Table 2 Clinical trials on neurohormonal modulation in pulmonary hypertension
From: Autonomic nervous system involvement in pulmonary arterial hypertension
Study | Treatment | Study design | Follow-up | Subjects | Patient description (n patient) | Changes in outcomes | Related side effects (n patient) |
|---|---|---|---|---|---|---|---|
Pharmacological therapies | |||||||
Grinnan and colleagues [25] | Carvedilol | Single-arm, open-label, pilot | 6 months | 6 | iPAH (3) HPAH (1) APAH (2) | ↑RVEF ↑BNP level | Bradycardia (1) Asymptomatic hypotension (1) Mild fatigue (1) |
Farha and colleagues [26] | Carvedilol | Single-center, double-blind, randomized, controlled trial | 6 months | 30 | iPAH (9) HPAH (12) APAH (5) PH due to lung disease and/or hypoxemia (2) Chronic thromboembolic PH (2) | ↓HR ↓ RVSP at 3 month follow-up ↑ RV fractional area change at 3 month follow-up ↑RV glycolytic rate ↑β-adrenergic receptor density | Fatigue (1) Dyspnea (2) Leg swelling (3) Site infection/acute bronchitis (2) Chest pain (1) Blurry vision (1) Cholecystitis (1) Bloating (1) Nausea/vomiting (1) Dizziness (1) |
van Campen and colleagues [29] | Bisoprolol | Prospective, randomised, placebo-controlled, crossover | 1 years | 18 | iPAH (18) | ↓HR ↑PAWP ↓Cardiac index ↓6-MWD | Worsening of fluid retention (1) Hypotension (1) Tiredness (1) Feelings of depression (1) |
Bandyopadhyay and colleagues [31] | Atenolol Bisoprolol Carvedilol Metaprolol Nebivelol Propranolol Sotalol | Retrospective cohort | 5Â years | 568 | iPAH (260) APAH (308) | None reported | Therapy discontinued (60): Hypotension (18) Shortness of breath (14) Volume overlaod (12) Fatigue (7) Bradycardia/Syncope (4) Intolerance (3) Other (2) |
Moretti and colleagues [32] | Atenolol Bisoprolol Metaprolol Nadolol Propranolol | Prospective cohort | 2 years | 94 | iPAH (14) APAH (27) Post pulmonary embolism (13) Out of proportion (8) Mixed (5) Unknown (27) | ↑TAPSE ↓RV diameter ↓HR ↓Systolic blood pressure | None reported |
So and colleagues [33] | Acebutolol Atenolol Bisoprolol Metaprolol Nadolol Propranolol | Prospective cohort | 2 years | 94 | iPAH (53) Drug/toxin-iduced PAH (2) APAH (39) | ↑Cardiac index | None reported |
Thenappan and colleagues[34] | Atenolol Carvedilol Labetalol Metaprolol Nadolol Propranolol | Retrospective cohort study, propensity score analysis | 5Â years | 564 | iPAH (250) HPAH (17) Drug/Toxin-induced (21) APAH (273) Other (3) | None reported | None reported |
Bozbas and colleagues [60] | Losartan Nifedipine | Prospective, randomized | 2 months | 63 | PH due to left heart disease (40) PH due to lung disease and/or hypoxemia (23) | ↓mean PAP ↑RVEF ↑6-MWD ↓VE ↓VE/VCO2 ↑PETCO2 ↑CPET test duration | None reported |
Maron and colleagues [69] | Spironolactone ±Ambrisentan | Retrospective analysis of randomized, placebo-controlled trials ARIES-1 and 2 | 2 months | 199 | Primary PAH (126) Nonprimary PAH (73) | ↑6-MWD ↓BNP level ↓WHO class | Pulmonary hypertension (21) Edema or prevention of edema (11) RV failure (7) Electrolyte imbalance (1) |
Invasive strategies | |||||||
Chen and colleague [74] | PADN | Prospective cohort | 3 months | 21 | iPAH (21) | ↓mean PAP ↓PVR ↓RVSP ↓TPG ↓Pericardial effusion ↑PA compliance ↑6-MWD ↓WHO class ↓NT-proBNP level ↓Rehospitalization | Chest pain (10) |
Chen and colleagues [75] | PADN | Prospective cohort, single-arm | 1 year | 66 | iPAH (20) APAH (19) PH due to left heart disease (18) Chronic thromboembolic PH (9) | ↓mean PAP ↓PVR ↓RVSP ↑Cardiac output ↓Right atrial diameter ↓RV diameter ↓pericardial effusion ↑6-MWD ↓NT-proBNP level | Chest pain (47) Sinus bradycardia (1) Intolerance to dyspnea (3) |