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Rosuvastatin vs Protease Inhibitor Switch for Hypercholesterolemia: Randomised Trial
Frederick J. Lee7, Polyana Monteiro3, David Baker1, Mark Bloch2, Robert Finlayson8, Richard Moore5, Norman Roth6, Jennifer F. Hoy4, Esteban Martinez3, Andrew Carr7
1 East Sydney Doctors, Sydney, NSW, Australia. 2 Holdsworth House Medical Practice, Sydney, NSW, Australia. 3 Hospital Clinic, University of Barcelona, Barcelona, Spain. 4 Monash University/Alfred Hospital, Melbourne, VIC, Australia. 5 Northside Clinic, Melbourne, VIC, Australia. 6 Prahran Market Clinic, Melbourne, VIC, Australia. 7 St. Vincent's Hospital, Sydney, NSW, Australia. 8 Taylor Square Private Clinic, Sydney, NSW, Australia.
Background: Optimal management of hypercholesterolaemia in adults receiving a ritonavir-boosted protease inhibitor (rPI) is unknown. The two proven options, statin therapy and rPI switching to a lipid-neutral alternative, have not been compared since the advent of current-generation statins and PIs, despite multiple studies (mostly industry-sponsored) focussed upon rPI switching.
Methods: Adults on rPI-based therapy with plasma viral load <50 cp/mL for ≥6 months, total cholesterol ≥5.5 mmol/L (213 mg/dL) and elevated cardiovascular risk (Framingham score ≥8% at 10 years or family history of premature cardiac disease), and not on lipid-lowering therapy, were randomised to open-label rosuvastatin 10 mg/day or to switch rPI, stratified by cholesterol (> or ≤ 7.0 mmol/L [272 mg/dL]) and rPI type (atazanavir or other); all subjects received standardised diet/lifestyle advice. The primary endpoint was change in fasting total cholesterol at Week 12 (ITT analysis, Wilcoxon rank-sum test); we hypothesized that rosuvastatin would be more effective. Final analyses are reported.
Results: Baseline characteristics (mean [SD] or n [%]) of the 43 subjects were: age 55 (8.5) years; n=42 (98%) male; n=41 (95%) white race; total cholesterol 6.2 mmol/L (240 mg/dL). Baseline rPI types were lopinavir (n=22; 51%), atazanavir (n=12; 28%) and darunavir (n=9; 21%). Within the switch group, the most common rPI substitutes were raltegravir (n=10; 50%) and rilpivirine (n=6; 30%). All subjects adhered to strategy through Week 12. By Week 4, rosuvastatin resulted in greater declines in total cholesterol (24.1% vs. 7.3%, p<0.001), LDL cholesterol, and total:HDL cholesterol ratio, than rPI switch. These changes were maintained at Week 12 (Table), with trends to greater declines in cardiovascular risk scores, despite similar weight changes. Conversely, rPI switch caused greater falls in VLDL cholesterol and triglycerides, but more study drug-related adverse events (11 vs. 1, p=0.001 [Ï‡2]; mostly grade 1 nausea or diarrhoea). HIV viral load rose to 360 cp/mL in 1 rosuvastatin subject by Week 12, but was <50 cp/mL 3 months later without therapy change. One serious adverse event occurred in each arm, both unrelated to study drug/switch. No grade 3-4 laboratory adverse event was seen. No adverse event led to discontinuation of rosuvastatin or switch drug.
Conclusions: In adults receiving an rPI, rosuvastatin 10 mg/day for 12 weeks yielded larger decreases in total and LDL cholesterol than rPI switching, and was better tolerated.