RESUMEN
BACKGROUND: Patients with peripheral artery disease requiring lower extremity revascularization (LER) are at high risk of adverse limb and cardiovascular events. The VOYAGER PAD trial (Vascular Outcomes Study of ASA [Acetylsalicylic Acid] Along With Rivaroxaban in Endovascular or Surgical Limb Revascularization for PAD) demonstrated that rivaroxaban significantly reduced this risk. The efficacy and safety of rivaroxaban has not been described in patients who underwent surgical LER. METHODS: The VOYAGER PAD trial randomized patients with peripheral artery disease after surgical and endovascular LER to rivaroxaban 2.5 mg twice daily plus aspirin or matching placebo plus aspirin and followed for a median of 28 months. The primary end point was a composite of acute limb ischemia, major vascular amputation, myocardial infarction, ischemic stroke, or cardiovascular death. The principal safety outcome was Thrombolysis in Myocardial Infarction major bleeding. International Society on Thrombosis and Haemostasis bleeding was a secondary safety outcome. All efficacy and safety outcomes were adjudicated by a blinded independent committee. RESULTS: Of the 6564 randomized, 2185 (33%) underwent surgical LER and 4379 (67%) endovascular. Compared with placebo, rivaroxaban reduced the primary end point consistently regardless of LER method (P-interaction, 0.43). After surgical LER, the primary efficacy outcome occurred in 199 (18.4%) patients in the rivaroxaban group and 242 (22.0%) patients in the placebo group with a cumulative incidence at 3 years of 19.7% and 23.9%, respectively (hazard ratio, 0.81 [95% CI, 0.67-0.98]; P=0.026). In the overall trial, Thrombolysis in Myocardial Infarction major bleeding and International Society on Thrombosis and Haemostasis major bleeding were increased with rivaroxaban. There was no heterogeneity for Thrombolysis in Myocardial Infarction major bleeding (P-interaction, 0.17) or International Society on Thrombosis and Haemostasis major bleeding (P-interaction, 0.73) on the basis of the LER approach. After surgical LER, the principal safety outcome occurred in 11 (1.0%) patients in the rivaroxaban group and 13 (1.2%) patients in the placebo group; 3-year cumulative incidence was 1.3% and 1.4%, respectively (hazard ratio, 0.88 [95% CI, 0.39-1.95]; P=0.75) Among surgical patients, the composite of fatal bleeding or intracranial hemorrhage (P=0.95) and postprocedural bleeding requiring intervention (P=0.93) was not significantly increased. CONCLUSIONS: The efficacy of rivaroxaban is associated with a benefit in patients who underwent surgical LER. Although bleeding was increased with rivaroxaban plus aspirin, the incidence was low, with no significant increase in fatal bleeding, intracranial hemorrhage, or postprocedural bleeds requiring intervention. Registration: URL: http://www.clinicaltrials.gov; Unique Identifier: NCT02504216.
Asunto(s)
Aspirina/uso terapéutico , Enfermedad Arterial Periférica/tratamiento farmacológico , Enfermedad Arterial Periférica/cirugía , Rivaroxabán/uso terapéutico , Anciano , Aspirina/farmacología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Rivaroxabán/farmacologíaRESUMEN
BACKGROUND: COVID-19 is associated with both venous and arterial thrombotic complications. While prophylactic anticoagulation is now widely recommended for hospitalized patients with COVID-19, the effectiveness and safety of thromboprophylaxis in outpatients with COVID-19 has not been established. STUDY DESIGN: PREVENT-HD is a double-blind, placebo-controlled, pragmatic, event-driven phase 3 trial to evaluate the efficacy and safety of rivaroxaban in symptomatic outpatients with laboratory-confirmed COVID-19 at risk for thrombotic events, hospitalization, and death. Several challenges posed by the pandemic have necessitated innovative approaches to clinical trial design, start-up, and conduct. Participants are randomized in a 1:1 ratio, stratified by time from COVID-19 confirmation, to either rivaroxaban 10 mg once daily or placebo for 35 days. The primary efficacy end point is a composite of symptomatic venous thromboembolism, myocardial infarction, ischemic stroke, acute limb ischemia, non-central nervous system systemic embolization, all-cause hospitalization, and all-cause mortality. The primary safety end point is fatal and critical site bleeding according to the International Society on Thrombosis and Haemostasis definition. Enrollment began in August 2020 and is expected to enroll approximately 4,000 participants to yield the required number of end point events. CONCLUSIONS: PREVENT-HD is a pragmatic trial evaluating the efficacy and safety of the direct oral anticoagulant rivaroxaban in the outpatient setting to reduce major venous and arterial thrombotic events, hospitalization, and mortality associated with COVID-19.
Asunto(s)
COVID-19/complicaciones , Inhibidores del Factor Xa/uso terapéutico , Hospitalización , Pacientes Ambulatorios , Rivaroxabán/uso terapéutico , Trombosis/prevención & control , Adulto , COVID-19/mortalidad , Causas de Muerte , Método Doble Ciego , Extremidades/irrigación sanguínea , Inhibidores del Factor Xa/efectos adversos , Femenino , Hemorragia/inducido químicamente , Hemorragia/mortalidad , Mortalidad Hospitalaria , Humanos , Isquemia/etiología , Accidente Cerebrovascular Isquémico/etiología , Masculino , Persona de Mediana Edad , Infarto del Miocardio/etiología , Placebos/uso terapéutico , Rivaroxabán/efectos adversos , Trombosis/mortalidad , Tromboembolia Venosa/mortalidad , Tromboembolia Venosa/prevención & controlRESUMEN
Importance: Identifying modifiable risk factors, such as stress, that could inform the design of peripheral artery disease (PAD) management strategies is critical for reducing the risk of mortality. Few studies have examined the association of self-perceived stress with outcomes in patients with PAD. Objective: To examine the association of high levels of self-perceived stress with mortality in patients with PAD. Design, Setting, and Participants: This cohort study analyzed data from the registry of the Patient-Centered Outcomes Related to Treatment Practices in Peripheral Arterial Disease: Investigating Trajectories (PORTRAIT) study, a multicenter study that enrolled patients with new or worsening symptoms of PAD who presented to 16 subspecialty clinics across the US, the Netherlands, and Australia from June 2, 2011, to December 3, 2015. However, the present study included only patients in the US sites because assessments of mortality for patients in the Netherlands and Australia were not available. Data analysis was conducted from July 2019 to March 2020. Exposure: Self-perceived stress was quantified using the 4-item Perceived Stress Scale (PSS-4), with a score range of 0 to 16. A score of 6 or higher indicated high stress in this cohort. Missing scores were imputed using multiple imputation by chained equations with predictive mean matching. Stress was assessed at baseline and at 3-, 6-, and 12-month follow-up. Patients who reported high levels of stress at 2 or more follow-up assessments were categorized as having chronic stress. Main Outcomes and Measures: All-cause mortality was the primary study outcome. Such data for the subsequent 4 years after the 12-month follow-up were obtained from the National Death Index. Results: The final cohort included 765 patients, with a mean (SD) age of 68.4 (9.7) years. Of these patients, 57.8% were men and 71.6% were white individuals. High stress levels were reported in 65% of patients at baseline and in 20% at the 12-month follow-up. In an adjusted Cox proportional hazards regression model accounting for demographics, comorbidities, disease severity, treatment type, and socioeconomic status, exposure to chronic stress during the 12 months of follow-up was independently associated with increased risk of all-cause mortality in the subsequent 4 years (hazard ratio, 2.12; 95% CI, 1.14-3.94; P = .02). Conclusions and Relevance: In thie cohort study of patients with PAD, higher stress levels in the year after diagnosis appeared to be associated with greater long-term mortality risk, even after adjustment for confounding factors. These findings suggest that, given that stress is a modifiable risk factor for which evidence-based management strategies exist, a holistic approach that includes assessment of chronic stress has the potential to improve survival in patients with PAD.
Asunto(s)
Enfermedad Arterial Periférica , Estrés Psicológico , Anciano , Enfermedad Crónica , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedad Arterial Periférica/complicaciones , Enfermedad Arterial Periférica/epidemiología , Enfermedad Arterial Periférica/mortalidad , Enfermedad Arterial Periférica/psicología , Factores de Riesgo , Estrés Psicológico/complicaciones , Estrés Psicológico/epidemiología , Estrés Psicológico/psicología , Estrés Psicológico/terapiaRESUMEN
BACKGROUND: Patients with peripheral artery disease who have undergone lower-extremity revascularization are at high risk for major adverse limb and cardiovascular events. The efficacy and safety of rivaroxaban in this context are uncertain. METHODS: In a double-blind trial, patients with peripheral artery disease who had undergone revascularization were randomly assigned to receive rivaroxaban (2.5 mg twice daily) plus aspirin or placebo plus aspirin. The primary efficacy outcome was a composite of acute limb ischemia, major amputation for vascular causes, myocardial infarction, ischemic stroke, or death from cardiovascular causes. The principal safety outcome was major bleeding, defined according to the Thrombolysis in Myocardial Infarction (TIMI) classification; major bleeding as defined by the International Society on Thrombosis and Haemostasis (ISTH) was a secondary safety outcome. RESULTS: A total of 6564 patients underwent randomization; 3286 were assigned to the rivaroxaban group, and 3278 were assigned to the placebo group. The primary efficacy outcome occurred in 508 patients in the rivaroxaban group and in 584 in the placebo group; the Kaplan-Meier estimates of the incidence at 3 years were 17.3% and 19.9%, respectively (hazard ratio, 0.85, 95% confidence interval [CI], 0.76 to 0.96; P = 0.009). TIMI major bleeding occurred in 62 patients in the rivaroxaban group and in 44 patients in the placebo group (2.65% and 1.87%; hazard ratio, 1.43; 95% CI, 0.97 to 2.10; P = 0.07). ISTH major bleeding occurred in 140 patients in the rivaroxaban group, as compared with 100 patients in the placebo group (5.94% and 4.06%; hazard ratio, 1.42; 95% CI, 1.10 to 1.84; P = 0.007). CONCLUSIONS: In patients with peripheral artery disease who had undergone lower-extremity revascularization, rivaroxaban at a dose of 2.5 mg twice daily plus aspirin was associated with a significantly lower incidence of the composite outcome of acute limb ischemia, major amputation for vascular causes, myocardial infarction, ischemic stroke, or death from cardiovascular causes than aspirin alone. The incidence of TIMI major bleeding did not differ significantly between the groups. The incidence of ISTH major bleeding was significantly higher with rivaroxaban and aspirin than with aspirin alone. (Funded by Bayer and Janssen Pharmaceuticals; VOYAGER PAD ClinicalTrials.gov number, NCT02504216.).
Asunto(s)
Aspirina/uso terapéutico , Inhibidores del Factor Xa/uso terapéutico , Isquemia/prevención & control , Extremidad Inferior/irrigación sanguínea , Enfermedad Arterial Periférica/tratamiento farmacológico , Inhibidores de Agregación Plaquetaria/uso terapéutico , Rivaroxabán/uso terapéutico , Anciano , Aspirina/efectos adversos , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/mortalidad , Enfermedades Cardiovasculares/prevención & control , Terapia Combinada , Método Doble Ciego , Quimioterapia Combinada , Procedimientos Endovasculares , Inhibidores del Factor Xa/efectos adversos , Femenino , Hemorragia/inducido químicamente , Hemorragia/epidemiología , Humanos , Incidencia , Isquemia/epidemiología , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Enfermedad Arterial Periférica/cirugía , Inhibidores de Agregación Plaquetaria/efectos adversos , Rivaroxabán/efectos adversosRESUMEN
BACKGROUND: Patients who are hospitalized for medical illness remain at risk for venous thromboembolism after discharge, but the role of extended thromboprophylaxis in the treatment of such patients is a subject of controversy. METHODS: In this randomized, double-blind trial, medically ill patients who were at increased risk for venous thromboembolism on the basis of a modified International Medical Prevention Registry on Venous Thromboembolism (IMPROVE) score of 4 or higher (scores range from 0 to 10, with higher scores indicating a higher risk of venous thromboembolism) or a score of 2 or 3 plus a plasma d-dimer level of more than twice the upper limit of the normal range (defined according to local laboratory criteria) were assigned at hospital discharge to either once-daily rivaroxaban at a dose of 10 mg (with the dose adjusted for renal insufficiency) or placebo for 45 days. The primary efficacy outcome was a composite of symptomatic venous thromboembolism or death due to venous thromboembolism. The principal safety outcome was major bleeding. RESULTS: Of the 12,024 patients who underwent randomization, 12,019 were included in the intention-to-treat analysis. The primary efficacy outcome occurred in 50 of 6007 patients (0.83%) who were given rivaroxaban and in 66 of 6012 patients (1.10%) who were given placebo (hazard ratio, 0.76; 95% confidence interval [CI], 0.52 to 1.09; P=0.14). The prespecified secondary outcome of symptomatic nonfatal venous thromboembolism occurred in 0.18% of patients in the rivaroxaban group and 0.42% of patients in the placebo group (hazard ratio, 0.44; 95% CI, 0.22 to 0.89). Major bleeding occurred in 17 of 5982 patients (0.28%) in the rivaroxaban group and in 9 of 5980 patients (0.15%) in the placebo group (hazard ratio, 1.88; 95% CI, 0.84 to 4.23). CONCLUSIONS: Rivaroxaban, given to medical patients for 45 days after hospital discharge, was not associated with a significantly lower risk of symptomatic venous thromboembolism and death due to venous thromboembolism than placebo. The incidence of major bleeding was low. (Funded by Janssen Research and Development; MARINER ClinicalTrials.gov number, NCT02111564 .).
Asunto(s)
Inhibidores del Factor Xa/uso terapéutico , Hospitalización , Rivaroxabán/uso terapéutico , Tromboembolia Venosa/prevención & control , Cuidados Posteriores , Anciano , Método Doble Ciego , Esquema de Medicación , Inhibidores del Factor Xa/administración & dosificación , Inhibidores del Factor Xa/efectos adversos , Femenino , Hemorragia/inducido químicamente , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Alta del Paciente , Rivaroxabán/administración & dosificación , Rivaroxabán/efectos adversos , Resultado del Tratamiento , Tromboembolia Venosa/epidemiología , Tromboembolia Venosa/mortalidad , Trombosis de la Vena/prevención & controlRESUMEN
Clinical trials of antithrombotic therapy require a cohesive assessment of benefit and risk. A new graphical method to represent the bivariate relation of benefit and risk in trials of antithrombotic drugs is described and illustrated using published data from the four major registration clinical trials of non-vitamin K oral anticoagulants (NOACs) totalling 71,683 patients for prevention of thromboembolic events (TE) in patients with atrial fibrillation (RE-LY, ROCKET AF, ARISTOTLE, and ENGAGE-AF TIMI48). A curve representing a null hypothesis defines a region of benefit on a two-dimensional plane. Trial results are summarised by a rectangle defined by standard 95 % confidence intervals (CI) for thrombosis and bleeding risks. Benefit is judged by whether the confidence rectangle contains the null curve. The treatment effect is measured by the distance from the null curve to the opposing corners of the confidence rectangle (termed "corner distance (CD)"). Across trials NOACs reduced the absolute risk of TE compared to warfarin by 0.30 % (95 % CI: -0.56 % to -0.05 %) and reduced major bleeding by 0.88 % (95 % CI: -1.26 % to -0.51 %). Bivariate evaluation showed NOAC superiority to warfarin overall and elucidated dose differences; low dose edoxaban increased bivariate TE-bleeding risk 0.08 % (CD = -0.85 % to 0.78 %), whereas high dose edoxaban reduced risk 1.41 % (CD = -2.07 % to -0.70 %). In conclusion, bivariate evaluation facilitates visual assessment of the safety-efficacy profile of antithrombotic drugs. Its application to trials in atrial fibrillation found NOACs superior to warfarin without substantial differences between agents.
Asunto(s)
Anticoagulantes/efectos adversos , Anticoagulantes/uso terapéutico , Fibrilación Atrial/complicaciones , Fibrilación Atrial/tratamiento farmacológico , Hemorragia/etiología , Tromboembolia/etiología , Administración Oral , Anticoagulantes/administración & dosificación , Ensayos Clínicos Fase III como Asunto/estadística & datos numéricos , Humanos , Modelos Estadísticos , Piridinas/administración & dosificación , Piridinas/efectos adversos , Piridinas/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto/estadística & datos numéricos , Factores de Riesgo , Tiazoles/administración & dosificación , Tiazoles/efectos adversos , Tiazoles/uso terapéutico , Warfarina/efectos adversos , Warfarina/uso terapéuticoRESUMEN
Hospital-associated venous thromboembolism (VTE) is a leading cause of premature death and disability worldwide. Evidence-based guidelines recommend that anticoagulant thromboprophylaxis be given to hospitalised medical patients at risk of VTE, but suggest against routine use of thromboprophylaxis beyond the hospital stay. The MARINER study is a randomised, double-blind, placebo-controlled trial to evaluate the efficacy and safety of thromboprophylaxis using rivaroxaban, begun at hospital discharge and continued for 45 days, for preventing symptomatic VTE in high-risk medical patients. Eligible patients are identified using the International Medical Prevention Registry on Venous Thromboembolism (IMPROVE VTE) risk score, combined with a laboratory test, D-dimer. The rivaroxaban regimen is 10 mg once daily for patients with CrCl ≥ 50 ml/min, or 7.5 mg once daily for patients with CrCl ≥ 30 ml/min and < 50 ml/min. The primary efficacy outcome is the composite of symptomatic VTE (lower extremity deep-vein thrombosis and non-fatal pulmonary embolism) and VTE-related death. The principal safety outcome is major bleeding. A blinded clinical events committee adjudicates all suspected outcome events. The sample size is event-driven with an estimated total of 8,000 patients to acquire 161 primary outcome events. Study design features that distinguish MARINER from previous and ongoing thromboprophylaxis trials in medically ill patients are: (i) use of a validated risk assessment model (IMPROVE VTE) and D-dimer determination for identifying eligible patients at high risk of VTE, (ii) randomisation at the time of hospital discharge, (iii) a 45-day treatment period and (iv) restriction of the primary efficacy outcome to symptomatic VTE events.
Asunto(s)
Inhibidores del Factor Xa/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto/métodos , Rivaroxabán/uso terapéutico , Tromboembolia Venosa/prevención & control , Adulto , Anciano , Anticoagulantes/administración & dosificación , Anticoagulantes/efectos adversos , Anticoagulantes/uso terapéutico , Método Doble Ciego , Esquema de Medicación , Inhibidores del Factor Xa/administración & dosificación , Inhibidores del Factor Xa/efectos adversos , Femenino , Hemorragia/etiología , Humanos , Masculino , Persona de Mediana Edad , Alta del Paciente , Factores de Riesgo , Rivaroxabán/administración & dosificación , Rivaroxabán/efectos adversos , Factores de TiempoRESUMEN
BACKGROUND: Omega-3 fatty acids have been used in the treatment and prevention of coronary artery disease although current evidence suggests they may be of limited benefit. Peripheral arterial disease and coronary artery disease share a similar pathogenesis so omega-3 fatty acids may have a similar effect on both conditions. This is an update of a review first published in 2004 and updated in 2007. OBJECTIVES: To determine the clinical and haematological effects of omega-3 supplementation in people with intermittent claudication. SEARCH METHODS: For this update the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched September 2012) and the Cochrane Central Register of Controlled Trials (CENTRAL) (2012, Issue 9). SELECTION CRITERIA: Randomised controlled trials of omega-3 fatty acids versus placebo or non-omega-3 fatty acids in people with intermittent claudication. DATA COLLECTION AND ANALYSIS: One review author identified potential trials. Two review authors independently assessed trial quality and extracted data. We contacted study authors for additional information if necessary. MAIN RESULTS: Nine studies were included representing 425 participants. All studies compared omega-3 fatty acid supplementation with placebo lasting from four weeks to two years. Three studies with long treatment periods administered additional substances, making any observed effects impossible to attribute to omega-3 fatty acids and were excluded from the statistical analyses. One study did not express any mean values and, therefore, could not be included in statistical analyses.No significant differences between intervention and control groups were observed in pain-free walking distance (mean difference (MD) 11.62 m, 95% confidence interval (CI) -67.74 to 90.98), maximal walking distance (MD 16.99 m, 95% CI -72.14 to 106.11), ankle brachial pressure index (MD -0.02, 95% CI -0.09 to 0.05), total cholesterol levels (MD 0.27 mmol/L, 95% CI -0.48 to 1.01), high-density lipoprotein cholesterol levels (MD 0.00 mmol/L, 95% CI -0.16 to 0.15), low-density lipoprotein cholesterol levels (MD 0.44 mmol/L, 95% CI -0.31 to 1.19), triglyceride levels (MD -0.39 mmol/L, 95% CI -1.10 to 0.33), systolic blood pressure (MD 5.00 mmHg, 95% CI -11.59 to 21.59) or plasma viscosity (MD 0.03 mPa/s, 95% CI -0.02 to 0.08).There was some limited evidence that blood but not plasma viscosity levels decreased with treatment and gastrointestinal side effects such as nausea, diarrhoea and flatulence were observed in two studies. AUTHORS' CONCLUSIONS: Omega-3 fatty acids appear to have little haematological benefit in people with intermittent claudication and there is no evidence of consistently improved clinical outcomes (quality of life, walking distance, ankle brachial pressure index or angiographic findings). Supplementation may also cause adverse effects such as nausea, diarrhoea and flatulence. Further research is needed to evaluate fully short- and long-term effects of omega-3 fatty acids on the most clinically relevant outcomes in people with intermittent claudication before they can be recommended for routine use.
Asunto(s)
Ácidos Grasos Omega-3/uso terapéutico , Claudicación Intermitente/dietoterapia , Suplementos Dietéticos , Ácidos Grasos Omega-6/uso terapéutico , Humanos , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
In patients with peripheral artery disease (PAD), statins may improve the symptoms of claudication. The Intermittent Claudication Proof of Principle (ICPOP) study tested the hypothesis that the combination of extended release niacin plus lovastatin would improve exercise performance in patients with PAD and claudication compared with a diet intervention. A phase 3 double-blind, parallel-group, multi-center, 28-week multi-national study evaluated subjects with a history of claudication who had an ankle-brachial index (ABI) < or = 0.90, a reproducible peak treadmill walking time (PWT) of 1-20 minutes, and a low-density lipoprotein (LDL)-cholesterol level < 160 mg/dl (< 4.1 mmol/l). Subjects were randomly assigned to low-dose niacin 1000 mg plus lovastatin 40 mg (low niacin-statin), high-dose niacin 2000 mg plus lovastatin 40 mg (high niacin-statin), or diet intervention (diet). The co-primary efficacy endpoint of percent change in PWT and claudication onset time (COT) at 28 weeks was assessed using a graded treadmill protocol. At completion, 385 subjects were analyzed for safety and 370 subjects were analyzed for efficacy. The primary efficacy analysis showed no statistical significance for overall treatment effect at week 28 for the co-primary endpoint of PWT and COT. The PWT component of the primary endpoint increased 26.5% on diet, 37.8% on high niacin-statin (p = 0.137) and 38.6% on low niacin-statin (p = 0.096). Flushing as the most common event leading to discontinuation and treatment was associated with increases in liver enzymes, fasting blood glucose concentration and a decrease in platelet count.
Asunto(s)
Inhibidores de Hidroximetilglutaril-CoA Reductasas/administración & dosificación , Claudicación Intermitente/tratamiento farmacológico , Lovastatina/administración & dosificación , Niacina/administración & dosificación , Enfermedad Arterial Periférica/tratamiento farmacológico , Vasodilatadores/administración & dosificación , Anciano , Preparaciones de Acción Retardada , Quimioterapia Combinada , Prueba de Esfuerzo , Femenino , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/efectos adversos , Claudicación Intermitente/diagnóstico , Claudicación Intermitente/dietoterapia , Lovastatina/efectos adversos , Masculino , Persona de Mediana Edad , Niacina/efectos adversos , Enfermedad Arterial Periférica/diagnóstico , Enfermedad Arterial Periférica/dietoterapia , Resultado del Tratamiento , Vasodilatadores/efectos adversosRESUMEN
BACKGROUND: Peripheral arterial disease (PAD) and diabetes are both associated with a high risk of ischemic events, but the role of intensive blood pressure control in PAD has not been established. METHODS AND RESULTS: The Appropriate Blood Pressure Control in Diabetes study followed 950 subjects with type 2 diabetes for 5 years; 480 of the subjects were normotensive (baseline diastolic blood pressure of 80 to 89 mm Hg). Patients randomized to placebo (moderate blood pressure control) had a mean blood pressure of 137+/-0.7/81+/-0.3 mm Hg over the last 4 years of treatment. In contrast, patients randomized to intensive treatment with enalapril or nisoldipine had a mean 4-year blood pressure of 128+/-0.8/75+/-0.3 mm Hg (P<0.0001 compared with moderate control). PAD, which is defined as an ankle-brachial index <0.90 at the baseline visit, was diagnosed in 53 patients. In patients with PAD, there were 3 cardiovascular events (13.6%) on intensive treatment compared with 12 events (38.7%) on moderate treatment (P=0.046). After adjustment for multiple cardiovascular risk factors, an inverse relationship between ankle-brachial index and cardiovascular events was observed with moderate treatment (P=0.009), but not with intensive treatment (P=0.91). Thus, with intensive blood pressure control, the risk of an event was not increased, even at the lowest ankle-brachial index values, and was the same as in a patient without PAD. CONCLUSIONS: In PAD patients with diabetes, intensive blood pressure lowering to a mean of 128/75 mm Hg resulted in a marked reduction in cardiovascular events.