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PubMed1976

Clinical trial in post-addicts with oxilorphan (levo-BC-2605): a new narcotic antagonist.

Oxilorphan (levo-BC-2605) is a new, long-acting, narcotic antagonist that has agonist properties. Twenty-one (21) heroin addicts in Los Angeles were detoxified and given at least one oral dose of oxilorphan. Only three (14.3%) patients took daily doses for 14 days, which was the maximal time allowed for oxilorphan administration in this study. The remainder discontinued oxilorphan because of subjective side effects or for unknown reasons. Side effects most responsible for dropouts were dysphoria, insomnia, weakness, hallucinations, nausea, drowsiness and anorexia. Oxilorphan provided 24-hour protection with a single, oral dose, but subjective side effects encountered during inductiolinical trials with oxilorphan should be attempted with other addict populations to fully determine its potential therapeutic value.

Adult↗

PubMed2026

Real-world emergence of nirsevimab resistance in breakthrough infections with respiratory syncytial virus-B: a multicentre observational study in France.

BACKGROUND: Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infection in infants. Nirsevimab, a long-acting monoclonal antibody targeting a conserved epitope on the prefusion F protein (site Φ), has shown high efficacy in clinical trials and early real-world studies. Although widespread resistance has not been reported, concerns remain about the emergence of escape variants, particularly among RSV-B viruses. During the 2024-25 RSV season in France, RSV-B predominated, providing a unique opportunity to examine breakthrough infections with RSV-B and resistance at a large scale. The study aimed to characterise RSV escape from nirsevimab using genotypic and phenotypic methods. METHODS: This POLYRES-2 project was a multicentre, national, observational study conducted in hospital settings (inpatients and outpatients) across France during the 2024-25 RSV season. We included infants aged 1 year or under with a RT-PCR-confirmed RSV infection in routine care, regardless of whether they had received nirsevimab. Infants were identified through hospital virology laboratory databases. Each participating centre was requested to include a balanced number of nirsevimab-exposed and non-exposed infected infants throughout the study period. Clinical data were retrieved from electronic medical records. We compared RSV susceptibility to nirsevimab in infants who received nirsevimab with that in nirsevimab-naive infants. Respiratory samples were sequenced for full-length RSV genomes. To ensure reliability, phylogenetic and mutational analyses were restricted to high-quality sequences with greater than or equal to 90% genome coverage and complete reads across the nirsevimab-binding site. Clinical RSV isolates were tested for neutralisation by nirsevimab. We analysed F candidate substitutions using a fusion inhibition assay. The primary outcomes were presence of resistance-associated substitutions (RASs) in the RSV F protein (site Φ) and phenotypic resistance to nirsevimab. FINDINGS: Among 1023 RSV-infected infants, 858 (83·9%) had full-length RSV genome sequences: 419 (48·8%) from nirsevimab-treated breakthrough infections (212 [50·6%] RSV-A, 207 [49·4%] RSV-B) and 439 (51·2%) from nirsevimab-naive infants (192 [43·7%] RSV-A, 247 [56·3%] RSV-B). RASs were identified in two of 195 RSV-A breakthrough infections (1·0%) and in 23 of 184 RSV-B breakthrough infections (12·5%). In RSV-A, the only RAS was F:K209E, conferring intermediate resistance. In RSV-B, resistance was more frequent and diverse than in RSV-A: 12 of 23 (52.2%) resistant viruses carried a substitution at residue 208 (F:N208D, F:N208I, F:N208K, F:N208S, or F:N208Y). Additional novel substitutions, including F:I64V/F:K65E, F:K68I, F:L204S, and F:P205S, also mediated resistance. Notably, a resistant RSV-B variant (F:N208S) was detected almost 1 year after prophylaxis. No resistant RSV was detected in nirsevimab-naive infants. INTERPRETATION: Resistance to nirsevimab in RSV-B can emerge in real-world settings, affecting around 12% of breakthrough infections and showing greater diversity than previously recognised, although the clinical impact remains constrained by available evidence. Detection of resistant variants long after prophylaxis highlights the need for extended genomic surveillance. Integration of clinical and virological data will be essential to sustain the long-term effectiveness of RSV monoclonal antibody programmes. FUNDING: This study was supported by a grant from the Agence Nationale de Recherche sur le Sida et les hépatites virales - Maladies Infectieuses Emergentes and the French Ministry of Health and Prevention.

Humans↗

PubMed2024

Genotypic and phenotypic characterisation of respiratory syncytial virus after nirsevimab breakthrough infections: a large, multicentre, observational, real-world study.

BACKGROUND: Nirsevimab, a long-acting monoclonal antibody, has been approved for the prevention of respiratory syncytial virus (RSV) infection in infants. In France, more than 210 000 single doses were administered in infants younger than 1 year during the 2023-24 season. In this context, the selection and spread of escape variants might be a concern. Here, we aimed to characterise RSV associated with breakthrough infection. METHODS: We did a multicentre, national, observational study in France during the 2023-24 RSV season in RSV-infected infants (aged <1 year) who either received or did not receive a dose of nirsevimab before their first RSV season. We excluded infants with insufficient information about nirsevimab treatment or without parental consent. We used respiratory samples collected in each laboratory for full-length RSV RNA sequencing to analyse changes in the nirsevimab binding site Ø. We tested clinical RSV isolates for neutralisation by nirsevimab. We analysed F candidate substitutions by fusion-inhibition assay. FINDINGS: Of the 695 RSV infected infants, we analysed 545 (78%) full-length RSV genome sequences: 260 (48%) from nirsevimab-treated breakthrough infections (236 [91%] RSV-A and 24 [9%] RSV-B) and 285 (52%) from untreated RSV-infected infants (236 [83%] RSV-A and 49 [17%] RSV-B). Analysis of RSV-A did not reveal any substitution in site Ø known to be associated with resistance to nirsevimab. Two (8%) of 24 RSV-B breakthrough infections had resistance-associated substitutions: F:N208D (dominant resistance-associated substitution) and a newly described F:I64M plus F:K65R combination (minority resistance-associated substitution), both of which induced high levels of resistance in the fusion-inhibition assay. INTERPRETATION: This study is, to the best of our knowledge, the largest genotypic and phenotypic surveillance study of nirsevimab breakthrough infections to date. Nirsevimab breakthrough variants remain very rare despite the drug's widespread use. The detection of resistance-associated substitutions in the RSV-B F protein highlights the importance of active molecular surveillance. FUNDING: ANRS Maladies Infectieuses Emergentes and the French Ministry of Health and Prevention.

Humans↗

PubMed2026

Liposomal bupivacaine versus ropivacaine for surgical site infiltration in lumbar fusion: a prospective randomized controlled trial.

INTRODUCTION: Effective postoperative pain control after lumbar spine surgery remains challenging, and excessive opioid use is associated with adverse outcomes. Evidence comparing liposomal bupivacaine (LB) with conventional long-acting local anesthetics in spine surgery is limited. PATIENTS AND METHODS: In this single-center, prospective, randomized, patient- and outcome assessor-blinded trial, adult undergoing one- or two-level posterior lumbar decompression and fusion were assigned (1:1) to surgical site infiltration with either LB (266 mg) plus 25 mg plain bupivacaine (LB group) or ropivacaine (R group). The primary outcome was 72 h cumulative opioid consumption (morphine milligram equivalents, MME). Secondary outcomes included time-profile opioid consumption, pain scores, rescue analgesia, safety, and functional recovery. RESULTS: A total of 202 patients were included in the modified intention-to-treat analysis. Cumulative MME within 72 h was significantly lower in the LB group compared with the R group [43.0 (37.0, 58.0) mg vs. 58.0 (46.0, 73.0) mg], corresponding to a 22% relative reduction (GMR 0.78, 95% CI 0.71-0.85; p < 0.001). The reduction was most pronounced during 8-24 h and 24-48 h postoperatively. Overall pain scores at rest and with movement, as well as 72-h pain AUC, were lower in the LB group. No significant between-group differences were observed in rescue analgesia, adverse events and functional recovery. CONCLUSION: In patients undergoing one- or two-level posterior lumbar decompression and fusion, surgical site infiltration with an LB-based combined regimen, compared with ropivacaine monotherapy, reduced 72-h opioid consumption and cumulative postoperative pain burden without an observed increase in adverse events or impairment of early functional recovery.

Humans↗

PubMed2026

Single-slice Functional Lung MRI During Metronome-Paced Tachypnea Detects Changes in Regional Ventilation Dynamics After a Single Dose of Dual Bronchodilator Treatment in COPD.

Dual long-acting bronchodilators are a standard treatment in chronic obstructive pulmonary disease (COPD), aimed at alleviating dyspnea, improving exercise tolerance, and preventing exacerbations. Metronome-paced tachypnea (MPT) offers a feasible alternative to exercise testing for the evaluation of dynamic hyperinflation (DH) in COPD. Because MPT can be performed during MRI, its combination with single-slice phase-resolved functional lung (PREFUL) MRI provides a promising approach to investigate changes in regional ventilation dynamics induced by DH. This approach was evaluated in a randomized, investigator-blinded, placebo-controlled, single-dose (SD) crossover trial with a two-week extension of once daily dual bronchodilator medication, in which patients with stable COPD underwent PREFUL MRI during resting tidal breathing (RTB) and during MPT. During RTB, no significant improvements in MRI-derived parameters were observed after SD treatment compared with placebo. During MPT, however, regional ventilation, flow-volume loop correlation, its defect percentage, and end-expiratory lung area improved significantly after SD treatment compared to the placebo scan (all p < 0.02). After multi-dose treatment, five out of six measured parameters improved during MPT, when compared to the baseline scan without bronchodilator treatment (all p < 0.03). In contrast to RTB, PREFUL MRI during MPT was able to detect changes in COPD patients already after SD treatment. The combination of MPT and PREFUL MRI represents a promising method to evaluate the effects of dual bronchodilators on regional ventilation dynamics and hyperinflation.

Humans↗

PubMed2025

Antifungal treatment strategies and their impact on resistance development in clinical settings.

Invasive fungal diseases, particularly among immunocompromised patients, represent a growing clinical challenge due to limited therapeutic options, diagnostic delays and escalating antifungal resistance. Fungal pathogens employ diverse resistance mechanisms, including genetic mutations of antifungal target enzymes, biofilm formation, efflux pump overexpression and reduced drug penetration, which compromise the efficacy of clinically available antifungal classes. This review explores antifungal treatment modalities and evaluates approaches to mitigate resistance development. Advanced diagnostics and therapeutic drug monitoring are pivotal for enabling timely, targeted therapies and personalizing treatment plans, thus minimizing reliance on broad-spectrum agents. New antifungal agents, such as rezafungin, olorofim and fosmanogepix, along with long-acting and advanced formulations plus combination regimens, show substantial promise for managing resistance and improving treatment outcomes. Additionally, the development of immunotherapies and antifungal vaccines offers new avenues for bolstering host defences against fungal pathogens. Addressing antifungal resistance demands a multifaceted 'One Health' approach that integrates robust diagnostics, antifungal stewardship (AFS), precision medicine and collaborative global efforts. By advancing drug formulations, enhancing diagnostic tools and implementing forward-thinking AFS practices, the healthcare community can better tackle the escalating burden of fungal infections and deliver improved patient outcomes.

Antifungal Agents↗

PubMed2026

Same-day initiation of tenofovir alafenamide-based pre-exposure prophylaxis with drug-level feedback for transgender women in Uganda.

OBJECTIVE: To evaluate the feasibility and acceptability of same-day initiation of emtricitabine/tenofovir alafenamide (F/TAF) pre-exposure prophylaxis (PrEP) and test the impact of drug-level feedback on PrEP adherence among transgender women (TGW) in Uganda. DESIGN: Randomized controlled trial. METHODS: HIV-negative TGW were randomly assigned 1 : 1 to intervention (drug-level feedback with tailored adherence counseling) or standard-of-care (SOC), and followed quarterly for 12 months (November 2021-July 2023; NCT04491422). Quarterly clinic visits included demographic and socio-behavioral data collection, PrEP refills, STI testing, and quarterly PrEP adherence assessment using tenofovir levels in dried blood spots (DBS; long-term) and urine (short-term). RESULTS: We enrolled 200 TGW (100 per arm), median age 21 years. Same-day F/TAF PrEP initiation was 100%. Tenofovir detection in urine (intervention arm) was 79, 80, 85, and 70% at the 3, 6, 9, and 12-month visits, respectively. Tenofovir detection in DBS was 46, 40, 35, and 31% at 3, 6, 9, and 12 months, respectively. Median tenofovir DBS concentrations were 40.6 and 47.0 fmol/punch in intervention and SOC arms, respectively. There was no intervention effect on PrEP adherence (DBS tenofovir levels) [adjusted incidence rate ratio (aIRR) 1.06; 95% CI: 0.82-1.37]. Never being harassed by police for being transgender (aIRR 1.66; 95% CI: 1.24-2.23), history of taking daily medication for more than 7 days (aIRR 1.51; 95% CI: 1.18-1.93) and higher monthly income (aIRR 1.44; 95% CI: 1.10-2.04) were associated with PrEP adherence. CONCLUSION: Oral F/TAF PrEP adherence among TGW in Uganda was low and not affected by drug-level feedback or tailored adherence counseling. Long-acting injectable PrEP formulations should be considered for this population.

Humans↗

PubMed1976

Effects of phospholine iodide on the metabolites of the glycolytic, pentose phosphate and sorbitol pathways in the rabbit lens.

Steady-state concentrations of the key intermediates from the glycolytic, pentose phosphate, and sorbitol pathways as well as the pyridine nucleotides were measured from the lens after 0.25% phospholine iodide had been instilled into rabbits' eyes twice a day for 18 weeks. In the lenses of those rabbits which had received treatment in both eyes fructose-1,6-diphosphate and pyruvate levels were increased, whereas 6-phosphogluconate, sorbitol and alpha-glycer0phosphate concentrations were decreased. alpha-Ketoglutarate and concentrations and ratios of NAD+ and NADH did not show any changes. In contrast, NADPH and total NADP concentrations as well as the NADPH/NADP+ ratio were decreased, and therefore total NAD/total NADP ratio increased after treatment. It appears that instillation of long-acting 0.25% phospholine iodide into rabbits' eyes results in increased glycolytic activity in the lens in response to the increased energy demand, wheras the activities of other metabolic pathways are suppressed.

Animals↗

PubMed1977

The pharmacology of benoxaprofen (2-[4-chlorophenyl]-alpha-methyl-5-benzoxazole acetic acid), LRCL 3794, a new compound with antiinflammatory activity apparently unrelated to inhibition of prostaglandin synthesis.

Benoxaprofen is a potent and long-acting anti-inflammatory and antipyretic compound. Its anti-inflammatory activity has been demonstrated in carrageenan-induced oedema, in cellulose pellet granuloma and in both developing and established adjuvant arthritis tests in rats. Its antipyretic activity is greater than either aspirin or paracetamol in tests inducing pyrexia with yeast of 'E' pyrogen in rats and rabbits. Benoxaprofen has analgesic activity in tests where pain is accompanied by inflammation but not in other experimental models of pain. The weak prostaglandin synthetase inhibiting properties of this compound differentiate it from other acid anti-inflammatory compounds. The low ulcerogenic potential of benoxaprofen seen in animal models may be related to its relative inability to inhibit PG synthetase.

Analgesics↗

PubMed1977

Treatment of chronic schizophrenia.

The comprehensive treatment of schizophrenia requires the full resources of a clinical team that is able to offer treatment for the acute psychotic state in a hospital environment, and appropriate rehabilitation following resolution of the florid symptoms. Following a second or subsequent relapse, maintenance therapy with long-acting injections of depot antipsychotics will be required for an unknown period. Although drugs form an essential part of all treatments, it is essential to examine the environment for precipitating factors and to involve the patient's family in the rehabilitation. Recent studies have reported that some patients still have a relatively poor prognosis; although this proportion may be in the minority, the strain on the whole family of an even moderately handicapped patient can be enormous, and it is important to examine the needs of the whole family in evaluating care within the community. The effect of antipsychotic drugs is much wider that the mere control of acute symptoms and can influence the patterns of social behaviour and rehabilitation, in addition to offering protection against stress. The proper use of depot injections requires that they be kept under constant review. The current widespread practice of prescribing anti-cholinergic drugs on a prophylactic basis, or even as the inital treatment of extrapyramidal side-effects, needs revision.

Antipsychotic Agents↗

PubMed1978

Drugs and depression.

Moderate or severe depression is now one of the most common diseases of our time with a prevalence of nearly 3%. It seems likely that this prevalence has increased as a result of the wider use of drugs which have an effect on the neurotransmitters. Changes in the levels of these neurotransmitters in the central nervous system are thought to be the biochemical basis for the development of at least some depressive illnesses. Drug-induced depressions are more likely to occur in those individuals who are genetically predisposed to depression or who have had a previous depressive illness. Other groups who are particularly susceptible to these effects are the elderly. Many groups of drugs have a primary or secondary action on the central nervous system neurotransmitter function. Some 200 drugs have been claimed to cause depression in certain patients, but only a relatively small number precipitate depressive symptoms with any frequency. Those most commonly implicated are the long-acting antipsychotics, barbiturates, ethanol, oral contraceptives and antihypertensive agents. It is important to remember that some drugs, such as reserpine, cause depression as a side-effect during their therapeutic use whereas others, such as fenfluramine, cause depression mainly when they are withdrawn too rapidly. In those patients presenting with depression, it is important to review the current drug therapy in order to assess the part played by these drugs in the development of the depression. Following this assessment, drug therapy should be adjusted appropriately. However, a distinction must be made between the symptoms of depression, those physiological changes which occur during treatment with a variety of drugs, and the patient's reaction to the disease for which they are being treated.

Analgesics↗

PubMed2026

Preclinical evaluation of AL-001, a gene therapy for wet age-related macular degeneration.

BACKGROUND: Frequent intravitreal administration of antivascular endothelial growth factor Vascular endothelial growth factor agents remains a major limitation in the management of wet age-related macular degeneration (wAMD). This study evaluated whether suprachoroidal delivery of an engineered recombinant adeno-associated viral (rAAV)-aflibercept vector could achieve sustained, targeted expression with improved efficacy and safety compared with intravitreal administration. METHODS: AL-001, an engineered rAAV vector expressing aflibercept, was developed and characterized. Its expression profile was first assessed in New Zealand white rabbits following suprachoroidal space (SCS) injection. Efficacy, pharmacokinetics, and safety were then evaluated in a nonhuman primate model of laser-induced choroidal neovascularization (CNV), comparing SCS and intravitreal (IVT) administration routes. RESULTS: AL-001 efficiently expressed aflibercept in relevant ocular cells in vitro. In rabbits, SCS administration produced sustained aflibercept levels in ocular tissues. In the nonhuman primate CNV model, a single SCS injection of AL-001 showed favorable efficacy to IVT injection and a notable mild inflammatory response. At week 4, grade IV lesion incidence was 0% (0/48) after SCS administration versus 14.3% (6/42) after IVT administration (absolute difference, -14.3 percentage points; 95% CI, 3.7%-27.8%; P = 0.0258). Throughout follow-up, mean leakage area and grade IV lesion incidence remained 0 with SCS, versus IVT peaks of approximately 0.3 mm2 and 33.0%, respectively, declining to 0.03 mm2 and 2.0% by day 100. Both the medium and high doses decreased pathological vascular leakage and subretinal hyperreflective material. Vector administration preceded laser-induced CNV modeling, demonstrating that sustained intraocular aflibercept expression in the retina and choroid provided durable antiangiogenic protection. Pharmacokinetic analysis confirmed distinct ocular exposure profiles between routes, with viral genomes confined predominantly to the injected eye and no significant systemic accumulation. AL-001 was well tolerated, without sustained intraocular pressure elevation or severe ocular inflammation, and only mild-to-moderate treatment-emergent adverse events. Low pre-existing anti-AAV2 immunity and time-dependent neutralizing antibody responses postdosing, informing a translational model for patient stratification and redosing feasibility. CONCLUSION: Suprachoroidal administration of AL-001 is well tolerated and provides durable, targeted aflibercept expression with pronounced antiangiogenic efficacy. These results support AL-001 as a promising, long-acting therapeutic candidate for wAMD.

AAV↗

PubMed1976

High-dose treatment with neuroleptics in the acute phase of mental disease.

More than 300 patients have been observed during treatment with either flupenthixol, haloperidol, fluphenazine enanthate or perphenazine enanthate in high doses, whilst suffering from severe mental disease, usually of psychotic nature. Used correctly, high-dose treatment gives a rapid control of psychotic symptoms, an earlier discharge from the ward, and (when using long-acting neuroleptics) pharmacological control even during a follow up period. This means a social availability gain of 30-50%. We have not seen any severe somatic effects except those of parkinsonian type which can be treated successfully by the well trained psychiatrist and a skilled staff.

Antipsychotic Agents↗

PubMed1977

Comparison of rimiterol and terbutaline, given by aerosol, in a long-term study.

In a double-blind long-term study, regular inhalations of a short-acting selective beta2-stimulator, rimiterol, was compared with a long-acting one, terbutaline. The trial comprised 60 patients with chronic obstructive lung disease, all patients were on a small dose of an oral beta2-stimulator. Both drugs were regularly given in aerosol form with a minimum dose of three inhalations three times daily. The main purpose was to study subjective and objective side effects. Haematological, hepatic and renal functions were screened for toxicity. Consumption of spray was recorded. No side effects occurred. There was no evidence of development of isoprenaline resistance. The consumption of spray was the same in both groups. In this study, regular inhalation treatment of rimiterol seemed to be as effective as terbutaline in long-term bronchodilator therapy.

Aerosols↗

PubMedDate not supplied

Metabolism and disposition of l-alpha-acetylmethadol in the rat.

The metabolism and disposition of the long-acting narcotic analygesic l-alpha-acetylmethadol (LAAM) were studied in the rat. 3H-LAAM was administered to male and female rats at doses of 5 mg/kg po and iv, and 10 mg/kg po. LAAM was rapidly absorbed and extensively metabolized. Five metabolites-noracetylmethadol, dinoracetylmethadol, methadol, normethadol, and N-acetylnormethadol-were identified in plasma and urine. Feces were the major route of elimination for the parent drug and metabolites. Less than 20% of the administered dose was excreted in the urine and, of this, greater than 90% was in the form of conjugates or polar metabolites. There is an apparent sex-related difference in LAAM disposition in the rat. LAAM and metabolites tended to persist in higher levels in female rats as compared with male rats. Similarly, male rats tended to excrete the drug at a faster rate than did females.

Administration, Oral↗

PubMed1975

[Comparative study of a new antihistamine, mequitazine, and placebos].

In a double-blind trial lasting 2 weeks, a new, long-acting antihistamine, Mequitazine, and a placebo, were compared. 115 allergic patients participated in this experiment (mequitazine n = 56, placebo n = 59). Therapeutic results and the effect on diurnal alertness were evaluated by means of a questionnaire filled in daily by the patients. Whether considering the day by day results or the results of the entire treatment period, statistically, Mequitazine (10 mg/24 hrs) is very significantly more active than the placebo. The daytime drowsiness induced by Mequitazine is statistically no greater than that induced by the placebo, whether analyzed on a day by day basis or over the entire treatment period (P = 0.23). The side effects, 8 for Mequitazine, 5 for placebo, are mild and did not lead to discontinuation of the treatment in the Mequitazine group.

Adult↗

PubMed1977

Serum LH, FSH and testosterone response to the administration of a new LH-RH analog, D-Trp6-LH-RH, in normal men.

A long-acting superactive analog of LH-RH, D-Trp6-LH-RH was given to 23 normal men by several routes of administration (iv, im, sc, continuous infusion) and in increasing doses of 1 to 50 microgram. LH and FSH responses were obtained at doses as low as 2.5 microgram. The maximal absolute LH and FSH increment in response to a 10 microgram iv bolus injection of this analog was similar to 100 microgram of LH-RH. In addition, after administration of the analog the LH and FSH level was maintained at a higher than basal level for at least 8 hours. With a 50 microgram iv bolus injection, from 30 minutes onwards the increases in LH levels were significantly greater (P less than 0.05) than those elicited by the 10 microgram dose for at least 8 hours. Maximum release of LH and RSH was observed when this same dose was given as continuous infusion for 8 hours (P less than 0.05). There seemed to be no significant differences between the im and sc routes. Following the administration of the D-Trp6-LH-RH, testosterone levels were maintained above the normal values (P less than 0.02). The high potency and prolonged duration of action of this compound suggest its potential usefulness for increasing testosterone levels and for stimulation of spermatogenesis in men.

Follicle Stimulating Hormone↗

PubMed1977

The medical management of angina pectoris.

The availability of excellent short-acting and long-acting drugs for the treatment of angina pectoris needs to be emphasized. Properly used in conjunction with other measures such as the treatment of hypertension and a graded exercise routine, they provide, for most patients with angina, a tested therapeutic program that is remarkably effective, well-tolerated, appropriate for long-term outpatient use, and quite inexpensive.

Adrenergic beta-Antagonists↗