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Combined Torcetrapib-Atorvastatin Provides Many Lipoprotein Benefits

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Combined Torcetrapib-Atorvastatin Provides Many Lipoprotein Benefits 50 Cardiovascular Medicine I NTERNAL M EDICINE N EWS • June 1, 2006 Combined Torcetrapib-Atorvastatin Higher Statin Copays Provides Many Lipoprotein Benefits Cut Adherence by 37% BY BRUCE JANCIN BY BRUCE JANCIN monotherapy, with one exception: There was a Denver Bureau Denver Bureau roughly 2-mm Hg increase in systolic blood pressure seen with torcetrapib alone or in combination with A TLANTA — Higher prescription statin copayments ATLANTA — The novel HDL cholesterol–boosting atorvastatin. have unintended negative consequences, Teresa B. Gibson, drug torcetrapib, which is being developed solely as a Torcetrapib is first in a new class of drugs that in- Ph.D., said at the annual meeting of the American College combination pill with atorvastatin, results in favorable hibit cholesterol ester transfer protein (CETP), which of Cardiology. lipoprotein changes of unprecedented magnitude, Dr. is responsible for transferring cholesterol from HDL Her study of the health records of more than 93,000 Tom Thuren reported at the annual meeting of the to LDL. statin users in employer-sponsored health plans demon- American College of Cardiology. Although the exuberant lipid changes seen with strated that higher copays were associated with signifi- He presented data from a multicenter, double-blind, torcetrapib/atorvastatin in this phase II study are en- cantly lower medication adherence, which in turn was phase II, dose-ranging study involving 493 patients with couraging, what really matters, according to Dr. linked to more emergency department visits and cardio- elevated LDL cholesterol in which torcetrapib 60 Thuren, is whether they translate into further reduc- vascular hospitalizations. mg/day plus atorvastatin 10-80 mg/day—the doses in tion in cardiovascular events beyond that obtained Health plan managers and policy makers use copays as clinical development—resulted in dose-dependent 44%- with aggressive statin therapy alone. That question is a means of controlling prescription drug costs. It’s a strat- 66% increases in cardioprotective HDL cholesterol, the subject of large, ongoing, phase III, randomized egy designed to reduce consumption of prescription drugs along with LDL cholesterol reductions of 41%-60%. clinical trials. and steer patients to preferred, less expensive medications. The combination of torcetrapib 60 mg plus atorvas- Pending outcome of these major trials, a new sec- The use of copays is likely to continue to rise. But in pa- tatin 80 mg also resulted in a 20% increase in apolipopro- ondary analysis of the landmark Treating to New Tar- tients with chronic medical conditions—such as known car- tein A-I compared with baseline in the 12-week study. gets (TNT) study may provide reason for optimism re- diovascular disease, or hyperlipidemia predisposing to The mean reduction in non-HDL cholesterol was 23% garding the potential incremental clinical benefits of heart disease—it’s a strategy with troublesome side effects, with torcetrapib 90 mg alone, 47% with atorvastatin 80 coupling HDL cholesterol–raising with LDL choles- according to Dr. Gibson of Thomson Medstat, a health care mg alone, and 61% with the two combined. terol–lowering. research services company in Ann Arbor, Mich. Moreover, the various torcetrapib/atorvastatin com- Dr. Philip Barter presented an analysis of the rela- “In this large cohort of continuing users of statins, we binations resulted in salutary changes in lipoprotein tionship between cardiovascular events and on-treat- saw increasing drug copayments are a financial barrier to particle size as assessed by nuclear magnetic reso- ment HDL cholesterol levels in TNT, a Pfizer-spon- statin adherence. Reduced cost-sharing might be an effec- nance. There was a marked shift away from small, sored, randomized, double-blind study in which 10,001 tive intervention for these patients,” she observed. dense LDL particles—the subclass thought to be most patients with coronary disease were assigned to 10 mg The average statin copay during the study period of 2000- highly atherogenic—in favor of large, buoyant LDL or 80 mg/day of atorvastatin. 2003 was $12 per month. Overall adherence to statin ther- particles. Indeed, levels of small, dense LDL cholesterol The 80-mg group showed a 22% relative risk reduc- apy during the first 18 months was 58%, meaning only 58% dropped by 23-70 mg/dL in dose-dependent fashion, tion in major cardiovascular events compared with of the 93,296 patients had a filled statin prescription on at whereas large LDL particles increased by 32-68 mg/dL those on 10 mg during 5 years of follow-up (N. Engl. J. least 80% of days during follow-up. Higher copays were as- over baseline, noted Dr. Thuren, director of clinical de- Med. 2005;352:1425-35). sociated with a 37% reduction in adherence. velopment at Pfizer Global Research and Development, A patient’s HDL cholesterol level remained predic- Total expenditures measured during the second 18 New London, Conn. tive of cardiovascular event risk both at high and low months of the study period didn’t differ significantly be- Simultaneously, the HDL2 subfraction, which is be- LDL cholesterol levels, suggesting that HDL choles- tween statin-adherent and nonadherent patients. lieved to be particularly cardioprotective, jumped by terol–raising may be a potential therapeutic target Adherent patients had lower medical expenditures, but 79%-198%, whereas HDL3 rose by 22%-45%. HDL par- even in patients on aggressive LDL cholesterol–lower- this was counterbalanced by higher prescription drug ex- ticle size increased in a dose-dependent fashion with ing therapy, noted Dr. Barter, professor of medicine at penditures and more physician office visits than for non- torcetrapib, but was unaffected by atorvastatin. the University of Sydney and director of the Heart Re- adherent patients. Side effects were those associated with statin search Institute, Camperdown, Australia. ■ Dr. Gibson’s study was funded by Pfizer. ■ Pill Burden Influences Patient Could Health Benefits of Omega-3 Adherence to Heart Drugs Fatty Acids Be Just a Fish Story? systematic review of data on the risks ied subjects who took supplements. BY BRUCE JANCIN adherence to concomitant antihyperten- Aand benefits of omega-3 fatty acids In an editorial, Eric Brunner, Ph.D., of Denver Bureau sive and lipid-lowering therapy and identi- showed no clear benefit for mortality, the Royal Free and University College fying predictors of treatment adherence. It cardiovascular disease, stroke, or cancer. London Medical School, emphasized ATLANTA — Adherence to concomitant involved 5,759 patients placed on both In a metaanalysis that included 48 ran- that despite the results of this meta- lipid-lowering and antihypertensive med- such medications within a 90-day period. domized, controlled trials and 41 cohort analysis, there still remains good evi- ications falls by an average of 9% with Adherence was poor overall, with 36% studies, Lee Hooper, Ph.D., of the Uni- dence that omega-3 fatty acids are ben- each additional background prescription of patients remaining adherent to both versity of East Anglia, Norwich, Eng- eficial for health. Extreme nutritional drug a patient is on, Joshua S. Benner, therapies at 12 months’ follow-up. Adher- land, and colleagues determined that the deficiency of these fats results in neu- Pharm.D., said at the annual meeting of ence was defined as having filled pre- lack of effect was even more pronounced ropathy, for example (BMJ March 24, the American College of Cardiology. scriptions for both medications on at least when studies with a high risk of bias 2006;doi:10.1136/bmj.38798.680185.47). However, the relationship between the 80% of the days of follow-up. were excluded (BMJ March 24, Furthermore, adequate intake of number of other drugs a patient is taking Another predictor of adherence was ini- 2006;doi:10.1136/bmj.38755.366331.2F). omega-3 fats is particularly important for and adherence to antihypertensive and tiating antihypertensive and lipid-lowering This result contradicts previous re- women of childbearing age, since an es- lipid-lowering drugs is curvilinear, not lin- therapy together. After adjustment for co- views of omega-3 trials that did show a timated 25 g of maternal docosa- ear: The decline in adherence is steepest morbidities and demographic variables, beneficial effect on mortality, perhaps in hexaenoic acid is needed during preg- in patients already on up to three other patients who started the second therapy part because the metaanalysis by Hoop- nancy and lactation to support the medications at baseline, and it flattens out within 30 days of the first were 54% more er et al includes the recently published re- development of the child’s brain. somewhat in those on four or more oth- likely to be adherent to both than were sults of a large trial. These results differed But Dr. Brunner pointed to a paradox. er drugs, according to Dr. Benner of Val- those who initiated the second therapy from the findings of the other large stud- Although nutrition experts advise in- ueMedics Research, Falls Church, Va. within 61-90 days. Sex and age were also ies on this topic. creasing consumption of oily fish con- “Pill burden matters most for the pa- closely linked to adherence. Women were Altogether, the metaanalysis included taining omega-3 fatty acids, industrial tients who take the fewest additional num- 20% less likely than men to adhere to both nearly 37,000 participants in random- fishing has depleted the world’s fish ber of medications,” he said. drugs at 1 year. Patients aged 55-64 were ized, controlled trials as well as more stocks by about 90% since 1950, and Dr. Benner presented a retrospective co- 76% more likely and 65- to 74-year-olds than 560,000 participants in cohort tri- therefore the world probably doesn’t hort study of patients enrolled in a large were 37% more likely to be adherent than als.
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