Friday, May 09, 2014

THE STORY OF THE POLYPILL FOR PREVENTION OF STROKE AND HEART ATTACKS. SPACE. SCIENTIFIC REPORTING AND LAY REPORTING

The World Congress of Cardiology has just ended in Melbourne. Amongst the many papers presented, one was carried in the "Free Malaysia Today" internet news. Initially, I was not keen to write on this paper as we had done it before and we have yet no outcome data. We have numbers crunching which should translate to better CV outcomes, but no conclusive data on this. Be that as it may, so I looked into the presentation. Please read both articles ( WCC presentation and FMT ), and draw your own conclusions. Doctors should do that.
At Melbourne, Dr Ruth Webster of the George Institute of Global Health, Sydney, presented the results of the SPACE ( Single Pill to Avert CVS Events ) study. This study was actually a combination of three different studies with a total enrolment of 3,140 patients 65% of which had CAD and the other 35% at high risk of CAD, meaning that they had multiple major coronary risk factors by Framingham Risk Score ( >15% in 5 yrs ). The studies involved was the Impact study from NZ, the Umpire study from Western Europe and India, and the Kanyini GAP study from Australia. ( One wonders with these large countries and continents involved, enrolment is only 3,140, so pathetic ). Anyway, these patients were randomised to receive a a single polypill daily, or to usual therapy by their doctors, which maybe 4 pills a day. The single polypill contained aspirin 75 mg, simvastatin 40 mg, lisinopril 10 mg and atenolol 50mg or some in a second batch, atenolol was substituted by HCT 12.5mg. After 12 months ( note, only 12 months ), there was a 78% adherence to therapy in the polypill group and 54% adherence in the usual therapy group. A difference of 24%, only ( not a 43% increase adherence as stated in FMT ). The treatment arm had a 2.84 mmHg reduction in BP and a 0.12 mMol/L reduction in LDL-Cholesterol. Very small reduction as you can see. Of course, master advocate of polypill ( Dr Salim Yusuff, estimates that this will translate into a 9% reduction in CV events in 5-10 years ). Remember, this is an expert's estimate.

A simple study to meta-analyse 3 clinical trials on this subject.
I had a few thoughts, viz., why did they get only 3,140 patients when the countries and continents involved were so large, and CAD is so prevalent. Imagine, Western Europe, India, Australia and NZ can only come up with 3,140 patients. Is it cost to carry out the trial? Is it that cardiologist do not like the idea, and so did not wish to co-operate?, Is it side effects and so drop out was high? I do not know. There is no clue in the presentation. Sure, to be convincing and meaningful, we need 10-20,000 patients enrolment.
Secondly, 12 months is obviously too soon to translate into outcome data, and outcome data ( besides safety analysis ) is what we need, There is no data on safety here, and we will have to wait 5-10 years for outcome data. I understand that there is TIPS 3 ( The International Polypill - 3 ) study underway, started in 2012, enrolment of 5,500 patients. So we need to wait till 2017 at least.
Of course lay reporting is a bit of sensationalism.

I still believe that Chronic non-communicable disease is a life style disease and the best prevention is life style modification. There is no short cut. You are responsible for yourself.

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