ramipril and Intermittent-Claudication

We recently reported that ramipril more than doubled maximum walking times in patients with peripheral artery disease with intermittent claudication.. Our aim was to conduct exploratory analyses of the effects of ramipril therapy on circulating biomarkers of angiogenesis/arteriogenesis, thrombosis, inflammation, and leukocyte adhesion in patients with intermittent claudication.. One hundred sixty-five patients with intermittent claudication (mean, 65.3 [SD, 6.7] years) were administered ramipril 10 mg per day (n=82) or matching placebo (n=83) for 24 weeks in a randomized, double-blind study. Plasma biomarkers of angiogenesis/arteriogenesis (vascular endothelial growth factor-A, fibroblast growth factor-2), thrombosis (D-dimer, von Willebrand factor, thrombin-antithrombin III), inflammation (high-sensitivity C-reactive protein, osteopontin), and leukocyte adhesion (soluble vascular cell adhesion molecule-1, soluble intracellular adhesion molecule-1) were measured at baseline and 24 weeks. Relative to placebo, ramipril was associated with increases in vascular endothelial growth factor-A by 38% (95% confidence interval [CI], 34%-42%) and fibroblast growth factor-2 by 64% (95% CI, 44-85%; P<0.001 for both), and reductions in D-dimer by 24% (95% CI, -30% to -18%), von Willebrand factor by 22% (95% CI, -35% to -9%), thrombin-antithrombin III by 16% (95% CI, -19% to -13%), high-sensitivity C-reactive protein by 13% (95% CI, -14% to -9%), osteopontin by 12% (95% CI, -14% to -10%), soluble vascular cell adhesion molecule-1 by 14% (95% CI, -18% to -10%), and soluble intracellular adhesion molecule-1 by 15% (95% CI, -17% to -13%; all P<0.001). With the exception of von Willebrand factor, all the above changes correlated significantly with the change in maximum walking time (P=0.02-0.001) in the group treated with ramipril.. Ramipril is associated with an increase in the biomarkers of angiogenesis/arteriogenesis and reduction in the markers of thrombosis, inflammation, and leukocyte adhesion. This study informs strategies to improve mobility in patients with intermittent claudication.. http://clinicaltrials.gov. Unique identifier: NCT00681226.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Antithrombin III; C-Reactive Protein; Double-Blind Method; Female; Fibroblast Growth Factor 2; Humans; Intermittent Claudication; Male; Middle Aged; Osteopontin; Peptide Hydrolases; Ramipril; Vascular Cell Adhesion Molecule-1; Vascular Endothelial Growth Factor A; von Willebrand Factor; Walking

The aim was to investigate the effect of ramipril on clinical parameters in patients with peripheral arterial disease.. Patients with intermittent claudication were randomized to receive ramipril or placebo for 24 weeks in a double-blind study. Outcome measures were walking distance, arterial stiffness measurement and quality of life (QoL).. A total of 33 patients were included (25 men; mean(s.d.) age 64.6(7.8) years); 14 received ramipril and 19 placebo. After 24 weeks, ramipril improved maximum treadmill walking distance by an adjusted mean (95 per cent confidence interval, c.i.) of 131 (62 to 199) m (P = 0·001), improved treadmill intermittent claudication distance by 122 (56 to 188) m (P = 0.001) and improved patient-reported walking distance by 159 (66 to 313) m (P = 0.043) compared with placebo. Ramipril reduced carotid femoral pulse wave velocity by -1.47 (95 per cent c.i. -2.40 to -0.57) m/s compared with placebo (P = 0.002). Resting ankle : brachial pressure index (ABPI) improved slightly in both ramipril and placebo groups (0.02 (95 per cent c.i. -0.08 to 0.11) versus 0.03 (-0.05 to 0.10); P = 0.830). Ramipril had a slight, non-significant effect on QoL physical domains compared with placebo.. Ramipril improved walking distance in patients with claudication; however, this improvement was not related to improved ABPI but might have been due to ramipril reducing arterial stiffness.. NCT01037530 (http://www.clinicaltrials.gov).

Topics: Angiotensin-Converting Enzyme Inhibitors; Ankle Brachial Index; Double-Blind Method; Female; Hemodynamics; Humans; Intermittent Claudication; Male; Middle Aged; Prospective Studies; Quality of Life; Ramipril; Treatment Outcome; Vascular Stiffness; Walking

Approximately one-third of patients with peripheral artery disease experience intermittent claudication, with consequent loss of quality of life.. To determine the efficacy of ramipril for improving walking ability, patient-perceived walking performance, and quality of life in patients with claudication.. Randomized, double-blind, placebo-controlled trial conducted among 212 patients with peripheral artery disease (mean age, 65.5 [SD, 6.2] years), initiated in May 2008 and completed in August 2011 and conducted at 3 hospitals in Australia.. Patients were randomized to receive 10 mg/d of ramipril (n = 106) or matching placebo (n = 106) for 24 weeks.. Maximum and pain-free walking times were recorded during a standard treadmill test. The Walking Impairment Questionnaire (WIQ) and Short-Form 36 Health Survey (SF-36) were used to assess walking ability and quality of life, respectively.. At 6 months, relative to placebo, ramipril was associated with a 75-second (95% CI, 60-89 seconds) increase in mean pain-free walking time (P < .001) and a 255-second (95% CI, 215-295 seconds) increase in maximum walking time (P < .001). Relative to placebo, ramipril improved the WIQ median distance score by 13.8 (Hodges-Lehmann 95% CI, 12.2-15.5), speed score by 13.3 (95% CI, 11.9-15.2), and stair climbing score by 25.2 (95% CI, 25.1-29.4) (P < .001 for all). The overall SF-36 median Physical Component Summary score improved by 8.2 (Hodges-Lehmann 95% CI, 3.6-11.4; P = .02) in the ramipril group relative to placebo. Ramipril did not affect the overall SF-36 median Mental Component Summary score.. Among patients with intermittent claudication, 24-week treatment with ramipril resulted in significant increases in pain-free and maximum treadmill walking times compared with placebo. This was associated with a significant increase in the physical functioning component of the SF-36 score.. clinicaltrials.gov Identifier: NCT00681226.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Double-Blind Method; Female; Humans; Intermittent Claudication; Male; Middle Aged; Pain; Peripheral Arterial Disease; Quality of Life; Ramipril; Severity of Illness Index; Treatment Outcome; Walking

The Heart Outcomes Prevention Study (HOPE) demonstrated that ramipril resulted in a blood-pressure-independent 25% reduction in cardiovascular events in patients with peripheral arterial disease (PAD). Despite this, general practitioners and vascular surgeons remain reluctant to prescribe ACE inhibitors in this group of patients because of concerns about renal artery stenosis (RAS). We aimed to define the effect of ramipril on renal function in patients with intermittent claudication (IC).. Of 132 unselected patients with IC entering the study 78 (59%) were excluded due to: current ACE inhibitor use (38%), renal impairment (serum creatinine above normal range) (15%), known severe RAS (1%) or unwillingness to participate (5%). The remaining 54 patients were titrated to 10 mg ramipril and renal function was monitored at 1, 5, and 12 weeks. Treatment was discontinued during titration in 5 patients due to symptoms (3) or lack of compliance (2). In the remainder, median [IQR] serum creatinine increased (94 [85.8-103.3] to 98 [88.0-106.5] micromol/L, p < or = 0.001) and median [IQR] GFR decreased (71.5 [64.6-82.3] to 68.7 [59.8-74.7] mL/min per 1.73 m2, p < or = 0.001) between baseline and 5 weeks. These changes were not considered clinically significant. By 12 weeks these values had returned almost to baseline (Cr 95.5 [88.0-103.25] micromol/L, GFR 71.8 [65.3-77.4] mL/min). No patient had a serum creatinine rise > 30%.. Most of patients with IC and a normal serum creatinine can be safely commenced on ramipril provided they are screened, titrated and monitored as described above. Studies in patients with borderline renal impairment (serum creatinine up to 30% above baseline) are on-going.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Creatinine; Female; Glomerular Filtration Rate; Humans; Intermittent Claudication; Kidney; Male; Middle Aged; Patient Selection; Peripheral Vascular Diseases; Ramipril; Time Factors; Treatment Outcome

Peripheral arterial disease (PAD) affects up to 12% of adults older than 50 years of age. Conventional therapies have only modest effects in improving symptoms.. To examine the effects of angiotensin-converting enzyme inhibition on walking ability in patients with PAD.. Randomized, double-blind, placebo-controlled trial initiated in March 2003 and completed in January 2005.. The Alfred Hospital, Melbourne, Australia.. 40 older adults with symptomatic PAD and no history of diabetes or hypertension.. 10 mg of ramipril (n = 20) or placebo (n = 20) once daily for 24 weeks. All patients completed the trial.. Pain-free and maximum walking time were recorded during a standard treadmill test, and the standard Walking Impairment Questionnaire was administered.. After adjustment for the baseline pain-free walking time, mean pain-free walking time after ramipril treatment was 227 seconds (95% CI, 175 seconds to 278 seconds; P < 0.001) longer than that after placebo treatment. Similarly, maximum walking time improved by 451 seconds in the ramipril group (CI, 367 seconds to 536 seconds; P < 0.001) but did not change in the placebo group. Ramipril improved the Walking Impairment Questionnaire median distance score from 5% (range, 1% to 39%) to 21% (range, 12% to 58%; P < 0.001), speed score from 3% (range, 3% to 39%) to 18% (range, 8% to 50%; P < 0.001), and stair-climbing score from 17% (range, 4% to 80%) to 67% (range, 38% to 88%; P < 0.001). No adverse events were reported.. The sample size is modest, and the strict inclusion criteria limit the applicability of the results to patients with claudication and infrainguinal disease and those without diabetes.. Ramipril improved pain-free and maximum walking time in some adults with symptomatic PAD.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Double-Blind Method; Exercise; Female; Humans; Intermittent Claudication; Male; Middle Aged; Peripheral Vascular Diseases; Ramipril; Regional Blood Flow; Surveys and Questionnaires; Walking

Topics: Angiotensin-Converting Enzyme Inhibitors; Biomedical Research; Humans; Intermittent Claudication; Ramipril; Retraction of Publication as Topic; Scientific Misconduct

Topics: Angiotensin-Converting Enzyme Inhibitors; Female; Humans; Intermittent Claudication; Male; Peripheral Arterial Disease; Ramipril; Walking

Topics: Angiotensin-Converting Enzyme Inhibitors; Female; Humans; Intermittent Claudication; Male; Peripheral Arterial Disease; Ramipril; Walking

Topics: Angiotensin-Converting Enzyme Inhibitors; Exercise Tolerance; Hemodynamics; Humans; Intermittent Claudication; Peripheral Arterial Disease; Quality of Life; Ramipril; Recovery of Function; Treatment Outcome; Walking

The objective of the trial was to examine whether ramipril, an angiotensin-converting enzyme (ACE), improves walking distance and health-related quality of life in patients with peripheral artery disease (PAD) associated with claudication.. The study enrolled 212 patients with risk factors and symptoms of PAD treated by conventional therapies at three centers in Australia. All patients had an ankle-brachial index (ABI) of less than 0.90 at rest and intermittent claudication in at least one leg, which were stable for at least 6 preceding months along with the medication regimen. The patients were excluded if blood pressure was not controlled (brachial blood pressure of 160/100 mmHg or greater); if there was current or recent use of either ACE inhibitors or angiotensin II receptor blockers, potassium-sparing diuretics, or potassium supplements; renal failure (serum creatinine level 2.3 mg/dL or greater [200 µmol/L]); renal artery stenosis; previous coronary or peripheral artery revascularizations, recent myocardial infarction and other health conditions other than PAD that could adversely influence walking ability at the time of screening and for 1 year thereafter.. This was a randomized, placebo-controlled, triple blinded study of ramipril at the high daily dose (10 mg) for 6 months. Primary outcomes were pain-free and maximum walking times assessed by a standard treadmill exercise test. Secondary outcomes were ABI changes; symptoms and functional status assessed by the Walking Impairment Questionnaire (WIQ)(1); health-related quality of life assessed by the Short-Form 36 Health Survey (SF-36)(2); and stenosis severity assessed by duplex ultrasound of the lower limb arteries. At baseline and at follow-up, pain-free and maximum walking distances were assessed by the standard constant load treadmill exercise test performed at a speed of 3.2 km/h and a grade of 12%.(3) ABI was calculated in both legs. Duplex ultrasonography was used to determine stenosis in lower-limb vessel segments. Functional changes per WIQ, and perceived disability assessed on the Physical Component Summary and the Mental Component Summary of the SF-36 were self-reported. Sample size was calculated as 100 patients per each group needed to provide a power of 80% at an α of 0.05 to detect a 120-second change in walking time and a 65-second change in pain-free walking time. A two-sided p-value of less than 0.05 was considered significant. Baseline variables were compared using the χ(2) test and one-way analysis of variance. The analysis of covariance model with baseline and post-treatment values after 6 months used Kruskal-Wallis analysis of variance. Imputations for missing 6-month data were performed. Data were analyzed on the intention-to-treat basis.. Of 921 potential participants screened, 212 eligible participants were randomized into equal-sized ramipril and placebo groups where baseline parameters were not different. Compliance was monitored by pill count and adverse effects were monitored through interval clinical assessments, laboratory tests, and telephone calls. There was a 100% adherence rate to the study medications among 200 patients who completed the study. Ramipril was associated with a 75-second increase in mean pain-free and a 255-second increase in maximum walking time. There was a modest (less than 5 mmHg) blood pressure reduction and a small (0.1) ABI increase at rest and after exercise compared to placebo. The maximum walking time increase after ramipril therapy compared to placebo was greater in the subgroup of patients with femoropopliteal disease (286 seconds) than in those with aortoiliac disease (127 seconds). Patients treated with ramipril showed improvement of the median distance, speed and stair climbing scores on the WIQ, as well as of the Physical, but not the Mental, Component Summary score on the SF-36. The most frequent side effect was dizziness, more common in the ramipril (8.5%) than in the placebo (2.8%) group. Persistent cough occurred in 6.6% of patients on ramipril, causing their withdrawal from the study.

Topics: Angiotensin-Converting Enzyme Inhibitors; Female; Humans; Intermittent Claudication; Male; Peripheral Arterial Disease; Ramipril; Walking

Topics: Angiotensin-Converting Enzyme Inhibitors; Female; Humans; Intermittent Claudication; Male; Peripheral Arterial Disease; Ramipril; Walking

This ACE inhibitor can help patients with peripheral artery disease walk longer while remaining pain free.

Topics: Angiotensin-Converting Enzyme Inhibitors; Female; Humans; Intermittent Claudication; Male; Peripheral Arterial Disease; Ramipril; Walking

Topics: Angiotensin-Converting Enzyme Inhibitors; Female; Humans; Intermittent Claudication; Male; Peripheral Arterial Disease; Ramipril; Walking

Topics: Adult; Aged; Aged, 80 and over; Angiotensin-Converting Enzyme Inhibitors; Australia; Female; Humans; Incidence; Intermittent Claudication; Male; Middle Aged; Ramipril

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Double-Blind Method; Exercise; Female; Humans; Intermittent Claudication; Male; Middle Aged; Peripheral Vascular Diseases; Ramipril; Regional Blood Flow; Surveys and Questionnaires; Walking

Topics: Adult; Anticoagulants; Antihypertensive Agents; Cilostazol; Drug Therapy, Combination; Femoral Artery; Fibrinolytic Agents; Humans; Hypertension; Intermittent Claudication; Leg; Male; Pain; Physical Exertion; Ramipril; Tetrazoles; Treatment Outcome; Warfarin