RESUMO
BACKGROUND: The role of lipid-lowering treatments in renoprotection for patients with diabetes is debated. We studied the renal effects of two statins in patients with diabetes who had proteinuria. METHODS: PLANET I was a randomised, double-blind, parallel-group trial done in 147 research centres in Argentina, Brazil, Bulgaria, Canada, Denmark, France, Hungary, Italy, Mexico, Romania, and the USA. We enrolled patients with type 1 or type 2 diabetes aged 18 years or older with proteinuria (urine protein:creatinine ratio [UPCR] 500-5000 mg/g) and taking stable angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or both. We randomly assigned participants to atorvastatin 80 mg, rosuvastatin 10 mg, or rosuvastatin 40 mg for 52 weeks. The primary endpoint was change from baseline to week 52 of mean UPCR in each treatment group. The study is registered with ClinicalTrials.gov, number NCT00296374. FINDINGS: We enrolled 353 patients: 118 were assigned to rosuvastatin 10 mg, 124 to rosuvastatin 40 mg, and 111 to atorvastatin 80 mg; of these, 325 were included in the intention-to-treat population. UPCR baseline:week 52 ratio was 0·87 (95% CI 0·77-0·99; p=0·033) with atorvastatin 80 mg, 1·02 (0·88-1·18; p=0·83) with rosuvastatin 10 mg, and 0·96 (0·83-1·11; p=0·53) with rosuvastatin 40 mg. In a post-hoc analysis to compare statins, we combined data from PLANET I with those from PLANET II (a similar randomised parallel study of 237 patients with proteinuria but without diabetes; registered with ClinicalTrials.gov, NCT00296400). In this analysis, atorvastatin 80 mg lowered UPCR significantly more than did rosuvastatin 10 mg (-15·6%, 95% CI -28·3 to -0·5; p=0·043) and rosuvastatin 40 mg (-18·2%, -30·2 to -4·2; p=0·013). Adverse events occurred in 69 (60%) of 116 patients in the rosuvastatin 10 mg group versus 79 (64%) of 123 patients in the rosuvastatin 40 mg group versus 63 (57%) of 110 patients in the atorvastatin 80 mg group; renal events occurred in nine (7·8%) versus 12 (9·8%) versus five (4·5%). INTERPRETATION: Despite high-dose rosuvastatin lowering plasma lipid concentrations to a greater extent than did high-dose atorvastatin, atorvastatin seems to have more renoprotective effects for the studied chronic kidney disease population. FUNDING: AstraZeneca.
Assuntos
Complicações do Diabetes/tratamento farmacológico , Nefropatias Diabéticas/tratamento farmacológico , Fluorbenzenos/uso terapêutico , Ácidos Heptanoicos/uso terapêutico , Rim/efeitos dos fármacos , Pirimidinas/uso terapêutico , Pirróis/uso terapêutico , Sulfonamidas/uso terapêutico , Adulto , Análise de Variância , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Atorvastatina , Creatinina/urina , Relação Dose-Resposta a Droga , Método Duplo-Cego , Europa (Continente) , Fluorbenzenos/farmacologia , Ácidos Heptanoicos/farmacologia , Humanos , Lipídeos/sangue , América do Norte , Proteinúria , Pirimidinas/farmacologia , Pirróis/farmacologia , Rosuvastatina Cálcica , América do Sul , Sulfonamidas/farmacologiaRESUMO
The key points of this article are: (1) A hypertensive crisis is present when markedly elevated blood pressure is accompanied by progressive or impending acute target organ damage. (2) Most instances of very elevated blood pressure encountered in the office setting will not be crises and will not require acute reduction of blood pressure. (3) Hypertensive crises are largely preventable and often result from inadequate management of hypertension or poor adherence to therapy. (4) Effective triage of patients into categories of severe hypertension, hypertensive urgency, and hypertensive emergency through an expeditious history, examination, and testing should guide therapy. (5) Hypertensive urgency is managed with oral medications and usually on an outpatient basis; a hypertensive emergency warrants intensive care unit admission and parenteral therapy. (6) Ensuring adequate follow-up after treatment of very elevated blood pressure is a critical step that is often mishandled.