Design and rationale of the XIENCE short DAPT clinical program: An assessment of the safety of 3-month and 1-month DAPT in patients at high bleeding risk undergoing PCI with an everolimus-eluting stent.

Dual antiplatelet therapy (DAPT) is key for the prevention of recurrent ischemic events after percutaneous coronary intervention (PCI); however, it increases the risk of bleeding complications. While new generation drug-eluting stents have been shown superior to bare-metal stents after a short DAPT course, the optimal DAPT duration in patients at high bleeding risk (HBR) remains to be determined. TRIAL DESIGN: The XIENCE Short DAPT program consists of three prospective, single-arm studies (XIENCE 90, XIENCE 28 Global and XIENCE 28 USA) investigating 3- or 1-month DAPT durations in HBR patients undergoing PCI with the XIENCE stent. The XIENCE 90 study is being conducted in the US and enrolled 2047 subjects who discontinued DAPT at 3 months if they were free from myocardial infarction (MI), repeat coronary revascularization, stroke, or stent thrombosis. The XIENCE 28 program includes the USA study, enrolling 642 patients in US and Canada, and the Global study, enrolling 963 patients in Europe and Asia. In XIENCE 28, patients were to discontinue DAPT at 1 month post-PCI if event-free. The primary hypothesis for both XIENCE 90 and XIENCE 28 is that a short DAPT regimen will be non-inferior to a conventional DAPT duration with respect to the composite of all-cause death or MI. Patients enrolled in the prospective multicenter post-market XIENCE V USA study will be used as historical control group in a stratified propensity-adjusted analysis. CONCLUSIONS: The XIENCE Short DAPT Program will provide insights into the safety and efficacy of 2 abbreviated DAPT regimens of 3- and 1-month duration in a large cohort of HBR patients undergoing PCI with the XIENCE stent.

Economic burden associated with inadequate antidepressant medication management among patients with depression and known cardiovascular diseases: insights from a United States-based retrospective claims database analysis.

Aims: The current study examined the association between insufficient major depressive disorder (MDD) care and healthcare resource use (HCRU) and costs among patients with prior myocardial infarction (MI) or stroke.Methods: This was a retrospective study conducted using the MarketScan Claims Database (2010-2015). The date of the first MI/stroke diagnosis was defined as the cardiovascular disease (CVD) index date and the first date of a subsequent MDD diagnosis was the index MDD date. Adequacy of MDD care was assessed during the 90 days following the index MDD date (profiling period) using 2 measures: dosage adequacy (average fluoxetine equivalent dose of ≥20 mg/day for nonelderly and ≥10 mg/day for elderly patients) and duration adequacy (measured as the proportion of days covered of 80% or higher for all MDD drugs). Study outcomes included all-cause and CVD-related HCRU and costs which were determined from the end of the profiling period until the end of study follow-up. Propensity-score adjusted generalized linear models (GLMs) were used to compare patients receiving adequate versus inadequate MDD care in terms of study outcomes.Results: Of 1,568 CVD patients who were treated for MDD, 937 (59.8%) were categorized as receiving inadequate MDD care. Results from the GLMs suggested that patients receiving inadequate MDD care had 14% more all-cause hospitalizations, 4% more all-cause outpatient visits, 17% more CVD-related outpatient visits, 13% more CVD-related emergency room (ER) visits, higher per patient per year CVD-related hospitalization costs ($21,485 vs. $17,756), higher all-cause outpatient costs ($2,820 vs. $2,055), and higher CVD-related outpatient costs ($520 vs. $434) compared to patients receiving adequate MDD care.Limitations: Clinical information such as depression severity and frailty, which are potential predictors of adverse CVD outcomes, could not be ascertained using administrative claims data.Conclusions: Among post-MI and post-stroke patients, inadequate MDD care was associated with a significantly higher economic burden.

Cardiovascular disease in the kidney transplant recipient: epidemiology, diagnosis and management strategies.

Kidney transplantation (KT) is the optimal therapy for end-stage kidney disease (ESKD), resulting in significant improvement in survival as well as quality of life when compared with maintenance dialysis. The burden of cardiovascular disease (CVD) in ESKD is reduced after KT; however, it still remains the leading cause of premature patient and allograft loss, as well as a source of significant morbidity and healthcare costs. All major phenotypes of CVD including coronary artery disease, heart failure, valvular heart disease, arrhythmias and pulmonary hypertension are represented in the KT recipient population. Pre-existing risk factors for CVD in the KT recipient are amplified by superimposed cardio-metabolic derangements after transplantation such as the metabolic effects of immunosuppressive regimens, obesity, posttransplant diabetes, hypertension, dyslipidemia and allograft dysfunction. This review summarizes the major risk factors for CVD in KT recipients and describes the individual phenotypes of overt CVD in this population. It highlights gaps in the existing literature to emphasize the need for future studies in those areas and optimize cardiovascular outcomes after KT. Finally, it outlines the need for a joint 'cardio-nephrology' clinical care model to ensure continuity, multidisciplinary collaboration and implementation of best clinical practices toward reducing CVD after KT.

Duration of Dual Antiplatelet Therapy in Patients with an Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention.

BACKGROUND: The recent American Heart Association/American College of Cardiology guidelines on duration of dual antiplatelet therapy (DAPT) recommend DAPT for 1 year in patients presenting with an acute coronary syndrome, with a Class IIb recommendation for continuation. We aim to assess the evidence for these recommendations using a meta-analytic approach. METHODS: We searched electronic databases for randomized trials comparing short-term (≤6 months) vs 12-month vs extended (>12 months) DAPT in patients with an acute coronary syndrome undergoing percutaneous coronary intervention. We evaluated all-cause mortality, cardiovascular mortality, myocardial infarction, stent thrombosis, and major bleeding. A random-effects model was used to calculate pooled relative risk (RR) and 95% confidence intervals (CI). RESULTS: We included 8 trials comprising 12,917 patients with an acute coronary syndrome; 5 trials compared short-term vs 12-month/extended DAPT, whereas 3 trials compared 12-month vs extended DAPT. There was no significant difference in cardiovascular mortality (RR 1.04; 95% CI, 0.67-1.60), myocardial infarction (RR 1.08; 95% CI, 0.79-1.47), or major bleeding (RR 0.91; 95% CI, 0.49-1.69) between short-term and 12-month/extended DAPT. However, compared with extended DAPT, 12-month DAPT showed significantly higher risk of myocardial infarction (RR 2.00; 95% CI, 1.47-2.73), but reduced risk of major bleeding (RR 0.58; 95% CI, 0.34-0.98). All-cause mortality was found to be similar between 12-month and extended DAPT. CONCLUSIONS: In acute coronary syndrome, short-term DAPT may be reasonable for some patients, whereas extended DAPT may be appropriate in select others. An individualized approach is needed, taking into account the competing risks of bleeding and ischemic events.

Drug-eluting stents versus bare metal stents prior to noncardiac surgery.

BACKGROUND: The safety of drug-eluting stents (DES) vs. bare metal stents (BMS) in the perioperative setting, a heightened state of inflammation and thrombosis is not well defined. METHODS: All adults undergoing noncardiac surgical (NCS) procedures within 1 year following percutaneous coronary intervention (PCI) in Massachusetts between April 1, 2004, and September 30, 2007, were identified from an administrative claims database. Patients were divided into those who received BMS vs. DES at index PCI. Primary net clinical outcome was death, myocardial infarction (MI) or bleeding within 30 days of NCS. Primary clinical outcome was 30-day death or MI. RESULTS: Among 8,415 (22% BMS) patients that satisfied our inclusion criteria, 1,838 BMS patients were matched with 3,565 DES patients with similar propensity scores. In the DES cohort, the 30-day primary net clinical outcome rate was lower with longer time from PCI to NCS (P = 0.02) with lowest rates if NCS was performed after 90 days from PCI (event rate 8.57, 7.53, 5.21, and 5.75% for 1-30, 31-90, 91-180, and 181-365 days from PCI to NCS). However, in the BMS cohort, the event rate was uniformly high regardless of the time from PCI to NCS (P = 0.60) (event rate 8.20, 6.56, 8.05, and 8.82% for 1-30, 31-90, 91-180, and 181-365 days from PCI to NCS). There was no significant difference between DES and the BMS group for 30-day primary net clinical outcome (6.64 vs. 7.89%; P = 0.10), but there was a 26% lower odds of primary clinical outcome (OR = 0.74, 95% CI 0.58-0.94) with DES when compared with BMS, driven mainly by differences in event rates when NCS was performed >90 days post PCI. CONCLUSION: DES implantation was not associated with higher adverse events after NCS. Moreover, the incidence of adverse events following NCS was lower when NCS was performed >90 days post-DES implantation suggesting that it may not be necessary to wait until 12 months post PCI with DES before NCS.

Prognostic value of fasting versus nonfasting low-density lipoprotein cholesterol levels on long-term mortality: insight from the National Health and Nutrition Examination Survey III (NHANES-III).

BACKGROUND: National and international guidelines recommend fasting lipid panel measurement for risk stratification of patients for prevention of cardiovascular events. However, the prognostic value of fasting versus nonfasting low-density lipoprotein cholesterol (LDL-C) is uncertain. METHODS AND RESULTS: Patients enrolled in the National Health and Nutrition Examination Survey III (NHANES-III), a nationally representative cross-sectional survey performed from 1988 to 1994, were stratified on the basis of fasting status (≥8 or <8 hours) and followed for a mean of 14.0 (±0.22) years. Propensity score matching was used to assemble fasting and nonfasting cohorts with similar baseline characteristics. The risk of outcomes as a function of LDL-C and fasting status was assessed with the use of receiver operating characteristic curves and bootstrapping methods. The interaction between fasting status and LDL-C was assessed with Cox proportional hazards modeling. Primary outcome was all-cause mortality. Secondary outcome was cardiovascular mortality. One-to-one matching based on propensity score yielded 4299 pairs of fasting and nonfasting individuals. For the primary outcome, fasting LDL-C yielded prognostic value similar to that for nonfasting LDL-C (C statistic=0.59 [95% confidence interval, 0.57-0.61] versus 0.58 [95% confidence interval, 0.56-0.60]; P=0.73), and LDL-C by fasting status interaction term in the Cox proportional hazards model was not significant (Pinteraction=0.11). Similar results were seen for the secondary outcome (fasting versus nonfasting C statistic=0.62 [95% confidence interval, 0.60-0.66] versus 0.62 [95% confidence interval, 0.60-0.66]; P=0.96; Pinteraction=0.34). CONCLUSIONS: Nonfasting LDL-C has prognostic value similar to that of fasting LDL-C. National and international agencies should consider reevaluating the recommendation that patients fast before obtaining a lipid panel.

Choosing the right coronary stent in the modern era.

Research and development in the field of coronary stent design is a fast-evolving and fascinating journey. A device that was once introduced to salvage acute closure associated with balloon angioplasty is now the standard of care for many patients with coronary artery disease. Newer generation stents are the product of remarkable progress in technology and innovation, driven by the need to make the stents easier to deliver and to improve their safety and efficacy. As such, the design of these stents has become quite sophisticated and complex. The number of available stents has increased giving patients and physicians more choices on one hand, but also created confusion in selecting the optimal stent for a given patient. Although a 'one size fits all' approach may not be reasonable, several randomized trials have attested to the efficacy and safety of newer generation durable polymer drug eluting stents. This article discusses the evidence base to support various stent choices in contemporary practice.

Health-related quality of life after transcatheter or surgical aortic valve replacement in high-risk patients with severe aortic stenosis: an updated review of literature.

Recent trials have highlighted the comparable mortality benefits and durability of the results for patients with severe aortic stenosis (AS) and high surgical risk managed with either transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (AVR). Various national guidelines and international regulatory bodies have approved TAVR, thereby leading to potential wide usage and dissemination of this technique worldwide. Quality-of-life outcomes, in spite of being an important measure of success and acceptability of the procedure, have not been publicized as extensively. For high risk patients with severe AS, implementation of TAVR has resulted in comparable survival, but different and novel adverse events compared with AVR. We present an updated review focusing on the quality-of-life outcomes and issues with this new and important procedural approach.

Drug-eluting versus bare-metal coronary stents: where are we now?

Drug-eluting stents have dramatically reduced the risk of restenosis, but concerns of an increased risk of stent thrombosis have provided uncertainty about their use. Recent studies have continued to show improved procedural and clinical outcomes with drug-eluting stents both in the setting of acute coronary syndromes and stable coronary artery disease. Newer generation drug-eluting stents (especially everolimus-eluting stents) have been shown to be not only efficacious but also safe with reduced risk of stent thrombosis when compared with bare-metal stents, potentially changing the benchmark for stent safety from bare-metal stents to everolimus-eluting stents. While much progress is being made in the development of bioabsorbable polymer stents, nonpolymer stents and bioabsorbable stent technology, it remains to be seen whether these stents will have superior safety and efficacy outcomes compared with the already much improved rates of revascularization and stent thrombosis seen with newer generation stents (everolimus-eluting stents and resolute zotarolimus-eluting stents).

The changing paradigm of stress echocardiography: risk stratification, prognosis, and future directions.

The use of stress echocardiography has undergone considerable evolution in the past 3 decades. Although stress echocardiography was first introduced as a noninvasive diagnostic tool for determining the presence or absence of coronary artery disease (CAD), it later served a prognostic role as well. The importance of stress echocardiography in risk stratification and prognosis is substantially undervalued by clinicians. The identification of patients at risk for future cardiac events has become a primary objective in noninvasive evaluation of patients with suspected or known CAD. In particular, the ability of stress echocardiography to identify patients at low (< 1%), intermediate (1%-5%), or high (> 5%) risk for future cardiac events is essential to decision making in patient management. Moreover, previous studies have conclusively demonstrated the incremental prognostic value of stress echocardiography over clinical and treadmill exercise data in predicting future cardiac events. This article presents a primarily single-center experience of retrospective and observational studies that address the current role of stress echocardiography and summarize its use for risk stratification, prognosis, and determining clinical outcomes, as well as cost-effective integration of such information in patient management decision making.

Fixed combination of amlodipine and atorvastatin in cardiovascular risk management: patient perspectives.

Hypertension and dyslipidemia are two of the most commonly co-occurring cardiovascular risk factors which together cause an increase in coronary heart disease-related events that is more than simply additive for anticipated event rates with each condition. Data have shown that even relatively small reductions in both blood pressure and cholesterol levels can lead to large reductions in the risk for cardiovascular events. However, though there are robust data on the beneficial effect of concomitant reduction in these risk factors, the reality is that this is achieved in <10% of patients. There is nonadherence with prescribed therapies with up to 50% of patients stopping their medications of their own volition for a variety of reasons. There is a reasonable evidence base to suggest that simplifying drug regimens and reducing pill burden will enhance patient adherence. The fixed-dose combination containing the antihypertensive agent amlodipine besylate and the statin atorvastatin is the first combination of its kind, which is both efficacious and safe and could potentially improve medication compliance, thereby improving the outcomes in these patients.

Assessment of left atrial appendage function with transthoracic tissue Doppler echocardiography.

AIMS: A transthoracic echocardiographic (TTE) parameter that would stratify atrial fibrillation (AF) risk would be useful. Tissue Doppler imaging can quantify left atrial appendage contraction velocity (LAA A(M)). METHODS AND RESULTS: We studied 141 patients referred for transoesophageal echocardiogram (TEE); 48 were in AF. We obtained TEE and TTE LAA A(M) velocities from the LAA apex on the parasternal short-axis and apical two-chamber views. Adequate traces were obtained in 118 patients (84%). In these patients, we measured 5382 LAA A(M) velocity tracings. There was a strong correlation between LAA A(M) on TEE and TTE parasternal short-axis (r = 0.741; P < 0.0001) and apical two-chamber views (r = 0.729; P < 0.0001). Patients in AF had lower LAA A(M) than those with sinus rhythm on parasternal short-axis (12 +/- 5 vs. 23 +/- 7 cm/s, P < 0.0001) and apical two-chamber (14 +/- 5 vs. 23 +/- 8 cm/s, P < 0.0001) views. On parasternal short axis, LAA A(M) velocities were lower in patients with spontaneous echo contrast, 11 +/- 4 vs. 22 +/- 8 cm/s (P < 0.0001), and in those with thrombus, 8 +/- 2 cm/s (P < 0.0001). On apical two-chamber, LAA A(M) velocities were also lower with spontaneous echo contrast, 12 +/- 4 vs. 22 +/- 7 cm/s (P < 0.0001), and with thrombus, 10 +/- 4 cm/s (P < 0.0001). In patients with AF and TTE LAA A(M) < or =11 cm/s, we found that nearly one-third had LAA thrombus. In patients with AF and a history of stroke or transient ischaemic attack (TIA), LAA A(M) velocities were lower compared with those without history of stroke or TIA in the parasternal short-axis (9 +/- 3 vs. 13 +/- 5 cm/s, P = 0.02) and apical two-chamber views (11 +/- 3 vs. 15 +/- 6 cm/s, P = 0.008). CONCLUSION: Acquiring and quantifying LAA A(M) contraction velocity is feasible on TTE in a high percentage of patients and correlates with TEE. LAA A(M) was lower in AF compared with sinus rhythm, with spontaneous echo contrast compared to without spontaneous echo contrast, and in AF patients with a history of stroke or TIA. Those with LAA thrombus had the lowest LAA A(M) velocities. LAA A(M) is a novel functional parameter that may prove useful for risk stratification of AF.

Compliance and fixed-dose combination therapy.

Despite data on the importance of blood pressure control in preventing cardiovascular and cerebrovascular events, only 34% of hypertensive patients have their blood pressure under control. The National Council on Patient Information and Education has estimated that the compliance rate is just over 30% for chronic conditions like hypertension. Polypharmacy and complex treatment regimens have been identified as important, modifiable risk factors for medication noncompliance. Fixed-dose combination regimens are attractive options because of the improved antihypertensive efficacy resulting from the dual mechanistic action of components targeting different effector mechanisms. One drug in the fixed-dose combination may negate an adverse effect of the other medication. Above all, fixed-dose combination therapy reduces pill burden and improves medication compliance, which can translate into better cardiovascular outcomes. Fixed-dose combinations should be used routinely for the management of hypertension and should also be considered when initiating therapy for patients with newly diagnosed hypertension.

Incremental prognostic value of stress echocardiography over clinical and stress electrocardiographic variables in patients with prior myocardial infarction: "warranty time" of a normal stress echocardiogram.

BACKGROUND: Patients with prior myocardial infarction (MI) are at increased risk of subsequent cardiac events (MI or cardiac death). The incremental prognostic value and warranty time of a normal stress echocardiogram in this high-risk population is not well defined. METHODS: We evaluated 251 consecutive patients (62 +/- 11 years; 64% males) with remote history of MI (>6 weeks) undergoing stress echocardiography (83% dobutamine). Ischemia was defined as a new reversible wall motion abnormality and/or biphasic response. Follow-up for up to 4 years (mean 2.9 +/- 1.0 years) for confirmed MI (n = 7) and cardiac death (n = 15) were obtained. RESULTS: Stress echocardiography effectively risk stratified patients into normal versus abnormal subgroups (Event rate 0.8% per year vs 4.2% per year; P = 0.01; RR = 5.6, 95% CI = 1.3-24.7). In patients with a normal stress echocardiogram, the event rate at the end of 6, 12, and 18 months were <1% per year. After 18 months the event rate in patients with a normal stress echocardiogram increased greatly (>1% per year). Stress echocardiography yields incremental prognostic value over clinical and stress electrocardiographic variables (Global chi-square increased from 12.4 to 25 to 31.1, P < 0.0001 both groups). CONCLUSIONS: Stress echocardiography yields appropriate risk stratification and prognosis and provides incremental prognostic value over clinical and stress electrocardiographic variables even in patients with prior MI. A normal stress echocardiogram portends a benign prognosis (<1% event rate/year) for up to 18 months.