pregabalin and Heart-Failure

Pregabalin is used in the treatment of postherpetic neuralgia, diabetic neuropathic pain, partial seizures, anxiety disorders and fibromyalgia. Recognized adverse effects associated with its use include cognitive impairment, somnolence and dizziness. Heart failure associated with pregabalin has been described, however the strength of this association has not been well characterized. To examine this further, we will conduct a systematic review of the risk of heart failure and edema associated with use of pregabalin.. We will include all studies (experimental, quasi-experimental, observational, case series/reports, drug regulatory reports) that examine the use of pregabalin compared to placebo, gabapentin or conventional care. Our primary outcome is heart failure and the secondary outcomes include edema and weight gain. We will search electronic databases (MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials), and grey literature sources (trial registries, conference abstracts) to identify relevant studies. To ensure literature saturation, we will contact drug manufacturers, conduct forward citation searching, and scan the reference lists of key articles and included studies. We will not restrict inclusion by language or publication status.Two reviewers will screen citations (titles and abstracts) and full-text articles, conduct data abstraction, and appraise risk of bias. Random-effects meta-analysis will be conducted if the studies are deemed heterogeneous in terms of clinical, statistical and methodological factors but still suitable for meta-analysis.. The results of this review will assist physicians to better appreciate pregabalin's risk for edema or congestive heart failure and will be pertinent to the thousands of patients worldwide who are administered this medication.Our protocol was registered in the PROSPERO database (CRD42012002948).

Topics: Edema; gamma-Aminobutyric Acid; Heart Failure; Humans; Outcome Assessment, Health Care; Pregabalin; Research Design; Review Literature as Topic; Risk; Weight Gain

Pregabalin is an analog of the neurotransmitter gamma-aminobutyric acid that exhibits analgesic, anticonvulsant, and anxiolytic properties. Owing to its pharmacologic properties, the drug has been used worldwide in the management of diabetic peripheral neuropathy, postherpetic neuralgia, generalized anxiety disorder, and social anxiety disorder. Although central nervous system disturbances account for the majority of pregabalin's side effects, dose-dependent peripheral edema and weight gain have also been reported. Recently, three case reports have been published documenting a possible association between pregabalin administration and chronic heart failure decompensation. We present three additional cases of possible heart failure exacerbation in patients with clinically stable heart failure who received pregabalin for neuropathic pain. Additionally, we review the literature addressing the nature and possible etiology for this adverse effect.

Topics: Aged; Analgesics; Female; gamma-Aminobutyric Acid; Heart Failure; Humans; Male; Middle Aged; Neuralgia; Pregabalin

Gabapentinoids are ligands of the α2-δ subunit of voltage-gated calcium channels (Cav) that have been associated with a risk of peripheral edema and acute heart failure in connection with a potentially dual mechanism, vascular and cardiac.. All cases of peripheral edema or heart failure involving gabapentin or pregabalin reported to the French Pharmacovigilance Centers between January 1, 1994 and April 30, 2020 were included to describe their onset patterns (e.g., time to onset). Based on these data, we investigated the impact of gabapentinoids on the myogenic tone of rat third-order mesenteric arteries and on the electrophysiological properties of rat ventricular cardiomyocytes.. A total of 58 reports were included (gabapentin n = 5, pregabalin n = 53). The female-to-male ratio was 4:1 and the median age was 77 years (IQR 57-85, range 32-95). The median time to onset were 23 days (IQR 10-54) and 17 days (IQR 3-30) for non-cardiogenic edema and acute heart failure, respectively. Cardiogenic and non-cardiogenic peripheral edema occurred frequently after a dose escalation (27/45, 60%), and the course was rapidly favorable after discontinuation of gabapentinoid (median 7 days, IQR 5-13). On rat mesenteric arteries, gabapentinoids significantly decreased the myogenic tone to the same extent as verapamil and nifedipine. Acute application of gabapentinoids had no significant effect on Ca. Gabapentinoids can cause concentration-dependent peripheral edema of early onset. The primary mechanism of non-cardiogenic peripheral edema is vasodilatory edema secondary to altered myogenic tone, independent of Ca

Topics: Aged; Aged, 80 and over; Animal Experimentation; Animals; Edema; Female; Gabapentin; Heart Failure; Humans; Male; Middle Aged; Pharmacovigilance; Pregabalin; Rats

Gabapentin and pregabalin are commonly prescribed medications to treat pain in patients with diabetic neuropathy. Gabapentin and pregabalin can cause fluid retention, which is hypothesized to be associated with cardiovascular diseases. However, whether long-term use of gabapentin and pregabalin is associated with adverse cardiovascular diseases remains unknown. This study aims to examine the association between gabapentin use, pregabalin use and several adverse cardiovascular events.. This retrospective cohort study used propensity score matching within patient electronic health records (EHRs) from a multicenter database with 106 million patients from 69 health care organizations in the US. The study population comprised 210,064 patients who had a diagnosis of diabetic neuropathy and were prescribed diabetic neuropathy medications in their EHRs. The exposure cohort comprised patients who were prescribed gabapentin or pregabalin to treat diabetic neuropathy. The comparison cohort comprised patients who were not prescribed either gabapentin or pregabalin but were prescribed other drugs to treat diabetic neuropathy. The outcomes of interest were myocardial infarcts, strokes, heart failure, peripheral vascular disease, and venous thromboembolic events. We calculated hazard ratios (HRs) and 95% confidence intervals (CIs) for 3-month and 5-year risk for adverse cardiovascular events between the propensity score-matched cohorts.. Both gabapentin and pregabalin were associated with increased risk of 5-year adverse cardiovascular events compared with the comparison group. In patients prescribed gabapentin, the highest risk was observed for deep venous thrombosis (HR: 1.58, 95% CI 1.37-1.82), followed by pulmonary embolism (HR: 1.5, 95% CI 1.27-1.76), peripheral vascular disease (HR: 1.37, 95% CI 1.27-1.47), stroke (HR: 1.31, 95% CI 1.2-1.43), myocardial infarction (HR: 1.25, 95% CI 1.14-1.38) and heart failure (HR: 1.14, 95% CI 1.07-1.21). In patients prescribed pregabalin, the highest risk was observed for deep venous thrombosis (HR: 1.57, 95% CI 1.31-1.88), followed by peripheral vascular disease (HR: 1.35, 95% CI 1.22-1.49), myocardial infarction (HR: 1.29, 95% CI 1.13-1.47), pulmonary embolism (HR: 1.28, 95% CI 1.04-1.59), stroke (HR: 1.26, 95% CI 1.12-1.42), and heart failure (HR: 1.2, 95% CI 1.11-1.3). There were significant associations between short-term (3 month) gabapentin use and heart failure, myocardial infarction, peripheral vascular disease, deep venous thrombosis, and pulmonary embolism. Short-term (3 month) pregabalin use was associated with deep venous thrombosis, peripheral vascular disease.. In patients with diabetic neuropathy who were prescribed gabapentin and pregabalin, there is an increased risk for heart failure, myocardial infarction, peripheral vascular disease, stroke, deep venous thrombosis, and pulmonary embolism with long-term use. Our findings suggest that increased risk for adverse cardiovascular events, along with other side effects, the efficacy of pain control and the degree of tolerance of the patient, should be considered when prescribing gabapentin and pregabalin long-term in patients with diabetic neuropathy.

Topics: Amines; Analgesics; Cardiovascular Diseases; Cyclohexanecarboxylic Acids; Diabetic Neuropathies; Gabapentin; gamma-Aminobutyric Acid; Heart Disease Risk Factors; Heart Failure; Humans; Myocardial Infarction; Pain; Peripheral Vascular Diseases; Pregabalin; Pulmonary Embolism; Retrospective Studies; Risk Factors; Stroke

Concerns regarding the increased risk of worsening heart failure with pregabalin have been raised. We assessed the association between use of pregabalin and risk of worsening heart failure in routine clinical practice.. We conducted a population-based cohort study in Denmark using data from nationwide registers, from 1 January 2008 to 31 December 2017. The study population consisted of patients 50 years of age or older with a diagnosis of heart failure who were new users of pregabalin or gabapentin (active comparator). We matched a total of 1395 new users of pregabalin to 1395 new users of gabapentin on a propensity score based on 55 covariates. Using proportional hazards regression, we estimated hazard ratios (HRs) for worsening heart failure (hospitalization with, or death from, heart failure) within 90 days of the start of treatment.. We observed 33 patients with worsening heart failure among users of pregabalin [incidence rate (IR) 105.7 per 1000 person-years] versus 43 patients among users of gabapentin (IR 133.8 per 1000 person-years), corresponding to an HR of 0.79 [95% confidence interval (CI) 0.50-1.23]. The corresponding absolute risk difference was - 28.6 (95% CI - 66.8 to 31.3) per 1000 person-years. In sensitivity analysis using duloxetine as an alternative active comparator, including 847 new users of pregabalin and 847 new users of duloxetine, the results were similar (HR 1.08, 95% CI 0.60-1.94).. The present study found no evidence to support an association between the use of pregabalin and increased risk of worsening heart failure, compared with gabapentin and duloxetine.

Topics: Adverse Drug Reaction Reporting Systems; Aged; Aged, 80 and over; Analgesics; Cohort Studies; Denmark; Female; Fibromyalgia; Heart Failure; Humans; Male; Middle Aged; Pregabalin; Propensity Score; Proportional Hazards Models; Registries; Risk Factors

Pregabalin (PRG) is highly effective in the treatment of epilepsy, neuropathic pain and anxiety disorders. Despite its potential benefits, PRG administration has been reported to induce or exacerbate heart failure (HF). It has been previously documented that overactivation of the renin angiotensin system (RAS) is involved in HF pathophysiological mechanism. The target of the current study was to examine the possible cardioprotective effect of telmisartan (Tel), an angiotensin II type 1 receptor (AT1R) blocker, compared with that of captopril (Cap), an angiotensin converting enzyme (ACE) inhibitor, in ameliorating PRG-induced HF in rats by assessing morphometric, echocardiographic and histopathological parameters. Furthermore, to investigate the role of RAS blockade by the two drugs in guarding against PRG-induced changes in cardiac angiotensin 1-7 (Ang 1-7) and angiotensin II (Ang II) levels, in addition to myocardial expression of ACE2, ACE, Mas receptor (MasR) and AT1R. Results showed that PRG administration induced morphometric, echocardiographic and histopathological deleterious alterations and significantly elevated cardiac Ang II, ACE and AT1R levels, while reduced Ang 1-7, ACE2 and MasR cardiac levels. Concurrent treatment with either Tel or Cap reversed PRG-induced morphometric, echocardiographic and histopathological abnormalities and revealed prominent protection against PRG-induced HF via downregulation of ACE/Ang II/AT1R and upregulation of ACE2/Ang 1-7/MasR axes. These are the first findings to demonstrate that the potential benefits of Tel and Cap are mediated by counteracting the altered balance between the RAS axes induced by PRG. Hence; Tel and Cap may attenuate PRG-induced HF partially through stimulation of ACE2/Ang 1-7/MasR pathway.

Topics: Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme 2; Angiotensin-Converting Enzyme Inhibitors; Animals; Captopril; Cyclic AMP-Dependent Protein Kinases; Drug Therapy, Combination; Echocardiography; Heart Failure; Male; Myocardium; Natriuretic Peptide, Brain; Peptide Fragments; Peptidyl-Dipeptidase A; Phosphatidylinositol 3-Kinases; Pregabalin; Proto-Oncogene Mas; Proto-Oncogene Proteins; Rats, Sprague-Dawley; Receptor, Angiotensin, Type 1; Receptors, G-Protein-Coupled; Telmisartan

The anticonvulsant pregabalin is increasingly prescribed for pain, seizures, and psychiatric disorders. Although evidence suggests pregabalin can cause edema and heart failure, its cardiac safety profile in clinical practice is unknown. We sought to examine the risk of heart failure among older patients receiving pregabalin compared to those receiving gabapentin.. We conducted a population-based cohort study of Ontarians aged 66 and older with a history of seizure who received pregabalin or gabapentin between April 2013 and March 2014. We used propensity scores to match patients commencing pregabalin to those commencing gabapentin. The primary outcome was an emergency department visit or hospitalization for heart failure within 90 days.. We studied 9855 patients who initiated pregabalin and an equal number treated with gabapentin. In the primary analysis, we found no difference in the risk of heart failure with pregabalin compared to gabapentin (1.2% versus 1.3%, hazard ratio of 0.77; 95% CI 0.58-1.03). Secondary analyses stratified for baseline history of heart failure yielded similar findings.. In a large cohort of older patients with a seizure disorder, pregabalin was not associated with an increased risk of heart failure relative to gabapentin.

Topics: Aged; Aged, 80 and over; Amines; Anticonvulsants; Calcium Channel Blockers; Cohort Studies; Cyclohexanecarboxylic Acids; Female; Gabapentin; gamma-Aminobutyric Acid; Heart Failure; Humans; Male; Ontario; Population Surveillance; Pregabalin; Retrospective Studies; Seizures

Topics: Alzheimer Disease; Analgesics; Cooperative Behavior; gamma-Aminobutyric Acid; Geriatrics; Germany; Health Services Needs and Demand; Heart Failure; Hospice Care; Humans; Interdisciplinary Communication; Neoplasms; Pain Management; Palliative Care; Patient Participation; Physician-Patient Relations; Pregabalin; Professional-Family Relations; Pruritus; Terminal Care; Uremia

Pregabalin and gabapentin are widely used analgesic, anticonvulsant and anxiolytic agents as they are relatively reliable and easily tolerated. However, they may cause some side effects such as dizziness, somnolence, dose-dependent peripheral edema, and weight gain, which may cause patients to abandon their use. Furthermore, there are a few reports in the literature addressing elderly patients with serious chronic disease and cardiac history, who develop heart failure during pregabalin application. In this report, we present a patient with no cardiac history treated with 300 mg/kg pregabalin due to neuropathic pain, who developed peripheral and then central edema, which were determined after advanced investigations. After stopping pregabalin, the situation regressed. Then, peripheral edema developed associated with the recommended dose of gabapentin, which was used in place of pregabalin. Despite the lack of any published evidence, the New York Heart Association issued a warning about using caution when prescribing pregabalin to type III-IV heart failure patients. Though the effect mechanisms of pregabalin and gabapentin are not well known, the calcium channel relationship may lead to these side effects. In summary, we believe that pregabalin and gabapentin, which is mostly used nowadays, should be administered with care not only in patients with advanced cardiac pathology but also in all patients, due to the potential side effects.

Topics: Amines; Analgesics; Back Pain; Cyclohexanecarboxylic Acids; Diagnosis, Differential; Edema; Female; Gabapentin; gamma-Aminobutyric Acid; Heart Failure; Humans; Middle Aged; Neuralgia; Pregabalin; Tramadol

Topics: Aged; Anticonvulsants; Bumetanide; Chronic Disease; gamma-Aminobutyric Acid; Heart Failure; Herpes Zoster; Humans; Male; Neuralgia, Postherpetic; Pregabalin; Treatment Outcome; Weight Gain

Pregabalin is similar in structure to gamma-aminobutyric acid. It is used for neuropathic pain, generalized anxiety disorders and as an adjunct therapy for partial seizures. Tachycardia is a rare side-effect. A 92-year-old patient with a history of paroxystic fibrillation was hospitalised for zoster. She developed a sinusal tachycardia followed by atrial fibrillation and congestive heart failure 15 h after a first dose of pregabalin. The imputation was considered as plausible. Even though the mechanism remains unclear, pregabalin might induce tachycardia in predisposed old patients.

Topics: Aged, 80 and over; Amines; Analgesics; Atrial Fibrillation; Cyclohexanecarboxylic Acids; Female; Gabapentin; gamma-Aminobutyric Acid; Heart Failure; Herpes Zoster; Humans; Neuritis; Pregabalin; Tachycardia, Paroxysmal

Topics: Aged; Anticonvulsants; gamma-Aminobutyric Acid; Heart Failure; Humans; Male; Middle Aged; Neuralgia; Pregabalin; Treatment Outcome

A case of a 62-year-old woman presenting with a 20-year history of vulvodynia previously unresponsive to medical treatment is described. The epidemiology, phenomenology and medical management of vulvodynia is reviewed. The case presentation illustrates the role of pregabalin in successful medical management of this chronic pain disorder, as well as the management of common psychiatric morbidities associated with this condition.

Topics: Amitriptyline; Analgesics; Anti-Ulcer Agents; Anticoagulants; Antidepressive Agents; Anxiety; Cardiotonic Agents; Cataract; Cataract Extraction; Cholecystectomy; Chronic Disease; Citalopram; Digoxin; Female; gamma-Aminobutyric Acid; Heart Failure; Humans; Hypertension; Hysterectomy; Lorazepam; Middle Aged; Mitral Valve Insufficiency; Omeprazole; Ovarian Neoplasms; Pain; Pregabalin; Sterilization, Tubal; Stomach Diseases; Vulvar Diseases

Topics: Amyloid; Analgesics; Anticonvulsants; Antiparkinson Agents; Diabetes Mellitus, Type 2; Diphtheria-Tetanus-Pertussis Vaccine; Drug Approval; Drug Combinations; Drug Therapy; Drug-Related Side Effects and Adverse Reactions; Exenatide; gamma-Aminobutyric Acid; Heart Failure; Humans; Hydralazine; Hypoglycemic Agents; Indenes; Indoles; Islet Amyloid Polypeptide; Isosorbide Dinitrate; Patient Education as Topic; Patient Selection; Peptides; Pregabalin; Sleep Wake Disorders; United States; United States Food and Drug Administration; Venoms