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Despite its limitations and methodological biases, this small open randomised trial generated a huge wave of enthusiasm, with up to 15 to 20,000 renal denervations performed in Europe, until Symplicity HTN-3 disclosed that many of the apparent benefits of renal denervation may be explained by patient and physician-related biases
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Analysis of 731 patients referred for renal denervation to 11 European expert centres. Careful screening and treatment adjustment removed indication of renal denervation in two-thirds of patients. The most frequent reason for ineligibility was blood pressure control after drug treatment adjustment in the expert centre
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Based on a meta-analysis of antihypertensive drug trials of 4,121 patients with focus on trial design, the authors predicted that office blood pressure decrease after renal denervation would converge with that of ambulatory blood pressure - and thus substantially shrink - in a blinded randomised study. This dense paper contains many interesting thoughts about possible biases in an open randomised study such as Symplicity HTN-2
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•• Howard JP, Nowbar AN, Francis DP. Size of blood pressure reduction from renal denervation: insights from meta-analysis of antihypertensive drug trials of 4,121 patients with focus on trial design: the CONVERGE report. Heart. 2013;99:1579-87. Based on a meta-analysis of antihypertensive drug trials of 4,121 patients with focus on trial design, the authors predicted that office blood pressure decrease after renal denervation would converge with that of ambulatory blood pressure - and thus substantially shrink - in a blinded randomised study. This dense paper contains many interesting thoughts about possible biases in an open randomised study such as Symplicity HTN-2.
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This carefully designed randomised study shows that, in patients with truly resistant hypertension and drug adherence demonstrated by drug witnessed intake, treatment adjustment is much superior to renal denervation
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•• Fadl Elmula FE, Hoffmann P, Larstorp AC, et al. Adjusted drug treatment is superior to renal sympathetic denervation in patients with true treatment-resistant hypertension. Hypertension. 2014;63: 991-9. This carefully designed randomised study shows that, in patients with truly resistant hypertension and drug adherence demonstrated by drug witnessed intake, treatment adjustment is much superior to renal denervation.
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In this large, US randomised trial including a sham procedure, the benefit assignable to renal denervation was found to be < 3 mmHg vs. 25-30 mmHg in Symplicity HTN-2 and other previous studies. The most likely explanation accounting for this huge discrepancy is blinding, which minimised patient and physician-related biases in Symplicity HTN-3. The failure of Symplicity HTN-3 to meet its primary endpoint shows unequivocally that renal denervation is not ready for clinical dissemination
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•• Bhatt DL, Kandzari DE, O'Neill WW, et al. A controlled trial of renal denervation for resistant hypertension. N Engl J Med. 2014;370:1393-401. In this large, US randomised trial including a sham procedure, the benefit assignable to renal denervation was found to be < 3 mmHg vs. 25-30 mmHg in Symplicity HTN-2 and other previous studies. The most likely explanation accounting for this huge discrepancy is blinding, which minimised patient and physician-related biases in Symplicity HTN-3. The failure of Symplicity HTN-3 to meet its primary endpoint shows unequivocally that renal denervation is not ready for clinical dissemination.
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