Authors:
Erin Connolly, PharmD
Katherine Duprey, PharmD, BCACP, CDOE, CVDOE
Laura Varnum, PharmD, BCACP
Reviewers:
Kathryn Litten, PharmD, BCACP
Joseph Saseen, PharmD, BCPS, BCACP
Citation:
Chow CK, Atkins ER, Hillis GS, et al. Initial treatment with a single pill containing quadruple combination of quarter doses of blood pressure medicines versus standard dose monotherapy in participants with hypertension (QUARTET): a phase 3, randomised, double-blind, active-controlled trial. Lancet. 2021;398(10305):1043-1052.
The Problem
Many adults with hypertension, globally and in the US, have uncontrolled blood pressure.1,2 Traditionally, hypertension management involves a stepwise approach where agents are titrated and added. Thus, achieving optimal BP control requires close follow-up, time, and resources. Outside of these logistics, providers are prone to clinical inertia (aka fail to advance therapy when they should) and sometimes “push back” from patients who experience the burdens of treatment and follow-up. Perhaps it’s time to reconsider our approach to managing hypertension. If we could somehow get more patients to goal with the initial treatment, we’d significantly reduce the burdens on patients and the healthcare system as well as potentially lower cost. The QUARTET trial tests this notion – using an initial combination “pill” containing ultra-low doses of four common hypertension medications instead of starting and titrating each medication class separately. Would a multicomponent combination approach be more efficient and well-tolerated?
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Interesting study and interesting podcast. One study we participated in many years ago that may be of interest to those following this issue is the ACCOMPLISH trial (see n engl j med 359;23 http://www.nejm.org december 4, 2008). The main “take away” for me is that this study demonstrated that the choice of drugs used to control BP may be at least as important as the degree of BP control. The study enrolled more than 11,000 high risk patients (concomitant diabetes, CAD, etc. with just over 80% caucasian) and compared an ACE+Ca blocker combo (Lotrel) vs. an ACE and a diuretic based on the concept that the former would provide greater CV protection via “ancillary” effects. Personally (and remember that this was in the early 2000s), I thought the ACE + diuretic was a good combination; but as the study went forward, I was surprised at how well the ACE+Ca blocker controlled BP and in the end, the composite endpoint (CV death + non-fatal stroke/MI + PCI, etc.) was indeed lower with the Lotrel (about 2% absolute difference and 20% relative risk reduction) even though BP was similarly controlled in both arms. As would be anticipated, there was more peripheral edema in the Lotrel arm; but these 2 drugs would appear to be a good start for the basis of a “quad pill” (as indicated in the QUARTET). Perhaps what is needed are three products – dos, tres, quatro pills. One could select the product with 2, 3, or 4 components based on degree of BP elevation and/or concomitant condition then switch from one to the other depending on degree of BP control. Sure, that would involve changing products; but the patient still could be treated with a single product rather than adding additional doses……oh, and maybe a “cinco” for those who need a statin? 🙂