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Aims Guidelines recommend the use of potent P2Y12 inhibitors over clopidogrel for the reduction of ischaemic events in patients with acute coronary syndrome (ACS). However, this comes at the expense of increased bleeding. A guided selection of P2Y12 inhibiting therapy has the potential to overcome this limitation. We aimed at evaluating the comparative safety and efficacy of guided vs. routine selection of potent P2Y12 inhibiting therapy in patients with ACS. Methods and results We performed a network meta-analysis of randomized controlled trials (RCTs) comparing different oral P2Y12 inhibitors currently recommended for the treatment of patients with ACS (clopidogrel, prasugrel, and ticagrelor). RCTs including a guided approach (i.e. platelet function or genetic testing) vs. standard selection of P2Y12 inhibitors among patients with ACS were also included. Incidence rate ratios (IRR) and associated 95% confidence intervals (CIs) were estimated. P -scores were used to estimate hierarchies of efficacy and safety. The primary efficacy endpoint was major adverse cardiovascular events (MACE) and the primary safety endpoint was all bleeding. A total of 61 898 patients from 15 RCTs were included. Clopidogrel was used as reference treatment. A guided approach was the only strategy associated with reduced MACE (IRR: 0.80, 95% CI: 0.65–0.98) without any significant trade-off in all bleeding (IRR: 1.22, 95% CI: 0.96–1.55). A guided approach and prasugrel were associated with reduced myocardial infarction. A guided approach, prasugrel, and ticagrelor were associated with reduced stent thrombosis. Ticagrelor was also associated with reduced total and cardiovascular mortality. Prasugrel was associated with increased major bleeding. Prasugrel and ticagrelor were associated with increased minor bleeding. The incidence of stroke did not differ between treatments. Conclusion In patients with an ACS, compared with routine selection of potent P2Y12 inhibiting therapy (prasugrel or ticagrelor), a guided selection of P2Y12 inhibiting therapy is associated with the most favourable balance between safety and efficacy. These findings support a broader adoption of guided approach for the selection of P2Y12 inhibiting therapy in patients with ACS. Study registration number This study is registered in PROSPERO (CRD42021258603). Key Question A guided selection of P2Y12 inhibiting therapy using platelet function or genetic testing improves outcomes among patients undergoing percutaneous coronary intervention. Nevertheless, the comparative safety and efficacy of a guided versus routine selection of potent P2Y12-inhibiting therapy in acute coronary syndrome has not been explored. Key Finding In a comprehensive network meta-analysis including the totality of available evidence and using clopidogrel as treatment reference, a guided approach was the only strategy associated with reduced major adverse cardiovascular events without any significant trade-off in bleeding. Prasugrel and ticagrelor increased bleeding and only ticagrelor reduced mortality. Take Home Message A guided selection of P2Y12-inhibiting therapy represents the strategy associated with the most favourable balance between safety and efficacy. These findings support a broader adoption of guided P2Y12 inhibiting therapy in patients with acute coronary syndrome. [ABSTRACT FROM AUTHOR]

Background: Carriers of cytochrome 2C19 (CYP2C19) loss of function (LoF) alleles treated with clopidogrel have impaired drug metabolism resulting in reduced active metabolite levels, high platelet reactivity (HPR), and an increased risk of thrombotic events. Several alternative antiplatelet therapies have been proposed to overcome HPR in these patients, but their comparative effects remain poorly explored., Methods: Randomized controlled trials (RCTs) comparing different oral antiplatelet therapies in carriers of CYP2C19 LoF alleles undergoing percutaneous coronary interventions (PCI) were included. A frequentist network meta-analysis was conducted to estimate mean difference (MD) or odds ratios (OR) and 95% confidence intervals (CI). The primary outcome was platelet reactivity assessed by VerifyNow and reported as P2Y12 reaction unit (PRU). The secondary outcome was the rate of HPR. Standard-dose of clopidogrel (75 mg daily) was used as reference treatment., Results: A total of 12 RCTs testing 6 alternative strategies (i.e., clopidogrel 150 mg, prasugrel 3.75 mg, 5 mg, and 10 mg, ticagrelor 90 mg bid, and adjunctive cilostazol 100 mg bid) were included in the network. Compared with standard-dose clopidogrel, the greatest reduction in PRU was observed with prasugrel 10 mg (MD -127.91; 95% CI -141.04; -114.78) and ticagrelor 90 mg bid (MD -124.91; 95% CI -161.78; -88.04), followed by prasugrel 5 mg (MD -76.33; 95% CI -98.01; -54.65) and prasugrel 3.75 mg (MD -73.00; 95% CI -100.28; -45.72). Among other strategies, adjunctive cilostazol (MD-42.64; 95% CI -64.72; -20.57) and high-dose clopidogrel (MD -32.11; 95% CI -51.33; -12.90) were associated with a modest reduction in PRU compared with standard-dose clopidogrel., Conclusion: Among carriers of CYP2C19 LoF alleles undergoing PCI, standard-dose prasugrel or ticagrelor are most effective in reducing platelet reactivity, while double-dose clopidogrel and additional cilostazol showed modest effects. Reduced-dose of prasugrel may represent a balanced strategy to overcome HPR without a significant increase in bleeding. The clinical implications of these pharmacodynamic findings warrant further investigation., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Chest pain affects more than 100 million people globally, however up to 70% of patients undergoing invasive angiography do not have obstructive coronary artery disease and ischemia with non-obstructive coronary artery disease (INOCA) is often a cause of the clinical picture. The symptoms reported by INOCA patients are very heterogeneous and often misdiagnosed as non-cardiac leading to under-diagnosis/investigation and under-treatment. The underlying pathophysiological mechanisms of INOCA are multiple and include coronary vasospasm and microvascular dysfunction. Most importantly, this condition must not be considered benign: compared to asymptomatic individuals, INOCA patients present an increased incidence of cardiovascular events, rehospitalizations, as well as impaired quality of life, with increasing costs for healthcare systems. The aims of this review are to describe the pathophysiological and clinical characteristics of INOCA and to provide guidance to the medical community on the diagnostic approaches and management of INOCA, also via a series of clinical case reports.

Pharmacological therapy is the cornerstone of chronic heart failure treatment. However, an increasing number of devices for monitoring and treatment of patients with heart failure are being used and developed to complement existing therapies. Pulmonary and systemic congestion, left ventricular remodeling, neurohormonal activation, low cardiac contractility and impaired cardiac output are the main pathophysiological targets of these devices. The aim of this review is to summarize rationale, functioning, evidence and current indications regarding new devices for the management of patients with chronic heart failure.

Aims: Low-dose (LD) direct oral anticoagulants (DOACs) in adjunct to antiplatelet therapy, known as dual-pathway inhibition (DPI), have been tested to prevent ischaemic events in patients with cardiovascular disease (CVD). We conducted a systematic review and meta-analysis to determine the overall safety and efficacy of LD DOACs vs placebo on a background of antiplatelet therapy., Methods and Results: All randomized controlled trials (RCTs) comparing LD DOAC (defined as a dosage below the lowest approved for stroke prevention) vs placebo among patients with CVD receiving single or dual antiplatelet therapy (DAPT) in at least 50% of the population and followed for at least 6 months, were included. Incidence rate ratios (IRRs) with 95% confidence intervals (CIs) were used to overcome different follow-up durations across trials. The primary efficacy endpoint was major adverse cardiovascular events (MACE) and the primary safety endpoint major bleeding. A pre-specified subgroup analysis was performed for different DOAC-dose regimens. A total of 49 802 patients from 7 RCTs were included. Low-dose DOACs vs placebo were associated with significant reductions in MACE (IRR 0.85, 95% CI 0.78-0.91, number needed to treat, NNT, 86) and myocardial infarction (IRR 0.86, 95% CI 0.78-0.95, NNT 355) and significant increases of major (IRR 2.05, 95% CI 1.50-2.80, number needed to harm, NNH, 89) or all bleeding (IRR 1.82, 95% CI 1.49-2.22, NNH 23). Cardiovascular death (IRR 0.90, 95% CI 0.79-1.03, NNT 784), intracranial (IRR 1.18, 95% CI 0.71-1.96, NNH 1810), and fatal bleeding (IRR 1.13, 95% CI 0.76-1.69, NNH 3170) did not differ significantly between strategies. Non-significant reductions of all-cause death (IRR 0.90, 95% CI 0.80-1.01, NNT 821) and stroke (IRR 0.73, 95% CI 0.53-1.01, NNT 315) favoured LD DOACs. Meta-regression analyses showed a significant interaction between percentage of DAPT use and increased risk of major bleeding (P = 0.04), intracranial haemorrhage (P = 0.035), and stroke (P = 0.0003). Subgroup analysis of very LD DOAC, defined as ≤1/3 of the lowest approved dose for stroke prevention (i.e. rivaroxaban 2.5 mg twice daily) seemed to mitigate the risk of bleeding without any trade-off in efficacy compared to other LD DOAC regimens., Conclusions: In patients with CVD, LD DOAC vs placebo on a background of antiplatelet therapy, reduced ischaemic events at the expense of increased major and all bleeding, but without significantly increasing intracranial or fatal bleeds, while the reduction of cardiovascular or total mortality and stroke was not statistically significant. A DPI with very LD DOAC (i.e. rivaroxaban 2.5 mg twice daily) appeared particularly advantageous, especially when combined with a single antiplatelet agent and used among patients at high ischaemic and low bleeding risk., Study Registration: This study is registered in PROSPERO (CRD42021232744)., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Aims: To compare the safety and efficacy of very short (≤3 months), short (6 months), standard (12 months), and extended (>12 months) dual antiplatelet therapy (DAPT), and of subsequent monotherapies, after coronary drug-eluting stent (DES) implantation., Methods and Results: Twenty-two randomized control trials (n = 110 059 patients/year) were selected and included in a Bayesian network meta-analysis. The primary efficacy endpoint (PEP) was a composite of cardiac death, myocardial infarction (MI), and stent thrombosis (ST), with each of the components of the PEP being a secondary efficacy endpoint. The primary safety endpoint was major bleeding rate. Compared to standard, we found a lower rate of MI [odds ratio (OR) 0.56, 95% confidence interval (CI) 0.44-0.77] in extended, a lower rate of major bleeding (OR 0.61, 95% CI 0.39-0.87) in very short, and a lower rate of any bleeding (OR 0.61, 95% CI 0.38-0.90) in short DAPT. All DAPT durations were comparable regarding the secondary efficacy endpoints. Very short DAPT followed by P2Y12 inhibition was the treatment of choice to reduce both major bleeding and MI. In the ACS subgroup, extended DAPT (as compared to standard) reduced PEP and ST rates (but not MIs)., Conclusion: The efficacy of short and very short is comparable with that of standard DAPT after DES implantation, whereas extended DAPT reduces MI rate. Very short DAPT is associated with lower haemorrhagic events and, followed by a P2Y12 inhibitor monotherapy, should be preferred in order to pursue a trade-off between major bleeding and ischaemic events., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Cardiogenic shock (CS) is a complex and relatively rare disease. Whilst its mortality remains unacceptably high, a multidisciplinary approach based on pre-established and shared protocols may improve prognosis and ensure appropriate resource allocation. Comprehensive hemodynamic assessment and monitoring as well as tailored, goal-directed medical therapy are part of an optimal management. Moreover, mechanical support devices may be helpful as they sustain hemodynamics to a greater extent as compared to inotropes and vasopressors, while lacking their cardiotoxic effects. Therefore, they are increasingly used in CS patients. In 2019, a new protocol for the management of patients with CS was adopted at the Ospedale Policlinico San Martino (HSM) in Genoa, Italy. Following in the footsteps of similar international experiences, the HSM protocol aims at streamlining the management of these high-risk patients improving the cooperation among healthcare specialists, and also addressing the key issues of mechanical support device implantation and appropriate referral for palliative care.

Aim: To provide an updated assessment of the efficacy-safety profile of very short (1 or 3 months) dual antiplatelet therapy (DAPT) compared with long (12 months) DAPT in patients undergoing percutaneous coronary interventions (PCIs)., Methods and Results: Seven randomized controlled trials (RCTs) comparing very short vs. long DAPT in 35 785 patients undergoing PCI were selected. The primary efficacy endpoint was major adverse cardiovascular events (MACE) and the primary safety endpoint trial-defined major bleeding through at least 1 year. Compared with longer duration, very short DAPT yielded comparable rates of MACE [odds ratio (OR) 0.93, 95% confidence interval (CI) 0.84-1.03, P = 0.19], all-cause mortality (OR 0.92, 95% CI 0.80-1.06, P = 0.25), myocardial infarction (OR 1.01, 95% CI 0.88-1.15, P = 0.91), stroke (OR 1.04, 95% CI 0.72-1.50, P = 0.83), stent thrombosis (OR 1.05, 95% CI 0.80-1.37, P = 0.73), target vessel revascularization (OR 0.99, 95% CI 0.82-1.18, P = 0.89), and comparable net clinical benefit (OR 0.92, 95% CI 0.84-1.01, P = 0.08). Very short DAPT was associated with reduced rates of major bleeding (OR 0.61, 95% CI 0.40-0.94, P = 0.03) or any bleeding (OR 0.65, 95% CI 0.47-0.90, P = 0.009). Subgroup analyses showed consistent results for 1 vs. 3 month DAPT and for aspirin vs. P2Y12 inhibitor monotherapy following very short DAPT., Conclusions: Compared with long DAPT, very short DAPT did not increase the odds of ischaemic complications, while reducing the odds of major or any bleeding by over 30%., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Cardiac computed tomography (CCT) has rapidly evolved, becoming a powerful integrated tool for the evaluation of coronary artery disease (CAD), and being superior to other noninvasive methods due to its high accuracy and ability to simultaneously assess both lumen stenosis and atherosclerotic plaque burden. Furthermore, CCT is regarded as an effective gatekeeper for coronary angiography, and carries independent important prognostic information. In the last decade, the introduction of new functional CCT applications, namely CCT perfusion (CCTP) imaging and CT-derived fractional flow reserve (FFR CTA ), has opened the door for accurate assessment of the haemodynamic significance of stenoses. These new CCT technologies, thus, share the unique advantage of assessing both myocardial ischemia and patient-specific coronary artery anatomy, providing an integrated anatomical/functional analysis. In the present review, starting from the pathophysiology of myocardial ischemia, we evaluate the existing evidence for functional CCT imaging and its value in relation to alternative, well-established, non-invasive imaging modalities and invasive indices of ischemia (currently the gold-standard). The knowledge of clinical applications, benefits, and limitations of these new CCT technologies will allow efficient and optimal use in clinical practice in the near future., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/cdt-20-414). The series “Clinical Impact of Cardiac CT in Clinical Practice” was commissioned by the editorial office without any funding or sponsorship. AIS reports grants from FORTH during the conduct of the study. FC serves as an unpaid editorial board member of Cardiovascular Diagnosis and Therapy from Jul 2019 to Jun 2021. FC served as the unpaid Guest Editors of the series. The other authors have no other conflicts of interest to declare., (2020 Cardiovascular Diagnosis and Therapy. All rights reserved.)

Background: Best timing for coronary revascularization in patients with severe aortic stenosis (AS) who was a candidate for transcatheter aortic valve implantation (TAVI) is still matter of debate., Case Summary: We here report the case of an 87-year-old man with severe AS presenting with non-ST-segment elevation myocardial infarction. Coronary angiography revealed a highly complex and calcific left main stem (LMS) lesion. Rotablation-assisted percutaneous coronary intervention (PCI) was attempted but was complicated by post-stenting rapidly evolving haemodynamic impairment. A rescue 'pacing-free' balloon aortic valvuloplasty (BAV) was performed to rescue the patients, allowing prompt restoration of cardiac output and coronary perfusion., Discussion: According to guidelines and preliminary evidence, decision should be performed case by case and based on the degree of severity and complexity of either AS or coronary disease. The strategy of treating coronary lesions first may limit the risk of potential ischaemic complications during TAVI. However, the downside of it is the risk of hemodynamic crash with potential catastrophic evolution in case of PCI complications in presence of severe AS. A 'bailout BAV' can be considered as a salvage-strategy in case of complex and complicated LMS-PCI in the context of severe AS and advanced status of haemodynamic impairment. This approach must be seen as very last resort, while appropriate pre-procedural planning is still highly recommended in order to prevent potentially fatal procedural complications in this fragile clinical setting., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.)