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IMPORTANCE At one end of the coronary artery disease (CAD) spectrum, there are patients with multiple recurrent acute coronary syndromes (rACS), and at the other end there are those with long-standing clinical stability. Predicting the natural history of these patients is challenging because unstable plaques often heal without resulting in ACS. OBJECTIVE To assess in vivo the coronary atherosclerotic phenotype as well as the prevalence and characteristics of healed coronary plaques by optical coherence tomography (OCT) imaging in patients at the extremes of the CAD spectrum. DESIGN, SETTING, AND PARTICIPANTS This is an observational, single-center cohort study with prospective clinical follow-up. From a total of 823 consecutive patients enrolled in OCT Registry of the Fondazione Policlinico A. Gemelli-IRCCS, Rome, Italy, from March 2009 to February 2016, 105 patients were included in the following groups: (1) patients with rACS, defined as history of at least 3 acute myocardial infarctions (AMIs) or at least 4 ACS with at least 1 AMI; (2) patients with long-standing stable angina pectoris (ls-SAP), defined as a minimum 3-year history of stable angina; and (3) patients with a single unheralded AMI followed by a minimum 3-year period of clinical stability (sAMI). Data were analyzed from January to August 2018. EXPOSURES Intracoronary OCT imaging of nonculprit coronary segments. MAIN OUTCOMES AND MEASURES Coronary plaque features and the prevalence of healed coronary plaques in nonculprit segments as assessed by intracoronary OCT imaging. RESULTS Of 105 patients, 85 were men (81.0%); the median (interquartile range) age was 68 (63-75) years. Median (interquartile range) time of clinical stability was 9 (5.0-15.0) years in the ls-SAP group and 8 (4.5-14.5) years in the sAMI group. Patients in the rACS and sAMI groups showed similar prevalence of lipid-rich plaque and thin-cap fibroatheroma, which was significantly higher than in those with ls-SAP (lipid-rich plaque 80.0% [n = 24 of 30] vs 76.3% [n = 29 of 38] vs 37.8% [n = 14 of 37], respectively; P < .001; thin-cap fibroatheroma 40.0% [n = 12 of 30] vs 34.2% [n = 13 of 38] vs 8.1% [n = 3 of 37], respectively; P = .006). Spotty calcifications were more frequently observed in patients with rACS than in those with ls-SAP and sAMI (70.0% [n = 21 of 30] vs 40.5% [n = 15 of 37] vs 44.7% [n = 17 of 38], respectively; P = .04). Healed coronary plaques were rarely observed in patients with rACS, whereas their prevalence was significantly higher in patients with ls-SAP and sAMI (3.3% [n = 1 of 30] vs 29.7% [n = 11 of 37] vs 28.9% [n = 11 of 38], respectively; P = .01). CONCLUSIONS AND RELEVANCE Patients with rACS have a distinct atherosclerotic phenotype compared with those with ls-SAP, including higher prevalence of thin-cap fibroatheroma and lower prevalence of healed coronary plaques, suggesting that atherosclerotic profile and plaque healing may play a role in leading the natural history of patients with CAD.

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.

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Aims: Fractional flow reserve (FFR) can be used to detect a suboptimal result after percutaneous coronary intervention (PCI). A lower post-procedure FFR (<0.90) has been shown to be associated with adverse clinical outcomes at follow-up. This pilot study aimed to understand the mechanisms resulting in a suboptimal FFR and whether optical coherence tomography (OCT)-guided optimisation could improve final FFR.Methods and results: Thirty-five patients undergoing complex PCI were prospectively enrolled. After stenting and post-dilatation, OCT and pressure wire were performed. An FFR threshold <0.90 after PCI was defined as suboptimal and mandated further PCI optimisation. A satisfactory post-PCI FFR (predefined as ≥0.90) was achieved immediately after conventional PCI in 14 patients (40%) and in this group no further treatment was performed. Minor abnormalities (stent malapposition of 200-500 µm) were observed with OCT in three of these patients. Suboptimal functional results after conventional stenting (predefined as an FFR <0.90) were found in 21 patients (60%). In thirteen out of these 21 patients (61.9%), OCT demonstrated a suboptimal stent result. Subsequent OCT-guided optimisation was performed resulting in a higher final FFR (increase from 0.80±0.02 to 0.88±0.01; p=0.008).Conclusions: Despite a satisfactory angiographic result, a suboptimal functional result is evident in a substantial proportion of patients undergoing complex PCI. Implementation of an OCT-guided PCI optimisation protocol may reveal potentially treatable causes, allowing optimisation of the post-PCI functional result.

AimsWe systematically reviewed the European real-world evidence (RWE) about sacubitril-valsartan for heart failure with reduced ejection fraction. Methods and results Twenty-one articles, including 16 952 subjects, were identified until 31 October 2020. Taking as reference the PARADIGM-HF cohort, few baseline characteristics were presented in >80% of these studies, most often with high heterogeneity. In random-effects model meta-analysis, age was higher (mean difference +3.84, 95% CI 1.92-5.76), ischaemic aetiology (OR 0.76, 95% CI 0.64-0.91), hypertension (OR 0.55, 95% CI 0.37-0.82), and diabetes (OR 0.77, 95% CI 0.64-0.92) were less common, and the use of mineralocorticoid receptor antagonists was more frequent (OR 3.54, 95% CI 2.27-5.53) in real-life than in PARADIGM-HF. Other clinical and medical features were presented in 19-76% of the selected publications and suggested more severe heart failure with reduced ejection fraction. Sacubitril-valsartan was titrated to 97/103 mg b.i.d. in 35% (95% CI 23-47) and discontinued in 12.8% (95% CI 7.4-18.3) patients. When reported, the incidence of hyperkalaemia (six studies, no. 1076), all-cause mortality (five studies, no. 684), and any hospitalization (three studies, no. 390) was 12 (95% CI 5-19)/100 person-year, 8 (95% CI 4-12)/100 person-year, and 24 (95% CI 5-42)/100 person-year, respectively. Knowledge contribution, a metric measuring the proportion of RWE provided by each article based on the number of reported variables and the sample size, was 58.8% and 13.6% for the two biggest investigations (12 082 and 2037 patients), and <5% for all others (most with <100 subjects). Conclusions Limited-quality RWE indicates that there are important differences between European patients prescribed sacubitril-valsartan and the PARADIGM-HF population, including the frequency of target dose achievement.

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%.

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