: 0.44-0.89] and 0.66 [95% CI: 0.53-0.82]). ConclusionsIn ISCHEMIA, early revascularization by PCI and CABG was associated with higher early risks and lower long-term risks of cardiovascular events compared with CON. The early risk was greatest after CABG, owing to protocol-defined procedural MIs.

Longer-term impact of PCSK9 inhibitors on major adverse cardiovascular events and all-cause mortality: a systematic review and meta-analysis of randomised controlled trials

Abstract Background The development of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors offers a novel treatment option for lowering cardiovascular risk profiles through significant reductions in low-density lipoprotein cholesterol. Whilst their effect on improving patients' lipid profiles has been well-established in clinical trials, their impact on major adverse cardiovascular events (MACE) and all-cause mortality in the longer-term is of interest since PCSK9 inhibitors are becoming an important addition to the current armament of lipid-lowering therapies. Purpose This systematic review and meta-analysis seeks to evaluate the longer-term effect (≥ 12 months) of PCSK9 inhibitors on MACE and all-cause mortality, compared to placebo, in patients with dyslipidaemia or atherosclerotic cardiovascular disease. Methods A systematic search of databases including PubMed, Ovid, and Cochrane Central Register of Controlled Trials was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines in January 2023. Two reviewers screened for phase 3 randomised-controlled trials (RCTs) comparing the anti-PCSK9 monoclonal antibodies currently in use (alirocumab and evolocumab) to placebo in adult patients. Trials were included if they had a follow-up of at least 12 months from initiation of treatment and reported on MACE or all-cause mortality. Demographic data, clinical characteristics, MACE outcomes such as rates of myocardial infarction, coronary revascularisation, cardiovascular death, hospitalisation for heart failure, hospitalisation for unstable angina, stroke and all-cause mortality outcomes were extracted. A random effects model was used for meta-analysis with dichotomous outcomes reported as odds ratio (OR), 95% confidence intervals (CI) and I² metric to assess heterogeneity. Results The incidence of myocardial infarction and coronary revascularisation was reported in ten studies (encompassing 57,890 participants) out of the eleven RCTs that met our inclusion criteria. Meta-analysis demonstrated statistically significant reduction in myocardial infarction (OR -0.27, 95% CI -0.40 to -0.15, p &amp;lt;0.01, I² = 25.5%) and coronary revascularisation (OR -0.20, 95% CI -0.28 to -0.11, p &amp;lt;0.01, I² =12.4%) for patients on PCSK9 inhibitors compared to placebo. Heterogeneity was considered moderate and low respectively for these outcomes. No statistically significant effect was observed for other MACE or all-cause mortality. Conclusions The results of this study suggest that PCSK9 inhibitors can significantly reduce rates of myocardial infarction and coronary revascularisation in patients over the long-term (≥ 12 months). Further studies with longer-term follow-up are needed to fully evaluate the impact of PCSK9 inhibitors across MACE outcomes, and to inform clinical decision-making.Myocardial Infarction Forest PlotCoronary Revascularisation Forest Plot

Routine functional testing in high-risk patients after imaging- or physiology-guided percutaneous coronary intervention

Abstract Background Imaging-guided or physiology-guided percutaneous coronary intervention (PCI) improved clinical outcomes in complex coronary artery disease. However, it is not known to what extent routine functional testing after imaging or physiology-guided PCI affect clinical outcomes among high-risk patients. Objectives To assess clinical impact of routine functional test or standard care alone after intravascular ultrasound (IVUS) or fractional flow reserve(FFR) guided PCI. Methods Of the 1706 randomized patients with high-risk anatomical or clinical features enrolled in the POST-PCI (Pragmatic Trial Comparing Symptom-Oriented versus Routine Stress Testing in High-Risk Patients Undergoing Percutaneous Coronary Intervention) trial, 1269 patients underwent IVUS-guided PCI and 609 patients underwent FFR-guided PCI. The primary outcome was a composite of death from any cause, myocardial infarction, or hospitalization for unstable angina at 2 years. Results The rate of the 2-year primary outcomes was similar between strategies of routine functional-testing or standard-care in IVUS use group (5.3% vs. 6.6%, respectively; HR, 0.79; 95% CI, 0.50–1.24; P=0.30) and in IVUS non-use group (5.7% vs. 3.8%, respectively; HR,1.52; 95% CI, 0.63–3.68; P=0.21); there was no significant interaction between IVUS use and follow up strategies (p for interaction=0.21). The rate of the 2-year outcomes was not significantly different with functional-testing or standard-care in FFR use group (2.6% vs. 3.9%, respectively; HR, 0.65; 95% CI, 0.26–1.58, P=0.34) and in FFR non-use group (7.0% vs. 7.1%, respectively; HR, 0.99; 95% CI, 0.63–1.55, P=0.97) without significant interaction (p for interaction=0.59). Conclusions In patients with high-risk PCI, IVUS and FFR use did not affect clinical outcome of routine surveillance stress testing and standard-care alone during follow-up.TableFigure

Two of a kind: mass and molar immunoassay-based lipoprotein (a) concentrations are similarly prognostic for MACE risk and predictive of alirocumab benefit in ODYSSEY OUTCOMES

Abstract Background Lipoprotein (a) (Lp(a)) is a risk factor for incident and recurrent ischemic cardiovascular (CV) events and may modify the benefit of PCSK9 inhibitors (PCSK9i). While Lp(a) concentration can be measured in either mass or molar units, to date there has been no direct, large-scale comparison of the relationships of mass vs. molar Lp(a) with CV risk and response to treatment. Purpose Using samples from ODYSSEY OUTCOMES where 18,924 patients with recent acute coronary syndrome were randomized 1:1 to the PCSK9i alirocumab (ALI) or placebo (PBO), baseline mass vs. molar Lp(a) were compared in terms of prognosis for first major adverse CV event (MACE, consisting of coronary heart disease death, nonfatal myocardial infarction, ischemic stroke, or hospitalization for unstable angina) in the placebo group and associations with ALI risk reduction. Methods Lp(a) mass and molar tests were the Siemens N latex immunonephelometric test and the Roche TinaQuant immunoturbidimetric assay, respectively. Both tests use polyclonal anti-apo(a) antibodies but are designed to be relatively apo(a)-size independent within allowable measurement uncertainty. Absolute risk of MACE at 4 years in the PBO group and treatment risk ratios (RR) by continuous Lp(a) concentrations were estimated by natural cubic splines from Poisson regression models with log follow-up time as an offset and adjustment for baseline LDL-C. For comparative modeling purposes Lp(a) values were transformed into percentiles; due to ties at the lower limits of quantification, minimum percentiles were 8th and 6th for mass and molar, respectively. All analyses were intention-to-treat. Results Baseline mass and molar Lp(a) concentrations, available in 11943 patients, were correlated (r=0.94). ALI MACE reduction in evaluable patients (1324 events; RR [95% CI] = 0.83 [0.74, 0.92]) was similar to the total population (1955 events; RR [95% CI] = 0.85 [0.78, 0.93]). Relationships with risk of MACE in the PBO group were nearly identical for mass (spline p=0.0001) and molar (spline p=0.0002) concentrations (Figure 1). Of note, the confidence boundaries around the splines were nearly superimposable, indicating similar precision of the estimated Lp(a)-associated risk with both measurement techniques. Risk reductions with ALI were similarly related to mass (spline p&amp;lt;0.0001) and molar (spline p&amp;lt;0.0001) concentrations (Figure 2). Conclusion Baseline mass and molar Lp(a) concentrations were similarly prognostic for MACE risk in the PBO group after adjustment for LDL-C. Mass and molar Lp(a) also similarly modified the ALI treatment effect on MACE, with trends towards less treatment benefit at lower concentrations. These results suggest that, at the treatment group level, the prognostic and predictive value of immunoassay-based Lp(a) tests for ischemic CV events in patients with recent acute coronary syndrome is not meaningfully different for the mass or molar concentration essays that were evaluated.Figure 1Figure 2

Abstract 12542: Effectiveness of Icosapent Ethyl on First and Total Cardiovascular Events in the Metabolic Syndrome: REDUCE-IT MetSyn

Introduction: The Metabolic Syndrome (MetSyn) is associated with persistently high risk of cardiovascular (CV) events despite statin treatment. Methods: REDUCE-IT was a multinational, double-blind trial that randomized 8179 high CV risk statin-treated patients with controlled low density lipoprotein cholesterol, and elevated triglycerides, to icosapent ethyl (IPE) 4 grams/day or placebo. In the overall trial, IPE reduced the risk of the primary composite endpoint (CV death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization or hospitalization for unstable angina) and the key secondary composite endpoint (CV death, nonfatal myocardial infarction or nonfatal stroke). Here we examine the prespecified patient subgroup with a history of MetSyn, but without diabetes at baseline. Results: Compared with placebo, IPE use in patients with MetSyn at baseline (n=2866) was associated with a 29% relative risk reduction for the primary composite endpoint (hazard ratio [HR], 0.71 [95% CI, 0.59-0.84]; P &lt;0.0001, absolute risk reduction [ARR]=5.9%; number needed to treat [NNT]=17) and 41% reduction in total (first plus subsequent) events (rate ratio [RR], 0.59 [95% CI, 0.48-0.72]; P &lt;0.0001) (Figure 1). The risk for the key secondary composite endpoint was reduced by 20% (P=0.05) with a 27% reduction in fatal/nonfatal MI (P=0.03), 47% reduction in urgent/emergent revascularization (P &lt;0.0001) and 58% reduction in hospitalization for unstable angina (P &lt;0.0001). Non-statistically significant reductions were observed in fatal/nonfatal stroke (27%), cardiac arrest (44%) and sudden cardiac death (34%). Conclusions: In statin-treated patients, the addition of IPE significantly reduced the risk of first and total CV events in REDUCE-IT patients with a history of MetSyn. The large relative and absolute risk reductions observed support IPE as a therapeutic consideration for high CV risk patients with MetSyn.

Abstract 12409: Ambient Fine Particulate Matter and Ozone Air Pollution Are Differentially Associated With Hospitalization for Unstable Angina and Acute Myocardial Infarction During Wildfire and Inversion Seasons

Background: Short-term increases (days to weeks) in fine particulate matter (PM 2.5 ) air pollution are associated with hospitalization for acute coronary syndromes (ACS). A changing climate is shifting sources of PM 2.5 toward summer wildfires in the western US. This study evaluated if short-term increases in PM 2.5 and ozone were associated with ACS risks in wildfire (June-October) and winter inversion (Nov.-March) seasons. Methods: Case-crossover analyses examined N=21,414 subjects with emergency or inpatient hospitalization at 11 Intermountain hospitals for ACS, including the primary diagnosis of myocardial infarction (AMI, n=20,287) or unstable angina (USA, n=1,127). PM 2.5 data were collected in January 1, 1999 to March 31, 2022 (ozone: 2006-2022) from community monitors on Utah’s Wasatch Front. Odds ratios (OR) and 95% confidence intervals (CI) were computed by Poisson regression with adjustment for weather data. Results: Subjects averaged 66±14 years of age and 31.0% were female. Overall PM 2.5 increases were associated with concurrent day (lag 0 days) ACS hospitalizations (OR=1.024 per +10 μg/m 3 , CI: 1.004, 1.043, p=0.019), driven by AMI (OR=1.025 per +10 μg/m 3 , CI: 1.004, 1.045, p=0.017). USA admissions were delayed to the second week [lag moving average (mAvg) days 7-13] after PM 2.5 increases (OR=1.090 per +10 μg/m 3 , CI: 1.024, 1.159, p=0.007) and PM 2.5 associations with USA were strengthened by adjustment for ozone. Analyzed by wildfire and inversion seasons, PM 2.5 associations differed for AMI and USA (Figure). Short-term increases in ozone in wildfire season were associated with lower USA risk at lag 1, lag 2, 3-day mAvg 0-2, and 1-week mAvg 0-6 and lower AMI risk at mAvg 7-13, but not with inversion season risks. Conclusions: Short-term increases in PM 2.5 air pollution were associated with ACS hospitalizations for AMI and USA, with patterns of risk differing between wildfire and inversion seasons. Ozone increases were not associated with greater risk.

Abstract 13043: LDL-C, Lp(a) and Hs-CRP Each Predict Future Cardiovascular Events After ACS on High-Intensity Statin Therapy. An Analysis of the ODYSSEY OUTCOMES Trial

Background: Atherosclerotic cardiovascular disease (ASCVD) risk has been jointly associated with levels of LDL cholesterol (LDL-C), lipoprotein [Lp](a)] and the inflammatory marker high-sensitivity C reactive protein (hsCRP). It is unclear whether and to what extent each of these biomarkers predict ASCVD risk after acute coronary syndrome (ACS), particularly in the era of intensive LDL-C lowering. Recent analysis of 3 trials in stable ASCVD patients with hypertriglyceridemia suggested that hsCRP may be a stronger predictor for recurrent events than LDL-C; however, only 52% received high-intensity statin. Methods: The ODYSSEY OUTCOMES trial enrolled post-ACS patients not at goal for atherogenic lipoproteins a median of 2.6 months after ACS and on treatment with maximum tolerated (89% high-intensity) atorvastatin or rosuvastatin. Absolute risk of major adverse cardiovascular events (MACE, the primary composite outcome of coronary heart disease death, nonfatal myocardial infarction, fatal/nonfatal ischemic stroke or unstable angina hospitalization) and all-cause death were analyzed as a function of baseline LDL-C, hs-CRP, and Lp(a) values in patients randomized to the placebo arm via natural cubic splines from Poisson regression models, adjusted for age, sex, diabetes, BMI, current smoking, and the other 2 predictor variables. Results: Among 9149 evaluable patients, median (Q1-Q3) LDL-C, hsCRP, and Lp(a) were 81 (71-97) mg/dL, 1.7 (0.8-3.9) mg/L, and 21.4 (6.6-60.1) mg/dL, respectively. For each parameter, a higher baseline value was associated with a substantial increase in risk of MACE ( Figure , all spline p&lt;0.0001). LDL-C and hsCRP were associated with all-cause death (p&lt;0.0001), but not Lp(a) (p&gt;0.05). Conclusion: In ACS patients receiving intensive statin therapy and not at goal for atherogenic lipoproteins, LDL-C, hs-CRP, and Lp(a) were independent predictors of MACE. LDL-C and hsCRP were independent predictors of all-cause death.

Abstract 13567: Comparison of Change in Lipoprotein(a) Mass and Molar Concentrations by Alirocumab and Risk of Subsequent Cardiovascular Events in ODYSSEY OUTCOMES

Background: Baseline (BL) lipoprotein(a) (Lp(a)) concentration is similarly related to cardiovascular (CV) risk when measured in either mass or molar units by immunoassay (IA). Because of Lp(a) isoform variation in mass, differences may exist between Lp(a) measurement methods in terms of relating change to risk reduction. We determined whether the reduction in major adverse cardiovascular events (MACE) by PCSK9 inhibitor alirocumab (ALI) had a similar relationship to the reduction in Lp(a) concentration as measured by 3 different methods. Methods: Lp(a) was measured by IA-mass (Siemens), IA-molar (Roche), and mass spectrometry (MS)-molar assays at BL and month 4 (M4) in a subgroup of patients in the ODYSSEY OUTCOMES trial which compared PCSK9 inhibitor ALI with placebo in patients with recent acute coronary syndrome. Changes in Lp(a) from BL to M4 were related to subsequent risk of MACE (coronary heart disease (CHD) death, nonfatal myocardial infarction (NFMI), fatal + nonfatal ischemic stroke, or unstable angina hospitalization) in the ALI group. Proportional hazards models were adjusted for BL Lp(a), BL LDL-C and its change from BL to M4, and other patient characteristics. Hazard ratios (HR) were calculated for the median change of each Lp(a) assay. All analyses were by intention-to-treat. Results: Among 5500 patients randomized to ALI with available data from all 3 Lp(a) assays, 443 experienced a subsequent MACE. Changes in Lp(a) IA-mass and MS-molar concentration were significantly related to reduced MACE risk, while change in IA-molar concentration was marginally significant; associations were more evident with CHD death + NFMI ( Figure ). MACE HRs for median change were similar across tests. Conclusion: With caveats of a modest number of MACE for analysis, moderately elevated Lp(a) levels, and intra-patient variability in serial values, 3 Lp(a) assay methods appeared similarly predictive of ALI MACE reduction.