Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan; Department of Cardiovascular Medicine, Okayama City General Medical Center, Okayama, Japan.
Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Heart Lung Circ. 2020 Mar;29(3):331-336. doi: 10.1016/j.hlc.2019.01.013. Epub 2019 Feb 7.
Transition to pulmonary arterial hypertension (PAH)-specific drugs is considered in patients with PAH and chronic thromboembolic pulmonary hypertension who do not respond to combination therapy or who experience side effects to the combination drugs. Riociguat directly stimulates soluble guanylate cyclase independently of nitric oxide. Therefore, transition from a phosphodiesterase type 5 inhibitor (PDE5i), which requires nitric oxide to exert its effects, to riociguat might be effective. The length of time of washout periods for transition is important because haemodynamic instability sometimes occurs during these periods or during transition with no washout period.
We investigated the feasibility of transitioning from a PDE5i to riociguat without washout periods by monitoring haemodynamics under right heart catheterisation in six patients with PAH and one with chronic thromboembolic pulmonary hypertension who had already received dual- or triple-combination therapy.
Reasons for transition were headache caused by a PDE5i in three patients, and an inadequate response to combination therapy in four. Transition was successful in all patients, with no haemodynamic instability observed. Pulmonary vascular resistance (from 797 ± 241 to 518 ± 230 dyne/s/cm) and systemic blood pressure (from 121 ± 13 to 100 ± 15 mmHg) were significantly reduced immediately after transition. There were no significant differences in the tricuspid regurgitation pressure gradient or systemic blood pressure during the post-transition and follow-up periods. Headaches caused by a PDE5i were diminished after transition to riociguat.
Transition from a PDE5i to riociguat without a washout period is safe. This transition may be a viable option for patients with headaches caused by a PDE5i, or who have an inadequate response to combination therapy that includes a PDE5i.
在对联合治疗无反应或联合药物治疗出现副作用的肺动脉高压(PAH)和慢性血栓栓塞性肺动脉高压患者中,考虑转为肺动脉高压特异性药物。利奥西呱直接刺激可溶性鸟苷酸环化酶,而不依赖于一氧化氮。因此,从需要一氧化氮发挥作用的磷酸二酯酶 5 型抑制剂(PDE5i)转为利奥西呱可能是有效的。转换期间冲洗期的长短很重要,因为在此期间或无冲洗期转换期间有时会出现血液动力学不稳定。
我们通过在 6 例 PAH 患者和 1 例慢性血栓栓塞性肺动脉高压患者接受双重或三重联合治疗后进行右心导管检查监测血液动力学,研究了无冲洗期从 PDE5i 转换为利奥西呱的可行性。
3 例患者因 PDE5i 引起头痛,4 例患者因联合治疗反应不足而转换。所有患者的转换均成功,未观察到血液动力学不稳定。转换后即刻,肺血管阻力(从 797±241 降至 518±230 达因/秒/厘米)和全身血压(从 121±13 降至 100±15 毫米汞柱)显著降低。转换后和随访期间三尖瓣反流压力梯度或全身血压无显著差异。转换为利奥西呱后,PDE5i 引起的头痛减轻。
无冲洗期从 PDE5i 转换为利奥西呱是安全的。对于因 PDE5i 引起头痛或因包含 PDE5i 的联合治疗反应不足的患者,这种转换可能是一种可行的选择。