Discontinuation rates of cholesterol-lowering medications: implications for primary care.

OBJECTIVE: To evaluate long-term continuation rates for cholesterol-lowering therapy (niacin, sequestrants, statins) in a multidisciplinary lipid clinic and to evaluate the effectiveness of 2 different dosing strategies designed to improve long-term continuation of therapy. STUDY DESIGN: An observational study was done at the Milwaukee Department of Veterans Affairs Medical Center Lipid Clinic, where healthcare personnel were trained to improve patient tolerance to cholesterol-lowering medications. Primary outcomes were recorded prospectively. PATIENTS AND METHODS: Patients were 970 consecutive veterans who began therapy with niacin, sequestrants, or statins between March 1988 and December 1995. In 1992, two different dosing strategies were initiated to reduce the discontinuation rates for niacin and sequestrants: (1) the niacin titration schedule was lengthened from 3 to 6 weeks and (2) the initial sequestrant dose was reduced from four to two scoops daily. RESULTS: Discontinuation rates for niacin and sequestrants were both very high. For niacin, 48% and 71% of all patients who began therapy discontinued the drug by 1 and 4 years, respectively. For sequestrants, drug discontinuation rates were 59% and 83% at 1 and 4 years, respectively. On the other hand, statin discontinuation rates at 1 and 4 years were only 10% and 28%, respectively. Neither the longer niacin titration schedule nor the lower sequestrant initiation dose reduced these high discontinuation rates. CONCLUSIONS: Despite initiation of niacin and sequestrant therapy in the setting of a multidisciplinary lipid clinic, drug discontinuation rates were high and were similar to rates observed in primary-care settings. Neither the specialized resources available in a lipid clinic nor protocols designed to improve tolerance to therapy reduced the high drug discontinuation rate. Unless more tolerable niacin and sequestrant formulations become available, reliance on statins as the preferred cholesterol-lowering agents will continue because they have fewer side effects and lower discontinuation rates.

Physician extenders for cost-effective management of hypercholesterolemia.

OBJECTIVE: Treatment of elevated cholesterol levels reduces morbidity and mortality from coronary heart disease in high-risk patients, but can be costly. The purpose of this study was to determine whether physician extenders emphasizing diet modification and, when necessary, effective and inexpensive drug algorithms can provide more cost-effective therapy than conventional care. DESIGN: Randomized controlled trial. SETTING: A Department of Veterans Affairs Medical Center. PATIENTS: Two hundred forty-seven veterans with type IIa hypercholesterolemia. INTERVENTIONS: Patients assigned to either a cholesterol treatment program (CTP) or usual health care provided by general internists (UHC). CTP included intensive dietary therapy administered by a registered dietitian utilizing individual and group counseling and drug therapy initiated by physician extenders for those failing to achieve goal low-density lipoprotein (LDL) levels with diet alone. A drug selection algorithm for CTP subjects utilized niacin as initial therapy followed by bile acid sequestrants and lovastatin. Subjects were followed prospectively for 2 years. MEASUREMENTS: Primary outcome measurements were effectiveness of therapy defined as reductions in LDL cholesterol (LDL-C), and whether goal LDL-C levels were achieved; costs of therapy; and cost-effectiveness defined as the cost per unit reduction in the LDL-C. MAIN RESULTS: Total program costs were higher for CTP patients than for UHC patients ($659 +/- $43 vs $477 +/- $42 per patient, p < .001). However, at 24 months the patients in CTP were more likely to achieve LDL goal levels (65% vs 44%, p < .005), and also achieved greater reductions in LDL-C 27% +/- 2% vs 14% +/- 2% at 24 months, p < .001). Program costs per unit (mmol/L) reduction in the LDL-C, a measure of cost-effectiveness, was significantly lower for CTP ($758 +/- $58 vs $1,058 +/- $70, p = .002). CONCLUSIONS: Although more expensive than usual care, the greater effectiveness of physician extenders implementing cholesterol treatment algorithms resulted in more cost-effective therapy.

The effect of warfarin on urine calcium oxalate crystal growth inhibition and urinary excretion of calcium and nephrocalcin.

Urine contains inhibitors of calcium oxalate (CaOx) crystal growth. One such inhibitor is nephrocalcin (NC), a glycoprotein which is made in the kidney and contains several residues of gamma-carboxyglutamic acid (Gla) per molecule. The presence of Gla may be important to its ability to inhibit crystal growth. Several studies suggest that vitamin K-dependent proteins may also play a role in renal calcium (Ca) handling, and that vitamin D deficiency may lead to excess urinary Ca loss, but the effect of the vitamin K antagonist warfarin on urinary Ca excretion and CaOx growth inhibition in humans is not known. We studied 11 men while they were taking warfarin for a mean of 252 days, and again a mean of 64 days after its discontinuation. Urinary Ca excretion did not differ between those on or off warfarin, or between those on warfarin and normal controls. The ability of the subjects' urine to inhibit CaOx crystal growth did not differ on or off warfarin, or from that of control urine, and the excretion of immunoreactive NC also did not differ between these groups. NC was found to be responsible for approximately 16% of the CaOx growth inhibition seen. These results do not suggest that vitamin K-dependent proteins play a major role in renal Ca excretion in men, or that interference with vitamin K alters NC excretion or inhibitory activity of the urine.

Lack of interaction between sulindac or naproxen and propranolol in hypertensive patients.

Seventeen patients with hypertension and osteoarthritis participated in a single-blind crossover study comparing the effects of sulindac 200 mg twice daily, naproxen 500 mg twice daily, and placebo on blood pressure. All patients were treated for hypertension with propranolol monotherapy. Blood pressures were back-titrated to achieve a baseline diastolic blood pressure of 90 to 100 mm Hg while taking naproxen. There were no significant differences in mean sitting or standing blood pressures among the patients receiving naproxen, sulindac, or placebo treatments. There was no change in pulse, weight, or any of the laboratory measurements at the end of each treatment phase. These results suggest that neither sulindac nor naproxen interferes with propranolol therapy for uncomplicated hypertension.

The limitations of predictability of success of femoral-popliteal bypass grafts.

This study was carried out to determine whether we could develop a model to identify predictive factors for success of femoral-popliteal (FP) bypass grafts. In a retrospective review of 199 operations, 24 factors influencing outcome were selected by stepwise logistic regression analysis, a sophisticated, multifactorial computer program. The top five indicators (excluding intraoperative technical problems) were runoff status, previous ipsilateral FP bypass, preoperative prediction of potential amputation level, concurrent proximal vascular reconstruction, and site of the distal anastomosis. We chose to validate the predictive model developed before applying it clinically. Data from 67 subsequent cases were presented to the computer without the known outcome, and the probability of 30-day patency was calculated. The model predicted 11 failures; there were actually eight thromboses in the 67 grafts. However, only three of the failures were predicted correctly, and eight cases of computer-anticipated thromboses were patent at 30 days. The high false positive rate makes the clinical application of the predictive model inappropriate. The success of FP bypass grafts appears to be related to factors that cannot be assessed preoperatively, such as technical problems during surgery. Even those which seem to have a poor runoff and other high-risk factors may succeed; thus an aggressive approach is justified in lower extremity reconstructions.