FDA: Long-term proton pump inhibitor use linked with hypomagnesemia
The FDA has issued a public safety communication warning that the long-term use of prescription proton pump inhibitors is potentially associated with low magnesium levels.
Citing a review of 38 cases from the Adverse Event Reporting System and 23 cases from medical literature, the agency determined there was an association between hypomagnesemia-related adverse events in adult patients who had been taking proton pump inhibitors (PPIs) for at least 3 months. Most of the events occurred after 1 year of taking PPIs, and approximately one quarter of the cases required the discontinuation of PPI treatment (as well as magnesium supplementation). The agency also noted that since hypomagnesemia is likely under-reported and under-recognized, available data was insufficient to quantify an incidence rate.
Among the clinically serious events reported in the review were tetany, seizures, tremors, carpo-pedal spasm, atrial fibrillation, supraventricular tachycardia and abnormal QT interval.
The FDA communication said that the mechanism responsible for the association was not known, and recommended that patients on PPIs exhibiting symptoms of hypomagnesemia first talk to their health care providers before discontinuing any prescription PPI regimens.
“Health care professionals should consider obtaining serum magnesium levels prior to initiation of prescription PPI treatment in patients expected to be on these drugs for long periods of time, as well as patients who take PPIs with medications such as digoxin, diuretics or drugs that may cause hypomagnesemia,” the agency wrote in the announcement. “For patients taking digoxin, this is especially important because low magnesium levels increase the likelihood of serious side effects.”
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Antihypertensive treatment improved outcomes in non-hypertensive patients with CVD
Thompson A. JAMA. 2011;305:913-922.
Ventura H. JAMA. 2011;305:940-941.
Rates of all-cause mortality, stroke, congestive HF and composite CVD events were reduced in CVD patients without hypertension who were treated with antihypertensive medication, meta-analysis data suggested.
In the analysis, investigators searched databases for randomized controlled trials that analyzed the use of antihypertensive treatment for the prevention of CVD events in those with systolic BP of less than 140 mm Hg or diastolic BP of less than 90 mm Hg. The final group of studies included in the analysis (n=25) featured 64,162 patients without hypertension.
Researchers found that compared with controls, participants who received antihypertensive medications had pooled RR reductions in stroke (RR=0.77; 95% CI, 0.61-0.98), congestive HF (RR=0.71; 95% CI, 0.65-0.77), MI (RR=0.80; 95% CI, 0.69-0.93), CVD mortality (RR=0.83; 95% CI, 0.69-0.99), composite CVD events (RR=0.85; 95% CI, 0.80-0.90) and all-cause mortality from random-effects models (RR=0.87; 95% CI, 0.80-0.95). This translated to an absolute risk reduction per 1,000 people of –7.7 for stroke, -43.6 for chronic HF events, -13.3 for MI, -27.1 for composite CVD events, -15.4 for CVD mortality and -13.7 for all-cause mortality.
“Our results show that persons with a history of CVD but with BPs in the normal and prehypertensive ranges can obtain significant benefit from antihypertensive treatments,” the researchers wrote. “Additional randomized trial data are necessary to assess these outcomes in patients without CVD clinical recommendations.”
In an accompanying editorial, Hector O. Ventura, MD, with the John Ochsner Heart and Vascular Institute, New Orleans, and Carl J. Lavie, MD, with the University of Queensland School of Medicine, Brisbane, Australia, said this study adds to the understanding of treatment benefits with agents designed to lower BP among patients with CVD.
“The clinical importance of this study is clear: Pharmacological intervention in patients with CVD and BP levels less than 140/90 mm Hg is associated with a decreased risk of CV morbidity and mortality,” they said. “However, this study does not determine whether lowering BP levels is the reason for improved clinical outcomes. These agents may improve clinical outcomes through multiple other mechanisms (eg, hemodynamic effects unrelated to BP, neurohormonal effects and tissue-level effects).”
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Meta-analysis: Glycoprotein IIb/IIIa inhibitors linked with reduced nonfatal MI in elective PCI
Bhatt D. J Am Coll Cardiol. 2011;57:1200-1201.
Winchester D. J Am Coll Cardiol. 2011;57:1190-1199.
Results from a meta-analysis suggested that glycoprotein IIb/IIIa inhibitors are associated with reduced nonfatal MI and a nonsignificant increase in major bleeding in patients undergoing elective percutaneous coronary intervention.
Researchers identified 22 studies from a search of Medline, Cochrane and ClinicalTrials.gov databases that included patients undergoing elective PCI who were randomly assigned to glycoprotein IIb/IIIa (GPIIb/IIIa) inhibitors vs. controls. The 22 study populations yielded 10,123 patients. They then looked at 30-day outcomes and used a DerSimonian-Laird model to construct random effects summary RRs and CIs.
According to the results, the incidence of MI with GPIIb/IIIa inhibitors was 5.1% vs. 8.3% with controls (RR=0.66; 95% CI, 0.55-0.79) across the studies, and the results were no different when the analysis was restricted to placebo-controlled trials. The incidence of major bleeding was 1.2% with GPIIb/IIIa inhibitors vs. 0.9% with controls (RR=1.37; 95% CI, 0.83-2.25), and this failed to attain statistical significance. The difference in minor bleeding was more significant, however (3% with GPIIb/IIIa inhibitors vs. 1.7% with controls; RR=1.70; 95% CI, 1.28-2.26). All-cause mortality within 30 days did not differ between the two populations (0.3% with GPIIb/IIIa inhibitors vs. 0.5% with controls; RR=0.70; 95% CI, 0.36-1.33).
“In the current era of elective PCI performed with stents and thienopyridines, [GPIIb/IIIa inhibitors] reduced nonfatal MI without a notable increase in major bleeding,” the researchers concluded. “However, these agents increase minor bleeding and thrombocytopenia. Overall, the use of [GPIIb/IIIa inhibitors] during elective modern PCI seems to be safe and effective.”
In an accompanying editorial, Deepak L. Bhatt, MD, of the VA Boston Healthcare System and Brigham and Women’s Hospital, said the necessity of the routine use of GPIIb/IIIa inhibitors has been challenged in the context of stenting with adenosine diphosphate receptor antagonists, but the potential role of GPIIb/IIIa inhibitors in patients undergoing non-urgent PCI was far from outdated.
“This meta-analysis demonstrates that even on a background of aspirin, standard thienopyridine regimens and heparin — the PCI cocktail most commonly used worldwide — [GPIIb/IIIa inhibitors] continue to have an important potential role,” Bhatt wrote. “Notably, this data set further validates the concept that additional platelet inhibition is warranted beyond that provided by aspirin and standard-dose thienopyridines. Whether this in fact will be [GPIIb/IIIa inhibitors] or one of the other novel antiplatelet regimens remains to be seen.”