The American College of Gastroenterology (ACG) released updated treatment guidelines for Helicobacter pylori (H. pylori), a gram-negative bacteria that infects the stomach and raises the risk of peptic ulcers and gastric cancer. In some parts of the world, H. pylori is prevalent in more than 50% of the population, while in the U.S., about 26% of people are infected. The new guidelines differ from those released in 2017 in that regimens with a PPI and clarithromycin (e.g., Prevpac) are no longer preferred due to clarithromycin resistance that has lowered their efficacy to less than 70%. The guidelines also recommend two regimens with vonoprazan, a new acid-reducing drug that works by competing with potassium ions at proton pumps instead of covalently binding them like PPIs. Recommended first-line therapies are listed below.

• Optimized bismuth quadruple therapy: PPI + bismuth subsalicylate or subcitrate + metronidazole + tetracycline; cost - $60; cure rate - 87%
• Rifabutin triple therapy: omeprazole + amoxicillin + rifabutin; cost - $150 (prescribed separately) or $800 (Talicia); cure rate - 84%
• Voquezna DualPak: vonoprazan + amoxicillin; cost - $660 (prescribed separately) or $830 (DualPak); cure rate - 79%
• Voquezna TriplePak: vonoprazan + clarithromycin + amoxicillin; cost - $690 (prescribed separately) or $830 (TriplePak); cure rate - 81%

The urea breath test and fecal antigen test are recommended for diagnosis because they detect active disease, whereas the serologic antibody test is nonspecific. A test for cure, using the same method performed for diagnosis, is recommended in all patients 30 or more days after treatment completion. Patients who are still positive should be treated with a salvage regimen with the choice based on prior therapy received and sensitivity testing if available. The recurrence rate in the U.S. after successful treatment is 1% per year. Regimen details for treatment-naive and treatment-experienced patients are available at the link below.

• Treatment-naive regimens with dosing
• Treatment-experienced regimens with dosing

Patients with atrial fibrillation (AF) and coronary artery disease (CAD) have indications for both an anticoagulant and an antiplatelet agent. Past guidance on managing these patients was indecisive. In 2019, the AFIRE study was published, which found that anticoagulant monotherapy was equally effective and safer than dual therapy (anticoagulant + antiplatelet). A second study addressing this issue was recently published. In the EPIC-CAD study, 1040 patients with AF and stable CAD were randomized to edoxaban monotherapy or dual therapy (edoxaban + aspirin or P2Y12 inhibitor). After 12 months, major ischemic events were similar between groups (edoxaban 1.6%, dual therapy 1.8%), while major bleeding or clinically relevant nonmajor bleeding was higher with dual therapy (4.7% vs 14.2%).

After AFIRE was published, AHA guidelines recommended anticoagulant monotherapy in AF with stable CAD, and EPIC-CAD supports this guidance.

I still encounter patients who are taking aspirin with anticoagulants. Since aspirin is not prescribed, providers sometimes forget to ask about it. Likewise, patients forget to report it. When initiating anticoagulants, it is important to take a moment and discuss antiplatelet agents with patients, including OTC NSAIDs like ibuprofen and naproxen. Conditions where dual therapy may still be recommended include AF with recent cardiac stent placement and a subgroup of patients with mechanical heart valves.

• EPIC-CAD - Edoxaban vs Dual Therapy in AF and CAD, NEJM (2924) [PubMed abstract]
• Antiplatelet therapy in CAD

Finerenone (Kerendia®), a nonsteroidal mineralocorticoid receptor antagonist (MRA) approved for diabetic kidney disease, was recently evaluated in heart failure with preserved ejection fraction (HFpEF). The FINEARTS-HF trial randomized 7463 patients with symptomatic heart failure and an EF of 40% or more to finerenone 20 - 40 mg/day or placebo. After a median of 32 months, the primary outcome, a composite of heart failure events and death from CVD causes, was lower in the finerenone group (14.9%/year vs 17.7%/year, p=0.007). There was no significant difference in overall mortality (16.4% vs 17.4%), while hyperkalemia (14.3% vs 6.9%) and hypotension (18.5% vs 12.4%) were more common in finerenone-treated patients.

Finerenone blocks aldosterone receptors in the renal collecting duct, similar to spironolactone and eplerenone. Spironolactone was studied in patients with HFpEF in the TOMCAT study (N=3445), where it reduced heart failure hospitalizations (12% vs 14.2%, p=0.04) but did not achieve significance for the primary outcome, a composite of CVD events (18.6% vs 20.4%, p=0.14). However, a post-hoc analysis that excluded data from Russia and Georgia, where events were unusually low, found a significant benefit for the primary outcome.

The ACC 2023 HFpEF guidelines recommend spironolactone or eplerenone in most patients with volume overload. Finerenone appears to provide a similar benefit with the drawback of no generic and higher cost. Regardless of the MRA used, patients should be monitored closely for hyperkalemia and hypotension.

• Finerenone (Kerendia®) review
• Heart failure review

Some patients and providers assume Paxlovid helps to prevent COVID in exposed patients, and it is often prescribed for this purpose. To evaluate this use, researchers randomized 2736 asymptomatic adults who had been exposed to a household contact with COVID within 96 hours to Paxlovid for 5 or 10 days or matching placebo. Other inclusion criteria included no known history of COVID and a negative baseline COVID antigen test. Only 13% of participants had received one or more COVID vaccines, and 73% had at least one risk factor for severe COVID. At the end of the trial, the primary outcome, symptomatic COVID confirmed by PCR or antigen testing through 14 days, occurred in 2.6% of the Paxlovid 5-day group, 2.4% of the 10-day group, and 3.9% of the placebo group. All Paxlovid-placebo comparisons were nonsignificant.

This is the second negative Paxlovid study Pfizer has funded. A study published in April found that Paxlovid did not shorten the time to symptom resolution, compared to placebo, in a mix of vaccinated and unvaccinated adults with new-onset COVID. For COVID protection, vaccination continues to be the clear winner.

• Paxlovid vs Placebo for COVID Postexposure Prophylaxis, NEJM (2019)
• Paxlovid vs Placebo for COVID in Vaccinated and Unvaccinated Adults, NEJM (2019)

Tirzepatide, the blockbuster GLP/GIP weight-loss drug marketed as Zepbound, was recently compared to placebo in patients with NASH, also known as metabolic dysfunction–associated steatohepatitis or fatty liver disease. The SYNERGY-NASH trial randomized 190 patients with NASH and F2 or F3 fibrosis to three doses of tirzepatide - 5 mg, 10 mg, and 15 mg - or placebo. After 52 weeks, NASH resolution occurred in 44%, 56%, 62%, and 10%, respectively, while a decrease in fibrosis stage of ≥ 1 was seen in 55%, 51%, 51%, and 30% (all tirzepatide-placebo comparisons were significant). Tirzepatide-treated patients lost 11 - 16% of their body weight, depending on the dose. Drug discontinuations due to side effects were rare in all groups (≤4%).

NASH is driven by hepatocellular adiposity, so it is not surprising that tirzepatide-induced weight loss improved liver pathology. In a previous trial, semaglutide was significantly better than placebo for NASH resolution but not fibrosis improvement. [PMID 33185364]

Resmetirom is the only medication currently FDA-approved to treat NASH, and while results from different studies are not comparable linearly, nothing in resmetirom's pivotal trial suggests that it is superior to tirzepatide. Furthermore, it does not cause weight loss, giving it no benefit in other obesity-related conditions.

• Tirzepatide vs Placebo for NASH, NEJM (2024)