ESC Guidelines on the diagnosis and treatment of peripheral artery ...

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progression. There is general consensus that renal revascularization
should be performed in patients with anatomically and functionally
significant RAS who present with particular clinical
scenarios such as sudden onset or ‘flash’ pulmonary oedema or
congestive heart failure with preserved left ventricular function
and acute oligo-/anuric renal failure with kidney ischaemia.
4.4.5.2.1 Impact of revascularization on blood pressure control
Twenty-one uncontrolled series of stenting/angioplasty published
before 2007 in 3368 patients gave no unifying pattern regarding
mortality rates. Cure, improvement, or worsening of arterial
hypertension was documented to range from 4% to 18%, from
35% to 79%, and from 0% to 13%, respectively. Two studies
reported a statistically significant reduction in the New York
Heart Association functional class after stent placement in patients
with either bilateral disease or stenosis to a solitary functioning
kidney (global ischaemia). For these patients with congestive
heart failure and repeated admissions for pulmonary oedema not
associated with CAD, improved volume management, restored
sensitivity to diuretics, and lowered rehospitalization rates
suggest that some individualized patient categories benefit substan-
185 – 188
tially from renal revascularization.
Three RCTs compared endovascular therapy with medical treatment
with ≥6 months of follow-up. 166,183,189 Notably, these trials
were small and had no adequate power for clinical outcomes.
Stents were rarely used and medical therapies varied both
between and within studies. In a randomized study including 49
patients, the investigators concluded that endovascular therapy in
unilateral atherosclerotic RAS enables reduction of the number of
antihypertensive drugs, 189 but that previous uncontrolled studies
overestimated the potential for lowering blood pressure. In the
Dutch Renal Artery Stenosis Intervention Cooperative (DRASTIC)
study involving 106 patients, 166 there were no significant differences
between the angioplasty and drug therapy groups in terms of systolic
and diastolic blood pressures or renal function, whereas daily drug
doses were reduced in the angioplasty group. However, a significant
improvement in systolic and diastolic blood pressures was reported
after angioplasty in a meta-analysis of these three studies. 190 Two
recent randomized trials comparing stent angioplasty combined
with medical therapy with medical therapy alone [Angioplasty and
Stenting for Renal Artery Lesions trial (ASTRAL) and the Stent Placement
in Patients With Atherosclerotic Renal Artery Stenosis and
Impaired Renal Function (STAR)] failed to demonstrate any significant
difference in blood pressure. 191,192 However, in the ASTRAL
trial, the daily drug dosage was reduced. 191
4.4.5.2.2 Impact of revascularization on renal function
The ASTRAL trial is so far the largest RCT to determine whether
percutaneous revascularization combined with medical therapy
compared with medical therapy alone improves renal function. 191
Eight-hundred and six patients with atherosclerotic RAS in whom
the need for revascularization was uncertain were enrolled. Fiftynine
per cent of patients were reported to have RAS .70%, and
60% had a serum creatinine of ≥150 mmol/L. At a mean follow-up
of 33.6 months (range 1–4 years), differences in renal function and
kidney and cardiovascular events were all similarly unimpressive,
even in the highest risk groups, which included patients with global
ischaemia or impaired or rapidly decreasing kidney function. The
<strong>ESC</strong> <strong>Guidelines</strong>
primary study endpoint—the decline in renal function over time—
calculated as the mean slope of the reciprocal of the serum creatinine
concentration over time, was slightly slower in the revascularization
group, but the difference was not statistically significant.
The STAR multicentre trial enrolled 140 patients to detect a
≥20% decrease in creatinine clearance. 192 At 2 years, the primary
endpoint was reached in 16% of patients in the stented group and
in 22% of patients in the medical treatment group. The difference
was not statistically significant and was inconclusive, given the wide
confidence intervals around the estimate of effect. It was noteworthy
that .50% of the patients randomized to stenting had a ,70%
diameter stenosis and 28% of patients did not receive a stent
(19%) because of no RAS .50%. This largely underpowered trial
showed that deterioration of renal function may progress despite
successful revascularization, underscoring the complex cause of
ischaemic nephropathy, with an important parenchymal component
affected by risk factors for atherosclerosis. It also showed that if
technical skills are insufficient, a considerable number of
stent-related complications can occur (two procedure-related
deaths, one death secondary to an infected haematoma, and one
case of deterioration of renal function resulting in dialysis).
4.4.5.2.3 Impact of revascularization on survival
In the ASTRAL and STAR trials no difference was seen in the secondary
endpoints—cardiovascular morbidity and death. A recent
analysis of two consecutive registries comparing conservative
treatment with revascularization showed a 45% reduction in mortality
for the revascularization cohort. 193 To date, no major differences
in survival are evident between patients undergoing either
surgical or endovascular procedures, although only a few studies
addressed this issue directly.
Several factors may argue against renal revascularization or predict
poorer outcomes, including the presence of proteinuria .1 g/24 h,
renal atrophy, severe renal parenchymal disease, and severe diffuse
intrarenal arteriolar disease. Moreover, adverse consequences of
renal atheroembolization at the time of surgical revascularization
have been documented. 194 Similarly, atheroembolization may be provoked
by percutaneous revascularization. 192,195,196
The potential physiological benefits of renal stent placement
include reperfusion of the ischaemic kidney(s), resulting in a
reduction in the stimulus to renin production, which decreases
angiotensin and aldosterone production, thereby decreasing peripheral
arterial vasoconstriction and preventing hypervolaemia.
Improvement in renal perfusion enhances glomerular filtration
and therefore promotes natriuresis. Moreover, reduction of
humoral activation may result in reduction of left ventricular
197 – 199
mass and improvement of diastolic dysfunction.
The ASTRAL study did not provide information on how to treat
patients with a clinical need for revascularization. This question is
being addressed by two ongoing RCTs. The Cardiovascular Outcomes
in Renal Atherosclerotic Lesions (CORAL) trial tests the
hypothesis that stenting atherosclerotic RAS .60% (systolic
pressure gradient .20 mmHg) in patients with systolic hypertension
reduces the incidence of cardiovascular and renal events.
The Randomized, Multicentre, Prospective Study Comparing Best
Medical Treatment Versus Best Medical Treatment Plus Renal
Artery Stenting in Patients With Haemodynamically Relevant