Baxdrostat在难治性及未控制高血压中的应用：系统评价与荟萃分析。
完整摘要 · 中文译文
背景：醛固酮失调正越来越被广泛认为是难治性高血压的关键因素。Baxdrostat是一种高度选择性的醛固酮合酶抑制剂，其对CYP11B2的亲和力是对CYP11B1的100:1，已在涉及不同高血压人群的多项随机对照试验中接受测试。我们进行了一项系统评价和荟萃分析，以评估baxdrostat治疗难治性高血压的有效性和安全性。 方法：我们纳入了自建库至2026年3月期间，针对成人高血压患者使用baxdrostat的随机、双盲、安慰剂对照试验。主要结局为经安慰剂校正的坐位收缩压（SBP）变化。次要结局包括舒张压（DBP）变化、达到坐位SBP < 130 mmHg的患者比例，以及高钾血症和其他不良事件的发生率。 结果：共纳入5项试验（N = 1,730）：BrigHTN、HALO、BaxHTN、FigHTN和Bax24。与安慰剂相比，baxdrostat显著降低坐位SBP（MD -6.90 mmHg；95% CI，-10.25至-3.55；P < 0.0001），但异质性较高（I² = 74%）。在较高剂量下观察到数值上更大的降幅：2 mg剂量产生最大降幅（MD -8.16 mmHg；P < 0.00001；I² = 45%），其次是1 mg（MD -6.06 mmHg；P = 0.010），而0.5 mg未达到显著差异（P = 0.14）。Baxdrostat增加了达到SBP < 130 mmHg的几率（OR 2.70；P = 0.01），尽管该效应的幅度在各试验间差异较大（I² = 89%）。DBP的降低在2 mg剂量下显著（MD -3.51 mmHg；P < 0.0001）以及1 mg剂量组（平均差异 -2.55 mmHg；P = 0.03）。安全性分析显示，高钾血症的发生率较高（8.9% vs. 1.2%；比值比 5.98；P = 0.008），其中baxdrostat治疗组有3.8%的患者血钾 > 6.0 mmol/L，而安慰剂组为0.2%。严重不良事件未显著增加（比值比 1.35；P = 0.37）。无死亡事件归因于baxdrostat。 结论：Baxdrostat在不同高血压人群中可使收缩压产生统计学显著降低，并提高达到血压目标（收缩压 < 130 mmHg）的可能性，尽管该效应的幅度在各试验间差异较大（I² = 89%）。高钾血症是主要的安全性问题，但在纳入的试验中未与严重临床后遗症相关。这些发现支持进一步研究醛固酮合酶抑制作为难治性和未控制高血压的治疗策略，其明确的临床定位有待正在进行的肾脏和心血管结局试验结果。
完整摘要 · 英文原文
BACKGROUND: Aldosterone dysregulation is becoming more widely acknowledged as a key factor in resistant hypertension. Baxdrostat, a highly selective aldosterone synthase inhibitor that shows a 100:1 preference for CYP11B2 over CYP11B1, has been tested in various randomized controlled trials involving different hypertensive groups. We carried out a systematic review and meta-analysis to assess the efficacy and safety of baxdrostat for treating resistant hypertension. METHODS: We included randomized, double-blind, placebo-controlled trials of baxdrostat in adults with hypertension from inception through March 2026. The primary outcome was the placebo-corrected change in seated systolic blood pressure (SBP). Secondary outcomes included the change in diastolic blood pressure (DBP), the proportion of patients achieving seated SBP < 130 mmHg, and the incidence of hyperkalemia and other adverse events. RESULTS: Five trials (N = 1,730) were included: BrigHTN, HALO, BaxHTN, FigHTN, and Bax24. Baxdrostat significantly reduced seated SBP vs. placebo (MD -6.90 mmHg; 95% CI, -10.25 to -3.55; P < 0.0001), with high heterogeneity (I2 = 74%). Numerically larger reductions were observed at higher doses: the 2 mg dose yielded the largest reduction (MD -8.16 mmHg; P < 0.00001; I2 = 45%), followed by 1 mg (MD -6.06 mmHg; P = 0.010), while 0.5 mg was non-significant (P = 0.14). Baxdrostat increased the odds of achieving SBP < 130 mmHg (OR 2.70; P = 0.01), although the magnitude of this effect varied substantially across trials (I² = 89%). DBP reduction was significant at the 2 mg dose (MD -3.51 mmHg; P < 0.0001) and the 1 mg dose (MD -2.55 mmHg; P = 0.03). Safety analysis showed higher odds of hyperkalemia (8.9% vs. 1.2%; OR 5.98; P = 0.008), with potassium > 6.0 mmol/L in 3.8% of baxdrostat-treated patients versus 0.2% with placebo. Serious adverse events were not significantly increased (OR 1.35; P = 0.37). No deaths were attributable to baxdrostat. CONCLUSIONS: Baxdrostat produces statistically significant reductions in systolic blood pressure among various hypertensive populations, increasing the likelihood of achieving blood pressure targets (SBP < 130 mmHg), although the magnitude of this effect varied substantially across trials (I² = 89%). Hyperkalemia was the principal safety concern but was not associated with serious clinical sequelae in the included trials. These findings support further investigation of aldosterone synthase inhibition as a therapeutic strategy for resistant and uncontrolled hypertension, with definitive clinical positioning awaiting results from ongoing cardiovascular and renal outcomes trials.