Lipid goal attainment in post‐acute coronary syndrome patients in China: Results from the 6‐month real‐world dyslipidemia international study II

BackgroundDyslipidemia International Study II (DYSIS II)‐China was conducted to determine the low‐density lipoprotein cholesterol (LDL‐C) goal (<1.8 mmol/L) attainment rate in patients with post‐acute coronary syndrome (ACS).HypothesisCompliance with treatment guideline recommendations improves the LDL‐C goal attainment rate in post‐ACS patients.MethodsThis multicenter prospective observational study conducted at 28 tertiary hospitals determined the LDL‐C goal attainment rates at admission and 6‐month follow‐up in patients on lipid‐lowering treatment (LLT) for ≥3 months and those not on LLT (LLT‐naive or off LLT for ≥3 months) at admission. Predictors of goal attainment at 6 months were identified using multivariate logistic regression.ResultsThe LDL‐C goal attainment rate at admission in 1102/1103 enrolled patients was 17.1%; it was 41.2% among 752 patients with available lipid results at 6 months. The distance to goal was 0.7 mmol/L at 6 months. Statin monotherapy was the most prescribed LLT. Only 7.7% of patients were receiving statin + ezetimibe and 8.4% of patients were receiving an atorvastatin‐equivalent dose of ≥40 mg/day at 6 months. Being male (odds ratio [OR] 1.7, 95% confidence interval [CI] 1.1–2.6) and undergoing percutaneous coronary intervention during index hospitalization (OR 1.5, 95% CI 1.1 to 2.1) were the independent predictors for LDL‐C goal attainment.ConclusionsThis real‐world DYSIS II study in China reports a low LDL‐C goal attainment rate in post‐ACS patients even after 6 months of LLT. Lack of intensification of statin therapy and underutilization of combinations suggest gaps between real‐world treatment practices and guideline recommendations.     

Current status of low‐density lipoprotein cholesterol for primary prevention of coronary artery disease in late‐stage elderly persons with type 2 diabetes mellitus: A retrospective,single‐center study

Aims/IntroductionThe importance of low‐density lipoprotein cholesterol (LDL‐C) in the primary prevention of cardiovascular disease has recently been reported in the population aged ≥75 years with hypercholesterolemia. Therefore, the current status of LDL‐C management for primary prevention of coronary artery disease in patients aged ≥75 years with type 2 diabetes mellitus was investigated.Materials and MethodsA total of 124 patients aged ≥75 years who had type 2 diabetes mellitus, but no coronary artery disease, were investigated. The patients'' background characteristics, LDL‐C, glycemic status, ankle‐brachial index and cardio‐ankle vascular index were compared between patients taking and not taking LDL‐C‐lowering agents, such as hydroxymethylglutaryl‐CoA reductase inhibitors (statins) and ezetimibe. The details of the antihyperlipidemic and antidiabetic agents used in the present study were also examined.ResultsLDL‐C was significantly lower in patients taking LDL‐C‐lowering agents (LDLCLT[+]) than in patients not taking them (LDLCLT[−]), although LDL‐C was maintained <120 mg/dL in both groups (93.0 mg/dL vs 102.1 mg/dL). Approximately half of the cases in the LDLCLT(+) group received moderate‐intensity statins, with pitavastatin being the most prescribed statin. Glycated hemoglobin was significantly lower in the LDLCLT(+) group than in the LDLCLT(−) group (6.9% vs 7.3%). Sodium‐glucose transporter 2 inhibitors were more frequently used in the LDLCLT(+) group than in the LDLCLT(−) group. The ankle‐brachial index/cardio‐ankle vascular index did not differ between the groups.ConclusionLow‐density lipoprotein cholesterol was properly managed for primary prevention of coronary artery disease in patients aged ≥75 years with type 2 diabetes mellitus regardless of the presence or absence of LDL‐C‐lowering agents.     

Cardiology clinic visit increases likelihood of evidence‐based cholesterol prescribing in severe hypercholesterolemia

BackgroundPatients with phenotypic severe hypercholesterolemia (SH), low‐density lipoprotein‐cholesterol (LDL‐c) ≥ 190 mg/dl, atherosclerotic cardiovascular disease (ASCVD) or adults 40–75 years with diabetes with risk factors or 10‐year ASCVD risk ≥20% benefit from maximally tolerated statin therapy. Rural patients have decreased access to specialty care, potentially limiting appropriate treatment.HypothesisPrior visit with cardiology will improve treatment of severe hypercholesterolemia.MethodsWe used an electronic medical record‐based SH registry defined as ever having an LDL‐c ≥ 190 mg/dl since January 1, 2000 (n = 18 072). We excluded 3205 (17.7%) patients not alive or age 20–75 years. Patients defined as not seen by cardiology if they had no visit within the past 3 years (2017–2019).ResultsWe included 14 867 patients (82.3%; mean age 59.7 ± 10.3 years; 58.7% female). Most patients were not seen by cardiology (n = 13 072; 72.3%). After adjusting for age, sex, CVD, hypertension, diabetes and obesity, patients seen by cardiology were more likely to have any lipid‐lowering medication (OR = 1.46, 95% CI: 1.29–1.65), high‐intensity statin (OR = 1.81, 95% CI: 1.61–2.03), or proprotein convertase subtilisin‐kexin type 9 (PCSK9) inhibitor (OR = 5.96, 95% CI: 3.34–10.65) compared to those not seen by cardiology. Mean recent LDL‐c was lower in patients seen by cardiology (126.8 ± 51.6 mg/dl vs. 152.4 ± 50.2 mg/dl, respectively; p < .001).ConclusionIn our predominantly rural population, a visit with cardiology improved the likelihood to be prescribed any statin, a high‐intensity statin, or PCSK9 inhibitor. This more appropriately addressed their high life‐time risk of ASCVD. Access to specialty care could improve SH patient''s outcomes.     

Prognostic implications of calculated Apo‐lipoprotein B in patients with ST‐segment elevation myocardial infarction undergoing primary percutaneous coronary intervention: Outcome is tied to lower cut‐points

BackgroundDebates still surround using lipoproteins including Apo‐B in risk assessment, management, and prognosis of patients with coronary artery disease. During an acute ST‐segment elevation myocardial infarction, Apo‐B might help to achieve incremental prognostic information.ObjectiveWe sought to determine the potential prognostic utility of calculated Apo‐B in a cohort of patients with STEMI undergoing primary PCI.MethodsA retrospective cohort study was conducted enrolling 2,259 patients with a diagnosis of acute STEMI who underwent primary PCI. Apo‐B was obtained using a valid equation based on initial lipid measurements. High Apo‐B was defined as a level of 65 or higher. Primary endpoint of the study was major adverse cardiovascular events (MACE).ResultsMean age of the participants was 59.54 years and 77.9% of them were male. After a Median follow up of 15 (6.2) months, high Apo‐B was associated with MACE and the OR (95% CI) was 3.02 (1.07–8.47), p = .036. Odds ratios for prediction of MACE pertaining to LVEF, and smoking were 0.97 (p = .044), and 1.07 (p = .033), respectively. However, High Apo‐B was not able to predict suboptimal TIMI flow. Accordingly, the Odds ratio was 0.56 (0.17–1.87), p = 0.349. The power of High LDL‐C and Non‐HDLC for prediction of MACE were assessed in distinct models. Attained odds ratios were [2.40 (0.90–6.36), p = .077] and [1.80 (0.75–4.35), p = 0.191], respectively.ConclusionCalculated Apo‐B appears to be a simple tool applicable for prediction of cardiovascular events in patients with STEMI superior to both Non‐HDLC and LDL‐C.     

Effectiveness of proprotein convertase subtilisin/kexin‐9 monoclonal antibody treatment on plasma lipoprotein(a) concentrations in patients with elevated lipoprotein(a) attending a clinic

BackgroundLipoprotein(a) (Lp[a]) is a causal risk factor for atherosclerotic cardiovascular disease (ASCVD). Proprotein convertase subtilisin/kexin‐9 monoclonal antibodies (PCSK9mAbs) can lower Lp(a) levels in clinical trials, but their effects in patients with elevated Lp(a) in clinical practice remain unclear.AimsTo investigate the effectiveness and safety of PCSK9mAbs in lowering plasma Lp(a) in patients with elevated Lp(a) concentrations in a lipid clinic.MethodsThis was an open‐label study of 53 adult patients with elevated Lp(a) concentration (≥0.5 g/L). Clinical, biochemical, and safety data were collected before and on treatment with evolocumab or alirocumab over a mean period of 11 months.ResultsTreatment with a PCSK9mAb resulted in a significant reduction of 0.29 g/L (−22%) in plasma Lp(a) concentration (p<.001). There were also significant reductions in low‐density lipoprotein‐cholesterol (LDL‐C) (−53%), remnant‐cholesterol (−12%) and apolipoprotein B (−43%) concentrations. The change in Lp(a) concentration was significantly different from a comparable group of 35 patients with elevated Lp(a) who were not treated with a PCSK9mAb (−22% vs. −2%, p<.001). The reduction in Lp(a) concentration was not associated with the corresponding changes in LDL‐C, remnant‐cholesterol, and apolipoprotein B (p>.05 in all). 7.5% and 47% of the patients attained a target concentration of Lp(a) <0.5 g/L and LDL‐C <1.8 mmol/L, respectively. PCSK9mAbs were well tolerated, the common adverse effects being pharyngitis (9.4%), nasal congestion (7.6%), myalgia (9.4%), diarrhoea (7.6%), arthralgia (9.4%) and injection site reactions (11%).ConclusionPCSK9mAbs can effectively and safely lower plasma Lp(a) concentrations in patients with elevated Lp(a) in clinical practice; the impact of the fall in Lp(a) on ASCVD outcomes requires further investigation.     

Prevalence of atherosclerotic cardiovascular disease and subsequent major adverse cardiovascular events in Alberta,Canada: A real‐world evidence study

BackgroundAtherosclerotic cardiovascular disease (ASCVD) is a leading cause of morbidity and mortality worldwide. Data from Canadian populations regarding the burden of ASCVD are limited. Therefore, we describe the 5‐year period prevalence of ASCVD and subsequent major adverse cardiovascular event (MACE) outcomes among patients with ASCVD in Alberta, Canada.MethodsA retrospective, observational study was conducted by linking provincial health services data, vital statistics, and pharmaceutical dispenses data. Five‐year period prevalence of clinical ASCVD was captured between 2011 and 2016, and a cohort of adult patients with an initial clinical ASCVD event were identified between 2012 and 2016. One‐year incidence rates (IRs) of subsequent MACE outcomes were calculated as composite and individual measures. A subgroup of patients with acute myocardial infarction (AMI) as their index event was examined.ResultsThere were 198 573 patients (mean [standard deviation] age: 63.9 [15.6] years; 56.6% males) identified with clinical ASCVD between 2012 and 2016. Overall, the 5‐year period prevalence of ASCVD in Alberta was 89.9 per 1000 persons and the 1‐year IR for a primary MACE outcome was 6.15 (95% confidence interval [CI]: 6.03–6.26) per 100 person‐years. Among the ASCVD cohort, 9465 had an AMI as their index event and the IR for a primary MACE outcome was 14.30 (95% CI: 13.45–15.20) per 100 person‐years.ConclusionsThis study found that the prevalence of ASCVD and the rate of subsequent MACE outcomes 1 year following the initial ASCVD event are substantial, particularly among patients with an AMI. Secondary prevention strategies aimed at lowering this risk are needed for patients with ASCVD.     

Management and outcome across the spectrum of high‐risk patients with myocardial infarction according to the thrmobolysis in myocardial infarction (TIMI) risk‐score for secondary prevention

BackgroundPatients with myocardial infarction (MI) are at increased risk for recurrent cardiovascular events, yet some patients, such as the elderly and those with prior comorbidities, are particularly at the highest risk. Whether these patients benefit from contemporary management is not fully elucidated.MethodsIncluded were consecutive patients with MI who underwent percutaneous coronary intervention (PCI) in a large tertiary medical center. Patients were stratified according to the thrombolysis in myocardial infarction (TIMI) risk score for secondary prevention (TRS2°P) to high (TRS2°P = 3), very high (TRS2°P = 4), or extremely high‐risk (TRS2°P = 5–9). Excluded were low and intermediate‐risk patients (TRS2°P < 3). Outcomes included 30‐day/1‐year major adverse cardiac events (MACE) and 1‐year mortality. Temporal trends were examined in the early (2004–2010) and late (2011–2016) time‐periods.ResultsAmong 2053 patients, 50% were high‐risk, 30% very high‐risk and 20% extremely high‐risk. Extremely high‐risk patients were older (age 74 ± 10 year) and had significant comorbidities (chronic kidney disease 68%, prior CABG 40%, heart failure 78%, peripheral artery disease 29%). Drug‐eluting stents and potent antiplatelets were more commonly used over time in all risk‐strata. Over time, 30‐day MACE rates have decreased, mainly attributed to the very high (11.3% to 5.1%, p = .006) and extremely high‐risk groups (15.9% to 8.0%, p = .016), but not the high‐risk group, with similar quantitative results for 1‐year MACE. The rates of 1‐year mortality remained unchanged in either group.ConclusionWithin a particularly high‐risk cohort of MI patients who underwent PCI, the implementation of guideline‐recommended therapies has improved over time, with the highest‐risk groups demonstrating the greatest benefit in outcomes.     

Clinical effectiveness and safety of amlodipine/losartan‐based single‐pill combination therapy in patients with hypertension: Findings from real‐world,multicenter observational databases

Various single‐pill combinations (SPCs) have been introduced to improve drug compliance and clinical efficacy. However, there is a lack of real‐world evidence regarding the effectiveness of these SPCs for hypertension. This study evaluated the real‐world clinical efficacy and safety of amlodipine/losartan‐based SPC therapies in patients with hypertension in a real‐world setting. A total of 15 538 patients treated with amlodipine/losartan‐based SPCs [amlodipine + losartan (AL), amlodipine + losartan + rosuvastatin (ALR), and amlodipine + losartan + chlorthalidone (ALC)] were selected from the database of three tertiary hospitals in Korea. The efficacy endpoints were target blood pressure (BP) and low‐density lipoprotein cholesterol (LDL‐C) achievement rates. Safety was evaluated based on laboratory parameters. Drug adherence was defined as the proportion of medication days covered (PDC). The target BP attainment rate was above 90% and was similar among the three groups. Although many patients in the AL and ALC groups took statins, the target LDL‐C attainment rate was significantly higher in the ALR group than in the AL and ALC groups. Safety endpoints were not significantly different among the groups, except serum uric acid level and incidence rate of new‐onset hyperuricemia, which were significantly lower in the AL and ALR groups than in the ALC group. The PDC was > 90% in all groups. In the real‐world hypertensive patients, amlodipine/losartan‐based SPC therapy demonstrated good target BP achievement rates. Especially, rosuvastatin‐combination SPC showed better target LDL‐C goal achievement rate compared to the other SPCs. All three amlodipine/losartan‐based SPC had excellent drug adherence.     

Insulin–glucagon‐like peptide‐1 receptor agonist relay and glucagon‐like peptide‐1 receptor agonist first regimens in individuals with type 2 diabetes: A randomized,open‐label trial study

Aims/IntroductionGlucagon‐like peptide‐1 receptor agonists (GLP‐1 RA) might be less effective in patients with severe hyperglycemia, because hyperglycemia downregulated the GLP‐1 receptor in an animal study. To examine this hypothesis clinically, we compared the glucose‐lowering effects of GLP‐1 receptor agonist liraglutide with and without prior glycemic control.Materials and MethodsIn an open‐label, parallel trial, participants with poorly controlled type 2 diabetes were recruited and randomized to receive once‐daily insulin therapy, degludec (Insulin–GLP‐1 RA relay group, mean 16.8 ± 11.4 IU/day), for 12 weeks and then liraglutide for 12 weeks or subcutaneous injections of GLP‐1 RA, liraglutide (GLP‐1 RA first group, 0.9 mg), for 24 weeks. The primary efficacy end‐points consisted of changes in the levels of fasting plasma glucose and glycated hemoglobin (HbA1c).ResultsThe median fasting plasma glucose and HbA1c before the study were 210.0 mg/dL and 9.8%, respectively. The levels of fasting plasma glucose and HbA1c significantly decreased in the Insulin–GLP‐1 RA relay group (P < 0.001) and GLP‐1 RA first group (P < 0.001) by week 24, although no intergroup differences were observed. The reduction of HbA1c in the Insulin–GLP‐1 RA relay group tended to be larger than that in the GLP‐1 RA first group in the lowest CPR (C‐peptide immunoreactivity) quartile (P = 0.072). The adverse events consisted of gastrointestinal problems, followed by hypoglycemia.ConclusionsThe GLP‐1 receptor agonist is overall effective without prior glycemic control with insulin in participants with poorly controlled type 2 diabetes. However, in participants with insulinopenic type 2 diabetes, prior glycemic control with insulin might overcome glucose toxicity‐induced GLP‐1 resistance.     

Proenkephalin and the risk of new‐onset heart failure: data from prevention of renal and vascular end‐stage disease

BackgroundEnkephalins of the opioid system exert several cardiorenal effects. Proenkephalin (PENK), a stable surrogate, is associated with heart failure (HF) development after myocardial infarction and worse cardiorenal function and prognosis in patients with HF. The association between plasma PENK concentrations and new‐onset HF in the general population remains to be established.HypothesisWe hypothesized that plasma PENK concentrations are associated with new‐onset HF in the general population.MethodsWe included 6677 participants from the prevention of renal and vascular end‐stage disease study and investigated determinants of PENK concentrations and their association with new‐onset HF (both reduced [HFrEF] and preserved ejection fraction [HFpEF]).ResultsMedian PENK concentrations were 52.7 (45.1–61.9) pmol/L. Higher PENK concentrations were associated with poorer renal function and higher NT‐proBNP concentrations. The main determinants of higher PENK concentrations were lower estimated glomerular filtration rate (eGFR), lower urinary creatinine excretion, and lower body mass index (all p < .001). After a median 8.3 (7.8–8.8) years follow‐up, 221 participants developed HF; 127 HFrEF and 94 HFpEF. PENK concentrations were higher in subjects who developed HF compared with those who did not, 56.2 (45.2–67.6) versus 52.7 (45.1–61.6) pmol/L, respectively (p = .003). In competing‐risk analyses, higher PENK concentrations were associated with higher risk of new‐onset HF (hazard ratio [HR] = 2.09[1.47–2.97], p < .001), including both HFrEF (HR = 2.31[1.48–3.61], p < .001) and HFpEF (HR = 1.74[1.02–2.96], p = .042). These associations were, however, lost after adjustment for eGFR.ConclusionsIn the general population, higher PENK concentrations were associated with lower eGFR and higher NT‐proBNP concentrations. Higher PENK concentrations were not independently associated with new‐onset HFrEF and HFpEF and mainly confounded by eGFR.     

Anti‐SARS‐CoV‐2 IgG antibody levels among Thai healthcare providers receiving homologous and heterologous COVID‐19 vaccination regimens

BackgroundWe examined SARS‐CoV‐2 anti‐spike 1 IgG antibody levels following COVID‐19 vaccination (AstraZeneca [AZ], Sinovac [SV], Pfizer‐BioNTech [PZ]) among Thai healthcare providers.MethodsBlood specimens were tested using enzyme‐linked immunosorbent assay. We analyzed seven vaccination regimens: (1) one dose of AZ or SV, (2) two doses of homologous (2AZ, 2SV) or heterologous (1AZ + 1PZ) vaccines, and (3) three doses of heterologous vaccines (2SV + 1AZ, 2SV + 1PZ). Differences in antibody levels were assessed using Kruskal–Wallis statistic, Mann–Whitney test, or Wilcoxon matched‐pairs signed‐rank test. Antibody kinetics were predicted using fractional polynomial regression.ResultsThe 563 participants had median age of 39 years; 92% were female; 74% reported no underlying medical condition. Antibody levels peaked at 22–23 days in both 1AZ and 2SV vaccinees and dropped below assay''s cutoff for positive (35.2 binding antibody units/ml [BAU/ml]) in 55 days among 1AZ vaccinees compared with 117 days among 2SV vaccinees. 1AZ + 1PZ vaccination regimen was highly immunogenic (median 2279 BAU/ml) 1–4 weeks post vaccination. 2SV + 1PZ vaccinees had significantly higher antibody levels than 2SV + 1AZ vaccinees 4 weeks post vaccination (3423 vs. 2105 BAU/ml; p‐value < 0.01), and during weeks 5–8 (3656 vs. 1072 BAU/ml; p‐value < 0.01). Antibodies peaked at 12–15 days in both 2SV + 1PZ and 2SV + 1AZ vaccinees, but those of 2SV + 1AZ declined more rapidly and dropped below assay''s cutoff in 228 days while those of 2SV + 1PZ remained detectable.Conclusions1AZ + 1PZ, 2SV + 1AZ, and 2SV + 1PZ vaccinees had substantial IgG levels, suggesting that these individuals likely mounted sufficient anti‐S1 IgG antibodies for possible protection against SARS‐CoV‐2 infection.     

SARS‐CoV‐2 infection rate in Antananarivo frontline health care workers,Madagascar

BackgroundHealth care workers (HCWs) represent a vulnerable population during epidemic periods. Our cohort study aimed to estimate the risk of infection and associated factors among HCWs during the first wave of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) in Madagascar.MethodsA prospective cohort study was carried out in three hospitals that oversaw the first cases of COVID‐19. Monthly ELISA‐based serological tests were conducted, and nasopharyngeal swabs were collected in the case of symptoms linked to COVID‐19 for RT–PCR analysis. Survival analyses were used to determine factors associated with SARS‐CoV‐2 infection.ResultsThe study lasted 7 months from May 2020. We included 122 HCWs, 61.5% of whom were women. The median age was 31.9 years (IQR: 26.4–42.3). In total, 42 (34.4%) had SARS‐CoV‐2 infections, of which 20 were asymptomatic (47.6%). The incidence of SARS‐CoV‐2 infection was 9.3% (95% CI [6.5–13.2]) person‐months. Sixty‐five HCWs presented symptoms, of which 19 were positive by RT–PCR. When adjusted for exposure to deceased cases, infection was more frequent in HCWs younger than 30 years of age (RR = 4.9, 95% CI [1.4–17.2]).ConclusionOur results indicate a high incidence of infection with SARS‐CoV‐2 among HCWs, with a high proportion of asymptomatic cases. Young HCWs are more likely to be at risk than others. Greater awareness among young people is necessary to reduce the threat of infection among HCWs.     

Chronic biopsy proven post‐COVID myoendocarditis with SARS‐Cov‐2 persistence and high level of antiheart antibodies

PurposeTo study the clinical signs and mechanisms (viral and autoimmune) of myoendocarditis in the long‐term period after COronaVIrus Disease 2019 (COVID‐19).MethodsFourteen patients (nine male, 50.1 ± 10.2 y.o.) with biopsy proven post‐COVID myocarditis were observed. The diagnosis of COVID‐19 was confirmed by IgG seroconversion. The average time of admission after COVID‐19 was 5.5 [2; 10] months. An endomyocardial biopsy (EMB) of the right ventricle was obtained. The biopsy analysis included polymerase chain reaction diagnosis of viral infection, morphological, immunohistochemical (IHC) examination with antibodies to CD3, CD45, CD68, CD20, SARS‐Cov‐2 spike, and nucleocapsid antigens. Coronary atherosclerosis was ruled out in all patients over 40 years.ResultsThe new cardiac symptoms (congestive heart failure 3–4 New York Heart Association class with severe right ventricular involvement, various rhythm, and conduction disturbances) appeared 1–5 months following COVID‐19. Magnetic resonance imaging showed disseminated or focal subepicardial and intramyocardial late gadolinium enhancement, hyperemia, edema, and increased myocardial native T1 relaxation time. Antiheart antibodies levels were increased 3–4 times in 92.9% of patients. The mean left ventricular (LV) ejection fraction (EF) was 28% (24.5; 37.8). Active lymphocytic myocarditis was diagnosed in 12 patients, eosinophilic myocarditis in two patients. SARS‐Cov‐2 RNA was detected in 12 cases (85.7%), in association with parvovirus B19 DNA—in one. Three patients had also endocarditis (infective and nonbacterial, with parietal thrombosis). As a result of steroid and chronic heart failure therapy, the EF increased to 47% (37.5; 52.5).ConclusionsCOVID‐19 can lead to long‐term severe post‐COVID myoendocarditis, that is characterized by prolonged persistence of coronavirus in cardiomyocytes, endothelium, and macrophages (up to 18 months) in combination with high immune activity. Corticosteroids and anticoagulants should be considered as a treatment option of post‐COVID myoendocarditis.     

Comparison of coronary atherosclerotic disease burden between ST‐elevation myocardial infarction and non‐ST‐elevation myocardial infarction: Non‐culprit Gensini score and non‐culprit SYNTAX score

BackgroundPatients with non‐ST‐elevation myocardial infarction (NSTEMI) have worse long‐term prognoses than those with ST‐elevation myocardial infarction (STEMI).HypothesisIt may be attributable to more extended coronary atherosclerotic disease burden in patients with NSTEMI.MethodsThis study consisted of consecutive 231 patients who underwent coronary intervention for myocardial infarction (MI). To assess the extent and severity of atherosclerotic disease burden of non‐culprit coronary arteries, two scoring systems (Gensini score and synergy between percutaneous coronary intervention with Taxus and cardiac surgery [SYNTAX] score) were modified by subtracting the score of the culprit lesion: the non‐culprit Gensini score and the non‐culprit SYNTAX score.ResultsPatients with NSTEMI had more multi‐vessel disease, initial thrombolysis in myocardial infarction (TIMI) flow grade 2/3, and final TIMI flow grade 3 than those with STEMI. As compared to STEMI, patients with NSTEMI had significantly higher non‐culprit Gensini score (16.3 ± 19.8 vs. 31.2 ± 25.4, p < 0.001) and non‐culprit SYNTAX score (5.8 ± 7.0 vs. 11.1 ± 9.7, p < 0.001).ConclusionsPatients with NSTEMI had more advanced coronary atherosclerotic disease burden including non‐obstruction lesions, which may at least in part explain higher incidence of cardiovascular events in these patients.     

Re‐adjudication of the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS) with study‐level meta‐analysis of hospitalization for heart failure from cardiovascular outcomes trials with dipeptidyl peptidase‐4 (DPP‐4) inhibitors

BackgroundTrial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS) assessed the cardiovascular (CV) safety of sitagliptin versus placebo on CV outcomes in patients with type 2 diabetes and CV disease and found sitagliptin noninferior to placebo. Subsequently, based on feedback from FDA, the Sponsor of the trial, Merck & Co., Inc., engaged a separate academic research organization, the TIMI Study Group, to re‐adjudicate a prespecified set of originally adjudicated events.MethodsTIMI adjudicated in a blinded fashion all potential hospitalization for heart failure (HHF) events, all potential MACE+ events previously adjudicated as not an endpoint event, and a random subset (~10%) of MACE+ events previously adjudicated as an endpoint event. An updated study‐level meta‐analysis of four randomized, placebo‐controlled, CV outcomes trials with dipeptidyl peptidase 4 (DPP‐4) inhibitors was then performed.ResultsAfter re‐adjudication of potential HHF events in the intent‐to‐treat population, there were 224 patients with a confirmed event in the sitagliptin arm (1.05/100 person‐years) and 239 patients in the placebo arm (1.13/100 person‐years), corresponding to a hazard ratio (HR) of 0.94 (95% confidence interval [95% CI]: 0.78–1.13, p = .49). Concordance between the outcome of the original adjudication and the re‐adjudication for HHF events was 82.7%. The meta‐analysis of CV outcomes trials with DPP‐4 inhibitors with placebo and involving 43 522 patients yielded an HR of 1.07 (95% CI: 0.83–1.39), with moderate heterogeneity (p = .45, I ² = 62.07%).ConclusionThe results of this independent re‐adjudication process and analyses of CV outcomes from TECOS were consistent with the original adjudication results and overall study findings. An updated study‐level meta‐analysis showed no overall significant risk for HHF with DPP‐4 inhibitors, but with statistical heterogeneity.     

Association between dipeptidyl peptidase‐4 inhibitors and increased risk for bullous pemphigoid within 3 months from first use: A 5‐year population‐based cohort study using the Japanese National Database

Aims/IntroductionWe assessed the association between dipeptidyl peptidase‐4 inhibitors (DPP‐4is) and bullous pemphigoid (BP) and time‐dependent changes in the risk for developing BP after DPP‐4i initiation.Materials and MethodsThe present population‐based, real‐world study was carried out using the Japanese National Database dataset collected between 2013 and 2018. To assess independent correlations between DPP‐4is and the development of BP, the self‐controlled case series method was used.ResultsAmong the cohort followed up for a median of 1,540 days, 53,027 patients were likely to develop BP. The possible incidence rate of BP in all 150,328,339 patients was 10.4/100,000 person‐years. Among the 9,705,814 patients with type 2 diabetes, 15,634 were likely to develop BP. The possible incidence rate of BP in patients with type 2 diabetes was 38.1/100,000 person‐years, whereas that in patients with type 2 diabetes who did and did not use DPP‐4is was 40.7 and 30.0/100,000 person‐years, respectively. Analysis of the 28,705 patients with type 2 diabetes likely to develop BP after initial DPP‐4i use showed a risk ratio of 2.15 (95% confidence interval [CI] 1.75–2.63), 1.70 (95% CI 1.37–2.11), 1.44 (95% CI 1.15–1.82), 1.25 (95% CI 0.98–1.59), 0.84 (95% CI 0.63–1.10), 0.84 (95% CI 0.64–1.11) and 1.05 (95% CI 0.92–1.20), for the risk period of ≤30, 31–60, 61–90, 91–120, 121–150, 151–180 and 181–365 days, respectively.ConclusionsAlthough DPP‐4is were associated with increased risk for BP, the risk was particularly significant within 3 months from first use.     

Visit‐to‐visit variability in albuminuria predicts renal function deterioration in patients with type 2 diabetes

Aims/IntroductionWe aimed to study the predictive ability of visit‐to‐visit variability in albuminuria for changes in renal function in patients with type 2 diabetes mellitus.Materials and MethodsThe cohort study was carried out in a single medical center. In the model development cohort of 1008 subjects, we developed the albuminuria variability score (AVS) to evaluate the visit‐to‐visit variability in albuminuria, which was the percentage of the number of changes in the urine albumin : creatinine ratio ≥3.39 mg/mmol among all visit‐to‐visit urine albumin : creatinine ratio differences within an individual. Multivariate logistic regression was applied to predict the influence of AVS levels on the occurrence of study end‐points. In another independent validation cohort of 310 participants, survival analysis was carried out to evaluate the ability of AVS in predicting the study end‐point.ResultsIn the model development cohort, a higher AVS was associated with higher adjusted odds of having a declined or rapidly declined estimated glomerular filtration rate (eGFR) trajectory (1.84, 95% confidence interval 1.23–2.76 and 5.70, 95% confidence interval 2.28–14.25, respectively), a resultant eGFR <60 mL/min/1.73 m² (2.61, 95% confidence interval 1.63–4.16) and a >40% decline in eGFR from baseline (6.44, 95% confidence interval 2.15–19.26). In the validation cohort, a higher AVS independently predicted a 5‐year decrease of >40% in eGFR to <60 mL/min/1.73 m² (adjusted hazard ratio 3.33, 95% confidence interval 1.10–10.05). Integrated discrimination index and concordance statistics showed that AVS significantly improved the predictive ability of the models.ConclusionsVisit‐to‐visit variability in albuminuria can independently predict long‐term renal function deterioration in patients with type 2 diabetes mellitus. Further investigations are warranted to elucidate the potential clinical applications.     

Anxiety and prognosis of patients with myocardial infarction: A meta‐analysis

Although anxiety is highly prevalent after myocardial infarction (MI), but the association between anxiety and MI is not well established. This study aimed to provide an updated and comprehensive evaluation of the association between anxiety and short‐term and long‐term prognoses in patients with MI. Anxiety is associated with poor short‐term and long‐term prognoses in patients with MI. We performed a systematic search in the PubMed and Cochrane databases (January 2000–October 2020). The study endpoints were complications, all‐cause mortality, cardiac mortality, and/or major adverse cardiac events (MACEs). Pooled data were synthesized using Stata SE12.0 and expressed as risk ratios (RRs) and 95% confidence intervals (CIs). We included 9373 patients with MI from 16 published studies. Pooled analyses indicated a correlation between high anxiety and poor clinical outcomes (RR: 1.19, 95% CI: 1.13–1.26, p < .001), poor short‐term complications (RR: 1.23, 95% CI: 1.09–1.38, p = .001), and poor long‐term prognosis (RR: 1.27, 95% CI: 1.13–1.44, p < .001). Anxiety was also specifically associated with long‐term mortality (RR: 1.16, 95% CI: 1.01–1.33, p = .033) and long‐term MACEs (RR: 1.54, 95% CI: 1.26–1.90, p < .001). This study provided strong evidence that increased anxiety was associated with poor prognosis in patients with MI. Further analysis revealed that MI patients with anxiety had a 23% increased risk of short‐term complications and a 27% increased risk of adverse long‐term prognosis compared to those without anxiety.     

Impact of regionalizing ST‐elevation myocardial infarction care on sex differences in reperfusion times and clinical outcomes

BackgroundWomen with ST‐elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention historically experience worse in‐hospital outcomes compared to men.HypothesisImplementation of a regional STEMI system will reduce care gaps in reperfusion times and in‐hospital outcomes between women and men.Methods1928 patients (413 women, 21.4%) presented with an acute STEMI between June 2007 and March 2016. The population was divided into an early cohort (n = 728 patients, 2007‐May 2011), and a late cohort (n = 1200 patients, June 2011–2016). The primary endpoints evaluated were reperfusion times and in‐hospital outcomes.ResultsCompared to men, women experienced significant delays in first medical contact (FMC) to arrival at the emergency room (26.0 vs. 22.0 min, p < 0.001) and FMC‐to‐device (109 vs. 101 min p = 0.001). Women had higher incidences of post‐PCI heart failure and death compared to men (p < 0.05). Following multivariable adjustment, no mortality difference was observed for women versus men (adjusted OR; 0.82; 95% confidence interval [CI], 0.51–1.34; p = 0.433) or for early versus late cohorts (adjusted OR; 1.04; 95% CI, 0.68–1.60; p = 0.856).ConclusionFollowing STEMI regionalization, women continued to experience significantly longer reperfusion times, although there was no difference in adjusted mortality. These results highlight the ongoing disparity of STEMI care between women and men, and suggest that regionalization alone is insufficient to close sex‐based care gaps.