Monday, May 25, 2009

Study heralds dawn of the cardiovascular polypill

Medical Tribune May 2009 P1&6
David Brill

A five-drug combination tablet could cut the risk of coronary heart disease by more than 60 percent and nearly halve the risk of stroke, results of the first major ‘polypill’ trial suggest.

The Indian Polycap Study (TIPS) found that combining the medications did not hinder their potency – offering effective blood pressure (BP) and lipid control with a simple once-daily capsule.

The study paves the way for further trials to see whether the pill improves clinical outcomes on a wide scale, say the researchers.

The Polycap formulation used in TIPS contains low doses of aspirin (100 mg), simvastatin (20 mg), thiazide (12.5 mg), atenolol (50 mg) and ramipril (5 mg).

It was tested in a double-blind randomized controlled trial of 2,053 people aged 45 to 80 who had one existing risk factor but no history of cardiovascular disease (CVD).

Lead researcher Dr. Salim Yusuf stressed the need for further trials but called the potential to lower CVD risk with a single pill “a huge step in the management of patients.” He said that the Polycap has “definite” applicability for secondary prevention, and would lower costs and improve compliance in CVD patients who are already taking the individual drugs.

“The big question … is whether you take the whole world at large, over a certain age group, don’t measure anything, and then give them all a polypill. I will withhold judgment on whether that’s the right thing to do or not right now,” he said at a press conference.

TIPS was presented at the 58th Annual Scientific Session of the American College of Cardiology and published online in The Lancet. [2009 Mar 30; Epub ahead of print]

The study, carried out at 50 centers in India, comprised nine groups: 412 patients took the Polycap, while around 200 each were assigned to one of eight different permutations of the drugs alone and in combination.

After 12 weeks of Polycap therapy, mean systolic and diastolic BPs decreased by 7.4 mmHg and 5.6 mmHg, respectively, as compared to people taking no BP-lowering drugs. This magnitude was similar to that achieved with three BP-lowering drugs, either with or without aspirin.

LDL cholesterol was reduced by 0.70 mmol/L in Polycap users – a slightly lesser reduction than with simvastatin alone (0.83 mmol/L; P=0.04) but still highly significant compared to people who did not take a statin (P less than 0.0001).

The Polycap, manufactured by Cadila Pharmaceuticals, India, was well tolerated: discontinuation rates were similar to other treatment groups and largely attributable to social reasons.

The projected risk reductions for taking the Polycap were 62 percent for coronary heart disease events and 48 percent for stroke. These were calculated using the methods of Drs. Wald and Law, who first proposed the polypill concept in a seminal British Medical Journal paper. [2003 Jun 28;326(7404):1419]

Yusuf, director of the Population Health Research Institute at McMaster University, Canada, said that clinical event-driven trials of polypills could be published within 6 months to a year.

He acknowledged concerns that polypills could promote the wrong message if marketed incorrectly, stressing that lifestyle modification is the “the crux and the fundamental basis of CVD prevention.” He rejected, however, the suggestion that widespread medication could be a difficult idea to promote.

“There’s something inherently repulsive to most of us to say we’re medicalizing the whole population. Just think of the millions of people in the world taking multivitamins with no evidence.

“The concept of taking a pill to improve your health is really not new – it is embedded in most cultures, whether it is Asian, Western or wherever else,” he said.

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