Lung Med Linked To Heart Attack And Deaths
4 CommentsBy Ed Silverman // September 23rd, 2008 // 9:22 pm
The blockbuster inhaled lung medication Spiriva, which is sold by Pfizer and Boehringer Ingelheim, significantly increased the risk of heart attack, stroke and death from heart disease, according to a meta-analysis of randomized trials published in the Journal of the American Medical Association.
Patients who took Spiriva or an older, generic drug called ipratropium, had a 58 percent higher risk, according to the study. The drug is an anticholinergic agent used to treat chronic obstructive pulmonary disease, which is the fourth leading causing of chronic illness and death in the US. Boehringer also sells ipratropium under the brand name Atrovent. Here is the study (subscription may be required).
“What this means is a reassessment of the cardiovascular safety of these agents is needed,” the study’s lead author Sonal Singh, assistant professor of internal medicine at Wake Forest University tells Bloomberg News. “This study is questioning whether this drug is safe for COPD patients. Regulatory reaction is needed to explain this risk.”
In a joint statement, Pfizer and Boehringer Ingelheim maintain their analysis of 30 studies involving 19,545 patients found no increased risk of heart attack, stroke or death from any cause among the chronic lung-disease patients taking Spiriva. The results of the study, called Uplift, will be presented on Oct. 5 during the European Respiratory Society 2008 Annual Congress.
“Once the complete study report for UPLIFT is submitted, the FDA plans to thoroughly review the data to confirm the preliminary findings for UPLIFT and also review all other available information,” an FDA spokesman tells Bloomberg.
Meanwhile, a Veterans Affairs study published last week in Annals of Internal Medicine found patients with COPD who used ipratropium had a 30 percent higher risk of dying from heart complications than those who took albuterol, an inhaler that relaxes breathing muscles, or no med, Bloomberg points out. Those on the treatment also had an 11 percent increased risk of dying from any cause.
The latest analysis indicated that inhaled anticholinergics significantly increased the risk, by 58 percent, of cardiovascular death, heart attack, or stroke (1.8 percent vs. 1.2 percent for controls). Among individual components of the primary outcome, inhaled anticholinergics significantly increased the risk of heart attack by 53 percent (1.2 percent vs. 0.8 percent for controls) and also significantly increased (by 80 percent) the risk of cardiovascular death (0.9 percent vs. 0.5 percent for controls).
Justice in MI
How does the active ingredient in Spiriva compare with the non-steroid part of Advair? Are they in the same essential class - also anticholinergic? Are there relevant differences? Thanks.
cut and paste
Spiriva:
Tiotropium bromide is a long-acting antimuscarinic and anticholinergic agent with the same affinity for muscarinic receptors, M(1) to M(5). It inhibits M(3) receptors at the smooth muscle promoting bronchodilation.
Advair:
Fluticasone propionate is a synthetic trifluorinated corticosteroid with powerful anti-inflammatory effects. It is a human glucocorticoid receptor agonist that inhibits multiple cell types and mediator production or secretion involved in asthmatic response.
Salmeterol xinafoate, a long-acting beta(2)-adrenergic agonist, stimulates intracellular adenyl cyclase in catalyzing the conversion of adenosine triphosphate (ATP) to cyclic-3′,5′-adenosine monophosphate (cyclic AMP). The increased cyclic AMP levels results in the relaxation of bronchial smooth muscle and inhibition of the release of mediators of instantaneous hypersensitivity from mast cells .
BATMAN
Drug classes in Advair are a steroid and long acting beta-2 agonist while Spiriva is a quaternary anti-cholinergic. This study raises the alarm bell for the anti-chloinergics like Spiriva and Atrovent.
bw
a more physiologically specific (and somewhat basic) answer to your question.
the ‘non-steroid’ component to advair, is salmeterol, a long-acting beta-adrenoceptor agonist.
adrenoceptors responsd to epinephrine (aka adrenaline), the major neurotransmitter and hormone released during sympathetic nervous system stimulation (the so-called flight/fight response).
stimulating these receptors (such as with salmeterol) causes increased flow through the airways, most-likely through relaxation of smooth muscle (where adrenoceptors have been localized) in the lung.
tiotroprium and ipratroprium, the active ingredients in spiriva and atrovent are anti-cholinergic agents. they antagonize acetylcholine receptors, in this case those found on muscle in the lung.
acetylcholine is the primary neurotransmitter at the neuromuscular junction–the connection between your nervous system and your muscles.
blocking these receptors at the lung, will decrease any nervous system control of the smooth muscle, and thereby allow dilation of the airways.
these two products have similar effects on tissue (namely airway smooth muscle), but do so through separate physiological pathways.
we could get further into how acetylcholine receptors and adrenoceptors specifically alter ability of smooth muscle to contract, but that may be a bit too much for this comment.