9: The Minions in Hypertension!

You probably recognize the minions. Those tiny yellow characters featured in three motion pictures. I personally love them. Capsule-like small creatures with wide eyes, blue overalls and peculiar cheerful funny laughs and squawks. And I share with them their love for bananas!Kevin, Stuart, Dave and Bob are four of the most familiar minions. Individually they are small but each one has a special talent and when they work together they can create marvelous tools and solve the most difficult problems for the film’s main character.Speaking of difficult problems, hypertension is one problem that affects billions of people. Most of us, if we live to our eighties, will become hypertensive. And the control rates are poor in the developed countries. The traditional treatment is based on giving one drug in the standard dose or combining two of those two also in standard doses to lower the blood pressure.But, how about combining four (mini doses) minions of antihypertensives in one pill! Would that pill do better than a standard dose of a single good antihypertensive?This question was tackled by a trial called QUARTET trial was presented at the ESC Congress last August then published in the Lancet last September.The trial was a multicentre, double-blind randomised, trial of 571 Australian adults with hypertension, who were untreated or receiving monotherapy. Patients were randomly assigned to either quadpill  or a mono therapy. The quad pill (contained 4 medications, each in one fourth of the standard dose; irbesartan 37·5 mg instead of 150, amlodipine at 1·25 mg not 5, indapamide at 0·625 mg not 2.5, and bisoprolol at 2·5 mg not 10 or even 5) or an indistinguishable monotherapy control (irbesartan 150 mg). If blood pressure was not at target, additional medications could be added in both groups. The researchers looked at BP control, safety and tolerability a 12 weeks then 12 months. And guess who won?SBP was about 7mmHg lower in the quadpil (allow me to call it the minion group) and control rates were 30% higher compared to the monotherapy group without difference in adverse events. The better BP control was sustained at one year with minions. Significantly less patients in the minion group) required additional BP medications compared to the mono therapy groupI consider this one of the key research papers in hypertension. I can think of several future implications of this conceptNumber 1: This is a further step in combination therapies for HTN. Not just two as recommended in many guidelines. With four mini doses, multiple pathophysiologic pathways tackled in one pill; sympathetic , RAS, sodium overload, vasoconstriction in small doses with less adverse effects. This can overcome physicians inertia and improve patients adherence to treatment.Number 2: Polypill is revived. Expect to see trials combining not just several BP medications, but also with statins and aspirin. NEJM trial on polypill in socioeconomic classes, cheap, more compliance, better BP and LDL reduction.Number 3: I expect the idea may be adopted by the pharma to manufacture different doses and different combinations not only triple combinations as we currently haveNumber 4: Boost to personalized medicine. Think of the tens of permutations that could come from different doses of four medications. Maybe in the future, the local pharmacist can add tailor your minion pill combinations; more beta blocker for the young, less diuretics for an elderly…etc