Dr. Victor Gurewich, a researcher and Harvard Medical College school member since 1965, found a breakthrough drug remedy for coronary heart assaults and strokes with the potential to avoid wasting thousands and thousands, however institutional resistance and a U.S. healthcare system that places earnings over sufferers are holding it out of attain.

Chest tightness. Arm ache. Panic. The warning indicators hit exhausting, and for a second, the considered a coronary heart assault is not only a worry—it’s taking place.

The ambulance tears via town, and shortly you’re within the ER. They offer you aspirin, nitroglycerin, and a drug referred to as tPA to attempt to dissolve the clot. However the physician’s face darkens. The blockage is extreme. You’ll want a PCI – a percutaneous coronary intervention – the place a catheter is threaded via your artery, a balloon is inflated to open the blockage, and a stent is positioned to maintain the artery open.

The issue? Your hospital doesn’t have a catheterization lab—solely two-thirds of hospitals do. The PCI ought to ideally occur inside 90 minutes, often known as the “door-to-balloon” window. An hour-long switch to a much bigger hospital is so as—and time is slipping away. And what is going to your insurer permit?

The fact hits: you may not make it.

Each 43 seconds, somebody in the USA has a coronary heart assault. Coronary heart illness has been the main reason behind dying within the U.S. for 100 years, and too many people simply preserve dying. Greater than one out of ten individuals who expertise the dreadful signs of a coronary heart assault won’t survive.

Dr. Victor Gurewich is on a mission to alter this. He insists that many coronary heart assault deaths might be averted with the right drug intervention, however catheterization—the go-to remedy—has main flaws that trigger unnecessary dying.

Gurewich’s argument boils down to 3 key factors. First, with so many U.S. hospitals missing cath labs, coronary heart assault victims usually face transfers that may result in delays—delays that may double mortality as blockages persist. Second, catheterization works solely on bigger vessels, leaving smaller arteries susceptible. Third, a easy, simpler clot-dissolving drug remedy exists—if solely docs might entry and use it. “Should you had a coronary heart assault proper now, I might deal with it by injecting a drug into your vein,” he says. “You’d be extra prone to survive.” (It is a hypothetical scenario, because the drug doesn’t but have full FDA approval).

In accordance with Gurewich, his drug remedy mirrors the physique’s pure clot-dissolving course of, making it a far superior different to introducing overseas supplies – stents that may trigger problems corresponding to allergic reactions, blood clots, scar tissue, and blood vessel collapse. Remedy, then again, works on the blood slightly than the vessel so it isn’t restricted by vessel dimension. And since no process or particular facility is required, it’s far less expensive than catheterization.

“There’s proof that it’s efficient for strokes, too,” provides Gurewich. “Coronary heart assaults and strokes are basically the identical illness course of — clots in numerous components of the physique.”

He’s assured that his remedy, which includes a mixture of two brokers that replicate the physique’s innate mechanism for dissolving undesirable clots, delivers higher outcomes than customary protocols – a declare backed up by research.

Gurewich—an unstoppable pressure in his discipline—is difficult medical traditions with relentless dedication. At 95, his thoughts is as sharp as ever, and he has been advocating for his revolutionary remedy because the Eighties, with no plans to again down.

The story of how an invasive process got here to be most well-liked over a probably superior drug remedy exposes a medical system that too usually resists progress and values earnings over affected person care, sabotaging public well being within the identify of monetary achieve.

Fibrinolysis: The Physique’s Pure Protection System

Born in Berlin, Gurewich hails from a household with a wealthy legacy in medication. His father, Vladimir, was certainly one of Sigmund Freud’s trusted docs in London, whereas his uncle, David, attended to none apart from Eleanor Roosevelt. Gurewich’s grandfather, David, was a doctor, and his grandmother, Maria, was famend for her unconventional therapeutic massage strategies, attracting high-profile sufferers, together with Roosevelt.

When the Nazis rose to energy, Gurewich’s household fled Germany, first to the U.Ok. and later to the U.S., the place his father constructed a profitable medical apply. He studied medication at Harvard, the place his ardour for vascular illness took root. When the Vietnam Conflict began, he obtained a deferment by serving two years within the Air Drive medical service in Florida. By 30, he was named chief of medication at a navy hospital in Tampa after the present chief fell ailing, and he began publishing vital work within the New England Journal of Drugs, together with a case examine of pulmonary bleeding. His profession has fused affected person care with scientific inquiry, culminating in over 200 revealed analysis papers.

After his navy service, Gurewich accomplished his cardiology residency at West Roxbury VA Hospital close to Boston. Although formally a heart specialist, his fascination with the vascular system led him to specialise in fibrinolysis— the physique’s fascinating pure course of that dissolves clots. Early in his profession, the dying of a younger girl from a pulmonary embolism after childbirth haunted him deeply. “Childbirth is a bloody enterprise,” he explains, noting that whereas he wasn’t the primary to find that clotting components surge throughout being pregnant, he could have been the primary to see simply how essential it’s. “The physique prepares to cease bleeding, however clotting will also be lethal,” he says. “I wished to know it higher.”

In different phrases, clotting is a protection mechanism that may typically go too far. Whilst you want blood to movement freely to hold oxygen and vitamins within the physique, it has to thicken into clots to cease bleeding whenever you’re damage. As soon as the wound heals, fibrinolysis breaks down the clot, stopping blockages in blood vessels. “Clotting has to occur on the skin of the vessel,” explains Gurewich. “If it’s on the within, you’ve obtained a significant issue.”

Clotting is thus each a lifesaver and, if unchecked, a possible killer. On this paradox lies the game-changing perception of Gurewich’s work.

Whereas medicine like heparin (fast-acting, intravenous) and warfarin (slower, oral) had lengthy been used to stop clots, Gurewich was excited about dissolving them. That’s why he zeroed in on thrombolytics, the category of medicine often known as “clot busters” —as a result of when you’ve obtained a clot, these different medicines gained’t assist you. He began an anticoagulant clinic to additional discover the method, treating sufferers with clots within the lungs, legs, coronary heart, and mind.

Again within the Forties, Danish researchers found an enzyme that finally led to the identification of a extra particular agent: tissue plasminogen activator (tPA), the primary clot-busting drug. The FDA permitted tPA for coronary heart assaults in 1987 and for acute ischemic strokes in 1995. Gurewich factors out that whereas tPA turned the usual drug remedy, “it was by no means as efficient as we’d hoped—an excessive amount of of it might trigger bleeding.” He notes that from the Fifties to the Seventies, early research explored different clot busters, however they, too, carried bleeding dangers, inflicting curiosity in thrombolytics to wane.

Right here’s the place Gurewich is available in. He might see that tPA’s mechanism made sense however realized it wasn’t the total reply. He likens using tPA by itself to placing the important thing in a automotive’s ignition: “The starter alone gained’t do it; you want the engine,” he says. So, he discovered the answer: mix tPA with one thing else—the engine—to get the clot-busting course of moving into simply the correct means.

Gurewich’s search to establish tPA’s pure accomplice led him to research urokinase, an enzyme that had been identified however was first described by him for its complementary function in blood clotting alongside tPA. Whereas urokinase helps break down clots, it doesn’t work properly within the bloodstream due to pure inhibitors that block its motion. In 1981, he found an enzyme in urine that was the “inactive” type of urokinase, which he named pro-urokinase (proUK). He then discovered that combining proUK with tPA created an much more highly effective clot-busting system than urokinase or tPA alone. “Now you’ve obtained the starter and the engine,” he says.

When tPA was first used to deal with coronary heart assaults, giant doses of 100 milligrams have been frequent, which might trigger harmful bleeding by concentrating on hemostatic fibrin and affecting different components of the physique. However Gurewich found that combining tPA with proUK allowed for simply 5 milligrams of tPA, a secure dose.

In 1995, he labored with an Italian firm, FarmItalia, on a small examine testing the mixture of tPA and proUK in 101 coronary heart assault sufferers. The outcomes have been spectacular: 82% in a subset of sufferers had their blocked artery totally open and simply 1% died. As compared, conventional therapies on the time solely confirmed 45% of sufferers with the blocked artery totally open and a 6% dying charge. “It blew all the opposite statistics out of the water,” he says. “No remedy has ever matched its efficacy and low mortality, and the examine confirmed that solely 5 milligrams of tPA have been needed, whereas additionally demonstrating {that a} 90-minute infusion of proUK was optimum.” The findings have been revealed within the prestigious Journal of the American School of Cardiology.

Regardless of promising outcomes from the Italian trial, progress on his drug remedy stalled. The sale of the agency shortly after the trial shifted priorities—although the corporate had licensed Gurewich’s remedy, cardiology was not a spotlight after the sale. It was an unlucky case of dangerous timing. What might have been a revolutionary breakthrough didn’t occur.

Whereas robust examine outcomes usually result in replication, this was not the case with Gurewich’s remedy. Alongside the misfortune surrounding the sale of FarmItalia, Gurewich believes a key issue within the stalling was the medical discipline’s rising fascination with high-tech procedures, which overshadowed the potential of creating medicine that harness the physique’s personal pure processes. Like a clot within the thoughts, as soon as it set, dislodging it turned a significant problem.

Regardless of Gurewich’s discoveries, docs continued to depend on tPA as the usual drug remedy for breaking apart blood clots—it’s nonetheless the one drug out there available on the market. He’s annoyed that fibrinolysis nonetheless revolves round tPA alone, though simpler alternate options can be found. Partly because of the restricted effectiveness of tPA by itself, the medical discipline has more and more turned to extra invasive procedures as a remedy choice. (He lately co-authored a paper within the Journal of Vascular Analysis outlining his considerations about this course).

“In a coronary heart assault, blood movement to a part of the guts muscle is blocked, so the highest precedence is restoring circulation as rapidly as doable,” Gurewich factors out. “But, present first-line therapies—corresponding to PCI or the present thrombolytics—are gradual, interventional, inpatient procedures. Why is that? Sufferers with coronary heart assaults appeared to fare higher 20 years in the past.”

Earnings Over Sufferers

Gurewich believes there’s one more reason invasive procedures have develop into customary: “They provide a giant monetary incentive,” he says. “Every catheterization is reimbursed round $23,000 within the U.S. – that’s the quantity the hospital will get for the process.”

Whereas hospitals don’t immediately regulate medicine, they’ve a major affect on which therapies are used. David Segarnick, a pharmacology professor at Rutgers New Jersey Medical College and advisor to Thrombolytic Science Worldwide (TSI)—a biopharmaceutical firm co-founded in 2006 by Gurewich to additional examine his drug remedy—factors to what he calls the “PCI Industrial Advanced.” This refers back to the expensive infrastructure constructed round cath labs, which require costly tools, specialised services, and expert employees. To justify these excessive prices, hospitals usually have to carry out a excessive quantity of procedures, which may result in a choice for invasive therapies over less expensive, non-invasive alternate options. To make issues worse, the grip of rapacious personal fairness companies on healthcare is tightening, with many of those shadowy companies now proudly owning hospitals and different medical services, laser-focusing on earnings, not human life.

In 1996, as an increasing number of coronary heart assault sufferers have been getting stents—or dying—Gurewich developed a drug that mixes a extra steady model of proUK—mutant prourokinase (mproUK)—with a small dose of tPA. He was hopeful that additional examine would assist persuade one other drug firm to license the drugs and make it out there. Nevertheless, medical trials are extremely expensive, and his small firm might solely stretch its assets to date.

Gurewich and Segarnick are at present attempting to draw funding from the NIH, enterprise capital companies, and established pharmaceutical firms to allow TSI to hold out the costly medical trials to show the efficacy of their therapeutic—however the skepticism that they face from the “PCI Industrial Advanced.” However enterprise capitalists and Massive Pharma may doubt that TSI’s remedy can entice sufficient curiosity from inventory merchants to lift the funds it wants—each whereas the corporate remains to be personal and later, throughout a possible preliminary public providing (IPO). With out this funding, they could not see the funding as worthwhile.

How might this be, with a drug remedy that would probably save so many lives? The reply lies in monetary incentives that will not align with the general public good. When giant profit-driven companies put money into a small drug developer, the objective isn’t at all times to get a drug permitted by the FDA. As economist William Lazonick factors out, primarily based on his analysis with Öner Tulum, “When VCs put money into a biopharma firm, their payoff shouldn’t be depending on whether or not the startup generates an FDA-approved drug.” He explains that “virtually all biopharma IPOs happen with no business product” and irrespective of how efficient the drug may be, “the VCs simply need sufficient hype surrounding the startup to rake in as a lot cash for as little fairness as doable previous to and thru the IPO.”

In different phrases, producing buzz and making fast earnings too usually takes precedence—whether or not or not sufferers get entry to getting life-saving medicines.

In Gurewich’s case, the hype round his type of remedy waned because the medical group shifted away from thrombolytics, and the promising 1995 examine pale in time. Nevertheless, one piece of reports was encouraging: unrelated analysis revealed in The Lancet in 2006 supplied oblique help for his idea. In a examine involving practically 100,000 sufferers, it was discovered that in 15% of circumstances, the artery blocked by the guts assault was totally opened, that means the blood clot had dissolved. This was because of the pure clot-dissolving enzymes, tPA and proUK, current within the blood, which helped break down the clot.

In a nutshell, the affected person’s physique did the clot-busting job by itself, exhibiting that it’s doable even with the small quantities of enzymes naturally within the physique. This gave an important instance of how Gurewich’s remedy might work. Some individuals might really recuperate from a coronary heart assault on their very own if they’ve a robust pure capability to interrupt down clots, which actually reveals how highly effective nature’s personal system is. He believed that many extra sufferers may gain advantage if larger, therapeutic ranges of those enzymes have been used.

However the issue stays that invasive procedures like catheter-based therapies for coronary heart assaults, surgical procedures, and high-tech interventions may be profitable for healthcare suppliers, usually overshadowing less complicated, cost-effective drug therapies that could be simply as efficient, if no more so. The monetary pursuits tied to medical units and procedures create a bias towards these choices that may imply extra medical prices and better dangers for sufferers.

In the end, shoppers and taxpayers foot the invoice for coronary heart assault catheterizations as a result of hospitals are reimbursed by insurance coverage firms (personal or government-funded), that are paid for via premiums from people, employers, and taxes. Sufferers may pay a part of the price via co-pays or deductibles, whereas the uninsured could depend on public packages, with the monetary burden in the end falling on the general public.

Gurewich criticizes the incentives of a healthcare system the place interventions categorized as “procedures,” irrespective of how expensive, are reimbursed generously, whereas “therapies,” corresponding to drug injections, aren’t. He explains, “Even when I injected gold, there’s no reimbursement as a result of an injection isn’t thought of a process.” He factors out that interventional procedures are so well-liked as a result of they pay properly. “I used to be on the board of a distant cardiac monitoring firm,” he says, “and the monetary incentives for docs—primarily based on what they have been paid per process—have been a key a part of the technique.”

He laments that even when a remedy has “clear, compelling well being economics,” docs gained’t use it until there’s a means for them to receives a commission. A drug injection remedy corresponding to his is probably cheap to fabricate at scale (although drug firms can nonetheless inflate the worth), doesn’t require specialised services, and might be administered by healthcare practitioners apart from docs— all of which might save Individuals cash.

In his view, the actual problem is the way in which monetary pursuits are shaping medication for the more serious. “It’s all about cash, cash, cash,” he complains. “As a substitute of bettering fibrinolysis, the medical discipline deserted it and changed it with high-cost procedures.”

He observes that stroke remedy has gone down the same highway. For bigger clots, docs can do surgical procedure to take away them, nevertheless it’s not an choice for smaller vessels. In these circumstances, tPA is usually used, however it might trigger seizures and lethal mind bleeds, making docs hesitant – no person desires to be sued for malpractice. Gurewich believes his combo of tPA and proUK can be far simpler at safely dissolving clots: “The protection of my sequential mixture was proven in each the 1995 trial for coronary heart assaults and a 2023 trial of twin thrombolytic remedy for stroke.”

Backside line: America’s profit-driven medical system is a textbook case of market failure—the place earnings drive choices, higher therapies are ignored, and affected person care is sidelined.

Growing Nations Main the Approach?

Gurewich has been inspired by a section 1 trial of his remedy in 2017, in addition to a section 2 trial in ischemic stroke. He’s excited a few present coronary heart assault trial of the remedy underway within the U.Ok. funded by TSI. “It’s a small trial, with simply 48 sufferers, however the outcomes to date are very promising,” he says. He’s assured that in only a 12 months, he’ll have the info to again up his remedy’s success once more.

Within the meantime, creating international locations are turning to Gurewich to assist get remedy for sufferers in a medical panorama the place extra invasive interventions are merely unaffordable. His firm is collaborating with Osman Khalid Waheed, the director of Ferozsons, a pharmaceutical firm in Pakistan, on a privately funded trial, hoping that the Pakistani authorities will finally undertake his remedy nationwide. “If we will get every thing in place,” he says, “they might begin in the course of subsequent 12 months on a trial.”

Gurewich stays hopeful {that a} U.S. firm will assist carry his drug remedy to American sufferers: he’s already cleared a significant hurdle—FDA approval for an IND (Investigational New Drug) standing. Securing an IND is step one in bringing a brand new drug to market, and Gurewich’s utility was accepted, which implies that the mixture of mproKU and tPA can be utilized to deal with individuals with coronary heart assaults and stroke in a managed examine. The Nationwide Coronary heart, Lung & Blood Institute (NHLBI) can be excited about working with TSI to help a bigger section 3 examine in coronary heart assault sufferers. He’s optimistic that these milestones, together with extra knowledge from the U.Ok. examine, will seize the eye of American traders.

Defenders of America’s healthcare system like to tout its “world-class” outcomes, claiming that its excessive price is justified by superior expertise and cutting-edge therapies. However right here’s the kicker: in some circumstances, creating international locations really get entry to cheaper, less complicated, and typically even higher drug therapies as a result of the U.S. is simply too busy pushing costly, invasive procedures. Pushed by revenue motives, the concentrate on high-cost interventions usually slows down or outright blocks higher, life-saving choices. In the meantime, locations like Pakistan, the place cost-efficiency is vital, can leapfrog to adopting easy therapies which can be way more sensible and accessible.

As 800,000 Individuals die from coronary heart illness and stroke yearly, the U.S. can’t afford to fall additional behind.