Relationship between adenosine A2a receptor polymorphism rs5751876 and fractional flow reserve during percutaneous coronary intervention.

Fractional flow reserve (FFR) assessed during adenosine-induced maximal hyperemia has emerged as a useful tool for the guidance of percutaneous coronary interventions (PCI). However, interindividual variability in the response to adenosine has been claimed as a major limitation to the use of adenosine for the measurement of FFR, carrying the risk of underestimating the severity of coronary stenoses, with potential negative prognostic consequences. Genetic variants of the adenosine receptor A2a (ADORA2A gene), located in the coronary circulation, have been involved in the modulation of the hyperemic response to adenosine. However, no study has so far evaluated the impact of the single nucleotide polymorphism rs5751876 of ADORA2A on the measurement of FFR in patients undergoing percutaneous coronary intervention that was, therefore, the aim of our study. We included patients undergoing coronary angiography and FFR assessment for intermediate (40-70%) coronary lesions. FFR measurement was performed by pressure-recording guidewire (Prime Wire, Volcano), after induction of hyperemia with intracoronary boli of adenosine (from 60 to 1440 µg, with dose doubling at each step). Restriction fragment length polymorphism (RFLP) analysis was performed to assess the presence of rs5751876 C>T polymorphism of ADORA2a receptor. We included 204 patients undergoing FFR measurement of 231 coronary lesions. A total of 134 patients carried the polymorphism (T allele), of whom 41 (30.6%) in homozygosis (T/T).Main clinical and angiographic features did not differ according to ADORA2A genotype. The rs5751876 C>T polymorphism did not affect mean FFR values (p = 0.91), the percentage of positive FFR (p = 0.54) and the duration of maximal hyperemia. However, the time to recovery to baseline FFR values was more prolonged among the T-allele carriers as compared to wild-type patients (p = 0.04). Based on these results, in patients with intermediate coronary stenoses undergoing FFR assessment with adenosine, the polymorphism rs5751876 of ADORA2A does not affect the peak hyperemic response to adenosine and the results of FFR. However, a more prolonged effect of adenosine was observed in T-carriers.

Very short dual antiplatelet therapy after PCI and new DES: a meta-analysis of 5 randomized trials.

INTRODUCTION AND OBJECTIVES: Very early (1-3 months) discontinuation of dual antiplatelet therapy (DAPT) has been recently proposed in percutaneous coronary interventions with modern drug-eluting stents (DES), with contrasting results. The aim of the present meta-analysis was to evaluate the prognostic impact of very short DAPT regimens vs the standard 12-month regimen in patients undergoing percutaneous coronary intervention with new DES. METHODS: Literature and main scientific session abstracts were searched for randomized clinical trials (RCT). The primary efficacy endpoint was mortality, and the primary safety endpoint was major bleeding events. A prespecified analysis was conducted according to the long-term antiplatelet agent. RESULTS: We included 5 RCTs, with a total of 30 621 patients; 49.97% were randomized to very short (1-3 months) DAPT, followed by aspirin or P2Y12I monotherapy. Shorter DAPT duration significantly reduced the rate of major bleeding (2% vs 3.1%, OR, 0.62; 95%CI, 0.46-0.84; P=.002; Phet=.02), but did not significantly condition overall mortality (1.3% vs 2%, OR, 0.97; 95%CI, 0.73-1.29; P=.84; Phet=.18). The reduction in bleeding events was even more significant in trials randomizing event-free patients at the time of DAPT discontinuation. The occurrence of myocardial infarction and stent thrombosis was similar between shorter vs standard 12-month DAPT. CONCLUSIONS: Based on the current meta-analysis, a very short (1-3 months) period is associated with a significant reduction in major bleeding compared with the standard 12-month therapy, with no increase in major ischemic events and comparable survival.

Impact of Age on the Functional Evaluation of Intermediate Coronary Stenoses With Instantaneous Wave-Free Ratio and Fractional Flow Reserve.

The optimal strategy for assessing the ischemic significance of intermediate coronary stenoses with adenosine-induced fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) is still debated. Few studies have previously assessed the impact of age on FFR and iFR, which was the aim of our study. Patients undergoing FFR and iFR evaluation for intermediate (40%-70%) coronary lesions were included and divided according to age. Fractional flow reserve was performed by intracoronary boluses of adenosine (60-1440 µg). Instantaneous wave-free ratio was automatically calculated. Among 148 patients undergoing FFR measurement of 166 lesions, 45.3% were ≥70 years. Elderly patients had higher minimal lumen diameter (P = .03). We also observed a linear relationship between iFR and FFR independently of age. Fractional flow reserve values were higher in the elderly patients, whereas iFR was not related to age. A total of 33 lesions had a positive iFR with no difference for age (17.3% vs 22%, P = .56), while FFR <0.80 was more infrequent in the elderly patients (17.1% vs 34.8%, P = .02). In intermediate coronary stenoses, iFR and FFR correlation is unaffected by age. Fractional flow reserve is higher in the elderly patients, whereas iFR is less affected by age. Future large-scale studies are needed to define whether iFR should be the preferred choice in elderly patients.

Duration of dual antiplatelet therapy and outcome in patients with acute coronary syndrome undergoing percutaneous revascularization: A meta-analysis of 11 randomized trials.

BACKGROUND: Acute coronary syndromes (ACS) represent a context of higher thrombotic risk, where larger advantages have been achieved by the administration of dual antiplatelet therapy (DAPT). However, the indication of 1 year DAPT after coronary angioplasty for ACS has been supported by an outdated randomized trial (PCI-CURE). In addition, the initial fear of late thrombotic events emerged with first generation drug-eluting stents (DES), that suggested the need of a prolonged DAPT prescription, has been completely overcome by the recent technological evolution of DES, that have shown faster re-endothelization and lower rates of late thrombotic complications. By keeping in mind the balance between thrombotic and bleeding complications, and due to the paucity of dedicated randomized trials, the identification of the optimal duration of DAPT after ACS is still matter of debate, and is therefore the aim of the present meta-analysis. METHODS: Literature and main scientific session abstracts were searched. The primary efficacy endpoint was mortality, primary safety endpoint was the occurrence of major bleedings. A pre-specified analysis was conducted according to the DAPT strategy allocation (<12 vs standard 12 months duration and 6-12 months vs extended DAPT). RESULTS: We included 3 RCTs and subanalyses from 8 RCTs, with a total of 17,941 patients. No difference in mortality was observed between shorter vs longer DAPT (OR[95%CI] = 1.11[0.90,1.36], p = 0.33; phet = 0.76). A shorter DAPT duration significantly reduced the rate of major bleeding events (1.5%, vs 1.9%, OR [95%CI] = 0.75 [0.60, 0.94], p = 0.01; phet = 0.43). The reduction in bleeding events was more significant in trials evaluating extended DAPT duration (OR[95%CI] = 0.62[0.45, 0.85], p = 0.003; phet = 0.49). No difference in cardiovascular mortality, myocardial infarction and stent thrombosis was observed with shorter vs standard 12-moth DAPT, whereas a more extended treatment (beyond 1 year), was associated with a significant reduction in recurrent ischemic events. Similar results were observed at a sensitivity analysis conducted according to the type of stent, time to randomization or DAPT duration. CONCLUSIONS: Based on the current meta-analysis including 17,941 ACS patients undergoing PCI, a short duration of DAPT may be safely considered, with similar rates of recurrent thrombotic complications as compared to the standard 12 months, and similar mortality. A more extended DAPT administration (beyond 1 year) provides benefits in ischemic events, but with an excess in haemorragic complications, with overall neutral effects on mortality.