Abstract Background The prospective, randomized FREEDOM (Comparison of Two Treatments for Multivessel Coronary Artery Disease in Individuals With Diabetes) trial found coronary artery bypass graft ...surgery (CABG) was associated with better clinical outcomes than percutaneous coronary intervention (PCI) in patients with diabetes and multivessel disease, managed with or without insulin. Objectives In this subgroup analysis of the FREEDOM trial, we examined the association of long-term clinical outcomes after revascularization in patients with insulin-treated diabetes mellitus (ITDM) compared with patients not treated with insulin. Methods A total of 1,850 FREEDOM subjects had an index revascularization procedure performed: 956 underwent PCI with drug-eluting stents (DES), and 894 underwent CABG. A total of 602 patients (32.5%) had ITDM (PCI/DES n = 325, 34%; CABG n = 277, 31%). Subjects were classified according to ITDM versus non-ITDM, with comparison of PCI/DES versus CABG for each group. Interaction analyses were performed for treatment by diabetes mellitus (DM) status alone and for treatment by DM status by coronary lesion complexity. Analyses were performed for the primary outcome composite of death/stroke/myocardial infarction (MI) using all available follow-up data. Results The overall 5-year event rate of death/stroke/MI was significantly higher in ITDM versus non-ITDM patients (28.7% vs. 19.5%, p < 0.001), which persisted even after adjustment for multiple baseline factors, angiographic complexity, and revascularization treatment group (death/stroke/MI hazard ratio HR: 1.35, 95% confidence interval CI: 1.06 to 1.73, p = 0.014). With respect to the primary composite endpoint, CABG was superior to PCI/DES in both DM types and the magnitude of treatment effect was similar (interaction p = 0.40) for ITDM (PCI vs. CABG HR: 1.21; 95% CI: 0.87 to 1.69) and non-ITDM patients (PCI vs. CABG HR: 1.46; 95% CI 1.10 to 1.94), even after adjusting for the angiographic SYNTAX score level. Based on 5-year event rates, the number needed to treat with CABG versus PCI to prevent 1 event is 12.7 in ITDM and 13.2 in non-ITDM. Conclusions In patients with diabetes and multivessel coronary artery disease, the rate of major adverse cardiovascular events (death, MI, or stroke) is higher in patients treated with insulin than in those not treated with insulin. Furthermore, we did not detect a significant difference in the magnitude of PCI versus CABG treatment effect for patients treated with insulin and those not treated with insulin. (Comparison of Two Treatments for Multivessel Coronary Artery Disease in Individuals With Diabetes FREEDOM; NCT00086450 ).
Objectives This study evaluated data from 3 federally funded trials that focused on optimal medical therapy to determine if formalized attempts at risk factor control within clinical trials are ...effective in achieving guideline-driven treatment goals for diabetic patients with coronary artery disease (CAD). Background Despite clear evidence of benefit for CAD secondary prevention, the level of risk factor control in clinical practice has been disappointing. Methods We obtained data from the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) diabetes subgroup, (n = 766 of 2,287), the BARI 2D (Bypass Angioplasty Revascularization Investigation 2 Diabetes) trial (n = 2,368), and the FREEDOM (Comparison of Two Treatments for Multivessel Coronary Artery Disease in Individuals With Diabetes) trial (n = 1,900) to evaluate the proportion of patients achieving guideline-based, protocol-driven treatment targets for systolic blood pressure, low-density lipoprotein cholesterol, smoking cessation, and hemoglobin A1c. The primary outcome measure was the proportion of diabetic CAD patients meeting all 4 pre-specified targets at 1 year after enrollment. Results The pooled data include 5,034 diabetic patients. The percentages of patients achieving the 1-year low-density lipoprotein cholesterol targets compared with baseline increased from 55% to 77% in COURAGE, from 59% to 75% in BARI 2D, and from 34% to 42% in FREEDOM. Although similar improved trends were seen for systolic blood pressure, glycemic control, and smoking cessation, only 18% of the COURAGE diabetes subgroup, 23% of BARI 2D patients, and 8% of FREEDOM patients met all 4 pre-specified treatment targets at 1 year of follow-up. Conclusions A significant proportion of diabetic CAD patients fail to achieve pre-specified targets for 4 major modifiable cardiovascular risk factors in clinical trials. We conclude that fundamentally new thinking is needed to explore approaches to achieve optimal secondary prevention treatment goals. (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation; NCT00007657 ) (Bypass Angioplasty Revascularization Investigation 2 Diabetes BARI 2D; NCT00006305 ) (Comparison of Two Treatments for Multivessel Coronary Artery Disease in Individuals With Diabetes FREEDOM; NCT00086450 )
Abstract Background There are scant outcomes data in patients with type 2 diabetes and stable coronary artery disease (CAD) stratified by detailed angiographic burden of CAD or left ventricular ...ejection fraction (LVEF). Objectives This study determined the effect of optimal medical therapy (OMT), with or without percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG), on long-term outcomes with respect to LVEF and number of diseased vessels, including proximal left anterior descending artery involvement. Methods A patient-level pooled analysis was undertaken in 3 federally-funded trials. The primary endpoint was the composite of death, myocardial infarction (MI), or stroke, adjusted for trial and randomization strategy. Results Among 5,034 subjects, 15% had LVEF <50%, 77% had multivessel CAD, and 28% had proximal left anterior descending artery involvement. During a median 4.5-year follow-up, CABG + OMT was superior to PCI + OMT for the primary endpoint (hazard ratio HR: 0.71; 95% confidence interval CI: 0.59 to 0.85; p = 0.0002), death (HR: 0.76; 95% CI: 0.60 to 0.96; p = 0.024), and MI (HR: 0.50; 95% CI: 0.38 to 0.67; p = 0.0001), but not stroke (HR: 1.54; 95% CI: 0.96 to 2.48; p = 0.074). CABG + OMT was also superior to OMT alone for prevention of the primary endpoint (HR: 0.79; 95% CI: 0.64 to 0.97; p = 0.022) and MI (HR: 0.55; 95% CI: 0.41 to 0.74; p = 0.0001), and was superior to PCI + OMT for the primary endpoint in patients with 3-vessel CAD (HR: 0.72; 95% CI: 0.58 to 0.89; p = 0.002) and normal LVEF (HR: 0.71; 95% CI: 0.58 to 0.87; p = 0.0012). There were no significant differences in OMT versus PCI + OMT. Conclusions CABG + OMT reduced the primary endpoint during long-term follow-up in patients with type 2 diabetes and stable CAD, supporting this as the preferred management strategy.
The prognostic significance of postprocedure sustained ventricular tachycardia or ventricular fibrillation (VT/VF) in patients undergoing primary percutaneous coronary intervention (PPCI) for ...ST-segment elevation myocardial infarction (STEMI) has rarely been studied, although a previous study has suggested that its occurrence portends decreased survival. We examined outcomes from the prospective large-scale multicenter randomized HORIZONS-AMI trial to evaluate the incidence, clinical correlates, and outcomes of in-hospital sustained VT/VF after PPCI. Of 3,485 patients undergoing PPCI in whom VT/VF did not occur before or during the procedure, 181 patients (5.2%) developed VT/VF after PPCI. Most postprocedural VT/VF episodes (85%) occurred in the first 48 hours. Patients with postprocedural VT/VF were more likely men with Killip class >I on presentation but had a lower prevalence of hypertension and diabetes. Patients with postprocedural VT/VF were also less frequently taking β blockers and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers at admission. Mean door-to-balloon time was shorter and Thrombolysis In Myocardial Infarction grade 0 flow before PPCI was more common in patients with VT/VF, although Thrombolysis In Myocardial Infarction grade 3 flow rates after PPCI did not vary. There were no significant differences in adjusted 3-year rates of mortality (hazard ratio 0.73, 95% confidence interval 0.30 to 1.79) or composite major adverse clinical events (death, myocardial infarction, target vessel revascularization, or stroke; hazard ratio 0.71, 95% confidence interval 0.44 to 1.15) in patients with versus without postprocedural sustained VT/VF. In conclusion, sustained VT/VF after PPCI in the HORIZONS-AMI trial was not significantly associated with 3-year mortality or major adverse clinical events. Further studies are required to address the prognostic significance of VT/VF in patients with STEMI undergoing PPCI.
Abstract Background Data prior to 2011 suggest that a low percentage of patients hospitalized for acute coronary syndromes filled high-intensity statin prescriptions upon discharge. Black-box ...warnings, generic availability of atorvastatin, and updated guidelines may have resulted in a change in high-intensity statin use. Objectives The aim of this study was to examine trends and predictors of high-intensity statin use following hospital discharge for myocardial infarction (MI) between 2011 and 2014. Methods Secular trends in high-intensity statin use following hospital discharge for MI were analyzed among patients 19 to 64 years of age with commercial health insurance in the MarketScan database (n = 42,893) and 66 to 75 years of age with U.S. government health insurance through Medicare (n = 75,096). Patients filling statin prescriptions within 30 days of discharge were included. High-intensity statins included atorvastatin 40 or 80 mg and rosuvastatin 20 or 40 mg. Results The percentage of beneficiaries whose first statin prescriptions filled following hospital discharge for MI were for high-intensity doses increased from 33.5% in January through March 2011 to 71.7% in October through November 2014 in MarketScan and from 24.8% to 57.5% in Medicare. Increases in high-intensity statin use following hospital discharge occurred over this period among patients initiating treatment (30.6% to 72.0% in MarketScan and 21.1% to 58.8% in Medicare) and those taking low- or moderate-intensity statins prior to hospitalization (from 27.8% to 62.3% in MarketScan and from 12.6% to 45.1% in Medicare). In 2014, factors associated with filling high-intensity statin prescriptions included male sex, filling beta-blocker and antiplatelet agent prescriptions, and attending cardiac rehabilitation within 30 days following discharge. Conclusions The use of high-intensity statins following hospitalization for MI increased progressively from 2011 through 2014.
A Polypill Strategy to Improve Adherence Castellano, José M., MD, PhD; Sanz, Ginés, MD, PhD; Peñalvo, José L., PhD ...
Journal of the American College of Cardiology,
11/2014, Letnik:
64, Številka:
20
Journal Article
Recenzirano
Odprti dostop
Abstract Background Adherence to evidence-based cardiovascular (CV) medications after an acute myocardial infarction (MI) is low after the first 6 months. The use of fixed-dose combinations (FDC) has ...been shown to improve treatment adherence and risk factor control. However, no previous randomized trial has analyzed the impact of a polypill strategy on adherence in post-MI patients. Objectives The cross-sectional FOCUS (Fixed-Dose Combination Drug for Secondary Cardiovascular Prevention) study (Phase 1) aimed to elucidate factors that interfere with appropriate adherence to CV medications for secondary prevention after an acute MI. Additionally, 695 patients from Phase 1 were randomized into a controlled trial (Phase 2) to test the effect of a polypill (containing aspirin 100 mg, simvastatin 40 mg, and ramipril 2.5, 5, or 10 mg) compared with the 3 drugs given separately on adherence, blood pressure, and low-density lipoprotein cholesterol, as well as safety and tolerability over a period of 9 months of follow-up. Methods In Phase 1, a 5-country cohort of 2,118 patients was analyzed. Patients were randomized to either the polypill or 3 drugs separately for Phase 2. Primary endpoint was adherence to the treatment measured at the final visit by the self-reported Morisky-Green questionnaire (MAQ) and pill count (patients had to meet both criteria for adherence at the in-person visit to be considered adherent). Results In Phase 1, overall CV medication adherence, defined as an MAQ score of 20, was 45.5%. In a multivariable regression model, the risk of being nonadherent (MAQ <20) was associated with younger age, depression, being on a complex medication regimen, poorer health insurance coverage, and a lower level of social support, with consistent findings across countries. In Phase 2, the polypill group showed improved adherence compared with the group receiving separate medications after 9 months of follow-up: 50.8% versus 41% (p = 0.019; intention-to-treat population) and 65.7% versus 55.7% (p = 0.012; per protocol population) when using the primary endpoint, attending the final visit with MAQ = 20 and high pill count (80% to 110%) combined, to assess adherence. Adherence also was higher in the FDC group when measured by MAQ alone (68% vs. 59%, p = 0.049). No treatment difference was found at follow-up in mean systolic blood pressure (129.6 mm Hg vs. 128.6 mm Hg), mean low-density lipoprotein cholesterol levels (89.9 mg/dl vs. 91.7 mg/dl), serious adverse events (23 vs. 21), or death (1, 0.3% in each group). Conclusions For secondary prevention following acute MI, younger age, depression, and a complex drug treatment plan are associated with lower medication adherence. Meanwhile, adherence is increased in patients with higher insurance coverage levels and social support. Compared with the 3 drugs given separately, the use of a polypill strategy met the primary endpoint for adherence for secondary prevention following an acute MI. (Fixed Dose Combination Drug Polypill for Secondary Cardiovascular Prevention FOCUS; NCT01321255 )
Summary Background Dalcetrapib modulates cholesteryl ester transfer protein (CETP) activity to raise high-density lipoprotein cholesterol (HDL-C). After the failure of torcetrapib it was unknown if ...HDL produced by interaction with CETP had pro-atherogenic or pro-inflammatory properties. dal-PLAQUE is the first multicentre study using novel non-invasive multimodality imaging to assess structural and inflammatory indices of atherosclerosis as primary endpoints. Methods In this phase 2b, double-blind, multicentre trial, patients (aged 18–75 years) with, or with high risk of, coronary heart disease were randomly assigned (1:1) to dalcetrapib 600 mg/day or placebo for 24 months. Randomisation was done with a computer-generated randomisation code and was stratified by centre. Patients and investigators were masked to treatment. Coprimary endpoints were MRI-assessed indices (total vessel area, wall area, wall thickness, and normalised wall index average carotid) after 24 months and18 F-fluorodeoxyglucose (18 F-FDG) PET/CT assessment of arterial inflammation within an index vessel (right carotid, left carotid, or ascending thoracic aorta) after 6 months, with no-harm boundaries established before unblinding of the trial. Analysis was by intention to treat. This trial is registered at ClinicalTrials.gov , NCT00655473. Findings 189 patients were screened and 130 randomly assigned to placebo (66 patients) or dalcetrapib (64 patients). For the coprimary MRI and PET/CT endpoints, CIs were below the no-harm boundary or the adverse change was numerically lower in the dalcetrapib group than in the placebo group. MRI-derived change in total vessel area was reduced in patients given dalcetrapib compared with those given placebo after 24 months; absolute change from baseline relative to placebo was −4·01 mm2 (90% CI −7·23 to −0·80; nominal p=0·04). The PET/CT measure of index vessel most-diseased-segment target-to-background ratio (TBR) was not different between groups, but carotid artery analysis showed a 7% reduction in most-diseased-segment TBR in the dalcetrapib group compared with the placebo group (–7·3 90% CI −13·5 to −0·8; nominal p=0·07). Dalcetrapib did not increase office blood pressure and the frequency of adverse events was similar between groups. Interpretation Dalcetrapib showed no evidence of a pathological effect related to the arterial wall over 24 months. Moreover, this trial suggests possible beneficial vascular effects of dalcetrapib, including the reduction in total vessel enlargement over 24 months, but long-term safety and clinical outcomes efficacy of dalcetrapib need to be analysed. Funding F Hoffmann-La Roche Ltd.
Abstract Background National guidelines recommend use of high-intensity statins after hospitalization for coronary heart disease (CHD) events. Objectives This study sought to estimate the proportion ...of Medicare beneficiaries filling prescriptions for high-intensity statins after hospital discharge for a CHD event and to analyze whether statin intensity before hospitalization is associated with statin intensity after discharge. Methods We conducted a retrospective cohort study using a 5% random sample of Medicare beneficiaries between 65 and 74 years old. Beneficiaries were included in the analysis if they filled a statin prescription after a CHD event (myocardial infarction or coronary revascularization) in 2007, 2008, or 2009. High-intensity statins included atorvastatin 40 to 80 mg, rosuvastatin 20 to 40 mg, and simvastatin 80 mg. Results Among 8,762 Medicare beneficiaries filling a statin prescription after a CHD event, 27% of first post-discharge fills were for a high-intensity statin. The percent filling a high-intensity statin post-discharge was 23.1%, 9.4%, and 80.7%, for beneficiaries not taking statins pre-hospitalization, taking low/moderate-intensity statins, and taking high-intensity statins before their CHD event, respectively. Compared with beneficiaries not on statin therapy pre-hospitalization, multivariable adjusted risk ratios for filling a high-intensity statin were 4.01 (3.58–4.49) and 0.45 (0.40–0.52) for participants taking high-intensity and low/moderate-intensity statins before their CHD event, respectively. Only 11.5% of beneficiaries whose first post-discharge statin fill was for a low/moderate-intensity statin filled a high-intensity statin within 365 days of discharge. Conclusions The majority of Medicare beneficiaries do not fill high-intensity statins after hospitalization for CHD.
Abstract Background EXCELS was a postmarketing commitment to the US Food and Drug Administration to assess long-term safety of omalizumab in an observational setting, focusing predominantly on ...malignancies. Objective To examine a potential association between omalizumab and cardiovascular (CV)/cerebrovascular (CBV) events in EXCELS. Methods Cohort study of patients (≥12 years of age) with moderate-to-severe allergic asthma followed ≤5 years, treated with omalizumab (n = 5007) or not treated with omalizumab (n = 2829) at baseline. Analyses included overall CV/CBV events, but focused on the subset of arterial thromboembolic events (ATE), comprising CV death, myocardial infarction, ischemic stroke, transient ischemic attack, or unstable angina. A prespecified analysis for the endpoint of ATE was conducted to control for available potential confounders. A blinded independent expert panel adjudicated all events. Results At baseline, cohorts had similar demographic characteristics, but severe asthma was more common in the omalizumab versus non-omalizumab cohorts (50% vs 23%). Omalizumab-treated patients had a higher rate of CV/CBV serious adverse events (13.4 per 1000 person-years PY) than non-omalizumab–treated patients (8.1 per 1000 PY). ATE rate per 1000 PY was 6.66 (101 patients/15,160 PY) for the omalizumab cohort and 4.64 (46 patients/9904 PY) for the non-omalizumab cohort. After controlling for available confounding factors, the hazard ratio was 1.32 (95% CI, 0.91-1.91). Conclusion Results from this observational study demonstrated a higher incidence rate of CV/CBV events in the omalizumab versus non-omalizumab cohorts. Differences in asthma severity between cohorts likely contributed to this imbalance, but some increase in risk cannot be excluded (NCT00252135). Clinical implications Current asthma management guidelines should not be affected. However, health professionals should be aware of a possible association of omalizumab and serious cardiovascular/cerebrovascular events.
Abstract Diabetic cardiomyopathy is the presence of myocardial dysfunction in the absence of coronary artery disease and hypertension. Hyperglycemia seems to be central to the pathogenesis of ...diabetic cardiomyopathy and to trigger a series of maladaptive stimuli that result in myocardial fibrosis and collagen deposition. These processes are thought to be responsible for altered myocardial relaxation characteristics and manifest as diastolic dysfunction on imaging. Sophisticated imaging technologies also have permitted the detection of subtle systolic dysfunction in the diabetic myocardium. In the early stages, these changes appear reversible with tight metabolic control, but as the pathologic processes become organized, the changes are irreversible and contribute to an excess risk of heart failure among diabetic patients independently of common comorbidities, such as coronary artery disease and hypertension. Therapeutic agents specifically targeting processes that lead to these pathophysiologic changes are in the early stages of development. Although glycemic control and early administration of neurohormonal antagonists remain the cornerstones of therapeutic approaches, newer treatment targets are currently being explored.
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