Quad-pill more effective than mono-therapy in hypertension

4th October 2021

An anti-hypertensive quad-pill has been shown to provide better blood pressure control than the standard initial approach with mono-therapy.

According to the World Health Organization (WHO), the number of adults aged 30–79 years with hypertension is estimated to be 1.28 billion. However, perhaps more concerning are the WHO statistics suggesting that approximately 46% of adults are unaware that they have hypertension and that only 21% of patients have their condition under control. Various hypertension guidelines recognise that adequate blood pressure control is often only achieved with several medicines, yet guidance from NICE, for example, still recommends initiating mono-therapy. The potential value of using combination therapy as an initial approach to the management of hypertension, was explored in a small trial with 55 patients in 2017. A research team from the George Institute for Global Health, Camperdown, Australia, examined the value of using a single quad-pill with four anti-hypertensives, at a quarter of the normal treatment dose, as an initial therapy for patients with high blood pressure compared with placebo. After only 4 weeks, all patients given the quad-pill achieved a satisfactory blood pressure control (<140/90mmHg). However, these results were not surprising given the findings of a 2009 meta-analysis, which concluded that the additional blood pressure reduction from combining drugs from two different classes was approximately five-times greater than doubling the dose of one drug.

Now, the same Australian team has published the results of a randomised trial which they termed Quadruple UltrA-low-dose tReaTment for hypErTension (QUARTET). This randomised, double-blind study in adults with hypertension, allocated individuals, on a 1:1 basis, to either the quad-pill, which contained irbesartan (37.5mg), amlodipine (1.25mg), indapamide (0.625mg) and bisoprolol (2.5mg), or an indistinguishable, mono-therapy with irbesartan 150mg. The primary outcome was the difference in unattended office systolic blood pressure at 12 weeks. Moreover, a sub-cohort of patients from the trial continued with treatment for up to 52 weeks.

Findings

A total of 591 patients with a mean age of 59 years (60% male) and a mean baseline unattended blood pressure of 141mm/85mmHg, were randomised to quad-pill (300) or mon-therapy with irbesartan . By week 12 only 15% of those receiving the quad-pill compared to 40% on mono-therapy, required additional blood pressure medication. Furthermore, at week 12, a higher proportion of patients given the quad-pill (76% vs 58%) achieved a blood pressure < 140/90mmHg (relative risk, RR = 1.30, 95% CI 1.20–1.50, p < 0.0001). In addition, a blood pressure of less than 120/80mmHg, was also achieved by more patients in the quad-pill group (46% vs 26%, RR = 1.75, 95% CI 1.38–2.22, p < 0.0001). After 52 weeks, mean unattended systolic blood pressure remained 7.7mmHg lower in the intervention group. At 12 months, blood pressure control rates were also higher for the intervention group (81% vs 62%, RR 1.32, 95% CI 1.16–1.50) as were the proportion achieving a blood pressure < 120/80mmHg (53% vs 25%, intervention vs control, RR = 2.1 95% CI 1.60–2.8, p < 0.0001).

The authors concluded that “a strategy with early treatment of a fixed-dose quadruple quarter-dose combination achieved and maintained greater blood pressure lowering compared with the common strategy of starting mono-therapy.”

Citation

Chow CK et al. Initial treatment with a single pill containing quadruple combination of quarter doses of blood pressure medicines versus standard dose mono-therapy in patients with hypertension (QUARTET): a phase 3, randomised, double-blind, active-controlled trial. Lancet 2021

Use of anti-hypertensives associated with reduced risk of colorectal cancer mortality

27th August 2021

An analysis of patients with colorectal cancer has shown the use of anti-hypertensives to be linked to a reduced risk of cancer mortality.

According to the World Cancer Research Fund, colorectal cancer (CRC) is the third most commonly cancer in men and the second most common cancer in women. Moreover, the most recent data from 2018, shows that worldwide, there were over 1.8 million new cases of CRC. The relationship between cancer and hypertension is uncertain although in a retrospective study of over 25,000 cancer patients, new onset hypertension was found in a third of individuals. This relationship might be related to the vascular endothelial growth factor (VEGF) proteins, which are mediators of angiogenesis and lymphangiogenesis in tumours and have been found to be elevated in patients with hypertension. It is conceivable therefore, that the use of anti-hypertensives may exert a protective effect in those with cancer. This was the theory behind a retrospective study of patients with CRC undertaken by a team from the University of Virginia, School of medicine, Virginia, US. They examined a Medicare database which contained patient demographic information for those with cancer. They focused on patients with CRC aged 65 years and older but excluded those with any stage of CRC prescribed anti-hypertensives prior to the cancer diagnosis. The researchers extracted data on the clinical characteristics of CRC including stage and tumour grade and examined adherence to anti-hypertensive therapy based on the proportion of days covered (PDC), which is a measure of adherence with values greater than 0.80 used to define patients who are adherent to their anti-hypertensive therapy. All classes of anti-hypertensives were included and the period of follow-up started 1 year after the initiation of blood pressure lowering therapy. The primary outcome was CRC-specific mortality and the team used hazard regression models to examine the association between the use of individual anti-hypertensives and mortality.

Findings
A total of 13,982 patients were included in the analysis. A range of factors were found to be associated with CRC mortality including male gender (hazard ratio, HR = 1.07, 95% CI 1.03 – 1.13) and interestingly, being single, rather than married (HR = 1.08). The use of anti-hypertensives was associated with a decreased CRC-specific mortality (HR = 0.79, 95% CI 0.75 – 0.83). Furthermore, there was a significant association between adherence to treatment (i.e., those with a PDC greater than 0.80 and decreased mortality (HR = 0.94, 95% CI 0.90 – 0.98). Among the different types of drugs, significant associations were found for only angiotensin enzyme converting enzyme inhibitors (HR = 0.84), beta-blockers (HR = 0.87) and thiazide diuretics (HR = 0.83).
In discussing these results, the authors were cautious that these novel findings would need to be researched further as a potential tool to improve cancer-related mortality. However, they concluded that anti-hypertensive medications might represent a promising pathway to supporting patients with CRC.

Citation
Balkrishnan R et al. Associations between initiating antihypertensive regimens on stage I–III colorectal cancer outcomes: A Medicare SEER cohort analysis. Cancer Med 2021