Triple therapy shows promise for severe PAH

Results of a small pilot study among patients with severe pulmonary arterial hypertension (PAH) support the long-term benefits of upfront triple combination therapy, French researchers report.

The 19 patients (mean age 39 years, 89% women), who had PAH in New York Heart Association (NYHA) functional class (FC) III/IV with severe haemodynamic impairment, were treated with epoprostenol (intravenous up to a maximum of 16 ng/kg per minute), bosentan (125 mg twice daily) and sildenafil (20 mg three times daily) between December 2007 and July 2013.

After 4 months of treatment, Olivier Sitbon (Université Paris-Sud, Le Kremlin-Bicêtre) and co-researchers observed significant clinical and haemodynamic improvements in 18 of the 19 patients. Indeed, 17 patients had moved to FC I/II and their 6-minute walking distance (6MWD) had increased from an average of 227 metres to 463 metres. One patient had an emergency heart and lung transplant at month 3 and was not included in the follow-up analyses.

At the final follow-up visit, a mean of 32 months after treatment initiation, all 18 patients were in FC I/II and their average 6MWD had increased to 514 metres, which was a further significant improvement on the 4-month visit. Initial improvements in haemodynamic variables were also maintained to the final visit.

The researchers used the French equation to calculate expected survival rates of 75%, 60% and 49% at 1, 2 and 3 years, respectively. The actual values of 100% at all time points may be partly due to the significant increase in cardiac index (from 1.66 to 3.64 L/min per m2) and fall in pulmonary vascular resistance (from 1718 to 492 dyn/sec per cm5), they note.

Jaw pain, manageable headache, diarrhoea and flushing were the most commonly reported adverse events, which are typical of epoprostenol therapy. Two patients discontinued bosentan (at 11.5 and 31.5 months) due to asymptomatic liver enzyme elevation, but they were maintained in FC I/II using epoprostenol and sildenafil.

Writing in the European Respiratory Journal, Sitbon and co-authors say that the success of the triple regimen in these patients is “particularly relevant given that, despite increasing awareness, the majority of PAH patients are in NYHA FC III/IV at diagnosis, with a significant proportion being in NYHA FC IV.”

They conclude: “The findings of this pilot study provide preliminary evidence supporting the long-term benefits of upfront triple combination therapy in patients with severe PAH.”

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  1. Charles Weber Charles Weber United States says:

    For a long time it has been assumed that it was the sodium in salt that contributed to high blood pressure. I have always had the sneaking suspicion that they were ignoring the chloride, and thus taking the chance of barking up the wrong tree, and now it looks as if my suspicions were in order. Experiments with potassium chloride supplements show that such supplements often raise blood pressure, as covered in this URL; . Now it is known that sodium must be combined with chloride to raise blood pressure. Sodium alone causes blood pressure to fall in salt sensitive people. [McCarty 2004 Should we restrict chloride rather than sodium? Medical Hypotheses 63; 138-148]. Sodium bicarbonate lowered blood pressure 5 mm of mercury [Luft FC Zemel MB Sowers JA Fineberg NS Weinberger MH 1990 Sodium bicarbonate and sodium chloride: effects on blood pressure and electrolyte homeostasis in normal and hypertensive man. Journal of Hypertension 8; 663-670], perhaps so little because the subjects were probably already on high salt intake (along with most of the rest of the country ). Also see; [Boegshold M Kotchen TA 1991 Importance of dietary chloride for salt sensitivity of blood pressure. Hypertension 17 (suppl) I 158-I161]. This must be intimately involved with pH regulation in some way, because adding sodium bicarbonate to potassium chloride neutralizes the affect of potassium chloride on pressure [McCarty]. This should have the same net affect as adding a sodium chloride supplement to a normal diet high in potassium. It has been known for a long time that higher potassium to sodium molar ratios have an inhibiting affect on blood pressure from salt hypertension [Dahl, et al 1972 Influence of dietary potassium and sodium/ potassium molar ratios on the development of salt hypertension. Journal of Experimental Medicine 136; 318-330]. See also  The link to pH regulation is plausible because 18 OH-DOC is deeply involved in one of the, at least three, forms of hypertension [Melby JC et al 1972 18-hydroxy 11 deoxycorticosterone (18 OH-DOC) secretion in experimental and human hypertension. Recent Progress in Hormone Research. 28; 287-351, on page 323] and 18OH-DOC is probably the steroid hormone that regulates hydrogen ion excretion [see;   ]There is no significant increased risk of cardiovascular disease statistically for serum potassium between 4.1 and 5.3 Meq per liter (4.8 is what the body aims for), but the incidence of hypertension is 3% in a 4.1 meq average, to 2% in a 4.5 meq average, to 1% in 4.8 meq average or 5.1 meq average [Walsh, et al 2002 Serum potassium and risk of heart disease. Archives of Internal Medicine 162; (9) 1007-1012].
    With at least three different forms of high blood pressure, as above, and all the other nutrients wildly varying in people’s diet, the situation is hopelessly complicated. But in so far as potassium being involved is concerned, supplements are not normally the way to go as a rule. Anyone should get as much potassium as possible from food. The reason is that you tend to avoid the possibility of imbalances or deficiencies with other nutrients. This is especially important with respect to magnesium since potassium is absorbed with difficulty in a magnesium deficiency, and a magnesium deficiency takes months to correct. The imbalance that can be most immediately dangerous is the interaction with thiamin (vitamin B-1) because heart disease can not occur when both are deficient [see; ]. There is another reason why so far as my own emotions are concerned. It seems kind of nutty to me to deliberately pay hard cash for food that has been ruined, and then try to correct the debacle with supplements, and I get itchy whenever I get involved in nutty procedures.
            The main important aspect of potassium, though, is to avoid heart attacks. High blood pressure is unlikely to cause a ruptured blood vessel in the presence of adequate copper [see ] and vitamin C, since healthy blood vessels are normally ten times as strong as they have to be to stand normal pressures. Heart involvement does not usually come from potassium unless the blood content sinks below 4.0 meq per liter at least. What really counts is the cell potassium content, and the only practical way that I know of to determine that is a whole body scintillation counter coupled with a fat content analyzer.  So it is imperative to get more than enough potassium in food or supplements since such machines are rarely available. 3500 milligrams per day total would be ideal.
             You also may find a book about potassium nutrition as it relates to heart disease, gout, rheumatoid arthritis, high blood pressure, and diabetes, useful for your library. Its availability along with its introduction and table of contents may be accessed in .
                Sincerely,  Charles Weber
    PS  Dr. Rastmanesh, a nutritionist from Iran, would like to secure a position in an English speaking university because of religious or political  problems. He has an impressive CV. If you know of an opening I will send you his CV. It would be a travesty to leave that fine scientist in that criminal country after he got rid of rheumatoid arthritis for us.

The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of News-Medical.Net.
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