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Single-pill combo could treat hypertension
Given the importance of medication adherence for patients with hypertension, simpler and more effective treatments are always welcomed. Chow and colleagues at the University of Sydney, the University of Tasmania, Monash University, the University of Western Australia, the University of New South Wales, and Western Sydney University hypothesized that a single pill containing ultra-low-dose quadruple combination therapy would be more effective than monotherapy.
To determine if the single pill was effective, the QUARTET team conducted a multicenter, double-blind, randomized, phase 3 trial among Australian adults (≥18 years) with hypertension who were either untreated or receiving monotherapy. Patients were randomly assigned to receive either the quadpill (37.5 mg irbesartan, 1.25 mg amlodipine, 0.625 mg indapamide, and 2.5 mg bisoprolol) or a monotherapy control (150 mg irbesartan). If BP was not at target, additional medications were added in both groups, starting with 5 mg amlodipine.
The primary outcome of the study, published in The Lancet on September 21, 2021, was the difference in unattended office systolic BP at 12 weeks. Secondary outcomes included BP control (standard office BP <140/90 mm Hg), safety, and tolerability. A subgroup continued randomly assigned allocation to 12 months to assess long-term effects.
By 12 weeks, 15% of 300 participants had received additional BP medications in the quadpill group compared with 40% in the control group. Systolic BP was lower by 6.9 mm Hg and BP control rate was 76% in the quadpill group versus 58% in the control group. At 52 weeks, mean unattended systolic BP remained lower by 7.7 mm Hg and BP control rates remained higher in the quadpill group (81%) compared with the control group (62%).
The authors concluded that early treatment of a fixed-dose quadruple quarter-dose combination medication achieved and maintained greater blood pressure control compared with the common strategy of starting monotherapy.
Minocycline effective against gram-negative pathogens
Infections from unusual gram-negative pathogens have increased with the growing number of immunocompromised patients. Shortridge and colleagues at JMI Laboratories (North Liberty, IA) analyzed the minocycline susceptibility of 3,856 isolates including Stenotrophomonas maltophilia, burkholderia, achromobacter, alcaligenes, and aeromonas species from the global SENTRY Antimicrobial Surveillance program (2014–19).
The study, published online September 7, 2021, in Antimicrobial Agents and Chemotherapy, showed that minocycline susceptibility was greater than 85% for the various species tested, including 99.2% susceptibility for aeromonas species, 98.8% for non-baumannii acinetobacter, 92.7% for achromobacter species, and 99.5% for S. maltophilia. The authors conclude that these data suggest that minocycline may be a useful treatment option for infections caused by unusual gram-negative pathogens.
Can probiotics prevent ventilator-associated pneumonia?
It has been suggested that microbiome modification with probiotics could reduce infection, particularly ventilator-associated pneumonia, although probiotic-associated infections have also been reported.
To further investigate the effectiveness of probiotics in reducing infections, researchers involved in the prevention of Severe Pneumonia and Endotracheal Colonization Trial (PROSPECT) trial and the Canadian Critical Care Trials Group conducted a randomized placebo-controlled trial in 44 ICUs in Canada, the United States, and Saudi Arabia, enrolling adults predicted to require mechanical ventilation for at least 72 hours.
A total of 2,653 patients were enrolled from October 2013 to March 2019 with a final follow-up in October 2020. Each patient received either enteral Lactobacillus rhamnosus GG (1 × 1010 colony-forming units) or placebo twice daily in the ICU.
The primary outcome was ventilator associated pneumonia determined by duplicate blinded central adjudication.
Secondary outcomes were other ICU-acquired infections including Clostridioides difficile infection, diarrhea, antimicrobial use, ICU and hospital length of stay, and mortality.
In the study, published online on September 21, 2021, in JAMA, 289 patients who received probiotics developed ventilator-associated pneumonia compared with 284 patients who received a placebo.
There was no significant difference between groups in any of the 20 prespecified secondary outcomes. The authors concluded that their findings do not support the use of L. rhamnosus GG in critically ill patients.
Acute kidney injury and other risks associated with thiazide diuretics
Although thiazide diuretics are commonly used in the management of hypertension, they have been associated with electrolyte disorders, syncope, and falls. To investigate the prevalence and risk factors of electrolyte disorders in patients taking thiazide diuretics as well as their association with syncope and falls, Lindner and colleagues at Buergerspital Solothurn (Switzerland), Klinik Ottakring (Austria), Pyhrn-Eisenwurzen Klinikum (Austria), and University Hospital Inselspital (Switzerland) conducted a cross-sectional analysis of all patients admitted to the ED of the Buergerspital Solothurn (Switzerland) between January 1, 2017, and December 31, 2018.
All patients 18 years and older admitted to the ED during the study period with measurements of sodium and potassium on admission and who consented to scientific use of their data were included in the study. Serum electrolytes and creatinine levels were analyzed to classify electrolyte disorders and acute kidney injury, while chart reviews were performed to screen for syncope or falls. Results of the study were published in the September 2021 issue of the American Journal of Medicine.
Of the patients included in the study, 604 received thiazides. The researchers found that acute kidney injury was significantly more common in patients prescribed thiazide than in the control population. Hyponatremia and hypokalemia were more frequent with thiazide use, with older and female patients more likely to develop these conditions.
A dose-dependent effect was found for electrolyte disorders, with the risk varying depending on the particular thiazide diuretic. Patients taking these medications also had significantly more episodes of syncope and falls.
Based on this data, the authors recommended a more careful approach to prescribing thiazide diuretics in patients who are older, female, and prone to falls.
ARBs may be safer than ACE inhibitors
Although ACE inhibitors and ARBs are both recommended as first-line treatments for hypertension, few studies have directly compared their effectiveness and safety.
In an observational study published in the September 2021 issue of Hypertension, Hripcsak and colleagues at Columbia University, Yale University, UCLA, Georgia Tech, the University of South Australia, and Ajou University (Korea) compared the real-world effectiveness and safety of ACE inhibitors versus ARBs in the first-line treatment of hypertension.
All patients with hypertension initiating monotherapy with an ACE inhibitor or ARB between 1996 and 2018 across 8 databases from the United States, Germany, and South Korea were included in the study. Over 2,000,000 patients initiating treatment with ACE inhibitors and over 650,000 patients who were prescribed ARBs were identified. The primary outcomes were acute myocardial infarction, heart failure, stroke, and composite cardiovascular events.
The researchers found no statistically significant difference in the primary outcomes of acute myocardial infarction, heart failure, stroke, or composite cardiovascular events between the 2 groups.
However, patients taking ARBs had significantly lower risk of angioedema, cough, pancreatitis, and GI bleeding than those taking ACE inhibitors. The authors concluded that while ARBs and ACE inhibitors don’t differ significantly in effectiveness as first-line treatment for hypertension, ARBs present a better safety profile.