Guazzi 2011a.

Methods	Randomised placebo‐controlled trial 12 months duration
Participants	Inclusion criteria: Participants with heart failure with preserved EF (heart failure signs and symptoms, diastolic dysfunction, EF 50%, and PASP 40 mmHg). (WHO Group 2) PASP > 40 mmHg at a preliminary ultrasound estimation Heart failure was independently adjudicated by 3 cardiologists on the basis of presence of 2 major criteria (nocturnal dyspnoea, distention of the jugular veins, moist rales over the lung bases, proto‐diastolic sound) or the presence of 1 major criterion together with 3 minor criteria (liver enlargement, oedema in the feet or ankles not resolving after a night’s rest, accentuation of P2, tricuspid systolic murmur, fatigue, signs of interstitial oedema at chest roentgenogram). LVEF 50%, sinus rhythm, and no hospitalisation in the 6 months preceding recruitment Exclusion criteria: People receiving nitrates history of pulmonary disease or in whom alternative causes of PH were likely angina pectoris acute coronary syndrome atrial flutter/fibrillation with more than a trace of mitral or aortic regurgitation or stenosis anaemia pericardial disease renal failure (creatinine 2 mg/dL) cardiac amyloidosis, genetically‐determined cardiomyopathy systemic diseases precluding participation PH was confirmed on right‐heart catheterisation n = 44
Interventions	Sildenafil (50 mg 3 times a day) (N=22) compared to placebo (N=22)
Outcomes	Haemodynamics, including: mean RAP, PASP, pulmonary artery diastolic pressure, mean PAP, mean wedge pulmonary pressure, transpulmonary gradient, pulmonary arteriolar resistance, pulmonary arterial elastance, RV end‐diastolic pressure, RV mean systolic ejection rate, TAPSE, RV maximal short‐axis dimension, cardiac index, systemic vascular resistance, systolic arterial pressure, diastolic arterial pressure Quality of life, including breathlessness, fatigue, emotional function Lung function tests including FEV1, FVC, and DLCO
Notes	Publicly funded Trial conducted at San Paolo Hospital in Milan, Italy, and at Virginia Commonwealth University, Richmond, USA, enrolled between January 15, 2006, and December 18, 2008
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Participants were randomly assigned in a 1:1 ratio according to computer‐generated random numbers
Allocation concealment (selection bias)	Low risk	Placebo‐controlled
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Placebo‐controlled, with nursing staff checking compliance unaware of the study aims or assignment to treatment
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Not explicitly stated but assumed
Incomplete outcome data (attrition bias) All outcomes	Low risk	Withdrawals were accounted for: Quote: "No participants in the sildenafil group was lost to follow‐up; in the placebo group, 2 participants were withdrawn at months 7 and 9 because at repeated Holter monitoring they showed persistent atrial fibrillation".
Selective reporting (reporting bias)	Low risk	Prespecified outcomes were reported
Other bias	Low risk	Other risk of bias is unlikely