Journal: Eur Heart J Cardiovasc Pharmacother

Sorted by: date / impact
Abstract

Patients selected for dual pathway inhibition in clinical practice have similar characteristics and outcomes to those included in the COMPASS randomized trial: The XATOA Registry.

Fox KAA, Aboyans V, Debus ES, Zeymer U, ... Vogtländer K, Anand SS
Aims
To determine the characteristics of patients with coronary artery disease (CAD), peripheral artery disease (PAD), or both, initiating dual pathway inhibition (DPI) using rivaroxaban 2.5 mg twice daily plus aspirin, and to report their clinical outcomes and bleeding rates in clinical practice compared to the COMPASS randomized trial, which provided the basis for using DPI in this patient population.
Methods and results
XATOA is a prospective registry of 5532 patients: of which, 72.7% had CAD, 58.9% had PAD, and 31.6% had both. The mean age of patients was 68 years and 25.5% were women. The mean follow-up period was 15 months. The most frequently reported reason for initiating DPI was the presence of existing, worsening or newly diagnosed risk characteristics (n = 4753, 85.9%). Before initiating DPI, 75.3% received a single antiplatelet and 18.3% received various antiplatelet combinations. The incidence of major adverse cardiovascular events (MACE), major adverse limb events (MALE) and acute or severe limb ischaemia was 2.26, 3.57, and 1.54 per 100 patient-years, respectively, among the 5532 patients in XATOA. Corresponding rates in COMPASS were 2.18, 0.19, and 0.12 per 100 patient-years, respectively. Major bleeding rates were 0.95 and 1.67 per 100 patient-years in XATOA and COMPASS, respectively.
Conclusion
High-risk vascular patients are prioritized for DPI in clinical practice, and rates of MACE are similar to COMPASS, but MALE rates are higher in XATOA, consistent with the greater proportion of PAD patients. Major bleeding rates were lower in XATOA. The findings provide support for favourable net clinical benefit of DPI in high-risk vascular patients.
One-sentence summary
The characteristics of patients initiated on dual pathway inhibition (DPI: rivaroxaban 2.5  mg twice daily plus aspirin) have not previously been defined in clinical practice and the XATOA registry findings demonstrate patient outcomes are consistent with those of the COMPASS trial, despite geographic differences in recruitment and the higher proportion of PAD patients.

© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.

Eur Heart J Cardiovasc Pharmacother: 20 May 2022; epub ahead of print
Fox KAA, Aboyans V, Debus ES, Zeymer U, ... Vogtländer K, Anand SS
Eur Heart J Cardiovasc Pharmacother: 20 May 2022; epub ahead of print | PMID: 35594542
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Abstract

Associations between medical therapy after surgical aortic valve replacement for aortic stenosis and long-term mortality: a report from the SWEDEHEART registry.

Baranowska J, Törngren C, Nielsen SJ, Lindgren M, ... Jeppsson A, Martinsson A
Aims
The association between use of statins, renin-angiotensin system (RAS) inhibitors and/or β-blockers and long-term mortality in patients with aortic stenosis who underwent surgical aortic valve replacement (SAVR) is unknown.
Methods and results
All patients with aortic stenosis who underwent isolated first time SAVR in Sweden from 2006 to 2017 and survived six months after discharge were included. Individual patient data from four mandatory nationwide registries were merged. Cox proportional hazards models, with time-updated data on medication status and adjusted for age, sex, comorbidities, type of prosthesis, and year of surgery, were used to investigate associations between dispensed statins, RAS inhibitors, and β-blockers, and all-cause mortality. In total, 9553 patients were included, and median follow-up time was 4.9 years (range 0-11); 1738 patients (18.2%) died during follow-up. Statins were dispensed to 49.1% and 49.0% of the patients within six months of discharge from hospital and after ten years, respectively. Corresponding figures were 51.4% and 53.9% for RAS inhibitors, and 79.3% and 60.7% for β-blockers. Ongoing treatment was associated with lower mortality risk for statins [adjusted hazard ratio (aHR) 0.67 (95% confidence interval 0.60-0.74), p < 0.001] and RAS inhibitors [aHR 0.84 (0.76-0.93), p < 0.001] but not for β-blockers [aHR 1.17 (1.05-1.30), p = 0.004]. The associations were robust in subgroups based on age, sex, and comorbidities (p for interactions > 0.05).
Conclusions
The results of this large population-based real-world study support the use of statins and RAS inhibitors for patients who underwent SAVR due to aortic stenosis.

© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.

Eur Heart J Cardiovasc Pharmacother: 18 May 2022; epub ahead of print
Baranowska J, Törngren C, Nielsen SJ, Lindgren M, ... Jeppsson A, Martinsson A
Eur Heart J Cardiovasc Pharmacother: 18 May 2022; epub ahead of print | PMID: 35583235
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Abstract

Recombinant human lecithin-cholesterol acyltransferase in patients with atherosclerosis: phase 2a primary results and phase 2b design.

Bonaca MP, George RT, Morrow DA, Bergmark BA, ... Hsia J, Sabatine MS
Aims
Reverse cholesterol transport (RCT) removes cholesterol and stabilizes vulnerable plaques. In addition, high-density lipoprotein (HDL) may be cardioprotective in acute myocardial infarction (MI). Lecithin-cholesterol acyltransferase (LCAT) may enhance RCT. The objective of this study was to investigate the pharmacokinetics, pharmacodynamics, and safety of multiple ascending doses of recombinant human LCAT (MEDI6012) to inform a Phase 2b programme.
Methods and results
This was a randomized, blinded, placebo-controlled, dose-escalation Phase 2a study of MEDI6012. Patients were randomized into one of four cohorts (40, 120, 300 mg IV weekly ×3 doses, or 300 mg IV-push, 150 mg at 48 h and 100 mg at 7 days). All cohorts were planned to randomize 6:2 (MEDI6012 vs. placebo). The primary endpoints were baseline-adjusted area under the curve (AUC) from 0 to 96 h post dose 3 (AUC 0-96 h) for HDL-C, HDL cholesteryl ester (HDL-CE), and total cholesteryl ester (CE). The primary safety endpoints were treatment-emergent adverse events. A total of 32 patients were randomized. MEDI6012 significantly increased AUC 0-96 h for HDL-C, HDL-CE and CE in a graded fashion with increasing doses. Relative to placebo, MEDI6012 increased HDL-C at Day 19 by 66% (95% CI 33-99, P = 0.014) with 120 mg and 144% (95% CI 108-181, P < 0.001) with 300 mg. An IV-push increased HDL-C by 40.8% at 30 min. Overall adverse events were similar between groups with no severe, life-threatening/fatal adverse events, or neutralizing antibodies.
Conclusions
Multiple ascending doses of MEDI6012 were safe and well tolerated and significantly increased HDL-C, HDL-CE and CE in a dose-related manner. These data support the ongoing Phase 2b programme investigating MEDI6012 in ST-elevation MI.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021.

Eur Heart J Cardiovasc Pharmacother: 05 May 2022; 8:243-252
Bonaca MP, George RT, Morrow DA, Bergmark BA, ... Hsia J, Sabatine MS
Eur Heart J Cardiovasc Pharmacother: 05 May 2022; 8:243-252 | PMID: 33493256
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Abstract

Epinephrine administration for adult out-of-hospital cardiac arrest patients with refractory shockable rhythm: time-dependent propensity score-sequential matching analysis from a nationwide population-based registry.

Matsuyama T, Komukai S, Izawa J, Gibo K, ... Ohta B, Kitamura T
Aims
Little is known about the effect of prehospital epinephrine administration in out-of-hospital cardiac arrest (OHCA) patients with refractory shockable rhythm, for whom initial defibrillation was unsuccessful.
Methods and results
This study using Japanese nationwide population-based registry included all adult OHCA patients aged ≥18 years with refractory shockable rhythm between January 2014 and December 2017. Patients with or without epinephrine during cardiac arrest were sequentially matched using a risk set matching based on the time-dependent propensity scores within the same minute. The primary outcome was 1-month survival. The secondary outcomes included 1-month survival with favourable neurological outcome (cerebral performance category scale: 1 or 2) and prehospital return of spontaneous circulation (ROSC). Of the 499 944 patients registered in the database during the study period, 22 877 were included. Among them, 8467 (37.0%) received epinephrine. After time-dependent propensity score-sequential matching, 16 798 patients were included in the matched cohort. In the matched cohort, positive associations were observed between epinephrine and 1-month survival [epinephrine: 17.3% (1454/8399) vs. no epinephrine: 14.6% (1224/8399); RR 1.22 (95% confidence interval, CI: 1.13-1.32)] and prehospital ROSC [epinephrine: 22.2% (1868/8399) vs. no epinephrine: 10.7% (900/8399); RR 2.07 (95% CI: 1.91-2.25)]. No significant positive association was observed between epinephrine and favourable neurological outcome [epinephrine: 7.8% (654/8399) vs. no epinephrine: 7.1% (611/8399); RR 1.13 (95% CI 0.998-1.27)].
Conclusion
Using the nationwide population-based registry with time-dependent propensity score-sequential matching analysis, prehospital epinephrine administration in adult OHCA patients with refractory shockable rhythm was positively associated with 1-month survival and prehospital ROSC.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021.

Eur Heart J Cardiovasc Pharmacother: 05 May 2022; 8:263-271
Matsuyama T, Komukai S, Izawa J, Gibo K, ... Ohta B, Kitamura T
Eur Heart J Cardiovasc Pharmacother: 05 May 2022; 8:263-271 | PMID: 33599265
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Abstract

Treatment of Fabry Disease management with migalastat-outcome from a prospective 24 months observational multicenter study (FAMOUS).

Lenders M, Nordbeck P, Kurschat C, Eveslage M, ... Canaan-Kühl S, Brand E
Aims
Fabry disease (FD) is an X-linked lysosomal storage disorder caused by a deficiency of the lysosomal enzyme α-galactosidase A (GLA/AGAL), resulting in the lysosomal accumulation of globotriaosylceramide (Gb3). Patients with amenable GLA mutations can be treated with migalastat, an oral pharmacological chaperone increasing endogenous AGAL activity. In this prospective observational multicentre study, safety as well as cardiovascular, renal, and patient-reported outcomes and disease biomarkers were assessed after 12 and 24 months of migalastat treatment under \'real-world\' conditions.
Methods and results
A total of 54 patients (26 females) (33 of these [61.1%] pre-treated with enzyme replacement therapy) with amenable mutations were analysed. Treatment was generally safe and well tolerated. A total of 153 events per 1000 patient-years were detected. Overall left ventricular mass index decreased after 24 months (all: -7.5 ± 17.4 g/m2, P = 0.0118; females: -4.6 ± 9.1 g/m2, P = 0.0554; males: -9.9 ± 22.2 g/m2, P = 0.0699). After 24 months, females and males presented with a moderate yearly loss of estimated glomerular filtration rate (-2.6 and -4.4 mL/min/1.73 m2 per year; P = 0.0317 and P = 0.0028, respectively). FD-specific manifestations/symptoms remained stable (all P > 0.05). A total of 76.9% of females and 50% of males suffered from pain, which has not improved under treatment. FD-specific disease scores (Disease Severity Scoring System and Mainz Severity Score Index) remained stable during treatment. AGAL activities and plasma lyso-Gb3 values remained stable, although some male patients presented with increasing lyso-Gb3 levels over time.
Conclusions
Treatment with migalastat was generally safe and resulted in most patients in an amelioration of left ventricular mass. However, due to the heterogeneity of FD phenotypes, it is advisable that the treating physician monitors the clinical response regularly.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021.

Eur Heart J Cardiovasc Pharmacother: 05 May 2022; 8:272-281
Lenders M, Nordbeck P, Kurschat C, Eveslage M, ... Canaan-Kühl S, Brand E
Eur Heart J Cardiovasc Pharmacother: 05 May 2022; 8:272-281 | PMID: 35512362
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Abstract

Rationale and design of the pragmatic clinical trial tREatment with Beta-blockers after myOcardial infarction withOut reduced ejection fracTion (REBOOT).

Rossello X, Raposeiras-Roubin S, Latini R, Dominguez-Rodriguez A, ... Ibáñez B, REBOOT-CNIC investigators
Aims
There is a lack of evidence regarding the benefits of β-blocker treatment after invasively managed acute myocardial infarction (MI) without reduced left ventricular ejection fraction (LVEF).
Methods and results
The tREatment with Beta-blockers after myOcardial infarction withOut reduced ejection fracTion (REBOOT) trial is a pragmatic, controlled, prospective, randomized, open-label blinded endpoint (PROBE design) clinical trial testing the benefits of β-blocker maintenance therapy in patients discharged after MI with or without ST-segment elevation. Patients eligible for participation are those managed invasively during index hospitalization (coronary angiography), with LVEF >40%, and no history of heart failure (HF). At discharge, patients will be randomized 1:1 to β-blocker therapy (agent and dose according to treating physician) or no β-blocker therapy. The primary endpoint is a composite of all-cause death, non-fatal reinfarction, or HF hospitalization over a median follow-up period of 2.75 years (minimum 2 years, maximum 3 years). Key secondary endpoints include the incidence of the individual components of the primary composite endpoint, the incidence of cardiac death, and incidence of malignant ventricular arrhythmias or resuscitated cardiac arrest. The primary endpoint will be analysed according to the intention-to-treat principle.
Conclusion
The REBOOT trial will provide robust evidence to guide the prescription of β-blockers to patients discharged after MI without reduced LVEF.

© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.

Eur Heart J Cardiovasc Pharmacother: 05 May 2022; 8:291-301
Rossello X, Raposeiras-Roubin S, Latini R, Dominguez-Rodriguez A, ... Ibáñez B, REBOOT-CNIC investigators
Eur Heart J Cardiovasc Pharmacother: 05 May 2022; 8:291-301 | PMID: 34351426
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Abstract

Effects of intensive urate lowering therapy with febuxostat in comparison with allopurinol on pulse wave velocity in patients with gout and increased cardiovascular risk: the FORWARD study.

Desideri G, Rajzer M, Gerritsen M, Nurmohamed MT, ... Tausche AK, Borghi C
Aims
Hyperuricaemia and gout are strongly related with traditional cardiovascular risk factors and vascular damage. This study aimed to assess whether febuxostat and allopurinol could differently influence carotid-femoral pulse wave velocity (cfPWV) in patients with gout and elevated serum uric acid (SUA) levels.
Methods and results
A multi-centre, multinational, phase IV, randomized, parallel-group, active-controlled, open-label trial with blind endpoints evaluation. One hundred and ninety-seven adults with gout and SUA levels ≥8 mg/dL were randomized to febuxostat or allopurinol in a 1:1 ratio for 36 weeks. The primary outcome was the comparison of the effects of febuxostat and allopurinol on changes in cfPWV. The mean cfPWV values at randomization and Week 36 were 8.69 and 9.00 m/s, respectively for subjects randomized to febuxostat and 9.02 and 9.05 m/s for subjects randomized to allopurinol. No statistically significant changes in cfPWV by treatment assignment were observed at any time point for any of the assessed parameters. More subjects who received febuxostat had serum urate concentrations ≤6 mg/dL following treatment (78.3% vs. 61.1% at Week 36, P = 0.0137). Treatment-emergent adverse events were reported by 51 (52.0%) patients randomized to febuxostat and 63 (62.5%) patients randomized to allopurinol. The majority of events were mild in both treatment groups and included gout flares and arthralgia.
Conclusion
In patients with gout and elevated SUA levels the arterial stiffness remained stable both with febuxostat and allopurinol. Febuxostat was more effective and faster than allopurinol in achieving the SUA target. Both treatments were safe and well tolerated.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021.

Eur Heart J Cardiovasc Pharmacother: 05 May 2022; 8:236-242
Desideri G, Rajzer M, Gerritsen M, Nurmohamed MT, ... Tausche AK, Borghi C
Eur Heart J Cardiovasc Pharmacother: 05 May 2022; 8:236-242 | PMID: 33410912
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Abstract

The cardiovascular effects of gonadotropin-releasing hormone antagonists in men with prostate cancer.

Cirne F, Aghel N, Petropoulos JA, Klotz L, ... Pinthus J, Leong DP
Aims
The aim of this study was to determine whether gonadotropin-releasing hormone (GnRH) antagonists (an emerging class of drugs to suppress testosterone synthesis in the treatment of prostate cancer) cause less adverse cardiovascular events than the more commonly use GnRH agonists.
Methods and results
We conducted a systematic review to identify all randomized, controlled trials in which a GnRH antagonist was compared with a GnRH agonist in men with prostate cancer. We identified 10 eligible studies including two different GnRH antagonists, degarelix (n = 1681) and relugolix (n = 734), which were compared with the GnRH agonists, leuprolide (n = 714) and goserelin (n = 600). The pooled risk ratios (95% confidence intervals) among GnRH antagonist recipients for adverse cardiovascular events, cardiovascular death, and all-cause mortality were 0.57 (0.39-0.81); 0.49 (0.25-0.96); and 0.48 (0.28-0.83), respectively. Important limitations of the included trials were their short duration of follow-up, unblinded study design and (in most of the studies) the identification of adverse cardiovascular events through safety reporting mechanisms rather than as a pre-specified outcome. There was no evidence of heterogeneity of findings among the studies.
Conclusions
There is consistent but methodologically limited data to suggest that GnRH antagonists-a relatively new class of androgen deprivation therapy for prostate cancer-cause significantly less cardiovascular adverse effects than the more frequently used GnRH agonists.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021.

Eur Heart J Cardiovasc Pharmacother: 05 May 2022; 8:253-262
Cirne F, Aghel N, Petropoulos JA, Klotz L, ... Pinthus J, Leong DP
Eur Heart J Cardiovasc Pharmacother: 05 May 2022; 8:253-262 | PMID: 33470403
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Abstract

Cost-effectiveness of ticagrelor in patients with type 2 diabetes and coronary artery disease: a European economic evaluation of the THEMIS trial.

Steg PG, Bhatt DL, James SK, Darlington O, ... Mellström C, McEwan P
Aims
To conduct a health economic evaluation of ticagrelor in patients with type 2 diabetes and coronary artery disease, from a multinational payer perspective. Cost-effectiveness and cost-utility of ticagrelor was evaluated in the overall THEMIS (effect of Ticagrelor on Health Outcomes in diabEtes Mellitus patients Intervention Study) trial population and in the predefined patient group with prior percutaneous coronary intervention.
Methods and results
A Markov model was developed to extrapolate patient outcomes over a lifetime horizon. The primary outcome was incremental cost-effectiveness ratios (ICERs), which was compared with conventional willing to pay (WTP) thresholds (47,000 €/quality-adjusted life year [QALY] in Sweden, 30,000 €/QALY in other countries).Treatment with ticagrelor resulted in QALY gains of up to 0.045 in the overall population and 0.099 in patients with PCI. Increased costs and benefits translated to ICERs ranged between €27,894 and €42,252/QALY across Sweden, Germany, Italy, and Spain in the overall population. In patients with prior PCI, estimated ICERs improved to €18,449, €20,632, €20,233, and €13,228/QALY in Sweden, Germany, Italy, and Spain, respectively, driven by higher event rates and treatment benefit.
Conclusion
Based on THEMIS results, ticagrelor plus aspirin compared with aspirin alone may be cost-effective in some European countries in patients with T2DM and CAD and no prior MI or stroke. Additionally, ticagrelor is likely to be cost-effective across European countries in patients with a history of PCI.

© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.

Eur Heart J Cardiovasc Pharmacother: 30 Apr 2022; epub ahead of print
Steg PG, Bhatt DL, James SK, Darlington O, ... Mellström C, McEwan P
Eur Heart J Cardiovasc Pharmacother: 30 Apr 2022; epub ahead of print | PMID: 35488865
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Abstract

The effect of CETP inhibitors on new-onset diabetes: a systematic review and meta-analysis.

Dangas K, Navar AM, Kastelein JJP
Background
Despite the increasing prevalence of type 2 diabetes, limited pharmacologic options are available for prevention. Cholesteryl ester transfer protein inhibitors (CETPi) have been studied primarily as a therapy to reduce cardiovascular disease, but have also been shown to reduce new-onset diabetes. As new trial data have become available, this meta-analysis examines the effect of CETP inhibitors on new-onset diabetes and related glycemic measures.
Methods
We searched MEDLINE, EMBASE, and Cochrane databases (all articles until March 4, 2021) for randomised controlled trials ≥one-year duration, with at least 500 participants, comparing CETPi to placebo, and that reported data on new-onset diabetes or related glycemic measures (haemoglobin A1C (HbA1C), fasting plasma glucose, insulin, Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)). A fixed effects meta-analysis model was applied to all eligible studies to quantify the effect of CETPi therapy on new-onset diabetes.
Results
Four RCTs (n = 75,102) were eligible for quantitative analysis of the effect of CETPi on new-onset diabetes. CETPi were found to significantly decrease the risk of new-onset diabetes by 16% (RR:0.84; 95%CI:0.78,0.91; p<0.001), with low between-trial heterogeneity (I2 = 4.1%). Glycemic measures were also significantly improved or trended towards improvement in those with and without diabetes across most trials.
Conclusions
Although RCTs have shown mixed results regarding the impact of CETPi on cardiovascular disease, they have shown a consistent reduction in the risk of new-onset diabetes with CETPi therapy. Future trials of CETPi and potentially other HDL-raising agents should therefore specify new-onset diabetes and reversal of existing T2DM as secondary endpoints.

© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.

Eur Heart J Cardiovasc Pharmacother: 20 Apr 2022; epub ahead of print
Dangas K, Navar AM, Kastelein JJP
Eur Heart J Cardiovasc Pharmacother: 20 Apr 2022; epub ahead of print | PMID: 35441656
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Abstract

Effects of renin-angiotensin system inhibitor type and dosage on survival after transcatheter aortic valve implantation.

Fischer-Rasokat U, Bänsch C, Renker M, Rolf A, ... Hamm CW, Kim WK
Aims
The objective of the study was to determine the effect of renin-angiotensin system inhibitors (RASI) on the survival of subgroups of patients with aortic stenosis after transcatheter aortic valve implantation (TAVI) and to assess the impact of types and dosages of RASI on outcomes.
Methods and results
This single-center, retrospective analysis included 2862 patients (n = 2227 with RASI and n = 635 without) after successful TAVI. Propensity-score matching established comparable patient populations (n = 625 per group). Survival was analyzed by Kaplan-Meier curves and Cox regression and was corrected for baseline, procedural, and medical parameters. Self-reported adherence to RASI therapy three months after hospital discharge was 94%. Three-year all-cause mortality rates were 12.3% and 20.2% for patients with or without RASI, respectively (log-rank < 0.001). In the matched study populations mortality rates were 14.2% vs. 20.0% (log-rank < 0.03). RASI was particularly beneficial in patients with ejection fraction < 40% (adjusted hazard ratio [HR] and 95% confidence interval 0.50 [0.29-0.87]), EuroScore II ≥ 4% (HR 0.47 [0.35-0.65]), or low-flow, low-gradient aortic stenosis (HR 0.53 [0.31-0.93]) who were also on beta-blockers and statins. An association between discharge dosage and survival was observed, with HR 0.75 (0.58-0.96) and 0.57 (0.44-0.72) for patients on < 50% and ≥ 50% target dose, respectively. Angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) reduced mortality rates similarly (13.9% vs. 9.8%, log-rank 0.103).
Conclusions
The beneficial association between RASI after TAVI and improved survival during follow-up is particularly evident in high-risk patients and may be dose dependent. No superiority was noted in the effectiveness of ACEI or ARB.

© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.

Eur Heart J Cardiovasc Pharmacother: 20 Apr 2022; epub ahead of print
Fischer-Rasokat U, Bänsch C, Renker M, Rolf A, ... Hamm CW, Kim WK
Eur Heart J Cardiovasc Pharmacother: 20 Apr 2022; epub ahead of print | PMID: 35441662
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Abstract

Antiplatelet effect, safety, and pharmacokinetics of vicagrel in patients with coronary artery disease undergoing percutaneous coronary intervention.

Zhao X, Ma S, Kang Y, Tang C, ... Li Y, Han Y
Aims
Vicagrel, a novel antiplatelet prodrug to overcome the residual high platelet reactivity of clopidogrel induced by inactive metabolism and cytochrome P450 (CYP) 2C19 polymorphisms, provides favorable antiplatelet inhibition in healthy volunteers. However, antiplatelet effect and safety in patients with coronary artery disease (CAD) is unclear.
Methods and results
This was a multicenter, randomized, double-blind, triple-dummy, dose-exploring phase II trial comparing antiplatelet activity and safety of vicagrel at different doses versus clopidogrel in CAD undergoing percutaneous coronary intervention (PCI). The primary endpoint was inhibition of platelet aggregation (%IPAs) after loading and maintenance doses (LD/MD) at 28 days. Safety endpoints included adverse events (AEs) and Bleeding Academic Research Consortium-defined any bleeding. Pharmacokinetic (PK) profiles and the influence of CYP2C19 polymorphisms were explored in subgroup analysis. 279 patients diagnosed with stable CAD (51.97%), unstable angina (40.86%) and myocardial infarction (7.17%) were randomized to receive vicagrel 20/5 mg (LD/MD), 24/6 mg or 30/7.5 mg or clopidogrel 300/75 mg in combination with aspirin. %IPAs on day 28 were 30.19%, 35.02%, 45.61% and 32.55% for vicagrel 20/5 mg, 24/6 mg, 30/7.5 mg and clopidogrel, respectively, and were comparable across all groups (P = 0.0694). The plasma concentration of the vicagrel active metabolite M15-2 had a similar AUC and Tmax to that of clopidogrel. There were no significant differences in AEs (4.35%, 0%, 1.45%, and 5.56% for vicagrel 20/5 mg, 24/6 mg, 30/7.5 mg and clopidogrel, P = 0.6667) or any bleeding (13.04%, 14.06%, 11.59%, and 11.11% for vicagrel 20/5 mg, 24/6 mg, 30/7.5 mg and clopidogrel, respectively, P = 0.95) across four groups. %IPAs and PK profiles of vicagrel did not vary significantly among different CYP2C19 metabolizers.
Conclusion
Vicagrel had comparable antiplatelet effect and safety to clopidogrel in patients with CAD undergoing PCI.

© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.

Eur Heart J Cardiovasc Pharmacother: 19 Apr 2022; epub ahead of print
Zhao X, Ma S, Kang Y, Tang C, ... Li Y, Han Y
Eur Heart J Cardiovasc Pharmacother: 19 Apr 2022; epub ahead of print | PMID: 35438151
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Abstract

Perioperative Management of P2Y12 Inhibitors in Patients Undergoing Cardiac Surgery within 1 Year of PCI.

Cao D, Swain JA, Sartori S, Nardin M, ... Kini AS, Mehran R
Objectives
To evaluate the impact of perioperative P2Y12-receptor inhibitor therapy among patients undergoing cardiac surgery within 1 year of percutaneous coronary intervention (PCI).
Methods and results
Patients undergoing cardiac surgery in the year post-PCI at 3 tertiary-care centers between 2011-2018 were stratified into those who had received at least one dose of P2Y12 inhibitor prior to surgery (within 5 days for clopidogrel or prasugrel, or within 3 days for ticagrelor) and those who had not. The outcomes of interest were major adverse cardiac and cerebrovascular events (MACCE) and bleeding. Among 20 279 PCI patients, 359 (1.8%) underwent cardiac surgery in the ensuing year, 76.3% of whom received coronary artery bypass grafts. Overall, 33 (9.2%) MACCE and 85 (23.7%) bleeding events occurred within 30 days post-cardiac surgery. Perioperative P2Y12 inhibition (N = 133, 37%) was not associated with the risk of MACCE or bleeding, despite numerically lower rates of myocardial infarction or stent thrombosis (0.0% vs. 2.6%; p = 0.089). Patients who continued the P2Y12 inhibitor until the day of surgery (N = 60, 17%) had significantly higher bleeding risk (adjOR 2.93, 95% CI 1.53-5.59). Predictors of MACCE included a time interval from PCI to cardiac surgery of ≤ 30 days and reduced ejection fraction, whereas urgent/emergent surgery predicted bleeding. Chronic kidney disease and myocardial infarction as indication for PCI predicted both MACCE and bleeding.
Conclusions
Among patients undergoing cardiac surgery in the year after PCI, the perioperative risk of ischemic and bleeding events might be influenced by P2Y12 inhibitor therapy in addition to other risk parameters, including the timing and urgency of the procedure.

© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.

Eur Heart J Cardiovasc Pharmacother: 07 Apr 2022; epub ahead of print
Cao D, Swain JA, Sartori S, Nardin M, ... Kini AS, Mehran R
Eur Heart J Cardiovasc Pharmacother: 07 Apr 2022; epub ahead of print | PMID: 35389474
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Abstract

Long-Term Treatment with the Combination of Rivaroxaban and Aspirin in Patients with Chronic Coronary or Peripheral Artery Disease: Outcomes During the Open Label Extension of the COMPASS trial.

Eikelboom JW, Bosch J, Connolly SJ, Tyrwitt J, ... Sharma M, Yusuf S
Aims
To describe outcomes of patients with chronic coronary artery disease (CAD) and/or peripheral artery disease (PAD) enrolled in The Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) randomized trial who were treated with the combination of rivaroxaban 2.5 mg twice daily and aspirin 100 mg once daily during long term open label extension (LTOLE).
Methods and results
Of 27 395 patients enrolled in COMPASS, 12 964 (mean age at baseline 67.2 years) from 455 sites in 32 countries were enrolled in LTOLE and treated with the combination of rivaroxaban and aspirin for a median of 374 additional days (range 1-1 191 days). During LTOLE, the incident events per 100 patient years were: for the primary outcome (cardiovascular [CV] death, stroke, or myocardial infarction [MI]) 2.35 (95% CI 2.11-2.61), mortality 1.87 (1.65-2.10), stroke 0.62 (0.50-0.76) and MI 1.02 (0.86-1.19), with confidence intervals that overlapped those seen during the randomized treatment phase with the combination of rivaroxaban and aspirin. The incidence rates for major bleeding were 1.01 (0.86-1.19) and for minor bleeding 2.49 (2.24-2.75), compared with 1.67 (1.48-1.87) and 5.11 (95% CI 4.77-5.47), respectively, during the randomized treatment phase with the combination.
Conclusion
In patients with chronic CAD and/or PAD, extended combination treatment for a median of 1 year and a maximum of 3 years was associated with incidence rates for efficacy and bleeding that were similar to or lower than those seen during the randomized treatment phase, without any new safety signals.

© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.

Eur Heart J Cardiovasc Pharmacother: 06 Apr 2022; epub ahead of print
Eikelboom JW, Bosch J, Connolly SJ, Tyrwitt J, ... Sharma M, Yusuf S
Eur Heart J Cardiovasc Pharmacother: 06 Apr 2022; epub ahead of print | PMID: 35383832
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Abstract

ESC/EAS Guidelines for the detection, prevention, and treatment of individuals at risk of a first myocardial infarction: effect of 5 years of updates and the new SCORE2.

Sulman D, Zeitouni M, Silvain J, Kerneis M, ... Montalescot G, ACTION group
Aims
The ESC has released 3 consecutive guidelines within 5 years addressing cardiovascular prevention, risk scores and cholesterol treatment. This study aims to evaluate whether 2021 ESC guidelines improved eligibility of individuals for primary prevention statin therapy before their first STEMI, and for intensive lipid-lowering treatments in secondary prevention.
Methods and results
The cardiovascular risk category of 2757 consecutive individuals admitted for a first STEMI was evaluated to assess whether they would have been eligible for primary prevention statins according to 2021 versus 2019 and 2016 ESC guidelines. Eligibility for intensive lipid-lowering therapy in secondary prevention was assessed according to the real-life follow-up LDL-C and the expected follow-up LDL-C. More individuals would have been eligible for primary prevention statins according to 2021, 2019 vs 2016 guidelines (61.8% vs. 38.7% vs. 23.6%, p < 0.01),  a finding observed in both men (62.3% vs 35.0% % vs 24.9%, p < 0.01) and women (60.2% vs 50.7% vs. 19.3%, p = 0.18). Only 27% of individuals reached the LDL-C objective of 55 mg/L in secondary prevention: using the ESC stepwise approach, 61.7% were eligible for higher doses of statins, 26.2% for Ezetimibe and 12.1% for PCSK9i. Based on expected LDL-C reductions, eligibility for PCSK9i in secondary prevention was greater with 2021 versus 2016 guidelines (44.5% vs. 22.5%, p < 0.01).
Conclusions
The 2021 ESC guidelines improved the detection and treatment of individuals at risk for a first MI. In secondary prevention, 70% of patients kept LDL-C levels above 55 mg/dL: increasing statin dose and adding ezetimibe were the most frequently recommended therapeutic actions.

© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.

Eur Heart J Cardiovasc Pharmacother: 05 Apr 2022; epub ahead of print
Sulman D, Zeitouni M, Silvain J, Kerneis M, ... Montalescot G, ACTION group
Eur Heart J Cardiovasc Pharmacother: 05 Apr 2022; epub ahead of print | PMID: 35381063
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Abstract

Platelet P2Y12 inhibiting therapy in adjunct to vascular dose of rivaroxaban or aspirin: A pharmacodynamic study of dual pathway inhibition versus dual antiplatelet therapy.

Galli M, Franchi F, Rollini F, Been L, ... Bass TA, Angiolillo DJ
Aim
Dual-pathway inhibition (DPI) by adding a vascular dose of rivaroxaban to a single antiplatelet agent has emerged as a promising antithrombotic strategy. However, in most studies the antiplatelet agent of choice used in adjunct to a vascular dose of rivaroxaban was aspirin, and data with a P2Y12 inhibitor and how this DPI regimen compares with standard dual antiplatelet therapy (DAPT) is limited.
Methods and results
This investigation was a sub-study analysis conducted in selected cohorts of patients with stable atherosclerotic disease enrolled from a larger prospective, open-label, parallel-group pharmacodynamics (PD) study. We analyzed data from 40 patients treated with either clopidogrel or ticagrelor-based DAPT first, and clopidogrel or ticagrelor-based DPI thereafter. PD measures explored key pathways involved in thrombus formation and included markers of: 1) P2Y12 reactivity, 2) platelet-mediated global thrombogenicity, 3) cyclooxygenase-1 activity, 3) TRAP-induced platelet aggregation; 4) tissue factor (TF)-induced platelet aggregation, and 5) thrombin generation. As compared to DAPT, on a background of the same P2Y12 inhibitor (clopidogrel or ticagrelor), DPI was associated with reduced thrombin generation, increased markers of cyclooxygenase-1 activity and TRAP-induced platelet aggregation and no differences in markers of P2Y12 signaling, platelet-mediated global thrombogenicity and TF-induced platelet aggregation. In an analysis according to P2Y12 inhibitor type, ticagrelor reduced markers of platelet-mediated global thrombogenicity, P2Y12 signaling and rates of high platelet reactivity compared to clopidogrel.
Conclusions
Compared to DAPT with aspirin and a P2Y12 inhibitor, the use of a P2Y12 inhibitor in adjunct to a vascular dose of rivaroxaban as part of a DPI strategy is associated with similar effects on platelet-mediated global thrombogenicity but reduced thrombin generation. A DPI strategy with ticagrelor is associated with enhanced antithrombotic efficacy, the clinical implications of which warrant larger scale investigations.
Clinical trial registration
ClinicalTrials.gov identifier: NCT03718429.

© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.

Eur Heart J Cardiovasc Pharmacother: 30 Mar 2022; epub ahead of print
Galli M, Franchi F, Rollini F, Been L, ... Bass TA, Angiolillo DJ
Eur Heart J Cardiovasc Pharmacother: 30 Mar 2022; epub ahead of print | PMID: 35353154
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Abstract

Extended, standard or De-escalation antiplatelet therapy for patients with CAD undergoing PCI? A trial-sequential, bivariate, influential and network meta-analysis.

Ullah W, Zahid S, Sandhyavenu H, Faisaluddin M, ... Savage MP, Fischman DL
Background
The relative safety and efficacy of de-escalation, extended duration (ED) (>12-months) and standard dual antiplatelet therapy for 12-months (DAPT-12) in patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI) remains controversial.
Methods
Online databases were queried to identify relevant randomized control trials (RCTs). ED-DAPT, high-potency (HP) DAPT, shorter duration (SD) DAPT and low-dose (LD) DAPT were compared with DAPT-12. A trial sequential, bivariate, influential and frequentist network meta-analysis (NMA) was performed to determine the pooled estimates.
Results
A total of 30 RCTs comprising 81 208 (40 839 experimental, 40 369 control arm) patients with CAD were included in the quantitative analysis. On NMA, compared with DAPT-12, all types of de-escalation, HP-DAPT-12 and ED-DAPT strategies had a statistically non-significant difference in the incidence of MACE at a median follow-up of 1-year. Similarly, there was no significant difference in the incidence of stroke, stent thrombosis, target lesion revascularization (TLR), target vessel revascularization (TVR) and all-cause mortality between DAPT-12 and all other strategies. The network estimates showed a significantly lower incidence of major bleeding with DAPT for 3-months followed by P2Y12-inhibitor monotherapy (RR 0.62, 95% CI 0.45-0.84), while a higher risk of bleeding with HP-DAPT for 12 months (RR 1.55, 95% CI 1.16-2.06). The net clinical benefit and rankograms also favored DAPT-3 (P2Y12) and discouraged the use of HP-DAPT-12 and ED-DAPT. A subgroup analysis of 19 RCTs restricted to patients who presented with acute coronary syndrome (ACS) mirrored the findings of pooled analysis. A sensitivity analysis revealed no influence of any individual study or individual strategy on net ischemic estimates. The trial sequential analysis (TSA) illustrated a consistently non-significant difference at the interim analysis of trials, reaching the futility area for MACE, while the cumulative Z-values line surpassed the monitoring boundary as well as the required information size for major bleeding favoring de-escalation strategy.
Conclusion
DAPT for 3 months followed by ticagrelor-only and use of aspirin + clopidogrel after a short period of high potency DAPT appears to be a safe strategy for treating post-PCI patients. However, given the methodological limitations and inclusion of a small number of trials in novel de-escalation strategies, these findings need validation by future large scale RCTs.

© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.

Eur Heart J Cardiovasc Pharmacother: 24 Mar 2022; epub ahead of print
Ullah W, Zahid S, Sandhyavenu H, Faisaluddin M, ... Savage MP, Fischman DL
Eur Heart J Cardiovasc Pharmacother: 24 Mar 2022; epub ahead of print | PMID: 35325105
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Abstract

Ticagrelor monotherapy after PCI in patients with concomitant diabetes mellitus and chronic kidney disease: TWILIGHT DM-CKD.

Dehghani P, Cao D, Baber U, Nicolas J, ... Pocock S, Mehran R
Aims
We aimed to evaluate the treatment effects of ticagrelor monotherapy in the very high-risk cohort of patients with concomitant diabetes mellitus (DM) and chronic kidney disease (CKD) undergoing percutaneous coronary intervention (PCI).
Methods and results
In the TWILIGHT trial, after 3-month dual antiplatelet therapy with ticagrelor and aspirin post-PCI, event-free patients were randomized to either aspirin or placebo in addition to ticagrelor for 12 months. Those with available information on DM and CKD status were included in this subanalysis and were stratified by the presence or absence of either condition: 3391 (54.1%) had neither DM nor CKD (DM-/CKD-), 1822 (29.0%) had DM only (DM+/CKD-), 561 (8.9%) had CKD only (DM-/CKD+), and 8.0% had both DM and CKD (DM+/CKD+). The incidence of the primary endpoint of Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding did not differ according to DM/CKD status (p-trend = 0.13), but there was a significant increase in BARC 3 or 5 bleeding (p-trend<0.001) as well as the key secondary endpoint of death, myocardial infarction, or stroke (p-trend<0.001). Ticagrelor plus placebo reduced bleeding events compared with ticagrelor plus aspirin across all four groups, including DM+/CKD+ patients with respect to BARC 2-5 (4.5% vs. 8.7%; HR 0.49, 95% CI 0.24-1.01) as well as BARC 3-5 (0.8% vs. 5.3%; HR 0.15, 95% CI 0.03-0.53) bleeding, with no evidence of heterogeneity. The risk of death, myocardial infarction, or stroke was similar between treatment arms across all groups.
Conclusions
Irrespective of the presence of DM, CKD, and their combination, ticagrelor monotherapy reduced the risk of bleeding without a significant increase in ischemic events compared with ticagrelor plus aspirin.

© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.

Eur Heart J Cardiovasc Pharmacother: 23 Mar 2022; epub ahead of print
Dehghani P, Cao D, Baber U, Nicolas J, ... Pocock S, Mehran R
Eur Heart J Cardiovasc Pharmacother: 23 Mar 2022; epub ahead of print | PMID: 35325085
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Abstract

Neuraminidase inhibitor treatment is associated with decreased mortality in COVID-19 patients: a retrospective analysis.

Wu J, Zhao M, Wei H, Li C, ... Zheng L, Wang DW
Aims
The aim of this study was to investigate the effects of Neuraminidase inhibitors (NI) on COVID-19 in a retrospective study.
Methods and results
The study included an overall COVID-19 patients (n = 3267) and a 1:1 propensity score-matched patients (n = 972). The levels of plasma N-acetylneuraminic acid and neuraminidase expression were further evaluated in a panel of hospitalized and 1-month post-infection recovered COVID-19 subjects. The mortality rate in the overall patients was 9.6% (313/3267) and 9.2% (89/972) in the propensity-score matched patients. The NI treatment lowered the mortality rate (5.7% versus 10.3%) and the critically ill conversion rate (14.1% versus 19.7%) compare to those in the non-NI group in the overall patients and evaluated in the propensity score-matched patients when applying the multivariate Cox model for adjusting imbalanced confounding factors. Furthermore, NI treatment was associated with attenuated cytokine storm levels and acute heart injury but not liver or kidney injuries. Further analysis in a small panel of patients found the levels of N-acetylneuraminic acid and neuraminidase (dominantly the NEU3 isoform) were elevated in the hospitalized COVID-19 subjects and recovered at the 1-month post-infection stage, suggesting increasing desialylation in COVID-19 patients.
Conclusion
These results suggest that NI treatment is associated with decreased mortality in COVID-19 subjects, especially for those subjects with acute heart injury.

© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.

Eur Heart J Cardiovasc Pharmacother: 15 Mar 2022; epub ahead of print
Wu J, Zhao M, Wei H, Li C, ... Zheng L, Wang DW
Eur Heart J Cardiovasc Pharmacother: 15 Mar 2022; epub ahead of print | PMID: 35294004
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Abstract

Photo-induced skin reactions of cardiovascular drugs - a systematic review.

Götzinger F, Reichrath J, Millenaar D, Lauder L, ... Böhm M, Mahfoud F
Purpose
This systemic review aims to provide a practical overview of the prevalence, clinical manifestation, and management of adverse photo-induced skin reactions caused by frequently used cardiovascular drugs and to assess their potential relevance for skin cancer development.
Methods
Data search included PubMed, Web of Science, and the Cochrane Library. A systematic review of peer-reviewed studies reporting the photosensitizing and/or skin cancer-inducing properties of common cardiovascular drugs was performed and a guide to clinical management of photo-induced skin eruptions by cardiovascular drugs was provided. Study quality was assessed for major methodological biases.
Results
A total of 58 studies were identified (i.e. 23 case reports, 14 observational studies, 10 review articles, 10 experimental studies, and 1 meta-analysis). Most commonly, drug-associated adverse photo-induced cutaneous reactions were caused by phototoxic and photoallergic mechanisms. There is evidence suggesting that amiodarone and dronedarone, thiazide-diuretics, thiazide-like-diuretics, angiotensin receptor blockers, dihydropyridine-type calcium channel blockers as well as certain ACE-inhibitors and statins may cause photo-induced adverse cutaneous reactions. Other drugs such as anticoagulants, antiplatelets, aldosterone antagonists, and fibrates have not been linked with photosensitizing reactions or adverse cutaneous reactions. Some drugs, i.e. thiazides and thiazide-like-diuretics, were associated with an increased risk of non-melanoma skin cancers (basal cell carcinoma, squamous cell carcinoma).
Conclusions
Certain commonly used cardiovascular drugs have been associated with adverse photo-induced cutaneous reactions. If they occur, further diagnosis and treatment might be needed, depending on the severity and progress. Whether photosensitizing drugs increase the risk of skin cancer remains elusive and further randomized, controlled trials are required.

© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.

Eur Heart J Cardiovasc Pharmacother: 11 Mar 2022; epub ahead of print
Götzinger F, Reichrath J, Millenaar D, Lauder L, ... Böhm M, Mahfoud F
Eur Heart J Cardiovasc Pharmacother: 11 Mar 2022; epub ahead of print | PMID: 35278085
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Abstract

Cardiorenal Risk of Celecoxib compared to Naproxen, or Ibuprofen in Arthritis Patients: Insights from the PRECISION trial.

Obeid S, Libby P, Husni E, Wang Q, ... Nissen SE, Lüscher TF
Introduction
Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most frequently used drugs both prescribed and over the counter. The long-term cardiovascular safety of NSAIDs in patients with arthritis has engendered controversy. Concerns remain regarding the relative incidence and severity of adverse cardiorenal effects, particularly in arthritis patients with established CV disease, or risk factors for disease as illustrated by the PRECISION trial participants (NCT00346216).
Hypothesis
The selective COX-2 Inhibitor celecoxib has a superior cardiorenal safety profile when compared to ibuprofen or naproxen in the PRECISION population.
Methods
24,081 patients who required NSAIDs for osteoarthritis or rheumatoid arthritis and had increased CV risk randomly received celecoxib, ibuprofen or naproxen. The current prespecified secondary analysis assessed the incidence, severity and NSAID-related risk of the pre-specified composite cardiorenal outcome [adjudicated renal event, hospitalization for congestive heart failure (CHF), or hospitalization for hypertension (HTN)] in the intention-to-treat (ITT) population. An on-treatment analysis assessed safety in those taking the study medication.
Results
Following a mean treatment duration of 20.3±16.0 months and a mean follow-up of 34.1±13.4 months, the primary cardiorenal composite outcome occurred in 423 patients (1.76%) in the ITT population. Of these 423 patients, 118 (28%) were in the celecoxib, 166 (39%) in the ibuprofen and 139 (33%) in the naproxen group. In a multivariable Cox regression model adjusted for independent clinical variables, celecoxib showed a significantly lower risk compared with ibuprofen (hazard ratio [HR] 0.67, confidence interval [CI] 0.53 - 0.85, p = 0.001) and a trend to lower risk compared to naproxen (HR 0.79, CI 0.61 - 1.00, p = 0.058).In the intention-to-treat analysis, clinically significant renal events occurred in 220 patients with events rates of 0.71%, 1.14% and 0.89% for celecoxib, ibuprofen and naproxen respectively (p = 0.052), while in the on -treatment analysis the rates were 0.52%, 0.91% and 0.78% (p<0.001).
Conclusion
In the current era, long-term NSAID use was associated with few cardiorenal events in arthritis patients. At the doses studied, celecoxib displayed fewer renal events and hence more favorable cardiovascular safety compared to ibuprofen or naproxen. These results have considerable clinical implications for practitioners managing individuals with chronic arthritis pain and high risk of impaired renal function and/or heart failure. (Funded by Pfizer) Clinical Trial Registration: NCT00346216.

© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.

Eur Heart J Cardiovasc Pharmacother: 01 Mar 2022; epub ahead of print
Obeid S, Libby P, Husni E, Wang Q, ... Nissen SE, Lüscher TF
Eur Heart J Cardiovasc Pharmacother: 01 Mar 2022; epub ahead of print | PMID: 35234840
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Abstract

Preadmission antiplatelet therapy and treatment effect of ticagrelor versus prasugrel in patients with acute coronary syndromes - a subgroup analysis of the ISAR-REACT 5 trial.

Lahu S, Ndrepepa G, Neumann FJ, Menichelli M, ... Schüpke S, Kastrati A
Aims
To assess whether the efficacy and safety of ticagrelor versus prasugrel in patients with acute coronary syndromes (ACS) are influenced by preadmission treatment with aspirin and/or clopidogrel.
Methods and results
Patients (n = 4018) were categorized into 2 groups: preadmission aspirin and/or clopidogrel group (n = 1455), and no preadmission aspirin or clopidogrel group (n = 2563). The primary endpoint was the composite of all-cause death, myocardial infarction, or stroke; the secondary safety endpoint was Bleeding Academic Research Consortium (BARC) type 3 to 5 bleeding, both at 1 year.Patients in the preadmission aspirin and/or clopidogrel group had a higher risk of ischemic events, but a similar risk of bleeding with patients in the no preadmission aspirin or clopidogrel group (cumulative incidences 10.5% vs. 6.7%, and 5.7% vs. 5.7%, respectively). The primary endpoint occurred in 81/717 patients assigned to ticagrelor and 69/738 patients assigned to prasugrel in the preadmission aspirin and/or clopidogrel group (11.5% vs. 9.5%; hazard ratio [HR] = 1.23; 95% confidence interval [CI], 0.89-1.69), and in 103/1295 patients assigned to ticagrelor and 68/1268 patients assigned to prasugrel in the no preadmission aspirin or clopidogrel group (8.0% vs. 5.4%; HR = 1.50 [1.10-2.03]; Pint = 0.382). BARC type 3 to 5 bleeding events did not differ between ticagrelor and prasugrel in patients in the preadmission aspirin and/or clopidogrel (6.2% vs. 4.5%), or no preadmission aspirin or clopidogrel (5.3% vs. 5.1%) groups (Pint = 0.541).
Conclusion
In patients with ACS, preadmission therapy with aspirin and/or clopidogrel has no influence on the relative efficacy and safety of ticagrelor and prasugrel.

© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.

Eur Heart J Cardiovasc Pharmacother: 21 Feb 2022; epub ahead of print
Lahu S, Ndrepepa G, Neumann FJ, Menichelli M, ... Schüpke S, Kastrati A
Eur Heart J Cardiovasc Pharmacother: 21 Feb 2022; epub ahead of print | PMID: 35191982
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This program is still in alpha version.