REVIEW ARTICLE

CalculatingRisks and Number-Needed-to-Treat: A Method of Data Interpretation

Michael G. Kendrach, Timothy R. Covington, Michelle W McCarthy, and M. Catherine Harris

OBJECTIVE: interpretation and/or discuss measures of CONCLUSION: To define four measures of association- association were evaluated. RR, ARR, RRR, and NNT can assist the (RR), absolute risk reduction reader in determining the association be- DATA (ARR), (RRR), and SYNTHESIS: tween treatment and a health outcome and The NNT number-needed-to-treat (NNT), demon- RR, ARR, RRR, and were calcu- can be calculated from results of studies lated for the study the strate the method of calculating these val- endpoints. For pri- reporting dichotomous endpoints. These mary endpoint (nonfatal MI or death from ues, and discuss the clinical relevance of values can assist in the interpretation of CHD), (ARR) of the each value. RR=0.70; 2.26% pa- clinical trials to determine the magnitude of receiving tients pravastatin were spared benefit from therapy. DATA SOURCES: the event; 30% (RRR) of the baseline risk a pravastatin KEY making, Risk, MEDLINE 1991 to present and bibliogra- was removed as result of WORDS: Decision patients interpretation, phies of pertinent articles. therapy and 44 need to be treated Treatment outcome, Data to prevent an adverse event. Attitude of health personnel STUDY SELECTION: Articles designed to assess statistical data J Managed Care Pharm 1997; 3: 179-83.

Advertisements and other sources of information present pretation of clinical.trial results prior to recommending the results of clinical trials evaluating drug therapy in a va- therapy. riety of ways, some of which may be misleading or misin- One technique to ascertain the clinical impact of drug terpreted. This especially is true when health care providers therapy is to examine four measures of association: relative are unaware of the different methods of data analysis and risk (RR), absolute risk reduction (ARR), relative risk re- presentation and their significance. Clearly, pharmacists are duction (RRR), and number-needed-to-treat (NNT). These active in decision making regarding drug utilization and values can assist health care practitioners in determining should be able to accurately and appropriately assess the the association between treatment and outcome. This validity of the biomedical literature. However, studies sug- article will define these measurements, demonstrate the gest that this isn't always the case. Furthermore, health care method of calculating these values, and discuss the rele- practitioners' willingness to select a therapy option may be vance of each value. influenced by the manner in which trial results were pre- sented. \.5 STUDY SELECTION The res~lts of clinical trials are key to managed care pharmacists and other practitioners in determining the The Pravastatin Primary Prevention OP) Trial was se- efficacy, side effect profile, and other aspects of a drug lected as a model to demonstrate how to calculate the mea- product. When this data is misleading or misinterpreted, sures of association using endpoint adverse event data. This the repercussions may be serious and widespread. Thus, study was designed to evaluate the efficacy of pravastatin, health care practitioners should be well versed in the inter- an HMG-CoA reductase inhibitor, in preventing coronary

. Authors

MICHAEL G. KENDRACH, PHARM.D., is Director, Drug Information Service, and Assistant Professor, McWhorter School of Pharmacy, Samford Universi- ty, Birmingham, AL. TIMOTHY R. COVINGTON, PHARM.D., M.S., is Executive Director, Managed Care Institute, and Bruno Professor of Pharmacy, McWhorter School of Pharmacy, Samford University. MICHELLE W MCCARTHY, PHARM.D, is Associate Director, Drug Information Service, and Assis- tant Professor, McWhorter School of Pharmacy, Samford University. M. CATHERINE HARRIS, PHARM.D., is Drug Information Specialist, University of Alabama at.J3irmingham Drug Resource Center, Birmingham, AL.

AUTHOR CORRESPONDENCE: Michael Kendrach, McWhorter School of Pharmacy, Samford' University; 800 Lakeside [)rive, Birmingham, AL 35229.

Copyright is) 1997, Academy of Managed Care Pharmacy, Ine. All rights reserved.

VoL 3, No.2 Mar/Apr 1997 fM(P Journal of Managed Care Pharmacy 179 REV1EW ARTICLE: A Method 01 Data Interpretation

Table 1. Selected Baseline Characteristics of the ratio of risk of an event occurring in one group compared Randomized Patients to another group. This value indicates the risk of the event af- ter the experimental treatment as a percentage of the original Variable Pravastatin risk.8,9 The interpretation of this calculation focuses around (N=3,293) (N=3,302) the whole number one (1.0). A value of < 1.0 indicates that developing Age (years)* 55.10105.5 55.3 010 5.5 therapy lessened the risk of the adverse outcome

* compared placebo. A RR = Total cholesterol t 272 010 22 272 010 23 in the treatment group to value 1.0 a RR Low-density lipoprotein (LDL)*t 19201017 191010 17 denotes no difference between treatments. However, val-

010 therapy High-density lipoprotein (LDL)*t 164 010 68 162 70 ue of> 1.0 indicates that increased the risk of devel- RR Triglycerides* t 164 010 68 162 010 70 oping the adverse outcome. The formula for calculating [A / (A + B)] / [C / D)] .8,9 Ex-smoker (%) 1,127 (34) 1,138 (34) from the gathered data is (C+

Current smoker (%) 1,460 (44) 1,445 (44)

Table 3. Number of Patients with the Primary Endpoint *Values expressed as mean 010 standard deviation. Result tUnits equal mgldL

Pravastatin Primary Prevention Trial Primary Endpoint events in men with moderate hypercholesterolemia (see Table 1) and no history of (MI). A total of Yes No 6,595 patients were randomized to either pravastatin 40 mg/day Pravastatin 174 3,128 (N = 3,302) or placebo (N = 3,293) and followed for a total of Placebo 248 3,045 32,216 subject-years (an average of 4.9 years/subject). The primary endpoint of the study was the occurrence of nonfatal MI or death from coronary heart (CHD) as a first risk (ARR) is defined the difference event; these two categories were combined. In addition, the Absolute reduction as the risk of the effect of treatment on death from any cause, the of in outcome between patients who have received therapy This nonfatal MI, and the frequency of coronary revascularization one from those who have received another. mea- provides the of spared the procedures were analyzed. The baseline characteristics of the sure percentage patients adverse patients enrolled were similar (see Table 1)6 Further details of outcome as a result of receiving the experimental rather than changes a change the study design are described elsewhere.''? the control therapy, and with in baseline risk.

The formula for calculating ARR is [C / (C + D)] - [A / (A + B)].S9 Relative risk reduction (RRR), a term used in clinical Table 2. Format of Outcome Data According to Therapy studies and medication advertisements, estimates the percent- age of baseline risk that is removed as a result of therapy. This Outcome' measure is used to compare the efficacy of treatment to the Yes No "control." Two methods of calculating this measurement are as A B Pravastatin follows: {[C / (C + D)] - [A / (A + B)]}![C / (C + D)] or

Placebo C D simply, 1 - RRB,9

* Number-needed-to-treat (NNT), indicates the number of Example: Pravastatin Primary Preventive Trial Primary Endpoint patients who require treatment to prevent one event, and can provide valuable insight into the benefits of therapy. NNT can taking ARR ARR)89 Since dichotomous measurements ("yes" or "no", but not be calculated by the reciprocal of the (1/ both) were collected as endpoints, these figures are used to cal- DATA SYNTHESIS culate the measures of association. Table 2 shows the format in which the arranged perform the outcomes were to calculations. Calculation examples of RR, ARR, RRR, and NNT for the The 3P Trial endpoint data entered this table by ad- were into primary endpoint of the 3P Trial are: and the verse event patient group to calculate additional mea- = ... Relative Risk: [174 / (174 + 3,128)]1 [248/ (248 + 3,045)] of association not provided by the study sures authors. 0.70 For instance, 174 pravastatin-treated patients and 248 ... Absolute Risk Reduction: [248/ (248 + 3,045)] - [174 / placebo-treated patients experienced the primary endpoint, (174 + 3,128)] = 2.26% while 3,128 pravastatin and 3,045 placebo-treated patients

Relative Risk Reduction: {[248 / (248 + 3,045)] - [174 / did not. Thus, the corresponding cell letter for each group ... (174 + [248/ (248 + 3,045)] = 0.30 would be A, C, B, and D, respectively (see Table 3). 3,128)])/ Once the outcome data was entered into Table 3, the or 1 - 0.70 = 0.30 measures of association were calculated. Relative risk (RR) is ... Number-Needed-to- Treat: 1 /0.0226 = 44

180 Journal of Managed Care Pharmacy jMCP Mar/Apr 1997 Vol. 3, No.2 REVIEW ARTICLE: A Method of Data Interpretation

Table 4. Relative Risk (RR), Absolute Risk Reduction (ARR), when clinically equivalent, lower-priced alternatives are avail- Relative Risk Reduction (RRR), and Number-Needed-to- able. In response, some manufacturers compensate through Treat (NNT) According to Study Endpoint more aggressive marketing techniques to maintain or increase market share. However, the medical literature has expressed Study Endpoint RR ARR RRR NNT some concern about pharmaceutical advertisements that pre- (%) (%) sent "misleading" information. In fact, one study by expert re- Nonfatal MI* 0.70 2.26 30 44 or viewers demonstrated that many pharmaceutical advertisements Death from CHD* contained deficiencies in areas where the Food and Drug Nonfatal MI 0.69 2.08 31 48 Administration (FDA) has established explicit standards of (silent MIs omitted) quality. 10 This is of particular when one considers the or Death from CHD concern data showing that advertisements influence clinical decisions Nonfatal MI 0.70 1.86 30 54 and physician prescribing. ][.13 Clearly, health care professionals Death from CHD 0.73 0.42 27 233 need to be aware of the limitations of advertisements and pro- 0.70 1.16 30 86 Coronary motional materials. But they also must be prepared to analyze Angiography them thoroughly and accurately. PTCAt or CABGt 0.64 0.88 36 Il3 Death from all 0.68 0.70 32 142 Deceptive Nature of Numbers Cardiovascular Causes One method of enhancing promotional materials is to dis- Any Death from Cause 0.78 0.89 22 Il2 play relative differences or advantages. However, "benefits" presented as relative changes be due to *MI = myocardial infarction; CHD = coronary heart disease can misinterpreted an absent or hidden in small-print) baseline value. For in- tPTCA = percutaeous transluminal coronary angioplasty; CABG = coronary (e.g., RRR artery bypass graft stance, RR and do not reflect the baseline risk in the con- trol population. A simple example from everyday life illustrates the decep- tive of relative numbers. A long-distance phone Table 4 shows the respective'values for RR, ARR, RRR, nature compa- customers for their plan by claiming and NNT according to measured adverse event endpoints of ny encourages to sign up calls be 42% faster than other long-distance the 3P Trial. will connected companies. Based on the television commercials and direct Using the primary endpoint to explain these values in a mail materials, the offer seems attractive. However, an analysis text format, patients randomized to the pravastatin group ben- of the data may show otherwise. efited compared to placebo-treated patients (indicated by the First, the consumers should determine what is the base- calculated measures of association). The risk of death or non- line time and magnitude of difference for the first company to fatal MI in the pravastatin group is approximately two-thirds connect the call versus the second company. If the first of the original risk (RR = 0.70). In addition, 75 pravastatin pa- com- pany takes 3.5 seconds and the second company takes six sec- tients were spared a nonfatal MI or death from CHD com- onds, the 42% difference may not be significant. However, if pared to placebo (ARR = 2.26%). Furthermore, approximately the first takes 35 minutes and the second company one-third of the baseline risk was removed as a result of company takes 60 minutes (still a 42% difference), there is a significant pravastatin therapy (RRR = 30%), and 44 patients need to be disparity. And the cost differences could be signficant. treated for an average of 4.9 years to prevent one nonfatal MI time This example is comparable to some situations in medical de- or death from CHD (NNT = 44). cision making. However, the clinical implications of the risk DISCUSSION reductions (3% to 1 % versus 60% to 20%) are very different. Consider a therapy with a 5% incidence of severe side ef- Measures of association (RR, ARR, RRR, NNT) can be cal- fects that also reduces the probability of an adverse outcome culated from studies designed to measure dichotomous out- from 3% to 1 % (RRR = 66%). This therapy may not be desir- comes as endpoints. Since most studies in general discuss only able due to the risk-benefit ratio. However, if the therapy re- the relative changes (RR and RRR), additional measures can be duces the probability of an adverse outcome from 60% to 20% calculated to more fully evaluate the clinical significance of the (also a RRR of 66%), it may be acceptable since, out of 100 results. The definitions and implications of these measures treated patients, 40 patients would benefit and only five provide a better understanding of the effect of medical inter- would experience side effectsB vention. Presentation of Findings Can Influence Decisions The Influx and Impact of Aggressive Advertising Results of several studies have indicated that the manner in As the economics of health care continue to be a major which research findings are presented can influence decisions. consideration in the delivery of patient care, payers may not For example, physicians have been surveyed to determine be willing to pay for services ancIJor goods at a premium price their willingness to prescribe drug therapy according to vari-

]MCP Vol. 3, No.2 Mar/Apr 1997 Journal of Managed Care Pharmacy .181 REVIEW ARTICLE: A Method of Data Interpretation

ous measures of association. Although each therapy "option" pies," each expressed as either RRR, ARR, NNT, percentage of was obtained from one study (but presented as ARR, NNT, or event-free patients, or RRR plus relative increase in total mor- RRR), the RRR was most favorable and selected most often.'-4 tality Although each drug "therapy" appeared to be a different Naylor et aI' and Bucher et aP conducted separate, but drug regimen, all were derived from the same outcome similarly designed, studies to determine physician perception (change in cardiac event incidence) of the Helsinki Heart 14 of the effectiveness of drug therapy In the Naylor study, house Study For each therapy, physicians were asked to place an staff and faculty (internal medicine and subspecialties) were "X" along a lO-cm visual analog scale labeled "I would defi- included; the Bucher study focused on primary care physi- nitely not prescribe this drug" on the left and "I would defi- cians (internists and general practitioners). The physicians nitely prescribe this drug" on the right. The highest response randomly received one of two separate questionnaires, each rate for agreement to prescribe the drug was for RRR (78%,) containing four statements enumerating the effects of therapy while the next highest response (37%) was percentage of for three endpoint measures (fatal plus non-fatal MI, fatal MI, event-free patients (p < 0.001). and total mortality) of the Helsinki Heart studyl4 The first A survey of authorities responsible for establishing health three statements were expressed as either RRR (form "A") or care policies5 produced similar results. Participants were pre- ARR (form "B"). The last statement on both forms was the sented with two disease state scenarios: breast cancer screen- same and expressed the effect of therapy in terms of NNT for ing and cardiac rehabilitation_ Following these scenarios, four fatal plus non-fatal MI. The physicians were asked to grade disease prevention "programs" described the effectiveness of each therapy according to their perception of therapy efficacy each one. The outcome of each "program" was presented as ei- using an ll-point scale (-5 to +5). The far left of the scale (-5) ther RRR, ARR, proportion of event-free patients, or NNT. Af- was labeled "therapy is harmful," while the opposite side of terwards, the individuals were asked to rate their willingness the scale (+5) was labeled "therapy is beneficial"; a zero value to implement the "program" by placing an "X" along a linear represented "no effect." Results demonstrated that ratings of scale marked from 0 ("I would not support purchasing of this therapeutic effectiveness were higher for the questionnaire dis- service") to 10 ("I would strongly support the purchasing of playing the results as relative reductions than absolute reduc- this service"). The highest mean score (95% confidence inter- tions (p < 0.001). Furthermore, physicians rated the effective- val) for both "programs" was for RRR: 79% (76-83%) and ness of therapy significantly higher for the endpoint represented 76% (72-80%), respectively (p < 0.05). The next highest as risk reduction (either RRR or ARR) than NNT (p < 0.001). mean score was for NNT, 51 % (47-55%) and 62% (58-66%). In addition, Forrow et aJ.3 conducted a study to deter- The results indicate that the method of reporting trial results mine if differences in presentation of research results (empha- influenced the policy decisions. sizing relative or absolute change in outcome rates) may lead to differences in perceived treatment benefits. Physicians at- Influencing Medical Therapy and Benefits tending educational conferences at either a selected teaching Survey results of pharmacists and patients have demon- or community hospital were surveyed; selected fellows and strated that views of medical therapy can be influenced by how faculty received a questionnaire via mail. Two different ques- potential benefits are presented. Papay et al.'s designed a ques- tionnaires (one for and one for hypercholes- tionnaire to determine if pharmacists were able to recognize dif- terolemia) were developed, each having six brief statements ferent presentation styles of the same study result. The 3P Trial6 summarizing information derived from published studies. Fol- primary endpoint was expressed as RRR, ARR, ARR represented lowing each statement, the participants were asked how this as "rate decreased from 7.9 to 5.5%", or NNT as though each of information would affect their decision to treat their patients these were four different "therapies." After reading a brief clini- with this condition. Two of the six questions on each ques- cal scenario, pharmacists were asked to select one of the four tionnaire reported the outcome of the same study in a differ- "therapies" that they would most likely recommend to the med- ent manner, either as RRR or ARR. Physicians were asked to ical staff. Preliminary results indicated that only 6.5% of the re- rate the likelihood of starting treatment based on each state- sponders were able to identify that all four "therapies" were ment using a seven-point scale (ranging from "definitely more equivalent; the highest number of responses (39%) was for ARR likely to treat" to "definitely less likely to treat"). Results represented as "rate decreased from 7.9 to 5.5%." 16 demonstrated that 46% of the physicians responded different- Hux et a!. distributed a questionnaire to patients de- ly to the same question presented in the two different man- scribing the effects of the same medication displayed in three ners; of these, approximately 90% indicated a stronger desire different formats: RRR, ARR, and NNT. Eighty-eight percent of to treat patients according to the relative, versus absolute, the patients were willing to take the medication when present- change in the outcome rate (p < 0.0001). ed as RRR, while the next highest response (56%) was NNT Bobbio et al.4 also surveyed general practitioners to deter- (p < 0.0001). Malenka et al.17 reported similar results -when mine whether reporting outcomes as various measures of asso- asked to select a therapy which appeared more beneficial, ciation affected physician opinions on the treatments' useful- patients selected the therapy results displayed as RRR most ness. The questionnaire presented five different drug "thera- often (56.8%), compared to ARR (14.7%).

182 Journal of Managed Care Pharmacy jMCP Mar/Apr 1997 Vol. 3. NO.2 REVIEW ARTICLE: A Method of Data Interpretation

Interpreting ARR and NNT biomedical literature and assist in the decision making process. Very few studies include ARR, while even fewer present Those in managed care, including managed care pharma- NNT. Both values incorporate the influence of any change in cists, should exercise caution in evaluating review literature, baseline risk. However, neither of these two measures provide studies, and other information and materials that they use in the magnitude of baseline risk. Since NNT is related to the ARR, developing drug benefit programs, formularies, and other a change in the underlying risk will cause an alteration in NNT. components of patient care. . Furthermore, NNT is directly related to the proportion of pa- suffer if tients in the control group that an adverse event. Thus, .... References the risk of an adverse event doubles, only half as many patients 1. Naylor CD, Chen E, Strauss B. Measured enthusiasm: does the method of re- need to be treated to prevent the same number of adverse events, porting trial results alter perceptions of therapeutic effectiveness' Ann Intern and vice versa.s Med 1992; 117: 916-21. A method assist in the interpretation of NNT preliminary to 2. Bucher HC, Weinbacher M, Gyr K. Influence of method of reporting study has been proposed by calculating a threshold NNT (T-NNT). In results on decision of physicians to prescribe drugs to lower cholesterol concen- BM] 1994; simple terms, the method for generating a T-NNT focuses on the tration. 309: 761-4. 3. Forrow L, Taylor WC, Arnold RM. Absolutely relative: how research results concept that the net cost of treating the number of patients to are summarized can affect treatment decisions. Am] Med 1992; 92: 121-4. prevent one adverse event equals the net value of the adverse 4. Bobbio M, Demichelis B, Giustetto G. Completeness of reporting trial results: prevented by that of 18 As events treating number patients. with effect on physicians' willingness to prescribe. Lancet 1994; 343: 1209-11. most therapies, both positive and negative consequences need to 5. Fahey T, Griffiths S, Peters Tj. Evidence based purchasing: understanding re- systematic BM] 1995; be considered in the decision to treat or not to treat. For in- sults of clinical trials and reviews. 311: 1056-60. Shepherd], Cobbe SM, Ford Isles CG, Lorimer AR, Macfarlane pw, et a1. stance, patients with elevated cholesterol can develop cardiac 6. I, Preverition of coronary heart disease 'Nith pravastatin in men with hypercholes- morbidity ancIJor mortality if no therapy is initiated. 19 If therapy terolemia. N Engl] Med 1995; 333: 1301-7. is the disease could and the patient's risk of initiated, regress 7. The West of Scotland Coronary Prevention Study Group. A coronary primary cardiac morbidity ancIJor mortality may be reduced20 However, prevention study of Scottish men aged 45-64 years: trial design.] Clin Epidemi- the side effects and costs of treatment should be considered. 011992;45:849-60. Jaeschke Guyatt Shannon Walter S, Cook Heddle Basic statis- Generating a T-NNT includes identifying the consequences of 8. R, G, H, D, N. tics for clinicians: 3. Assessing the effects of treatment: measures of association. treating patients (e.g., side effects) versus not treating (e.g., Can Med AssocJ 1995; 152: 351-7. adverse addition, the associated costs (costs of event). In treating, 9. Guyatt GH, Sackett DL, Cook DJ, for the Evidence-Based Working Group. costs saved by preventing the adverse event, and costs of treating User's guides to the medical literature, II. How to use an article about therapy or help side effects caused by the treatment) are incorporated into the prevention. B: what are the results and will they me in caring for my pa- IS JAMA 1994; 271: calculations. Although the calculation of the T-NNT is beyond tients' 59-63. 10. Wilkes MS, Doblin BH, Shapiro MF. Pharmaceutical advertisements in lead- the scope of this article, if a patient's risk of an adverse event ing medical journals: experts' assessments. Ann Intern Med 1992; 116: 912-19. therapy is high and the calculated NNT is below the without 11. Avorn], Chen M, Hartley R. Scientific versus commercial sources of influ- I" T-NNT, therapy should be considered, and vice versa. ence on the prescribing behaviors of physicians. Am] Med 1982; 73: 4-8. Otherwise, the decision to start therapy can be based on 12. McGavock H, Webb CH,Johnson GD, Milligan E. Market penetration of drugs in United Kingdom region: implications for general practitioners the patient's risk of the adverse event if left untreated versus the new one and administrators BM] 1993; 307: 118-20. risk of harm from therapy side effects) and/or costs9 For (e.g., 13. Ferner RE, Scott DK. Whatalotwegot-the messages in drug advertisements. produces myalgia 3% example, if pravastatin in of treated BMJ 1994; 309: 1734-6. patients, the NNT to cause myalgia is 1/0.03 or 33. Thus, for 14. Frick MH, Elo O,Haapa K, Heinonen Op, Heinsalmi P, Helo P, et a1. Helsin- ki Study: gemfibrozil middle-aged every nonfatal MI or death from CHD prevented, 1.3 patients Heart primary-prevention trial with in men with dyslipidemia: safety of changes in risk factors, and incidence of can experience myalgia. On the other hand, treating 233 treatment, coronary heart disease. N EnglJ Med 1987; 317: 1237-45. patients to prevent one death due to CHD (see Table 4) can 15. Papay JI, Kendrach MG, McCarthy MW, Fancher MG, Henderson Rp, Wool- developing myalgia. Despite this result in seven individuals ley 1. The influence of different reporting methods on pharmacists' therapeutic simple example, this approach cannot be applied to severe, recommendations (Abstract). 1997 Spring Practice and Research Forum, Ameri- College episodic events. The number of adverse events per life saved can of Clinical Phannacists. 16. Naylor CD. Communicating the benefits of chronic preventative (or, if the events are rare enough, the number of lives saved per Hux]E, therapy: does the fonnat of efficacy data detennine patients' acceptance of treat- adverse event) can provide a compelling picture of the trade- ment? Med Decision Making 1995; 15: 152-7. offs clinical associated with the intervention9 17. Malenka D], BaronJA, Johansen S, Wahrenberer Jw, RossJM. The framing effect of relative and absolute risk. J Gen Intern Med 1993; 8: 543-8. CONCLUSION 18. Guyatt GH, Sackett DL, Sinclair ]C, for the Evidence-Based Working Group. User's guides to the medical literature, IX. A method for grading health care rec- 1995; Health care professionals need to remind themselves of the ommendations. JAMA 274: 1800-4. blood choleslerollo "limitations" of the medical literature and not be mislead by the 19. Anonymous. Consensus conference. Lowering prevent heart disease JAMA 1985; 253: 2080-6. presentation styles. As demonstrated by the measures of associ- 20. Law MR, Wald NJ, Thompson SG. By how much and how quickly does re- these be easily calculated ation formulas, values can to provide duction in serum cholesterol concentration lower risk of ischaemic heart clis- additional data that can be used to evaluate and interpret the ease? BMJ 1994; 308: 367-72

Vol. 3, No.2 Mar/Apr 1997 fM{,p Journal of Managed Care Pharmacy 183