-
1.
Impact of the presence of heart disease, cardiovascular medications and cardiac events on outcome in COVID-19.
Cabezón Villalba, G, Amat-Santos, IJ, Dueñas, C, Lopez Otero, D, Catala, P, Aparisi, A, López-Pais, J, Cacho Antonio, CE, Candela, J, Antúnez Muiños, P, et al
Cardiology journal. 2021;(3):360-368
Abstract
BACKGROUND Cardiovascular risk factors and usage of cardiovascular medication are prevalent among coronavirus disease 2019 (COVID-19) patients. Little is known about the cardiovascular implications of COVID-19. The goal herein, was to evaluate the prognostic impact of having heart disease (HD) and taking cardiovascular medications in a population diagnosed of COVID-19 who required hospitalization. Also, we studied the development of cardiovascular events during hospitalization. METHODS Consecutive patients with definitive diagnosis of COVID-19 made by a positive real time- -polymerase chain reaction of nasopharyngeal swabs who were admitted to the hospital from March 15 to April 14 were included in a retrospective registry. The association of HD with mortality and with mortality or respiratory failure were the primary and secondary objectives, respectively. RESULTS A total of 859 patients were included in the present analysis. Cardiovascular risk factors were related to death, particularly diabetes mellitus (hazard ratio in the multivariate analysis: 1.810 [1.159- -2.827], p = 0.009). A total of 113 (13.1%) patients had HD. The presence of HD identified a group of patients with higher mortality (35.4% vs. 18.2%, p < 0.001) but HD was not independently related to prognosis; renin-angiotensin-aldosterone system inhibitors, calcium channel blockers, diuretics and beta-blockers did not worsen prognosis. Statins were independently associated with decreased mortality (0.551 [0.329-0.921], p = 0.023). Cardiovascular events during hospitalization identified a group of patients with poor outcome (mortality 31.8% vs. 19.3% without cardiovascular events, p = 0.007). CONCLUSIONS The presence of HD is related to higher mortality. Cardiovascular medications taken before admission are not harmful, statins being protective. The development of cardiovascular events during the course of the disease is related to poor outcome.
-
2.
Ivabradine for chronic heart rate control in persistent atrial fibrillation. Design of the BRAKE-AF project.
Fontenla, A, López-Gil, M, Tamargo-Menéndez, J, Matía-Francés, R, Salgado-Aranda, R, Rey-Blas, JR, Miracle-Blanco, Á, Mejía-Martínez, E, Pastor-Fuentes, A, Toquero-Ramos, J, et al
Revista espanola de cardiologia (English ed.). 2020;(5):368-375
Abstract
INTRODUCTION AND OBJECTIVES Ivabradine is an inhibitor of the If channel, the main determinant of the pacemaker function of the sinus node. The drug has been approved for the treatment of angina and heart failure. There is some evidence of its role as an inhibitor of atrial-ventricular node (AVN) conduction. The aim of the BRAKE-AF project is to assess ivabradine use for rate control in atrial fibrillation (AF). METHODS A multicenter, randomized, parallel, open-label, noninferiority phase III clinical trial will be conducted to compare ivabradine vs digoxin in 232 patients with uncontrolled permanent AF despite beta-blockers or calcium channel blockers. The primary efficacy endpoint is the reduction in daytime heart rate measured by 24-hour Holter monitoring at 3 months. This clinical trial will be supported by an electrophysiological study of the effect of ivabradine on the action potential of the human AVN. To do this, an experimental model will be used with Chinese hamster ovarium cells transfected with the DNA encoding the expression of the t channels involved in this action potential and recording of the ionic currents with patch clamp techniques. RESULTS New data will be obtained on the effect of ivabradine on the human AVN and its safety and efficacy in patients with permanent AF. CONCLUSIONS The results of the BRAKE-AF project might allow inclusion of ivabradine within the limited arsenal of drugs currently available for rate control in AF. CLINICAL TRIAL REGISTRATION http://www.clinicaltrials.gov. Identifier: NCT03718273.
-
3.
Baseline characteristics of patients with heart failure with preserved ejection fraction in the EMPEROR-Preserved trial.
Anker, SD, Butler, J, Filippatos, G, Shahzeb Khan, M, Ferreira, JP, Bocchi, E, Böhm, M, Brunner-La Rocca, HP, Choi, DJ, Chopra, V, et al
European journal of heart failure. 2020;(12):2383-2392
-
-
Free full text
-
Abstract
AIMS: EMPEROR-Preserved is an ongoing trial evaluating the effect of empagliflozin in patients with heart failure with preserved ejection fraction (HFpEF). This report describes the baseline characteristics of the EMPEROR-Preserved cohort and compares them with patients enrolled in prior HFpEF trials. METHODS AND RESULTS EMPEROR-Preserved is a phase III randomized, international, double-blind, parallel-group, placebo-controlled trial in which 5988 symptomatic HFpEF patients [left ventricular ejection fraction (LVEF) >40%] with and without type 2 diabetes mellitus (T2DM) have been enrolled. Patients were required to have elevated N-terminal pro B-type natriuretic peptide (NT-proBNP) concentrations (i.e. >300 pg/mL in patients without and >900 pg/mL in patients with atrial fibrillation) along with evidence of structural changes in the heart or documented history of heart failure hospitalization. Among patients enrolled from various regions (45% Europe, 11% Asia, 25% Latin America, 12% North America), the mean age was 72 ± 9 years, 45% were women. Almost all patients had New York Heart Association class II or III symptoms (99.6%), and 23% had prior heart failure hospitalization within 12 months. Thirty-three percent of the patients had baseline LVEF of 41-50%. The mean LVEF (54 ± 9%) was slightly lower while the median NT-proBNP [974 (499-1731) pg/mL] was higher compared with previous HFpEF trials. Presence of comorbidities such as diabetes (49%) and chronic kidney disease (50%) were common. The majority of the patients were on angiotensin-converting enzyme inhibitors/angiotensin receptor blockers/angiotensin receptor-neprilysin inhibitors (80%) and beta-blockers (86%), and 37% of patients were on mineralocorticoid receptor antagonists. CONCLUSION When compared with prior trials in HFpEF, the EMPEROR-Preserved cohort has a somewhat higher burden of comorbidities, lower LVEF, higher median NT-proBNP and greater use of mineralocorticoid receptor antagonists at baseline. Results of the EMPEROR-Preserved trial will be available in 2021.
-
4.
Prediction of Residual Risk by Ceramide-Phospholipid Score in Patients With Stable Coronary Heart Disease on Optimal Medical Therapy.
Hilvo, M, Wallentin, L, Ghukasyan Lakic, T, Held, C, Kauhanen, D, Jylhä, A, Lindbäck, J, Siegbahn, A, Granger, CB, Koenig, W, et al
Journal of the American Heart Association. 2020;(10):e015258
Abstract
Background Identification of patients with stable coronary heart disease who are at significant residual risk could be helpful for targeted prevention. Our aim was to determine the prognostic value of the recently introduced ceramide- and phospholipid-based risk score, the Cardiovascular Event Risk Test (CERT2), in patients with stable coronary heart disease on optimal medical therapy and to identify biological processes that contribute to the CERT2 score. Methods and Results Plasma samples (n=11 222) obtained from the STABILITY (Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy) trial were analyzed using a tandem liquid chromatography-mass spectrometry method. STABILITY was a trial in patients with stable coronary heart disease randomized to the lipoprotein-associated phospholipase A2 inhibitor darapladib or placebo on optimized medical therapy at baseline, with a median follow-up of 3.7 years. Hazard ratios per SD for the CERT2 risk score were 1.32 (95% CI, 1.25-1.39) for major adverse cardiovascular event, 1.47 (95% CI, 1.35-1.59) for cardiovascular death, 1.32 (95% CI, 1.16-1.49) for stroke, 1.23 (95% CI, 1.14-1.33) for myocardial infarction, and 1.56 (95% CI, 1.39-1.76) for hospitalization due to heart failure, when adjusted for traditional cardiovascular risk factors. CERT2 showed correlation (P<0.001, r>0.2) with inflammatory markers high-sensitivity C-reactive protein, interleukin 6, the heart failure marker N-terminal pro-B-type natriuretic peptide, and low-density lipoprotein cholesterol. After also adjusting for levels of other prognostic biomarkers, the CERT2 score was still independently related to the risk of cardiovascular death but not to nonfatal events. Conclusions The CERT2 risk score can detect residual risk in patients with stable coronary heart disease and is associated with biomarkers indicating inflammation, myocardial necrosis, myocardial dysfunction, renal dysfunction, and dyslipidemia. REGISTRATION URL https://www.clinicaltrials.gov. Unique identifier: NCT00799903.
-
5.
Antithrombotic Therapy in Patients With Atrial Fibrillation and Acute Coronary Syndrome Treated Medically or With Percutaneous Coronary Intervention or Undergoing Elective Percutaneous Coronary Intervention: Insights From the AUGUSTUS Trial.
Windecker, S, Lopes, RD, Massaro, T, Jones-Burton, C, Granger, CB, Aronson, R, Heizer, G, Goodman, SG, Darius, H, Jones, WS, et al
Circulation. 2019;(23):1921-1932
Abstract
BACKGROUND The safety and efficacy of antithrombotic regimens may differ between patients with atrial fibrillation who have acute coronary syndromes (ACS), treated medically or with percutaneous coronary intervention (PCI), and those undergoing elective PCI. METHODS Using a 2×2 factorial design, we compared apixaban with vitamin K antagonists and aspirin with placebo in patients with atrial fibrillation who had ACS or were undergoing PCI and were receiving a P2Y12 inhibitor. We explored bleeding, death and hospitalization, as well as death and ischemic events, by antithrombotic strategy in 3 prespecified subgroups: patients with ACS treated medically, patients with ACS treated with PCI, and those undergoing elective PCI. RESULTS Of 4614 patients enrolled, 1097 (23.9%) had ACS treated medically, 1714 (37.3%) had ACS treated with PCI, and 1784 (38.8%) had elective PCI. Apixaban compared with vitamin K antagonist reduced International Society on Thrombosis and Haemostasis major or clinically relevant nonmajor bleeding in patients with ACS treated medically (hazard ratio [HR], 0.44 [95% CI, 0.28-0.68]), patients with ACS treated with PCI (HR, 0.68 [95% CI, 0.52-0.89]), and patients undergoing elective PCI (HR, 0.82 [95% CI, 0.64-1.04]; Pinteraction=0.052) and reduced death or hospitalization in the ACS treated medically (HR, 0.71 [95% CI, 0.54-0.92]), ACS treated with PCI (HR, 0.88 [95% CI, 0.74-1.06]), and elective PCI (HR, 0.87 [95% CI, 0.72-1.04]; Pinteraction=0.345) groups. Compared with vitamin K antagonists, apixaban resulted in a similar effect on death and ischemic events in the ACS treated medically, ACS treated with PCI, and elective PCI groups (Pinteraction=0.356). Aspirin had a higher rate of bleeding than did placebo in patients with ACS treated medically (HR, 1.49 [95% CI, 0.98-2.26]), those with ACS treated with PCI (HR, 2.02 [95% CI, 1.53-2.67]), and those undergoing elective PCI (HR, 1.91 [95% CI, 1.48-2.47]; Pinteraction=0.479). For the same comparison, there was no difference in outcomes among the 3 groups for the composite of death or hospitalization (Pinteraction=0.787) and death and ischemic events (Pinteraction=0.710). CONCLUSIONS An antithrombotic regimen consisting of apixaban and a P2Y12 inhibitor without aspirin provides superior safety and similar efficacy in patients with atrial fibrillation who have ACS, whether managed medically or with PCI, and those undergoing elective PCI compared with regimens that include vitamin K antagonists, aspirin, or both. CLINICAL TRIAL REGISTRATION URL: https://www.clinicaltrials.gov. Unique identifier: NCT02415400.
-
6.
Healthy Behavior, Risk Factor Control, and Survival in the COURAGE Trial.
Maron, DJ, Mancini, GBJ, Hartigan, PM, Spertus, JA, Sedlis, SP, Kostuk, WJ, Berman, DS, Teo, KK, Weintraub, WS, Boden, WE, et al
Journal of the American College of Cardiology. 2018;(19):2297-2305
Abstract
BACKGROUND Individual risk factor control improves survival in patients with stable ischemic heart disease (SIHD). It is uncertain if multiple risk factor control further extends survival. OBJECTIVES This study determined whether a greater number of risk factors at goal predicted improved survival in SIHD patients. METHODS Of 2,287 participants in the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) trial, 2,102 (92%) had complete ascertainment of 6 pre-specified risk factors: systolic blood pressure, low-density lipoprotein cholesterol, smoking, physical activity, diet, and body mass index. Participants received interventions to control these risk factors. The outcome measure was mortality. RESULTS During a mean follow-up of 6.8 years, 473 (22.5%) subjects died. In univariate analysis, the greater the number of risk factors controlled, the higher the probability of survival (unadjusted log rank: p < 0.001). In multivariate analysis, the strongest predictors at 1 year of improved survival were being a nonsmoker, regular physical activity, having a systolic blood pressure <130 mm Hg, and following the American Heart Association Step 2 diet. Baseline risk factor values and evidence-based medications did not independently predict survival once risk factor control at 1 year was included in the model. Having 4 to 6 risk factors compared with 0 to 1 risk factor at goal predicted lower mortality (hazard ratios for 4 and 6 controlled risk factors: 0.64; 95% confidence interval: 0.41 to 0.98, and 0.27; 95% confidence interval: 0.09 to 0.79, respectively). CONCLUSIONS The greater the number of risk factors in control, the higher the probability of survival in patients with SIHD. More effective strategies are needed to achieve comprehensive risk factor control, including healthy behaviors. (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation [COURAGE]; NCT00007657).
-
7.
Deprescribing preventive cardiovascular medication in patients with predicted low cardiovascular disease risk in general practice - the ECSTATIC study: a cluster randomised non-inferiority trial.
Luymes, CH, Poortvliet, RKE, van Geloven, N, de Waal, MWM, Drewes, YM, Blom, JW, Smidt, N, Assendelft, WJJ, van den Hout, WB, de Ruijter, W, et al
BMC medicine. 2018;(1):5
Abstract
BACKGROUND The use of cardiovascular medication for the primary prevention of cardiovascular disease (CVD) is potentially inappropriate when potential risks outweigh the potential benefits. It is unknown whether deprescribing preventive cardiovascular medication in patients without a strict indication for such medication is safe and cost-effective in general practice. METHODS In this pragmatic cluster randomised controlled non-inferiority trial, we recruited 46 general practices in the Netherlands. Patients aged 40-70 years who were using antihypertensive and/or lipid-lowering drugs without CVD and with low risk of future CVD were followed for 2 years. The intervention was an attempt to deprescribe preventive cardiovascular medication. The primary outcome was the difference in the increase in predicted (10-year) CVD risk in the per-protocol (PP) population with a non-inferiority margin of 2.5 percentage points. An economic evaluation was performed in the intention-to-treat (ITT) population. We used multilevel (generalised) linear regression with multiple imputation of missing data. RESULTS Of 1067 participants recruited between 7 November 2012 and 18 February 2014, 72% were female. Overall, their mean age was 55 years and their mean predicted CVD risk at baseline was 5%. Of 492 participants in the ITT intervention group, 319 (65%) quit the medication (PP intervention group); 135 (27%) of those participants were still not taking medication after 2 years. The predicted CVD risk increased by 2.0 percentage points in the PP intervention group compared to 1.9 percentage points in the usual care group. The difference of 0.1 (95% CI -0.3 to 0.6) fell within the non-inferiority margin. After 2 years, compared to the usual care group, for the PP intervention group, systolic blood pressure was 6 mmHg higher, diastolic blood pressure was 4 mmHg higher and total cholesterol and low-density lipoprotein-cholesterol levels were both 7 mg/dl higher (all P < 0.05). Cost and quality-adjusted life years did not differ between the groups. CONCLUSIONS The results of the ECSTATIC study show that an attempt to deprescribe preventive cardiovascular medication in low-CVD-risk patients is safe in the short term when blood pressure and cholesterol levels are monitored after stopping. An attempt to deprescribe medication can be considered, taking patient preferences into consideration. TRIAL REGISTRATION This study was registered with Dutch trial register on 20 June 2012 ( NTR3493 ).
-
8.
Current management and treatment of patients with stable coronary artery diseases presenting to cardiologists in different clinical contexts: A prospective, observational, nationwide study.
De Luca, L, Temporelli, PL, Lucci, D, Gonzini, L, Riccio, C, Colivicchi, F, Geraci, G, Formigli, D, Maras, P, Falcone, C, et al
European journal of preventive cardiology. 2018;(1):43-53
Abstract
Background Stable coronary artery disease (CAD) is a leading cause of mortality worldwide. Few studies document the complete sequence of investigation of the overall stable CAD population during outpatient visits or hospitalisation. Aim To obtain accurate and up-to-date information on current management of patients with stable CAD. Methods START (STable coronary Artery diseases RegisTry) was a prospective, observational, nationwide study aimed at evaluating the presentation, management, treatment and quality of life of stable CAD patients presenting to cardiologists during outpatient visits or discharged from cardiology wards. Results Over a 3-month period, 5070 consecutive patients were enrolled in 183 participating centres: 72% managed by a cardiologist during outpatient or day hospital visits and 28% discharged from cardiology wards. The vast majority of patients (87%) received a coronary angiography (86% of patients managed during outpatient visits and 90% during hospitalisation; p < 0.0001). Outpatients more frequently received optimal medical therapy (OMT; i.e. aspirin or thienopyridine, β-blockers and statins) compared to hospitalised patients (70.2% vs 67.1%; p = 0.03). A personalised diet was prescribed in 58% (60.5% in outpatients and 52.9% in those admitted to hospitals; p < 0.0001), physical activity programmes were suggested in 65% (69.4% and 54.3%; p < 0.0001) and smoking cessation was recommended in 71% of currently smoking patients (73.2% and 65.2%; p = 0.02). Conclusions In this large, contemporary registry, patients with stable CAD discharged from cardiology wards more commonly underwent diagnostic imaging procedures and less frequently received OMT or lifestyle modification programmes compared to patients manged by cardiologists during outpatient visits.
-
9.
Impact of switching to polypill based therapy by baseline potency of medication: Post-hoc analysis of the SPACE Collaboration dataset.
Webster, R, Bullen, C, Patel, A, Selak, V, Stepien, S, Thom, S, Rodgers, A
International journal of cardiology. 2017;:443-447
-
-
Free full text
-
Abstract
BACKGROUND Fixed dose combinations of cardiovascular therapy ('polypills') have now been launched in several dozen countries. There is considerable clinical interest in the effects of switching to polypill-based care from typical current treatment regimens, especially if polypills contain components at sub-maximal dosage. METHODS The SPACE Collaboration includes three trials of polypill based care vs usual care in patients with established CVD or at high calculated risk. Individual patient data for 3140 trial participants were combined. Patients were categorized according to the potency of the statin and the number of BP lowering medications they were taking at baseline. Effects on adherence to anti-platelet medication, systolic blood pressure (SBP) and LDL cholesterol stratified by baseline potency of medication were determined using fixed effects models. RESULTS Randomisation to the polypill group was associated with improved SBP at 12months, but this improvement varied according to baseline BP regimen: -3.3, -5.9, -2.5 and +1mmHg for patients taking 0, 1, 2 and 3+ BP lowering medications at baseline. For changes in LDL cholesterol at 12months, significant improvements in LDL cholesterol were seen for those taking no statin (-0.21mmol/L; 95% CI: -0.34 to -0.07), less potent statin (-0.16mmol/L; 95% CI: -0.29 to -0.04) and equipotent statins (-0.14mmol/L; 95% CI -0.26 to -0.02) at baseline. CONCLUSION The adherence benefits of polypills tend to offset the loss of potency from use of individual components with lower dose potency, and to facilitate improvements in multiple risk factors.
-
10.
Cardiovascular medication and intraocular pressure: results from the Gutenberg Health Study.
Höhn, R, Mirshahi, A, Nickels, S, Schulz, A, Wild, PS, Blettner, M, Pfeiffer, N
The British journal of ophthalmology. 2017;(12):1633-1637
Abstract
BACKGROUND Intraocular pressure (IOP) is well known to be associated with blood pressure and other cardiovascular risk factors. The influence of systemic cardiovascular, in particular antihypertensive, medication on IOP is still controversial. This study analyses the association between the use of cardiovascular medications and IOP in a large European cohort. METHODS The Gutenberg Health Study is a population-based, prospective,observational cohort study in mid-western Germany. IOP was measured using a non-contact tonometer. The medication classes examined were peripheral vasodilators, diuretics, β-blockers (overall, selective and non-selective), calcium channel blockers, renin-angiotensin blockers (overall, ACE inhibitors and angiotensin-receptor blockers), nitrates, other antihypertensive medications, aspirin and statins. Subjects with missing IOP values, topical IOP-lowering medication or previous ocular surgery were excluded. In total, 13 527 subjects were enrolled in this study. Association analyses between medication use and IOP were performed using multivariable linear regression (p<0.0038). RESULTS Neither selective nor non-selective systemic β-blocker intake was associated with statistically significant lower IOP (-0.12 mm Hg, p=0.054 and -0.70 mm Hg, p=0.037, respectively). IOP was not associated with the use of ACE inhibitors after adjustment for body mass index, systolic blood pressure and central corneal thickness (0.11 mm Hg; p=0.07). CONCLUSIONS None of the cardiovascular medications, in particular systemic β-blocking agents, showed an association with IOP in non-glaucoma subjects. The long-term drift phenomenon of topical and systemic β-blocker might explain this result. Our results suggest that systemic β-blockers have a negligible effect on IOP reduction.