ramipril and Peripheral-Vascular-Diseases

The Heart Outcomes Prevention Evaluation (HOPE) study has provided evidence for the use of ramipril for secondary cardiac prevention for patients with peripheral arterial disease. Despite this many vascular surgeons and general practitioners are reluctant to prescribe ACE inhibitors in a group of patients perceived to have a high incidence of renal artery stenosis. This review aims to review the pathophysiology of the renin-angiotensin system and make evidence based recommendations for commencing ACE inhibitors as part of a comprehensive delivery of best medical therapy to patients with peripheral arterial disease.

Topics: Algorithms; Angiotensin II; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Comorbidity; Humans; Peripheral Vascular Diseases; Ramipril; Renal Artery Obstruction; Renin-Angiotensin System

Topics: Aged; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Benzimidazoles; Benzoates; Drug Therapy, Combination; Female; Global Health; Humans; Incidence; Male; Peripheral Vascular Diseases; Ramipril; Risk Factors; Telmisartan; Treatment Outcome

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

Claudication is a debilitating consequence of peripheral arterial disease. Evidence is accumulating to suggest that large artery stiffness may influence peripheral perfusion and walking time through effects on peripheral hemodynamics as well as microvascular structure and function. We have previously shown that the angiotensin-converting enzyme inhibitor ramipril increased systemic arterial compliance by 64%, and increased maximum walking time by over 200% in patients with peripheral arterial disease. In the current analysis in the same patient cohort, we hypothesized that this relationship may, in part, be causal.. Forty patients with peripheral arterial disease [66 +/- 4 years (mean +/- SD); n = 20 per group] were randomized to ramipril, 10 mg once daily, or placebo for 24 weeks in a double-blind study. Maximum walking time was recorded during a standard treadmill test. Indices of arterial stiffness were assessed globally by systemic arterial compliance and augmentation index and regionally via central pulse wave velocity.. Ramipril increased maximum walking time by 243% and improved arterial stiffness parameters by between 17 and 64% (all P < 0.001 compared with placebo). There were moderately strong correlations between the pre/post intervention change in maximum walking time and the change in indices of arterial stiffness (systemic arterial compliance, r = 0.65, P < 0.001; central pulse wave velocity, r = -0.57, P < 0.001; augmentation index, r = -0.79, P < 0.001; time to pressure augmentation, r = 0.52, P = 0.001).. The present data support the hypothesis that the beneficial effects of ramipril on maximum walking time observed in our peripheral arterial disease population are, at least partly, a consequence of reduced arterial stiffness.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Double-Blind Method; Exercise Test; Exercise Tolerance; Female; Humans; Male; Middle Aged; Peripheral Vascular Diseases; Pulsatile Flow; Ramipril; Vasodilation; Walking

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

Ramipril improves cardiovascular outcome in patients with peripheral arterial disease; however, the precise mechanisms of benefit remain to be elucidated. The effect of ramipril on large-artery stiffness in patients with peripheral arterial disease was examined. In addition, we determined the effect of ramiprilat on extracellular matrix from human aortic smooth muscle cell culture. Forty patients with peripheral arterial disease were randomized to receive ramipril, 10 mg once daily or placebo for 24 weeks. Arterial stiffness was assessed globally via systemic arterial compliance and augmentation index (carotid tonometry and Doppler velocimetry), and regionally via carotid-femoral pulse wave velocity. Angiotensin-converting enzyme inhibition increased arterial compliance by 0.10+/-0.02 mL/mm Hg, (P<0.001, all probability values relative to placebo) and reduced pulse wave velocity by 1.7+/-0.2 m/s (P<0.001), augmentation index by 4.1+/-0.3% (P<0.001), and systolic blood pressure by 5+/-1 mm Hg (P<0.001). Ramipril did not reduce mean arterial pressure significantly compared with placebo (P=0.59). In cell culture, ramiprilat decreased collagen deposition by >50% and increased elastin and fibrillin-1 deposition by >3- and 4-fold respectively (histochemistry and immunohistochemistry). Fibrillin-1 gene expression was increased 5-fold (real-time reverse-transcriptase polymerase chain reaction). Ramiprilat also reduced gene and protein (Western) expression of both matrix metalloproteinase (MMP)-2 and MMP-3. In conclusion, ramipril promoted an elastogenic matrix profile that may contribute to the observed clinical reduction in large-artery stiffness and carotid pressure augmentation, which occurred independently of mean arterial blood pressure reduction in patients with peripheral arterial disease.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Aorta; Arteries; Blood Pressure; Carotid Arteries; Cells, Cultured; Collagen; Compliance; Double-Blind Method; Elasticity; Elastin; Extracellular Matrix; Female; Fibrillin-1; Fibrillins; Humans; Infant; Microfilament Proteins; Middle Aged; Peripheral Vascular Diseases; Ramipril; Ultrasonography

The aim of this study was to assess the prognostic importance of peripheral arterial disease (PAD) as evaluated by ankle blood pressure index (ABI), and the impact of ramipril on the prevention of major cardiovascular events in PAD patients included in the Heart Outcomes Prevention Evaluation (HOPE) study.. Patients were randomized to treatment with ramipril or placebo and followed for 4.5 years. Ankle brachial blood pressure index was measured, mainly by digital palpation of the foot pulse, at baseline in 8986 patients. The ABI was subnormal (< or =0.9) in 3099 patients and normal in 5887 patients. A low ABI was a strong predictor of morbidity and mortality during the follow-up even in patients with no clinical symptoms of PAD (n=6769). This was so for the primary outcome of the study; ABI>0.9:13.1%, 0.6-0.9: 18.2% and <0.6: 18.0% (P<0.0001) and for mortality from all causes: in those with a normal ABI it was 8.5%, in those with ABI >0.6-0.9, 12.4% and 14.2% in those with an ABI lower than 0.6 (P<0.0001). Ramipril reduced the risk of clinical outcomes in those with a clinical history of PAD as well as in the patients with subclinical PAD.. The ABI even if measured simply by palpation of the foot arteries is a strong predictor for future cardiovascular events and for all-cause mortality. Ramipril prevented major cardiovascular events in patients with clinical as well as subclinical PAD.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Ankle; Arteries; Blood Pressure; Brachial Artery; Female; Follow-Up Studies; Humans; Male; Middle Aged; Peripheral Vascular Diseases; Ramipril; Single-Blind Method; Treatment Outcome

In the HOPE-trial, the ACE inhibitor ramipril significantly reduced cardiovascular morbidity and mortality in patients at high risk for cardiovascular events. The benefit could only partly be attributed to the modest mean reduction of office blood pressure (OBP) during the study period (3/2 mm Hg). However, because according to the HOPE protocol ramipril was given once daily at bedtime and blood pressure was measured during the day, the 24-hour reduction of blood pressure may be underestimated based on OBP. Thirty-eight patients with peripheral arterial disease enrolled in the HOPE study underwent 24-hour ambulatory blood pressure (ABP) measurement before randomization and after 1 year. OBP was measured in the sitting position immediately before fitting the ABP measuring equipment to the patients. Ramipril did not significantly reduce OBP (8/2 mm Hg, P=NS) or day ABP (6/2 mm Hg, P=NS) after 1 year. Twenty-four-hour ABP was significantly reduced (10/4 mm Hg, P=0.03), mainly because of a more pronounced blood pressure lowering effect during nighttime (17/8 mm Hg, P<0.001). The night/day ratio was also significantly lowered in the ramipril group. ABP shows greater falls, especially at night, than OBP during treatment with ramipril given once daily at bedtime. Although, OBP is the correct comparator when comparing with previous large intervention trials and epidemiological studies, the effects on cardiovascular morbidity and mortality seen with ramipril in the HOPE study may, to a larger extent than previously ascribed, relate to effects on blood pressure patterns over the 24-hour period.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure Monitoring, Ambulatory; Cardiovascular Diseases; Circadian Rhythm; Female; Humans; Hypertension; Male; Peripheral Vascular Diseases; 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: Angiotensin-Converting Enzyme Inhibitors; Arteries; Elasticity; Humans; Peripheral Vascular Diseases; Ramipril