Lorenzo Ramón Álvarez

Clinical outcome in patients with peripheral artery disease. Results from a prospective registry (FRENA)

BACKGROUND The risk of future cardiovascular events in patients with peripheral artery disease (PAD) is often underestimated. PATIENTS AND METHODS FRENA is an ongoing, observational registry of consecutive outpatients with symptomatic PAD, coronary artery disease (CAD) or cerebrovascular disease (CVD). We compared the incidence of major cardiovascular events (i.e., myocardial infarction, ischemic stroke, critical limb ischemia, or cardiovascular death) during a 12-month follow-up period in a series of consecutive outpatients with PAD, CAD or CVD. RESULTS As of December 2006, 1265 patients had been enrolled in FRENA who completed the 12-month follow-up. Of these, 417 patients (33%) had PAD, 474 (37%) had CAD, 374 (30%) had CVD. Patients with PAD had an increased incidence of major cardiovascular events per 100 patient-years: 17 (95% CI: 13-22) vs. 7.9 (5.5-11) in those with CAD, or 8.9 (6.1-13) in those with CVD. Compared to patients with CAD or CVD those with PAD had a similar incidence of myocardial infarction or stroke, but a higher incidence of critical limb ischemia, limb amputation and death. This incidence increased with the severity of the symptoms: 8.7 (95% CI: 5.3-13) in patients in Fontaine stage IIa; 25 (95% CI: 16-38) in stage IIb; 26 (95% CI: 13-47) in stage III; 42 (95% CI: 24-67) in stage IV. CONCLUSIONS Our data confirm a higher incidence of major cardiovascular events for patients with PAD, as well as a correlation of these events with the severity of PAD.

Smoking cessation and outcome in stable outpatients with coronary, cerebrovascular, or peripheral artery disease

Background: The influence of smoking cessation on outcome in patients with peripheral arterial disease (PAD) has not been thoroughly studied. Methods: FRENA is an ongoing registry of stable outpatients with symptomatic coronary artery disease (CAD), cerebrovascular disease (CVD), or PAD. We compared the mortality rate of those who quit vs. those who continued smoking. Results: As of December 2010, 3523 patients were recruited, of whom 1182 (34%) were current smokers. Of these, 475 patients (40%) had CAD, 240 (20%) had CVD, and 467 (40%) had PAD. In all, 512 patients (43%) quit smoking. Over a mean follow-up of 14 months, 32 patients (2.7%) died and 95 (8.0%) had subsequent ischaemic events (myocardial infarction 32, ischaemic stroke 20, critical limb ischaemia/disabling claudication 53). In patients with CAD, the mortality rate was significantly lower in recent quitters (0.77 vs. 3.73 deaths per 100 patient-years; p = 0.013) than in persistent smokers. No quitter with CVD died (0.0 vs. 2.18 deaths; p = 0.092); but in patients with PAD there was a trend towards a higher mortality in quitters than in those who continued smoking (4.29 vs. 2.27 deaths; p = 0.357). On multivariate analysis, the relative risk for death in quitters was 0.20 (95% CI 0.05–0.75) in patients with CAD, 0.0 in those with CVD, and 1.83 (95% CI 0.65–5.15) in those with PAD. Conclusions: Smoking cessation was associated with a significant decrease in mortality in patients with CAD, a non-significant decrease in those with CVD, and a non-significant increase in those with PAD.

Differences in cardiovascular mortality in smokers, past-smokers and non-smokers: Findings from the FRENA registry

BACKGROUND The influence of smoking on outcome in patients with coronary artery disease (CAD) is controversial. Even less is known about its influence in patients with cerebrovascular (CVD), or peripheral artery (PAD) disease. PATIENTS AND METHODS FRENA is an ongoing, observational registry of consecutive outpatients with symptomatic CAD, CVD, or PAD. We reviewed their cardiovascular mortality according to smoking status. RESULTS As of May 2008, 2501 patients had been enrolled in FRENA. Of these, 439 (18%) were current smokers, 1086 (43%) past-smokers, 976 (39%) had never smoked. Current- and past-smokers were 10 years younger, more often males, and more likely to have chronic lung disease, but had diabetes, hypertension, heart failure, or renal insufficiency less often than non-smokers. Over a mean follow-up of 14 months, 123 patients died (cardiovascular death, 68). On univariate analysis, current smokers had a significantly lower rate of cardiovascular death: 1.1 (95% CI: 0.4-2.4) per 100 patient-years in current smokers; 1.9 (95% CI: 1.2-2.8) in past-smokers; 3.5 (95% CI: 2.5-4.7) in non-smokers, with no differences between patients with CAD, CVD or PAD. Mean age at cardiovascular death was 82+/-6.4; 70+/-9.9 and 67+/-15 years, respectively. On multivariate analysis, smoking status was not independently associated with a lower risk for cardiovascular death. CONCLUSIONS Current and past-smokers with CAD, CVD or PAD had a less than half cardiovascular mortality than those who never smoked, but this may be explained by the confounding effect of additional variables. They died over 10 years younger than non-smokers.

Renal function and short-term outcome in stable outpatients with coronary, cerebrovascular or peripheral artery disease

BACKGROUND The influence of renal function on outcome in stable outpatients with atherosclerotic disease has not been thoroughly studied. METHODS We used the FRENA Registry data to compare the incidence of subsequent ischemic events (myocardial infarction [MI], ischemic stroke or limb amputation) in patients with coronary (CAD), cerebrovascular (CVD) or peripheral artery disease (PAD), according to their estimated glomerular filtration rate (eGFR) at baseline. RESULTS As of April 2012, 3860 patients were recruited in FRENA: 1439 with CAD, 1118 with CVD and 1303 with PAD. Over a mean follow-up of 14 ± 12 months, 97 patients suffered subsequent MI, 93 had ischemic stroke and 46 underwent limb amputation. In all, 2699 patients (70%) had eGFR > 60 mL/min/1.73 m(2), 1022 (26%) had 30-60 mL/min/1.73 m(2), and 139 (3.6%) had <30 mL/min/1.73 m(2). Among patients with CAD, the rate of subsequent MI was: 1.38 (95% CI: 0.85-2.11), 5.79 (95% CI: 3.90-8.31) and 18.8 (95% CI: 9.14-34.4) events per 100 patient-years, respectively. On multivariable analysis, the hazard ratio for MI (compared with patients with eGFR > 60 mL/min/1.73 m(2)) was of 1.77 (95% CI: 1.15-2.73) for patients with eGFR of 30-60 mL/min/1.73 m(2), and 3.15 (95% CI: 1.61-6.14) for those with eGFR < 30 mL/min/1.73 m(2). Among patients with CVD or PAD, there was no increasing rate of subsequent ischemic events with decreasing renal function. CONCLUSIONS Among stable outpatients with CAD, there is an increasing rate of subsequent MI with decreasing renal function, independently of potentially confounding variables. These findings were not observed in patients with CVD or PAD.

Efficacy of bosentan in patients with refractory thromboangiitis obliterans (buerger disease): A case series and review of the literature

AbstractThe cornerstone of therapy in thromboangiitis obliterans (TAO) is complete abstinence from tobacco. In addition to discontinuation of cigarette smoking, very few pharmacological and surgical options of controversial efficacy are available to date. New therapeutic options with greater efficacy are clearly needed to properly manage these patients.In this preliminary study, we assessed the effectiveness and safety of bosentan in a case series of 8 adults with TAO and severe ischemic ulceronecrotic lesions who were treated with bosentan after inadequate response to platelet inhibitors, vasodilators, and intravenous alprostadil. Additionally, we reviewed 18 well-documented patients with refractory TAO treated with bosentan, which was previously reported (PubMed 1965–2015). These 26 patients formed the basis of our present analysis. All were current smokers.The median duration of bosentan treatment (SD) was 4.5 ± 4 months (range 3–16). Eleven patients (42%) were unable to completely abstain from smoking during their follow-up. With bosentan treatment, no new ischemic lesions were observed in the target extremities. A complete therapeutic response was achieved in 80% of patients, whereas a partial response was observed in 12%. Two patients (8%) ultimately required amputation despite treatment.After discontinuation of bosentan, patients were followed for a median of 20 ± 14 months (range 3–60). Two patients whose trophic lesions had healed relapsed.When comparing patients who gave up smoking with those who were unable to completely abstain from smoking during follow-up, no significant differences were found in efficacy outcomes. Four patients (15%) developed adverse events, requiring bosentan discontinuation in 1 case.These preliminary data suggest that bosentan may be considered a therapeutic option for treatment of cases of severe TAO refractory to conventional treatment, and merit further evaluation in larger controlled, randomized clinical studies.

Cardiac Rehabilitation and Outcome in Stable Outpatients With Recent Myocardial Infarction

OBJECTIVE To compare the mortality rate and the rate of subsequent ischemic events (myocardial infarction [MI], ischemic stroke, or limb amputation) in patients with recent MI according to the use of cardiac rehabilitation or no rehabilitation. DESIGN Longitudinal observational study. SETTING Ongoing registry of outpatients. PARTICIPANTS Patients (N=1043) with recent acute MI were recruited; of these, 521 (50%) participated in cardiac rehabilitation. INTERVENTIONS Not applicable. MAIN OUTCOME MEASURES Subsequent ischemic events and mortality rates were registered. RESULTS Over a mean follow-up of 18 months, 50 patients (4.8%) died and 49 (4.7%) developed 52 subsequent ischemic events (MI: n=43, ischemic stroke: n=6, limb amputation: n=3). Both the mortality rate (.16 vs 5.57 deaths per 100 patient-years; rate ratio=.03; 95% confidence interval [CI], 0.0-0.1]) and the rate of subsequent ischemic events (1.65 vs 4.54 events per 100 patient-years; rate ratio=0.4; 95% CI, 0.2-0.7) were significantly lower in cardiac rehabilitation participants than in nonparticipants. Multivariate analysis confirmed that patients in cardiac rehabilitation had a significantly lower risk of death (hazard ratio=.08; 95% CI, .01-.63; P=.016) and a nonsignificant lower risk of subsequent ischemic events (hazard ratio=.65; 95% CI, .30-1.42). CONCLUSIONS The use of cardiac rehabilitation in patients with recent MI was independently associated with a significant decrease in the mortality rate and a nonsignificant decrease in the rate of subsequent ischemic events.

Supervised versus non-supervised exercise in patients with recent myocardial infarction: A propensity analysis

Background The influence of supervised versus non-supervised exercise training on outcome in patients with a recent myocardial infarction (MI) is controversial. Design Longitudinal observational study. Methods FRENA is an ongoing registry of stable outpatients with symptomatic coronary, cerebrovascular or peripheral artery disease. We compared the rate of subsequent ischaemic events (MI, ischaemic stroke or lower limb amputation) and the mortality rate in patients with recent MI, according to the use of supervised versus non-supervised exercise training. The influence of physical activity on outcomes was estimated by using propensity score method in multivariate analysis. Results As of February 2014, 1124 outpatients with recent MI were recruited, of whom 593 (53%) participated in a supervised exercise training programme. Over a mean follow-up of 15 months, 25 patients (3.3%) developed 26 subsequent ischaemic events – 24 MI, one stroke, one lower-limb amputation – and 12 (1.6%) died. The mortality rate (0.15 vs. 2.89 deaths per 100 patient-years; rate ratio = 0.05; 95% confidence interval, 0.01–0.39) was significantly lower in supervised exercise than in non-supervised exercise patients. On propensity score analysis, the rate of the composite outcome was significantly lower in supervised exercise patients (1.80 vs. 6.51 events per 100 patient-years; rate ratio = 0.28; 95% confidence interval, 0.12–0.64). Conclusions The use of supervised exercise training in patients with recent MI was associated with a significant decrease in the composite outcome of subsequent ischaemic events and death.

Raised Fibrinogen Levels and Outcome in Outpatients With Peripheral Artery Disease

The influence of raised fibrinogen levels on outcome in stable outpatients with peripheral arterial disease (PAD) has not been consistently investigated. We used data from the Factores de Riesgo y ENfermedad Arterial (FRENA) registry to compare ischemic events, major bleeding, and mortality in stable outpatients with PAD, according to their baseline plasma fibrinogen levels. Of 1363 outpatients with PAD recruited in FRENA, 558 (41%) had fibrinogen levels >450 mg/100 mL. Over 18 months, 43 patients presented with acute myocardial infarction, 37 had an ischemic stroke, 51 underwent limb amputation, 19 had major bleeding, and 90 died. Compared to patients with normal levels, those with raised fibrinogen levels had an over 2-fold higher rate of ischemic stroke (rate ratio [RR]: 2.30; 95% confidence interval [CI]: 1.19-4.59), limb amputation (RR: 2.58; 95% CI: 1.46-4.67), or death (RR: 2.27; 95% CI: 1.49-3.51) and an over 3-fold higher rate of major bleeding (RR: 3.90; 95% CI: 1.45-12.1). On multivariate analysis, patients with raised fibrinogen levels had an increased risk of developing subsequent ischemic events (hazard ratio [HR]: 1.61; 95% CI: 1.11-2.32) and major bleeding (HR: 3.42; 95% CI: 1.22-9.61). Stable outpatients with PAD and raised plasma fibrinogen levels had increased rates of subsequent ischemic events and major bleeding.

Lipoprotein (a) levels and outcomes in stable outpatients with symptomatic artery disease

BACKGROUND AND AIMS Although genetic and epidemiological studies support that people with high lipoprotein (a) [Lp(a)] levels are at an increased risk for arterial disease, its prognostic value in patients with established artery disease has not been consistently evaluated. METHODS FRENA is a prospective registry of consecutive outpatients with coronary, cerebrovascular or peripheral artery disease. We assessed the risk for subsequent myocardial infarction, ischemic stroke or limb amputation according to Lp(a) levels at baseline. RESULTS As of December 2016, 1503 stable outpatients were recruited. Of these, 814 (54%) had levels <30 mg/dL, 319 (21%) had 30-50 mg/dL and 370 (25%) had ≥50 mg/dL. Over a mean follow-up of 36 months, 294 patients developed subsequent events (myocardial infarction 122, ischemic stroke 114, limb amputation 58) and 85 died. On multivariable analysis, patients with Lp(a) levels of 30-50 mg/dL were at a higher risk for myocardial infarction (hazard ratio [HR]: 4.67; 95%CI: 2.77-7.85), ischemic stroke (HR: 8.27; 95%CI: 4.14-16.5) or limb amputation (HR: 3.18; 95%CI: 1.36-7.44) than those with normal levels. Moreover, patients with levels ≥50 mg/dL were at increased risk for myocardial infarction (HR: 19.5; 95%CI: 10.5-36.1), ischemic stroke (HR: 54.5; 95%CI: 25.4-116.7) or limb amputation (HR: 22.7; 95%CI: 9.38-54.9). CONCLUSIONS Stable outpatients with symptomatic artery disease and Lp(a) levels >30 mg/dL were at a 5-fold higher risk for subsequent myocardial infarction, stroke or limb amputation. Those with levels >50 mg/dL were at an over 10-fold higher risk.