Risk Of Nonfatal Myocardial Infarction Research Articles

Update on the Efficacy and Safety of Sodium–Glucose Co-Transporter 2 Inhibitors in Patients with Chronic Diseases: A Systematic Review and Meta-Analysis

Background: Sodium–glucose co-transporter-2 (SGLT2) inhibitors have emerged as vital medications for the management of type 2 diabetes mellitus (T2DM). Numerous studies have highlighted the cardioprotective and renal protective benefits of SGLT2 inhibitors. Consequently, it is essential to assess their efficacy and safety in patients with chronic diseases. Method: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) evaluating the effects of SGLT2 inhibitors on major cardiovascular and safety outcomes in patients with T2DM, heart failure (HF), and chronic kidney disease (CKD). We searched the PubMed, Cochrane, and Embase databases for trials published between 30 September 2021 and 17 May 2023. The primary outcomes of interest included nonfatal myocardial infarction (MI), hospitalization for heart failure (HHF), cardiovascular death, and nonfatal stroke. The safety outcomes assessed were hypoglycemia, urinary tract infections (UTIs), and acute kidney injury (AKI). Result: We identified 13 RCTs involving 90,413 participants. In patients with T2DM, SGLT2 inhibitors significantly reduced the risk of nonfatal MI by 12% (hazard ratio [HR] = 0.88, 95% confidence interval [CI]: 0.78–0.98), HHF by 33% (HR = 0.67, 95% CI: 0.62–0.74), and cardiac death by 15% (HR = 0.95, 95% CI: 0.80–1.13). However, they did not significantly reduce the risk of nonfatal stroke (HR = 0.85, 95% CI: 0.75–0.95). In patients with HF, SGLT2 inhibitors reduced the risk of HHF by 28% (HR = 0.72, 95% CI: 0.66–0.77) and cardiac death by 12% (HR = 0.88, 95% CI: 0.80–0.96). For patients with CKD, SGLT2 inhibitors reduced the risk of HHF by 35% (HR = 0.65, 95% CI: 0.55–0.76) and cardiac death by 16% (HR = 0.84, 95% CI: 0.73–0.96). Regarding safety outcomes, SGLT2 inhibitors did not significantly increase the risk of hypoglycemia in patients with T2DM, HF, or CKD, nor did they increase the risk of urinary tract infections (UTIs) in patients with HF or CKD, or the risk of acute kidney injury (AKI) in patients with HF. However, they did increase the risk of UTIs by 8% (risk ratio [RR] = 1.08, 95% CI: 1.01–1.16) in patients with T2DM and reduced the risk of AKI by 22% (RR = 0.78, 95% CI: 0.67–0.89) and 19% (RR = 0.81, 95% CI: 0.69–0.97) in patients with T2DM and CKD, respectively. Conclusions: SGLT2 inhibitors have demonstrated a significant improvement in cardiovascular outcomes for patients with T2DM, HF, and CKD while also maintaining a favorable safety profile. These findings advocate for the broader application of SGLT2 inhibitors in the management of chronic diseases, particularly in reducing the incidence of nonfatal MI, HHF, and cardiac death. Further research is essential to optimize their use across diverse patient populations and stages of disease.

Effect of PCSK9 inhibitors on major cardiac adverse events and lipoprotein-a in patients with coronary heart disease: a meta-analysis.

Lipoprotein(a) [Lp(a)] is an independent risk factor for cardiovascular disease due to its unique apo(a) component and its association with atherosclerosis and thrombogenesis. This meta-analysis was conducted to evaluate the effects of PCSK9 inhibitors on major adverse cardiac events (MACE) and Lp(a) levels in patients with coronary heart disease. Randomized controlled trials (RCTs) were systematically searched in PubMed, the Cochrane Library, and other databases. Stata 15.1 software was used for data analysis, and a random- or fixed-effects model was selected based on inter-study heterogeneity. Egger's test was applied to detect publication bias. A total of 12 RCTs were included, involving 48 116 patients with a mean age of 62 years, comprising 65% males and diverse ethnic backgrounds. The results showed that compared with the control group, PCSK9 inhibitors significantly reduced low-density lipoprotein cholesterol (WMD = -1.24 mmol/L, 95% confidence interval (CI): -1.28 to -1.20), total cholesterol, triglycerides, and Lp(a) levels while increasing high-density lipoprotein cholesterol levels. In terms of safety, there was no increased risk of adverse reactions other than injection site reactions. For MACE, PCSK9 inhibitors significantly reduced the risk of nonfatal myocardial infarction, stroke, and coronary revascularization events (RR = 0.87, 95% CI: 0.84-0.89). PCSK9 inhibitors not only significantly improve blood lipid profiles and reduce Lp(a) levels but also reduce the risk of MACE in patients with coronary heart disease. Therefore, PCSK9 inhibitors offer an effective and safe treatment option for these patients.

Safety of Triptans in Patients Who Have or Are at High Risk for Cardiovascular Disease: A Target Trial Emulation

ObjectiveTo evaluate the safety of triptans in migraine patients with cardiovascular disease or elevated cardiovascular risk. Patients and MethodsWe retrieved data from a multistate US-based health system (January 2000 to August 2022) on adults with migraine and confirmed cardiovascular/cerebrovascular disease, or at least two cardiovascular risk factors. We compared the effect of triptans to nontriptan treatments on major adverse cardiovascular events (MACE) and its components at 60 days of starting treatments. We emulated a target trial and used propensity score matching for analysis. ResultsThe 3518 patients in the triptan group were matched to the 3518 patients in the nontriptan group (median age, 55 years; 80.60% female). At 60 days, 52 patients (1.48%) in the triptan group had MACE, compared with 13 patients (0.37%) in the nontriptan group (relative risk [RR], 4.00; 95% CI, 2.24 to 7.14). Patients treated with triptans also had significantly higher risk of nonfatal myocardial infarction (15 patients (0.43%) vs 0 patients (0.00%)); heart failure (RR, 4.50; 95% CI, 1.91 to 10.61); and nonfatal stroke (RR, 8.00; 95% CI, 1.00 to 63.96). Five patients (0.14%) in each group died. The findings were consistent when analyses were restricted to sumatriptan, oral administration of triptan, patients with chronic migraine, history of cardiovascular disease, or history of cerebrovascular disease. ConclusionTriptans likely increase the risk of MACE; however, the incidence of MACE remains low in migraine patients with cardiovascular disease or elevated cardiovascular risk. Trial RegistrationTreatments of Migraine With Triptans in Individuals With Elevated Cardiovascular Risk and in Pregnant Women. ClinicalTrials.gov Identifier: NCT05854992 (https://classic.clinicaltrials.gov/ct2/show/NCT05854992)

Myocardial Bridging Increases the Risk of Adverse Cardiovascular Events in Patients without Coronary Atherosclerosis.

Background: Myocardial bridging (MB) is a congenital coronary anomaly and an important cause of chest pain. The long-term effects of MB on cardiovascular events remain elusive. Methods: We used the National Health Insurance Research Database of Taiwan to conduct an analysis. All patients who had undergone coronary angiography were considered for inclusion. The primary endpoint was a composite of nonfatal myocardial infarction, nonfatal ischemic stroke, and cardiovascular death. Results: We identified 10,749 patients from 2008 to 2018 and matched them with an equal number of controls by propensity-score matching. The mean follow-up period was 5.78 years. In patients without coronary artery disease, MB increased the risk of the composite endpoint (hazard ratio [HR]: 1.57, 95% confidence interval [CI]: 1.44-1.72, p < 0.001), which was driven by increased risks of nonfatal myocardial infarction and cardiovascular death. In patients with significant coronary artery disease, MB did not increase the risk of major adverse cardiovascular events. MB was identical to insignificant coronary artery disease from the viewpoint of clinical outcomes. Conclusions: The presence of MB significantly increases cardiovascular risks in patients with normal coronary vessels. Atherosclerotic coronary artery disease mitigates the effect of MB on cardiovascular outcomes. MB can be considered an insignificant coronary artery disease equivalent.

Glycaemic control and macrovascular and microvascular outcomes: A systematic review and meta-analysis of trials investigating intensive glucose-lowering strategies in people with type 2 diabetes.

We aimed to determine the macrovascular and microvascular outcomes of intensive versus standard glucose-lowering strategies in type 2 diabetes (T2D) and investigate the relationships between these outcomes and trial arm glycated haemoglobin (HbA1c) reduction. In this systematic review and meta-analysis, we identified relevant trials from MEDLINE, Embase, the Cochrane Library, and bibliographies up to August 2023. Macrovascular and microvascular outcomes, along with safety outcomes, were evaluated. Pooled study-specific hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated, and meta-regression was employed to analyse the relationships between outcomes and HbA1c reduction. We included 11 unique RCTs involving 51 469 patients with T2D (intensive therapy, N = 26 691; standard therapy, N = 24 778). Intensive versus standard therapy reduced the risk of non-fatal myocardial infarction (MI) (HR 0.84; 95% CI 0.75-0.94) with no difference in the risk of major adverse cardiovascular events (HR 0.97; 95% CI 0.92-1.03) and other adverse cardiovascular outcomes. Intensive versus standard therapy reduced the risk of retinopathy (HR 0.85; 0.78-0.93), nephropathy (HR 0.71; 0.58-0.87) and composite microvascular outcomes (HR 0.88; 0.77-1.00). Meta-regression analyses showed modest evidence of inverse linear relationships between HbA1c reduction and the outcomes of major adverse cardiovascular events, non-fatal MI, stroke and retinopathy, but these were not statistically significant. In people with T2D, intensive glucose control was associated with a reduced risk of non-fatal MI and several microvascular outcomes, particularly retinopathy and nephropathy. The lack of an effect of intensive glucose-lowering on most macrovascular outcomes calls for a more comprehensive approach to managing cardiovascular risk factors alongside glycaemic control.

Liver fibrosis is associated with an increased risk of non-fatal myocardial infarction.

Liver fibrosis is a risk factor for liver-related adverse outcomes and cardiovascular disease (CVD). Recently, the non-invasive Hepamet fibrosis score (HFS) has been validated as a tool capable to identify with good diagnostic accuracy subjects with advanced liver fibrosis. It is unsettled whether HFS is capable to identify individuals at higher risk of CVD. To investigate whether individuals with liver fibrosis measured with HFS have higher risk of myocardial infarction (MI) in adults participating in the CATAnzaro MEtabolic RIsk factors (CATAMERI) study. Participants (n = 2948) were divided into three groups according to HFS: low risk of fibrosis (<0.12); intermediate risk of fibrosis (≥0.12 to <0.47); high risk of fibrosis (≥0.47). The association between the liver fibrosis risk and MI was analysed by a logistic regression analysis. As compared with those having the lowest risk (5.3%), a higher proportion of subjects with moderate or high risk of liver fibrosis had MI (12.9% and 24.4%, respectively; p < 0.001). In a logistic regression analysis, individuals at increased risk of liver fibrosis exhibited a threefold increased risk of having MI as compared to those with low risk (OR 3.18; 95% CI 1.31-7.70) independently of confounders including smoking, cholesterol, triglycerides, anti-hypertensive, lipid-lowering and glucose-lowering therapies. In this cross-sectional study, individuals with higher values of HFS show a higher risk of MI, suggesting that HFS may be a useful tool to identify not only individuals with liver fibrosis but also those at the increased risk of CVD.

1234-P: Derivation of a Claims-Computable Major Adverse Cardiovascular Event Estimator (ACME) in Adults with Type 2 Diabetes

Major adverse cardiovascular events (MACE) are a major cause of morbidity and mortality among adults with type 2 diabetes. Currently available risk prediction models estimate long-term risk (typically 10-year) and require clinical data not routinely available in real-world data sources, which limit their use on population level. Using de-identified claims data from OptumLabs® Data Warehouse for enrollees in private and Medicare Advantage health plans linked to 100% sample of Medicare fee-for-service beneficiaries between 2014 and 2021, we derived ACME to estimate annualized risk of non-fatal myocardial infarction, non-fatal stroke, or all-cause mortality in patients with type 2 diabetes aged ≥21 years (N=6,623,526). The Cox proportional hazards model, combined with an estimate of the baseline hazard using the Nelson-Aalen estimator to allow conditional survival predictions, included 28 covariates available in claims (age, sex, cardiovascular comorbidities, and cardiovascular medications). The study population had mean age 68.1 (SD, 10.6) years, 49.8% were women, and 73.0% were non-Hispanic White. ACME’s concordance index was 0.74 (se = 0.0002) and it performed comparably in all racial and ethnic groups. Strongest predictors of MACE were acute myocardial infarction and stroke within the past 3 months, heart failure hospitalization within the past year, and end-stage kidney disease. Overall, 4.2% of patients were predicted to have low (&amp;lt;1%) annualized MACE risk, 62.8% were predicted to have moderate (≥1 to &amp;lt;5%) annualized risk, and 33.0% were predicted to have high (≥5%) annualized risk. Other thresholds can be chosen for individualized applications. ACME can support population risk stratification and health management efforts at the health system and payer levels, participant identification for decentralized pragmatic clinical trials of cardiovascular disease and its prevention, and risk-stratified observational studies using real-world data. Disclosure R.G.Mccoy: Consultant; Emmi. G.Umpierrez: Research Support; Abbott, Dexcom, Inc., Baxter. R.J.Galindo: Consultant; Novo Nordisk, Eli Lilly and Company, Sanofi, Pfizer Inc., Bayer Inc., WW (Weight Watchers), Research Support; Novo Nordisk, Eli Lilly and Company, Dexcom, Inc. J.Brito: None. M.Mickelson: None. E.Polley: None. K.Swarna: None. Y.Deng: None. J.Herrin: Consultant; Johnson &amp; Johnson Medical Devices Companies. J.Ross: Research Support; Johnson &amp; Johnson. D.M.Kent: Research Support; W.L. Gore. B.Borah: Consultant; Boehringer Ingelheim Inc., Exact Sciences. W.Crown: Consultant; Janssen Scientific Affairs, LLC, UnitedHealth Group, Viatris Inc. V.M.Montori: None. Funding Patient-Centered Outcomes Research Institute (DB-2020C2-20306)

Increased risk of adverse events in patients with low-on clopidogrel platelet reactivity after percutaneous coronary intervention: A systematic review and meta-analysis.

Clinical evidence has been controversial regarding the influence of low platelet reactivity (LPR), ischemic and bleeding outcomes among patients receiving coronary stent implantation. Hence, the present study performed a meta-analysis to systematically evaluate the significance of LPR on adverse cardiovascular events. MEDLINE, EMBASE and CENTRAL databases were searched up to November 2020 for relevant studies including patients with acute coronary syndrome undergoing percutaneous coronary intervention. LPR was the exposed arm while the non-LPR group represented the control. The primary outcome of interest was bleeding risk including major and minor bleeding events. Secondary outcomes included all-cause mortality, repeated revascularization, nonfatal myocardial infarction, and stent thrombosis. Study-level outcomes were evaluated in random-effect models. A total of 20 studies with 19,064 patients were included. Pooled analysis showed that LPR was associated with an increased bleeding risk (relative risk [RR] 2.80, 95% confidence interval [CI] 1.95-4.02, p < 0.01). Patients with LPR had a lower risk of non-fatal myocardial infarction (RR 0.59, 95% CI 0.38-0.91, p < 0.05) and of serious vascular events (RR 0.50, 95% CI 0.30-0.84, p < 0.01). Low platelet reactivity is associated with an increased bleeding risk of patients who underwent coronary stent implantation. The results suggest possible benefits of this marker in risk stratification, with potential improvement in risk prediction. There are potential advantages using combinations with other factors in prediction models, however, they require further study. PROSPERO registration number: CRD42019136393).

Elevated low-density lipoprotein cholesterol: An inverse marker of morbidity and mortality in patients with myocardial infarction.

The incidence of atherosclerotic cardiovascular disease increases with levels of low-density lipoprotein cholesterol (LDL-C). Yet, a paradox may exist where lower LDL-C levels at myocardial infarction (MI) are associated with poorer prognoses. To assess the association between LDL-C levels at MI with risk factor burden and cause-specific outcomes. Statin-naive patients hospitalized for a first MI and registered in SWEDEHEART were included. Data were linked to Swedish registers. Primary outcomes were all-cause mortality and nonfatal MI. Associations between LDL-C and outcomes were assessed using adjusted proportional hazards models. Among 63,168 patients (median age, 66 years), the median LDL-C level was 3.0mmol/L (interquartile range 2.4-3.6). Patient age and comorbidities increased as LDL-C decreased. During a median follow-up of 4.5 years, 10,236 patients died, and 4973 had nonfatal MI. Patients with the highest LDL-C had a lower risk of mortality (hazard ratio [HR] 0.75; 95% confidence interval [CI] 0.71-0.80). The risk of hospitalization for pneumonia, hip fracture, chronic obstructive pulmonary disease, and new cancer diagnosis was lower with higher LDL-C (HR range, 0.40-0.81). Patients with the highest LDL-C had a greater risk of recurrent MI (HR 1.16; 95% CI 1.07-1.26). Patients with the highest LDL-C levels at MI had the lowest incidence of mortality and morbidity. This seems to reflect lower age at MI, less underlying morbidities, paired with the modifiability of LDL-C. However, supporting the causal association between LDL-C and ischemic heart disease, elevated LDL-C was simultaneously associated with an increased risk of nonfatal MI.

Cardiovascular outcomes of β-blocker-calcium channel blocker initial dual therapy vs. other initial dual therapies in Chinese patients with hypertension: A real-world retrospective study.

This retrospective study compared cardiovascular (CV) outcomes between initial β-blocker (BB)+calcium channel blocker (CCB) dual therapy ("B+C") and other initial dual therapies in Chinese newly diagnosed hypertensive patients. In this study, all patients in a regional electronic database with newly diagnosed hypertension from January 01, 2012 to December 31, 2016 who received any initial optimal dual therapy recommended by the Chinese hypertension guideline were included. 1:2 propensity score matching (PSM) was used to balance baseline characteristics between patients receiving B+C and patients receiving other initial dual therapies ("Others"). The primary outcome was major adverse cardiovascular events (MACE) that occurred from January 01, 2012 to December 31, 2017, consisting of non-fatal stroke, non-fatal myocardial infarction (MI), non-fatal chronic heart failure (CHF), and all-cause death. Cox proportional hazard models were used to compare these CV outcomes in the 2 matched cohorts. After the PSM, 6227 patients receiving B+C and 12454 patients receiving Others were included. Compared to patients receiving Others, patients receiving B+C had a significantly lower risk of MACE (hazard ratio [HR] 0.85; 95% confidential interval [CI] 0.78-0.92; p<.001), non-fatal stroke (HR 0.89; 95% CI 0.81-0.98; p=.018) and non-fatal CHF (HR 0.74; 95% CI 0.63-0.86; p<.0001). Additionally, differences in risks of non-fatal MI and all-cause death between the 2 treatment cohorts were not statistically significant. In conclusion, BB+CCB initial dual therapy was associated with a lower risk of MACE, stroke, and CHF than other optimal initial dual therapies recommended by the Chinese hypertension guideline in Chinese newly diagnosed hypertensive patients.

Prognostic value of coronary CT angiography in heart failure patients with preserved ejection fraction.

To investigate the prognostic value of coronary CT angiography (CCTA) in heart failure patients with preserved ejection fraction (HFpEF). Between January 2009 and December 2013, 6497 participants (mean age 63 ± 9.4 [range 32-86] years; 4111 men) who underwent CCTA and echocardiography were prospectively included. Participants were divided into HFpEF group and without HFpEF group. The primary endpoint was major adverse cardiovascular events (MACEs), including cardiovascular mortality, nonfatal myocardial infarction (MI), or hospitalization for heart failure (HF). Among those participants, 3096 were identified with HFpEF and 3401 were without HFpEF. Higher prevalence of coronary atherosclerosis was observed in HFpEF group than those without (78.3% vs. 64.9%, p < 0.001). During a median of 11.0 [IQR: 9.0-12.0] years follow-up, participants with HFpEF exhibit a heightened risk of MACEs in CAD-RADS = 0, 1-2, and ≥ 3 respectively (p < 0.001 for all). In the risk-adjusted hazard analysis among participants with HFpEF, CAD-RADS = 1-2 increased a 2.5-time risk for non-fatal MI (adjusted HR: 2.5, 95% CI: 1.5 to 4.3, p < 0.001), while CAD-RADS ≥ 3 conferred 3.9-fold and 3.1-fold higher risk for cardiovascular mortality (adjusted HR: 3.9, 95% CI: 2.2 to 7.1, p < 0.001) and hospitalization due to HF (adjusted HR: 3.1, 95% CI: 1.9 to 5.3, p < 0.001) with reference to CAD-RADS = 0 respectively. Coronary artery disease is common in participants with HFpEF and associated with MACEs. Among those participants, the presence of CAD-RADS = 1-2 increased the risk of nonfatal MI, while CAD-RADS ≥ 3 were correlated with cardiovascular mortality and hospitalization due to HF. • Higher median of CACS and higher CAD-RADS categories were observed in the HFpEF group than those without (p < 0.001 for both). • Participants with HFpEF exhibit a heightened risk of MACEs in CAD-RADS = 0, 1-2, and ≥ 3 respectively (p < 0.001 for all). • In the risk-adjusted hazard analysis among participants with HFpEF, CAD-RADS =1-2 increased a 2.5-time risk for non-fatal MI (adjusted HR: 2.5, 95% CI: 1.5 to 4.3, p < 0.001) with reference to CAD-RADS = 0 respectively.

Abstract 11634: Fatty Acid Length Dictates Association of Sphingomyelins With Sudden Cardiac Death

Background: Sudden cardiac death (SCD) is a leading cause of mortality worldwide and is precipitated primarily by ventricular tachyarrhythmias related to coronary artery disease. Sphingolipids, composed of ceramides and sphingomyelins, may influence the pathophysiology and risk of SCD through multiple biological activities. Whether the length of the fatty acid conjugated to the sphingolipid species is associated with SCD risk is not known. Methods and Results: Among 4612 Cardiovascular Health Study participants, we identified 215 patients who experienced SCD over a median follow up of 10.2 years. We examined 8 sphingolipids: ceramide and sphingomyelin species containing palmitic acid and species containing, respectively, the very-long-chain saturated fatty acids (VLSFA) arachidic, behenic, and lignoceric acids. In adjusted Cox regression analyses, ceramides and sphingomyelins with palmitic acid were associated with increased SCD risk per standard deviation log difference (ceramide with palmitic acid: hazard ratio 1.34, 95% CI 1.12-1.59; sphingomyelin with palmitic acid: hazard ratio 1.37, 95% CI 1.12-1.67). In contrast, one sphingomyelin with a VLSFA trended towards an association with reduced SCD risk (sphingomyelin with arachidic acid: hazard ratio 0.83, 95% CI 0.71-0.98). Associations were weakened when adjusted for C-reactive protein (CRP), B-type natriuretic peptide, and troponin-T, but did not differ significantly by age, sex, race, body-mass index, or history of coronary heart disease. In comparison, ceramide with palmitic acid was associated with higher risk of nonfatal myocardial infarction, and ceramide with the VLSFA lignoceric acid trended towards lower risk. Conclusions: Our results suggest associations between sphingolipid species and SCD, differing by the length of the acylated saturated fatty acid. Palmitic acid-containing sphingolipids were strongly associated with increased SCD risk, whereas VLSFA-containing sphingomyelins trended toward reduced SCD risk. The study indicates that plasma sphingolipids may influence the risk of SCD, independent of traditional cardiovascular risk factors. Our findings may provide further insight into the pathogenesis of SCD and enhance risk stratification tools.

Triggering of myocardial infarction by heat exposure is modified by medication intake.

Acute myocardial infarction (MI) can be triggered by heat exposure, but it remains unknown whether patients taking certain cardiovascular medications have elevated vulnerability. Based on a validated and complete registration of all 2,494 MI cases in Augsburg, Germany, during warm seasons (May to September) from 2001 to 2014, here we show that heat-related non-fatal MI risk was elevated among users of anti-platelet medication and beta-receptor blockers, respectively, but not among non-users, with significant differences between users and non-users. We also found that these effect modifications were stronger among younger patients (25-59 years), who had a lower prevalence of pre-existing coronary heart disease (CHD, a potential confounder by indication), than among older patients (60-74 years), who had a higher prevalence of pre-existing CHD. Users of these medications may be more vulnerable than non-users to non-fatal MI risk due to heat exposure. Further research is needed to disentangle effect modification by medication use from effect modification by pre-existing CHD.

Clopidogrel Monotherapy versus Aspirin Monotherapy in Patients with Established Cardiovascular Disease: Systematic Review and Meta-Analysis.

There is no clear consensus on whether aspirin offers better outcomes in terms of secondary cardiovascular disease prevention compared with clopidogrel. The aim of the study was to compare the safety and efficacy of clopidogrel versus aspirin in patients with established cardiovascular disease. A systematic review of MEDLINE (via PubMed), Scopus, and Cochrane Library databases (last search date: August 28, 2021) was performed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) statement for randomized control trials (RCTs) of clopidogrel versus aspirin as monotherapy in patients with established cardiovascular disease. Random-effects meta-analyses were performed. Five RCTs incorporating 26,855 patients (clopidogrel: 13,426; aspirin: 13,429) were included. No statistically significant difference was observed between clopidogrel and aspirin in terms of all-cause mortality (odds ratio [OR]: 1.01 [95% confidence interval, CI: 0.91-1.13]; p = 0.83), ischemic stroke (OR: 0.87 [95% CI: 0.71-1.06]; p = 0.16), and major bleeding rates (OR: 0.77 [95% CI: 0.56-1.06]; p = 0.11). Patients receiving clopidogrel had borderline lower risk for major adverse cardiovascular events (MACE) (OR: 0.84 [95% CI: 0.71-1.00]; p = 0.05) and lower risk for nonfatal myocardial infarction (OR: 0.83 [95% CI: 0.71-0.97]; p = 0.02, relative risk reduction = 16.9%, absolute risk reduction = 0.5%, number needed to treat = 217 for a mean period of 20 months) compared with patients receiving aspirin. In patients with established cardiovascular disease, clopidogrel was associated with a 17% relative-risk reduction for nonfatal MI, borderline decreased risk for MACE, and similar risk for all-cause mortality, stroke, and major bleeding compared with aspirin. PROSPERO CRD42021283866.

Unique Case of Management of Severe Hypertriglyceridemia Secondary to Familial Chylomicronemia Syndrome

<h3>Lead Author's Financial Disclosures</h3> Nothing to disclose. <h3>Study Funding</h3> None. <h3>Background/Synopsis</h3> We review a case of a 61-year-old female diagnosed at age 21 with severe hypertriglyceridemia with debilitating, recurrent episodes of acute pancreatitis. <h3>Objective/Purpose</h3> To review a clinical scenario involving severe hypertriglyceridemia and the role of novel therapies in management. <h3>Methods</h3> Clinical management at tertiary care lipid program. <h3>Results</h3> A 61-year-old slightly overweight female with a history of congenital aplasia of the pancreas, coronary artery disease post stents, pre-diabetes, and non-alcoholic fatty liver disease was diagnosed with severe hypertriglyceridemia secondary to chylomicronemia syndrome at age 21. No secondary causes were identified. She was trialed on several cholesterol and triglyceride lowering medications including niacin, rosuvastatin, gemfibrozil, fenofibrate, fish oil supplements with minimal improvement in symptoms and/or reduction in recurrent hospitalizations for acute pancreatitis. Interestingly, she showed a dramatic ∼70% reduction in triglycerides on evinacumab based on compassionate use, resulting in significant improvement in quality of life with no episodes of acute pancreatitis while on therapy for 12 months. <h3>Conclusions</h3> Familial chylomicronemia syndrome (FCS) is an autosomal recessive disorder with a lack of lipoprotein lipase (LPL) functionality, thereby markedly impairing clearance of chylomicrons from the plasma. The primary reason for concern is an increased risk of acute pancreatitis with an estimated odds ratio of 360 in patients with FCS. Acute pancreatitis, in fact, is responsible for a significant economic burden in the United States with an estimated annual cost of care of over $2 billion, accounting for about 50% higher healthcare-related costs compared to patients without acute pancreatitis. Additionally, studies have shown that patients on statin with high residual cardiovascular risk as well as high triglycerides had higher risk for nonfatal myocardial infarction and nonfatal stroke compared to patients with normal triglycerides. Unfortunately, there are currently no FDA-approved treatments for FCS. For this reason, novel therapies are crucially needed to relieve the debilitating state of these patients. One such concept is the use of ANGPTL3 inhibitor, evinacumab, currently FDA approved for homozygous familial hypercholesterolemia. ANGPTL3 inhibition enhances the activities of endothelial lipase and lipoprotein lipase, thereby reducing levels of LDL-C independent of LDL receptor activity, HDL and triglycerides. Based on meta-analysis and a few Phase 1-2 trials, evinacumab is shown to reduce triglycerides from 50% to 80% in patients with severe hypertriglyceridemia. In our patient, with TG/TC ratio >8:1 and normal to low apoB, FCS is more likely the culprit for severe triglyceride burden, contributing to recurrent acute pancreatitis. Furthermore, our patient also suffers from mixed dyslipidemia and metabolic syndrome, which significantly raises her lifetime atherosclerotic cardiovascular risk. Thus, we propose the use of evinacumab in such patients to not only target high triglycerides to reduce risk of acute pancreatitis but also optimize overall cardiovascular risk.

CARDIOVASCULAR OUTCOMES OF INITIAL BETA-BLOCKER + CALCIUM CHANNEL BLOCKER THERAPY VS OTHER DUAL THERAPIES IN CHINESE PATIENTS WITH NEWLY DIAGNOSED HYPERTENSION: A REAL-WORLD STUDY

Objective: This study aimed to compare cardiovascular (CV) outcomes associated with initial beta-blocker (BB) + calcium channel blocker (CCB) dual therapy and other initial dual therapies in Chinese patients with newly diagnosed hypertension. Design and method: In this retrospective study, all patients in a regional electronic database with newly diagnosed hypertension from January 01, 2012 to December 31, 2016 who received initial dual therapy recommended by the 2018 Chinese Guidelines for Prevention and Treatment of Hypertension were included. The recommended dual therapies included BB+CCB (B+C), ARB/ACEI+C (A+C), A+Diuretic (A+D) and C+D. 1:2 PSM was used to balance baseline characteristics between patients receiving B+C and patients receiving other initial dual therapies (Others). Primary outcome was major adverse cardiovascular events (MACE) consisting of non-fatal stroke, non-fatal myocardial infarction (MI), non-fatal chronic heart failure (CHF) and all-cause death during a median follow-up of 2.02 years (IQR: 1.07–3.36 years). Cox proportional hazard models were used to compare these CV outcomes in the 2 matched cohorts. Results: After the PSM, 6,227 patients in the B+C group and 12,454 patients in the Others group were included. The B+C group and the Others group had comparable age (59.5 ± 12.7 years vs. 59.8 ± 12.3 years) and diastolic blood pressure (91.2 ± 6.7 mmHg vs. 91.2 ± 6.9 mmHg), although their heart rate (88.0 ± 6.8 vs. 88.4 ± 7.1) and systolic blood pressure (156.2 ± 7.0 mmHg vs. 155.9 ± 7.1 mmHg) still had differences. Compared to the Others group, the B+C group had significantly lower risks of MACE (HR 0.85; 95%CI 0.78–0.92; P &lt; 0.001), non-fatal stroke (HR 0.89; 95% CI 0.81–0.98; P = 0.018) and non-fatal CHF (HR 0.74; 95% CI 0.63–0.86; P &lt; 0.0001) (Figure 1). Differences in risks of non-fatal MI and all-cause death in the 2 groups were statistically insignificant. Additionally, A+D (HR 1.71; 95% CI 1.52–1.92) and C+D (HR 1.77; 95% CI 1.45–2.15) were associated with significantly higher risk of MACE than B+C, and the difference between A+C (HR 1.04; 95% CI 0.96–1.14) and B+C was small. Conclusions: BB+CCB initial dual therapy was associated with lower risks of MACE, stroke and CHF than other recommended initial dual therapies in Chinese patients with newly diagnosed hypertension.

Soluble suppression of tumorigenesis-2 is a strong predictor of all-cause, cardiovascular and infection-related mortality risk in haemodialysis patients with diabetes mellitus

ABSTRACTBackgroundSoluble suppression of tumorigenesis-2 (sST2) is a strong prognostic biomarker of cardiovascular (CV) disease. End-stage kidney disease (ESKD) patients are at high risk of CV events and infections. Herein we investigated the utility of sST2 to predict all-cause and cause-specific mortality in haemodialysis (HD) patients with diabetes mellitus.MethodssST2 concentrations were measured in plasma samples of 1196 participants of the German Diabetes and Dialysis (4D) study who had type 2 diabetes mellitus and received maintenance HD for ESKD. Hazard ratios (HRs) for prespecified, adjudicated endpoints were determined according to sST2 levels at baseline by multivariate Cox proportional hazards analysis.ResultsParticipants (mean age 66 years, 54% male) had a median sST2 concentration of 25 ng/mL and were followed up for 4 years. After adjustment for possible confounders, participants with sST2 concentrations in the highest (>32.6 ng/mL) compared with the lowest (<20.1 ng/mL) quartile exhibited a 2-fold higher all-cause mortality risk {[HR 2.06 95% confidence interval (CI) 1.61–2.61]; P < .001}. High sST concentrations (fourth versus first quartile) were strongly associated with the risk of cardiac death [HR 2.29 (95% CI 1.55–3.39); P < .001]. Analysis of individual components of cardiac causes of death showed an increased risk of sudden death [HR 2.24 (95% CI 1.33–3.77); P < .001], death due to myocardial infarction [HR 2.12 (95% CI 0.9–5.0); P = .087] and heart failure [HR 3.34 (95% CI 1.15–9.75); P = .027] in participants with sST2 levels in the highest compared with the lowest quartile. Likewise, participants with the highest sST2 levels had an increased risk of fatal stroke [HR 1.92 (95% CI 1.17–3.14); P = .009] and fatal infections [HR 2.01 (95% CI 1.2–3.37); P = .008]. In contrast to fatal CV events, sST2 was not associated with the risk of non-fatal myocardial infarction [HR 0.68 (95% CI 0.41–1.12); P = .132] or non-fatal stroke [HR 1.28 (95% CI 0.64–2.53); P = .485].ConclusionsIn HD patients with diabetes mellitus, high concentrations of sST2 were strongly and independently associated with an increased risk of all-cause mortality, CV mortality and death due to infection but not non-fatal CV events.

The Association of Dispositional Optimism and Pessimism With Cardiovascular Disease Events in Older Adults: A Prospective Cohort Study.

Objective: Positive psychosocial factors may protect against cardiovascular disease (CVD). We aimed to determine the association of optimism and pessimism with CVD events in community-dwelling older adults. Methods: 11,651 adults aged 70years and over, participants of the ASPREE Longitudinal Study of Older Persons (ALSOP), were followed-up for 4.7years (median). The association of optimism and pessimism (assessed as separate constructs by revised Life Orientation Test) and incident CVD events (composite and components) was assessed by Cox regression adjusted for demographic, socioeconomic and health factors. Results: No association was observed between optimism and pessimism with composite CVD events. Being more pessimistic was associated with a greater risk of fatal coronary heart disease, while being more optimistic was associated with a lower risk of non-fatal myocardial infarction. Conclusions: Optimism and pessimism may shape cardiovascular health of older adults; and we argue these psychosocial factors should be researched as separate constructs.

Cardiovascular outcomes associated with prescription of sodium-glucose co-transporter-2 inhibitors versus dipeptidyl peptidase-4 inhibitors in patients with diabetes and chronic kidney disease.

To determine the association with cardiovascular (CV) outcomes of sodium-glucose co-transporter-2 (SGLT-2) inhibitors compared with dipeptidyl peptidase-4 (DPP-4) inhibitors in patients with type 2 diabetes (T2D) and chronic kidney disease (CKD). We conducted a population-based cohort study of new users of SGLT-2 inhibitors and DPP-4 inhibitors with T2D and CKD using data from Optum Clinformatics DataMart. We assembled three cohorts: T2D/no CKD, T2D/CKD 1-2, and T2D/CKD 3a. The study outcomes were (a) time to first heart failure (HF) hospitalization and (b) time to a composite CV endpoint comprised of non-fatal myocardial infarction (MI) or stroke. After inverse probability of treatment weighting, we used proportional hazards regression to estimate hazard ratios (HR) and 95% confidence intervals (CI). New users of SGLT-2 inhibitors versus DPP-4 inhibitors had lower risks of HF hospitalization in the T2D/no CKD (HR, 0.76; 95% CI, 0.70, 0.82) and T2D/CKD 1-2 (HR, 0.63; 95% CI, 0.48, 0.84) cohorts, but no significant association was present in the T2D/CKD 3a cohort. Compared with prescription of DPP-4 inhibitors, SGLT-2 inhibitors were associated with lower risks of non-fatal MI or stroke of 23% (HR, 0.77; 95% CI, 0.70, 0.85) in the T2D/no CKD cohort, but no significant associations were present in the T2D/CKD 1-2 and T2D/CKD 3a cohorts. Incident prescription of SGLT-2 inhibitors was associated with lower risks of HF hospitalization but not with non-fatal MI or stroke despite suggesting benefit, relative to prescription of DPP-4 inhibitor across different stages of CKD.

Prognostic Analysis of Patients with Acute Myocardial Infarction Undergoing Implantation of Different Stents for the First Time.

For patients with acute myocardial infarction scheduled to undergo percutaneous coronary stent implantation, in most cases a drug-eluting stent is recommended as the first choice for treatment. However, there is a lack of research on the effectiveness of bare-metal stents and drug-eluting stents on patients with different types of myocardial infarction. Our objective was to explore the effects of bare-metal stents and drug-eluting stents on patients with different types of myocardial infarction in terms of major cardiovascular incidents. This retrospective cohort study included 934 patients with myocardial infarction undergoing coronary artery stent implantation for the first time at the cardiac catheter room of the Tri-Service General Hospital in the Neihu District between 2014 and 2018. Patients’ information, including demographic data, laboratory data, cardiac echocardiography results, and angiocardiography results, was collected by reviewing medical records. Cox proportional hazards regression was used to adjust the potential confounding factors, and the adjusted data were then used to compare the correlation between different types of stents and major cardiovascular incidents in patients with ST-elevation myocardial infarction and non-ST-elevation myocardial infarction. After the confounding factors were adjusted, in patients with ST-elevation myocardial infarction receiving a drug-eluting stent compared with those receiving a bare-metal stent, it was found that the mortality risk was lower in terms of all causes of death (Adj-HR = 0.26, 95% CI = 0.14–0.48, p < 0.001) and cardiogenic death (Adj-HR = 0.20, 95% CI = 0.08–0.55, p = 0.002), the risk of non-fatal myocardial infarction was lower (Adj-HR = 0.17, 95% CI = 0.04–0.73, p = 0.017), and there was no difference in the risk of revascularization at the lesion site (Adj-HR = 0.59, 95% CI = 0.24–1.43, p = 0.243). It terms of the findings in patients with non-ST-elevation myocardial infarction, those receiving a drug-eluting stent had a lower risk of revascularization at the lesion site (Adj-HR = 0.48, 95% CI = 0.24–0.97, p = 0.04); however, there was no difference in the mortality risk in terms of all causes of death (Adj-HR = 0.71, 95% CI = 0.37–1.35, p = 0.296) or cardiogenic death (Adj-HR = 0.59, 95% CI = 0.18–1.90, p = 0.379),or in the risk of non-fatal myocardial infarction (Adj-HR = 0.27, 95% CI = 0.06–1.25, p = 0.093). Compared with bare-metal stents, drug-eluting stents provide better protection against death to receivers with ST-elevation myocardial infarction; however, this protection is decreased in receivers with non-ST-elevation myocardial infarction. It is recommended that for patients with non-ST-elevation myocardial infarction who are indicated to receive a drug-eluting stent, the clinical effectiveness of the treatment must be considered.