Background. Randomized trials have shown superiority of the novel P2Y12 inhibitors over clopidogrel in patients with acute coronary syndrome (ACS), but clinical benefit in the community remains controversial. Our objective was to compare the safety and efficacy of clopidogrel to ticagrelor and prasugrel in patients with ACS undergoing percutaneous coronary intervention (PCI) in a real-world population. Methods. We conducted a retrospective cohort study of patients with ACS who underwent PCI and were discharged with clopidogrel, ticagrelor, or prasugrel from 2012 to 2018 within Kaiser Permanente Northern California. We used Cox proportional hazard models with propensity-score matching to evaluate the association of the P2Y12 agent with the primary outcomes of all-cause mortality, myocardial infarction (MI), stroke, and bleeding events. Results. The study included 15,476 patients (93.1% on clopidogrel, 3.6% on ticagrelor and 3.2% on prasugrel). Compared to the clopidogrel group, ticagrelorand prasugrel patients were younger with less comorbidities. In multivariable models with propensity-score matching, we found a lower risk of all-cause mortality in the ticagrelor vs the clopidogrel group (HR (95% CI) 0.43 (0.20–0.92)), but no differences in the other endpoints, and no difference between prasugrel and clopidogrel among any endpoints. A larger proportion of patients on ticagrelor or prasugrel switched to an alternative P2Y12 agent vs. clopidogrel (p < 0.01), and a higher level of persistence was seen among patients on clopidogrel vs. ticagrelor (p = 0.03) or prasugrel (p < 0.01). Conclusion. Among patients with ACS who underwent PCI, we observed a lower risk of all-cause mortality in patients treated with ticagrelor vs clopidogrel, but no difference in other clinical endpoints nor any differences in endpoints between prasugrel vs. clopidogrel users. These results suggest that further study is needed to identify an optimal P2Y12 inhibitor in a real-world population.

The optimal duration of dual antiplatelet therapy (DAPT) after treatment of chronic total occlusions (CTO) with percutaneous coronary intervention (PCI) is unknown. We aimed to determine if extended (> 12 months) DAPT was associated with a net clinical benefit. The study population included patients who underwent successful CTO PCI within Kaiser Permanente Northern California between 2009 and 2016. Baseline demographic, clinical, and procedural characteristics were compared for patients on DAPT <= versus > 12 months. Clinical outcomes (death, myocardial infarction (MI), and >= Academic Research Consortium type 3a bleeding) were compared beginning 12 months after PCI using Cox proportional hazards models. We also adjudicated individual causes of death. 1,069 patients were followed for a median of 3.6 years (Interquartile Range = 2.2 to 5.5) following CTO PCI. Patients on DAPT = 12 months (n = 597, 56%) were more likely to have anemia, end stage renal disease, and previous MI. After adjustment for between group differences, > 12 months of DAPT was associated with lower death or MI (hazard ratio [HR]: 0.66; 95% confidence interval [CI]: 0.47 to 0.93) and lower death (HR: 0.54; 95% CI: 0.36 to 0.82). There were no associations with MI (HR: 0.91; 95% CI: 0.55 to 1.5) or bleeding (HR 1.1; 95% CI: 0.50 to 2.4), but a numerically higher proportion of patients on shorter v. longer DAPT died of a cardiovascular cause (37% vs 20%, p = 0.10). In conclusion, > 12 months of DAPT was associated with lower death or MI, without an increase in bleeding. Prospective studies are needed to evaluate the optimal duration of DAPT in this unique subgroup. (C) 2020 Elsevier Inc. All rights reserved.

The optimal duration of thienopyridine therapy after PCI for CTOs is unknown. We aimed to determine if extended (> 12 months) thienopyridine therapy was associated with a net clinical benefit. The study population included patients undergoing successful CTO PCI within Kaiser Permanente Northern

Objectives This study sought to examine the pattern of death and myocardial infarction (MI) after clopidogrel cessation in patients undergoing percutaneous coronary intervention (PCI) of the saphenous vein graft (SVG).Background The timing and incidence of adverse events by different durations of clopidogrel therapy after SVG PCI remain unknown.Methods This is a cohort study of patients undergoing SVG PCI between 2000 and 2009, followed for all-cause mortality or MI after stopping clopidogrel. Incidence rates were calculated across different time periods after clopidogrel cessation. Adjusted incidence rate ratios (IRR) were calculated with multivariable regression (piecewise exponential and Poisson).Results There were 603 patients who underwent SVG PCI, of which 411 were event-free at the time of clopidogrel cessation. The incidence rate (95% confidence interval: [CI])/1,000 person-days of death or MI after stopping clopidogrel in the time intervals of 0 to 90 days, 91 to 365 days, and 1 to 2 years were 1.26 (95% CI: 0.93 to 1.70), 0.41 (95% CI: 0.30 to 0.56), and 0.41 (95% CI: 0.30 to 0.55), respectively. In multivariable analyses, the overall IRR (95% CI) for death or MI in the 0- to 90-day interval after stopping clopidogrel compared with the 91- to 365-day interval was 2.58 (95% CI: 1.64 to 4.07). Similar results were observed over a broad range of clopidogrel treatment durations (<6 months, 6 months to 1 year, 1 to 2 years, or >2 years). The results were also consistent across subgroups, including sex, stent type, stent diameter, PCI period, and diabetes status. When death alone was evaluated, there remained a significant increase in the event rate in the 0- to 90-day interval compared with the 91- to 365-day interval (IRR: 2.33; 95% CI: 1.32 to 4.11).Conclusions A clustering of events was observed in the initial 0 to 90 days after clopidogrel cessation in all treatment durations of clopidogrel investigated after SVG PCI. These results might have important implications in high-risk cohorts undergoing PCI. Additional studies are needed to elucidate the mechanisms underlying the early clustering of events after clopidogrel cessation. (J Am Coll Cardiol 2012; 60: 2357-63) (C) 2012 by the American College of Cardiology Foundation

B-type natriuretic peptide (BNP), peak oxygen consumption (VO2), blood urea nitrogen (BUN), systolic blood pressure (SBP), and pulmonary capillary wedge pressure are all established predictors of mortality or urgent transplantation in patients with advanced heart failure (HF). However, their comparative predictive ability in estimating prognosis has not been well studied. We analyzed 1,215 patients with advanced systolic HF referred to a university center from 1999 to 2009. BUN, BNP, VO2, SBP, and pulmonary capillary wedge pressure were measured as a part of the initial evaluation. The patients were divided into groups according to the best cutoffs for predicting both 1- and 2-year mortality from the analysis of the receiver operating characteristic curves (BNP >= 579 pg/ml, peak VO2 <14 ml/kg/min, BUN >= 53 mg/dl, SBP <118 mm Hg, and pulmonary capillary wedge pressure >= 21 mm Hg). During a 2-year follow-up, 234 patients (19%) died, and 208 (17%) required urgent transplantation. BNP (odds ratio 4.3, 95% confidence interval 3.3 to 5.5) and peak VO2 (odds ratio 4.5, 95% confidence interval 2.6 to 7.8) were the strongest predictors for death or urgent transplantation. On multivariate analyses, BNP and peak VO2 were the strongest predictors for both death or urgent transplantation and all-cause mortality. The c-statistic was 0.756 for BNP, 0.701 for VO2, 0.659 for BUN, 0.638 for SBP, and 0.650 for pulmonary capillary wedge pressure. In conclusion, of the 5 established predictors of outcomes in advanced HF, BNP was the most robust discriminator of risk and thus could be useful, along with other more traditional prognostic variables, in patient counseling regarding prognosis and determining the timing for heart transplantation. (C) 2010 Elsevier Inc. All rights reserved. (Am J Cardiol 2010;106:830-835)

Dopamine is an endogenous natriuretic amine that contributes to the maintenance of sodium homeostasis. Deficiencies in the renal production of dopamine and the action of dopamine on renal tubular receptors have been observed in human hypertension and may contribute to salt sensitivity of blood pressure. Ethnic differences in the sodium‐to‐dopamine relationship may contribute to the higher prevalence of salt sensitivity in blacks. The authors assessed dopaminergic activity in two studies. In the first, daytime and nighttime excretion of sodium and dopamine were compared in 11 black and 17 white normotensive patients. No racial difference in the rate of sodium or dopamine excretion during either period was observed. In the second study, a graded infusion of the dopamine‐1 receptor agonist, fenoldopam, was performed in 14 black and 17 white normotensive patients. There was no racial difference in the natriuretic responses. Previously described lower rates of renal free water clearance and potassium excretion in blacks compared with whites were maintained during fenoldopam infusion, suggesting that dopamine is not a mediator of those differences. The authors conclude that there are no race‐related differences in dopamine excretion or activity in normotensive patients.

Background Lipid levels among contemporary patients hospitalized with coronary artery disease (CAD) have not been well studied. This study aimed to analyze admission lipid levels in a broad contemporary population of patients hospitalized with CAD.Methods The Get With The Guidelines database was analyzed for CAD hospitalizations from 2000 to 2006 with documented lipid levels in the first 24 hours of admission. Patients were divided into low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), and triglyceride categories. Factors associated with LDL and HDL levels were assessed along with temporal trends.Results Of 231,986 hospitalizations from 541 hospitals, admission lipid levels were documented in 136,905 (59.0%). Mean lipid levels were LDL 104.9 +/- 39.8, HDL 39.7 +/- 13.2, and triglyceride 161 +/- 128 mg/dL. Low-density lipoprotein cholesterol <70 mg/dL was observed in 17.6% and ideal levels (LDL <70 with HDL >= 60 mg/dL) in only 1.4%. High-density lipoprotein cholesterol was <40 mg/dL in 54.6% of patients. Before admission, only 28,944 (21.1%) patients were receiving lipid-lowering medications. Predictors for higher LDL included female gender, no diabetes, history of hyperlipidemia, no prior lipid-lowering medications, and presenting with acute coronary syndrome. Both LDL and HDL levels declined over time (P < .0001).Conclusions In a large cohort of patients hospitalized with CAD, almost half have admission LDL levels <100 mg/dL. More than half the patients have admission HDL levels <40 mg/dL, whereas <10% have HDL >= 60 mg/dL. These findings may provide further support for recent guideline revisions with even lower LDL goals and for developing effective treatments to raise HDL. (Am Heart J 2009;157:111-7.)

A recent report demonstrated a racial difference in response to furosemide compatible with increased ion reabsorption in the thick ascending limb of the loop of Henle in blacks. Urinary dilution is another function of the loop-diuretic–sensitive Na,K,2Cl cotransporter in the thick ascending limb, and racial differences in urinary diluting capacity have not been reported previously. We assessed diluting segment (cortical thick ascending limb and distal convoluted tubule) function in black and white normotensives in 2 studies using a water-loading approach. In both studies, we found that whites excreted a water load more rapidly than blacks. In the first study, the final free water clearance rates (mean±SD) were 7.3±4.7 mL/min in whites (n=17, 7 females and 10 males) and 3.8±3.6 mL/min in blacks (n=14, 9 females and 5 males; P <0.03). In the second study, final free water clearance rates were 8.3±2.6 mL/min in whites (n=17, 8 females and 9 males) and 6.4±1.8 mL/min in blacks (n=11, 8 females and 3 males; P <0.01). We found no evidence of a racial difference in renal proximal tubular fluid reabsorption as assessed by renal endogenous lithium clearance or in plasma vasopressin level that could explain the difference in free water excretion. We conclude that our observations are most consistent with a lower capacity of ion reabsorption in the renal diluting segment in blacks. Slower excretion of an acute water load may have been an advantage during natural selection of humans living in arid, hot climates.