Pneumococcal Vaccine Ineffective at CAP Prevention

Pharmacology Watch

Pneumococcal vaccine protects older adults from developing pneumococcal bacteremia but does not prevent community-acquired pneumonia (CAP), according to a new study from Group Health Cooperative in Seattle. The study reviewed records of more than 47,000 adults aged 65 and older who were followed for more than 3 years. During that period 1428 were hospitalized with CAP, 3061 were diagnosed with outpatient pneumonia, and 61 had pneumococcal bacteremia. Prior receipt of the pneumococcal vaccine was associated with a reduction in the risk of pneumococcal bacteremia (HR 0.56; 95% CI, 0.33-0.93), but an increased risk of hospitalization with CAP (HR, 1.14; 95% CI, 1.02-1.28). The pneumococcal vaccination did not change the risk of outpatient CAP (HR, 1.04; 95% CI, 0.96-1.13), or the combined outcome of inpatient and outpatient CAP (HR, 1.7; 95% CI, 0.99-1.14). The authors point out that these results are consistent with those of 4 meta-analyses, which also showed no reduction of CAP with the pneumococcal vaccine. They state, however, that the reduction in pneumococcal bacteremia, which is also consistent with results of other studies, is reason enough to administer the vaccine (N Engl J Med. 2003;348:1747-1755). A separate study in the same issue suggests that vaccinating children with pneumococcal vaccine may also benefit adults. Using CDC surveillance statistics, a dramatic reduction in invasive pneumococcal disease was found between the years 1998 and 1999 and the year 2001, one year after the licensing of the protein-polysaccharide conjugate vaccine with the largest decline in children younger than the age of 2, when a 69% reduction was seen. A reduction in disease rates for adults and, especially young adults, was also noted over this time period. Interestingly, the 35% reduction in penicillin-resistant pneumococcus was also noted over the same timeframe (N Engl J Med. 2003; 348:1737-1746).

Flu Vaccine Limits Hospitalization

The influenza vaccine is highly effective at preventing hospitalization and death during the influenza season. A recent study reviewed the records of more than 140,000 adults aged 65 and older during the 1998-1999 and 1999-2000 influenza seasons, during which 55.5% and 59.7%, respectively, were immunized. The flu vaccine was associated with a reduction in the risk of hospitalization for cardiac disease (reduction of 19% during both seasons [P < 0.001]), cerebrovascular disease (reduction of 16% during the 1998-1999 season [P < 0.018] and 23% during the 1999-2000 season [P < 0.001]), and pneumonia or influenza (reduction of 32% during the 1998-1999 season [P < 0.001] and 29% during the 1999-2000 season [P < 0.001]) and a reduction in the risk of death from all causes (reduction of 48% during the 1998-1999 season [P < 0.001] and 50% during the 1999-2000 season [P < 0.001]). The subgroups were well matched for major medical illnesses. The authors point out the extraordinary effectiveness of the influenza vaccine, which has also been seen in other studies, but they also point out that the national rate of vaccination against influenza was only 63% of adults older than the age of 65 in 2001 (N Engl J Med. 2003;348:1322-1332).

Verapamil Not Up To Competition

Controlled-onset extended-release (COER) verapamil "is not equivalent to atenolol or hydrochlorothiazide in preventing cardiovascular disease-related events" is the conclusion of the CONVINCE trial (Controlled Onset Verapamil Investigation of Cardiovascular Endpoints). The study was terminated early by the sponsor for "commercial reasons." CONVINCE was initially designed to test the hypothesis that control of early morning blood pressure might reduce cardiovascular mortality given that acute myocardial infarction (MI), cardiovascular event-related death, and stroke all have their highest incidence during the early morning hours (6 am to noon). More than 16,000 patients were randomized to receive COER verapamil or either of atenolol 50 mg or hydrochlorothiazide 12.5 mg. Other antihypertensives were added if needed. The main outcome was stroke, MI, or cardiovascular related death. Blood pressure control was virtually identical between the 2 groups. There were fewer myocardial infarctions in the COER verapamil group, but more strokes, and cardiovascular deaths were similar (hazard ratios: MI 0.82, CVA 1.15, CV death 1.09, all-cause mortality 1.08). Both groups had more cardiovascular deaths between 6 am and noon (COER verapamil 99/277, atenolol or HCTZ 88/274). The authors state that low-dose thiazide diuretics and/or beta blockers remain first-line therapy for hypertension, a recommendation that is in line with the recent Sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JAMA. 2003;289:2073-2082).

International Companies Unite Against SARS

As researchers move closer to identifying the etiologic agent of SARS, several international drug companies are collaborating to develop a vaccine. GlaxoSmithKline has announced it is working with France’s Institut Pasteur along with several other pharmaceutical companies to develop a vaccine. The SARS vaccine would have a massive worldwide market, and traditionally companies would compete to bring a product to market. But partially under urging from US government officials, companies such as Merck, Wyeth, Chiron, Baxter, J&J, and others have committed to collaborating in this important effort. Scientists involved in this process warn, however, that this process will likely take years.

New FDA Comissioner Brings Controversy

The pharmaceutical industry is still analyzing whether Mark McClellan, the FDA’s new Commissioner, is friend or foe. The 38-year-old Commissioner has hit the floor running but has generated controversy in the process. Harvard trained as a physician and economist, McClellan was teaching medicine and economics at Stanford, and advising the Bush administration on health-care economics when he was tapped to head the FDA. The new Commissioner has pleased the pharmaceutical industry by pledging to speed the new drug evaluation process. But a new proposal to force drugmakers to switch some prescription drugs to over-the-counter (OTC) status is strongly opposed by the industry. Dr. McClellan confirmed to the Washington Post in late April that forced switches are being "actively considered." The controversy centers on nonsedating antihistamines. Schering-Plough recently took loratadine (Claritin®) OTC with urging from the FDA. Now 2 competitor drugs, Aventis’s fexofenadine (Allegra®) and Schering-Plough’s cetirizine (Zyrtec®) are under consideration for forced switches to OTC status. Both these drugs have several years of lucrative patent protection during which time they are unlikely to pursue OTC status on their own. All 3 drugs are sold OTC in many other countries and are considered safer than current OTC antihistamines. The price of most drugs drop significantly when they are available OTC, a fact that is not lost on pharmaceutical companies or consumer groups. Opposing the powerful pharmaceutical lobby has never been politically savvy, but Dr. McClellan may choose to court an even more powerful lobby—the American health care consumer.

Janssen: Dear Doctor’ Letter for Risperidone

Janssen pharmaceuticals has issued a "Dear Doctor" letter concerning its antipsychotic medication risperidone (Risperdal®). The letter warns health-care providers about a possible increased risk of stroke among elderly patients taking the drug. "Cerebrovascular adverse events (eg, stroke, transient ischemic attack), including fatalities, were reported in patients (mean age, 85 years; range 73-97) in trials of risperidone in elderly patients with dementia-related psychosis. In placebo-controlled trials, there was a significantly higher incidence of cerebrovascular adverse events in patients treated with risperidone compared to patients treated with placebo." Risperidone is approved for treatment of schizophrenia, but it is commonly used off label to treat delusional or aggressive behavior in elderly patients with dementia.

This supplement was written by William T. Elliott, MD, FACP, Chair, Formulary Committee, Kaiser Permanente, California Division; Assistant Clinical Professor of Medicine, University of California-San Francisco. Telephone: (404) 262-5517. E-mail: In order to reveal any potential bias in this publication, we disclose that Dr. Elliott reports no consultant, stockholder, speaker’s bureau, research, or other financial relationships with companies having ties to this field of study.