Book Review

Clinical Trials in Cardiovascular Disease: A companion to Braunwald's Heart Disease

N Engl J Med 1999; 341:927-928September 16, 1999

Article

Clinical Trials in Cardiovascular Disease: A companion to Braunwald's Heart Disease
Edited by Charles H. Hennekens. 472 pp., illustrated. Philadelphia, W.B. Saunders, 1999. $130. ISBN: 0-7216-6867-4

This outstanding, thoroughly comprehensible and comprehensive, well-edited book succeeds admirably in its intention to serve as a resource on clinical trials in cardiovascular disease for those in research and in clinical practice. It provides an extensive, instructive review of statistical methods, a critical review of treatment trials, and a review of trials regarding prevention — all of which explain and epitomize modern evidence-based medicine. This book is a worthy companion to Braunwald's Heart Disease, permitting readers to decide on their own the appropriateness of clinical guidelines and therapies, and is well worth the expense.

The first section explains and clarifies the methodologies of research, such as the often-difficult-to-understand case–control study, cohort study, meta-analysis, and prospective randomized trial; the role of the safety monitoring board; and the meaning of the various statistical manipulations used to demonstrate the success or lack of success of a specific study. It is good, basic, and easily understood by the nonepidemiologist, such as myself.

Section II, expertly edited by Paul Ridker, focuses on treatment trials. Treatment based on the results of large, randomized trials, which are the cornerstone of modern evidence-based medicine, has markedly reduced morbidity and mortality from cardiovascular causes over the past 20 or so years. In this section of the book, many, if not most, of the important trials regarding various cardiovascular diseases are covered in detail; extensive tables and diagrams will allow the reader to review the database and make decisions regarding treatment. The trials described include those on aspirin, heparin, or both for unstable coronary syndromes; beta-blockers, including modern indications for heart failure and hypertension; angiotensin-converting–enzyme inhibitors for myocardial infarction, congestive heart failure, and hypertension; calcium-channel blockers, including a critical review of their indications and contraindications in ischemic heart disease and hypertension and the controversial use of short-acting calcium-channel blockers for hypertension; nitrates for ischemia and during acute myocardial infarction; various thrombolytic regimens and controversies such as streptokinase versus tissue plasminogen activator (t-PA); various antithrombotic regimens, including the direct antithrombins such as hirudin and low-molecular-weight heparin; the IIb/IIIa receptor inhibitors and catheter-based intervention, on which multiple and confusing studies have been done; the treatment of dyslipidemia; antiarrhythmic (sometimes proarrhythmic) drugs and the defibrillator; anticoagulant therapy for myocardial infarction and atrial fibrillation; and exercise and congestive heart failure.

The third section, on prevention trials, reviews important topics, such as serum lipids, hypertension, hormone-replacement therapy before and after coronary events, diet and exercise (including fish and supplements of n–3 fatty acids), and community-based interventions (where a great deal can be done for many at a very low cost, as compared with less being done for a few at great expense — secondary prevention).

International experts contributed to specific chapters, which have been carefully edited and ordered by the section editors. The index is excellent. For the most part, the reviews and the editing are evenhanded. For example, regarding thrombolytic trials, Braunwald and his group were instrumental in initiating the Thrombolysis in Myocardial Infarction trials, the results of which advised the use of t-PA, but a review by Baigent and Collins explains and compares the results of the streptokinase and t-PA trials, allowing the reader to compare the advantages and disadvantages of these important methods of therapy. It includes an excellent table and descriptive figures, leaving the reader to decide which therapy may be more appropriate without merely stating that t-PA is a better drug than streptokinase because of earlier vessel patency and improved left ventricular function. The result of their analysis is a reassuring recommendation that suggests that the earliest possible thrombolytic therapy (t-PA or streptokinase) leads to the best outcomes in terms of a reduction in mortality and morbidity and the preservation of ventricular function. Similarly, the controversy over calcium-channel blockers receives a nonjudgmental review that allows the reader to reach an independent conclusion, such as avoiding short-acting dihydropyridines but not necessarily diltiazem or verapamil.

Several important trials such as the Hypertension Optimal Treatment trial and the Systolic Hypertension in Europe trial are mentioned but not reviewed, although their results were published before the publication of this book. The debate regarding monotherapy for hypertension — the use of diuretics versus the use of beta-blockers — is well and fairly stated, so that I remain comfortable using beta-blockers as first-line therapy.

Among the most up-to-date chapters was that on postmenopausal hormone-replacement therapy. It includes a critical review of the recently published Heart and Estrogen/Progestin Replacement Study (HERS), in which the results of a randomized, placebo-controlled trial of estrogen and progesterone versus placebo in 2800 postmenopausal women (with preexisting coronary artery disease and an average age of 67 years) showed that there is a possible increase in cardiovascular events during the first year of therapy but a possible decreased risk of these events over the subsequent three years. Of course, this result surprised the medical community because it was counterintuitive and contrary to the current advice regarding the routine use of hormone-replacement therapy in postmenopausal women for the prevention of stroke, coronary artery disease, and osteoporosis. The current advice was based on retrospective meta-analyses or cohort investigations but not specifically prospective, randomized studies, such as HERS. This again demonstrates the need for prospective, randomized trials.

I find this important book very useful in my teaching of medical students, medical staff, and cardiac fellows and for reaffirming the appropriateness of therapy for my patients while insisting on testing the validity of certain studies by means of the statistical techniques that the book explains. Every physician investigating or treating patients with cardiovascular disease will gain from the instructive objectivity of this book.

One small negative point: the remarkable prevalence of acronyms may confuse the reader and obfuscate the information presented. This problem could be alleviated in the next edition by a list of acronyms.

Oscar E. Starobin, M.D.
University of Massachusetts Medical Center, Worcester, MA 01655-0214