Sonora semiannulata

Number of Pages: 4Integrative BiologyGeological Science

Phylogeny of plecotine bats (Chiroptera: “Vespertilionidae”): summary of the evidence and proposal of a logically consistent taxonomy

Using standard phylogenetic techniques, 25 transformation series of morphological characters and 11 of karyological characters are evaluated in an attempt to recover the phylogenetic history of plecotine vespertilionid bats. Plecotini contains four genera in the topology (Euderma (Barbastella (Plecotus Corynorhinus))). The Plecotini of Hill and Harrison (1987), including Rhogeessa, Baeodon, Nycticeius, and Otonycteris, is rejected because this view is based solely on subjective evaluations of bacular overall similarity, and is clearly in disagreement with other lines of evidence from anatomy and karyology. Idionycteris is synonymized with Euderma because I. phyllotis and E. maculatum are sister species. Corynorhinus is removed from the synonymy of Plecotus. The relationships within Corynorhinus and Plecotus are not resolved

THE AMPHIBIAN TREE OF LIFE

The evidentiary basis of the currently accepted classification of living amphibians is discussed and shown not to warrant the degree of authority conferred on it by use and tradition. A new taxonomy of living amphibians is proposed to correct the deficiencies of the old one. This new taxonomy is based on the largest phylogenetic analysis of living Amphibia so far accomplished. We combined the comparative anatomical character evidence of Haas (2003) with DNA sequences from the mitochondrial transcription unit H1 (12S and 16S ribosomal RNA and tRNAValine genes, ø 2,400 bp of mitochondrial sequences) and the nuclear genes histone H3, rhodopsin, tyrosinase, and seven in absentia, and the large ribosomal subunit 28S (ø 2,300 bp of nuclear sequences; ca. 1.8 million base pairs; x¯ 5 3.7 kb/terminal). The dataset includes 532 terminals sampled from 522 species representative of the global diversity of amphibians as well as seven of the closest living relatives of amphibians for outgroup comparisons. The primary purpose of our taxon sampling strategy was to provide strong tests of the monophyly of all ‘‘family-group’’ taxa. All currently recognized nominal families and subfamilies were sampled, with the exception of Protohynobiinae (Hynobiidae). Many of the currently recognized genera were also sampled. Although we discuss the monophyly of genera, and provide remedies for nonmonophyly where possible, we also make recommendations for future research. A parsimony analysis was performed under Direct Optimization, which simultaneously optimizes nucleotide homology (alignment) and tree costs, using the same set of assumptions throughout the analysis. Multiple search algorithms were run in the program POY over a period of seven months of computing time on the AMNH Parallel Computing Cluster. Results demonstrate that the following major taxonomic groups, as currently recognized, are nonmonophyletic: Ichthyophiidae (paraphyletic with respect to Uraeotyphlidae), Caeciliidae (paraphyletic with respect to Typhlonectidae and Scolecomorphidae), Salamandroidea (paraphyletic with respect to Sirenidae), Leiopelmatanura (paraphyletic with respect to Ascaphidae), Discoglossanura (paraphyletic with respect to Bombinatoridae), Mesobatrachia (paraphyletic with respect to Neobatrachia), Pipanura (paraphyletic with respect to Bombinatoridae and Discoglossidae/Alytidae), Hyloidea (in the sense of containing Heleophrynidae; paraphyletic with respect to Ranoidea), Leptodactylidae (polyphyletic, with Batrachophrynidae forming the sister taxon of Myobatrachidae 1 Limnodynastidae, and broadly paraphyletic with respect to Hemiphractinae, Rhinodermatidae, Hylidae, Allophrynidae, Centrolenidae, Brachycephalidae, Dendrobatidae, and Bufonidae), Microhylidae (polyphyletic, with Brevicipitinae being the sister taxon of Hemisotidae), Microhylinae (poly/paraphyletic with respect to the remaining non-brevicipitine microhylids), Hyperoliidae (para/polyphyletic, with Leptopelinae forming the sister taxon of Arthroleptidae 1 Astylosternidae), Astylosternidae (paraphyletic with respect to Arthroleptinae), Ranidae (paraphyletic with respect to Rhacophoridae and Mantellidae). In addition, many subsidiary taxa are demonstrated to be nonmonophyletic, such as (1) Eleutherodactylus with respect to Brachycephalus; (2) Rana (sensu Dubois, 1992), which is polyphyletic, with various elements falling far from each other on the tree; and (3) Bufo, with respect to several nominal bufonid genera. A new taxonomy of living amphibians is proposed, and the evidence for this is presented to promote further investigation and data acquisition bearing on the evolutionary history of amphibians. The taxonomy provided is consistent with the International Code of Zoological Nomenclature (ICZN, 1999). Salient features of the new taxonomy are (1) the three major groups of living amphibians, caecilians/Gymnophiona, salamanders/Caudata, and frogs/Anura, form a monophyletic group, to which we restrict the name Amphibia; (2) Gymnophiona forms the sister taxon of Batrachia (salamanders 1 frogs) and is composed of two groups, Rhinatrematidae and Stegokrotaphia; (3) Stegokrotaphia is composed of two families, Ichthyophiidae (including Uraeotyphlidae) and Caeciliidae (including Scolecomorphidae and Typhlonectidae, which are regarded as subfamilies); (4) Batrachia is a highly corroborated monophyletic group, composed of two taxa, Caudata (salamanders) and Anura (frogs); (5) Caudata is composed of two taxa, Cryptobranchoidei (Cryptobranchidae and Hynobiidae) and Diadectosalamandroidei new taxon (all other salamanders); (6) Diadectosalamandroidei is composed of two taxa, Hydatinosalamandroidei new taxon (composed of Perennibranchia and Treptobranchia new taxon) and Plethosalamandroidei new taxon; (7) Perennibranchia is composed of Proteidae and Sirenidae; (8) Treptobranchia new taxon is composed of two taxa, Ambystomatidae (including Dicamptodontidae) and Salamandridae; (9) Plethosalamandroidei new taxon is composed of Rhyacotritonidae and Xenosalamandroidei new taxon; (10) Xenosalamandroidei is composed of Plethodontidae and Amphiumidae; (11) Anura is monophyletic and composed of two clades, Leiopelmatidae (including Ascaphidae) and Lalagobatrachia new taxon (all other frogs); (12) Lalagobatrachia is composed of two clades, Xenoanura (Pipidae and Rhinophrynidae) and Sokolanura new taxon (all other lalagobatrachians); (13) Bombinatoridae and Alytidae (former Discoglossidae) are each others’ closest relatives and in a clade called Costata, which, excluding Leiopelmatidae and Xenoanura, forms the sister taxon of all other frogs, Acosmanura; (14) Acosmanura is composed of two clades, Anomocoela (5 Pelobatoidea of other authors) and Neobatrachia; (15) Anomocoela contains Pelobatoidea (Pelobatidae and Megophryidae) and Pelodytoidea (Pelodytidae and Scaphiopodidae), and forms the sister taxon of Neobatrachia, together forming Acosmanura; (16) Neobatrachia is composed of two clades, Heleophrynidae, and all other neobatrachians, Phthanobatrachia new taxon; (17) Phthanobatrachia is composed of two major units, Hyloides and Ranoides; (18) Hyloides comprises Sooglossidae (including Nasikabatrachidae) and Notogaeanura new taxon (the remaining hyloids); (19) Notogaeanura contains two taxa, Australobatrachia new taxon and Nobleobatrachia new taxon; (20) Australobatrachia is a clade composed of Batrachophrynidae and its sister taxon, Myobatrachoidea (Myobatrachidae and Limnodynastidae), which forms the sister taxon of all other hyloids, excluding sooglossids; (21) Nobleobatrachia new taxon, is dominated at its base by frogs of a treefrog morphotype, several with intercalary phalangeal cartilages—Hemiphractus (Hemiphractidae) forms the sister taxon of the remaining members of this group, here termed Meridianura new taxon; (22) Meridianura comprises Brachycephalidae (former Eleutherodactylinae 1 Brachycephalus) and Cladophrynia new taxon; (23) Cladophrynia is composed of two groups, Cryptobatrachidae (composed of Cryptobatrachus and Stefania, previously a fragment of the polyphyletic Hemiphractinae) and Tinctanura new taxon; (24) Tinctanura is composed of Amphignathodontidae (Gastrotheca and Flectonotus, another fragment of the polyphyletic Hemiphractinae) and Athesphatanura new taxon; (25) Athesphatanura is composed of Hylidae (Hylinae, Pelodryadinae, and Phyllomedusinae, and excluding former Hemiphractinae, whose inclusion would have rendered this taxon polyphyletic) and Leptodactyliformes new taxon; (26) Leptodactyliformes is composed of Diphyabatrachia new taxon (composed of Centrolenidae [including Allophryne] and Leptodactylidae, sensu stricto, including Leptodactylus and relatives) and Chthonobatrachia new taxon; (27) Chthonobatrachia is composed of a reformulated Ceratophryidae (which excludes such genera as Odontophrynus and Proceratophrys and includes other taxa, such as Telmatobius) and Hesticobatrachia new taxon; (28) Hesticobatrachia is composed of a reformulated Cycloramphidae (which includes Rhinoderma) and Agastorophrynia new taxon; (29) Agastorophrynia is composed of Bufonidae (which is partially revised) and Dendrobatoidea (Dendrobatidae and Thoropidae); (30) Ranoides new taxon forms the sister taxon of Hyloides and is composed of two major monophyletic components, Allodapanura new taxon (microhylids, hyperoliids, and allies) and Natatanura new taxon (ranids and allies); (31) Allodapanura is composed of Microhylidae (which is partially revised) and Afrobatrachia new taxon; (32) Afrobatrachia is composed of Xenosyneunitanura new taxon (the ‘‘strange-bedfellows’’ Brevicipitidae [formerly in Microhylidae] and Hemisotidae) and a more normal-looking group of frogs, Laurentobatrachia new taxon (Hyperoliidae and Arthroleptidae, which includes Leptopelinae and former Astylosternidae); (33) Natatanura new taxon is composed of two taxa, the African Ptychadenidae and the worldwide Victoranura new taxon; (34) Victoranura is composed of Ceratobatrachidae and Telmatobatrachia new taxon; (35) Telmatobatrachia is composed of Micrixalidae and a worldwide group of ranoids, Ametrobatrachia new taxon; (36) Ametrobatrachia is composed of Africanura new taxon and Saukrobatrachia new taxon; (37) Africanura is composed of two taxa: Phrynobatrachidae (Phrynobatrachus, including Dimorphognathus and Phrynodon as synonyms) and Pyxicephaloidea; (38) Pyxicephaloidea is composed of Petropedetidae (Conraua, Indirana, Arthroleptides, and Petropedetes), and Pyxicephalidae (including a number of African genera, e.g. Amietia [including Afrana], Arthroleptella, Pyxicephalus, Strongylopus, and Tomopterna); and (39) Saukrobatrachia new taxon is the sister taxon of Africanura and is composed of Dicroglossidae and Aglaioanura new taxon, which is, in turn, composed of Rhacophoroidea (Mantellidae and Rhacophoridae) and Ranoidea (Nyctibatrachidae and Ranidae, sensu stricto). Many generic revisions are made either to render a monophyletic taxonomy or to render a taxonomy that illuminates the problems in our understanding of phylogeny, so that future work will be made easier. These revisions are: (1) placement of Ixalotriton and Lineatriton (Caudata: Plethodontidae: Bolitoglossinae) into the synonymy of Pseudoeurycea, to render a monophyletic Pseudoeurycea; (2) placement of Haideotriton (Caudata: Plethodontidae: Spelerpinae) into the synonymy of Eurycea, to render a monophyletic Eurycea; (3) placement of Nesomantis (Anura: Sooglossidae) into the synonymy of Sooglossus, to assure a monophyletic Sooglossus; (4) placement of Cyclorana and Nyctimystes (Anura: Hylidae: Pelodryadinae) into Litoria, but retaining Cyclorana as a subgenus, to provide a monophyletic Litoria; (5) partition of ‘‘Limnodynastes’’ (Anura: Limnodynastidae) into Limnodynastes and Opisthodon to render monophyletic genera; (6) placement of Adenomera, Lithodytes, and Vanzolinius (Anura: Leptodactylidae) into Leptodactylus, to render a monophyletic Leptodactylus; (7) partition of ‘‘Eleutherodactylus’’ (Anura: Brachycephalidae) into Craugastor, ‘‘Eleutherodactylus’’, ‘‘Euhyas’’, ‘‘Pelorius’’, and Syrrhophus to outline the taxonomic issues relevant to the paraphyly of this nominal taxon to other nominal genera; (8) partition of ‘‘Bufo’’ (Anura: Bufonidae) into a number of new or revived genera (i.e., Amietophrynus new genus, Anaxyrus, Chaunus, Cranopsis, Duttaphrynus new genus, Epidalea, Ingerophrynus new genus, Nannophryne, Peltophryne, Phrynoidis, Poyntonophrynus new genus; Pseudepidalea new genus, Rhaebo, Rhinella, Vandijkophrynus new genus); (9) placement of the monotypic Spinophrynoides (Anura: Bufonidae) into the synonymy of (formerly monotypic) Altiphrynoides to make for a more informative taxonomy; (10) placement of the Bufo taitanus group and Stephopaedes (as a subgenus) into the synonymy of Mertensophryne (Anura: Bufonidae); (11) placement of Xenobatrachus (Anura: Microhylidae: Asterophryinae) into the synonymy of Xenorhina to render a monophyletic Xenorhina; (12) transfer of a number of species from Plethodontohyla to Rhombophryne (Microhylidae: Cophylinae) to render a monophyletic Plethodontohyla; (13) placement of Schoutedenella (Anura: Arthroleptidae) into the synonymy of Arthroleptis; (14) transfer of Dimorphognathus and Phrynodon (Anura: Phrynobatrachidae) into the synonymy of Phrynobatrachus to render a monophyletic Phrynobatrachus; (15) placement of Afrana into the synonymy of Amietia (Anura: Pyxicephalidae) to render a monophyletic taxon; (16) placement of Chaparana and Paa into the synonymy of Nanorana (Anura: Dicroglossidae) to render a monophyletic genus; (17) recognition as genera of Ombrana and Annandia (Anura: Dicroglossidae: Dicroglossinae) pending placement of them phylogenetically; (18) return of Phrynoglossus into the synonymy of Occidozyga to resolve the paraphyly of Phrynoglossus (Anura: Dicroglossidae: Occidozyginae); (19) recognition of Feihyla new genus for Philautus palpebralis to resolve the polyphyly of ‘‘Chirixalus’’; (20) synonymy of ‘‘Chirixalus’’ with Chiromantis to resolve the paraphyly of ‘‘Chirixalus’’; (21) recognition of the genus Babina, composed of the former subgenera of Rana, Babina and Nidirana (Anura: Ranidae); (22) recognition of the genera Clinotarsus, Humerana, Nasirana, Pelophylax, Pterorana, Pulchrana, and Sanguirana, formerly considered subgenera of Rana (Anura: Ranidae), with no special relationship to Rana (sensu stricto); (23) consideration of Glandirana (Anura: Ranidae), formerly a subgenus of Rana, as a genus, with Rugosa as a synonym; (24) recognition of Hydrophylax (Anura: Ranidae) as a genus, with Amnirana and most species of former Chalcorana included in this taxon as synonyms; (25) recognition of Hylarana (Anura: Ranidae) as a genus and its content redefined; (26) redelimitation of Huia to include as synonyms Eburana and Odorrana (both former subgenera of Rana); (27) recognition of Lithobates (Anura: Ranidae) for all species of North American ‘‘Rana’’ not placed in Rana sensu stricto (Aquarana, Pantherana, Sierrana, Trypheropsis, and Zweifelia considered synonyms of Lithobates); (28) redelimitation of the genus Rana as monophyletic by inclusion as synonyms Amerana, Aurorana, Pseudoamolops, and Pseudorana, and exclusion of all other former subgenera; (29) redelimitation of the genus Sylvirana (Anura: Ranidae), formerly a subgenus of Rana, with Papurana and Tylerana included as synonyms

Polychrotid lizards

38 p. : ill. (1 col.) ; 26 cm.Includes bibliographical references (p. 15-18).Using the techniques of direct optimization and sensitivity analysis, the phylogenetics of polychrotid lizards were examined on the basis of both molecular and morphological data (ca. 1040 bp of 12S rDNA, valine tDNA, and 16S rDNA, and 82 characters of morphology). A sensitivity analysis of sequence alignment and morphological change cost functions demonstrated that equal weighting provided the most parsimonious solution for all data. The Polychrotidae is found not to be monophyletic, containing instead the Corytophanidae as the sister taxon of Anolis plus Polychrus. Based on these and other results over the last 12 years, the taxonomy of the Iguania is reformulated, with the Iguania composed of two subsidiary taxa, Acrodonta and Pleurodonta, the Acrodonta containing the likely paraphyletic and basally unresolved "Agamidae" as well as the Chamaeleonidae, and the Pleurodonta containing the Corytophanidae, Crotaphytidae, Hoplocercidae, Iguanidae, Leiocephalidae (newly elevated from its former status as a subfamily of the Tropiduridae), Leiosauridae (new taxon including Anisolepis, Aperopristis, Diplolaemus, Enyalius, Leiosaurus, Pristidactylus, and Urostrophus), Liolaemidae (newly elevated from its former status as a subfamily of the Tropiduridae), Opluridae, Phrynosomatidae, Polychrotidae (restricted to Anolis and Polychrus), and Tropiduridae (excluding the former subfamilies Leiocephalinae and Liolaeminae)

Is The Amphibian Tree of Life really fatally flawed?

Wiens (2007, Q. Rev. Biol. 82, 55–56) recently published a severe critique of Frost et al.\u27s (2006, Bull. Am. Mus. Nat. Hist. 297, 1–370) monographic study of amphibian systematics, concluding that it is “a disaster” and recommending that readers “simply ignore this study”. Beyond the hyperbole, Wiens raised four general objections that he regarded as “fatal flaws”: (1) the sampling design was insufficient for the generic changes made and taxonomic changes were made without including all type species; (2) the nuclear gene most commonly used in amphibian phylogenetics, RAG-1, was not included, nor were the morphological characters that had justified the older taxonomy; (3) the analytical method employed is questionable because equally weighted parsimony “assumes that all characters are evolving at equal rates”; and (4) the results were at times “clearly erroneous”, as evidenced by the inferred non-monophyly of marsupial frogs. In this paper we respond to these criticisms. In brief: (1) the study of Frost et al. did not exist in a vacuum and we discussed our evidence and evidence previously obtained by others that documented the non-monophyletic taxa that we corrected. Beyond that, we agree that all type species should ideally be included, but inclusion of all potentially relevant type species is not feasible in a study of the magnitude of Frost et al. and we contend that this should not prevent progress in the formulation of phylogenetic hypotheses or their application outside of systematics. (2) Rhodopsin, a gene included by Frost et al. is the nuclear gene that is most commonly used in amphibian systematics, not RAG-1. Regardless, ignoring a study because of the absence of a single locus strikes us as unsound practice. With respect to previously hypothesized morphological synapomorphies, Frost et al. provided a lengthy review of the published evidence for all groups, and this was used to inform taxonomic decisions. We noted that confirming and reconciling all morphological transformation series published among previous studies needed to be done, and we included evidence from the only published data set at that time to explicitly code morphological characters (including a number of traditionally applied synapomorphies from adult morphology) across the bulk of the diversity of amphibians (Haas, 2003, Cladistics 19, 23–90). Moreover, the phylogenetic results of the Frost et al. study were largely consistent with previous morphological and molecular studies and where they differed, this was discussed with reference to the weight of evidence. (3) The claim that equally weighted parsimony assumes that all characters are evolving at equal rates has been shown to be false in both analytical and simulation studies. (4) The claimed “strong support” for marsupial frog monophyly is questionable. Several studies have also found marsupial frogs to be non-monophyletic. Wiens et al. (2005, Syst. Biol. 54, 719–748) recovered marsupial frogs as monophyletic, but that result was strongly supported only by Bayesian clade confidence values (which are known to overestimate support) and bootstrap support in his parsimony analysis was \u3c 50%. Further, in a more recent parsimony analysis of an expanded data set that included RAG-1 and the three traditional morphological synapomorphies of marsupial frogs, Wiens et al. (2006, Am. Nat. 168, 579–596) also found them to be non-monophyletic. Although we attempted to apply the rule of monophyly to the naming of taxonomic groups, our phylogenetic results are largely consistent with conventional views even if not with the taxonomy current at the time of our writing. Most of our taxonomic changes addressed examples of non-monophyly that had previously been known or suspected (e.g., the non-monophyly of traditional Hyperoliidae, Microhylidae, Hemiphractinae, Leptodactylidae, Phrynobatrachus, Ranidae, Rana, Bufo; and the placement of Brachycephalus within “Eleutherodactylus”, and Lineatriton within “Pseudoeurycea”), and it is troubling that Wiens and others, as evidenced by recent publications, continue to perpetuate recognition of non-monophyletic taxonomic groups that so profoundly misrepresent what is known about amphibian phylogeny

On the Monophyly and Relationships of Several Genera of Hylini (Anura: Hylidae: Hylinae), with Comments on Recent Taxonomic Changes in Hylids

We present a molecular phylogenetic analysis of the hylid tribe Hylini, with the goals of testing the monophyly of the genera Duellmanohyla, Isthmohyla, and Ptychohyla and providing a discussion on the monophyly of Bromeliohyla, Charadrahyla, Ecnomiohyla, Exerodonta, Megastomatohyla, and Sarcohyla. Our results indicate the paraphyly of Ptychohyla, with Bromeliohyla and Duellmanohyla nested within it, and, as in previous analyses, the paraphyly of Duellmanohyla (due to Ptychohyla legleri and P. salvadorensis being nested within it). To resolve this situation, we restrict the contents of Ptychohyla, redelimit those of Duellmanohyla and Bromeliohyla, and erect two new genera, one to include the former Ptychohyla panchoi and P. spinipollex, and the other for the former Ptychohyla acrochorda, P. sanctaecrucis, P. zoque, and tentatively, P. erythromma. Exerodonta as currently defined is not monophyletic, inasmuch as Exerodonta juanitae is nested within Charadrahyla. Consequently, we transfer this species and, tentatively, E. pinorum to Charadrahyla. Also, we discuss some possible taxonomic problems within Exerodonta. Our results indicate that Isthmohyla is polyphyletic, the bromeliad-dwelling Isthmohyla melacaena being the sister taxon of our only exemplar of Bromeliohyla, B. bromeliacia. For this reason, we transfer I. melacaena to Bromeliohyla, rendering Isthmohyla monophyletic. The former Isthmohyla pictipes Group is shown to be paraphyletic due to having the non-monophyletic I. pseudopuma Group within it. Accordingly, we recognize a redelimited I. pseudopuma Group (contents: I. infucata and I. pseudopuma), an I. zeteki Group (contents: I. picadoi and I. zeteki), and a newly defined I. tica Group (contents: I. angustilineata, I. calypsa, I. debilis, I. graceae, I. lancasteri, I. pictipes, I. tica, I. rivularis, and, tentatively, I. insolita and I. xanthosticta). The three groups of Isthmohyla are supported by molecular evidence with jackknife support values > 90%, and two of them by putative morphological synapomorphies. We discuss the recognition of Dryophytes, Hyliola, Rheohyla, and Sarcohyla and whether it is useful to recognize Anotheca, Diaglena, and Triprion as three distinct, monotypic genera. Finally, we discuss a recent taxonomic proposal involving changes in rank and from ranked to unranked names in hylids that overall we consider to have been poorly justified and only superficially discussed.Fil: Faivovich, Julián. Universidad de Buenos Aires; ArgentinaFil: Pereyra, Martín Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales “Bernardino Rivadavia”; ArgentinaFil: Luna, María Celeste. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales “Bernardino Rivadavia”; ArgentinaFil: Hertz, Andreas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales “Bernardino Rivadavia”; ArgentinaFil: Blotto Acuña, Boris Leonardo. University Of Massachusetts Boston;Fil: Vásquez-Almazán, Carlos R.. Senckenberg Forschungsinstitut Und Naturmuseum;Fil: McCranie, James R.. Universidade de Sao Paulo; BrasilFil: Sánchez, David A.. Universidad de San Carlos de Guatemala; GuatemalaFil: Baêta, Délio. Universidad de San Carlos de Guatemala; GuatemalaFil: Araujo-Vieira, Katyuscia. University Of Texas At Arlington;Fil: Köhler, Gunther. Unesp-universidade Estadual Paulista;Fil: Kubicki, Brian. Universidade Federal do Rio de Janeiro; BrasilFil: Campbell, Jonathan A.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales “Bernardino Rivadavia”; ArgentinaFil: Frost, Darrel R.. Senckenberg Forschungsinstitut Und Naturmuseum;Fil: Wheeler, Ward C.. Costa Rican Amphibian Research Center; Costa RicaFil: Haddad, Célio F.B.. University Of Texas At Arlington

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)