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Journal Club 25 June 2014

Paper

A Controlled Trial of Renal Denervation for Resistant Hypertension

Presenter

IM

Summary

Background

Prior unblinded studies have suggested that catheter-based renal-artery denervation
reduces blood pressure in patients with resistant hypertension.

Methods

We designed a prospective, single-blind, randomized, sham-controlled trial. Patients
with severe resistant hypertension were randomly assigned in a 2:1 ratio to undergo
renal denervation or a sham procedure. Before randomization, patients were receiving
a stable antihypertensive regimen involving maximally tolerated doses of at
least three drugs, including a diuretic. The primary efficacy end point was the
change in office systolic blood pressure at 6 months; a secondary efficacy end point
was the change in mean 24-hour ambulatory systolic blood pressure. The primary
safety end point was a composite of death, end-stage renal disease, embolic events
resulting in end-organ damage, renovascular complications, or hypertensive crisis
at 1 month or new renal-artery stenosis of more than 70% at 6 months.

Results

A total of 535 patients underwent randomization. The mean (±SD) change in systolic
blood pressure at 6 months was −14.13±23.93 mm Hg in the denervation
group as compared with −11.74±25.94 mm Hg in the sham-procedure group
(P<0.001 for both comparisons of the change from baseline), for a difference of
−2.39 mm Hg (95% confidence interval [CI], −6.89 to 2.12; P = 0.26 for superiority
with a margin of 5 mm Hg). The change in 24-hour ambulatory systolic blood pressure
was −6.75±15.11 mm Hg in the denervation group and −4.79±17.25 mm Hg in
the sham-procedure group, for a difference of −1.96 mm Hg (95% CI, −4.97 to 1.06;
P = 0.98 for superiority with a margin of 2 mm Hg). There were no significant differences
in safety between the two groups.

Conclusions

This blinded trial did not show a significant reduction of systolic blood pressure in
patients with resistant hypertension 6 months after renal-artery denervation as
compared with a sham control.

Supplementary Material

Supplementary material
Editorial
Schmieder commentary
Review

Categories: Journal Club Tags:

Mortality Morbidity Meeting

This is a meeting placeholder.

Categories: Mortality Morbidity

Journal Club 11 June 2014

Paper

A 52-Week Placebo-Controlled Trial of Evolocumab in Hyperlipidemia

Presenter

CC

Summary

Background

Evolocumab, a monoclonal antibody that inhibits proprotein convertase subtilisin/
kexin type 9 (PCSK9), significantly reduced low-density lipoprotein (LDL) cholesterol
levels in phase 2 studies. We conducted a phase 3 trial to evaluate the safety and
efficacy of 52 weeks of treatment with evolocumab.

Methods

We stratified patients with hyperlipidemia according to the risk categories outlined
by the Adult Treatment Panel III of the National Cholesterol Education Program. On
the basis of this classification, patients were started on background lipid-lowering
therapy with diet alone or diet plus atorvastatin at a dose of 10 mg daily, atorvastatin
at a dose of 80 mg daily, or atorvastatin at a dose of 80 mg daily plus ezetimibe at
a dose of 10 mg daily, for a run-in period of 4 to 12 weeks. Patients with an LDL
cholesterol level of 75 mg per deciliter (1.9 mmol per liter) or higher were then
randomly assigned in a 2:1 ratio to receive either evolocumab (420 mg) or placebo
every 4 weeks. The primary end point was the percent change from baseline in LDL
cholesterol, as measured by means of ultracentrifugation, at week 52.

Results

Among the 901 patients included in the primary analysis, the overall least-squares
mean (±SE) reduction in LDL cholesterol from baseline in the evolocumab group, taking
into account the change in the placebo group, was 57.0±2.1% (P<0.001). The mean
reduction was 55.7±4.2% among patients who underwent background therapy with
diet alone, 61.6±2.6% among those who received 10 mg of atorvastatin, 56.8±5.3%
among those who received 80 mg of atorvastatin, and 48.5±5.2% among those who
received a combination of 80 mg of atorvastatin and 10 mg of ezetimibe (P<0.001 for
all comparisons). Evolocumab treatment also significantly reduced levels of apolipoprotein
B, non–high-density lipoprotein cholesterol, lipoprotein(a), and triglycerides.
The most common adverse events were nasopharyngitis, upper respiratory tract
infection, influenza, and back pain.

Conclusions

At 52 weeks, evolocumab added to diet alone, to low-dose atorvastatin, or to highdose
atorvastatin with or without ezetimibe significantly reduced LDL cholesterol
levels in patients with a range of cardiovascular risks.

Contrast Induced Nephropathy: Causal or Coincidence

This provocative question is explored in this paper.

Categories: Uncategorized

Journal Club 4 June 2014

Paper

Riociguat for the Treatment of Pulmonary Arterial Hypertension

Presenter

DBC

Summary

BACKGROUND

Riociguat, a soluble guanylate cyclase stimulator, has been shown in a phase 2 trial
to be beneficial in the treatment of pulmonary arterial hypertension.

METHODS

In this phase 3, double-blind study, we randomly assigned 443 patients with symptomatic
pulmonary arterial hypertension to receive placebo, riociguat in individually adjusted
doses of up to 2.5 mg three times daily (2.5 mg–maximum group), or riociguat in
individually adjusted doses that were capped at 1.5 mg three times daily (1.5 mg–
maximum group). The 1.5 mg–maximum group was included for exploratory purposes,
and the data from that group were analyzed descriptively. Patients who were receiving
no other treatment for pulmonary arterial hypertension and patients who were
receiving endothelin-receptor antagonists or (nonintravenous) prostanoids were eligible.
The primary end point was the change from baseline to the end of week 12
in the distance walked in 6 minutes. Secondary end points included the change in pulmonary
vascular resistance, N-terminal pro–brain natriuretic peptide (NT-proBNP) levels,
World Health Organization (WHO) functional class, time to clinical worsening,
score on the Borg dyspnea scale, quality-of-life variables, and safety.

RESULTS

By week 12, the 6-minute walk distance had increased by a mean of 30 m in the
2.5 mg–maximum group and had decreased by a mean of 6 m in the placebo group
(least-squares mean difference, 36 m; 95% confidence interval, 20 to 52; P<0.001).
Prespecified subgroup analyses showed that riociguat improved the 6-minute walk
distance both in patients who were receiving no other treatment for the disease and
in those who were receiving endothelin-receptor antagonists or prostanoids. There
were significant improvements in pulmonary vascular resistance (P<0.001), NT-proBNP
levels (P<0.001), WHO functional class (P = 0.003), time to clinical worsening
(P = 0.005), and Borg dyspnea score (P = 0.002). The most common serious adverse
event in the placebo group and the 2.5 mg–maximum group was syncope (4% and
1%, respectively).

CONCLUSIONS

Riociguat significantly improved exercise capacity and secondary efficacy end points
in patients with pulmonary arterial hypertension.

Supplementary Material

Also presented: Riociguat for the Treatment of Chronic Thromboembolic Pulmonary Hypertension.

The editorial is available here.

Categories: Journal Club