Reduction In Risk Of Myocardial Infarction Research Articles

Association between physical activity changes and incident myocardial infarction after ischemic stroke: a nationwide population-based study

BackgroundThe impact of changes in physical activity after ischemic stroke (IS) on the subsequent myocardial infarction (MI) risk is not fully understood. We aimed to investigate the effects of changes in physical activity on the risk of MI after acute IS using data from the Korean National Health Insurance Services Database.Methods224,764 patients newly diagnosed with IS between 2010 and 2016 who underwent two serial biannual health checkups were included. The participants were divided into four categories according to changes in their physical activity: persistent non-exercisers, new exercisers, exercise dropouts, and exercise maintainers. The primary outcome was a new diagnosis of incident MI. Multivariable Cox proportional models were used to assess the effects of changes in exercise habits on the risk of MI.ResultsAfter a median of 4.25 years of follow-up, 6,611 (2.94%) MI cases were observed. After adjusting for confounders, new exercisers and exercise maintainers were significantly associated with a lower risk of incident MI than persistent non-exercisers (aHR, 0.849; 95% CI, 0.792–0.911; P-value < 0.001; and aHR, 0.746; 95% CI, 0.696–0.801; P-value < 0.001, respectively). Effects were consistent across sexes, more pronounced in those > 65 years. Notably, any level of physical activity after stroke was associated with a reduced MI risk compared to no exercise.ConclusionsIn this nationwide cohort study, commencing or sustaining physical activity after an IS corresponded to a diminished likelihood of subsequent MI development. Advocating physical activity in ambulatory stroke survivors could potentially attenuate the prospective risk of MI.

Effects of albiglutide on myocardial infarction and ischaemic heart disease outcomes in patients with type 2 diabetes and cardiovascular disease in the Harmony Outcomes trial

Abstract Aims Large outcome trials have demonstrated cardiovascular benefits of selected glucagon-like peptide-1 (GLP-1) receptor agonists. We examined coronary disease outcomes in the Harmony Outcomes trial of the GLP-1 receptor agonist albiglutide. Methods and results Harmony Outcomes was an event-driven, multicenter, double-blind, and placebo-controlled trial involving 9463 patients &amp;gt;40 years of age with type-2 diabetes and established atherosclerotic cardiovascular disease. It tested the effects of albiglutide on the occurrence of a composite primary endpoint, consisting of cardiovascular death, myocardial infarction (MI), or stroke. Within this post-hoc analysis, the effects of albiglutide on MI subtypes and other ischaemic endpoints were analysed. During the median-follow up of 1.6 years, a total of 421 patients (4.5%) experienced at least one MI, with 72 patients having more than one event. Treatment with albiglutide reduced both first events [hazard ratio (HR) 0.75 (0.62–0.91)] and overall events [HR 0.75 (0.61–0.91)] as well as first type 1 [HR 0.73 (0.57–0.92)] and type 2 myocardial infarctions [HR 0.65 (0.46–0.92)]. The effect of albiglutide treatment was consistent for ST-segment elevation [HR 0.69 (0.38–1.26)] and non-ST elevation (HR 0.86 (0.66–1.2) MI. Conclusion Treatment with the GLP-1 receptor agonist albiglutide resulted in a 25% relative risk reduction in MI that was consistent for type of infarction and presence or absence of ST elevation. Our findings add novel information about the effects of GLP-1 receptor agonists on ischaemic events in patients with type 2 diabetes.

Independent causal effect of remnant cholesterol on atherosclerotic cardiovascular outcomes: a Mendelian randomization study

Abstract Background Observational studies suggested that residual risk of cardiovascular events following LDL-cholesterol (LDL-C) lowering may be linked to remnant cholesterol (RC). Purpose We conducted a large-scale Mendelian Randomization (MR) study to investigate the causal role of RC to predict coronary artery disease (CAD), myocardial infarction (MI) and stroke risk. Methods Outcome sources included 19,273 subjects of European ancestry from 14 cohorts, as well as data in 115,078 individuals from the OpenGWAS public data infrastructure. Over 12,000,000 SNPs were screened. We estimated the genetic association with outcomes from the Coronary Artery Disease (C4D) Genetics (CARDIoGRAMplusC4D) consortium, the Metastroke consortium as well as the Global Lipids Genetics Consortium. Our approach was to use genetic variants as instruments, thereby minimizing residual confounding, and reverse causation biases of observational studies. Results By leveraging data from a combined sample of ∼917,000 participants, we found evidence for a significant causal effect of RC on the risk of CAD (OR 1.51 per each mg/dL unit increase in RC, 95% CI 1.42–1.60), MI (OR 1.57, 1.21–2.05) and stroke (OR 1.23,1.12–1.35). There was no evidence of pleiotropy. Mediation analysis showed that the total effect of RC on CAD and MI was mainly direct: ORDirect 1.49 (1.37-1.61) for CAD and ORDirect 1.80 (1.70-19.1) for MI without a meaningful indirect effect exerted on these outcomes via the LDL-C mediator. Lifelong genetic inhibition of RC led to a 40% MI risk reduction which is superior to any intensity of pharmacological reduction from clinical trials with an average 3.5 years follow-up. Conclusions This large-scale MR study showed a robust genetic causal association between RC and cardiovascular outcomes. The effect on CAD and MI is independent of LDL-C. Early screening for RC along with long-term inhibition of RC should be the focus of future therapeutic interventions.

Dietary precursors and cardiovascular disease: A Mendelian randomization study.

The Dietary precursor has been identified as a contributor in the development of cardiovascular disease. However, it is inconsistent if dietary precursors could affect the process of cardiovascular disease. Here we performed Mendelian randomization (MR) analysis of the data from genome-wide association study of European ancestry to evaluate the independent effects of three dietary precursors on cardiovascular disease (CVD), myocardial infarction (MI), heart failure (HF), atrial fibrillation (AF), and valvular disease (VHD). Inverse variance weighting method was used for the MR estimation. Sensitivity was determined by MR-PRESSO analysis, weighted median analysis, MR-Egger analysis, and Leave-one-out analysis. We found that elevated choline level had a causal relationship with VHD [odds ratio (OR) = 1.087, 95% confidence interval (CI), 1.003-1.178, P = 0.041] and MI (OR = 1.250, 95% CI, 1.041-1.501, P = 0.017) by single-variable MR analysis. Furthermore, elevated carnitine level was associated with MI (OR = 5.007, 95% CI, 1.693-14.808, P = 0.004) and HF (OR = 2.176, 95% CI, 1.252-3.780, P = 0.006) risk. In addition, elevated phosphatidylcholine level can increase the risk of MI (OR = 1.197, 95% CI, 1.026-1.397, P = 0.022). Our data show that choline increases VHD or MI risk, carnitine increases the risk of MI or HF, and phosphatidylcholine increases HF risk. These findings suggest the possibility that decrease in choline level in circulation may be able to reduce overall VHD or MI risk, reduce in carnitine level could be decrease MI and HF risks as well as decrease in phosphatidylcholine could reduce MI risk.

Aspirin With or Without Statin in Individuals Without Atherosclerotic Cardiovascular Disease Across Risk Categories

BackgroundThe effects of aspirin in adults without atherosclerotic cardiovascular disease (ASCVD), stratified by statin use across different ASCVD risks, remain uncertain. ObjectivesThe purpose of this study was to examine the effects of aspirin in adults without ASCVD, stratified by statin use across different ASCVD risks. MethodsWe searched databases through March 2022 and selected randomized controlled trials of aspirin without ASCVD and follow-up of ≥1 year. We used random-effects models and estimated relative and absolute risks for cardiovascular outcomes, major bleeding, and mortality over 5 years. We calculated absolute risk differences assuming constant relative risks (RRs) across statin use and ASCVD risks. The Cholesterol Treatment Trialists Collaboration, and the ASCEND (A Study of Cardiovascular Events in Diabetes) trial were used to estimate baseline risks. ResultsIn 16 trials [171,215 individuals; median age, 64 (Q1-Q3: 60-65) years], aspirin vs control reduced myocardial infarction (MI) [RR: 0.85 (95% CI: 0.77-0.95)] but increased major bleeding [RR: 1.48 (95% CI: 1.32-1.66)]. Aspirin did not reduce mortality. Statin vs no statin was associated with lower bleeding and MI risk; the bleeding and MI risk were proportional to ASCVD risk. For every 10,000 adults, aspirin reduced MI (very low risk: 3 events as monotherapy or 1 event with statin; very high risk: 49 events as monotherapy or 37 events with statin) and increased major bleeding (very low risk: 21 events as monotherapy or 20 events with statin; very high risk: 98 events as monotherapy or 94 events with statin) proportional to baseline ASCVD risk. ConclusionsIn adults without ASCVD, concomitant statin appeared to significantly reduce absolute risk reduction for MI associated with aspirin without influencing bleeding risk. The anticipated absolute risk of major bleeding with aspirin exceeds absolute MI benefits for every level of ASCVD risk.

Colchicine linked with risk reduction for myocardial infarction in gout patients: systematic review and meta-analysis.

This meta-analysis aimed to identify the effect of colchicine on myocardial infarction (MI) in patients with gout. In February 2021, asystematic computer-based search was conducted in PubMed, EMBASE, and Cochrane Database of Systematic Reviews. Data on patients with gout that compared colchicine versus others (no use of colchicine) were retrieved. The endpoints were the incidence rate for MI. After testing for heterogeneity between studies, data were aggregated for fixed-effects models when necessary. Three clinical studies with 3012patients (colchicine group = 1523, control group = 1489) were finally included in the meta-analysis. Colchicine was associated with adecreased risk for myocardial infarction (pooled odds ratio 0.35, 95% confidence interval 0.23-0.55, p < 0.00001). Colchicine was effective in reducing the incidence of MI in patients with gout.

Age-Specific Relation of Cardiovascular Health Metrics With Incident Cardiovascular Disease

We examined the age-related differences in cardiovascular health (CVH) metrics for incident cardiovascular disease (CVD). Analyses were conducted using data from the JMDC Claims Database from 2005 to 2020 (n=2,728,427; mean age 44.9 ± 11.0years; 56.2% men). Participants were categorized on the basis of age: 20 to 49years (n=1,800,161), 50 to 59years (n=644,703), and 60 to 75years (n=283,563). Ideal CVH metrics included nonsmoking, body mass index <25kg/m2, physical activity at goal, not skipping breakfast, blood pressure <120/80mm Hg, fasting plasma glucose <100mg/dL, and total cholesterol <200mg/dL. Over a mean follow-up of 1,194 ± 917days, 5,988 myocardial infarction (MI), 53,409 angina pectoris, 26,530 stroke, and 52,712 heart failure (HF) events were recorded. Number of the nonideal CVH metrics was associated with incident MI, angina pectoris, stroke, and HF in all age categories. However, the association of the number of nonideal CVH metrics with incident CVD was modified by age categories and was more pronounced in participants aged 20 to 49years. Similarly, the relative risk reduction at 1year for each CVD event under the virtual condition that an individual with 2 nonideal CVH metrics has decreased them to zero, decreased with age. For example, relative risk reduction for MI was 0.51 in participants aged 20 to 49years, 0.48 in those aged 50 to 59years, and 0.40 in those aged 60 to 75years. In conclusion, CVH metrics were more strongly associated with incident CVD including HF among younger individuals suggesting the importance of optimizing modifiable risk factors and lifestyles in young participants for the primary CVD prevention.

Comparing Patient Preferences for Antithrombotic Treatment During the Acute and Chronic Phases of Myocardial Infarction: A Discrete-Choice Experiment.

BackgroundAntithrombotic drugs are used as preventive treatment in patients with a prior myocardial infarction (MI) in both the acute and chronic phases of the disease. To support patient-centered benefit–risk assessment, it is important to understand the influence of disease stage on patient preferences.ObjectiveThe aim of this study was to examine patient preferences for antithrombotic treatments and whether they differ by MI disease phase.MethodsA discrete-choice experiment was used to elicit preferences of adults in the acute (≤ 365 days before enrolment) or chronic phase (> 365 days before enrolment) of MI for key ischemic events (risk of cardiovascular [CV] death, non-fatal MI, and non-fatal ischemic stroke) and bleeding events (risk of non-fatal intracranial hemorrhage and non-fatal other severe bleeding). Preference data were analyzed using the multinomial logit model. Trade-offs between attributes were calculated as the maximum acceptable increase in the risk of CV death for a decrease in the risk of the other outcomes. To assess the potential effect of sociodemographic and clinical characteristics on patient preferences, subgroups were introduced as interaction terms in logit models.ResultsThe evaluable population included 155 patients with MI in the acute phase of disease and 180 in the chronic phase. The overall population was 82% male, mean age was 64.2 ± 9.6 years, and 93% had not experienced bleeding events or key ischemic events other than MI. Patients valued reduction in the risk of non-fatal intracranial hemorrhage more than CV death (p < 0.01) and CV death more than non-fatal ischemic events (p < 0.01). Preferences were similar in the acute and chronic populations (p = 0.17). However, older patients valued reduction in risk of MI more than younger patients (p = 0.04), and patients with bleeding risk factors valued reduction in the risk of CV death (p = 0.01) and MI (p = 0.01) less than patients without bleeding risk factors. Also, patients who were at high risk of future ischemic events valued reduction of the risk of CV death less than those at low risk (p = 0.01).ConclusionPatient preferences for antithrombotic treatments were unaffected by disease stage but varied by bleeding risk and other factors. This heterogeneity in preferences is an important consideration because it can affect the benefit–risk balance and the acceptability of antithrombotic treatments to patients.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40271-021-00548-6.

PCSK9 Gene Polymorphisms Associated With the Risk of Myocardial Infarction in Iranian Patients

Introduction: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key regulatory protein in lipid metabolism and a candidate gene in the etiology of cardiovascular diseases. The present study aimed to evaluate the prevalence and significance of PCSK9 rs505151 and rs11591147 variants with myocardial infarction (MI) risk in the Iranian population. Patients and Methods: The frequency of the PCSK9 rs505151 and rs11591147 variants were compared between 600 cases of MI and 600 healthy age- and sex-matched individuals. Tetra-primer amplification refractory mutation system-polymerase chain reaction (T-ARMS PCR) was used for rs505151, and amplification refractory mutation system-polymerase chain (ARMS-PCR) was utilized to detect the rs11591147 polymorphism. Finally, SPSS and SHEsis software were applied for data analysis. Results: Carriers of the GG genotype of rs505151 polymorphism (OR: 1.57, 95% CI: 1.05–2.35, P = 0.02; age-adjusted; OR: 1.54, 95% CI: 1.03–2.32, P = 0.03) and at least one G-allele including GG+AG vs. AA (OR: 1.54, 95% CI: 1.04–2.28, P = 0.03; age-adjusted; OR: 1.51, 95% CI: 1.01–2.24, P = 0.04) have an increased risk of MI. No association between PCSK9 rs505151 alleles and MI risk was observed. The ratio of individuals with the rs11591147GT variant was higher in healthy individuals vs. patients with MI (48.6% vs. 41.7%), indicating a reduced risk of developing MI (OR: 0.75; 95% CI: 0.59–0.95; P = 0.01; age-adjusted; OR: 0.74; 95% CI: 0.58–0.95; P = 0.01). The carriers of at least one T allele (TT+GT vs. GG) (OR: 0.78; 95% CI: 0.62–0.98; P = 0.03; age-adjusted; OR: 0.78; 95% CI: 0.62–0.98; P = 0.03) showed a significant reduction in MI risk. The allelic frequencies at this polymorphic site did not differ between MI patients and healthy counterparts. No association was found between the haplotypes constructed from the alleles of these two polymorphisms. Conclusion: Our study provides the first evidence that PCSK9 gene polymorphisms may serve as independent prognostic markers for MI patients in Iran.

Effects of Colchicine on Cardiovascular Outcomes in Patients with Coronary Artery Disease: A Systematic Review and One-Stage and Two-Stage Meta-Analysis of Randomized-Controlled Trials.

Colchicine has received emerging interest due to its cardiovascular benefits in patients with coronary artery disease (CAD). We conducted a one-stage meta-analysis of reconstructed individual patient data (IPD) from randomized-controlled trials to summarize the effects of colchicine on cardiovascular outcomes in patients with CAD. Four databases (PubMed, Embase, Cochrane, SCOPUS) were searched for articles published from inception to 30th September 2020, examining the effect of colchicine on cardiovascular outcomes in patients with CAD, yielding 10 randomized-controlled trials with a combined cohort of 12,781 patients. IPD was reconstructed from Kaplan-Meier curves published in 3 studies and analysed using the shared-frailty Cox model. Aggregate data meta-analysis of all 10 studies was performed for outcomes unsuitable for IPD reconstruction. In patients receiving colchicine compared to placebo, one-stage meta-analysis demonstrated a hazard ratio of 0.70 (95% CI 0.61-0.80) for the composite outcome of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and urgent hospitalization for angina requiring coronary revascularization. Aggregate data meta-analysis demonstrated a significant reduction in hazard rate for stroke (HR 0.45; 95% CI 0.27-0.75) and urgent revascularization (HR 0.59; 95% CI 0.38-0.91); and a relative risk reduction for myocardial infarction (RR 0.72; 95% CI of 0.52-1.00) and post-operative atrial fibrillation (RR 0.64; 95% CI 0.48-0.86). Given the significant benefits of colchicine demonstrated on IPD, and its consistent benefits when analyzed using aggregate data meta-analysis, we propose that colchicine may be considered as an additional pharmacological adjunct to the first line therapy for patients with coronary artery disease.

Current aspects of stable ischemic heart disease. ISСHEMIA study: breakthrough or constant optimism in approaches to treatment. Myocardial ischemia in non-obstructive coronary arteries (INOCA)

Approaches to stable coronary artery disease (CАD) treatment have been subject to debate for a long time. One of the first and fundamental studies in stable coronary artery disease patients treatment is the COURAGE study, which showed the advantage of rational drug therapy in comparison with percutaneous intervention in such patients. However, CAD high prevalence with medical and social significance cause the need for future development of relationship between conservative and invasive approaches in the problem of this disease treatment. It was particularly the focus of recently completed multicentre ISCHEMIA trail. The aim of review is to analyze the available data on the management of stable coronary artery disease patients based on the ISCHEMIA study data. Results. In the largest multicenter randomized clinical trial ISCHEMIA, the primary outcome (cardiovascular death, myocardial infarction, cardiac arrest with effective resuscitation, hospitalization due to heart failure) rate was 13.3% in the routine invasive strategy group and 15.5% in the conservative strategy group (p = 0.34). The main secondary outcome rate also does not differ between groups significantly. Quality of life in the non-invasive group was higher only in those patients who had angina at baseline. Study subanalysis demonstrated that left coronary artery borderline stenosis accompanied by a poor prognosis, and an invasive strategy improves angina symptoms. Also, low density lipoprotein cholesterol target values achievement predictors were determined. In addition, women, participated in ISCHEMIA study had more frequent angina episodes, regardless less extensive coronary artery damage, and less severe ischemia manifestations than men. Among stable CAD accompanied moderate to severe ischemia and severe chronic kidney disease patients, no evidence initial invasive strategy, compared initial conservative strategy, in relation of death or non-fatal myocardial infarction risk reduction was found. Conclusion: ISCHEMIA trial data demonstrated necessity more carefully stable coronary artery disease patients selection for invasive treatment, taking into account angina pectoris severity and modern antianginal therapy possibilities.

Sphingosine-1-phosphate: A mediator of the ARB-MI paradox?

BackgroundAngiotensin converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB) are important in the prevention of cardiovascular disease. The “ARB-MI paradox” implies that no risk reduction of myocardial infarction (MI) was found in ARB-treated patients despite target blood pressure control. Sphingosine-1-phosphate (S1P) is a cardioprotective sphingolipid which is released by platelets during activation. In this study we aimed to investigate differences of S1P homeostasis mediated by bradykinin and sphingosine kinases during ACEI/ARB treatment. MethodsIn this hypothesis generating pilot study, we investigated S1P plasma concentrations in 34 patients before and 3 months after ARB/ACEI medication. S1P levels were measured via liquid chromatography–tandem mass spectrometry. Bradykinin levels were measured by an enzyme-linked immunosorbent assay. ResultsPatient characteristics were not different between the ACEI and ARB group. Baseline S1P plasma concentrations were similar before ARB and ACEI treatment (7.4 SD 1.9 pmol vs. 7.8 SD 2.7 pmol, p = 0.54). After 3 months, S1P plasma levels were significantly higher in ACEI (9.3 SD 2.2 pmol) as compared to ARB treated patients (7.4 SD 2.4 pmol, p = 0.001). Pearson correlation showed no significant association between bradykinin and S1P levels before (r = −0.219; 95% CI [−0.54–0.15]; p = 0.245) or after three months of treatment with ACEI or ARB (r = −0.015; 95% CI [−0.48–0.45]; p = 0.95). ConclusionsS1P plasma concentrations are higher in ACE treated patients as compared to ARB treatment. This leads to the hypothesis, that differences in S1P metabolism might partially explain the ARB-MI paradox. This needs to be tested in clinical trials.

The impact of SSRIs on mortality and cardiovascular events in patients with coronary artery disease and depression: systematic review and meta-analysis.

Depression is common in patients after acute coronary syndromes (ACS) and with stable coronary artery disease (CAD) and has been associated with increased mortality and morbidity. However, it is unclear whether selective serotonin receptor inhibitors (SSRIs) reduce mortality or cardiac events in patients with CAD and depression. We conducted a systematic review and meta-analysis to assess the effects of SSRIs on cardiovascular events in depressed CAD patients. The CENTRAL, MEDLINE, and PsycINFO databases were searched (April 2020) for randomized controlled trials (RCTs) and extended follow-up analyses of RCTs that compared SSRIs with placebo or no intervention in patients with CAD and depression. The primary outcomes were all-cause mortality, cardiovascular mortality, and myocardial infarction incidence. The results were calculated through random-effect meta-analyses and reported in terms of risk ratio (RR) with 95% confidence intervals (CI). We retrieved 8 RCTs (2 of which with extended follow-up analyses), comprising a total of 1148 patients. 7 studies only included post-ACS patients. SSRIs were associated with a significantly lower risk of myocardial infarction in patients with CAD and depression (RR 0.54, 95% CI 0.34-0.86), and in post-ACS patients with depression (RR 0.56, 95% CI 0.35-0.90). We found no statistically significant difference in all-cause mortality, cardiovascular mortality, hospitalizations, angina, congestive heart failure, or stroke incidence. The use of SSRIs in post-ACS patients with depression was associated with a 44% relative risk reduction of myocardial infarction. No difference in mortality was found. Given that the quality of the evidence was low, further research is warranted.

Monotherapy with a P2Y12 inhibitor or aspirin for secondary prevention in patients with established atherosclerosis: a systematic review and meta-analysis

Antiplatelet therapy is recommended among patients with established atherosclerosis. We compared monotherapy with a P2Y12 inhibitor versus aspirin for secondary prevention. In this systematic review and meta-analysis, all randomised trials comparing P2Y12 inhibitor with aspirin monotherapy for secondary prevention in patients with cerebrovascular, coronary, or peripheral artery disease were evaluated for inclusion. On Dec 18, 2019, we searched PubMed, Embase, BioMedCentral, Google Scholar, and the Cochrane Central Register of Controlled Trials. Additionally, we reviewed references from identified articles and searched abstracts from 2017 to 2019 presented at relevant scientific meetings. Data about year of publication, inclusion and exclusion criteria, sample size, baseline patients' features including the baseline condition determining study inclusion (ie, cerebrovascular, coronary, or peripheral artery disease), P2Y12 inhibitor type and dosage, aspirin dosage, endpoint definitions, effect estimates, follow-up duration, and percentage of patients lost to follow-up were collected. Odds ratios (ORs) and 95% CIs were used as metric of choice for treatment effects with random-effects models. Co-primary endpoints were myocardial infarction and stroke. Key secondary endpoints were all-cause death and vascular death. Heterogeneity was assessed with the I2 index. This study is registered with PROSPERO (CRD42018115037). A total of nine randomised trials were identified and included in this study, and 42 108 patients randomly allocated to a P2Y12 inhibitor (n=21 043) or aspirin (n=21 065) were included in our analyses. Patients who received a P2Y12 inhibitor had a borderline reduction for the risk of myocardial infarction compared with those who received aspirin (OR 0·81 [95% CI 0·66-0·99]; I2=10·9%). Risks of stroke (OR 0·93 [0·82-1·06]; I2=34·5%), all-cause death (OR 0·98 [0·89-1·08]; I2=0%), and vascular death (OR 0·97 [0·86-1·09]; I2=0%) did not differ between patients who received a P2Y12 inhibitor and those who received aspirin. Similarly, the risk of major bleeding (OR 0·90 [0·74-1·10]; I2=3·9%) did not differ between patients who received a P2Y12 inhibitor and those who received aspirin. The number needed to treat to prevent one myocardial infarction with P2Y12 inhibitor monotherapy was 244 patients. Findings were consistent regardless of the type of P2Y12 inhibitor used. Compared with aspirin monotherapy, P2Y12 inhibitor monotherapy is associated with a risk reduction for myocardial infarction and a comparable risk of stroke in the setting of secondary prevention. The benefit of P2Y12 inhibitor monotherapy is of debatable clinical relevance, in view of the high number needed to treat to prevent a myocardial infarction and the absence of any effect on all-cause and vascular mortality. Italian Ministry of Education.

Cardiovascular Outcomes With the Use of Sodium-Glucose Cotransporter-2 Inhibitors in Patients With Type 2 Diabetes and Chronic Kidney Disease: An Updated Meta-Analysis of Randomized Controlled Trials.

Diabetes mellitus (DM) and chronic kidney disease (CKD) significantly increase the risk of cardiovascular morbidity and mortality. Sodium-glucose cotransporter-2 (SGLT-2) inhibitors are a new class of hypoglycemic agents that have shown significant promise in the reduction of cardiovascular events. Current guideline recommendations do not support the use of these agents in patients with CKD stage 3 or higher. We performed a comprehensive meta-analysis to evaluate their cardiovascular effects in patients with type 2 DM and CKD stage 3 or higher. A comprehensive search was performed in PubMed, Cochrane central, and Embase. Software R was utilized to perform a meta-analysis via the generic inverse variance method. Additionally, we conducted a network meta-analysis to compare the relative efficacy and safety of each agent. Data from 7 randomized controlled trials and 6527 participants were available. In patients with type 2 DM and CKD, SGLT-2 inhibitor use resulted in a significant relative risk reduction of myocardial infarction (22%), heart failure hospitalization (39%), and major adverse cardiac events (20%) (all P-value < 0.05). There was also a trend towards a reduction in stroke and cardiovascular mortality. In a network meta-analysis, canagliflozin was the most effective in reducing myocardial infarction, stroke, and heart failure hospitalization. Empagliflozin performed better for the outcome of cardiovascular mortality, but the results failed to reach significance. In conclusion, SGLT-2 inhibitors significantly improve cardiovascular outcomes in patients with type 2 DM and CKD stage 3 or higher, providing a compelling reason for their use in this population subgroup.

Mediating Effects of High-density Lipoprotein for Alcohol Consumption and Myocardial Infarction: The Multi-Ethnic Study of Atherosclerosis (OR19-07-19)

Abstract Objectives The aim of this study was to investigate whether and to what extent the association between alcohol intake and incident myocardial infarction (MI) is mediated through high density lipoprotein cholesterol (HDL-C), and HDL particles (HDL-P). Methods A total of 6,704 participants from the Multi-Ethnic Study of Atherosclerosis were included in the analysis. Alcohol consumption information was assessed via a questionnaire at baseline (exam 1). HDL-C concentrations and HDL-P were both measured at exam 1. Cox regression was used to model the association of habitual alcohol intake and risk for MI before and after adjusting HDL-C and HDL-P, in addition to adjustment of all potential covariates. Mediated effects through HDL-C, and HDL-P were estimated using the causal mediation analysis. Results After a median of 8 years follow-up, 171 incident MI cases were documented. Alcohol intake was associated with a lower risk for incident MI (adjusted Hazard Ratio (HR) = 0.69, 95% Confidence Interval (CI): 0.50-0.95), relative to non-drinkers. The relation between alcohol intake and MI became nonsignificant after further adjusting HDL-P. The HRs of the indirect effect of alcohol through HDL-C and HDL-P were 0.97 (95% CI: 0.93, 1.01) (P = 0.16) and 0.94 (95% CI: 0.90, 0.99) (P = 0.02), indicating that on average, alcohol intake reduced the risk of MI by 6% through its effect on HDL-P and not through HDL-C. The proportion of the effect of alcohol on MI mediated by HDL-P was 14.6%. Conclusions This study indicates that the lower risk of MI related to alcohol intake appears to partially work through increasing HDL-P, however, the mechanism for much of alcohol's effect to reduce MI risk remains unexplained. This suggests that HDL-P can be a target for MI prevention, however the mediating effect of HDL-P is very moderate. Funding Sources N/A.

Protective Effects of Arabinogalactan-Peptide Isolated from Wheat Flour against Myocardial Injury in an Ischemia/Reperfusion Rat Model.

We have previously shown that supplementation of wheat with hot-water extract reduces myocardial injury by inhibiting apoptosis in a rat model of myocardial infarction (MI). Arabinogalactan-peptide (AGP), a cell wall polysaccharide of wheat, was also responsible for the protection. However, the underlying mechanisms were not elucidated. In this study, we investigated the underlying mechanisms for how AGP supplementation reduces myocardial injury. First, we isolated highly pure AGP from all-purpose wheat flour. We supplemented rats with AGP at a dose of 100 mg/kg/d for 3 days, and subjected the rats to ischemia (30 min) through ligation of the left anterior descending coronary artery followed by reperfusion (3 h) through a release of the ligation. Supplementation with AGP significantly reduced the infarct size in the heart. In addition, AGP intake inhibited the apoptotic cascade, determined through decreased mitogen-activated protein kinases (p38 and c-Jun N-terminal kinase) phosphorylation, decreased Bcl-2-associated X protein/B-cell lymphoma ratios, and decreased generation of nicked DNA, which was confirmed through western blotting and terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling staining. These findings indicate that AGP intake can protect against myocardial injury. Traditionally, consumption of dietary fiber such as AGP has been shown to reduce MI risk by inhibiting preocclusion steps through reducing risk factors. Our findings suggest that AGP intake can also reduce MI risk by inhibiting postocclusion steps. This study describes a better dietary recommendation and new prevention strategy for reducing MI risk through regular consumption of wheat rich in AGP.

Association of Weather With Day-to-Day Incidence of Myocardial Infarction

Whether certain weather conditions modulate the onset of myocardial infarction (MI) is of great interest to clinicians because it could be used to prevent MIs as well as guide allocation of health care resources. To determine if weather is associated with day-to-day incidence of MI. In this prospective, population-based and nationwide setting, daily weather data from the Swedish Meteorological and Hydrological Institute were extracted for all MIs reported to the Swedish nationwide coronary care unit registry, Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART), during 1998 to 2013 and then merged with each MI on date of symptom onset and coronary care unit. All patients admitted to any coronary care unit in Sweden owing to MI were included. A total of 280 873 patients were included, of whom 92 044 were diagnosed as having ST-elevation MI. Weather data were available for 274 029 patients (97.6%), which composed the final study population. Data were analyzed between February 2017 and April 2018. The nationwide daily mean air temperature, minimum air temperature, maximum air temperature, wind velocity, sunshine duration, atmospheric air pressure, air humidity, snow precipitation, rain precipitation, and change in air temperature. The nationwide daily counts of MI as outcome. In 274 029 patients, mean (SD) age was 71.7 (12) years. Incidence of MI increased with lower air temperature, lower atmospheric air pressure, higher wind velocity, and shorter sunshine duration. The most pronounced association was observed for air temperature, where a 1-SD increase in air temperature (7.4°C) was associated with a 2.8% reduction in risk of MI (unadjusted incidence ratio, 0.972; 95% CI, 0.967-0.977; P <.001). Results were consistent for non-ST-elevation MI as well as ST-elevation MI and across a large range of subgroups and health care regions. In this large, nationwide study, low air temperature, low atmospheric air pressure, high wind velocity, and shorter sunshine duration were associated with risk of MI with the most evident association observed for air temperature.

Risk of Myocardial Infarction in Anticoagulated Patients With Atrial Fibrillation

BackgroundEvidence is conflicting as to the efficacy of direct oral anticoagulation (DOAC) and vitamin K antagonist (VKA) for prevention of myocardial infarction (MI). ObjectivesThis study aimed to investigate the risk of MI associated with the use of apixaban, dabigatran, rivaroxaban, and VKA in patients with atrial fibrillation. MethodsPatients with atrial fibrillation were identified using Danish health care registers and stratified by initial oral anticoagulant treatment. Standardized absolute 1-year risks were estimated based on Cox regression for hazard rates of MI hospitalizations and mortality. Reported were absolute risks separately for the oral anticoagulation treatments and standardized to the characteristics of the study population. ResultsOf the 31,739 patients included (median age, 74 years; 47% females), the standardized 1-year risk of MI for VKA was 1.6% (95% confidence interval [CI]: 1.3 to 1.8), apixaban was 1.2% (95% CI: 0.9 to 1.4), dabigatran was 1.2% (95% CI: 1.0 to 1.5), and rivaroxaban was 1.1% (95% CI: 0.8 to 1.3). No significant risk differences were observed in the standardized 1-year risks of MI among the DOACs: dabigatran versus apixaban (0.04%; 95% CI: −0.3 to 0.4), rivaroxaban versus apixaban (0.1%; 95% CI: −0.4 to 0.3), and rivaroxaban versus dabigatran (−0.1%; 95% CI: −0.5 to 0.2). The risk differences for DOACs versus VKA were all significant: −0.4% (95% CI: −0.7 to −0.1) for apixaban, −0.4% (95% CI: −0.7 to −0.03) for dabigatran, and −0.5% (95% CI: −0.8 to −0.2) for rivaroxaban. ConclusionsNo significant risk differences of MI were found in the direct comparisons of DOACs, and DOACs were all associated with a significant risk reduction of MI compared with VKA.

PCV74 - Three-Part Pricing to Reward Pharmaceutical Innovation and Increase Access: Case of PCSK9 Inhibitors

High launch prices of new drugs may inhibit access to innovative treatments, especially in cases where budget impact is substantial. We use PCSK9 inhibitors (PCSK9i) for hypercholesterolemia to present a novel three-part pricing strategy that simultaneously improves access while better rewarding effective therapies. We propose a novel three-part pricing (TPP) schedule that introduces three phases prior patent expiration: evaluation, reward, and access. In the evaluation phase, the drug is priced at 50% off list price to encourage rapid adoption. In the reward phase, the prices are determined based on drug’s performance during the evaluation phase, measured by risk reduction in myocardial infarction and stroke. Prices fall close to the generic level in the access phase to facilitate widespread adoption. We use a widely-published microsimulation, the Future Elderly Model (FEM), to estimate clinical benefits associated with various efficacy scenarios for PCSK9i, and develop an economic model to demonstrate the results of TPP versus traditional fee-per-dose (status quo) pricing. Efficacy thresholds of PCSK9i are estimated based on a key randomized clinical trial (FOURIER). If PCSK9i efficacy in the evaluation phase is worse than clinical trial data suggest, TPP reduces total spending by $30 billion versus fee-per-dose pricing. If the drug demonstrates comparable efficacy, TPP generates comparable discounted cash flow to the manufacturer (by design) but delivers revenues faster. If the drug shows better efficacy, discounted cash flow to the manufacturer increases by $30 billion, but this increase is driven by higher uptake. Overall, TPP reduces the cost per adverse event avoided under both the expected and low efficacy scenarios (by $50,000 and $296,000, respectively). By tying reimbursement to efficacy targets, three-part pricing can improve access to PCSK9i and lower spending risk to payers over traditional fee-for-dose pricing. The model shows promise for other innovative treatments as well.