How to choose drugs in Pulmonary Art HT

Dr. Akshay Mehta

Nanavati Superspeciality HospitalAsian Heart InstituteHoly Family Hospital

Comprehensive Classification of PH - WHO

• Group 1 – PAH -idiopathic (iPAH), heritable (HPH), drugs (DPH), CTD, portal H, CHD, Schistosomiasis

• Group 2 – PH due to left heart disease

• Group 3 – PH due to lung disease

• Group 4 – Chronic thromboembolic pulmonary hypertension (CTEPH)

• Group 5 – PH due to unclear multifactorial mechanisms

Specific drugs for which patients ?

27-year-old Female

• Class III DOE• 3 months duration• CHF – JVP +, Hepatomegaly • TR velocity 78 mm Hg• CT Angio – Dilated pulmonary artery, No cause

found• HIV, ANA, RF - Negative

Q: Which one of the following drug therapy is not ideal for her?

1. Torasamide 5 mg OD

2. Digoxin 0.25 mg ½ OD (6/7)

3. Sildenafil 20 mg tds

4. Diltiazem 120 mg OD

Contraindications to CCB

• Overt evidence of right-sided heart failure.

• In patients with IPAH (or any other form of PAH), a cardiac index of less than 2 L/min/m2 or a right atrial pressure above 15 mm Hg is a contraindication to CCB therapy, as these agents may worsen right ventricular failure in such cases.

Indications for CCB

1. Type of PAH – iPAH, hPAH, dPAH

2. Vasodilator response : A positive response is defined as a reduction of mean PAP >/=10 mmHg to reach an absolute value of mean PAP </= 40 mmHg with an increased or unchanged CO.

…..CCB therapy

• Only 10 to 15 % are responders to vasodilator challenge and 50% out of these have long term benefit

• High dose beneficial• Preferential action on pulm vessels• Sudden withdrawal dangerous• Contraindicated in patients with frank right

sided failure

Supposing a patient is unsuitable for CCB or non responsive to vasodilator challenge.

Which drug to give?

Oral Therapies for PAH

Selection of drugs :Variables to consider

• Vasoresponsiveness

• WHO functional class

Q: Specific oral drug therapy is generally recommended for which WHO class ?

A. Patients in WHO FC I ?

B. Patients in WHO FC II ?

C. Patients in WHO FC III ?

D. Patients in WHO FC IV ?

Best drugs for WHO class II & III patients

Best drugs for WHO class IV patients

Other factors for drug selection

• Rapidity of oral effectiveness (PDE5i)• Patient comorbidities (liver & bosentan)• Drug side effects (liver, ILD, edema, anemia)• Potential Interactions with other drugs

(nitrates)• Availability, Cost

All of the following are proven benefits of PDE5 inhibitors except :

1. Improved 6MWD

2. Rapidity of action

3. Reduces esophageal reflux

4. Cost & availability

5. Once daily dosage

1

Improvement less than satisfactory on PDE5i-what next ?

1. Increase Sildenafil dose

2. Switch to Tadalafil

3. Add another class of drug- combination Rx

4. Replace with Bosentan

1

SERAPHIN Placebo vs Macitentan 3 mg vs Macitentan 10 mg (1:1:1)

If addition of an ERA to PDE5i is ineffective, add….

• Guanylate cyclase stimulators- Riociguat ???• Epoprostenol - I.V. ?• Iloprost - Inhaled (or I.V.)• Treprostinil -Subcutaneous or inhaled (or I.V.)?• Selexipag ?

Recommendations for efficacy ofsequential drug combination therapy- 2015 ESC/ERS

What about combination therapy from the start-

UPFRONT COMBINATION THERAPY ?

Upfront triple combination therapy in pulmonary arterial hypertension: a pilot study : June 2014

(epoprostenol, bosentan and sildenafil)

Parameters with triple therapy- 18 patients-100% survival at 3 yrs

Recommendations for efficacy of initialdrug combination therapy-2015 ESC/ERS

Anticoagulants are most recommended for which of the following groups of PH ?

• Group 1• Group 2• Group 3• Group 4• Group 5

Paradigm shift in PAH management

Goals more ambitious- 6MWD not enough Like HF, cancer, etc- the mantra is : Treat quickly Hit hard Use upfront combos rather than wait & rescue- even in relatively stable patients for better long term outcomes Larger RCT’s of triple upfront therapy needed

Thank you