The dual-antiplatelet therapy (DAPT) score was developed to identify patients more likely to derive harm (score <2) or benefit (score ≥2) from prolonged DAPT after percutaneous coronary intervention ...(PCI).
To evaluate the safety and efficacy of DAPT duration according to DAPT score.
Retrospective assessment of DAPT score-guided treatment duration in a randomized clinical trial. (ClinicalTrials.gov: NCT00611286).
PCI patients.
1970 patients undergoing PCI.
DAPT (aspirin and clopidogrel) for 24 versus 6 months.
Primary efficacy outcomes were death, myocardial infarction, or cerebrovascular accident. The primary safety outcome was type 3 or 5 bleeding according to the Bleeding Academic Research Consortium definition. Outcomes were assessed between 6 and 24 months.
884 patients (44.9%) had a DAPT score of at least 2, and 1086 (55.1%) had a score less than 2. The reduction in the primary efficacy outcome with 24- versus 6-month DAPT was greater in patients with high scores (risk difference RD for score ≥2, -2.05 percentage points 95% CI, -5.04 to 0.95 percentage points; RD for score <2, 2.91 percentage points CI, -0.43 to 6.25 percentage points; P = 0.030). However, the difference by score for the primary efficacy outcome varied by stent type; prolonged DAPT with high scores was effective only in patients receiving paclitaxel-eluting stents (RD, -7.55 percentage points CI, -12.85 to -2.25 percentage points). The increase in the primary safety outcome with 24- versus 6-month DAPT was greater in patients with low scores (RD for score ≥2, 0.20 percentage point CI, -1.20 to 1.60 percentage points; RD for score <2, 2.58 percentage points CI, 0.71 to 4.46 percentage points; P = 0.046).
Retrospective calculation of the DAPT score.
Prolonged DAPT resulted in harm in patients with low DAPT scores undergoing PCI but reduced risk for ischemic events in patients with high scores receiving paclitaxel-eluting stents. Whether prolonged DAPT benefits patients with high scores treated with contemporary drug-eluting stents requires further study.
None.
The human Subthalamic Nucleus (STh) is a diencephalic lens-shaped structure located ventrally to the thalamus and functionally implicated in the basal ganglia circuits. Despite recent efforts to ...characterize the neurochemical and functional anatomy of the STh, little to no information is available concerning the expression and distribution of receptors belonging to the dopaminergic and purinergic system in the human STh. Both systems are consistently implicated in basal ganglia physiology and pathology, especially in Parkinson’s Disease, and represent important targets for the pharmacological treatment of movement disorders. Here, we investigate the topography and distribution of A
2A
adenosine and D
2
dopamine receptors in the human basal ganglia and subthalamic nucleus. Our findings indicate a peculiar topographical distribution of the two receptors throughout the subthalamic nucleus, while colocalization between the receptors opens the possibility for the presence of A
2A
R- D
2
R heterodimers within the dorsal and medial aspects of the structure. However, further investigation is required to confirm these findings.
Abstract Objectives The aim of this study was to assess the impact of sex on 2-year outcomes after percutaneous coronary intervention (PCI) in patients randomly allocated to 24-month versus 6-month ...dual-antiplatelet therapy (DAPT). Background The optimal duration of DAPT after PCI is highly debated. Whether sex per se should drive decision making on DAPT duration remains unclear. Methods The primary efficacy endpoint of PRODIGY (Prolonging Dual Antiplatelet Treatment After Grading Stent-Induced Intimal Hyperplasia Study) was the composite of death, myocardial infarction, or cerebrovascular accident at 24-month follow-up. The key safety endpoint was type 2, 3, or 5 bleeding according to the Bleeding Academic Research Consortium criteria. Results Women (n = 459 23.3%) were older and more likely to have hypertension, lower creatinine clearance, and acute coronary syndrome but had a lower severity of coronary artery disease. After adjustment, prolonged DAPT, compared with 6-month treatment, did not reduce the primary endpoint in both men (adjusted hazard ratio: 1.080; 95% confidence interval: 0.766 to 1.522; p = 0.661) and women (adjusted hazard ratio: 1.013; 95% confidence interval: 0.588 to 1.748; p = 0.962) (interaction p = 0.785). No sex disparity was identified across multiple secondary ischemic endpoints, including overall or cardiovascular mortality, myocardial infarction, and stent thrombosis. There was also no clear sex-related effect on clinically relevant bleeding, including Bleeding Academic Research Consortium type 3 or 5, TIMI (Thrombolysis in Myocardial Infarction), and GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) scales. Conclusions The present findings suggest that men and women undergoing PCI have similar adjusted 2-year ischemic and bleeding outcomes, despite being characterized by different clinical presentation. Sex failed to emerge as a treatment modifier with respect to DAPT duration, suggesting that decision making on DAPT duration in female patients should weigh ischemic versus bleeding risks.
New-generation drug-eluting stents (DES) have mostly been investigated in head-to-head non-inferiority trials against early-generation DES and have typically shown similar efficacy and superior ...safety. How the safety profile of new-generation DES compares with that of bare-metal stents (BMS) is less clear.
We did an individual patient data meta-analysis of randomised clinical trials to compare outcomes after implantation of new-generation DES or BMS among patients undergoing percutaneous coronary intervention. The primary outcome was the composite of cardiac death or myocardial infarction. Data were pooled in a one-stage random-effects meta-analysis and examined at maximum follow-up and a 1-year landmark. Risk estimates are reported as hazard ratios (HRs) with 95% CIs. This study is registered in PROSPERO, number CRD42017060520.
We obtained individual data for 26 616 patients in 20 randomised trials. Mean follow-up was 3·2 (SD 1·8) years. The risk of the primary outcome was reduced in DES recipients compared with BMS recipients (HR 0·84, 95% CI 0·78–0·90, p<0·001) owing to a reduced risk of myocardial infarction (0·79, 0·71–0·88, p<0·001) and a possible slight but non-significant cardiac mortality benefit (0·89, 0·78–1·01, p=0·075). All-cause death was unaffected (HR with DES 0·96, 95% CI 0·88–1·05, p=0·358), but risk was lowered for definite stent thrombosis (0·63, 0·50–0·80, p<0·001) and target-vessel revascularisation (0·55, 0·50–0·60, p<0·001). We saw a time-dependent treatment effect, with DES being associated with lower risk of the primary outcome than BMS up to 1 year after placement. While the effect was maintained in the longer term, there was no further divergence from BMS after 1 year.
The performance of new-generation DES in the first year after implantation means that BMS should no longer be considered the gold standard for safety. Further development of DES technology should target improvements in clinical outcomes beyond 1 year.
Bern University Hospital.
The aim of this study was to assess the impact of sex on 2-year outcomes after percutaneous coronary intervention (PCI) in patients randomly allocated to 24-month versus 6-month dual-antiplatelet ...therapy (DAPT).
The optimal duration of DAPT after PCI is highly debated. Whether sex per se should drive decision making on DAPT duration remains unclear.
The primary efficacy endpoint of PRODIGY (Prolonging Dual Antiplatelet Treatment After Grading Stent-Induced Intimal Hyperplasia Study) was the composite of death, myocardial infarction, or cerebrovascular accident at 24-month follow-up. The key safety endpoint was type 2, 3, or 5 bleeding according to the Bleeding Academic Research Consortium criteria.
Women (n = 459 23.3%) were older and more likely to have hypertension, lower creatinine clearance, and acute coronary syndrome but had a lower severity of coronary artery disease. After adjustment, prolonged DAPT, compared with 6-month treatment, did not reduce the primary endpoint in both men (adjusted hazard ratio: 1.080; 95% confidence interval: 0.766 to 1.522; p = 0.661) and women (adjusted hazard ratio: 1.013; 95% confidence interval: 0.588 to 1.748; p = 0.962) (interaction p = 0.785). No sex disparity was identified across multiple secondary ischemic endpoints, including overall or cardiovascular mortality, myocardial infarction, and stent thrombosis. There was also no clear sex-related effect on clinically relevant bleeding, including Bleeding Academic Research Consortium type 3 or 5, TIMI (Thrombolysis in Myocardial Infarction), and GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) scales.
The present findings suggest that men and women undergoing PCI have similar adjusted 2-year ischemic and bleeding outcomes, despite being characterized by different clinical presentation. Sex failed to emerge as a treatment modifier with respect to DAPT duration, suggesting that decision making on DAPT duration in female patients should weigh ischemic versus bleeding risks.
New-generation drug-eluting stents (DES) strongly reduce restenosis and repeat revascularization compared with bare-metal stents (BMS) for percutaneous coronary intervention. There is residual ...uncertainty as to whether other prognostically relevant outcomes are affected by DES versus BMS concerning initial presentation (chronic coronary syndrome CCS vs acute coronary syndrome ACS). We performed an individual patient data meta-analysis of randomized trials comparing new-generation DES versus BMS (CRD42017060520). The primary outcome was the composite of cardiac death or myocardial infarction (MI). Outcomes were examined at maximum follow-up and with a 1-year landmark. Risk estimates are expressed as hazard ratio (HR) with 95% confidence interval (CI). A total of 22,319 patients were included across 14 trials; 7,691 patients (34.5%) with CCS and 14,628 patients (65.5%) with ACS. We found evidence that new-generation DES versus BMS consistently reduced the risk of cardiac death or MI in both patients with CCS (HR 0.83, 95% CI 0.70 to 0.98, p <0.001) and ACS (HR 0.83, 95% CI 0.75 to 0.92, p <0.001) (p-interaction = 0.931). This benefit was mainly driven by a similar reduction in the risk of MI (p-interaction = 0.898) for both subsets (HRCCS 0.80, 95% CI 0.65 to 0.97; HRACS 0.79, 95% CI 0.70 to 0.89). In CCS and ACS, we found a time-dependent treatment effect, with the benefit from DES accumulating during 1-year follow-up, without offsetting effects after that. In conclusion, patients with CCS were slightly underrepresented in comparative clinical trials. Still, they benefited similarly to patients with ACS from new-generation DES instead of BMS with a sustained reduction of cardiac death or MI because of lower event rates within 1 year.
Patients with concomitant peripheral arterial disease (PAD) experience worse cardiovascular outcomes after percutaneous coronary intervention (PCI).
To assess the efficacy and safety of prolonged (24 ...months) vs short (≤6 months) dual antiplatelet therapy (DAPT) in patients with PAD undergoing PCI.
This subanalysis of the randomized Prolonging Dual Antiplatelet Treatment After Grading Stent-Induced Intimal Hyperplasia Study (PRODIGY) trial assessed unselected patients from tertiary care hospitals with stable coronary artery disease or acute coronary syndromes with or without concomitant PAD from December 2006 to December 2008. Data analysis was performed from January 7 to April 4, 2016.
Percutaneous coronary intervention.
Rates of the primary efficacy end point, composite of death, myocardial infarction, or cerebrovascular accidents, and occurrence of the key safety end point, a composite of Bleeding Academic Research Consortium type 2, 3, or 5.
This analysis comprised 246 and 1724 patients with and without PAD, respectively. In the patients with PAD, mean (SD) age was 73.2 (9.2) in the prolonged group and 75.7 (8.7) years in the short DAPT group, and 97 (82.2%) were male in the prolonged group and 92 (71.9%) were male in the short DAPT group. In the patients without PAD, mean (SD) age was 67.1 (11.2) years in the prolonged group and 66.8 (11.3) years in the short DAPT group, and 667 (76.8%) were male in the prolonged group and 655 (76.6%) were male in the short DAPT group. Status of PAD was associated with a higher risk of death and ischemic events (hazard ratio HR, 2.80; 95% CI, 2.05-3.83; P < .001). Prolonged vs short DAPT conveyed a lower risk of the primary efficacy end point in patients with PAD (19 16.1% vs 35 27.3%; HR, 0.54; 95% CI, 0.31-0.95; P = .03) but not in patients without PAD (81 9.3% vs 63 7.4%; HR, 1.28; 95% CI, 0.92-1.77; P = .15), with positive interaction (P = .01). The risk of definite or probable stent thrombosis was significantly lower in patients with PAD treated with prolonged compared with short DAPT (HR, 0.07; 95% CI, 0-1.21; P = .01). Bleeding Academic Research Consortium type 2, 3, or 5 bleeding occurred in 6 patients with PAD (5.2%) receiving prolonged DAPT relative to 8 (6.9%) of those receiving short DAPT (HR, 0.77; 95% CI, 0.27-2.21; P = .62), with a significant interaction (P = .04) compared with patients without PAD.
Peripheral artery disease confers a poor prognosis in patients undergoing PCI in the setting of stable coronary artery disease or acute coronary syndromes. Prolonged DAPT lowers the risk of ischemic events with no apparent bleeding liability in this high-risk group.
clinicaltrials.gov Identifier: NCT00611286.
Several studies established a link between bleeding and mortality in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI); however, it ...is unclear whether bleeding has a direct role in worsening the prognosis or if it is simply a marker of patient frailty. We investigated whether bleeding is an independent predictor of mortality in patients with STEMI treated with pPCI. The relationship between the presence of heart failure on presentation (Killip classification), bleeding occurrence, and outcome was also assessed. Bleeding was defined as the combination of Thrombolysis in Myocardial Infarction major and minor bleeding. Short- and long-term mortalities were estimated using the Kaplan–Meyer analysis. Multivariable analysis was performed by the Cox regression model. As an alternative method to address the potential confounding factors, we performed a propensity-matched analysis adjusted for all variables included in the CRUSADE score. In the 1,911 consecutive patients with STEMI considered, bleeding (observed in 11.4% of patients) was an independent predictor of 30-day (hazard ratio 2.61, 95% confidence interval 1.30 to 5.25, p = 0.007) and 1-year mortality (hazard ratio 1.98, 95% confidence interval 1.13 to 3.47, p = 0.017) but not in a landmark analysis starting from 30 days to 1 year. Bleeding was significantly associated with higher 30-day and 1-year mortality in patients with Killip class ≥II, but not in patients with Killip class I. In conclusion, in-hospital bleeding is independently associated with increased mortality in the early period after STEMI, also after adjusting for variables associated with the risk of bleeding. Bleeding was associated with increased mortality in patients with signs of heart failure at admission, whereas it had no effects in patients with Killip class I.
The aim of this study was to investigate whether the platelet to lymphocyte ratio (PLR), an aspecific inflammatory marker associated in previous studies with adverse cardiovascular outcomes, could be ...a predictor of CIN.
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