How to choose drugs in pulmonary arterial hypertension
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Transcript of How to choose drugs in pulmonary arterial hypertension
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