Patients with prior myocardial infarction, stroke, or symptomatic peripheral arterial disease in the CHARISMA trial.

OBJECTIVES: The purpose of this study was to determine the possible benefit of dual antiplatelet therapy in patients with prior myocardial infarction (MI), ischemic stroke, or symptomatic peripheral arterial disease (PAD). BACKGROUND: Dual antiplatelet therapy with clopidogrel plus aspirin has been validated in the settings of acute coronary syndromes and coronary stenting. The value of this combination was recently evaluated in the CHARISMA (Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance) trial, where no statistically significant benefit was found in the overall broad population of stable patients studied. METHODS: We identified the subgroup in the CHARISMA trial who were enrolled with documented prior MI, ischemic stroke, or symptomatic PAD. RESULTS: A total of 9,478 patients met the inclusion criteria for this analysis. The median duration of follow-up was 27.6 months. The rate of cardiovascular death, MI, or stroke was significantly lower in the clopidogrel plus aspirin arm than in the placebo plus aspirin arm: 7.3% versus 8.8% (hazard ratio [HR] 0.83, 95% confidence interval [CI] 0.72 to 0.96, p = 0.01). Additionally, hospitalizations for ischemia were significantly decreased, 11.4% versus 13.2% (HR 0.86, 95% CI 0.76 to 0.96, p = 0.008). There was no significant difference in the rate of severe bleeding: 1.7% versus 1.5% (HR 1.12, 95% CI 0.81 to 1.53, p = 0.50); moderate bleeding was significantly increased: 2.0% versus 1.3% (HR 1.60, 95% CI 1.16 to 2.20, p = 0.004). CONCLUSIONS: In this analysis of the CHARISMA trial, the large number of patients with documented prior MI, ischemic stroke, or symptomatic PAD appeared to derive significant benefit from dual antiplatelet therapy with clopidogrel plus aspirin. Such patients may benefit from intensification of antithrombotic therapy beyond aspirin alone, a concept that future trials will need to validate. (Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance [CHARISMA]; http://clinicaltrials.gov/ct/show/NCT00050817?order=1; NCT00050817).     

Complete Revascularization in Patients With STEMI and Multi-Vessel Disease: A Meta-Analysis of Randomized Controlled Trials

BackgroundPercutaneous coronary intervention (PCI) is the treatment of choice for ST-elevation myocardial infarction (STEMI). However, efficacy of complete vs culprit only revascularization in patients with STEMI and multivessel disease remains unclear.MethodsWe searched PubMed/MEDLINE, and Cochrane library. The primary endpoint was major adverse cardiovascular events (MACE). Secondary outcomes were all-cause mortality, cardiovascular mortality, myocardial infarction (MI), repeat revascularization, stroke, major bleeding, and contrast induced nephropathy. Estimates were calculated as random effects hazard ratios (HRs) with 95% confidence intervals (CI).ResultsTwelve trials with 7592 patients were included. There was a significantly lower risk of MACE [HR 0.61; 95% CI (0.43–0.60); p = 0.0009; I² = 72%], cardiovascular mortality [HR 0.74; 95% CI (0.56–0.99); p = 0.04; I² = 2%], and repeat revascularization [HR 0.43; 95% CI (0.31–0.59); p < 0.00001; I² = 67%] in patients treated with complete compared with culprit-only revascularization. There was no statistically significant difference in MI [HR 0.77; 95% CI (0.52–1.12); p = 0.17; I² = 49%], all-cause mortality [HR 0.86; 95% CI (0.65–1.13); p = 0.28; I² = 14%], heart failure [HR 0.82 95% CI (0.51–1.32); p = 0.42; I² = 26%], major bleeding [HR 1.07; 95% CI (0.66–1.75); p = 0.78; I² = 25%], stroke [HR 0.67; 95% CI (0.24–1.89); p = 0.45; I² = 54%], or contrast induced nephropathy, although higher contrast volumes were used in the complete revascularization group [HR 1.22; 95% CI (0.78–1.92); p = 0.39; I² = 0%].ConclusionComplete revascularization was associated with a significantly lower risk of MACE, cardiovascular mortality, and repeat revascularization compared with culprit-only revascularization. These results suggest complete revascularization with PCI following STEMI and multivessel disease should be considered.     

Low-dose versus high-dose aspirin after percutaneous coronary intervention: analysis from the guthrie health off-label StenT (GHOST) registry

Background: The optimal dose of aspirin therapy after percutaneous coronary intervention (PCI) remains unclear. We sought to compare the effectiveness and safety of low and high doses of aspirin in preventing adverse outcomes after PCI. Methods: We studied 2,820 consecutive patients who underwent coronary stenting for stable or unstable coronary artery disease (excluding cardiogenic shock) discharged alive without any complications between 2001 and 2007. Patients were categorized based on the discharge aspirin dose into low‐dose (81 mg/day, N = 313) or high‐dose (162–325 mg/day, N = 2,507) groups. The primary end‐points (adjusted using Cox Proportional Hazard and propensity scores) were major adverse cardiovascular events (MACE; a composite of death, myocardial infarction [MI], stent thrombosis [ST], or target vessel revascularization) and net adverse clinical events (NACE; a composite of MACE and thrombolysis in myocardial infarction [TIMI][major or minor] bleeding) at 1 year. Results: In the low‐dose versus high‐dose groups, MACE occurred in 8.6 versus 9.2% (log rank P = 0.71) and NACE in 11 versus 10% (log rank P = 0.58). In multivariable analysis, low‐dose aspirin was not associated with worse outcomes (adjusted HR [95% CI] 0.74 [0.49–1.14] for MACE; 1.03 [0.71–1.50] for NACE). Conclusion: Low‐dose aspirin, as prescribed in this study of routine practice, was not associated with worse outcomes compared to high‐dose aspirin. (J Interven Cardiol 2011;24:307–314)     

Carvedilol protects better against vascular events than metoprolol in heart failure: results from COMET.

OBJECTIVES: We explored whether vascular protection by carvedilol could contribute to its superior effects in the treatment of heart failure (HF) compared with metoprolol tartrate in the COMET (Carvedilol Or Metoprolol European Trial) study. BACKGROUND: Full adrenergic blockade by carvedilol and additional (e.g., antioxidative) properties may lead to vascular protection relative to beta-1 blockade alone, and contribute to its efficacy in HF treatment. METHODS: Three thousand twenty-nine patients with HF due to ischemic (51%) or idiopathic cardiomyopathy (44%) were randomized double-blind to carvedilol (n = 1,511) or metoprolol (n = 1,518) and followed for 58 months. Vascular end points were cardiovascular death, stroke, stroke death, myocardial infarction (MI), and unstable angina. RESULTS: The effect of carvedilol on cardiovascular death improved consistently in subgroups with prespecified baseline variables. Myocardial infarctions were reported in 69 carvedilol and 94 metoprolol patients (hazard ratio [HR] 0.71, 95% confidence interval [CI] 0.52 to 0.97, p = 0.03). Cardiovascular death or nonfatal MI combined were reduced by 19% in carvedilol (HR 0.81, 95% CI 0.72 to 0.92, p = 0.0009 vs. metoprolol). Unstable angina was reported as an adverse event in 56 carvedilol and in 77 metoprolol patients (HR 0.71, 95% CI 0.501 to 0.998, p = 0.049). A stroke occurred in 65 carvedilol and 80 metoprolol patients (HR 0.79, 95% CI 0.57 to 1.10). Stroke or MI combined occurred in 130 carvedilol and 168 metoprolol patients (HR 0.75, 95% CI 0.60 to 0.95, p = 0.015), and fatal MI or fatal stroke occurred in 34 carvedilol and in 72 metoprolol patients (HR 0.46, 95% CI 0.31 to 0.69, p = 0.0002). Death after a nonfatal MI or stroke occurred in 61 of 124 carvedilol and in 106 of 160 metoprolol patients (HR 0.66, 95% CI 0.48 to 0.90, p = 0.0086). CONCLUSIONS: Carvedilol improves vascular outcomes better than metoprolol. These results suggest a ubiquitous protective effect of carvedilol against major vascular events.     

The impact of long-term systemic glucocorticoid use in severe asthma: A UK retrospective cohort analysis

Objective: Systemic glucocorticoids (SGCs) are a treatment option for severe asthma but are associated with the development of adverse events (AEs). Evidence on the extent of SGC use and the relationship between SGC dose and AE risk in severe asthma is limited. Methods: Patients with severe asthma (Global Initiative for Asthma step 4/5), with no SGC use during the <6–12 months before severe asthma determination (index date) were identified in the UK-based Clinical Practice Research Datalink database (2004–2012). Patients were assessed for SGC exposure and an incident diagnosis of an SGC-related AE (cataracts, diabetes, myocardial infarction [MI], osteoporosis, peptic ulcer or stroke) during the 8-year observation phase. The dose-related risk of an SGC-related AE was determined using AE-specific Cox proportional hazards models. Results: Overall, 75% of 60,418 patients identified with severe asthma received SGC during the 8-year follow-up, with the majority receiving an average of >0–≤2.5 mg/day. The risk of diabetes (hazard ratio [HR]:1.20 [95% confidence interval (CI): 1.11, 1.30]), MI (HR: 1.25 [95% CI: 1.09, 1.43]) and osteoporosis (HR: 1.64 [95% CI: 1.51, 1.78]) was increased at low SGC doses (0–2.5 mg/day), with further risk increases at doses >2.5 mg/day versus no SGC use. Compared with no SGC use, SGC increased the risk of peptic ulcer in a non-dose-dependent manner, but the risk of stroke was unchanged. Conclusions: Most patients with severe asthma are exposed to SGC, which increases SGC-related AE risk. This suggests that SGC exposure should be minimized as recommended by asthma treatment guidelines.     

Triple antiplatelet therapy during percutaneous coronary intervention is associated with improved outcomes including one-year survival: results from the Do Tirofiban and ReoProGive Similar Efficacy Outcome Trial (TARGET)

OBJECTIVE: We sought to examine if clopidogrel treatment initiated before coronary stenting improved clinical outcomes among patients receiving aspirin and a glycoprotein (GP) IIb/IIIa inhibitor. BACKGROUND: Antiplatelet therapy plays a pivotal role in contemporary percutaneous coronary interventions (PCI). METHODS: Outcomes among 4,809 patients randomized to tirofiban or abciximab during PCI with stent placement were compared according to whether they received 300 mg of clopidogrel before PCI (93.1%) versus immediately after the procedure. RESULTS: The 30-day primary composite end point (death, myocardial infarction [MI], or urgent target vessel revascularization [TVR]) was lower among clopidogrel-pretreated patients (6.6% vs. 10.4%, p = 0.009), mainly because of reduction of MI (6.0% vs. 9.5%, p = 0.012). The benefit of clopidogrel pretreatment was sustained at six months (death, MI, any TVR: 14.6% vs. 19.8%, HR = 0.71, p = 0.010), and this was due mainly to lowering of death and MI (7.8% vs. 13.0%, p = 0.001). At one year, clopidogrel pretreatment was associated with a lower mortality rate (1.7% vs. 3.6%, p = 0.011). Because clopidogrel pretreatment was not randomized, multivariable and propensity analyses were performed. After adjusting for baseline heterogeneity, clopidogrel pretreatment was an independent predictor for death or MI at 30 days (HR = 0.63, p = 0.012) and at six months (HR = 0.61, p = 0.003), and survival at one year (HR = 0.53, p = 0.044). No excess in 30-day bleeding events was noted with clopidogrel pretreatment. CONCLUSIONS: Among patients undergoing coronary stent placement with aspirin and a GP IIb/IIIa inhibitor, clopidogrel pretreatment is associated with a reduction of death and MI irrespective of the type of GP IIb/IIIa inhibitor used.     

Comparison of Long-Term Outcome After Percutaneous Coronary Intervention Versus Coronary Artery Bypass Grafting in Patients With Unprotected Left Main Coronary Artery Disease (from the CREDO-Kyoto PCI/CABG Registry Cohort-2)

The long-term outcome of percutaneous coronary intervention (PCI) compared to coronary artery bypass grafting (CABG) for unprotected left main coronary artery disease (ULMCAD) remains to be investigated. We identified 1,005 patients with ULMCAD of 15,939 patients with first coronary revascularization enrolled in the CREDO-Kyoto PCI/CABG Registry Cohort-2. Cumulative 3-year incidence of a composite of death/myocardial infarction (MI)/stroke was significantly higher in the PCI group than in the CABG group (22.7% vs 14.8%, p = 0.0006, log-rank test). However, the adjusted outcome was not different between the PCI and CABG groups (hazard ratio [HR] 1.30, 95% confidence interval [CI] 0.79 to 2.15, p = 0.30). Stratified analysis using the SYNTAX score demonstrated that risk for a composite of death/MI/stroke was not different between the 2 treatment groups in patients with low (<23) and intermediate (23 to 33) SYNTAX scores (adjusted HR 1.70, 95% CI 0.77 to 3.76, p = 0.19; adjusted HR 0.86, 95% CI 0.37 to 1.99, p = 0.72, respectively), whereas in patients with a high SYNTAX score (≥33), it was significantly higher after PCI than after CABG (adjusted HR 2.61, 95% CI 1.32 to 5.16, p = 0.006). In conclusion, risk of PCI for serious adverse events seemed to be comparable to that after CABG in patients with ULMCAD with a low or intermediate SYNTAX score, whereas PCI compared with CABG was associated with a higher risk for serious adverse events in patients with a high SYNTAX score.     

Prior aspirin use and outcomes in elderly patients hospitalized with acute myocardial infarction.

OBJECTIVES: We sought to assess the association between prior aspirin use and mortality, all-cause readmission, and condition-specific readmission at one month and six months in a national sample of Medicare beneficiaries hospitalized with a confirmed myocardial infarction (MI). BACKGROUND: Prior aspirin use is considered a marker of higher risk in patients with MI, yet the prognostic significance of this factor has been debated. METHODS: Medicare beneficiaries > or =65 years old hospitalized with MI were evaluated to determine whether there was an association between prior aspirin use and mortality (n = 118,992), all-cause readmission, and condition-specific readmission (n = 78,975) at one month and six months. RESULTS: One-third of the patients (n = 39,531, 33.2%) were using aspirin before admission. Those with prior aspirin use had significantly lower mortality at one month (16.1% vs. 19.0%, p < 0.0001) and six months (24.7% vs. 27.5%, p < 0.0001). After multivariable adjustment, prior aspirin use was found to be associated with a lower risk of one-month (relative risk ratio 0.93, 95% confidence interval [CI] 0.90 to 0.96) and six-month mortality (hazard ratio 0.94, 95% CI 0.91 to 0.96). Prior aspirin use tended to reduce all-cause or coronary artery disease readmissions at one month or six months. CONCLUSIONS: Prior aspirin use is not a marker of increased mortality in patients > or =65 years old hospitalized with MI.     

Impact of platelet reactivity after clopidogrel administration on drug-eluting stent thrombosis.

OBJECTIVES: We sought to determine whether nonresponsiveness to clopidogrel as revealed by high in vitro post-treatment platelet reactivity is predictive of drug-eluting stent (DES) thrombosis. BACKGROUND: No data exist about the impact of nonresponsiveness to clopidogrel on the risk of DES thrombosis. METHODS: We conducted a prospective observational cohort study from July 2005 to August 2006 in an academic hospital. A total of 804 patients who had successful sirolimus- or paclitaxel-eluting stent implantation were assessed for post-treatment platelet reactivity after a loading dose of 600 mg of clopidogrel. Patients with platelet aggregation by 10 mumol adenosine 5'-diphosphate > or =70% were defined as nonresponders. All patients received chronic dual antiplatelet treatment (aspirin 325 mg and clopidogrel 75 mg daily) for 6 months. The primary end point was the incidence of definite/probable early, subacute, and late stent thrombosis at 6-month follow-up. RESULTS: The incidence of 6-month definite/probable stent thrombosis was 3.1%. All stent thromboses were subacute or late. Of 804 patients, 105 (13%) were not responsive to clopidogrel. The incidence of stent thrombosis was 8.6% in nonresponders and 2.3% in responders (p < 0.001). By multivariate analysis, the predictors of stent thrombosis were as follows: nonresponsiveness to clopidogrel (hazard ratio [HR] 3.08, 95% confidence interval [CI] 1.32 to 7.16; p = 0.009), left ventricular ejection fraction (HR 0.95, 95% CI 0.92 to 0.98; p = 0.001), total stent length (HR 1.01, 95% CI 1.00 to 1.02; p = 0.010), and ST-segment elevation acute myocardial infarction (HR 2.41, 95% CI 1.04 to 5.63; p = 0.041). CONCLUSIONS: Nonresponsiveness to clopidogrel is a strong independent predictor of stent thrombosis in patients receiving sirolimus- or paclitaxel-eluting stents.     

A prospective,blinded determination of the natural history of aspirin resistance among stable patients with cardiovascular disease

OBJECTIVES: This study was designed to determine if aspirin resistance is associated with clinical events. BACKGROUND: Aspirin resistance, defined by platelet function testing and presumed clinical unresponsiveness to aspirin, has been previously reported by our group and others. However, little information exists linking the laboratory documentation of aspirin resistance and long-term clinical events. METHODS: We prospectively enrolled 326 stable cardiovascular patients from 1997 to 1999 on aspirin (325 mg/day for > or =7 days) and no other antiplatelet agents. We tested for aspirin sensitivity by optical platelet aggregation using adenosine diphosphate (ADP) and arachidonic acid (AA). The primary outcome was the composite of death, myocardial infarction (MI), or cerebrovascular accident (CVA). Mean follow-up was 679 +/- 185 days. Aspirin resistance was defined as a mean aggregation of > or =70% with 10 microM ADP and > or =20% with 0.5 mg/ml AA. RESULTS: Of the patients studied, 17 (5.2%) were aspirin resistant and 309 (94.8%) were not aspirin resistant. During follow-up, aspirin resistance was associated with an increased risk of death, MI, or CVA compared with patients who were aspirin sensitive (24% vs. 10%, hazard ratio [HR] 3.12, 95% confidence interval [CI] 1.10 to 8.90, p = 0.03). Stratified multivariate analyses identified platelet count, age, heart failure, and aspirin resistance to be independently associated with major adverse long-term outcomes (HR for aspirin resistance 4.14, 95% CI 1.42 to 12.06, p = 0.009). CONCLUSIONS: This study demonstrates the natural history of aspirin resistance in a stable population, documenting a greater than threefold increase in the risk of major adverse events associated with aspirin resistance.     

Left Ventricular Hypertrophy Does Not Affect 1-Year Clinical Outcomes in Patients Undergoing Transcatheter Aortic Valve Replacement

Objectives

The aim of this study was to evaluate the association between pre-procedural left ventricular hypertrophy (LVH) patterns and clinical outcomes after transcatheter aortic valve replacement (TAVR).

Warfarin and antiplatelet combination use among commercially insured patients enrolled in an anticoagulation management service

BACKGROUND: Although warfarin and antiplatelet medications have documented efficacy for prevention of primary and secondary cardiovascular events, the appropriateness of warfarin and antiplatelet combination therapy is not well described in national consensus guidelines. METHODS AND RESULTS: Cross-sectional data from 4,557 Kaiser Permanente Colorado members > or = 18 years old who were receiving warfarin anticoagulation therapy were used to quantify the prevalence of warfarin and antiplatelet agent (ie, aspirin, clopidogrel, dipyridamole, and/or dipyridamole/aspirin) combination therapy as of September 30, 2005, and to identify characteristics of patients receiving combination therapy. The prevalence of warfarin and any antiplatelet combination therapy was 385/1,000 (95% confidence interval [CI], 371/1,000 to 399/1,000). The majority of combination therapy was warfarin and aspirin (prevalence, 378/1,000) with a daily dose of aspirin, 81 mg, being the most reported dose (prevalence, 328/1,000). Patients receiving combination therapy were more likely to be male (63.6% vs 46.4%; adjusted odds ratio, 1.5; 95% CI, 1.3 to 1.7) and have a comorbidity of heart failure (29.0% vs 15.6%; adjusted odds ratio, 1.2; 95% CI, 1.1 to 1.5), coronary artery disease (62.4% vs 17.5%; adjusted odds ratio, 7.6; 95% CI, 6.5 to 8.8), and/or stroke/transient ischemic attack (5.2% vs 1.6%; adjusted odds ratio, 3.5; 95% CI, 2.3 to 5.3). CONCLUSION: Nearly 4 of 10 patients receiving warfarin management care were receiving warfarin and antiplatelet combination therapy. The findings suggest that this practice is widespread, especially among patients with established cardiovascular disease, and involves a substantially higher number of patients than previously reported. The clinical outcomes associated with this practice require further investigation.     

Comparative Stroke,Bleeding, and Mortality Risks in Older Medicare Patients Treated with Oral Anticoagulants for Nonvalvular Atrial Fibrillation

BackgroundNonvitamin K antagonist oral anticoagulants (NOACs) are alternatives to warfarin in patients with nonvalvular atrial fibrillation. Randomized trials compared NOACs with warfarin, but none have compared individual NOACs against each other for safety and effectiveness.MethodsWe performed a retrospective new-user cohort study of patients with nonvalvular atrial fibrillation enrolled in US Medicare who initiated warfarin (n = 183,318), or a standard dose of dabigatran (150 mg twice daily; n = 86,198), rivaroxaban (20 mg once daily; n = 106,389), or apixaban (5 mg twice daily; n = 73,039) between October 2010 and September 2015. Propensity score-adjusted Cox proportional hazards regression was used to estimate adjusted hazard ratios (HR) and 95% confidence intervals (CI) for the outcomes of thromboembolic stroke, intracranial hemorrhage, major extracranial bleeding, and all-cause mortality, comparing each NOAC with warfarin, and with each other NOAC.ResultsCompared with warfarin, each NOAC was associated with reduced risks of thromboembolic stroke (20%-29% reduction; P = .002 [dabigatran], P < 0.001 [rivaroxaban, apixaban]), intracranial hemorrhage (35%-62% reduction; P < 0.001 [each NOAC]), and mortality (19%-34% reduction; P < .001 [each NOAC]). The NOACs were similar for thromboembolic stroke but rivaroxaban was associated with increased risks of intracranial hemorrhage (vs dabigatran: HR = 1.71; 95% CI, 1.35-2.17), major extracranial bleeding (vs dabigatran: HR = 1.32; 95% CI, 1.21-1.45; vs apixaban: HR = 2.70; 95% CI, 2.38-3.05), and death (vs dabigatran: HR = 1.12; 95% CI, 1.01-1.24; vs apixaban: HR = 1.23; 95% CI, 1.09-1.38). Dabigatran was associated with reduced risk of intracranial hemorrhage (HR = 0.70; 95% CI ,0.53-0.94) and increased risk of major extracranial bleeding (HR = 2.04; 95% CI, 1.78-2.32) compared with apixaban.ConclusionsAmong patients treated with standard-dose NOAC for nonvalvular atrial fibrillation and warfarin users with similar baseline characteristics, dabigatran, rivaroxaban, and apixaban were associated with a more favorable benefit–harm profile than warfarin. Among NOAC users, dabigatran and apixaban were associated with a more favorable benefit–harm profile than rivaroxaban.     

Relation between aspirin dose, all-cause mortality, and bleeding in patients with recent cerebrovascular or coronary ischemic events (from the BRAVO Trial)

Despite aspirin's established role in the treatment of atherosclerotic vascular disease, considerable controversy exists regarding its most effective dosing strategy. In a retrospective observational study, we examined the relation between prescribed aspirin dose (<162 mg vs > or =162 mg/day aspirin) and clinical outcome in 4,589 placebo-treated patients enrolled in the Blockage of the Glycoprotein IIb/IIIa Receptor to Avoid Vascular Occlusion (BRAVO) trial over a median follow-up of 366 days. Standard Cox regression analysis was employed because propensity analysis was not feasible. Compared with lower aspirin doses, higher doses were associated with lower unadjusted all-cause mortality (2.9 vs 1.6%, respectively; log rank chi-square 8.6, p = 0.0034). Higher aspirin dose remained independently predictive of lower all-cause mortality in a multivariable Cox proportional hazards model (hazard ratio 0.64, 95% confidence interval 0.42 to 0.97, p = 0.037). However, there was no significant difference in the incidence of the composite endpoint death, nonfatal myocardial infarction, or nonfatal stroke (6.1% vs 6.2%, p = 0.74). Higher aspirin dose was a significant independent predictor of any (hazard ratio 1.32, 95% confidence interval 1.12 to 1.55, p = 0.001) but not serious bleeding. In conclusion, our findings suggest that aspirin doses of > or =162 mg/day may be more beneficial than those <162 mg/day at preventing death.     

Dabigatran and Warfarin for Secondary Prevention of Stroke in Atrial Fibrillation Patients: A Nationwide Cohort Study

Background

This register-based observational study compares dabigatran to warfarin for secondary stroke prevention in atrial fibrillation patients among both “new starters” on dabigatran and “switchers” to dabigatran from warfarin.

Methods

We identified, in nationwide Danish registries, 2398 patients with atrial fibrillation and a history of stroke/transient ischemic attack, making a first-time purchase of dabigatran 110 mg twice a day (bid; D110) and 150 mg bid (D150). Patients were categorized as either vitamin K antagonist (VKA) naive or experienced. Warfarin controls were identified using a complete (for VKA-naive dabigatran patients) or matched sampling approach (for VKA-experienced dabigatran patients). Subjects were followed for an average of 12.6 months for stroke and transient ischemic attacks. Confounder-adjusted Cox regression models were used to compare event rates between treatments.

Results

Among patients with a history of stroke/transient ischemic attack and prior VKA experience, switching to dabigatran was associated with an increased stroke/transient ischemic attack rate for both dabigatran doses compared with continuing on warfarin (D110 hazard ratio [HR] 1.99; 95% confidence interval [CI], 1.42-2.78; D150 HR 2.34; 95% CI, 1.60-3.41). Among prior stroke/transient ischemic attack patients who were new starters on dabigatran or warfarin, the rate of stroke/transient ischemic attack for both doses of dabigatran was similar to or lower than warfarin (D110 HR 0.64; 95% CI, 0.50-0.80; D150 HR 0.92l; 95% CI, 0.73-1.15).

Conclusions

In this register-based study, VKA-experienced patients with a history of stroke or transient ischemic attack who switched to dabigatran therapy had an increased rate of stroke compared with patients persisting with warfarin therapy.     

Effect of risk factors on complicated and uncomplicated ulcers in the TARGET lumiracoxib outcomes study

BACKGROUND & AIMS: Selective cyclooxygenase-2 inhibitors were developed to reduce the gastrointestinal risk associated with nonsteroidal anti-inflammatory drugs (NSAIDs). The Therapeutic Arthritis Research and Gastrointestinal Event Trial was the largest study to evaluate primarily the gastrointestinal safety outcomes of selective cyclooxygenase-2 inhibitors. Data from the Therapeutic Arthritis Research and Gastrointestinal Event Trial were used to identify risk factors and investigate the safety of lumiracoxib in subgroups. METHODS: Patients with osteoarthritis (age, >or=50 y) were randomized to receive lumiracoxib 400 mg once daily, naproxen 500 mg twice daily, or ibuprofen 800 mg 3 times daily for 12 months. Events were categorized by a blinded adjudication committee. The primary end point was all definite or probable ulcer complications. RESULTS: For patients taking NSAIDs, factors associated with an increased risk of ulcer complications were age 65 years or older (hazard ratio [HR], 2.30; 95% confidence interval [CI], 1.48-3.59), previous history of gastrointestinal bleed or ulcer (HR, 3.61; 95% CI, 1.86-7.00), non-Caucasian racial origin (HR, 2.10; 95% CI, 1.35-3.27), and male sex (HR, 1.70; 95% CI, 1.08-2.68). With lumiracoxib, significant risk factors were age 65 years or older (HR, 3.18; 95% CI, 1.40-7.20), male sex (HR, 2.60; 95% CI, 1.25-5.40), non-Caucasian racial origin (HR, 2.16; 95% CI, 1.02-4.59), and concomitant aspirin use (HR, 2.89; 95% CI, 1.40-5.97). Increased risks in patients age 65 years and older were increased further if other risk factors were present. Lumiracoxib maintained an advantage over NSAIDs across all subgroups except aspirin use. CONCLUSIONS: Lumiracoxib was associated with a reduced risk of ulcer complications compared with NSAIDs in all significant subgroups except aspirin users.     

Impact of aspirin treatment on long-term outcome (over 10 years) after percutaneous coronary intervention

Aspirin has been shown to reduce cardiovascular morbidity and mortality following percutaneous coronary intervention (PCI). However, its effects on long-term (over 10 years) mortality have not been fully elucidated. This retrospective study recorded the patient characteristics and admission medication for all patients undergoing PCI over an 8-year period from 1984 to 1992. Follow-up information was available for 748 patients (100%) for a mean of 143.6 +/- 43.4 months. A propensity analysis was performed to adjust for presumed selection biases in the administration of aspirin. The baseline clinical characteristics were similar between the group that received aspirin and the group that did not, except for the administration of statins and PCI procedural success rate. Of the 748 patients, 535 (71.5%) received aspirin treatment at the time of PCI. During the 12-year follow-up, 54 patients died from any cause and 20 patients from cardiac death. Kaplan-Meier analysis showed that aspirin treatment led to a significant reduction in all cause mortality (10% versus 16.4%; P = 0.01) and cardiac death (3.7% versus 8.0%; P = 0.02) compared to other antiplatelet drugs. The hazard ratio (HR) for the total mortality and cardiac mortality rates was adjusted using the Cox-proportional hazard model for confounding variables and propensity score. The all cause (HR, 0.49; 95%CI [0.29-0.80], P = 0.005) and cardiac mortality rates (HR, 0.32; 95%CI [0.14-0.72], P = 0.006) for patients receiving aspirin remained lower than for those not receiving aspirin. Aspirin treatment at the time of PCI significantly reduced the risk of death from any cause and cardiac death. The administration of aspirin had a positive impact on the over 10-year long-term outcomes of patients who underwent PCI.     

Predictors of outcome in stable outpatients with peripheral artery disease

Patients with peripheral artery disease (PAD) are at increased risk for subsequent ischemic events. We used data from the FRENA Registry to find predictors of subsequent myocardial infarction (MI), ischemic stroke, and limb amputation in stable outpatients with PAD. As of January 2012, 1,270 patients with PAD were recruited, of whom 1,042 (82 %) had Fontaine stage II; 113 (8.9 %) stage III; and 115 (9.1 %) stage IV. Over a mean follow-up of 14 months, 35 patients developed MI, 25 had stroke, 39 underwent limb amputation, and 91 died. Among patients with Fontaine stage II, the incidence of MI (2.09 events per 100 patient-years; 95 % CI 1.43–2.97) or stroke (0.93; 95 % CI 0.52–1.56) was similar to that of limb amputation (3.22; 95 % CI 2.37–4.29). On multivariate analysis, patients with diabetes [hazard ratio (HR) 2.09; 95 % CI 1.05–4.18], prior coronary disease (HR 5.35; 95 % CI 2.24–12.8), or atrial fibrillation (HR 3.11; 95 % CI 1.52–6.37) were at increased risk for MI; female (HR 2.94; 95 % CI 1.32–6.67), those with prior stroke (HR 5.21; 95 % CI 1.22–22.2) or atrial fibrillation (HR 3.37; 95 % CI 1.45–7.85) at increased risk for stroke; and female (HR 2.38; 95 % CI 1.23–4.55), those with diabetes (HR 3.50; 95 % CI 1.58–7.73) or advanced stages of PAD were at increased risk for limb amputation. Prior coronary artery disease, diabetes and atrial fibrillation predicted subsequent MI; female gender, prior stroke and atrial fibrillation predicted stroke; and female gender, diabetes, and advanced stages of PAD predicted limb amputation.     

Impact of red blood cell transfusion on clinical outcomes in patients with acute myocardial infarction

Divergent views remain regarding the safety of treating anemia with red blood cell (RBC) transfusion in patients with acute coronary syndrome (ACS). We used a prospective database to study effect of RBC transfusion in patients with acute myocardial infarction (MI; n = 2,358). Cox regression models were used to determine the association between RBC transfusion and 6-month outcomes, incorporating transfusion as a time-dependent variable. The models adjusted for baseline variables, propensity for transfusion, and nadir hemoglobin previous to the transfusion. One hundred ninety-two patients (8.1%) received RBC transfusion. Six-month mortality rates were higher in patients receiving transfusion (28.1% vs 11.7%, p <0.0001). The adjusted hazard ratio (HR) for mortality was 1.9 in transfused patients (95% confidence interval [CI] 1.3 to 2.9). Interaction between RBC transfusion and nadir hemoglobin with respect to mortality (p = 0.004) was significant. Stratified analyses showed a protective effect of transfusion in patients with nadir hemoglobin < or=8 g/dL (adjusted HR 0.13, 95% CI 0.03 to 0.65, p = 0.013). By contrast, transfusion was associated with increased mortality in patients with nadir hemoglobin >8 g/dL (adjusted HR 2.2, 95% CI 1.5 to 3.3; p <0.0001). Similar results were obtained for the composite end point of death/MI/heart failure (p for interaction = 0.04). In conclusion, RBC transfusion in patients with acute MI and hemoglobin < or =8 g/dL may be appropriate. The increased mortality observed in transfused patients with nadir hemoglobin above 8 g/dL underscores the clinical difficulty of balancing risks and benefits of RBC transfusion in the setting of ACS.     

Comparison of outcomes using sirolimus-eluting stenting in diabetic versus nondiabetic patients with comparison of insulin versus non-insulin therapy in the diabetic patients

The effect of insulin therapy on adverse cardiovascular outcomes in diabetic patients has been debated and a reduced benefit in clinical restenosis outcomes after sirolimus stenting has been reported among diabetic patients requiring insulin therapy. We analyzed 297 diabetic patients receiving sirolimus-eluting stents, including 115 (39%) on insulin therapy, and compared outcomes with 541 nondiabetic patients treated consecutively during the same interval. The rates of target lesion revascularization (9.5% vs 3.5%, p = 0.003) and cardiac death or myocardial infarction (MI, 7.1% vs 3.1%, p = 0.012) were significantly higher for diabetic patients. Insulin treatment was independently associated with increased risk for target lesion revascularization (odds ratio [OR] 2.48, 95% confidence interval [CI] 1.22 to 5.00) and cardiac death or MI (hazard ratio [HR] 2.85, 95% CI 1.41 to 5.77), whereas the adjusted risk for diabetic patients not treated with insulin was not significantly different from patients without diabetes for target lesion revascularization (OR 1.32, 95% CI 0.66 to 2.62) or cardiac death or MI (HR 1.04, 95% CI 0.50 to 2.17). In conclusion, diabetes mellitus is associated with increased risk for target lesion revascularization and cardiac death or MI after receiving sirolimus-eluting stenting, and is significantly exaggerated by the requirement for insulin therapy.